美国
证券交易委员会
华盛顿特区，邮编：20549
形式
(标记一)
根据1934年《证券交易法》第13或15(D)条规定的季度报告 |
截至本季度末
或
根据1934年证券交易法第13或15（d）条提交的过渡报告 |
由_的过渡期
委员会文件号：
(注册人的确切姓名载于其章程)
(述明或其他司法管辖权 公司或组织) |
(税务局雇主 |
（主要行政办公室地址） |
(邮政编码) |
(
(注册人的电话号码，包括区号)
不适用
(前姓名、前地址和前财政年度，如果自上次报告以来发生变化)
根据该法第12(B)条登记的证券：
每个班级的标题 |
|
交易 符号 |
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注册的每个交易所的名称 |
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用复选标记表示注册人(1)是否在过去12个月内(或注册人被要求提交此类报告的较短时间内)提交了1934年《证券交易法》第13条或15(D)节要求提交的所有报告，以及(2)在过去90天内是否符合此类提交要求。
用复选标记表示注册人是否在过去12个月内(或在注册人被要求提交此类文件的较短时间内)以电子方式提交了根据S-T规则第405条(本章232.405节)要求提交的每个交互数据文件。
用复选标记表示注册人是大型加速申报公司、加速申报公司、非加速申报公司、较小的报告公司或新兴成长型公司。请参阅《交易法》第12b-2条规则中“大型加速申报公司”、“加速申报公司”、“较小申报公司”和“新兴成长型公司”的定义。
大型加速文件服务器 |
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☐ |
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☒ |
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非加速文件服务器 |
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☐ |
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规模较小的报告公司 |
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新兴成长型公司 |
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如果是一家新兴的成长型公司，用复选标记表示注册人是否已选择不使用延长的过渡期来遵守根据《交易所法》第13(A)节提供的任何新的或修订的财务会计准则。☐
用复选标记表示注册人是否是空壳公司(如《交易法》第12b-2条所定义)。是，☐不是
截至2024年10月31日，登记人已
AMYLY PHARMACEUTICALS，Inc.
Form 10-Q季度报告
截至2024年9月30日的四分之一期
目录表
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页面 |
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第一部分： |
3 |
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第1项。 |
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第二项。 |
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第三项。 |
30 |
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第四项。 |
31 |
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第二部分。 |
其他信息 |
32 |
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第1项。 |
32 |
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第1A项。 |
32 |
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第二项。 |
91 |
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第三项。 |
91 |
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第四项。 |
91 |
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第五项。 |
91 |
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第六项。 |
92 |
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93 |
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我们可能会不时使用我们的网站或LinkedIn个人资料www.linkedin.com/company/amylyx来分发材料信息。我们的财务和其他材料信息定期发布到我们网站的投资者部分并在该部分访问，网址为www.amylyx.com。鼓励投资者查看我们网站的投资者部分，因为我们可能会在该网站上发布我们不会以其他方式传播的重要信息。包含在我们的网站或LinkedIn页面中并可以通过我们的网站或LinkedIn页面访问的信息不包含在本10-Q表格季度报告中，也不构成其一部分。
i
关于前瞻性陈述的特别说明
本10-Q表格季度报告或季度报告包含根据经修订的1933年证券法第27 A条或证券法的安全港条款和1934年证券交易法第21 E条（经修订）或交易法的前瞻性陈述。本季度报告中包含的历史事实陈述除外的所有陈述均为前瞻性陈述。在某些情况下，您可以通过“预期”、“相信”、“继续”、“可能”、“估计”、“预期”、“意图”、“可能”、“计划”、“潜力”、“预测”、“项目”、“应该”、“目标”、“将”或这些术语的否定或其他类似术语。这些陈述并不是对未来结果或绩效的保证，并且涉及巨大的风险和不确定性。本季度报告中的前瞻性陈述包括但不限于有关以下内容的明确或暗示陈述：
1
本季度报告中的任何前瞻性陈述反映了我们对未来事件和未来财务业绩的当前看法，并涉及已知和未知的风险、不确定性和其他因素，可能导致我们的实际结果、业绩或成就与这些前瞻性陈述所表达或暗示的任何未来结果、业绩或成就存在重大差异。可能导致实际结果与当前预期存在重大差异的因素包括标题为“风险因素”的部分和本季度报告其他地方所描述的因素。鉴于这些不确定性，您不应过度依赖这些前瞻性陈述。除法律要求外，我们没有义务以任何原因更新或修改这些前瞻性陈述，即使未来有新信息可用。
我们所有的前瞻性陈述仅限于本季度报告发布之日。在每一种情况下，实际结果都可能与这些前瞻性信息大不相同。我们不能保证这样的期望或前瞻性陈述将被证明是正确的。本季度报告中提及或包括在我们的其他公开披露或其他定期报告或其他文件或提交给美国证券交易委员会或美国证券交易委员会的其他文件或文件中提到的一个或多个风险因素或风险和不确定因素的发生或任何重大不利变化，可能会对我们的业务、前景、财务状况和运营结果产生重大不利影响。除法律另有要求外，我们不承诺或计划更新或修改任何此类前瞻性陈述，以反映本季度报告日期后发生的实际结果、计划、假设、估计或预测的变化或其他影响此类前瞻性陈述的情况，即使此类结果、变化或情况明确表示任何前瞻性信息将无法实现。我们在本季度报告之后发表的任何公开声明或披露，如果修改或影响本季度报告中包含的任何前瞻性陈述，将被视为修改或取代本季度报告中的此类陈述。
我们可能会不时提供有关我们的行业、一般商业环境和某些疾病的市场的估计、预测和其他信息，包括对这些市场的潜在规模和某些疾病的估计发病率和流行率的估计。基于估计、预测、预测、市场研究或类似方法的信息本身就会受到不确定因素的影响，实际事件、情况或数字，包括实际的疾病患病率和市场规模，可能与本季度报告中反映的信息大不相同。除非另有明确说明，否则我们从市场研究公司和其他第三方、行业、医疗和一般出版物、政府数据和类似来源准备的报告、研究调查、研究和类似数据中获得本行业、商业信息、市场数据、流行率信息和其他数据，在某些情况下应用我们自己的假设和分析，这些假设和分析在未来可能被证明不准确。
商标
仅为方便起见，本报告中提及我们的商标和商品名称时没有使用®和™符号，但此类提及不应被解释为任何表明我们不会根据适用法律最大限度地主张我们的权利。
2
第一部分-财务信息
项目1.财务报表
AMYLY PHARMACEUTICALS，Inc.
CONDENSED CONSOLIDATED BALANCE SHEETS
(以千为单位，不包括每股和每股数据)
(未经审计)
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2024年9月30日 |
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2023年12月31日 |
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资产 |
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流动资产： |
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现金及现金等价物 |
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有价证券 |
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应收账款净额 |
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库存 |
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— |
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预付费用和其他流动资产 |
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财产和设备，净额 |
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受限现金等价物 |
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经营性租赁使用权资产 |
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长期库存 |
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其他资产 |
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总资产 |
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$ |
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$ |
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负债与股东权益 |
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流动负债： |
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应付帐款 |
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$ |
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应计费用 |
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经营租赁负债，本期部分 |
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经营租赁负债，扣除当期部分 |
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股东权益： |
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优先股，$ |
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普通股，$ |
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额外实收资本 |
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累计赤字 |
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累计其他综合收益 |
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股东权益总额 |
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总负债和股东权益 |
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$ |
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$ |
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附注是这些未经审计的简明综合财务报表的组成部分。
3
AMYLY PHARMACEUTICALS，Inc.
简明合并业务报表
(in数千，份额和每股数据除外）
(未经审计)
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截至9月30日的三个月， |
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截至9月30日的9个月， |
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2024 |
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2023 |
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2024 |
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2023 |
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$ |
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$ |
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$ |
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$ |
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运营费用： |
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销售成本 |
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— |
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销售成本-库存减损和确定采购承诺损失 |
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— |
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— |
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收购正在进行的研究和开发 |
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— |
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— |
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研发 |
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销售、一般和行政 |
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重组费用 |
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— |
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总运营支出 |
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营业收入(亏损) |
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其他收入，净额： |
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利息收入 |
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其他费用，净额 |
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其他收入合计，净额 |
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所得税前收入(亏损) |
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所得税拨备 |
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净(亏损)收益 |
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每股净(亏损)收益 |
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基本信息 |
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$ |
( |
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$ |
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$ |
( |
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$ |
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稀释 |
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$ |
( |
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$ |
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$ |
( |
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$ |
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用于计算每股净（损失）收益的加权平均股份 |
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基本信息 |
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稀释 |
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附注是这些未经审计的简明综合财务报表的组成部分。
4
AMYLY PHARMACEUTICALS，Inc.
综合（损失）的浓缩综合报表）收入
(单位：千)
(未经审计)
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截至9月30日的三个月， |
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截至9月30日的9个月， |
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2024 |
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2023 |
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2024 |
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2023 |
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净(亏损)收益 |
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$ |
( |
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$ |
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$ |
( |
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$ |
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其他综合(亏损)收入 |
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外币折算收益(亏损) |
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( |
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可供出售证券的未实现净收益 |
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其他综合(亏损)收入 |
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( |
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( |
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综合(亏损)收益 |
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$ |
( |
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$ |
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$ |
( |
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$ |
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附注是这些未经审计的简明综合财务报表的组成部分。
5
AMYLY PHARMACEUTICALS，Inc.
简明合并股东权益报表
(单位：千，共享数据除外)
(未经审计)
|
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普通股 |
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其他内容 |
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累计 |
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累计 |
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总 |
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股份 |
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量 |
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资本 |
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收入(亏损) |
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赤字 |
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股权 |
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截至2023年12月31日的余额 |
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$ |
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$ |
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$ |
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$ |
( |
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$ |
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行使股票期权时发行普通股 |
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— |
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— |
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— |
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在归属RSU时发行普通股 |
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— |
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— |
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— |
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— |
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— |
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基于股票的补偿费用 |
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— |
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— |
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— |
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— |
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其他综合损失 |
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— |
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— |
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— |
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( |
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— |
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净亏损 |
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— |
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— |
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— |
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— |
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( |
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( |
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截至2024年3月31日余额 |
|
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$ |
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$ |
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$ |
( |
) |
|
$ |
( |
) |
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$ |
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行使股票期权时发行普通股 |
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— |
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— |
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— |
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在归属RSU时发行普通股 |
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— |
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— |
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— |
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— |
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— |
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基于股票的补偿费用 |
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— |
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— |
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— |
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— |
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其他综合损失 |
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— |
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— |
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— |
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( |
) |
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— |
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净亏损 |
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— |
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— |
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— |
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— |
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( |
) |
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( |
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截至2024年6月30日余额 |
|
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$ |
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$ |
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$ |
( |
) |
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$ |
( |
) |
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$ |
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行使股票期权后发行普通股 |
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— |
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— |
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— |
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在归属RSU时发行普通股 |
|
|
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
基于股票的补偿费用 |
|
|
— |
|
|
|
— |
|
|
|
|
|
|
— |
|
|
|
— |
|
|
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|
||
其他综合收益 |
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
|
|
|
— |
|
|
|
|
||
净亏损 |
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
( |
) |
|
|
( |
) |
截至2024年9月30日余额 |
|
|
|
|
$ |
|
|
$ |
|
|
$ |
|
|
$ |
( |
) |
|
$ |
|
|||||
|
|
普通股 |
|
|
其他内容 |
|
|
累计 |
|
|
累计 |
|
|
总 |
|
|||||||||
|
|
股份 |
|
|
量 |
|
|
资本 |
|
|
收入(亏损) |
|
|
赤字 |
|
|
股权 |
|
||||||
截至2022年12月31日的余额 |
|
|
|
|
$ |
|
|
$ |
|
|
$ |
( |
) |
|
$ |
( |
) |
|
$ |
|
||||
行使股票期权后发行普通股 |
|
|
|
|
|
— |
|
|
|
|
|
|
— |
|
|
|
— |
|
|
|
|
|||
在归属RSU时发行普通股 |
|
|
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
基于股票的补偿费用 |
|
|
— |
|
|
|
— |
|
|
|
|
|
|
— |
|
|
|
— |
|
|
|
|
||
其他综合收益 |
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
|
|
|
— |
|
|
|
|
||
净收入 |
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
|
|
|
|
||
截至2023年3月31日余额 |
|
|
|
|
$ |
|
|
$ |
|
|
$ |
|
|
$ |
( |
) |
|
$ |
|
|||||
行使股票期权后发行普通股 |
|
|
|
|
|
— |
|
|
|
|
|
|
— |
|
|
|
— |
|
|
|
|
|||
在归属RSU时发行普通股 |
|
|
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
基于股票的补偿费用 |
|
|
— |
|
|
|
— |
|
|
|
|
|
|
— |
|
|
|
— |
|
|
|
|
||
其他综合损失 |
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
( |
) |
|
|
— |
|
|
|
( |
) |
净收入 |
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
|
|
|
|
||
截至2023年6月30日的余额 |
|
$ |
|
|
$ |
|
|
$ |
|
|
$ |
( |
) |
|
$ |
( |
) |
|
$ |
|
||||
行使股票期权后发行普通股 |
|
|
|
|
|
— |
|
|
|
|
|
|
— |
|
|
|
— |
|
|
|
|
|||
在归属RSU时发行普通股 |
|
|
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
基于股票的补偿费用 |
|
|
— |
|
|
|
— |
|
|
|
|
|
|
— |
|
|
|
— |
|
|
|
|
||
其他综合损失 |
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
( |
) |
|
|
— |
|
|
|
( |
) |
净收入 |
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
|
|
|
|
||
截至2023年9月30日的余额 |
|
|
|
|
$ |
|
|
$ |
|
|
$ |
( |
) |
|
$ |
( |
) |
|
$ |
|
||||
附注是这些未经审计的简明综合财务报表的组成部分。
6
AMYLY PHARMACEUTICALS，Inc.
简明合并现金流量表
(单位：千)
(未经审计)
|
|
截至9月30日的9个月， |
|
|||||
|
|
2024 |
|
|
2023 |
|
||
经营活动中使用的现金流： |
|
|
|
|
|
|
||
净(亏损)收益 |
|
$ |
( |
) |
|
$ |
|
|
对净(亏损)收入与经营活动中使用的现金净额进行调整： |
|
|
|
|
|
|
||
基于股票的补偿费用 |
|
|
|
|
|
|
||
折旧费用 |
|
|
|
|
|
|
||
投资折扣的增加，净 |
|
|
( |
) |
|
|
( |
) |
库存减损和确定采购承诺损失 |
|
|
|
|
|
— |
|
|
购买IPR & D资产的费用 |
|
|
|
|
|
— |
|
|
其他非现金项目 |
|
|
|
|
|
— |
|
|
经营资产和负债变化： |
|
|
|
|
|
|
||
应收账款净额 |
|
|
|
|
|
( |
) |
|
库存 |
|
|
( |
) |
|
|
( |
) |
应收利息 |
|
|
|
|
|
|
||
预付费用和其他流动资产 |
|
|
|
|
|
( |
) |
|
经营性租赁使用权资产 |
|
|
|
|
|
|
||
其他资产 |
|
|
|
|
|
( |
) |
|
应付帐款 |
|
|
( |
) |
|
|
|
|
应计费用 |
|
|
( |
) |
|
|
|
|
经营租赁负债 |
|
|
( |
) |
|
|
( |
) |
用于经营活动的现金净额 |
|
|
( |
) |
|
|
( |
) |
投资活动提供的现金流： |
|
|
|
|
|
|
||
购置财产和设备 |
|
|
( |
) |
|
|
( |
) |
购买IPR & D资产，包括交易成本 |
|
|
( |
) |
|
|
— |
|
购买投资 |
|
|
( |
) |
|
|
( |
) |
有价证券到期日收益 |
|
|
|
|
|
|
||
投资活动提供的现金净额 |
|
|
|
|
|
|
||
融资活动提供的现金流： |
|
|
|
|
|
|
||
支付后续发行费用 |
|
|
— |
|
|
|
( |
) |
行使股票期权和受限制股份单位归属的收益 |
|
|
|
|
|
|
||
对股票奖励支付的预扣税 |
|
|
( |
) |
|
|
( |
) |
融资活动提供的现金净额 |
|
|
|
|
|
|
||
汇率变化对现金、现金等值物和受限制现金等值物的影响 |
|
|
|
|
|
( |
) |
|
现金、现金等值物和限制性现金等值物净（减少）增加 |
|
|
( |
) |
|
|
|
|
现金、现金等值物和受限制现金等值物，期末 |
|
|
|
|
|
|
||
现金、现金等值物和受限制现金等值物，期末 |
|
$ |
|
|
$ |
|
||
现金、现金等值物和受限制现金等值物的对账： |
|
|
|
|
|
|
||
现金及现金等价物 |
|
$ |
|
|
$ |
|
||
受限现金等价物 |
|
|
|
|
|
|
||
现金、现金等值物和受限制现金等值物总额： |
|
$ |
|
|
$ |
|
||
补充披露现金流量信息： |
|
|
|
|
|
|
||
有价证券的未实现收益 |
|
$ |
|
|
$ |
|
||
对计入应计费用的股票奖励预扣税 |
|
$ |
|
|
$ |
|
||
应付账款中所列财产和设备的购置 |
|
$ |
— |
|
|
$ |
|
|
已缴纳的所得税 |
|
$ |
|
|
$ |
|
||
附注是这些未经审计的简明综合财务报表的组成部分。
7
AMYLY PHARMACEUTICALS，Inc.
公司简明综合财务报表附注
(未经审计)
1.业务性质
Amylyx制药公司及其全资子公司Amylyx或公司是一家生物技术公司，致力于为有高度未得到满足的需求的社区发现和开发新的治疗方案，包括患有严重和致命的神经退行性疾病和内分泌疾病的人。
2024年7月9日，Amylyx完成了对avexitide的收购，用于潜在治疗内分泌系统疾病--高胰岛素低血糖。Avexitide是一种研究中的、一流的胰高血糖素样肽-1或GLP-1受体拮抗剂，已在五项临床试验中进行了减肥后低血糖(PBH)的评估，并已用于先天性高胰岛素血症(HI)的研究，这两种适应症的特点是高胰岛素低血糖。美国食品和药物管理局(FDA)已批准这两种适应症的Avexitide突破性治疗指定，先天性HI罕见儿科疾病的指定，以及治疗高胰岛素低血糖(包括PBH和先天性HI)的孤儿药物指定。Amylyx预计将于2025年第一季度开始PBH中avexitide的第三阶段计划。
该公司还在研究由Amylyx开发的AMX0035在神经退行性疾病和内分泌疾病中的作用，这些疾病涉及内质网(ER)、应激和线粒体功能障碍，包括进行性核上性瘫痪(PSP)和Wolfram综合征。
2024年4月，该公司宣布，它已与FDA和加拿大卫生部启动程序，自愿终止RELYVRIO和ALBRIOZA(AMX0035)对ALS的营销授权，并根据全球第三阶段菲尼克斯试验的TOPLINE结果将该产品从市场上移除，该试验不符合其预先指定的主要和次要终点。Amylyx按计划结束了Open Label的扩展。该公司将继续分享从菲尼克斯学到的经验，帮助为未来的肌萎缩侧索硬化症研究提供信息。
风险和不确定性
该公司会受到生物技术行业公司常见的风险和不确定因素的影响，这些风险和不确定因素包括但不限于：临床前研究和临床试验的结果；监管审批程序在时间上的潜在困难或延误；竞争对手开发新技术创新的可能性；对关键人员的依赖；对专有技术的保护；对政府法规的遵守；获得额外资金以资助运营的能力；以及与地缘政治不稳定和冲突导致的全球不同市场的经济不确定性造成的经济挑战相关的风险。该公司及其承包商可能会遇到对其研发活动至关重要的项目的供应中断，例如，该公司从欧洲和加拿大进口的用于制造AMX0035、Avexitide和任何其他或未来候选产品的原材料和散装药物物质.
8
2.主要会计政策摘要
重大会计政策
公司的重要会计政策在截至2023年12月31日的年度经审计的综合财务报表及其附注中披露，这些报表包括在公司最新的10-k表格年度报告中。除下文所述外，自该等综合财务报表编制之日起，其主要会计政策并无重大变动。
列报和合并的基础
随附的简明综合财务报表未经审计，并按照美国公认会计原则或公认会计原则编制，其中包括本公司及其全资子公司的账目。所有公司间余额和交易均已在合并中冲销。公司管理层认为，为实现公平列报所需的所有正常和经常性调整都已得到反映。本说明中对适用指导的任何提及均指在财务会计准则委员会(FASB)的ASC和会计准则更新(ASU)中找到的权威GAAP。
预算的使用
企业合并和资产收购
本公司评估收购资产及其他类似交易，以评估交易是否应计入业务合并或资产收购，方法是首先应用筛选测试，以确定所收购总资产的公允价值是否基本上全部集中于单一可识别资产或一组类似可识别资产。如果符合筛选测试，该交易将作为资产收购入账。如果不符合筛选测试，则需要进一步确定公司是否已获得能够创建满足业务要求的输出的输入和流程。如果被确定为资产收购，本公司将根据美国会计准则第805-50条对交易进行会计处理，该条款要求资产收购中的收购实体根据收购实体的成本按相对公允价值确认收购的资产和承担的负债，该相对公允价值除给予对价外还包括交易成本。商誉不在资产收购中确认，任何超过收购净资产公允价值的额外对价均按相对公允价值分配给可识别资产。进行中研发或IPR&D，指未来无其他用途的项目，于收购时记入研发开支，而与资产收购有关而产生的或有对价责任，则于有可能发生且可合理估计时，予以记录。
尚未采用的新会计公告
2023年12月，FASB发布了ASU 2023-09号，所得税(专题740)：改进所得税披露，或ASU 2023-09，以提高所得税披露的透明度和决策有用性。ASU 2023-09在预期的基础上，从2024年12月15日之后的年度期间生效。允许及早采用和追溯应用。该公司目前正在评估这一ASU对其合并财务报表和相关披露的影响。
2023年11月，FASB发布了ASU 2023-07号，分部报告(主题280)：改进可报告分部披露，或ASU 2023-09，要求公共实体披露其可报告部门的中期和年度重大支出信息。ASU 2023-07从截至2024年12月31日的年度开始对公司有效。该公司目前正在评估这一ASU对其合并财务报表和相关披露的影响。
9
3.产品收入净额
到目前为止，该公司产品收入的唯一来源是销售RELYVRIO，在加拿大被称为ALBRIOZA。考虑到历史经验、付款人渠道组合(例如，Medicare或Medicaid)、适用计划下的当前合同价格、未开账单的索赔和处理时间延迟以及分销渠道中的库存水平，在估计毛净比或GTN调整时需要做出重大判断。2024年4月，该公司宣布已与FDA和加拿大卫生部启动一项程序，以自愿终止RELYVRIO®/ALBRIOZA™的营销授权，并根据第三阶段凤凰试验的TOPLINE结果将该产品从美国和加拿大的市场上移除。结果，该公司做到了
|
|
截至9月30日的三个月， |
|
|
截至9月30日的9个月， |
|
||||||||||
|
|
2024 |
|
|
2023 |
|
|
2024 |
|
|
2023 |
|
||||
产品收入，毛收入 |
|
$ |
— |
|
|
$ |
|
|
$ |
|
|
$ |
|
|||
GTN调整 |
|
|
|
|
|
( |
) |
|
|
( |
) |
|
|
( |
) |
|
产品收入，净额 |
|
$ |
|
|
$ |
|
|
$ |
|
|
$ |
|
||||
GTN调整的活动和期末准备金余额如下截至2024年9月30日和2023年9月30日的9个月(单位：千)：
|
|
按存储容量使用计费和现金折扣 |
|
|
医疗补助和医疗保险回扣 |
|
|
其他回扣、退货、折扣和调整 |
|
|
总 |
|
||||
截至2023年12月31日的期末余额 |
|
$ |
|
|
$ |
|
|
$ |
|
|
$ |
|
||||
与本年度销售有关的拨备 |
|
|
|
|
|
|
|
|
|
|
|
|
||||
与前期销售相关的调整 |
|
|
( |
) |
|
|
— |
|
|
|
( |
) |
|
|
( |
) |
贷方和付款 |
|
|
( |
) |
|
|
( |
) |
|
|
( |
) |
|
|
( |
) |
截至2024年9月30日的期末余额 |
|
$ |
— |
|
|
$ |
|
|
$ |
|
|
$ |
|
|||
|
|
按存储容量使用计费和现金折扣 |
|
|
医疗补助和医疗保险回扣 |
|
|
其他回扣、退货、折扣和调整 |
|
|
总 |
|
||||
截至2022年12月31日的期末余额 |
|
$ |
|
|
$ |
|
|
$ |
|
|
$ |
|
||||
与本年度销售有关的拨备 |
|
|
|
|
|
|
|
|
|
|
|
|
||||
与前期销售相关的调整 |
|
|
— |
|
|
|
( |
) |
|
|
( |
) |
|
|
( |
) |
贷方和付款 |
|
|
( |
) |
|
|
( |
) |
|
|
( |
) |
|
|
( |
) |
截至2023年9月30日的期末余额 |
|
$ |
|
|
$ |
|
|
$ |
|
|
$ |
|
||||
GTN调整的期末准备金余额包括因合同承诺以低于向直接从本公司购买产品的客户收取的标价向合格医疗保健提供商销售产品而产生的退款、向客户及时付款的折扣以及对产品退货的估计。扣款、贴现和退回被记录为应收账款的减少，只要有应收账款余额需要减少，就会在简明的综合资产负债表上净额。如果有欠客户的净余额，则在简明综合资产负债表中作为应计费用的一部分入账。此外，GTN调整的期末准备金余额包括医疗补助和医疗保险回扣、自愿患者援助计划下义务的其他回扣，以及应向客户支付的应计费用。医疗补助和医疗保险回扣、其他回扣和费用在简明合并资产负债表上作为应计费用的一部分记录。
4.有价证券
公司已于2024年9月30日对其所有有价证券进行分类 作为“可供出售”。公司按公允价值记录可供出售证券，未实现损益作为其他累计全面收益（亏损）的单独组成部分。有
该公司调整可供出售债务证券的成本，以满足溢价摊销和到期折扣的增加。该摊销和增值计入利息收入。出售证券的成本基于具体
10
识别方法。公司将分类为可供出售证券的利息和股息计入利息收入。与公司可供出售证券相关的应计应收利息在随附的简明综合资产负债表中的预付费用和其他流动资产中列示，金额为 低于$
截至2024年9月30日，有几个
分类为可供出售的有价证券包括以下内容（以千计）：
2024年9月30日余额： |
|
摊销 |
|
|
未实现 |
|
|
未实现 |
|
|
公平 |
|
||||
国库券 |
|
$ |
|
|
$ |
|
|
$ |
— |
|
|
$ |
|
|||
有价证券总额 |
|
$ |
|
|
$ |
|
|
$ |
— |
|
|
$ |
|
|||
于二零二三年十二月三十一日之结余： |
|
摊销 |
|
|
未实现 |
|
|
未实现 |
|
|
公平 |
|
||||
国库券 |
|
$ |
|
|
$ |
|
|
$ |
— |
|
|
$ |
|
|||
美国机构债券 |
|
|
|
|
|
— |
|
|
|
( |
) |
|
|
|
||
有价证券总额 |
|
$ |
|
|
$ |
|
|
$ |
( |
) |
|
$ |
|
|||
5.库存
库存包括以下内容（以千计）：
|
|
2024年9月30日 |
|
|
2023年12月31日 |
|
||
原料 |
|
$ |
— |
|
|
$ |
|
|
Oracle Work in Process |
|
|
— |
|
|
|
|
|
成品 |
|
|
— |
|
|
|
|
|
总库存 |
|
$ |
— |
|
|
$ |
|
|
2024年4月，该公司宣布已与FDA和加拿大卫生部启动一项程序，自愿终止RELY VRIO的上市授权®/ALBRIOZA™并根据全球第3阶段PHOENIX试验的总体结果将该产品从美国和加拿大的市场上撤下。因此，公司记录了约 $
6.应计费用
应计费用包括以下各项(以千计)：
|
|
2024年9月30日 |
|
|
2023年12月31日 |
|
||
应计外部研究和开发 |
|
$ |
|
|
$ |
|
||
应计福利和激励薪酬 |
|
|
|
|
|
|
||
应计制造业 |
|
|
|
|
|
|
||
应计咨询和其他专业费用 |
|
|
|
|
|
|
||
应计回报、回扣和自付援助 |
|
|
|
|
|
|
||
应计版税 |
|
|
— |
|
|
|
|
|
未来购买承诺的应计损失 |
|
|
|
|
|
— |
|
|
其他应计费用 |
|
|
|
|
|
|
||
应计费用总额 |
|
$ |
|
|
$ |
|
||
11
7.公平值计量
下表列出了有关公司按经常性公允价值计量的金融资产和负债的信息，并指出了用于确定此类公允价值的公允价值层级的级别（以千计）：
|
|
2024年9月30日 |
|
|||||||||||||
|
|
1级 |
|
|
2级 |
|
|
3级 |
|
|
总 |
|
||||
资产： |
|
|
|
|
|
|
|
|
|
|
|
|
||||
现金等价物 |
|
$ |
|
|
$ |
— |
|
|
$ |
— |
|
|
$ |
|
||
有价证券： |
|
|
|
|
|
|
|
|
|
|
|
|
||||
国库券 |
|
|
|
|
|
— |
|
|
|
— |
|
|
|
|
||
有价证券总额 |
|
|
|
|
|
— |
|
|
|
— |
|
|
|
|
||
受限现金等价物 |
|
|
|
|
|
— |
|
|
|
— |
|
|
|
|
||
金融资产总额 |
|
$ |
|
|
$ |
— |
|
|
$ |
— |
|
|
$ |
|
||
|
|
2023年12月31日 |
|
|||||||||||||
|
|
1级 |
|
|
2级 |
|
|
3级 |
|
|
总 |
|
||||
资产： |
|
|
|
|
|
|
|
|
|
|
|
|
||||
现金等价物 |
|
$ |
|
|
$ |
— |
|
|
$ |
— |
|
|
$ |
|
||
有价证券： |
|
|
|
|
|
|
|
|
|
|
|
|
||||
国库券 |
|
|
|
|
|
— |
|
|
|
— |
|
|
|
|
||
美国机构债券 |
|
|
— |
|
|
|
|
|
|
— |
|
|
|
|
||
有价证券总额 |
|
|
|
|
|
|
|
|
— |
|
|
|
|
|||
受限现金等价物 |
|
|
|
|
|
— |
|
|
|
— |
|
|
|
|
||
金融资产总额 |
|
$ |
|
|
$ |
|
|
$ |
— |
|
|
$ |
|
|||
该公司将其货币市场基金和国库券归类为公允价值等级下的一级资产，因为这些资产是使用活跃市场相同资产的市场报价进行估值的，没有进行任何估值调整。该公司将其美国机构债券归类为公允价值层级下的第2级资产，因为这些资产是使用每个资产负债表日通过第三方定价服务获得的信息进行估值的，使用类似资产的可观察市场输入，其中可能包括贸易信息、经纪人或交易商报价、出价、报价或这些数据源的组合.
8.股票期权和授予计划
股票激励计划
一般选项信息
期权活动摘要 截至2024年9月30日的九个月如下：
|
|
数量 |
|
|
加权的- |
|
|
加权的- |
|
|
集料 |
|
||||
截至2023年12月31日的未偿还债务 |
|
|
|
|
$ |
|
|
|
|
|
$ |
|
||||
授与 |
|
|
|
|
$ |
|
|
|
|
|
|
|
||||
已锻炼 |
|
|
( |
) |
|
$ |
|
|
|
|
|
$ |
|
|||
取消或没收 |
|
|
( |
) |
|
$ |
|
|
|
|
|
|
|
|||
截至2024年9月30日未完成 |
|
|
|
|
$ |
|
|
|
|
|
$ |
|
||||
截至2024年9月30日可行使的期权 |
|
|
|
|
$ |
|
|
|
|
|
$ |
|
||||
截至2024年9月30日未归属的期权 |
|
|
|
|
$ |
|
|
|
|
|
$ |
|
||||
期内授予期权的加权平均授予日公允价值 |
|
$ |
|
|
|
|
|
|
|
|
|
|
||||
截至2024年9月30日和2023年9月30日止九个月期间行使的期权的总内在价值为 $
截至2024年9月30日和2023年9月30日止九个月内归属的股票期权的总公允价值为 $
12
限制性股票单位活动
受限制股票单位活动摘要 截至2024年9月30日的九个月如下：
|
|
股份数量 |
|
|
加权平均授予日期公允价值 |
|
||
截至2023年12月31日未归属 |
|
|
|
|
$ |
|
||
授与 |
|
|
|
|
$ |
|
||
既得 |
|
|
( |
) |
|
$ |
|
|
被没收 |
|
|
( |
) |
|
$ |
|
|
截至2024年9月30日未归属 |
|
|
|
|
$ |
|
||
股票补偿发票摘要
|
|
截至9月30日的三个月， |
|
|
截至9月30日的9个月， |
|
||||||||||
|
|
2024 |
|
|
2023 |
|
|
2024 |
|
|
2023 |
|
||||
研发 |
|
$ |
|
|
$ |
|
|
$ |
|
|
$ |
|
||||
销售、一般和行政 |
|
|
|
|
|
|
|
|
|
|
|
|
||||
基于股票的薪酬总支出 |
|
$ |
|
|
$ |
|
|
$ |
|
|
$ |
|
||||
下表总结了截至 2024年9月30日，按奖励类型（单位：千）以及预计确认该费用的加权平均期（单位：年）。未确认的基于股票的补偿费用总额将根据实际没收进行调整。
|
|
2024年9月30日 |
|
|||||
|
|
未确认费用 |
|
|
加权平均认可期 |
|
||
股票期权 |
|
$ |
|
|
|
|
||
限制性股票单位 |
|
$ |
|
|
|
|
||
9.每股净（损失）收入
每股净（损失）收益
每股基本收益是通过净利润（亏损）除以本期已发行普通股的加权平均数计算的。每股稀释收益是根据普通股和潜在稀释性股票的合并加权平均数计算的，其中包括假设的员工股票期权和未归属的限制性股票单位的行使。在计算稀释每股收益时，公司采用库存股法。
13
计算每股收益时使用的分子和分母摘要如下(以千为单位，股票和每股数据除外)：
|
|
截至9月30日的三个月， |
|
|
截至9月30日的9个月， |
|
||||||||||
|
|
2024 |
|
|
2023 |
|
|
2024 |
|
|
2023 |
|
||||
分子： |
|
|
|
|
|
|
|
|
|
|
|
|
||||
净(亏损)收益 |
|
$ |
( |
) |
|
$ |
|
|
$ |
( |
) |
|
$ |
|
||
分母： |
|
|
|
|
|
|
|
|
|
|
|
|
||||
用于计算每股基本净(亏损)收益的加权平均股数 |
|
|
|
|
|
|
|
|
|
|
|
|
||||
员工股票期权和限制性股票单位的稀释效应 |
|
|
— |
|
|
|
|
|
|
— |
|
|
|
|
||
加权平均-用于计算每股摊薄净(亏损)收益的股票 |
|
|
|
|
|
|
|
|
|
|
|
|
||||
每股净(亏损)收益 |
|
|
|
|
|
|
|
|
|
|
|
|
||||
基本信息 |
|
$ |
( |
) |
|
$ |
|
|
$ |
( |
) |
|
$ |
|
||
稀释 |
|
$ |
( |
) |
|
$ |
|
|
$ |
( |
) |
|
$ |
|
||
由于该公司报告了截至2024年9月30日的三个月和九个月的净亏损，普通股股东的基本净亏损和稀释后每股净亏损是相同的。所有股票期权和限制性股票单位都被排除在稀释加权平均流通股的计算之外，因为这些证券将对截至2024年9月30日的三个月和九个月产生反稀释影响。.
|
|
截至9月30日的三个月， |
|
|
截至9月30日的9个月， |
|
||||||||||
|
|
2024 |
|
|
2023 |
|
|
2024 |
|
|
2023 |
|
||||
购买普通股的期权 |
|
|
|
|
|
|
|
|
|
|
|
|
||||
限制性股票单位 |
|
|
|
|
|
|
|
|
|
|
|
|
||||
排除在外的普通股总等价物 |
|
|
|
|
|
|
|
|
|
|
|
|
||||
10.收购
2024年7月9日，该公司完成了对艾格生物制药公司(简称Eiger)开发、制造和商业化Avexitide的几乎所有资产和权益的收购，价格为1美元
由于所获得的资产不符合企业的定义，这笔交易被记为资产购置。该公司没有收购任何产出，也没有收购的实质性程序来创造产出。购买总对价为$
在收购完成时，公允价值已分配给知识产权研发资产，这些资产未来没有其他用途。因此，该公司记录了#美元的费用。
作为交易的一部分，公司承担了Eiger的某些合同义务，包括
14
11.承付款和或有事项
信用证
受限现金等价物包括#美元
法律诉讼
2024年2月9日，美国纽约南区地区法院对该公司及其某些现任和前任高级管理人员(Shih诉Amylyx制药公司等人案。，案件编号1：24-CV-00988，或施正荣投诉)。原告于2024年6月24日提交了修改后的起诉书。施正荣的起诉书就所有被告涉嫌违反交易所法案第10(B)节及其颁布的第100亿.5条，以及根据第20(A)条向若干现任及前任高级人员提出被指为控制人的申索。施正荣的起诉书称，被告就RELYVRIO的商业结果和前景做出了重大虚假和误导性陈述。施正荣的诉状要求未指明的损害赔偿、利息、费用和律师费，以及法院认为适当的其他未指明的救济。
2024年8月12日，该案从美国纽约南区地区法院移交给美国马萨诸塞州地区法院，并分配了1：24-CV-12068的案卷编号。移交后，2024年9月6日，被告采取行动驳回施正荣的申诉。原告于2024年10月21日提出反对被告的驳回动议，被告的答辩截止日期为2024年11月20日或之前。该公司打算对施正荣的投诉进行有力的辩护。目前，无法估计施正荣投诉中的索赔的影响(如果有的话)。
专利权使用费支付
2016年8月至2019年2月，本公司与ALS协会、ALS Finding a Cure Foundation、阿尔茨海默氏症药物发现基金会、阿尔茨海默氏症协会和治愈阿尔茨海默氏症基金会或授权者签订了赠款协议。根据公司、阿尔茨海默氏症药物发现基金会、阿尔茨海默氏症协会和治疗阿尔茨海默氏症基金之间的各自赠款协议的条款，公司将支付最高金额为$
如附注10所披露收购，该公司承担了版税义务 来自艾格的收购与Avexitide有关。由于根据协议将触发特许权使用费支付的条件尚未出现，
购买承诺
本公司在正常业务过程中与合同制造组织就原材料采购和制造服务订立协议。截至2024年9月30日，该公司约有$
该公司确认了以下购买承诺的亏损$
设施租赁
15
12.结构调整
2024年4月，该公司宣布了一项重组计划，旨在将公司的资源集中在关键的临床和临床前项目上，即重组计划。重组计划包括裁员，该计划将公司的员工人数减少了约
重组费用主要包括员工遣散费和解雇福利、合同终止成本、长期资产减值和其他成本。与重组活动相关的成本负债在发生负债时确认，并按公允价值计量。根据ASC 420，退出或处置费用债务一次性员工遣散费和解雇福利在实体通知员工计划之日支出，除非员工必须提供未来服务，在这种情况下，福利在服务结束时支出。一次性解雇福利主要包括遣散费、继续医疗保险覆盖范围以及其他福利，如在指定时间段内的再就业支持服务。
关于重组计划，本公司对其长期资产进行减值评估，导致减值费用为$
重组支出 截至2024年9月30日的三个月情况如下(单位：千)：
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遣散费和员工福利成本 |
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合同终止费用、资产减值和其他费用 |
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截至2024年9月30日，与此重组活动相关的所有应计成本均已支付.
13.后续活动
该公司考虑在资产负债表日期之后但在财务报表发布之前发生的事件或交易，以提供与某些估计有关的额外证据，或确定需要额外披露的事项。本公司已对2024年9月30日之后至本申请日期的所有后续事件进行了评估，除以下描述外，没有重大后续事件需要披露：
2024年10月2日，美国马萨诸塞州地区法院向美国马萨诸塞州地区法院提起衍生品诉讼，指控某些现任和前任董事和高级职员被告，将该公司列为名义被告(琼斯诉科恩等人案.、1：24-CV-12527或衍生产品投诉)。这些实质性指控与施正荣的指控如出一辙，但也包括涉嫌违反《交易所法》第14(A)条、违反受托责任、内幕交易和不当得利的指控。衍生品诉讼要求向该公司支付未指明的损害赔偿金，以及利息、费用和律师费、恢复原状、未指明的公司治理以及内部程序改革和改进。2024年10月31日，法院下令暂停诉讼，直至有偏见地驳回施正荣的申诉，包括用尽所有上诉，或被告对施正荣的申诉提出答复。公司打算对衍生品投诉进行有力的抗辩。目前，无法估计衍生品起诉书中提出的索赔的影响(如果有的话)。
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项目2.管理层对财务状况和经营结果的讨论和分析.
以下信息应与本季度报告其他地方出现的简明合并财务信息及其注释一起阅读。
本讨论和本季度报告的其他部分包含涉及风险和不确定性的前瞻性陈述，例如我们的计划、目标、预期和意图的陈述。由于许多因素，包括我们最近的10-k表格年度报告或2023年年度报告以及随后的季度报告中列出的风险因素，我们的实际结果可能与以下讨论和分析中所述或暗示的结果存在重大差异。前瞻性陈述包含。
概述
我们是一家生物技术公司，致力于为需求未满足的社区（包括患有严重和致命疾病的人）发现和开发新的治疗选择。我们正在进行神经退行性疾病和内分泌疾病的临床前和临床开发项目。我们的项目管道包括用于治疗高胰岛素血症性低血糖的阿维西肽、用于治疗沃尔夫勒姆综合征的AMX 0035、用于治疗进行性核上性麻痹（PSP）的AMX 0035以及AMX 0114（我们的靶向钙蛋白酶-2的用于治疗肌萎缩性侧索硬化症（ALS））的反作用寡核苷酸AMX 0114。
Avexitide是一种研究中的一流高血糖素样多肽-1或GLP-1受体拮抗剂，已在五项临床试验中进行了减肥后低血糖(PBH)的评估，并已用于先天性高胰岛素血症(HI)的研究，这两种适应症的特点是高胰岛素低血糖。美国食品和药物管理局(FDA)已批准这两种适应症的Avexitide突破性治疗指定，先天性HI罕见儿科疾病的指定，以及治疗高胰岛素低血糖(包括PBH和先天性HI)的孤儿药物指定。Avexitide旨在与胰岛β细胞上的GLP-1受体结合，并阻断GLP-1通过减少胰岛素分泌和稳定血糖水平来缓解低血糖的作用。在PBH中，过量的GLP-1可能会导致胰岛素的过度分泌和随后的严重低血糖事件，包括自主神经和神经降糖症状，如果不加以解决，这一适应症在美国约有160,000人受到影响。Avexitide总体上耐受性良好，在PBH患者的五项临床试验中重复了良好的安全性。
在之前的PBH II期和20亿期研究中，阿维西肽显示，以低血糖为特征的低血糖事件（包括需要帮助的精神和/或身体功能改变的严重低血糖事件）在统计学上显着减少。FDA糖尿病行业指南，结合针对阿维西肽治疗PBH关键3期项目的FDA初步反馈，表明低血糖事件的减少可能是支持关键3期临床试验取得积极结果后批准的终点。我们预计将于2025年第一季度在PBH开始阿维西肽的第三阶段项目，预计2026年将公布顶线数据。我们正在积极与更广泛的先天性HI群体进行讨论，以开辟前进的道路。
AMX0035是一种特殊配方的口服固定剂量苯丁酸钠(Pb)和牛磺酸二醇(Turso)的组合，开发用于治疗广泛的神经退行性疾病。AMX0035是由Amylyx开发的，旨在通过同时靶向内质网(ER)、应激和线粒体功能障碍来缓解神经变性，这两条相互连接的中枢通路导致细胞死亡和神经变性。我们已经在多个模型中表明，AMX0035可以在各种不同的条件和压力下保持神经元的存活。这些条件包括体外培养神经退行性变、内质网应激、线粒体功能障碍、氧化应激和各种其他疾病特有模型，以及体内在临床试验中，AMX0035在ALS、Wolfram综合征、阿尔茨海默病或多发性硬化症或多发性硬化症的模型中已经显示出降低与神经退行性疾病相关的标记物的能力，包括分别降低tau和YKL-40的能力，tau是几种神经退行性疾病共有的关键蛋白质聚集体，YKL-40是神经炎症的标志。
AMX 0035的安全性特征已在临床试验和上市后监测中得到充分证实。数千名成年人已接受AMX 0035治疗，无论是通过针对多种神经退行性疾病的临床试验还是在批准后环境中。AMX 0035总体耐受性良好，最常见的不良反应是胃肠道副作用（例如腹泻、恶心、排便、食欲下降、腹痛、胀气），更常见于治疗的前3周，并且通常不严重。AMX 0035的获益风险平衡仍然有利于正在进行的临床开发项目。
我们正在研究AMX 0035在涉及ER应激和线粒体功能障碍的神经退行性疾病和内分泌疾病中的作用，包括PSP和Wolfram综合征。
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Wolfram综合征是一种罕见的进行性单基因疾病，由WFS 1基因突变引起，导致ER应激和线粒体功能障碍，导致多器官细胞功能障碍和死亡。我们相信Wolfram综合征影响了美国约3，000人。圣路易斯华盛顿大学医学院的研究人员与Amylyx合作，发布了临床前数据，探索AMX 0035作为Wolfram综合征新型治疗方法的潜力同行评审 临床调查洞察杂志.这些数据表明，AMX 0035能够抑制ER压力和线粒体功能障碍对受WFS1突变影响的患者源β细胞和神经元的影响，从而可能稳定并在某些情况下改善细胞功能和活力。Amylyx宣布，FDA于2020年11月授予AMX 0035治疗Wolfram综合征的孤儿药称号。
2024年10月17日，我们宣布了HELIOS试验的阳性背线数据，这是一项正在进行的开放标签第二阶段研究，旨在评估AMX0035是否减缓Wolfram综合征患者的糖尿病、视力和其他指标的进展，并评估安全性和耐受性。在接受AMX0035(该研究的主要疗效终点)治疗24周后，根据C-肽反应来衡量，Helios显示出胰腺功能的改善，这与随着疾病进展而预期的胰腺功能下降形成对比。所有次级终点都观察到类似的总体改善或稳定，包括血红蛋白A1c(HbA1c)、通过持续血糖监测评估的目标血糖范围的时间和视力。患者和医生报告的全球变化印象显示，所有参与者的疾病稳定或改善，满足预先指定的应答者标准。此外，完成第36周(n=10)和第48周(n=6)评估的所有参与者的长期数据显示，随着时间的推移，持续改善。执行的分析包括所有12名参与者的第24周数据，以及截至数据截止点完成第36周(n=10)和第48周(n=6)评估的所有参与者的数据。
HEIOS显示其主要终点C-肽反应有所改善，从基线到第24周120分钟时变化为+3.8分钟 *ng/mL（min*ng/mL）[标准误（SE）：19.3]意向治疗组（N=12）和+20.2分钟 *ng/mL [SE：11.2]符合方案组（N=11）。此外，如下表所述，通过葡萄糖代谢标志物测量，接受AMX 0035的参与者的血糖控制得到了改善;通过斯内伦图表测量，一些参与者的视敏度得到了改善;通过临床医生报告的总体印象变化（CGIC）和患者报告的总体印象变化（PGIC）测量，疾病得到了改善或稳定。
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第24周 |
第24周 |
第36周 |
第48周 |
C-肽反应 |
+3.8 |
+20.2 |
+30.7 |
+36.7 |
血红蛋白A1 c（%） |
-0.09 |
-0.16 |
-0.35 |
-0.30 |
目标葡萄糖的绝对时间 |
+5.2 |
+5.7 |
+12.3 |
+5.8 |
平均外来胰岛素剂量 |
-0.01 |
-0.01 |
0.01 |
0.02 |
视觉敏锐度（LogTAR） |
-0.04 |
-0.04 |
此处未收集 |
-0.11 |
全球临床医生报告 |
100% |
100% |
100% |
100% |
全球报告患者 |
100% |
100% |
100% |
100% |
†经过基因审查，一名参与者不符合HEIOS的入选/排除标准。该参与者被发现患有常染色体隐性突变，该突变被证实仅对两个基因中的一个具有致病性，而对另一个基因具有不确定意义的变异。该参与者的C肽、血糖指标和视力在正常范围内，表明缺乏典型的沃尔夫勒姆综合征表型。提供了与该参与者一起或不包括该参与者的数据（分别为意向治疗和符合方案）。
†在非糖尿病患者中，C-肽在餐后约30分钟达到峰值;在Wolfram综合征中，峰值速度较慢，但在HelIOS中，峰值通常在120分钟或之前。膳食激发后120分钟内的曲线下面积（AUR）反映了β细胞对膳食的反应。Amylyx目前计划将120分钟的曲线下面积作为未来研究的C肽指标。
† ððSES将CGIC和PGIC的“响应者”定义为考虑到Wolfram综合征的进展性，没有变化或改善。
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该试验的主要疗效终点衡量C-肽较基线的变化，C-肽是胰腺β细胞功能和血糖控制的既定客观实验室指标，在第24周使用混合餐耐量测试进行评估。次要和探索性结果包括测量其他糖尿病反应和受疾病影响的其他领域。AMX 0035的安全性特征与在该药物已广泛研究的其他人群中观察到的安全性特征一致。我们正在与包括FDA在内的利益相关者接触，并计划进行一项3期临床试验，并将在最终确定后分享有关临床试验设计的更多细节。
我们正在追逐AMX0035基于AMX002‘S的PSP治疗机制，临床前数据，以及在AMX0035在AD中的飞马2期试验中看到的tau减少。这些数据发表在同行评议的医学杂志上阿尔茨海默病与痴呆：翻译研究与临床干预，阿尔茨海默氏症协会的期刊，在2024年8月。PSP是一种罕见的神经退行性疾病，影响身体运动、行走、平衡和眼睛运动，其特征是广泛的神经退行性病变，与大脑皮质下区域的tau蛋白沉积有关。基于 在体外，在体内临床数据，AMX0035可能会影响tau病理，这是PSP患者的一个关键标志。遗传证据表明，PSP的一个危险因素可能是大脑受疾病影响的区域激活的未折叠蛋白质反应。PB可以上调和招募伴侣蛋白，稳定蛋白质折叠，减少内质网应激和未折叠的蛋白质反应，而Turso则被证明抑制代谢应激诱导的tau磷酸化。除了分别关于铅和图索的临床前数据外，铅和图索的组合在靶向神经变性的标志性途径以同时防止或减缓神经细胞死亡方面显示出协同效应。目前还没有被批准的治疗PSP的方法，据报道，全世界每10万人中就有7人受到这种疾病的影响。
治疗PSP的AMX0035的2b/3期全球试验--Orion试验仍在进行中。Orion试验的主要疗效终点通过28个项目的进行性核上性麻痹评定量表(PSPRS)的变化率、第52周的总分来评估疾病进展，这是PSP临床试验中确定和验证的终点。次级疗效终点是指以改良的10项PSPRS评分衡量的疾病进展，以及由运动障碍协会-统一帕金森病评定量表第二部分(MDS-UPDRS第二部分)衡量的日常生活活动的运动方面。探索性结果包括日常生活能力、认知功能、生活质量、总存活率、脑区域体积、神经元损伤/炎症的液体生物标志物和照顾者负担的变化。安全性和耐受性将通过评估治疗紧急不良事件(TEAE)和严重不良事件(SAE)的频率来评估。对PSP中AMX0035的猎户座研究的中期分析数据预计将于2025年年中公布。
此外，我们仍然坚定地承诺对ALS社区。ALS是一种疾病，其特征是运动皮质和脊髓的运动神经元变性，导致进行性肌肉无力。与体内大多数其他定期死亡并作为健康功能的一部分被替换的细胞不同，成熟的中枢神经系统（中枢神经系统）神经元通常能够抵抗细胞死亡，并且通常无法再生。美国约有30，000人患有ALS。ALS是一种影响任何背景的人的疾病，全球约有200，000人患有ALS。
为此，我们已经完成了AMX0114的IND使能研究，AMX0114是一种有效的反义寡核苷酸，靶向抑制Calain-2，Calain-2是轴突(也称为沃勒)变性途径的关键贡献者。轴突变性已被认为是ALS和其他神经退行性疾病的临床表现和发病机制的重要早期因素。在已发表的研究中，Calain-2被认为是轴突变性过程中的一种必不可少的蛋白质，并被反复与神经丝生物学联系在一起。到目前为止已完成的临床前研究表明，AMX0114可以有效、剂量依赖和持久地下调人运动神经元中CAPN2mRNA的表达和Calain-2的蛋白水平。此外，在临床前疗效研究中，AMX0114治疗降低了神经毒性损伤后诱导的多能干细胞(IPSC)来源的人类运动神经元的细胞外神经丝轻链水平，并提高了携带ALS相关致病TDP-43突变的IPSC来源的人类运动神经元的存活率。神经丝是肌萎缩侧索硬化症中被广泛研究的生物标志物。
在ALS中，我们获得了加拿大卫生部的批准，在ALS患者中进行AMX 0114的临床试验申请。我们计划于2024年底或2025年初在加拿大开始名为LUMINA的1期多次剂量给药剂量。我们将评估大约48名ALS成年人的安全性和生物活性，并评估四种剂量水平，从12.5毫克开始。我们上个月在东北ALS联盟年会上提交了我们的研究计划。
我们还向FDA提交了AMX 0114的研究性新药申请。FDA将剂量限制在低于公司提议的12.5毫克起始剂量的剂量，并要求提供更多信息，导致临床暂停。研究的毒理学数据显示，根据独立毒理学公司确定的无明显不良作用水平（BEP），12.5毫克起始剂量的安全裕度大于10倍。我们正在努力回应FDA的评论。我们相信，如果需要，试验可以在美国境外完成。我们预计将于2025年获得LUMINA的早期队列数据。
2024年4月4日，我们宣布已与FDA和加拿大卫生部启动一项程序，自愿终止RELY VRIO的上市授权®/ALBRIOZA™ （苯丁酸钠和牛磺酸二醇[也称为
19
治疗肌萎缩侧索硬化症，并将该产品从美国和加拿大的市场上移除，或“RELYVRIO”®/ALBRIOZA™ 停产。这一决定是由全球3期菲尼克斯试验的TOPLINE结果、与监管机构的接触以及与ALS社区的讨论决定的，该试验未能满足其预先指定的主要和次要终点。截至2024年4月4日，RELYVRIO/ALBRIOZA不再适用于新患者。目前在美国和加拿大接受治疗的患者，在咨询他们的医生后，希望继续治疗的患者可以选择过渡到免费药物计划。患者和他们的医生被告知，免费药物的最终发货已经发货，以便在2025年初之前进行治疗。NDA现在被列入了橙色书的停产药物产品名单。我们将继续收集有关生存的现有数据，并分享从凤凰城学到的经验，以帮助为未来的ALS研究提供信息。我们按计划结束了Open Label扩展。
自成立以来，我们投入了大量精力用于研究与开发以及商业化前和商业化活动，包括招聘管理和技术人员、筹集资金、生产临床前研究和临床试验材料以及建设支持此类活动的基础设施。截至2024年9月30日，我们主要通过公开发行普通股、私募出售优先股、可转换票据以及分别在美国和加拿大销售RELY VRIO和ALBRIOZA的收入为我们的运营提供资金。
截至2024年9月30日，我们拥有现金、现金等值物和有价证券23440万美元。2024年4月，我们宣布进行重组，将财务资源集中在即将到来的临床里程碑上。在重组中，我们裁员约70%，并减少了优先领域以外的外部财务承诺。我们相信，随着这些变化，截至2024年9月30日，我们的现有现金、现金等值物和有价证券将足以满足我们自本季度报告发布以来至少一年内的预期运营和资本支出要求。我们的这一估计是基于可能被证明是错误的假设，我们可能会比预期更早耗尽可用的资本资源。见“流动性与资本资源“下面。
当我们推进avexitide、AMX 0035、AMX 0114以及通过临床前和临床开发推进或收购任何未来候选产品时，我们将继续产生巨额费用，设置和启动额外的试验，雇用额外的临床、科学、管理和行政人员，寻求监管机构批准并寻求任何已批准的候选产品的商业化。我们还可能产生与业务开发活动相关的费用，例如候选产品的内部许可。
我们预计通过现有现金、现金等值物和有价证券为我们的短期运营提供资金，如果需要，还通过出售股权、债务融资或其他资本来源，包括与其他公司的潜在合作、特许权使用费融资或其他战略交易。我们无法在需要时筹集资本或获得其他资金，可能会对我们的财务状况和实施业务战略的能力产生负面影响。无法保证我们当前的运营计划能够实现，或者如果需要，将以我们可以接受的条款或根本无法保证额外资金。
我们运营结果的组成部分
产品收入，净额
截至2024年9月30日和2023年9月30日止三个月和九个月确认的产品净收入主要与在加拿大和美国销售的ALBRIOZA和RELY VRIO单位有关，分别2024年4月，我们宣布已与FDA和加拿大卫生部启动一项程序，自愿终止RELY VRIO的上市授权®/ALBRIOZA™ 并根据全球三期PHOENIX试验的总体结果，将该产品从美国和加拿大的市场上撤下。因此，我们将不会从出售RELY VRIO中产生收入®/ALBRIOZA™在未来时期。
运营费用
销售成本
销售成本主要包括与RELY VRIO、ALBRIOZA的制造相关的成本、某些期间成本以及与合同制造组织的采购承诺损失。在我们宣布终止RELY VRIO营销授权的流程后®/ALBRIOZA™并将产品从美国和加拿大市场下架，我们将不会报告未来期间的产品销售成本。
20
获得的在制品研发费用
收购的过程中研发（IPR & D）费用包括从艾格购买Avexitide开发、制造和商业化中几乎所有资产和权益的对价。
研究和开发费用
研究和开发费用主要包括与AMX 0035、avexitide、AMX 0114和其他潜在未来候选产品的研究和开发相关的成本。我们将研究和开发费用按发生时支付。这些费用包括：
我们为未来收到用于研发活动的商品或服务支付的预付款被记录为预付费用。此类金额在交付货物或提供相关服务时确认为费用，或直至不再预期交付货物或提供服务为止。
对于AMX 0035，我们的某些间接研发费用并未按适应症进行跟踪。我们不会将员工成本和设施（包括折旧或其他间接成本）分配给特定适应症，因为这些成本分布在多个适应症中，因此没有单独分类。我们利用内部资源来监督研究和发现，以及管理我们的临床前开发、工艺开发、制造和临床开发活动。这些员工在多个适应症中工作，因此我们不会通过适应症来跟踪他们的成本。
研究和开发活动是我们商业模式的核心。处于临床开发后期阶段的候选产品（例如AMX 0035）通常比处于临床开发早期阶段的候选产品（例如AMX 0114）的开发成本更高，这主要是由于后期临床试验规模和持续时间的增加以及相关产品制造费用。我们预计，短期和未来，我们的研发费用将与我们计划的临床开发活动一起继续增加。目前，我们无法准确估计或了解完成AMX 0035、阿维西肽和任何未来候选产品的临床开发所需的工作的性质、时间和成本。我们的临床开发成本可能会因以下因素而存在显着差异：
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由于与产品开发和商业化相关的众多风险和不确定性，AMX 0035、avexitide和任何其他当前或未来候选产品的成功开发和商业化存在高度不确定性，包括以下内容：
与AMX 0035、avexitide或任何其他当前或未来候选产品开发相关的任何这些变量的结果发生变化，都可能对与我们候选产品开发相关的成本和时间产生重大影响。我们可能永远无法成功获得或维持对AMX 0035、Avexitide或任何其他当前或未来候选产品的监管批准（如适用）。
销售、一般和行政费用
销售、一般和行政费用主要包括行政、财务、销售、营销和行政职能人员的工资和相关费用。销售、一般和行政费用还包括与专利和公司事务有关的法律费用；会计、审计、税务、遵守萨班斯-奥克斯利法案第404条或第404条的专业费用，以及行政咨询服务；公司保险费；行政差旅费用；销售和营销费用；信息技术；对独立慈善基金会的慈善捐款；与设施有关的费用和其他运营费用。2024年4月，我们宣布了重组计划，旨在将我们的资源集中于关键的临床和临床前项目。重组包括裁减人员，预计将使我们的工作人员减少约70%，并减少我们优先领域以外的外部财政承诺。因此，我们预计2024年我们的销售、一般和管理费用将比2023年减少。
22
重组费用
重组费用主要包括员工遣散费和解雇福利、合同终止成本、长期资产减损和其他成本。我们根据FASb ASC主题420“退出或处置成本义务”记录与退出和处置活动相关的成本和负债。该等成本基于负债发生期间的公允价值估计。随着更多信息的可用，我们根据情况的变化评估和调整这些成本。
所得税
所得税采用资产负债法确定。递延税项资产及负债指财务报表账面值与资产及负债的计税基准之间的暂时性差异所产生的未来税项后果，而就税项属性而言，则指采用预期于差异倒转的年度生效的制定税率结转的税项。我们递延税项资产的变现取决于未来应税收入的产生，其金额和时间尚不确定。如果根据现有证据的份量，部分或全部递延税项资产很可能无法变现，则会提供估值免税额。我们继续根据管理层对所有可用证据的评估，包括我们在运营中遭受重大亏损的历史，对我们所有的递延税项资产保持全额估值准备金。因此，我们预计在可预见的未来不会产生物质所得税。
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经营成果
截至2024年9月30日与2023年9月30日的三个月比较
下表总结了我们在所列期间的运营业绩（以千计）：
|
|
截至9月30日的三个月， |
|
|
|
|
|
|
|
|||||||
|
|
2024 |
|
|
2023 |
|
|
$Change |
|
|
更改百分比 |
|
||||
产品收入，净额 |
|
$ |
416 |
|
|
$ |
102,693 |
|
|
$ |
(102,277 |
) |
|
|
(100 |
)% |
运营费用： |
|
|
|
|
|
|
|
|
|
|
|
|
||||
销售成本 |
|
|
— |
|
|
|
5,218 |
|
|
|
(5,218 |
) |
|
|
(100 |
)% |
销售成本-库存减损和确定采购承诺损失 |
|
|
809 |
|
|
|
— |
|
|
|
809 |
|
|
*NM |
|
|
收购正在进行的研究和开发 |
|
|
36,203 |
|
|
|
— |
|
|
|
36,203 |
|
|
*NM |
|
|
研发 |
|
|
21,237 |
|
|
|
30,037 |
|
|
|
(8,800 |
) |
|
|
(29 |
)% |
销售、一般和行政 |
|
|
17,828 |
|
|
|
48,718 |
|
|
|
(30,890 |
) |
|
|
(63 |
)% |
总运营支出 |
|
|
76,077 |
|
|
|
83,973 |
|
|
|
(7,896 |
) |
|
|
(9 |
)% |
营业收入(亏损) |
|
|
(75,661 |
) |
|
|
18,720 |
|
|
|
(94,381 |
) |
|
|
(504 |
)% |
其他收入，净额： |
|
|
|
|
|
|
|
|
|
|
|
|
||||
利息收入 |
|
|
3,098 |
|
|
|
4,179 |
|
|
|
(1,081 |
) |
|
|
(26 |
)% |
其他费用，净额 |
|
|
(141 |
) |
|
|
(488 |
) |
|
|
347 |
|
|
|
(71 |
)% |
其他收入合计，净额 |
|
|
2,957 |
|
|
|
3,691 |
|
|
|
(734 |
) |
|
|
(20 |
)% |
所得税前收入(亏损) |
|
|
(72,704 |
) |
|
|
22,411 |
|
|
|
(95,115 |
) |
|
|
(424 |
)% |
所得税拨备 |
|
|
— |
|
|
|
1,518 |
|
|
|
(1,518 |
) |
|
|
(100 |
)% |
净(亏损)收益 |
|
$ |
(72,704 |
) |
|
$ |
20,893 |
|
|
$ |
(93,597 |
) |
|
|
(448 |
)% |
产品收入、净收入和销售成本
由于RELyVNIO ®/ALBRIOZA™停产，截至2024年9月30日止三个月，我们没有从产品销售中产生大量收入，余额主要代表反映了本期实际回扣和退货活动的毛额与净利润的调整。截至2023年9月30日止三个月，产品净收入主要与在美国和加拿大销售的RELY VRIO和ALBRIOZA单位有关。
截至2024年9月30日止三个月的销售成本主要与确定采购承诺的损失有关。截至2023年9月30日止三个月，销售成本包括在美国和加拿大采购、制造和分销RELY VRIO和ALBRIOZA单元的成本。
获得的在制品研发费用
2024年7月9日，我们完成了艾格收购。截至2024年9月30日的三个月内，我们记录了与收购的Avexitide在制品研发资产相关的费用约3620万美元，未来没有替代用途。
研究和开发费用
下表总结了截至2024年9月30日和2023年9月30日三个月的研发费用（单位：千）：
|
|
截至9月30日的三个月， |
|
|
|
|
|
|
|
|||||||
|
|
2024 |
|
|
2023 |
|
|
$Change |
|
|
更改百分比 |
|
||||
AMX 0035- ALS |
|
$ |
3,478 |
|
|
$ |
12,955 |
|
|
$ |
(9,477 |
) |
|
|
(73 |
)% |
AMX 0035- PSP |
|
|
4,995 |
|
|
|
1,571 |
|
|
|
3,424 |
|
|
|
218 |
% |
薪资和人事相关 |
|
|
7,464 |
|
|
|
11,788 |
|
|
|
(4,324 |
) |
|
|
(37 |
)% |
其他 |
|
|
5,300 |
|
|
|
3,723 |
|
|
|
1,577 |
|
|
|
42 |
% |
|
|
$ |
21,237 |
|
|
$ |
30,037 |
|
|
$ |
(8,800 |
) |
|
|
(29 |
)% |
截至2024年9月30日的三个月，研发费用为2120万美元，而截至2023年9月30日的三个月为3000万美元。这一减少主要是由于根据PHOENIX试验的总体数据，AMX 0035用于治疗ALS的支出减少了950万美元，以及工资和人事相关费用减少了430万美元，主要与重组计划导致的员工数量减少有关。减少
24
研究和开发费用被AMX 0035治疗PSP的支出增加340万美元和其他成本增加160万美元所抵消。AMX 0035用于治疗PSP的支出增加主要与支持ORION 2b/3期全球临床试验继续进行的成本有关，其他成本的增加主要是由于临床前开发活动的增加。
销售、一般和行政费用
截至2024年9月30日的三个月，销售、一般和行政费用为1780万美元，而截至2023年9月30日的三个月为4870万美元。减少的主要原因是工资和人事相关成本减少1450万美元，咨询和专业服务减少1070万美元，其他费用减少570万美元。工资和人事相关成本的减少主要与重组计划导致员工数量减少有关。咨询和专业服务的减少主要是由于RELY VRIO导致商业销售和营销活动的减少®/ALBRIOZA™ 停止。其他费用的减少主要是由于结束商业运营的活动减少。
所得税拨备
截至2024年9月30日和2023年9月30日的三个月，我们分别记录了零和150万美元的所得税拨备。截至2024年9月30日的三个月没有所得税拨备是受当年估计有效税率的推动。截至2023年9月30日的三个月的所得税优惠主要由当年估计的年度有效税率以及10万美元的离散所得税优惠推动。
25
截至2024年9月30日和2023年9月30日的九个月比较
下表总结了我们在所列期间的运营业绩（以千计）：
|
|
截至9月30日的9个月， |
|
|
|
|
|
|
|
|||||||
|
|
2024 |
|
|
2023 |
|
|
$Change |
|
|
更改百分比 |
|
||||
产品收入，净额 |
|
$ |
88,036 |
|
|
$ |
272,337 |
|
|
$ |
(184,301 |
) |
|
|
(68 |
)% |
运营费用： |
|
|
|
|
|
|
|
|
|
|
|
|
||||
销售成本 |
|
|
5,953 |
|
|
|
16,081 |
|
|
|
(10,128 |
) |
|
|
(63 |
)% |
销售成本-库存减损和确定采购承诺损失 |
|
|
118,680 |
|
|
|
— |
|
|
|
118,680 |
|
|
*NM |
|
|
收购正在进行的研究和开发 |
|
|
36,203 |
|
|
|
— |
|
|
|
36,203 |
|
|
*NM |
|
|
研发 |
|
|
81,192 |
|
|
|
83,273 |
|
|
|
(2,081 |
) |
|
|
(2 |
)% |
销售、一般和行政 |
|
|
97,234 |
|
|
|
136,115 |
|
|
|
(38,881 |
) |
|
|
(29 |
)% |
重组费用 |
|
|
22,851 |
|
|
|
— |
|
|
|
22,851 |
|
|
*NM |
|
|
总运营支出 |
|
|
362,113 |
|
|
|
235,469 |
|
|
|
126,644 |
|
|
|
54 |
% |
营业收入(亏损) |
|
|
(274,077 |
) |
|
|
36,868 |
|
|
|
(310,945 |
) |
|
|
(843 |
)% |
其他收入，净额： |
|
|
|
|
|
|
|
|
|
|
|
|
||||
利息收入 |
|
|
11,493 |
|
|
|
11,784 |
|
|
|
(291 |
) |
|
|
(2 |
)% |
其他费用，净额 |
|
|
(1,371 |
) |
|
|
(831 |
) |
|
|
(540 |
) |
|
|
65 |
% |
其他收入合计，净额 |
|
|
10,122 |
|
|
|
10,953 |
|
|
|
(831 |
) |
|
|
(8 |
)% |
所得税前收入(亏损) |
|
|
(263,955 |
) |
|
|
47,821 |
|
|
|
(311,776 |
) |
|
|
(652 |
)% |
所得税拨备 |
|
|
242 |
|
|
|
3,281 |
|
|
|
(3,039 |
) |
|
|
(93 |
)% |
净(亏损)收益 |
|
$ |
(264,197 |
) |
|
$ |
44,540 |
|
|
$ |
(308,737 |
) |
|
|
(693 |
)% |
产品收入，净额
截至2024年9月30日的九个月，产品净收入为8800万美元，而截至2023年9月30日的九个月为27230万美元。在此期间，产品净收入主要与分别在美国和加拿大销售的RELY VRIO和ALBRIOZA单位有关。由于RELyVRIO®/ALBRIOZA™ 终止后，我们在2024年第二或第三季度没有从产品销售中产生重大收入。
销售成本
截至2024年9月30日止九个月的销售成本为12460万美元，而截至2023年9月30日止九个月的销售成本为1610万美元。在这些期间，销售成本包括采购、制造和分销我们的市售产品RELY VRIO和ALBRIOZA的成本。由于RELyVRIO®/ALBRIOZA™ 终止后，该公司在截至2024年9月30日的九个月内记录了与库存减记和确定采购承诺损失相关的费用约11870万美元。
获得的在制品研发费用
2024年7月9日，公司完成了艾格收购。截至2024年9月30日的九个月内，该公司记录了与收购的Avexitide在制品研发资产相关的费用约3620万美元，未来无替代用途。
研究和开发费用
下表总结了截至2024年9月30日和2023年9月30日的九个月的研发费用（单位：千）：
|
|
截至9月30日的9个月， |
|
|
|
|
|
|
|
|||||||
|
|
2024 |
|
|
2023 |
|
|
$Change |
|
|
更改百分比 |
|
||||
AMX 0035- ALS |
|
$ |
25,577 |
|
|
$ |
41,858 |
|
|
$ |
(16,281 |
) |
|
|
(39 |
)% |
AMX 0035- PSP |
|
|
12,277 |
|
|
|
2,782 |
|
|
|
9,495 |
|
|
|
341 |
% |
薪资和人事相关 |
|
|
30,322 |
|
|
|
31,186 |
|
|
|
(864 |
) |
|
|
(3 |
)% |
其他 |
|
|
13,016 |
|
|
|
7,447 |
|
|
|
5,569 |
|
|
|
75 |
% |
|
|
$ |
81,192 |
|
|
$ |
83,273 |
|
|
$ |
(2,081 |
) |
|
|
(2 |
)% |
26
截至2024年9月30日的九个月，研发费用为8120万美元，而截至2023年9月30日的九个月为8330万美元。小幅下降主要是由于PHOENIX试验的总体数据显示，AMX 0035用于治疗ALS的支出减少了1630万美元，以及与重组计划导致员工数量减少相关的工资和人员相关成本减少了90万美元。研究和开发费用的减少被AMX 0035治疗PSP的支出增加了950万美元，以及由于临床前开发活动增加而导致其他成本增加了560万美元，抵消了研发费用的减少。AMX 0035用于治疗PSP的支出增加主要与支持ORION 2b/3期全球临床试验继续进行的成本有关。
销售、一般和行政费用
截至2024年9月30日的九个月，销售、一般和行政费用为9720万美元，而截至2023年9月30日的九个月为13610万美元。减少的主要原因是工资和人事相关成本减少2310万美元，咨询和专业服务减少1490万美元，但被其他费用增加90万美元所抵消。工资和人事相关成本的减少主要与重组计划导致员工数量减少有关。咨询和专业服务的减少主要是由于RELY VRIO导致商业销售和营销活动的减少®/ALBRIOZA™ 停止。其他费用的增加主要是由于上市公司运营支出和其他费用的增加。
重组费用
截至2024年9月30日的九个月内，重组费用约为2290万美元，其中包括员工遣散费和解雇福利约2190万美元、合同终止成本、长期资产减损和其他成本100万美元。我们于2024年第二季度基本完成了重组计划。
所得税拨备
截至2024年9月30日和2023年9月30日的九个月，我们分别记录了20万美元的所得税拨备和330万美元的所得税优惠。截至2024年9月30日止九个月的所得税拨备由2000万美元的离散所得税费用推动。截至2023年9月30日的九个月的所得税优惠主要由当年估计的有效税率以及50万美元的离散所得税优惠推动。
流动性与资本资源
流动资金来源
2022年下半年，我们开始通过销售已批准的药品RELY VRIO（在加拿大称为ALBRIOZA）产生收入。2024年4月，我们宣布停止RELY DVIO ®/ALBRIOZA™。我们还宣布了重组计划，该计划旨在将我们的资源集中在关键的临床和临床前项目上，其中包括裁员，使我们的员工人数减少了约70%，并减少了优先领域以外的外部财务承诺。我们于2024年下半年完成了重组计划。迄今为止，我们主要通过销售已批准的产品、销售和发行普通股、可转换优先股和可转换票据的收入为我们的运营提供资金。截至2024年9月30日，我们拥有现金、现金等值物和有价证券23440万美元。
根据我们当前的运营计划和假设，我们相信我们现有的现金、现金等值物和有价证券将足以满足我们在本季度报告提交之日后至少十二个月内的预期运营和资本支出要求。我们的这些估计是基于可能被证明是错误的假设，我们可以比预期更快地利用可用的资本资源。
资本资源和用途
我们预计将因我们正在进行的活动而产生巨额费用，特别是当我们推进AMX 0035、阿维西肽和任何其他当前或未来候选产品的临床前活动、制造和临床试验时，或者收购或许可额外的候选产品或产品时。此外，我们预计将继续产生与作为
27
上市公司，包括重大法律、会计、投资者关系和其他费用。我们预计将产生大量费用，因为我们：
由于与候选产品和项目的研究、开发和商业化相关的众多风险和不确定性，我们无法估计运营资金需求的确切金额。我们未来的资金需求将取决于许多因素，并可能因许多因素而大幅增加，包括：
28
在我们能够产生足够的产品收入以恢复和维持盈利能力之前，我们可能会通过股权发行、债务融资、政府或其他第三方资金、营销和分销安排以及其他合作、战略联盟和许可安排来为我们的现金需求融资。在一定程度上，我们通过出售普通股、可转换证券或其他股权证券来筹集额外资本，目前的所有权权益将被稀释。如果我们通过与第三方的合作或营销、分销或许可安排筹集更多资金，我们可能不得不放弃对我们的技术、未来收入来源或候选产品的宝贵权利，或者以可能对我们不利的条款授予许可证。此外，债务融资(如果可行)可能导致固定支付义务，并可能涉及一些协议，其中包括限制我们采取具体行动的能力的限制性契约，例如招致额外债务、进行资本支出、创建留置权、赎回股票或宣布股息，这些可能对我们开展业务的能力产生不利影响。如果我们无法在需要时筹集额外资金，我们可能会被要求推迟、限制、减少或终止我们的产品开发或未来的商业化努力，或者授予我们开发和营销我们本来更愿意自己开发和营销的候选产品的权利。
现金流
截至2024年9月30日和2023年9月30日的九个月比较
下表总结了我们在所列期间的现金来源和用途（以千计）：
|
|
截至9月30日的9个月， |
|
|
|
|
|
|
|
|||||||
|
|
2024 |
|
|
2023 |
|
|
$Change |
|
|
更改百分比 |
|
||||
用于经营活动的现金净额 |
|
$ |
(108,639 |
) |
|
$ |
(1,632 |
) |
|
$ |
(107,007 |
) |
|
*NM |
|
|
投资活动提供的现金净额 |
|
|
10,674 |
|
|
|
71,128 |
|
|
|
(60,454 |
) |
|
|
(85 |
)% |
融资活动提供的现金净额 |
|
|
238 |
|
|
|
3,313 |
|
|
|
(3,075 |
) |
|
|
(93 |
)% |
汇率变化对现金、现金等值物和受限制现金等值物的影响 |
|
|
87 |
|
|
|
(77 |
) |
|
|
164 |
|
|
|
(213 |
)% |
现金、现金等值物和限制性现金等值物净（减少）增加 |
|
$ |
(97,640 |
) |
|
$ |
72,732 |
|
|
$ |
(170,372 |
) |
|
|
(234 |
)% |
经营活动
截至2024年9月30日的九个月内，经营活动使用现金10860万美元，主要是由于我们的净亏损26420万美元、投资折扣净增加810万美元以及我们的经营资产和负债变动使用的净现金1910万美元，被11870万美元的库存减损和确定采购承诺损失以及2630万美元的非现金股票补偿费用所抵消。我们的净损失非现金调整还包括3620万美元的收购IPR & D资产，这些资产被归类为投资活动。
我们的经营资产和负债变化使用的净现金主要包括应收账款净减少3830万美元，但被本期资本化库存（扣除库存核销）增加930万美元、应计费用减少3340万美元和应付账款减少2060万美元所抵消。
截至2023年9月30日的九个月内，经营活动使用了160万美元的现金，主要来自我们4450万美元的净利润和2760万美元的非现金股票补偿费用，但被740万美元的投资折扣净增加和6720万美元的运营资产和负债变化使用的净现金抵消。
我们的经营资产和负债中使用的净现金主要包括本期资本化库存增加4660万美元、应收账款净额增加1400万美元以及预付费用和其他流动资产增加760万美元。
29
投资活动
截至2024年9月30日的九个月内，投资活动提供的净现金为1070万美元，主要来自27900万美元的到期投资，被23200万美元的有价证券购买和3620万美元的现金流出所抵消，用于收购与avexitide资产收购相关的IPR & D资产。
截至2023年9月30日的九个月内，投资活动提供的净现金为7110万美元，主要来自24620万美元的到期投资，部分被本期有价证券购买17420万美元所抵消。
融资活动
截至2024年9月30日的九个月内，融资活动提供的净现金为20万美元。该金额主要包括行使股票期权和授予股票奖励的2000万美元收益，扣除对股票奖励支付的预扣税。
截至2023年9月30日的九个月内，融资活动提供的净现金为330万美元。该金额主要包括行使股票期权和授予股票奖励的340万美元收益，扣除为这些奖励支付的员工税。
合同义务和承诺
我们在正常业务过程中与合同制造组织就原材料采购和制造服务达成协议。截至2024年9月30日，我们在这些协议下有约2720万美元的剩余债务，预计将在2025年之前支付。
关键会计政策、最近的会计公告以及重要判断和估计
我们的简明综合财务报表是根据美国公认会计原则编制的。编制简明综合财务报表和相关披露要求我们做出影响资产、负债、成本和费用的报告金额以及简明综合财务报表中或有资产和负债的披露的估计和判断。我们的估计基于历史经验、已知趋势和事件以及我们认为在当时情况下合理的各种其他因素，其结果构成了对无法从其他来源明显看出的资产和负债的公允价值做出判断的基础。我们持续评估我们的估计和假设。在不同的假设或条件下，我们的实际结果可能与这些估计不同。
我们的关键会计政策与“中所述的政策没有发生重大变化管理层对财务状况和经营成果的探讨与分析”，在我们的2023年年度报告中披露。
第3项关于市场风险的定量和定性披露。
市场风险是与我们的业务或现有或预测的金融交易相关的市场变化可能导致的潜在损失。我们在日常业务过程中面临各种市场风险，具体讨论如下。
利率风险
我们面临着与利率变化相关的市场风险。截至2024年9月30日和2023年12月31日，我们分别拥有23440美元万和37140美元万的现金、现金等价物和有价证券。我们的现金等价物主要投资于银行存款和货币市场共同基金。我们对市场风险的主要敞口是利率敏感性，利率敏感性受到美国利率总体水平变化的影响。我们的投资受到利率风险的影响，如果市场利率上升，我们的投资可能会贬值。由于我们的投资组合持续时间较长，而且我们的投资风险较低，我们认为利率立即变化100个基点不会对我们投资组合的公平市场价值产生实质性影响。我们有能力持有我们的投资直到到期，因此我们预计我们的经营业绩或现金流不会受到市场利率变化对我们投资的影响的任何重大影响。
30
外币和货币兑换风险
我们目前没有面临与外币汇率变化相关的重大市场风险;然而，我们已经与美国以外的供应商签订了合同，并可能继续与美国以外的供应商签订合同。因此，我们的业务未来可能会受到外币汇率波动的影响。
Inflation Risk
我们认为，截至2024年9月30日和2023年9月30日的九个月内，通货膨胀对我们的业务、财务状况或经营业绩没有产生重大影响。然而，通货膨胀已经并可能继续对我们吸引和留住合格人员所产生的劳动力成本产生影响。
项目4.控制和程序
Evaluation of Disclosure Controls and Procedures
We maintain “disclosure controls and procedures,” as defined in Rules 13a-15(e) and 15d-15(e) under the Exchange Act, that are designed to ensure that information required to be disclosed in the reports that we file or submit under the Exchange Act is (1) recorded, processed, summarized and reported, within the time periods specified in the SEC’s rules and forms and (2) accumulated and communicated to our management, including our principal executive officers and principal financial officer, to allow timely decisions regarding required disclosure. Management recognizes that any controls and procedures, no matter how well designed and operated, can provide only reasonable assurance of achieving their objectives and management necessarily applies its judgment in evaluating the cost-benefit relationship of possible controls and procedures.
截至2024年9月30日，我们的管理层在首席执行官和首席财务官的参与下评估了我们披露控制和程序的有效性。根据对截至2024年9月30日披露控制和程序的评估，我们的首席执行官和首席财务官得出的结论是，截至该日期，我们的披露控制和程序在合理的保证水平上有效。
Changes in Internal Control over Financial Reporting
There were no changes in our internal control over financial reporting that occurred during the three months ended September 30, 2024 that have materially affected, or are reasonably likely to materially affect, our internal control over financial reporting. While we experienced changes in personnel resulting from our Restructuring Plan, these changes did not necessitate changes in internal control process design or operation that have materially affected, or are reasonably likely to materially affect, our internal control over financial reporting.
31
PART II—OTHER INFORMATION
Item 1. Legal Proceedings.
2024年2月9日，美国纽约南区地区法院对公司和我们的某些现任和前任官员(Shih诉Amylyx制药公司等人案。，案件编号1：24-CV-00988，或施正荣投诉)。原告于2024年6月24日提交了修改后的起诉书。施正荣的起诉书就所有被告涉嫌违反交易所法案第10(B)节及其颁布的第100亿.5条，以及根据第20(A)条向若干现任及前任高级人员提出被指为控制人的申索。施正荣的起诉书称，被告就RELYVRIO的商业结果和前景做出了重大虚假和误导性陈述。施正荣的诉状要求未指明的损害赔偿、利息、费用和律师费，以及法院认为适当的其他未指明的救济。2024年8月12日，该案从美国纽约南区地区法院移交给美国马萨诸塞州地区法院，并分配了1：24-CV-12068的案卷编号。移交后，2024年9月6日，被告采取行动驳回施正荣的申诉。原告于2024年10月21日提出反对被告的驳回动议，被告的答辩截止日期为2024年11月20日或之前。
2024年10月2日，针对某些现任和前任董事和高管被告向美国马萨诸塞州地区地方法院或法院提起衍生诉讼，将该公司列为名义被告（琼斯诉科恩等人案., 1：24-CV-12527，或衍生投诉）。实质性指控与施氏诉状的指控相同，但还包括涉嫌违反《交易法》第14（a）条、违反受托义务、内幕交易和不当致富的指控。衍生品投诉寻求向公司赔偿未具体说明的损害赔偿，以及利息、费用和律师费、赔偿以及未具体说明的公司治理和内部程序改革和改进。2024年10月31日，法院下达命令，暂停诉讼，直至以偏见驳回Shih诉状（包括用尽所有上诉）或被告对Shih诉状提出答复（以较早者为准）。
该公司打算大力抗辩施投诉和衍生投诉。目前，无法估计Shih投诉和衍生投诉中提出的索赔的影响（如果有的话）。
第1A项。风险因素。
在评估我们的业务和前景时，除了本季度报告和我们向SEC提交的其他文件中列出的其他信息外，还应仔细考虑以下风险因素。投资我们的普通股涉及很高的风险。如果实际发生以下任何风险和不确定性，我们的业务、前景、财务状况和经营业绩可能会受到重大不利影响。以下描述的风险并非详尽无遗，也不是我们面临的唯一风险。新的风险因素可能会不时出现，无法预测任何因素或因素组合可能对我们的业务、前景、财务状况和经营业绩产生的影响。
风险因素摘要
与我们的财务状况和资金需求相关的风险
与发现和开发我们当前和未来候选产品相关的风险
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与我们对第三方的依赖相关的风险
与AMX 0035、Avexitide或未来候选产品商业化相关的风险
与我们的知识产权有关的风险
与我们的业务运营和员工事务相关的风险
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与我们普通股相关的风险
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与我们的财务状况和资金需求相关的风险
我们已停止在美国和加拿大营销和销售我们唯一的商业产品，因此不会继续从该产品中产生收入用于治疗ALS。我们预计在可预见的未来将产生重大损失。
对生物制药产品开发的投资具有很高的投机性，因为它需要大量的前期资本支出，并存在重大风险，即任何潜在的候选产品将无法证明足够的效果或可接受的安全状况，无法获得监管部门的批准，无法在商业上可行。我们在AMX0035的产品开发工作中投入了大量资源，并将AMX0035作为ALS的RELYVRIO(已获得FDA批准)和ALBRIOZA(获得加拿大卫生部有条件的营销授权)商业化。我们自愿终止了针对ALS的RELYVRIO/ALBRIOZA(AMX0035)的营销授权，并根据第三阶段Phoenix试验的TOPLINE结果将该产品从美国和加拿大的市场上移除，该试验未能满足其预先指定的主要和次要终端。在RELYVRIO/ALBRIOZA分别从美国和加拿大市场退出后，我们没有任何产品被批准用于商业销售，我们将继续产生与临床开发和我们当前和未来候选产品的潜在批准有关的大量研究和开发以及其他费用，包括AMX0035用于ALS以外的其他适应症、avexitide和持续运营。自成立以来，我们将我们的大部分财务资源和努力投入到研发中，包括临床前研究和临床试验，为商业化和商业化活动做准备。我们的财务状况和经营结果，包括我们的收入、支出和净收益(亏损)，过去有过，未来可能会随着季度和年度的变化而大幅波动。例如，我们在2023年通过销售RELYVRIO/ALBRIOZA产生了38080美元的万收入，但在该产品退出后，我们将不再从该产品中获得收入。因此，您不应依赖之前任何季度或年度的业绩作为未来经营业绩的指标。此外，净亏损和负现金流已经并可能在未来对我们的股东权益和营运资本产生不利影响。截至2024年9月30日，我们的累计赤字为56910美元万。在可预见的未来，我们预计会蒙受重大损失。
我们预计，如果我们：
除非我们成功将任何当前或未来的候选产品商业化，否则我们不会恢复盈利能力。
我们实现盈利并保持盈利的能力取决于我们创造收入的能力。虽然我们通过RELYVRIO/ALBRIOZA的商业化产生收入的历史有限，但我们预计不会产生大量收入，除非我们能够单独或与合作伙伴获得监管部门的批准，并成功将AMX0035用于ALS、Avexitide或任何其他当前或未来的产品候选或我们可能开发或许可的产品。成功的商业化将需要实现许多关键里程碑，这些里程碑因司法管辖区而异，可能包括在临床试验中证明安全性和有效性，获得监管，包括营销，批准这些候选产品，制造、营销和销售我们或我们未来的任何合作伙伴可能获得监管批准的产品，满足任何上市后要求，以及从私人保险或政府付款人那里获得我们产品的报销。由于与这些活动相关的不确定性和风险，我们无法准确和准确地预测收入的时间和金额、任何进一步亏损的程度或我们是否或何时可能实现盈利。我们和任何未来的合作者可能永远不会在这些活动中成功，即使我们成功了，或者任何未来的合作者成功了，我们也可能永远不会产生足够大的收入来实现盈利。即使我们确实实现了盈利，我们也可能无法维持或提高季度或年度的盈利能力。
Our failure to regain profitability may continue to depress the market price of our common stock and could impair our ability to raise capital or obtain other financing, expand our business, diversify our product offerings or continue our operations. If we continue to suffer losses as we have in the past, prior to the commercialization of RELYVRIO and ALBRIOZA, investors may not receive any return on their investment and may lose their entire investment.
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We have a limited operating history and, following the withdrawal of RELYVRIO and ALBRIOZA, do not have any commercial products, which may make it difficult to evaluate the prospects for our future viability.
Our operations to date have been primarily limited to organizing, staffing and financing our company, raising capital, conducting research and development activities, including preclinical studies and clinical trials, prior to discontinuation, preparing for and commercializing AMX0035 for the treatment of ALS and, more recently, restructuring, reprioritizing our assets and acquiring and incorporating avexitide into our pipeline. Accordingly, you should consider our prospects in light of the costs, uncertainties, delays and difficulties frequently encountered by companies in clinical development, especially clinical-stage biopharmaceutical companies such as ours. Any predictions you make about our future success or viability may not be as accurate as they could be if we had a longer operating history or if we continued to have a marketed product.
We may require substantial additional funding in the future to meet our financial needs and to pursue our business objectives. If we are unable to obtain funding if and when needed, we could be forced to delay, reduce or eliminate our product discovery and development activities or commercialization efforts.
Our operations have consumed substantial amounts of cash since inception. We expect to spend substantial amounts to continue the clinical development of AMX0035 in indications other than ALS, for the clinical development of avexitide and for the preclinical and clinical development of additional product candidates, or in the in-license, acquisition or development of other product candidates or products. If we are unable to obtain additional marketing approvals for AMX0035, for avexitide or for any other current or future product candidates that we develop, in-license or acquire, we may require significant additional amounts of cash in order to continue to develop AMX0035, avexitide and any other current or future product candidates and fund our operations. In addition, other unanticipated costs may arise in the course of our development efforts. Because the design and outcome of our ongoing and anticipated clinical trials is highly uncertain, we cannot reasonably estimate the actual amounts necessary to successfully complete the development and commercialization of any product candidate we develop.
Our future capital requirements depend on many factors, including:
We cannot be certain that additional funding will be available on acceptable terms, or at all. As a result of the challenges caused by economic uncertainty in various global markets due to geopolitical instability and conflict, including the ongoing wars in Ukraine and Israel, the escalating conflict in the Middle East, the presidential elections in the United States, the global credit and financial markets have experienced in recent periods significant volatility and disruptions, including diminished liquidity and credit availability, declines in consumer confidence, high rates of inflation and interest rates and uncertainty about economic stability. If the equity and credit markets deteriorate, it may make any necessary debt or equity financing more difficult, more costly or more dilutive.
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We have no committed source of additional capital and if we are unable to raise additional capital or secure other financing, if needed, in sufficient amounts or on terms acceptable to us, we may have to significantly delay, scale back or discontinue the development of AMX0035, avexitide or any other current or future product candidates or other research and development initiatives. We may need to seek collaborators for AMX0035, avexitide and any other current or future product candidates at an earlier stage than otherwise would be desirable or on terms that are less favorable than might otherwise be available or relinquish or license on unfavorable terms our rights to AMX0035, avexitide and any other current or future product candidates in markets where we otherwise would seek to pursue development or commercialization ourselves. Any of the above events could significantly harm our business, prospects, financial condition, and results of operations and cause the price of our common stock to decline.
We believe that our existing cash, cash equivalents, and marketable securities, will be sufficient to meet our anticipated operating and capital expenditure requirements for at least twelve months after the date of this Quarterly Report. However, our estimate may prove to be wrong, and we could use our available capital resources sooner than we currently expect. Further, changing circumstances, some of which may be beyond our control, could cause us to consume capital significantly faster than we currently anticipate, and we may need to seek additional funds sooner than planned.
Raising additional capital may cause dilution to our stockholders, restrict our operations or require us to relinquish rights to our technologies or product candidates.
We expect our expenses to continue to increase in connection with our planned operations. Unless and until we can generate a substantial amount of revenue on a sustained basis, if at all, we may be required to finance our future cash needs through public or private equity offerings, royalty-based or debt financings, collaborations, licensing arrangements or other sources, or any combination of the foregoing. In addition, we may seek additional capital due to favorable market conditions or strategic considerations, even if we believe that we have sufficient funds for our current or future operating plans.
To the extent that we raise additional capital through the sale of common stock, convertible securities or other equity securities, your ownership interest may be diluted, and the terms of these securities could include liquidation or other preferences and anti-dilution protections that could adversely affect your rights as a common stockholder. In addition, debt financing, if available, may result in fixed payment obligations and may involve agreements that include restrictive covenants that limit our ability to take specific actions, such as incurring additional debt, making capital expenditures, creating liens, redeeming stock or declaring dividends, that could adversely impact our ability to conduct our business. Securing financing could also require a substantial amount of time and attention from our management and may divert a disproportionate amount of their attention away from day-to-day activities, which may adversely affect our management’s ability to oversee the development of AMX0035, avexitide or any future product candidates.
If we raise additional funds through collaborations or marketing, distribution or licensing arrangements with third parties, we may have to relinquish valuable rights to our technologies, future revenue streams or product candidates or grant licenses on terms that may not be favorable to us.
Changes in tax law could adversely affect our business and financial condition.
The rules dealing with U.S. federal, state, local and international income taxation are constantly under review by persons involved in the legislative process and by the Internal Revenue Service and the U.S. Treasury Department. Changes to tax laws (which changes may have retroactive application) could adversely affect us or holders of our common stock. In recent years, many such changes have been made and changes are likely to continue to occur in the future. Future changes in tax laws could have a material adverse effect on our business, cash flow, financial condition or results of operations. We urge investors to consult with their legal and tax advisers regarding the implications of potential changes in tax laws on an investment in our common stock.
Adverse developments affecting the financial services industry, such as actual events or concerns involving liquidity, defaults or non-performance by financial institutions or transactional counterparties, could adversely affect our current and projected business operations and our financial condition and results of operations.
Events involving limited liquidity, defaults, non-performance or other adverse developments that affect financial institutions, transactional counterparties or other companies in the financial services industry or the financial services industry generally, or concerns or rumors about any events of these kinds or other similar risks, have in the past and may in the future lead to market-wide liquidity problems. Although we do not currently have investments with any financial institution that has experienced such events, if any financial institution with which we have a relationship were to be placed into receivership, we may be unable to access such funds. In addition, if any parties with whom we conduct business are unable to access funds pursuant to instruments or lending arrangements with such a financial institution, such parties’ ability to pay their obligations to us or to enter into new commercial arrangements requiring additional payments to us could be adversely affected.
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Inflation and rapid increases in interest rates have led to a decline in the trading value of previously issued government securities with interest rates below current market interest rates. Although the U.S. Department of Treasury, FDIC and Federal Reserve Board have announced a program to provide up to $25 billion of loans to financial institutions secured by certain government securities held by financial institutions to mitigate the risk of potential losses on the sale of such instruments, widespread demands for customer withdrawals or other liquidity needs of financial institutions for immediate liquidity may exceed the capacity of such program. Additionally, there is no guarantee that the U.S. Department of Treasury, FDIC and Federal Reserve Board will provide access to uninsured funds in the event of the closure of other banks or financial institutions in the future, or that they would do so in a timely fashion.
Although we assess our banking relationships as we believe necessary or appropriate, our access to funding sources in amounts adequate to finance or capitalize our current and projected future business operations could be significantly impaired by factors that affect us, the financial institutions with which we have financial arrangements directly, or the financial services industry or economy in general. These factors could include, among others, events such as liquidity constraints or failures, the ability to perform obligations under various types of financial, credit or liquidity agreements or arrangements, disruptions or instability in the financial services industry or financial markets, or concerns or negative expectations about the prospects for companies in the financial services industry.
In addition, investor concerns regarding the U.S. or international financial systems could result in less favorable commercial financing terms, including higher interest rates or costs and tighter financial and operating covenants, or systemic limitations on access to credit and liquidity sources, thereby making it more difficult for us to acquire financing on acceptable terms or at all. Any decline in available funding or access to our cash and liquidity resources could, among other risks, adversely impact our ability to meet our operating expenses, financial obligations or fulfill our other obligations, result in breaches of our financial and/or contractual obligations or result in violations of federal or state wage and hour laws. Any of these impacts, or any other impacts resulting from the factors described above or other related or similar factors not described above, could have material adverse impacts on our liquidity and our current and/or projected business operations and financial condition and results of operations.
Risks Related to the Discovery and Development of Our Current and Future Product Candidates
We currently depend heavily on the success of AMX0035, one of our most advanced product candidates, and avexitide, our recently acquired product candidate. If we are unable to successfully complete clinical trials for, obtain regulatory approvals for, and successfully commercialize, AMX0035 or avexitide, or experience significant delays in doing so, our business may be materially harmed.
Our future success depends significantly on our ability to successfully develop, and obtain regulatory approvals for and commercialize, AMX0035 in indications other than ALS, including Wolfram syndrome and PSP, and avexitide. To date, we have obtained limited clinical trial data supporting AMX0035 in indications other than ALS, having only completed a clinical trial in 95 patients with AD. We are conducting a Phase 2 clinical trial of AMX0035 in Wolfram syndrome, and a global Phase 3 clinical trial of AMX0035 in PSP, and intend to conduct additional clinical trials for other indications and product candidates in the future. Our business success depends heavily on our ability to successfully complete clinical trials for our product candidates. In connection with the Eiger Acquisition, we acquired substantially all of the rights, title and interests in, to avexitide, an investigational, first-in-class GLP-1 receptor antagonist that has been evaluated in five Phase 2 clinical studies for PBH and Congenital HI. We expect to begin a Phase 3 program for avexitide for PBH in the first quarter of 2025. We are also conducting IND enabling studies of AMX0114 in ALS and plan to initiate the Phase 1 multiple ascending dose, placebo-controlled trial in Canada by the end of 2024 or in early 2025.
We will need to have sufficient funds for, and successfully complete, our clinical development of AMX0035 for the treatment of PSP, Wolfram syndrome and other indications, avexitide and AMX0114 in ALS.
The future regulatory and commercial success of AMX0035, avexitide or any other current or future product candidates are subject to a number of risks, including the following:
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Many of these risks are beyond our control, including the risks related to clinical development, the regulatory submission process, potential threats to our intellectual property rights and the manufacturing, marketing and sales efforts of any future collaborator. If we are unable to develop, obtain or maintain regulatory approvals for, or successfully commercialize AMX0035, avexitide or any of our other current or future product candidates, or if we experience delays as a result of any of these risks or otherwise, our business could be materially harmed.
In addition, of the large number of drugs in development in the pharmaceutical industry, only a small percentage result in the submission of marketing applications to regulatory authorities, and even fewer are approved for commercialization. Furthermore, even if we do receive regulatory approval for our current or any of our future product candidates, any such approval may be subject to limitations on the indications or uses or the patient populations for which we may market the product. Additionally, we may not realize the full commercial potential of AMX0035, avexitide or any other current or future product candidates that receive marketing approval if we are unable to appropriately identify patients with the diseases targeted by such product candidates. Accordingly, even if we are able to obtain the requisite financing to continue to fund our development activities, we cannot assure you that we will successfully develop or commercialize our current or any future product candidates for any indication in any jurisdiction. If we or any of our future collaborators are unable to develop, maintain, or obtain regulatory approvals for, or, if approved, successfully commercialize our current or any future product candidates for our initial or potential additional indications, we may not be able to generate sufficient revenue to continue our business. In addition, our failure to demonstrate positive results in our clinical trials in any indication for which we are developing our current product candidates, or to satisfy other regulatory requirements, could adversely affect our development efforts for AMX0035 in other indications, avexitide or for AMX0114.
The delay or denial of regulatory approval for our current or any future product candidates in any jurisdiction could adversely impact our business and our results of operations, and could cause us to delay or even cease operations.
The research, testing, manufacturing, labeling, approval, sale, marketing, distribution and post-market obligations of drug products are subject to extensive regulation by the FDA and other regulatory agencies in the U.S. and other countries, and such regulations differ from country to country.
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The FDA or any other foreign regulatory agency can delay, limit, deny or withdraw approval to market AMX0035, avexitide or any future product candidates for many reasons, including:
Of the large number of drugs in development, only a small percentage successfully complete the FDA other regulatory approval processes and are commercialized.
The FDA or the applicable foreign regulatory agency may also approve AMX0035, avexitide or any future product candidates for a more limited indication and/or a narrower patient population than we originally request, and the FDA or any other applicable foreign regulatory agency may not approve the labeling that we believe is necessary or desirable for the successful commercialization of AMX0035, avexitide or any future product candidates. Any delay in obtaining, or inability to obtain, applicable regulatory approval would delay or prevent commercialization of AMX0035, avexitide or any future product candidates and would materially adversely impact our business and prospects.
AMX0035 is a fixed-dose combination drug product and certain regulatory authorities may require a demonstration that each component makes a contribution to the claimed effects in addition to demonstrating that the combination is safe and effective for the intended population.
Under the FDA’s combination rule, the FDA may not file or approve an NDA for a fixed-dose combination product unless each component of a proposed drug product is shown to make a contribution to the claimed effects and the dosage of each component (amount, frequency, duration) is safe and effective for the intended population. For additional information on FDA’s combination rule, see the section entitled “Business—Government Regulation—Combination Rule for Fixed-Dose Combination Products” in our 2023 Annual Report.
Similar requirements may be imposed on us by the EMA in the EU and comparable regulatory authorities in other jurisdictions where we intend to seek regulatory approval. See the section entitled “Business—Government Regulation—Fixed-Dose Combination Guideline” in our 2023 Annual Report. For any fixed-dose combination products we may develop, we may be required to produce clinical data supporting the contribution of each component when present at the levels included in the fixed-dose combination in order to obtain marketing authorization in the U.S. or EU.
While the FDA approved AMX0035 (known as RELYVRIO) as a fixed-dose combination product for the treatment of ALS in adults, we may be required by the FDA and comparable foreign regulatory authorities to satisfy the fixed-dose combination rule for AMX0035 or any other fixed-dose combination products we may develop for the treatment of any other indications we may pursue in advance of approval.
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If the FDA or other comparable foreign regulatory authorities require us to conduct one or more clinical trials to support such a demonstration, such as a factorial study, the design, duration, and scope of such clinical trials will be decided upon after further discussions with those agencies and other comparable foreign regulatory authorities. As a result, we are unable to predict with certainty the estimated timing or scope of any future clinical trials of AMX0035 we may be required to conduct to satisfy these requirements governing fixed dose combination products in various jurisdictions. Ongoing third-party data in neurology, specifically within ALS, on our products or other products may influence regulatory decision making, including for fixed-dose combinations.
We have historically concentrated our research and development efforts on the treatment of neurodegenerative and CNS disorders, a field that has seen very limited success in product development, and have only recently further expanded upon our existing development efforts in the endocrine and metabolic field.
We have focused our research and development efforts on addressing neurodegenerative and CNS disorders and have only recently further expanded upon our existing development efforts in the endocrine and metabolic field with the acquisition of avexitide. Thus, this shift in focus may result in additional costs arising from operating expenses and hiring personnel, challenges with building our expertise in the endocrine and metabolic field, or diversion of management’s attention away from AMX0035. Historically, efforts by pharmaceutical companies in the field of neurodegenerative and CNS disorders have experienced limited successes in product development. The development of neurodegenerative and CNS therapies presents unique challenges, including an imperfect understanding of the biology, the presence of the blood brain barrier that can restrict the flow of drugs to the brain, a frequent lack of translatability of preclinical study results in subsequent clinical trials and dose selection, and the product candidate having an effect that may be too small to be detected using the outcome measures selected in clinical trials or if the outcomes measured do not reach statistical significance. There are few approved therapeutic options available for patients with ALS and other neurodegenerative disorders. Our future success is highly dependent on the successful development and commercialization of AMX0035, avexitide and any other current or future product candidates for treating neurodegenerative and CNS disorders or for treating endocrine and metabolic disorders. Developing and commercializing AMX0035, avexitide and any other current or future product candidates for treatment of neurodegenerative and CNS disorders or for treating PBH and Congenital HI subjects us to a number of challenges, including ensuring that we have selected the optimal doses, executing an appropriate clinical trial to test for efficacy and obtaining and maintaining regulatory approval from the FDA and other comparable foreign regulatory authorities.
The regulatory approval processes of the FDA and other comparable foreign authorities are lengthy, time-consuming and inherently unpredictable, and if we are ultimately unable to obtain regulatory approval for our current or any future product candidates, our business will be substantially harmed.
We, and any future collaborators, are not permitted to commercialize, market, promote or sell any product candidate in the U.S. or elsewhere without obtaining regulatory approval from the FDA and other comparable foreign regulatory authorities. Regulatory authorities in other jurisdictions may have similar requirements. The time required to obtain approval by the FDA and other comparable foreign regulatory authorities is unpredictable, and typically takes many years following the commencement of clinical trials and depends upon numerous factors, including substantial discretion of such regulatory authorities. In addition, approval policies, regulations, or the type and amount of clinical data necessary to gain approval may change during the course of a product candidate’s clinical development and may vary among jurisdictions. For example, the U.S. Supreme Court’s July 2024 decision to overturn prior established case law giving deference to regulatory agencies’ interpretations of ambiguous statutory language has introduced uncertainty regarding the extent to which FDA’s regulations, policies, and decisions may become subject to increasing legal challenges, delays, and/or changes. In addition, the FDA in any approval needs to determine that there is substantial evidence of effectiveness. This finding can be substantiated based on two adequate and well-controlled studies, or in certain circumstances on a single, large, multicenter, adequate and well-controlled study that is very persuasive or from a single adequate and well-controlled study together with confirmatory evidence. FDA regulations and guidance also allow for greater flexibility and tolerance for uncertainty in the context of rare and fatal diseases.
Clinical testing is expensive, difficult to design and implement, can take many years to complete and is inherently uncertain as to outcome. We cannot guarantee that any clinical trials will be conducted as planned or completed on schedule, if at all. The clinical development of AMX0035 for our indications other than ALS, avexitide or any current or future product candidates is susceptible to the risk of failure inherent at any stage of development, including failure to demonstrate efficacy in a clinical trial or across a broad population of patients, the occurrence of adverse events that are severe or medically or commercially unacceptable, failure to comply with protocols or applicable regulatory requirements, and determination by the FDA or any other comparable foreign regulatory authority that a product candidate may not continue development or is not approvable. For example, our Phase 3 clinical trial of AMX0035 for the treatment of ALS failed to meet its primary and secondary endpoints. Additionally, our expenses could increase if we are required by the FDA or any other comparable foreign regulatory authority to perform clinical trials in addition to those currently expected, or if there are any delays in completing our clinical trials or the development of AMX0035 in additional indications, avexitide and any current or future product candidates. It is possible that even if AMX0035, avexitide or any other current or future product candidate has a beneficial effect, that effect will not be detected during clinical evaluation as a result of one or more
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of a variety of factors, including the size, duration, design, measurements, conduct or analysis of our clinical trials. Conversely, as a result of the same factors, our clinical trials may indicate an apparent positive effect of AMX0035, avexitide or any other current or future product candidate that is greater than the actual positive effect, if any. Similarly, in our clinical trials we may fail to detect toxicity of or intolerability caused by AMX0035, avexitide or any other current or future product candidate, or mistakenly believe that AMX0035, avexitide or any other current or future product candidates are toxic or not well-tolerated when that is not in fact the case.
AMX0035, avexitide and any current or future product candidates could fail to obtain regulatory approvals, and any of our future product candidates could fail to obtain regulatory approvals, for many reasons, including the following:
This lengthy approval process as well as the unpredictability of clinical trial results may result in our failing to obtain regulatory approval to market AMX0035, avexitide or any future product candidate we develop, which would significantly harm our business, results of operations and prospects. There is no assurance that the endpoints and trial designs used for the approval of currently approved drugs for the treatment of neurodegenerative diseases will be acceptable for future approvals, including for AMX0035, avexitide and any current or future product candidates. Similarly, there is no assurance that the endpoints and trial designs for avexitide will be acceptable for its future approval. The FDA and other comparable foreign authorities have substantial discretion in the approval process and determining when or whether regulatory approval will be obtained for any product candidate that we develop. Even if we believe the data collected from past or future clinical trials of AMX0035, avexitide or any other current or future product candidates are promising, such data may not be sufficient to support approval by the FDA or any other regulatory authority.
The FDA reviews an NDA to determine whether the product is safe and effective for its intended use(s), with the latter determination being made on the basis of substantial evidence. This finding can be substantiated based on two adequate and well-controlled studies, or in certain circumstances on a single, large, multicenter, adequate and well-controlled study that is very persuasive or from a single adequate and well-controlled study together with confirmatory evidence. The FDA may not agree that this standard is met. Accordingly, there can be no assurance that for AMX0035, avexitide or any other current or future product candidates the FDA and other regulatory agencies will not require additional clinical trials beyond what we may plan to conduct.
In addition, disruptions caused by any future public health crisis may increase the likelihood that we encounter difficulties or delays in initiating, screening, enrolling, conducting, or completing our ongoing and planned preclinical studies and clinical trials. Clinical site initiation and patient screening and enrollment may be delayed due to prioritization of hospital resources in the event of a future public health crisis. Investigators and patients may not be able to comply with clinical trial protocols if quarantines impede patient movement or interrupt healthcare services. Similarly, our ability to recruit and retain patients and principal investigators and site staff who, as healthcare providers, may have heightened exposure to such future highly infectious or contagious diseases, could be limited, which in turn could adversely impact our clinical trial operations. Additionally, we may experience interruption of key clinical trial activities, such as clinical trial site monitoring, due to limitations on travel, quarantines or social distancing protocols imposed or recommended by federal or state governments, employers and others in connection with any future outbreak of any highly infectious or contagious
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diseases. As a result of a future public health crisis, we may face delays in meeting our anticipated timelines for our ongoing and planned clinical trials.
In addition, regulatory authorities may subject our clinical or manufacturing operations to inspections, including routine surveillance, bioresearch monitoring and pre-approval inspections. In addition, even if we were to obtain approval, regulatory authorities may approve AMX0035, avexitide or any other current or future product candidates for fewer or more limited indications than we request, may not approve the price we intend to charge for our products, may grant approval contingent on the performance of costly post-marketing preclinical studies and clinical trials, or may approve a product candidate with a label that does not include the labeling claims necessary or desirable for the successful commercialization of that product candidate. Any of the foregoing scenarios could materially harm the commercial prospects for AMX0035, avexitide or any other current or future product candidates.
We may incur unexpected costs or experience delays in completing, or ultimately be unable to complete, the development of AMX0035, avexitide or any other current or future product candidates.
To obtain regulatory approval to commercialize AMX0035, avexitide and any other current or future product candidates, we must demonstrate through extensive preclinical studies and clinical trials that such product candidates are safe and effective in humans. Preclinical and clinical testing are expensive and can take many years to complete, and their outcome is inherently uncertain. Failure can occur at any time during the clinical trial process and our future clinical trial results may not be successful, which could impact our ability to obtain regulatory approvals for AMX0035, avexitide or any other current or future product candidates.
We may experience delays in completing our clinical trials or preclinical studies and initiating or completing additional clinical trials. We may also experience numerous unforeseen events during our clinical trials that could delay or prevent our ability to receive marketing approval or commercialize AMX0035, avexitide or any other current or future product candidates we develop, including:
Regulators, IRBs of the institutions in which clinical trials are being conducted or data monitoring committees may suspend or terminate a clinical trial due to a number of factors, including failure to conduct the clinical trial in accordance with regulatory requirements or our clinical protocols, inspection of the clinical trial operations or trial site by the FDA or other regulatory authorities resulting in the imposition of a clinical hold, unforeseen safety issues or adverse side effects, failure to demonstrate a benefit from using a drug, changes in governmental regulations or administrative actions or lack of adequate funding to continue the clinical trial.
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For example, we submitted an Investigational New Drug application to the FDA for AMX0114. The FDA restricted dosing to an amount that is lower than the Company's proposed starting dose of 12.5 mg and has requested additional information, which resulted in a clinical hold. Toxicology studies showed a greater than 10X safety margin at the starting dose of 12.5 mg based on the no observed adverse effect level (NOAEL) determined by independent toxicology firms. We are working to address FDA comments. We believe the trial can be completed outside of the U.S if needed.
Negative or inconclusive impressions of the results from our earlier clinical trials of AMX0035 for the treatment of ALS or AD, the results from earlier clinical trials of avexitide performed by Eiger or any other clinical trial or preclinical studies in animals that we or Eiger, with respect to avexitide, have conducted, could mandate repeated or additional preclinical studies or clinical trials and could delay marketing approvals or result in changes to or delays in preclinical studies or clinical trials of AMX0035 in other indications. We do not know whether any clinical trials that we may conduct will demonstrate adequate efficacy and safety to result in regulatory approval to market AMX0035 for our intended indications, avexitide or any future product candidate.
Our failure to successfully initiate and complete clinical trials of AMX0035 for Wolfram syndrome, PSP, or potential additional indications or avexitide and to demonstrate the efficacy and safety of AMX0035 and avexitide, including each component thereof, necessary to obtain regulatory approval to market AMX0035 and avexitide, would significantly harm our business and ability to continue developing and marketing AMX0035 and avexitide for any indications. Our product candidate development costs will also increase if we experience delays in testing or obtaining and maintaining regulatory approvals and we may be required to obtain additional funds to complete clinical trials. We cannot assure you that our clinical trials will begin as planned or be completed on schedule, if at all, or that we will not need to restructure our trials after they have begun. Significant clinical trial delays or the need for additional data from our clinical trials also could shorten any periods during which we may have the exclusive right to commercialize AMX0035, avexitide or any other current or future product candidates or allow our competitors to bring products to market before we do and impair our ability to successfully commercialize such product candidates, which may harm our business and results of operations. In addition, many of the factors that cause, or lead to, delays of clinical trials may ultimately lead to the denial of regulatory approval of AMX0035, avexitide or any future product candidate.
Even if we complete the necessary preclinical studies and clinical trials, the marketing approval process is expensive, time-consuming and uncertain and may prevent us or any future collaboration partners from obtaining or maintaining approvals for the commercialization of our current or any future product candidate we develop.
Any product candidate we may develop and the activities associated with its development and commercialization, including its design, testing, manufacture, safety, efficacy, recordkeeping, labeling, storage, approval, advertising, promotion, sale, and distribution, are subject to comprehensive regulation by the FDA and other regulatory authorities in the U.S. and in other countries. Failure to obtain marketing approval for a product candidate will prevent us from commercializing that product candidate in a given jurisdiction. Although we have invested substantial time and resources to date in pursuit of regulatory approval and toward potential commercialization, we have only received regulatory approval for AMX0035 (RELYVRIO) in the U.S. and marketing authorization with conditions for AMX0035 (ALBRIOZA) in Canada, which products we have since ceased marketing and selling from the market, and have not received any other regulatory approvals to market any product candidates from regulatory authorities in any jurisdiction, and it is possible that none of the product candidates we may seek to develop in the future will ever obtain regulatory approval. We have no experience in filing and supporting the applications necessary to gain marketing approvals and rely on third-party CROs or regulatory consultants to assist us in this process. Securing regulatory approval requires the submission of extensive preclinical and clinical data and supporting information to the various regulatory authorities for each therapeutic indication to establish the product candidate’s safety, purity, efficacy and potency. Securing regulatory approval also requires the submission of information about the product manufacturing process to, and inspection of manufacturing facilities by, the relevant regulatory authority. Any product candidates we develop may not be effective, may be only moderately effective, or may prove to have undesirable or unintended side effects, toxicities or other characteristics that may preclude our obtaining marketing approval or prevent or limit commercial use.
The process of obtaining marketing approvals, in the U.S. and other foreign jurisdictions, is expensive, may take many years if additional clinical trials are required, if approval is obtained at all, and can vary substantially based upon a variety of factors, including the type, complexity, and novelty of the product candidates involved. Changes in marketing approval policies during the development period, changes in or the enactment of additional statutes or regulations, or changes in regulatory review for each submitted product application, may cause delays in the approval or rejection of an application. The FDA and comparable authorities in other countries have substantial discretion in the approval process and may refuse to accept any application or may decide during the review process that our data are insufficient for approval and require additional preclinical, clinical or other studies. In addition, varying interpretations of the data obtained from preclinical and clinical testing could delay, limit, or prevent marketing approval of, or limit the approved labeling for, a product candidate. Additionally, the FDA has discretion to refer an application for a novel drug or a drug that presents difficult questions of safety or efficacy to an advisory committee. For example, our approval of RELYVRIO in the U.S. underwent two Advisory Committee reviews, which delayed ultimate approval.
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If we experience delays in obtaining approval or if we fail to maintain or obtain approval of AMX0035, avexitide or of any product candidates we may develop, the commercial prospects for those product candidates, including for AMX0035 or avexitide, may be harmed, and our ability to generate revenues will be materially impaired.
The results of early-stage clinical trials and preclinical studies may not be predictive of future results. Initial or preliminary data in our clinical trials may not be indicative of results obtained when these trials are completed or in later stage trials.
The results of preclinical studies may not be predictive of the results of clinical trials, and the results of any early-stage clinical trials we commence may not be predictive of the results of the later-stage clinical trials. In addition, initial data in clinical trials may not be indicative of results obtained when such trials are completed. There can be no assurance that any of our clinical trials will ultimately be successful or support further clinical development of AMX0035, avexitide or any other current or future product candidates. For example, the clinical results seen in the CENTAUR trial were different than the results seen in our global Phase 3 PHOENIX clinical trial. There is a high failure rate for drugs and biologics proceeding through clinical trials. A number of companies in the pharmaceutical and biotechnology industries have suffered significant setbacks in clinical development even after achieving promising results in earlier studies, and any such setbacks in our clinical development could have a material adverse effect on our business and operating results.
Additionally, we have in the past utilized and may in the future utilize an “open-label” clinical trial design. An “open-label” clinical trial is one where both the patient and investigator know whether the patient is receiving the investigational product candidate or either an existing approved drug or placebo. Most open-label clinical trials test only the investigational product candidate and sometimes may do so at different dose levels. Open-label clinical trials are subject to various limitations that may exaggerate any therapeutic effect as patients in open-label clinical trials are aware when they are receiving treatment. Open-label clinical trials may be subject to a “patient bias” where patients perceive their symptoms to have improved merely due to their awareness of receiving an experimental treatment. In addition, open-label clinical trials may be subject to an “investigator bias” where those assessing and reviewing the physiological outcomes of the clinical trials are aware of which patients have received treatment and may interpret the information of the treated group more favorably given this knowledge. The results from an open-label trial may not be predictive of future clinical trial results with AMX0035, avexitide or any future product candidates when studied in a controlled environment with a placebo or active control.
Interim topline and preliminary data from our clinical trials that we announce or publish from time to time may change as more patient data become available and are subject to audit and verification procedures that could result in material changes in the final data.
From time to time, we may publish interim topline or preliminary data from our clinical trials. Interim data from clinical trials that we may complete are subject to the risk that one or more of the clinical outcomes may materially change as patient enrollment continues and more patient data become available. Preliminary or topline results also remain subject to audit and verification procedures that may result in the final data being materially different from the preliminary data we previously published. As a result, interim and preliminary data should be viewed with caution until the final data are available. Adverse differences between preliminary or interim data and final data could significantly harm our reputation and business prospects.
Enrollment and retention of patients in clinical trials is an expensive and time-consuming process and could be made more difficult or rendered impossible by multiple factors outside our control.
Patient enrollment is a significant factor in the timing of clinical trials, and the timing of our clinical trials depends, in part, on the speed at which we can recruit patients to participate in our trials, as well as completion of required follow-up periods. We may not be able to initiate or continue clinical trials for AMX0035, avexitide or any other current or future product candidates if we are unable to locate and enroll a sufficient number of eligible patients to participate in these trials to such trial’s conclusion as required by the FDA or other comparable foreign regulatory authorities. Additionally, certain clinical trials for AMX0035, avexitide and any other current or future product candidates may be focused on indications with relatively small patient populations, which may further limit enrollment of eligible patients or may result in slower enrollment than we anticipate. The eligibility criteria of our clinical trials, once established, may further limit the pool of available trial participants. For example the number of patients suffering from Wolfram syndrome and PBH, is small and, in some cases, has not been established with precision. If the actual number of patients with these diseases is smaller than we anticipate, we may encounter difficulties in enrolling patients in our clinical trials, thereby delaying or preventing development and approval of AMX0035, avexitide or any other current or future product candidates. Even once enrolled, we may be unable to retain a sufficient number of patients to complete any of our trials. Neurodegenerative diseases have particular challenges, including significant mobility issues, morbidities and other complications that have historically made retention in clinical trials more challenging. In the past, we have had discontinuations in our clinical trials, including in our CENTAUR trial and our PHOENIX trial, and their open label extensions. Discontinuations may occur in current or future trials and could result in delays of
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completion of our clinical trials and affect our ability to enroll additional patients in our clinical trials and impact the integrity of data from our clinical trials.
Patient enrollment and retention in clinical trials depends on many factors, including the size of the patient population, the severity of the disease under investigation, the nature of the trial protocol, the existing body of safety and efficacy data for the product candidate, the number and nature of competing treatments and ongoing clinical trials of or expanded access to competing therapies for the same indication, the proximity of patients to clinical sites, the eligibility criteria for the trial, the ability to adequately monitor patients during a trial, clinicians’ and patients’ perceptions as to the potential advantages of the product candidate being studied, and the risk that patients will drop out of a trial before completing all site visits. There are limited patient pools from which to draw in order to complete our clinical trials in a timely and cost-effective manner, including due to the fact that the diseases we target are rare. Moreover, for example, the patient population for PBH may decrease due to the development of novel treatments for obesity, reducing the potential need for bariatric surgery. Furthermore, our efforts to build relationships with patient communities may not succeed, which could result in delays in patient enrollment in our clinical trials.
Any negative results we may report in clinical trials of AMX0035, avexitide or any future product candidate may also make it difficult or impossible to recruit and retain patients in other clinical trials of that same product candidate. For example, the PHOENIX trial did not meet its primary or secondary endpoints, which may discourage patients from participating in clinical trials of AMX0035 in other indications. Delays or failures in planned patient enrollment or retention may result in increased costs, program delays or both, which could have a harmful effect on our ability to develop AMX0035 in Wolfram syndrome, PSP and additional indications, avexitide and any other current or future product candidates, or could render further development impossible. Further, if patients drop out of our clinical trials, miss scheduled doses or follow-up visits, or otherwise fail to follow clinical trial protocols, whether as a result of public health epidemics and related illness, the integrity of data from our clinical trials may be compromised or not accepted by the FDA or other regulatory authorities, which would represent a significant setback for the applicable program. In addition, we may rely on CROs and clinical trial sites to ensure proper and timely conduct of our future clinical trials and, while we intend to enter into agreements governing their services, we will be limited in our ability to compel their actual performance.
Changes in methods of product candidate manufacturing or formulation may result in additional costs or delay.
As product candidates proceed through preclinical studies to late-stage clinical trials towards potential approval and commercialization, it is common that various aspects of the development activities, such as manufacturing methods and formulation, are altered along the way in an effort to optimize processes and results. Any of these changes could cause AMX0035, avexitide or any other current or future product candidates to perform differently and affect the results of ongoing clinical trials or other future clinical trials conducted with the materials manufactured using altered processes. For example, in seeking approval of AMX0035 in Europe, we submitted data supporting a different formulation of AMX0035 from the formulation evaluated in the CENTAUR trial. Changes to commercial formulations from those studied clinically could lead regulatory authorities to delay the approval of our marketing applications until we can demonstrate through additional clinical data that there is comparability in the bioavailability of the two different formulations or may require us to revert to the prior formulation evaluated clinically. Should we have to conduct comparability testing to bridge earlier clinical data obtained from product candidates produced under earlier manufacturing methods or formulations with the planned commercial formulation, regulatory authorities may disagree on the interpretation of results from this testing. This could delay completion of clinical trials, require the repetition of one or more clinical trials, increase clinical trial costs, delay approval of AMX0035, avexitide or any other current or future product candidates and jeopardize our ability to commence sales and generate revenue.
Certain of our product candidates require specific shipping, storage, handling and administration, which in some cases, may require cold-chain logistics and subject our product candidates to risk of loss or damage if failures occur.
Certain of our product candidates are sensitive to temperature, storage and handling conditions. They must be stored at very low temperatures in specialized freezers or specialized shipping containers until immediately prior to use. The handling and administration of the product, if approved, may need to be performed according to specific instructions and in some steps within specific time periods. Failure to correctly handle our product could negatively impact the efficacy and or safety of our product, or cause a loss of product. In addition, if approved, certain of our products may need to be frozen using specialized equipment and maintained following specific procedures in order to be stored without damage in a cost-efficient manner and without degradation. We will need to scale-up a cost-effective and reliable cold-chain distribution and logistics network, which we may be unable to accomplish. Failure to effectively scale-up our cold-chain supply logistics, by us or third parties, could in the future lead to additional manufacturing costs and delays in our ability to supply required quantities for commercial supply. For these and other reasons, we may not be able to manufacture our current or future product candidates at commercial scale or in a cost-effective manner. Even if we are able to manufacture and distribute the product candidates, if our products require specific procedures to maintain and use them, we may be limited in commercial opportunity.
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AMX0035, avexitide or any future product candidate may cause undesirable side effects or have other properties that could delay or prevent its regulatory approval, limit the commercial profile of an approved label, or result in significant negative consequences following regulatory approval, if obtained.
Undesirable side effects caused by AMX0035, avexitide or any future product candidate, could cause us or regulatory authorities to interrupt, delay or halt clinical trials and could result in a more restrictive label or the delay, denial or withdrawal of regulatory approval by the FDA or comparable foreign regulatory authorities. Results of our preclinical studies or clinical trials could reveal a high and unacceptable severity and prevalence of side effects or unexpected characteristics. In clinical trials of AMX0035 to date, AMX0035 has been generally well-tolerated, with most common treatment-emergent adverse events including diarrhea, abdominal pain, nausea, upper respiratory infection, constipation, headache, fatigue, proteinuria, and decreased appetite. In addition, it has been reported that patients experience a bad taste when taking AMX0035. In animal studies, administration of AMX0035 to rats throughout pregnancy and lactation resulted in increased offspring mortality at all doses tested, which were less than or similar to the clinical doses tested in our clinical trials. However, there can be no guarantee that we would observe a similar tolerability profile of AMX0035 in future clinical trials or for other indications. Many compounds that initially showed promise in clinical or earlier stage testing are later found to cause undesirable or unexpected side effects that prevented further development of the compound.
In clinical trials to date of avexitide, avexitide was generally well-tolerated. The most common adverse events were injection site bruising, headache, and nausea; these occurred more often with placebo than either avexitide dose. However, there can be no guarantee that we would observe a similar tolerability profile of avexitide in future clinical trials or for other indications.
If unacceptable or severe side effects arise in the development of AMX0035, avexitide or any other current or future product candidates, we, the FDA or comparable foreign regulatory authorities, the IRBs, or independent ethics committees at the institutions in which our trials are conducted, or the independent safety monitoring committee could suspend or terminate our clinical trials or regulatory authorities could order us to cease clinical trials or deny approval of AMX0035, avexitide or any other current or future product candidates for any or all targeted indications. Treatment-emergent side effects that are deemed to be drug-related could also affect subject recruitment or the ability of enrolled subjects to complete the trial or result in potential product liability claims. Undesirable side effects in one of our clinical trials for AMX0035 in one indication or avexitide could adversely affect enrollment in clinical trials, regulatory approval and commercialization of AMX0035 in other indications or avexitide. Additionally, there may be negative findings regarding components of AMX0035, avexitide or future product candidates by other parties. Any negative findings by third parties may impact the future approvability or labeling of AMX0035, avexitide or other product candidates we may develop. In addition, side effects may not be appropriately recognized or managed by the treating medical staff. Inadequate training in recognizing or managing the potential side effects of AMX0035, avexitide or any future product candidates could result in patient injury or death. Any of these occurrences may harm our business, financial condition and prospects significantly.
Bitter taste was frequently observed in our clinical trials of AMX0035. While bitter taste, by itself, does not present a safety risk for patients, it may lead to higher levels of patient non-compliance, which could have the effect of reducing the observed efficacy of AMX0035 in our clinical trials, or limit its commercial adoption. AMX0035 is a combination of TURSO and PB. PB has been approved by the FDA and other regulatory authorities for the treatment of patients with certain urea cycle disorders and TURSO has been approved in Italy for diseases of cirrhotic liver disorders such as primary biliary cirrhosis. It is possible that one or more of the active moieties in AMX0035 has also been approved by FDA or other regulatory authorities. Even if AMX0035 receives marketing approval and is commercialized in a jurisdiction, we would continue to be subject to the risks that the applicable regulatory authorities could revoke approval of PB or TURSO or any active moiety in AMX0035, if applicable, or that efficacy, manufacturing or supply issues could arise with PB or TURSO or any active moiety in AMX0035, if applicable. This could result in our own products being removed from the market or being less commercially successful.
Finally, clinical trials of AMX0035 and avexitide are conducted in carefully defined sets of patients who have agreed to enter into clinical trials. Consequently, it is possible that our clinical trials, or those of any future collaborator, may indicate an apparent positive effect of AMX0035, avexitide or any other current or future product candidate that is greater than the actual positive effect, if any, or alternatively fail to identify undesirable side effects.
Demand for expanded access to AMX0035 could negatively affect our reputation and harm our business.
We are developing AMX0035 for the treatment of Wolfram syndrome, PSP and other potential future indications for which there are currently limited or no available therapeutic options. It is possible for individuals or groups to target companies with disruptive social media campaigns related to a request for access to unapproved drugs for patients with significant unmet medical need. If we experience a similar social media campaign regarding our decision to provide or not provide access to AMX0035 or any of our future product candidates under an expanded access policy, our reputation may be negatively affected and our business may be harmed.
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In the past, media attention to individual patients’ expanded access requests has resulted in the introduction and enactment of legislation at the local and national level, including “Right to Try” laws, such as the federal Right to Try Act of 2017, which are intended to allow patients access to unapproved therapies earlier than traditional EAPs. A possible consequence of both activism and legislation in this area may be the need for us to initiate an EAP beyond that which we have submitted to the FDA or to make AMX0035 or any future product candidates more widely available sooner than anticipated.
In addition, some patients who receive access to drugs prior to their commercial approval through compassionate use, EAPs or right to try access have life-threatening illnesses and have exhausted all other available therapies. The risk for SAEs in this patient population is high, which could have a negative impact on the safety profile of AMX0035 or future product candidates, which could cause significant delays or an inability to successfully commercialize AMX0035 or future product candidates, which could materially harm our business. We may in the future need to restructure or pause any future compassionate use and/or EAP we initiate in order to perform the controlled clinical trials required for regulatory approval and successful commercialization of AMX0035 or future product candidates, which could prompt adverse publicity or other disruptions related to current or potential participants in such programs.
If we fail to develop and commercialize AMX0035 for additional indications or avexitide or fail to discover, develop or acquire and commercialize other product candidates, we may be unable to grow our business and our ability to achieve our strategic objectives would be impaired.
We are currently, and plan to continue to, evaluate AMX0035 in other indications other than ALS, to continue to develop and evaluate avexitide and develop other product candidates. We intend to evaluate internal opportunities from AMX0035, avexitide or other potential product candidates, and also may choose to in-license or acquire other product candidates as well as commercial products to treat patients suffering from neurodegenerative diseases and CNS or other disorders with significant unmet medical needs and limited treatment options. For example, we recently completed the acquisition of substantially all of the rights, title and interests in, to and under those assets and interests used by Eiger in the development, manufacture and commercialization of avexitide. Avexitide has been evaluated in five Phase 2 clinical studies for PBH and Congenital HI, both diseases with unmet need, and we intend to initiate a Phase 3 program in PBH.
Avexitide and any other potential product candidates have and will require additional, time-consuming development efforts prior to commercial sale, including preclinical studies, clinical trials and approval by the FDA and/or other applicable foreign regulatory authorities. All product candidates are prone to the risks of failure that are inherent in pharmaceutical product development, including the possibility that the product candidate will not be shown to be sufficiently safe and effective for approval by regulatory authorities. In addition, we cannot assure you that any such products that are approved will be manufactured or produced economically, successfully commercialized or widely accepted in the marketplace or be more effective than other commercially available alternatives.
Research activities to identify product candidates require substantial technical, financial and human resources, whether or not any product candidates are ultimately identified. Our research activities or observation of third-party research activities may initially show promise in identifying potential product candidates, yet fail to yield product candidates for clinical development for many reasons, including the following:
If we are unsuccessful in identifying and developing additional product candidates, our potential for growth and achieving our strategic objectives may be impaired.
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We may not be successful in our efforts to expand our pipeline by identifying additional product candidates or indications and modifications for which to investigate AMX0035 or avexitide in the future. We may expend our limited resources to pursue particular product candidates or indications or formulations for AMX0035 or avexitide and fail to capitalize on such product candidates or indications or formulations of AMX0035 or avexitide that may be more profitable or for which there is a greater likelihood of success.
Because we have limited financial and managerial resources, we are focused on specific indications and modifications for AMX0035, avexitide and AMX0114. As a result, we may fail to generate additional clinical development opportunities for such candidates for a number of reasons, including, that such candidates may in certain indications, on further study, be shown to have harmful side effects, limited to no efficacy, or other characteristics that suggest it is unlikely to receive marketing approval and achieve market acceptance in such additional indications.
We plan to conduct several clinical trials for AMX0035 in parallel over the next several years, including clinical trials in patients with Wolfram syndrome, PSP and other indications, which may make our decision as to which indication to prioritize more difficult. Moreover, we intend to conduct a clinical trial of avexitide in PBH and may conduct others in other indications as well. As a result, we may forgo or delay pursuit of opportunities with other indications that we believe could have had greater commercial potential or likelihood of success. In addition, we are continuing to evaluate plans to explore the use of AMX0035 in patients with AD, and other product candidates in ALS and additional neurodegenerative diseases. However, we may focus on or pursue one or more of our target indications over other potential indications and product candidates and such development efforts may not be successful, which would cause us to delay the clinical development and approval of AMX0035, avexitide, and other product candidates. Furthermore, research activities to identify additional indications for AMX0035, avexitide and other product candidates require substantial technical, financial, and human resources. We may not successfully develop these additional modifications for chemistry-related, stability-related, or other reasons. We have recently announced the development of AMX0114, an antisense oligonucleotide, targeting Calpain-2 for ALS and other neurodegenerative diseases. We are currently advancing AMX0114 through IND-enabling studies and expect to enter the clinic in 2024. Our resource allocation decisions may cause us to fail to capitalize on viable commercial products or profitable market opportunities. Our spending on current and future research and development activities for specific indications or formulations of AMX0035 or for AMX0114 or other product candidates may not yield any commercially viable products.
Additionally, we may pursue in-licenses or acquisitions of development-stage assets or programs, which entails additional risk to us. For example, we recently completed the acquisition of substantially all of the rights, title and interests in, to and under those assets and interests used by Eiger in the development, manufacture and commercialization of avexitide. Avexitide has been evaluated in five Phase 2 clinical studies for PBH and congenital HI, both diseases with unmet need, and we intend to initiate a Phase 3 program in PBH. Identifying, selecting and acquiring promising product candidates requires substantial technical, financial, and human resources expertise and, once acquired, requires us to devote substantial resources. Efforts to do so may not result in the actual acquisition or license of a particular product candidate, and, if acquired, may results in extensive diligence and preparation efforts, each of which may potentially result in a diversion of our management’s time and the expenditure of our resources with no resulting benefit.
For example, if we are unable to identify programs that ultimately result in approved products, we may spend material amounts of our capital and other resources evaluating, acquiring and developing products that ultimately do not provide a return on our investment.
Competitive products may reduce or eliminate the commercial opportunity for AMX0035 for our intended indications or avexitide. If our competitors develop technologies or product candidates more rapidly than we do, or their technologies or product candidates are more effective or safer than ours, our ability to develop and successfully commercialize AMX0035 or avexitide may be adversely affected.
The clinical and commercial landscape for the treatment of the diseases we are focused on is highly competitive and subject to rapid and significant technological change. We will face competition with respect to any future indications of AMX0035, avexitide or other candidates that we may seek to develop or commercialize in the future, from major pharmaceutical companies, specialty pharmaceutical companies and biotechnology companies worldwide. There are also a number of large pharmaceutical and biotechnology companies that currently market and sell drugs or are pursuing the development of drug candidates for the treatment of the indications that we are pursuing. Potential competitors also include academic institutions, government agencies and other public and private research organizations that conduct research, seek patent protection and establish collaborative arrangements for research, development, manufacturing and commercialization.
Many of our competitors have significantly greater financial resources, established presence in the market, expertise in research and development, manufacturing, preclinical and clinical testing, obtaining regulatory approvals and reimbursement and marketing approved products than we do. Accordingly, our competitors may be more successful than we may be in obtaining regulatory approval for therapies and achieving widespread market acceptance. Our competitors’ products may be more effective, or more effectively marketed and sold, than any product candidate we may commercialize and may render AMX0035, avexitide or any future product
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candidates obsolete or non-competitive before we can recover development and commercialization expenses. If AMX0035 or avexitide is approved for the indications we are currently pursuing, it could compete with a range of therapeutic treatments that are in development. In addition, our competitors may succeed in developing, acquiring or licensing technologies and products that are more effective or less costly than AMX0035, avexitide or any future product candidates that we may develop, which could render such product candidates obsolete and noncompetitive.
Following any approval for AMX0035, avexitide or any other future product candidate, we may face competition based on many different factors, including the efficacy, safety and tolerability of our products, the ease with which our products can be administered, the timing and scope of regulatory approvals for these products, the availability and cost of manufacturing, marketing and sales capabilities, price, reimbursement coverage and patent position. Existing and future competing products could present superior treatment alternatives, including being more effective, safer, less expensive or marketed and sold more effectively than any products we commercialize. Competitive products may make any products we commercialize obsolete or noncompetitive before we recover the expense of developing and commercializing our product candidates. Such competitors could also recruit our employees, which could negatively impact our level of expertise and our ability to execute our business plan.
In addition, our competitors may obtain patent protection, regulatory exclusivities or regulatory approval and commercialize products more rapidly than we do, which may impact future approvals or sales of any of our product candidates that receive regulatory approval. Following approval by the FDA or other foreign regulatory bodies for the commercial sale of AMX0035, avexitide or any future product candidates, we will also be competing with respect to marketing capabilities and manufacturing efficiency. We expect competition among products will be based on product efficacy and safety, the timing and scope of regulatory approvals, availability of supply, marketing and sales capabilities, product price, reimbursement coverage by government and private third-party payors, regulatory exclusivities and patent position. Our profitability and financial position will suffer if our product candidates receive regulatory approval, but cannot compete effectively in the marketplace.
Mergers and acquisitions in the pharmaceutical and biotechnology industries may result in even more resources being concentrated among a smaller number of our competitors. Smaller and other early stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies. These third parties compete with us in recruiting and retaining qualified scientific and management personnel and establishing clinical trial sites, as well as in acquiring technologies complementary to, or necessary for, our activities.
Obtaining and maintaining regulatory approval of AMX0035, avexitide or any future product candidates in one jurisdiction does not mean that we will be successful in obtaining regulatory approval of those product candidates in other jurisdictions.
Obtaining and maintaining regulatory approval of AMX0035, avexitide and any future product candidates in one jurisdiction does not guarantee that we will be able to obtain or maintain regulatory approval in any other jurisdiction, while a failure or delay in obtaining regulatory approval in one jurisdiction may have a negative effect on the regulatory approval process in others. Approval procedures vary among jurisdictions and can involve requirements and administrative review periods different from, and greater than, those in the U.S. and other jurisdictions, including additional preclinical studies or clinical trials, as clinical trials conducted in one jurisdiction may not be accepted by regulatory authorities in other jurisdictions. In many jurisdictions outside the U.S., including Canada, and certain jurisdictions in the EU, a product candidate must be approved for reimbursement before it can be approved for sale in that jurisdiction. In some cases, the price that we intend to charge for our products is also subject to approval.
Regulatory authorities in jurisdictions outside of the U.S. have requirements for approval of product candidates with which we must comply prior to marketing in those jurisdictions and such regulatory requirements can vary widely from country to country. Obtaining other regulatory approvals and compliance with other regulatory requirements could result in significant delays, difficulties and costs for us and could require additional preclinical studies or clinical trials, which could be costly and time-consuming and could delay or prevent the introduction of our products in certain countries. The foreign regulatory approval process involves all of the risks associated with FDA approval. We do not have experience in obtaining regulatory approval in international markets outside of Canada. If we fail to comply with the regulatory requirements in international markets and/or obtain and maintain applicable marketing approvals, our target market will be reduced and our ability to realize the full market potential of AMX0035, avexitide or any future product candidates will be harmed.
Even though we have obtained orphan drug designation for AMX0035 for the treatment of Wolfram syndrome and for avexitide for the treatment of hyperinsulinemic hypoglycemia (which includes PBH and Congenital HI) in the U.S. and for Congenital HI in Europe by the EMA, we may not be able to obtain or maintain the benefits associated with orphan drug status, including market exclusivity.
Regulatory authorities in some jurisdictions, including the U.S. and the EU, may designate drugs for relatively small patient populations as orphan drugs. Under the Orphan Drug Act, the FDA may designate a drug as an orphan drug if it is intended to treat a
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rare disease or condition, which is generally defined as a patient population of fewer than 200,000 people in the U.S., or a patient population of greater than 200,000 people in the U.S., but for which there is no reasonable expectation that the cost of developing the drug will be recovered from sales in the U.S. In the EU, an orphan designation may be granted in respect of products that are intended for the diagnosis, prevention or treatment of a life-threatening or chronically debilitating condition affecting no more than five in 10,000 people in the EU when the application is made. Additionally, designation is granted for products intended for the diagnosis, prevention or treatment of a life-threatening or chronically debilitating condition when, without incentives, it is unlikely that sales of the product in the EU would be sufficient to justify the necessary investment in developing the product. In either case, the applicant for orphan designation must also demonstrate that no satisfactory method of diagnosis, prevention, or treatment for the condition has been authorized (or, if such a method exists, the new product would be a significant benefit to those affected compared to the product available).
We received orphan drug status for AMX0035 for the treatment of patients with Wolfram syndrome in the U.S. in November 2020. Eiger received orphan drug status for avexitide for the treatment of hyperinsulinemic hypoglycemia (which includes PBH and Congenital HI) in the U.S. in December 2016 and for Congenital HI in Europe by the EMA in November 2019. Generally, if a drug with an orphan drug designation subsequently receives the first marketing approval for the indication for which it has such designation, the drug may be entitled to a period of marketing exclusivity, which precludes the FDA or the other regulatory bodies from approving another marketing authorization application for the same drug for that time period. Another drug may receive marketing approval prior to AMX0035 or avexitide. The applicable period is seven years in the U.S. and ten years in the EU, which may be extended by six months and two years, respectively, in the case of product candidates that have complied with the respective regulatory agency’s agreed upon pediatric investigation plan. The exclusivity period in the EU may be reduced to six years if, at the end of the fifth year, it is demonstrated that a product no longer meets the criteria for orphan designation or if the product is sufficiently profitable so that market exclusivity is no longer justified. In the EU, during the ten-year period of orphan marketing exclusivity, neither the competent authorities of the EU Member States, the EMA, or the European Commission are permitted to accept applications or grant marketing authorization for similar medicinal products to the authorized orphan product. A “similar medicinal product” is defined as a medicinal product containing a similar active substance or substances as contained in an authorized orphan medicinal product, and which is intended for the same therapeutic indication. Legislation has been proposed by the European Commission that, if implemented, has the potential in some cases to shorten the ten-year period of orphan marketing exclusivity. Orphan drug exclusivity may be lost if the FDA or the EMA determines that the request for designation was materially defective or if the manufacturer is unable to assure sufficient quantity of the drug to meet the needs of patients with the rare disease or condition. In addition, even after a drug is granted orphan exclusivity and approved, the FDA and the EMA can subsequently approve another drug for the same condition before the expiration of the seven-year (or ten-year in the EU) exclusivity period if the FDA or the EMA concludes that the later drug is clinically superior in that it is shown to be safer, more effective or makes a major contribution to patient care. In addition, if an orphan designated product receives marketing approval for an indication broader than or different from what is designated, such product may not be entitled to orphan exclusivity. Even though the FDA has granted orphan drug designation to AMX0035 for the treatment of Wolfram syndrome, if we receive approval for AMX0035 for a modified or different indication, our current orphan designation may not provide us with exclusivity.
Orphan drug designation does not convey any advantage in, or shorten the duration of, the regulatory review or approval process. Also, regulatory approval for any product candidate may be withdrawn, and other product candidates may obtain approval before us and receive orphan drug exclusivity, which could block us from entering the market.
Even if we obtain orphan drug exclusivity for AMX0035 or avexitide, that exclusivity may not effectively protect us from competition because different drugs can be approved for the same condition before the expiration of the orphan drug exclusivity period. For example, even though AMX0035 is entitled to orphan drug exclusivity, that exclusivity may not prevent the approval of TURSO by the FDA or other regulatory authorities as a monotherapy treatment for Wolfram syndrome if those regulatory agencies determine that TURSO is a different drug product from AMX0035. In addition, the regulatory authorities may find that this monotherapy treatment is clinically superior to our fixed dose product and approve it even if we are granted orphan drug exclusivity. U.S. lawmakers have also recently raised the possibility that regulatory or legislative changes might need to be made to the Orphan Drug Act to foster competition. This includes the introduction of legislation that, if adopted into law, would require us to demonstrate to the FDA that AMX0035 or avexitide would be economically unviable when facing competition to maintain our exclusivity.
We may pursue orphan drug designation for AMX0035 or avexitide for the treatment of additional indications. The incidence and prevalence of the target patient populations for these indications will be based on our estimates and third-party data. If the market opportunity for these target populations is larger than we estimate, we may be unable to receive orphan drug designation. Additionally, if orphan drug designation is granted, we may be unable to maintain any benefits associated with orphan drug designation, including market exclusivity.
Periodically, we make estimates regarding the incidence and prevalence of target patient populations based on various third-party sources and internally generated analysis. Our estimates may be inaccurate or based on imprecise data. As described above, under the
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Orphan Drug Act, the FDA may designate a drug as an orphan drug if it is intended to treat a rare disease or condition, which is generally defined as a patient population of fewer than 200,000 people in the U.S., or a patient population of greater than 200,000 people in the U.S., but for which there is no reasonable expectation that the cost of developing the drug will be recovered from sales in the U.S. If our incidence or prevalence estimates for future indications for which we may seek orphan drug designation are incorrect, we may be unable to receive orphan drug designation.
Even if the FDA grants orphan drug designation for AMX0035 or avexitide for other indications, exclusive marketing rights in the U.S. may be limited if we seek FDA marketing approval for an indication broader than the orphan designated indication. Additionally, any product candidate that initially receives orphan drug status designation, may lose such designation if the FDA later determines that the request for designation was materially defective or if the manufacturer is unable to assure sufficient quantities of the product to meet the needs of patients with the rare disease or condition. In addition, others may obtain orphan drug status for products addressing the same diseases or conditions as products we are developing, thus limiting our ability to compete in the markets addressing such diseases or conditions for a significant period of time. As a result, our business and prospects could suffer.
We may pursue Priority Review Designation for product candidates that we may develop, but we might not receive such designations, and Priority Review Designations may not lead to a faster development or regulatory review or approval process.
If the FDA determines that a product candidate offers a treatment for a serious condition and, if approved, the product would provide a significant improvement in safety or effectiveness, the FDA may designate the product candidate for priority review. A Priority Review Designation means that the goal for the FDA to review an application is six months, rather than the standard review period of ten months. For example, we received priority review for AMX0035 for the treatment of ALS, and we may in the future request Priority Review Designation for any future product candidates, however, we cannot assume that any application for future indications of AMX0035, avexitide or any other product candidate we may develop will meet the criteria for that designation. The FDA has broad discretion with respect to whether or not to grant priority review status to a product candidate, so even if we believe a particular product candidate is eligible for such designation or status, the FDA may decide not to grant it. Moreover, a Priority Review Designation does not necessarily mean a faster development or regulatory review or approval process or necessarily confer any advantage with respect to approval compared to standard FDA review and approval. For example, the FDA originally set the PDUFA date for AMX0035 for the treatment of ALS, for June 29, 2022, and then extended the review timeline for our NDA to September 2022. Receiving priority review from the FDA does not guarantee approval within the six-month review cycle or at all.
We may seek Fast Track Designation by the FDA for a product candidate that we develop, and we may be unsuccessful. If we are successful, the designation may not actually lead to a faster development or regulatory review or approval process.
We may seek Fast Track Designation for future product candidates we develop. If a product is intended for the treatment of a serious or life-threatening condition and preclinical or clinical data demonstrate the potential to address an unmet medical need for this condition, the product sponsor may apply for Fast Track Designation. The FDA has broad discretion whether or not to grant this designation, so even if we believe a particular product candidate is eligible for this designation, we cannot assure you that the FDA would decide to grant it. Even if we do receive Fast Track Designation, we may not experience a faster development process, review or approval compared to conventional FDA procedures. The FDA may rescind the Fast Track Designation if it believes that the designation is no longer supported by data from our clinical development activities.
Avexitide has been granted Breakthrough Therapy Designation for PBH and Congenital HI and we may seek Breakthrough Therapy Designation by the FDA for additional product candidates that we may develop, and we may be unsuccessful. If we are successful, the designation may not lead to a faster development or regulatory review or approval process, and it does not increase the likelihood that our product candidates will receive marketing approval, nor does such designation for avexitide guarantee a faster review process or marketing approval.
Avexitide has been granted Breakthrough Therapy Designation for PBH and Congenital HI and we may seek Breakthrough Therapy Designation for any additional product candidate that we may develop. A breakthrough therapy is defined as a drug that is intended, alone or in combination with one or more other drugs, to treat a serious or life-threatening disease or condition, and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over currently approved therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development. For drugs that have been designated as breakthrough therapies, interaction and communication between the FDA and the sponsor of the trial can help to identify the most efficient path for clinical development while minimizing the number of patients placed in ineffective control regimens. Drugs designated as breakthrough therapies by the FDA are also eligible for accelerated approval and priority review.
Designation as a breakthrough therapy is within the discretion of the FDA. Accordingly, even if we believe a product candidate we develop meets the criteria for designation as a breakthrough therapy, the FDA may disagree and instead determine not to make such designation. In any event, the receipt of Breakthrough Therapy Designation for a product candidate, such as avexitide, may not result
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in a faster development process, review or approval compared to drugs considered for approval under conventional FDA procedures and does not assure ultimate approval by the FDA. In addition, even if any product candidate we develop qualifies as a breakthrough therapy, the FDA may later decide that the drug no longer meets the conditions for qualification and rescind the designation.
The FDA has granted rare pediatric disease designation to avexitide for the treatment of Congenital HI. However, a marketing application for avexitide or any other product candidate, if approved, may not meet the eligibility criteria for a priority review voucher.
The FDA has granted rare pediatric disease designation to avexitide for the treatment of Congenital HI. Designation of a drug as a drug for a rare pediatric disease does not guarantee that an NDA for such drug will meet the eligibility criteria for a rare pediatric disease priority review voucher at the time the application is approved. Under the FDCA, we will need to request a rare pediatric disease priority review voucher in our original NDA for avexitide. The FDA may determine that an NDA for avexitide, if approved, does not meet the eligibility criteria for a priority review voucher, including for the following reasons:
The authority for the FDA to award rare pediatric disease priority review vouchers for drugs and biologics is currently limited to those candidates that receive rare pediatric disease designation on or prior to December 20, 2024, and the FDA may only award rare pediatric disease priority review vouchers through September 30, 2026. However, it is possible the FDA’s authority to award rare pediatric disease priority review vouchers will be further extended by Congress as reauthorization legislation is currently pending. Absent any such extension, if an NDA for avexitide is not approved prior to September 30, 2026 for any reason, regardless of whether it meets the criteria for a rare pediatric disease priority review voucher, it will not be eligible for a priority review voucher.
Product liability lawsuits against us or any of our future collaborators could divert our resources and attention, cause us to incur substantial liabilities and limit commercialization of AMX0035, avexitide or any other current or future product candidates.
We are exposed to potential product liability and professional indemnity risks that are inherent in the research, development, manufacturing, marketing and use of pharmaceutical products. The use of AMX0035, avexitide or any other current or future product candidates by us and any collaborators in clinical trials, and the prior sales of AMX0035 in the U.S. and Canada and continued use pursuant to the free drug program may expose us to liability claims. Product liability claims may be brought against us or our partners by participants enrolled in our clinical trials, patients, health care providers, pharmaceutical companies, our collaborators or others using, administering or selling any of our future approved products. If we cannot successfully defend ourselves against any such claims, we may incur substantial liabilities or be required to limit commercialization of AMX0035, avexitide or any other current or future product candidates. Regardless of the merits or eventual outcome, liability claims may result in:
Although the clinical trial process is designed to identify and assess potential side effects, clinical development does not always fully characterize the safety and efficacy profile of a new drug, and it is always possible that a drug, even after regulatory approval, may
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exhibit unforeseen side effects. If AMX0035, avexitide or any other current or future product candidates was to cause adverse side effects during clinical trials or after approval, we may be exposed to substantial liabilities. Physicians and patients may not comply with any warnings that identify known potential adverse effects and patients who should not use AMX0035, avexitide or any of our future product candidates. If any of our current or future product candidates are approved for commercial sale, we will be highly dependent upon consumer perceptions of us and the safety and quality of our products. We could be adversely affected if we are subject to negative publicity associated with illness or other adverse effects resulting from patients’ use or misuse of our products or any similar products distributed by other companies.
Although we maintain product liability insurance coverage in the amount of up to $10.0 million in the aggregate, including clinical trial liability, this insurance may not fully cover potential liabilities that we may incur. The cost of any product liability litigation or other proceeding, even if resolved in our favor, could be substantial. We may need to increase our insurance coverage as we commercialize AMX0035 or avexitide in the U.S. and other jurisdictions, if approved, or any other current or future product candidate that receives regulatory approval. In addition, insurance coverage is becoming increasingly expensive. If we are unable to maintain sufficient insurance coverage at an acceptable cost or to otherwise protect against potential product liability claims, it could prevent or inhibit the development and commercial production and sale of AMX0035, avexitide or any other current or future product candidates, which could harm our business, financial condition, results of operations and prospects.
Even if we, or any future collaborators, obtain and maintain regulatory approvals for AMX0035, avexitide or any other current or future product candidate, the terms of approvals and ongoing regulation of our products may limit how we manufacture and market our products, which could impair our ability to generate revenue.
Once regulatory approval has been granted, an approved product and its manufacturer and marketer are subject to ongoing review and extensive regulation. We, and any future collaborators, must therefore comply with requirements concerning advertising and promotion for AMX0035, avexitide or any other current or future product candidate for which we or they obtain regulatory approval. Promotional communications with respect to prescription drugs are subject to a variety of legal and regulatory restrictions and must be consistent with the information in the product’s approved labeling. Thus, we and any future collaborators will not be able to promote any products we develop for indications or uses for which they are not approved.
In addition, manufacturers of approved products and those manufacturers’ facilities are required to comply with extensive FDA and other regulatory bodies’ requirements, including ensuring that quality control and manufacturing procedures conform to cGMPs, which include requirements relating to quality control and quality assurance as well as the corresponding maintenance of records and documentation and reporting requirements. We, our contract manufacturers, any future collaborators and their contract manufacturers could fail to conform to cGMPs and be subject to periodic unannounced inspections by the FDA and other regulatory bodies to monitor and ensure compliance with cGMPs. Despite our efforts to inspect and verify regulatory compliance, one or more of our third-party manufacturing vendors may be found on regulatory inspection by the FDA or other authorities to be not in compliance with cGMP regulations, which may result in shutdown of the third-party vendor or invalidation of drug product lots or processes. In some cases, a product recall may be warranted or required, which would materially affect our ability to supply and market our drug products.
Accordingly, in any jurisdiction where we or any future collaborators, receive regulatory approval for AMX0035, avexitide or one or more future product candidates, we, and any future collaborators, and our and their contract manufacturers will continue to expend time, money and effort in all areas of regulatory compliance, including manufacturing, production, product surveillance and quality control.
If we, and any future collaborators, are not able to comply with post-approval regulatory requirements, we, and any future collaborators, could have the regulatory approvals for AMX0035, avexitide or any other current or future products withdrawn by regulatory authorities and our, or any future collaborators’, ability to market any future products could be limited, which could adversely affect our ability to achieve or sustain profitability. Further, the cost of compliance with post-approval regulations may have a negative effect on our operating results and financial condition.
Laws and regulations governing any international operations we expect to have in the future may preclude us from developing, manufacturing and selling certain products outside of the U.S. and will require us to develop and implement costly compliance programs.
The Foreign Corrupt Practices Act, or FCPA, prohibits any U.S. individual or business from paying, offering, authorizing payment or offering of anything of value, directly or indirectly, to any foreign official, political party or candidate for the purpose of influencing any act or decision of the foreign entity in order to assist the individual or business in obtaining or retaining business. The FCPA also obligates companies whose securities are listed in the U.S. to comply with certain accounting provisions requiring us to maintain
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books and records that accurately and fairly reflect all transactions of the corporation, including international subsidiaries, and to devise and maintain an adequate system of internal accounting controls for international operations.
Compliance with the FCPA is expensive and difficult, particularly in countries in which corruption is a recognized problem. In addition, the FCPA presents particular challenges in the pharmaceutical industry, because, in many countries, hospitals are operated by the government, and doctors and other hospital employees are considered foreign officials. Certain payments to hospitals in connection with clinical trials and other work have been deemed to be improper payments to government officials and have led to FCPA enforcement actions.
Various laws, regulations and executive orders, including export control and trade sanctions laws, also restrict the use and dissemination outside of the U.S., or the sharing with certain non-U.S. nationals, of information classified for national security purposes, as well as certain products and technical data relating to those products. If we expand our presence outside of the U.S., it will require us to dedicate additional resources to comply with these laws, and these laws may preclude us from developing, manufacturing, or selling certain products and product candidates outside of the U.S., which could limit our growth potential and increase our development costs.
The failure to comply with laws governing international business practices may result in substantial civil and criminal penalties and suspension or debarment from government contracting. The SEC also may suspend or bar issuers from trading securities on U.S. exchanges for violations of the FCPA’s accounting provisions.
If we fail to comply with environmental, health and safety laws and regulations, we could become subject to fines or penalties or incur costs that could harm our business.
We are subject to numerous environmental, health and safety laws and regulations, including those governing laboratory procedures and the handling, use, storage, treatment and disposal of hazardous materials and wastes. From time to time and in the future, our operations may involve the use of hazardous and flammable materials, including chemicals and biological materials, and may also produce hazardous waste products. Even if we contract with third parties for the disposal of these materials and waste products, we cannot completely eliminate the risk of contamination or injury resulting from these materials. In the event of contamination or injury resulting from the use or disposal of our hazardous materials, we could be held liable for any resulting damages, and any liability could exceed our resources. We also could incur significant costs associated with civil or criminal fines and penalties for failure to comply with such laws and regulations.
We maintain workers’ compensation insurance to cover us for costs and expenses we may incur due to injuries to our employees, but this insurance may not provide adequate coverage against potential liabilities. However, we do not maintain insurance for environmental liability or toxic tort claims that may be asserted against us.
In addition, we may incur substantial costs in order to comply with current or future environmental, health and safety laws and regulations. Environmental laws and regulations may impair our research, development or production efforts. In addition, failure to comply with these laws and regulations may result in substantial fines, penalties or other sanctions.
Risks Related to Our Dependence on Third Parties
We may seek to establish collaborations and if we are not able to establish and maintain them on commercially reasonable terms, we may have to alter our development and future commercialization plans.
The advancement of AMX0035, avexitide, and any other current or future product candidates and development programs or activities, will require substantial additional cash to fund expenses. For some indications of AMX0035, avexitide, or other current or future product candidates, we may decide to collaborate with additional pharmaceutical and biotechnology companies with respect to development and potential commercialization. Likely collaborators may include large and mid-size pharmaceutical companies, regional and national pharmaceutical companies and biotechnology companies. In addition, if we are able to obtain regulatory approval for product candidates from foreign regulatory authorities, we may enter into collaborations with international biotechnology or pharmaceutical companies for the commercialization of such product candidates.
We face significant competition in seeking appropriate collaborators. Whether we reach a definitive agreement for a collaboration will depend, among other things, upon our assessment of the collaborator’s resources and expertise, the terms and conditions of the proposed collaboration and the proposed collaborator’s evaluation of a number of factors. Those factors may include the potential differentiation of our product candidate from competing product candidates, design or results of clinical trials, the likelihood of approval by the FDA or other comparable foreign regulatory authorities and the regulatory pathway for any such approval, the potential market for the product candidate, the costs and complexities of manufacturing and delivering the product to patients and the
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potential of competing products. The collaborator may also consider alternative product candidates or technologies for similar indications that may be available for collaboration and whether such a collaboration could be more attractive than the one with us for our product candidate. If we elect to increase our expenditures to fund development or commercialization activities on our own, we may need to obtain additional capital, which may not be available to us on acceptable terms or at all. If we do not have sufficient funds, we may not be able to further develop AMX0035, avexitide, or any other current or future product candidates or bring them to market and generate product revenue.
Collaborations are complex and time-consuming to negotiate and document. Further, there have been a significant number of recent business combinations among large pharmaceutical companies that have resulted in a reduced number of potential future collaborators. Any collaboration agreements that we enter into in the future may contain restrictions on our ability to enter into potential collaborations or to otherwise develop specified product candidates. We may not be able to negotiate collaborations on a timely basis, on acceptable terms, or at all. If we are unable to do so, we may have to curtail the development of the product candidate for which we are seeking to collaborate, reduce or delay its development program or one or more of our other development programs or activities, delay its potential commercialization or reduce the scope of any sales or marketing activities, or increase our expenditures and undertake development or future commercialization activities at our own expense.
We have entered and may in the future enter into collaborations with third parties for the development and commercialization of AMX0035, avexitide or any other current or future product candidates, and our prospects with respect to AMX0035, avexitide and our other current or future product candidates will depend in significant part on the success of those collaborations.
We may rely on collaborations for the development and future commercialization of AMX0035, avexitide and any other current or future product candidates. For example, we may utilize a variety of distribution, collaboration and other marketing arrangements with one or more third parties to facilitate commercialization of AMX0035 or avexitide or to identify novel drug candidates for neurodegenerative or other diseases. Our likely collaborators for any distribution, development, sales, marketing, licensing or broader collaboration arrangements include large and mid-size pharmaceutical companies, regional and national pharmaceutical companies and biotechnology companies. If we enter into such collaborations, we may have limited control over the amount and timing of resources that our collaborators dedicate to the development or commercialization of AMX0035, avexitide or any other current or future product candidates. Our ability to generate revenues from these arrangements will depend on any future collaborators’ abilities to successfully perform the functions assigned to them in these arrangements. In addition, any future collaborators may have the right to abandon research or development projects and terminate applicable agreements, including funding obligations, prior to or upon the expiration of the agreed upon terms.
Collaborations involving AMX0035, avexitide and any other current or future product candidates pose a number of risks, including the following:
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Collaboration agreements may not lead to development or commercialization of product candidates in the most efficient manner or at all. If any future collaborator of ours is involved in a business combination, it could decide to delay, diminish or terminate the development or commercialization of any product candidate licensed to it by us.
We rely on third parties to assist in conducting our clinical trials. If they do not perform satisfactorily, we may not be able to obtain regulatory approval or successfully commercialize AMX0035, avexitide or any other current or future product candidates, or such approval or commercialization may be delayed, and our business could be substantially harmed.
We have relied upon and plan to continue to rely on third parties, such as CROs, clinical data management organizations, medical institutions and clinical investigators, to conduct our clinical trials and expect to rely on these third parties to conduct clinical trials of any future product candidate that we develop. Any of these third parties may terminate their engagements with us under certain circumstances. We may not be able to enter into alternative arrangements or do so on commercially reasonable terms. In addition, there is a natural transition period when a new CRO begins work. As a result, delays may occur, which could negatively impact our ability to meet our expected clinical development timelines and harm our business, financial condition and prospects. Clinical trials involve multiple clinical sites, vendors and other third parties and we are dependent on these vendors to ensure appropriate study conduct, statistical analysis and randomization. Errors or deviations they make in any of these activities could impact the usefulness and interpretability of clinical trial results by regulatory authorities. For example, at the Advisory Committee meeting on March 30, 2022, the FDA noted a number of concerns that, in the FDA’s view, impacted the interpretability of the results from the CENTAUR trial. Clinical trials from time to time have deviations where a protocol or standard operating procedure is not perfectly carried out and where corrective actions are taken. While we may perceive these events as low risk, our perception of risk and appropriate corrective actions may differ from that of the regulators’ view. Deviations from protocols or standard operating procedures during studies could result in negative regulatory opinions and outcomes.
Further, although our reliance on these third parties for clinical development activities limits our control over these activities, we remain responsible for ensuring that each of our trials is conducted in accordance with the applicable protocol, legal and regulatory requirements and scientific standards. Moreover, the FDA and competent authorities of the EU Member States require us to comply with Good Clinical Practices, or GCPs, for conducting, recording and reporting the results of clinical trials to assure that data and reported results are credible and accurate and that the rights, integrity and confidentiality of trial participants are protected. The FDA enforces these GCPs through periodic inspections of trial sponsors, principal investigators, clinical trial sites and IRBs. If we or our third-party contractors fail to comply with applicable GCPs, the clinical data generated in our clinical trials may be deemed unreliable and the FDA or other regulatory body may require us to perform additional clinical trials before approving AMX0035 or avexitide, including for additional indications, or any other current or future product candidates, which would delay the regulatory approval process. We cannot be certain that, upon inspection, the FDA or other regulatory body will determine that any of our clinical trials comply with GCPs. For example, our clinical trial sites and investigators have in the past and may in the future engage in protocol deviations which could impact the overall interpretability of the outcomes of our clinical trials. We are also required to register certain clinical trials and post the results of completed clinical trials on a government-sponsored database, such as ClinicalTrials.gov, within certain timeframes. Failure to do so can result in fines, adverse publicity and civil and criminal sanctions.
Furthermore, the third parties conducting clinical trials on our behalf are not our employees, and except for remedies available to us under our agreements with such contractors, we cannot control whether or not they devote sufficient time, skill and resources to our ongoing development activities. These contractors may also have relationships with other commercial entities, including our competitors, for whom they may also be conducting clinical trials or other drug development activities, which could impede their ability to devote appropriate time to our clinical activities. If these third parties, including clinical investigators, do not successfully carry out their contractual duties, meet expected deadlines or conduct our clinical trials in accordance with regulatory requirements or our stated protocols, we may not be able to obtain, or may be delayed in obtaining, clinical data necessary for regulatory approvals for AMX0035, avexitide or any other current or future product candidates. If that occurs, we will not be able to, or may be delayed in our efforts to, successfully commercialize AMX0035, avexitide or any other current or future product candidates. In such an event, our financial results and the commercial prospects for AMX0035, avexitide or any other current or future product candidates that we seek to develop could be harmed, our costs could increase and our ability to generate revenues could be delayed, impaired or foreclosed.
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We also rely on other third parties to store and distribute drug supplies for our clinical trials. Any performance failure on the part of our distributors could delay clinical development or regulatory approval of AMX0035, avexitide or any other current or future product candidates or commercialization of any resulting products, producing additional losses and depriving us of potential product revenue.
Our use of third parties to manufacture AMX0035 or avexitide in compliance with cGMP may increase the risk that we will not have sufficient cGMP-compliant quantities of AMX0035 or avexitide or necessary quantities of such materials on time or at an acceptable cost.
We do not own or operate manufacturing facilities for the production of clinical or commercial quantities of AMX0035 or avexitide, and we currently lack the resources and the capabilities to do so. As a result, we currently rely on third parties for the manufacture and supply of the active pharmaceutical ingredients, or APIs, in AMX0035 and avexitide, and for the blending and packaging of AMX0035 and avexitide in accordance with applicable law, regulations and standards. Our current strategy is to outsource all manufacturing of AMX0035 and avexitide and any other current or future product candidates to third parties.
We currently engage third-party manufacturers to provide the APIs of AMX0035 and avexitide and for the final drug product formulation of AMX0035 and avexitide that is or will be being used in our clinical trials and for expanded access and commercial supply, as applicable (currently being supplied without cost to patients who remained on RELYVRIO or ALBRIOZA after April 4, 2024), and we engage separate third-parties for the blending and packaging of finished clinical materials. We must be able to demonstrate comparability of drug substance across suppliers along with stability data across suppliers. We currently rely on a single manufacturer to supply one of our APIs and a separate manufacturer to supply the other. Although we believe that there are several potential alternative manufacturers who could manufacture each of the APIs in AMX0035 and avexitide, we may incur added costs and delays in identifying and qualifying any such replacement. Moreover, the extent to which geopolitical events or global health crises may impact our ability to procure sufficient supplies for the development of AMX0035 and avexitide, and any other current or future products and product candidates will depend on whether the economic challenges caused by such events continue to impact the global economy and supply chains, among many other factors. There is no assurance that we will be able to timely secure needed supply arrangements on satisfactory terms, or at all. Our failure to secure these arrangements as needed could have a material adverse effect on our ability to complete the development of AMX0035, avexitide or any other current or future product candidates or, to commercialize them, if approved. We may be unable to conclude agreements for commercial supply with third-party manufacturers, or may be unable to do so on acceptable terms. There may be difficulties in scaling up to commercial quantities and formulation of AMX0035 and avexitide, and the costs of manufacturing could be prohibitive.
Following our announcement to begin the process to voluntarily withdraw RELYVRIO and ALBRIOZA from the market, we entered into negotiations with each of our third-party manufacturers to redefine our relationship going forward. These negotiations are ongoing and may result in irreparable damage to our relationship with one or more suppliers, making our further development and potential commercialization challenging.
Even if we are able to establish and maintain arrangements with third-party manufacturers, reliance on third-party manufacturers entails additional risks, including:
If we do not maintain our key manufacturing relationships, or if any of our contract manufacturers fail to perform their obligations, we may fail to find replacement manufacturers or develop our own manufacturing capabilities, which could delay or impair our ability to obtain regulatory approval for our products. If we do find replacement manufacturers, we may not be able to enter into agreements with them on terms and conditions favorable to us and there could be a substantial delay before new facilities could be qualified and registered with the FDA and other foreign regulatory authorities.
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Any change in manufacturer may also involve changes in manufacturing procedures and processes, which could require that we conduct bridging studies between our prior clinical supply used in our clinical trials and that of any new manufacturer. In addition, we will need to verify that any new manufacturing process will produce our product candidate according to the specifications previously submitted to the FDA or another regulatory authority. We may be unsuccessful in demonstrating the comparability of clinical supplies which could require the conduct of additional clinical trials.
In some cases, the technical skills required to manufacture AMX0035, avexitide, or any other current or future products or product candidates may be unique or proprietary to the original contract manufacturer and we may have difficulty, or there may be contractual restrictions prohibiting us from, transferring such skills to a back-up or alternate supplier, or we may be unable to transfer such skills at all. Furthermore, a contract manufacturer may possess or acquire technology related to the manufacture of AMX0035, avexitide or any other current or future product candidate that such contract manufacturer owns independently. This would increase our reliance on such contract manufacturer or require us to obtain a license from such contract manufacturer in order to have another contract manufacturer manufacture AMX0035, avexitide or any other current or future product candidates. If AMX0035 for any of our initial or potential additional indications, avexitide or any future product candidate is approved by any regulatory agency, we intend to utilize arrangements with third-party contract manufacturers for the commercial production of those products. This process is difficult and time consuming and we may face competition for access to manufacturing facilities as there are a limited number of contract manufacturers operating under cGMPs that are capable of manufacturing AMX0035, avexitide or any other current or future product candidates. Consequently, we may not be able to reach agreement with third-party manufacturers on satisfactory terms, which could delay our commercialization.
Our failure, or the failure of our third-party manufacturers, to comply with applicable regulations could result in sanctions being imposed on us, including clinical holds, fines, injunctions, civil penalties, delays, suspension or withdrawal of approvals, seizures or voluntary recalls of AMX0035, avexitide or any other current or future product candidates, operating restrictions and criminal prosecutions, any of which could significantly affect supplies of AMX0035, avexitide or any other current or future product candidates. The facilities used by our contract manufacturers to manufacture AMX0035, avexitide or any other current or future product candidates must be evaluated by the FDA and certain other foreign regulatory authorities. We do not control the manufacturing process of, and are completely dependent on, our contract manufacturing partners for compliance with cGMPs. If our contract manufacturers cannot successfully manufacture material that conforms to our specifications and the strict regulatory requirements of the FDA or others, we may not be able to secure and/or maintain regulatory approval for our product manufactured at these facilities. In addition, we have no control over the ability of our contract manufacturers to maintain adequate quality control, quality assurance and qualified personnel. If the FDA or other comparable foreign regulatory authority finds deficiencies or does not approve these facilities for the manufacture of AMX0035, avexitide or any other current or future product candidates, or if it withdraws any such approval in the future, we may need to find alternative manufacturing facilities, which would significantly impact our ability to develop, obtain regulatory approval for or market AMX0035, avexitide or any other current or future product candidates, if approved. Furthermore, if we are required to change contract manufacturers, we will be required to verify that the new contract manufacturer maintains facilities and procedures that comply with quality standards and with all applicable regulations, which could result in further costs and delays. Contract manufacturers may face manufacturing or quality control problems causing drug substance production and shipment delays or a situation where the contractor may not be able to maintain compliance with the applicable cGMP requirements. Any failure to comply with cGMP requirements or other FDA and comparable foreign regulatory requirements could adversely affect our clinical research activities and our ability to develop AMX0035, avexitide or any other current or future product candidates and market our products, if approved.
The FDA and other foreign regulatory authorities require manufacturers to register manufacturing facilities. The FDA and corresponding foreign regulators also inspect these facilities to confirm compliance with cGMPs. Contract manufacturers may face manufacturing or quality control problems causing drug substance production and shipment delays or a situation where the contractor may not be able to maintain compliance with the applicable cGMP requirements. Any failure to comply with cGMP requirements or other FDA and comparable foreign regulatory requirements could adversely affect our clinical research activities and our ability to develop AMX0035, avexitide or any future product candidates and market our products following approval.
We may need to maintain licenses for active ingredients from third parties to develop and commercialize AMX0035, avexitide or a future product candidate, which could increase our development costs and delay our ability to commercialize such product candidate.
Should we decide to use API in any of AMX0035, avexitide or any other current or future product candidates that are proprietary to one or more third parties, we would need to maintain licenses to those active ingredients from those third parties. If we are unable to gain or continue to access rights to these active ingredients prior to conducting preclinical toxicology studies intended to support clinical trials, we may need to develop alternate product candidates from these programs by either accessing or developing alternate active ingredients, resulting in increased development costs and delays in commercialization of these product candidates. If we are
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unable to gain or maintain continued access rights to the desired active ingredients on commercially reasonable terms or develop suitable alternate active ingredients, we may not be able to commercialize product candidates from these programs.
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Risks Related to Commercialization of AMX0035, Avexitide or Future Product Candidates
The market for AMX0035 for Wolfram syndrome, PSP and other neurodegenerative diseases and of avexitide for PBH and congenital HI, and for any other product candidates we are currently developing or may in the future develop or acquire may be smaller than we expect.
We have historically focused our research and product development on treatments of neurodegenerative diseases, and recently expanded into other diseases, many of which are rare diseases with small addressable patient populations. We base our market opportunity estimates on a variety of factors, including our estimates of the number of people who have these diseases, the potential scope of our approved product labels, the subset of people with these diseases who have the potential to benefit from treatment with AMX0035, avexitide or any other current or future product candidates, various pricing scenarios, and our understanding of reimbursement policies for rare diseases in particular countries. These estimates are based on many assumptions and may prove incorrect, and new studies may reduce the estimated incidence or prevalence of these diseases. Estimating market opportunities can be particularly challenging for rare indications, such as the ones we currently address, as epidemiological data is often more limited than for more prevalent indications and can require additional assumptions to assess potential patient populations. If we are unable to identify patients and successfully commercialize AMX0035, avexitide or any other current or future product candidates with attractive market opportunities, our future product revenues may be smaller than anticipated, and our business may suffer.
Patient identification efforts also influence the ability to address a patient population. If efforts in patient identification are unsuccessful or less impactful than anticipated, for instance, because of a lack of diagnostic initiatives, inadequate disease awareness among healthcare professionals, difficulties in identifying and accessing patients outside of larger treatment centers or otherwise, we may not address the entirety of the opportunity we are seeking. As a result, patients may be difficult to identify and access, the addressable patient population in the countries in which we are seeking authorization and elsewhere may turn out to be lower than expected, or patients may not be otherwise amenable to treatment with our products, all of which would adversely affect our business, financial condition, results of operations and prospects.
If we are unable in the future to expand our sales, marketing, manufacturing and distribution capabilities or enter into agreements with third parties to market and sell AMX0035, avexitide or other current or future product candidates for which we obtain marketing approval, we will be unable to generate any additional product revenue.
To successfully commercialize any products that may result from our development activities or that we may acquire, we would need to continue to expand our sales, marketing, pharmacovigilance, manufacturing and distribution capabilities, either on our own or with others. RELYVRIO/ALBRIOZA, formerly sold in Canada and the U.S. for the treatment of ALS before being voluntarily withdrawn
from the market, was the first product that we commercialized and built a global marketing and sales team for. The development of our own marketing and distribution effort was expensive and time-consuming and any efforts to do so in connection with our other product candidates may be expensive and time-consuming and could delay any further product launches. Moreover, we cannot be certain that we will be able to develop this capability successfully again in the future, despite our experience. We may enter into collaborations regarding any approved product candidates with other entities to utilize their established marketing and distribution capabilities, however, we may be unable to enter into such agreements on favorable terms, if at all. If any future collaborators do not commit sufficient resources to commercialize AMX0035, avexitide or any other current or future product candidates, or we are unable to develop the necessary capabilities on our own, we will be unable to generate sufficient product revenue to sustain our business. We compete with many companies that currently have extensive, experienced and well-funded sales, distribution and marketing operations to recruit, hire, train and retain marketing and sales personnel. We may also face competition in our search for third parties to assist us with the sales and marketing efforts of AMX0035, avexitide and any other current or future product candidates, if approved. Without an internal team or the support of a third-party to perform marketing and sales functions, we may be unable to compete successfully against these more established companies.
Even if any future product candidate of ours receives regulatory approval, it may fail to maintain the degree of market acceptance by physicians, patients, third-party payors and others in the medical community necessary for continued commercial success or to remain profitable.
Even if AMX0035 for the treatment of any indication, avexitide or any other current or future product candidate of ours, is approved by the appropriate regulatory authorities for marketing and sale, it may nonetheless fail to gain sufficient market acceptance by physicians, patients, third-party payors and others in the medical community. Physicians may be reluctant to add AMX0035, avexitide or another product to their patients’ treatment regimen, or may cease to add AMX0035, avexitide or such product to their patients’ treatment regimen. Further, patients often acclimate to the treatment regime they are currently taking and do not want to add additional treatments unless their physicians recommend it. Further, patients may be unable to add AMX0035, avexitide or such other product to their treatment regimen due to lack of coverage and adequate reimbursement. In addition, even if we are able to demonstrate our product candidates’ safety and efficacy to the FDA and other regulators, safety or efficacy concerns in the medical community may
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hinder market acceptance. Our ability to proactively educate health care professionals and patients may be limited based on the marketing restrictions in a given jurisdiction, specifically as they relate to the particular labeling approved by the applicable health authority.
Efforts to educate the medical community and third-party payors on the benefits of our current and any future product candidates may require significant resources, including management time and financial resources, and may not be successful. If AMX0035, avexitide or any other current or future product candidate is approved but does not achieve an adequate level of market acceptance, we may not generate significant revenues and we may not remain profitable. The degree of market acceptance of AMX0035, avexitide and any other future product candidates, if approved for commercial sale, will depend on a number of factors, including:
Any failure by AMX0035, avexitide or any other current or future product candidate of ours that obtains regulatory approval to achieve market acceptance or commercial success would adversely affect our business prospects.
AMX0035, avexitide or any future product candidates for which we, or any future collaborators, obtain regulatory approval in the future will be subject to ongoing obligations and continued regulatory review, which may result in significant additional expense. If approved, AMX0035, avexitide and any future product candidates could be subject to post-marketing restrictions or withdrawal from the market and we, or any future collaborators, may be subject to substantial penalties if we, or they, fail to comply with regulatory requirements or if we, or they, experience unanticipated problems with our products following approval.
AMX0035, avexitide or any other current or future product candidates for which we, or any future collaborators, obtain regulatory approval, as well as the manufacturing processes, post-approval studies, labeling, advertising and promotional activities for such product, among other things, will be subject to ongoing requirements of and review by the FDA and other applicable regulatory authorities. These requirements include submissions of safety and other post-marketing information and reports, registration and listing requirements, requirements relating to manufacturing, quality control, quality assurance and corresponding maintenance of records and documents, requirements regarding the distribution of samples to physicians and recordkeeping. For certain commercial prescription drug products, manufacturers and other parties involved in the supply chain must also meet chain of distribution requirements and build electronic, interoperable systems for product tracking and tracing and notify the FDA of counterfeit, diverted, stolen and intentionally adulterated products or other products that are otherwise unfit for distribution in the U.S. We and our contract manufacturers will also be subject to user fees and periodic inspection by regulatory authorities to monitor compliance with these requirements and the terms of any product approval we may obtain. Even if regulatory approval of a product candidate is granted, the approval may be subject to limitations on the indications or uses for which the product may be marketed or to the conditions of approval, including the requirement in the U.S. to implement a Risk Evaluation and Mitigation Strategy, or REMS.
The FDA and other regulatory authorities may also impose requirements for costly post-marketing studies or clinical trials and surveillance to monitor the safety or efficacy of a product. Additionally, the FDA and other agencies, including the Department of Justice, closely regulate and monitor the post-approval marketing and promotion of products to ensure that they are manufactured, marketed and distributed only for the approved indications and in accordance with the provisions of the approved labeling. Regulatory authorities impose stringent restrictions on manufacturers’ communications regarding off-label use. However, companies generally
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may share truthful and not misleading information that is otherwise consistent with a product’s approved labeling. If we, or any future collaborators, do not market AMX0035, avexitide or any of our other current or future product candidates for which we, or they, receive regulatory approval for only their approved indications, we, or they, may be subject to warnings or enforcement action for off-label marketing if it is alleged that we are doing so. Violation of laws and regulations relating to the promotion and advertising of prescription drugs may lead to investigations or allegations of violations of federal and state health care fraud and abuse laws and state consumer protection laws, including the False Claims Act and any comparable foreign laws. In the EU, the direct-to-consumer advertising of prescription-only medicinal products is prohibited. Violations of the rules governing the promotion of medicinal products in the EU could be penalized by administrative measures, fines and imprisonment. These laws may further limit or restrict the advertising and promotion of our products to the general public, if approved, and may also impose limitations on our promotional activities with health care professionals.
In addition, later discovery of previously unknown adverse events or other problems with our products or their manufacturers or manufacturing processes, or failure to comply with regulatory requirements, may yield various results, including:
If we are not able to comply with post-approval regulatory requirements, we could have the marketing approvals for AMX0035, avexitide or any future approved products withdrawn or restricted by regulatory authorities, or we may voluntarily do so, and our ability to market AMX0035, avexitide or any future approved products, to develop AMX0035 or avexitide in the U.S. or additional jurisdictions or for additional indications, and to develop and seek approval for additional product candidates could become limited, which could adversely affect our ability to achieve or sustain profitability. As a result, the cost of compliance with post-approval regulatory requirements may have a negative effect on our operating results and financial condition.
If we fail to obtain coverage and reimbursement for AMX0035, avexitide or any other current or future product candidates in new geographies, it could make it difficult for us to sell AMX0035, avexitide or any other current or future product candidates profitably.
The success of AMX0035, avexitide and any of our other current or future product candidates, if approved, depends on the availability of adequate coverage and reimbursement from third-party payors. Because AMX0035, avexitide and any other current or future product candidates represent new approaches to the treatment of the diseases they target, we cannot be sure that coverage and reimbursement will be available for, or accurately estimate the potential revenue from, AMX0035, avexitide and any other current or future product candidates or for any product that we may develop. If we are unable to obtain adequate levels of reimbursement, our ability to successfully market and sell any such product candidates will be adversely affected. The manner and level at which reimbursement is provided for services related to any current or future product candidates we may develop (e.g., for the administration of our product candidate to patients) is also important. Inadequate reimbursement for such services may lead to physician and payor resistance and adversely affect our ability to market or sell AMX0035, avexitide or any other current or future product candidates we may develop. In addition, we may need to develop new reimbursement models, in order to realize adequate value. Payors may not be
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able or willing to adopt such new models and patients may be unable to afford that portion of the cost that such models may require them to bear. If we determine such new models are necessary, but we are unsuccessful in developing them, or if payors do not adopt such models, our business, financial condition, results of operations and prospects could be adversely affected. For additional information on coverage and reimbursement, see the section entitled “Business—Government Regulation—Coverage and Reimbursement” in our 2023 Annual Report.
Patients who are provided medical treatment for their conditions generally rely on third-party payors to reimburse all or part of the costs associated with their treatment. Adequate coverage and reimbursement from governmental healthcare programs, such as Medicare and Medicaid, and commercial payors, such as private health insurers and health maintenance organizations, are critical to new product acceptance. Government authorities and other third-party payors decide which drugs and treatments they will cover and the reimbursement amount. Coverage and reimbursement by a third-party payor may depend upon a number of factors.
In the U.S., no uniform policy of coverage and reimbursement for products exists among third-party payors. As a result, obtaining coverage and reimbursement approval of a product from a government or other third-party payor is a time consuming and costly process that could require us to provide to each payor supporting scientific, clinical and cost-effectiveness data for the use of our products on a payor-by-payor basis, with no assurance that coverage and adequate reimbursement from third-party payors will be obtained. There is significant uncertainty related to the insurance coverage and reimbursement of newly approved products, which uncertainty may be heightened where the product is subject to post-marketing conditions or requirements to provide additional clinical data. In the U.S., the principal decisions about reimbursement for new medicines are typically made by the Centers for Medicare & Medicaid Services, or CMS, an agency within the U.S. Department of Health and Human Services, as CMS decides whether and to what extent a new medicine will be covered and reimbursed under Medicare. Private payors tend to follow CMS to a substantial degree. Even if we obtain coverage for a given product, the resulting reimbursement payment rates might not be adequate for us to achieve or sustain profitability or may require co-payments that patients find unacceptably high. Future coverage and reimbursement may be subject to increased restrictions, such as prior authorization requirements, both in the U.S. and in international markets. Orphan drugs are typically placed on the highest cost-sharing tier and a substantial percentage are subject to prior authorization requirements. Reimbursement agencies in the EU may be more conservative than CMS.
Outside the U.S., international operations are generally subject to extensive governmental price controls and other market regulations, and we believe the increasing emphasis on cost-containment initiatives in Canada, the EU and other countries has and will continue to put pressure on the pricing and usage of drug products such as AMX0035, avexitide and any other current or future product candidates we may develop, if approved. We may also incur additional challenges when seeking reimbursement from public and private payers where AMX0035, avexitide or any future product candidate has been approved subject to post-marketing conditions. Moreover, we might obtain marketing approval for a product in a particular country, but then be subject to price regulations that delay or might even prevent our commercial launch of the product, possibly for lengthy periods of time. To obtain reimbursement or pricing approval in some countries, we may be required to conduct a clinical trial that compares the cost-effectiveness of our product candidate to other available therapies. In general, the prices of products under such systems are substantially lower than in the U.S. Other countries allow companies to fix their own prices for products but monitor and control company profits. Additional foreign price controls or other changes in pricing regulation could restrict the amount that we are able to charge for product candidates. Accordingly, in markets outside the U.S., the reimbursement for AMX0035, avexitide and any other current or future product candidates we may develop may be reduced compared with the U.S. and may be insufficient to generate commercially reasonable revenues and profits.
Ongoing healthcare legislative and regulatory reform measures may have a material adverse effect on our business and results of operations.
Changes in regulations, statutes or the interpretation of existing regulations could impact our business in the future by requiring, for example: (i) changes to our manufacturing arrangements; (ii) additions or modifications to product labeling; (iii) the recall or discontinuation of our products; or (iv) additional record-keeping requirements. If any such changes were to be imposed, they could adversely affect the operation of our business. For more information, see the section entitled “Business – Government Regulation – Current and Future U.S. Healthcare Reform Legislation” in our 2023 Annual Report.
We cannot predict the initiatives that may be adopted in the future. The continuing efforts of the government, insurance companies, managed care organizations and other payors of healthcare services to contain or reduce costs of healthcare and/or impose price controls may adversely affect:
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These laws and future state and federal healthcare reform measures that may be adopted in the future may result in additional reductions in Medicare and other healthcare funding and otherwise affect the prices we may obtain for AMX0035, avexitide or any other current or future product candidates for which we may obtain regulatory approval or the frequency with which any such product candidate is prescribed or used. For example, the Inflation Reduction Act of 2022, or IRA, contains provisions that require companies to pay rebates to Medicare for certain drug prices that increase faster than inflation. In addition, any reduction in reimbursement from Medicare or other government programs may result in a similar reduction in payments from private payors. The implementation of cost containment measures or other healthcare reforms may prevent us from being able to generate revenue, sustain profitability or commercialize our product candidates.
Moreover, increasing efforts by governmental and third-party payors in the U.S. and abroad to cap or reduce healthcare costs may cause such organizations to limit both coverage and the level of reimbursement for newly approved products and, as a result, they may not cover or provide adequate payment for our product candidates. There has been increasing legislative and enforcement interest in the U.S. with respect to specialty drug pricing practices. Specifically, there have been several recent U.S. Congressional inquiries and proposed and enacted federal and state legislation designed to, among other things, bring more transparency to drug pricing, reduce the cost of prescription drugs under Medicare, review the relationship between pricing and manufacturer patient programs, and reform government program reimbursement methodologies for drugs. The effect of these reform efforts on our business and the healthcare industry in general is not yet known.
Additional state and federal healthcare reform measures are expected to be adopted in the future, any of which could limit the amounts that federal and state governments will pay for healthcare products and services, which could result in reduced demand for certain pharmaceutical products or additional pricing pressures.
While some of these and other proposed measures may require additional authorization to become effective, Congress and the Biden administration have each indicated that it will continue to seek new legislative and/or administrative measures to control drug costs.
Governments outside the U.S. may impose strict price controls, which may adversely affect our revenues, if any.
In some countries, including Canada and certain Member States of the EU, the pricing of prescription drugs is, in part, subject to governmental control. Additional countries may adopt similar approaches to the pricing of prescription drugs. In such countries, pricing negotiations with governmental authorities can take considerable time after receipt of regulatory approval for a product. In addition, there can be considerable pressure by governments and other stakeholders on prices and reimbursement levels, including as part of cost containment measures. Political, economic and regulatory developments may further complicate pricing negotiations, and pricing negotiations may continue after coverage and reimbursement have been obtained. Reference pricing used by various countries and parallel distribution, or arbitrage between low-priced and high-priced countries, can further reduce prices. In some countries, we may be required to conduct a clinical trial or other trials that compare the cost-effectiveness of AMX0035, avexitide or any other current or future product candidates to other available therapies in order to obtain or maintain reimbursement or pricing approval, which is time-consuming and costly. We cannot be sure that such prices and reimbursement will be acceptable to us. Publication of discounts by third-party payors or authorities may lead to further pressure on the prices or reimbursement levels within the country of publication and other countries. If pricing is set at unsatisfactory levels or if reimbursement of our products is unavailable or limited in scope or amount, our revenues from sales by us or our strategic partners and the potential profitability of AMX0035, avexitide or any other current or future product candidates in those countries would be negatively affected.
Our relationships with healthcare providers, physicians, patients and third-party payors may be subject to applicable anti-kickback, fraud and abuse and other healthcare laws and regulations, which could expose us to criminal sanctions, civil penalties, contractual damages, reputational harm and diminished profits and future earnings.
Healthcare providers, physicians and third-party payors in the U.S. and elsewhere play a primary role in the recommendation and prescription of pharmaceutical products. Arrangements with third-party payors and customers can expose pharmaceutical manufacturers to broadly applicable fraud and abuse and other healthcare laws and regulations, including, without limitation, the federal Anti-Kickback Statute and the federal False Claims Act, or FCA, which may constrain the business or financial arrangements and relationships through which such companies conduct research, sell, market and distribute pharmaceutical products. In particular, the promotion, sales and marketing of healthcare items and services, as well as certain business arrangements in the healthcare industry, are subject to extensive laws designed to prevent fraud, kickbacks, self-dealing and other abusive practices. These laws and regulations may restrict or prohibit a wide range of pricing, discounting, marketing and promotion, structuring and commission(s), certain customer incentive programs and other business arrangements generally. Activities subject to these laws also involve the
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improper use of information obtained in the course of patient recruitment for clinical trials. For more information, see the section entitled “Business – Government Regulation - Other U.S. Healthcare Laws” in our 2023 Annual Report.
In the U.S., to help patients afford our approved product, we offer programs to assist them or support third-party organizations’ programs to assist patients, including patient assistance programs and co-pay coupon programs for eligible patients. Government enforcement agencies have shown increased interest in pharmaceutical companies’ product and patient assistance programs, including reimbursement support services, and a number of investigations into these programs have resulted in significant civil and criminal settlements. In addition, at least one insurer has directed its network pharmacies to no longer accept co-pay coupons for certain specialty drugs the insurer identified. Our co-pay coupon programs could become the target of similar insurer actions. In September 2014, the HHS Office of Inspector General, or OIG, issued a Special Advisory Bulletin warning manufacturers that they may be subject to sanctions under the federal anti-kickback statute and/or civil monetary penalty laws if they do not take appropriate steps to exclude Part D beneficiaries from using co-pay coupons. Accordingly, companies exclude these Part D beneficiaries from using co-pay coupons. It is possible that changes in insurer policies regarding co-pay coupons and/or the introduction and enactment of new legislation or regulatory action could restrict or otherwise negatively affect these patient support programs, which could result in fewer patients using affected products, and therefore could have a material adverse effect on our sales, business, and financial condition.
Third party patient assistance programs that receive financial support from companies have also become the subject of enhanced government and regulatory scrutiny. The OIG has established guidelines that suggest that it is lawful for pharmaceutical manufacturers to make donations to charitable organizations who provide co-pay assistance to Medicare patients. However, donations to patient assistance programs have received some negative publicity and have been the subject of multiple government enforcement actions, related to allegations regarding their misuse to promote branded pharmaceutical products over other less costly alternatives. Specifically, in recent years, there have been multiple settlements resulting out of government claims challenging the legality of third party patient assistance programs under a variety of federal and state laws. We have in the past and may, from time to time, make charitable grants to independent charitable foundations that help financially needy patients with their premium, co-pay, and co-insurance obligations. If we choose to do so, and if we or our vendors or donation recipients are deemed to fail to comply with relevant laws, regulations or evolving government guidance in the provision of charitable donations or operation of these programs, we could be subject to damages, fines, penalties, or other criminal, civil, or administrative sanctions or enforcement actions. We cannot ensure that our compliance controls, policies, and procedures will be sufficient to protect against acts of our employees, business partners, vendors or charitable foundations that may violate the laws or regulations of the jurisdictions in which we operate. Regardless of whether we have complied with the law, a government investigation, including of any business partners, vendors or charitable foundations, could impact our business practices, harm our reputation, divert the attention of management, increase our expenses, and reduce the availability of foundation support for our patients who need assistance.
The distribution of pharmaceutical products is also subject to additional requirements and regulations, including extensive recordkeeping, licensing, storage and security requirements intended to prevent the unauthorized sale of pharmaceutical products. Ensuring that our internal operations and future business arrangements with third parties comply with applicable healthcare laws and regulations will involve substantial costs. It is possible that governmental authorities will conclude that our business practices do not comply with current or future statutes, regulations, agency guidance or case law involving applicable fraud and abuse or other healthcare laws and regulations. The scope and enforcement of each of these laws is uncertain and subject to rapid change in the current environment of healthcare reform. If our operations are found to be in violation of any of the laws described above or any other governmental laws and regulations that may apply to us, we may be subject to significant penalties, including civil, criminal and administrative penalties, damages, fines, exclusion from U.S. government-funded healthcare programs, such as Medicare and Medicaid, or similar programs in other countries or jurisdictions, disgorgement, imprisonment, contractual damages, reputational harm, diminished profits, additional reporting requirements and oversight if we become subject to a corporate integrity agreement or similar agreement to resolve allegations of non-compliance with these laws and the delay, reduction, termination or restructuring of our operations. Further, defending against any such actions can be costly and time-consuming, and may require significant financial and personnel resources. Therefore, even if we successfully defend against any such actions that may be brought against us, our business may be impaired. If any of the physicians or other providers or entities with whom we expect to do business is found to not comply with applicable laws, they may be subject to significant criminal, civil or administrative sanctions, including exclusions from government-funded healthcare programs and imprisonment. If any of the above occur, it could adversely affect our ability to operate our business and our results of operations.
If we fail to comply with our reporting and payment obligations under the Medicaid Drug Rebate Program or other governmental pricing programs, we could be subject to additional reimbursement requirements, penalties, sanctions and fines, which could have a material adverse effect on our business, financial condition, results of operations and growth prospects.
We participate in the Medicaid Drug Rebate Program, the 340B program, the U.S. Department of Veterans Affairs, Federal Supply Schedule, or FSS, pricing program, and the Tricare Retail Pharmacy program, which require us to disclose average manufacturer pricing, and, in the future may require us to report the average sales price for certain of our drugs to the Medicare program. Pricing
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and rebate calculations vary across products and programs, are complex, and are often subject to interpretation by us, governmental or regulatory agencies and the courts. Furthermore, regulatory and legislative changes, and judicial rulings relating to these programs and policies (including coverage expansion), have increased and will continue to increase our costs and the complexity of compliance, have been and will continue to be time-consuming to implement, and could have a material adverse effect on our results of operations, particularly if CMS or another agency challenges the approach we take in our implementation. For example, in the case of our Medicaid pricing data, if we become aware that our reporting for a prior quarter was incorrect or has changed as a result of recalculation of the pricing data, we are generally obligated to resubmit the corrected data for up to three years after those data originally were due. Such restatements increase our costs and could result in an overage or underage in our rebate liability for past quarters. Price recalculations also may affect the ceiling price at which we are required to offer our products under the 340B program and give rise to an obligation to refund entities participating in the 340B program for overcharges during past quarters impacted by a price recalculation.
Civil monetary penalties can be applied if we are found to have knowingly submitted any false price or product information to the government, if we are found to have made a misrepresentation in the reporting of our average sales price, if we fail to submit the required price data on a timely basis, or if we are found to have charged 340B covered entities more than the statutorily mandated ceiling price. Additionally, our agreement to participate in the 340B program or our Medicaid drug rebate agreement could be terminated, in which case federal payments may not be available under Medicaid or Medicare Part D for our covered outpatient drugs. Additionally, if we overcharge the government in connection with our arrangements with FSS or Tricare Retail Pharmacy, we are required to refund the difference to the government. Failure to make necessary disclosures and/or to identify contract overcharges can result in allegations against us under the FCA and other laws and regulations. Unexpected refunds to the government, and responding to a government investigation or enforcement action, would be expensive and time-consuming, and could have a material adverse effect on our business, financial condition, results of operations and growth prospects.
Further, legislation may be introduced that, if passed, would, among other things, further expand the 340B program to additional covered entities or would require participating manufacturers to agree to provide 340B discounted pricing on drugs used in an inpatient setting, and any additional future changes to the definition of average manufacturer price or the Medicaid rebate amount could affect our 340B ceiling price calculations and negatively impact our results of operations. Additionally, certain pharmaceutical manufacturers are involved in ongoing litigation regarding contract pharmacy arrangements under the 340B program. For example, on November 3, 2023, the U.S. District Court of South Carolina issued an opinion in Genesis Healthcare Inc. v. Becerra et al. that may lead to an expansion of the scope of patients eligible to access prescriptions at 340B pricing. The outcome of this and other judicial proceedings on the 340B program and the potential impact on the way in which manufacturers extend discounts to covered entities through contract pharmacies under the 340B program remain uncertain.
Compliance with global privacy and data security requirements could result in additional costs and liabilities to us or inhibit our ability to collect and process data globally, and the failure to comply with such requirements could subject us to significant fines and penalties, which may have a material adverse effect on our business, financial condition or results of operations.
The regulatory framework for the collection, use, safeguarding, sharing, transfer and other information processing worldwide is rapidly evolving and is likely to remain uncertain for the foreseeable future. Globally, virtually every jurisdiction in which we operate has established its own data security and privacy frameworks with which we must comply. For example, the collection, use, disclosure, transfer, or other processing of personal data regarding individuals in the European Economic Area, or, EEA, including personal health data, is subject to the EU General Data Protection Regulation, or the GDPR, and similarly, processing of personal data regarding individuals in the United Kingdom, or the UK, including personal health data, is subject to the UK General Data Protection Regulation and the UK Data Protection Act 2018, or, collectively the UK GDPR, and together with the EU GDPR, the GDPR. The GDPR is wide-ranging in scope and imposes numerous requirements on companies that process personal data, including requirements relating to processing health and other sensitive data, obtaining the consent of the individuals to whom the personal data relates, providing detailed information to individuals regarding data processing activities, implementing safeguards to protect the security and confidentiality of personal data, providing notification of data breaches, and taking certain measures when engaging third-party processors. The GDPR also imposes strict rules on the transfer of personal data to countries outside the EEA/UK that are not considered by the European Commission and the UK government as providing “adequate” protection to personal data, including the U.S., and, as a result, increases the scrutiny that clinical trial sites located in the EEA should apply to transfers of personal data from such sites to countries that are considered to lack an adequate level of data protection, such as the U.S. Such transfers of personal data outside of the EEA and UK are prohibited unless a valid GDPR transfer mechanism (for example, the European Commission approved Standard Contractual Clauses, or SCCs, and the UK International Data Transfer Agreement/Addendum, or UK IDTA) has been put in place. Where relying on the SCCs /UK IDTA for data transfers, we may also be required to carry out transfer impact assessments to assess whether the recipient is subject to local laws which allow public authority access to personal data. The international transfer obligations under the EEA/UK data protection regimes will require significant effort and cost, and may result in us needing to make strategic considerations around where EEA/UK personal data is transferred and which service providers we can utilize for the processing of EEA/UK personal data. Any inability to transfer personal data from the EEA and UK to the United States
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in compliance with data protection laws may impede our ability to conduct trials and may adversely affect our business and financial position. The GDPR also permits data protection authorities to require the destruction of improperly gathered or used personal information and or impose substantial fines for violations of the GDPR, which can be up to four percent of global revenues or €20 million (£17.5 million under the UK GDPR), whichever is greater and it also confers a private right of action on data subjects and consumer associations to lodge complaints with supervisory authorities, seek judicial remedies, and obtain compensation for damages resulting from violations of the GDPR. Although the UK is regarded as a third country under the EU GDPR, the European Commission has now issued a decision recognizing the UK as providing adequate protection under the EU GDPR, or Adequacy Decision, and, therefore, transfers of personal data originating in the EEA to the UK remain unrestricted. The UK Government has introduced a Data Protection and Digital Information Bill, or UK Bill, into the UK legislative process to reform the UK’s data protection regime, and if passed, the final version of the UK Bill may have the effect of further altering the similarities between the UK and EEA data protection regimes and threaten the UK Adequacy Decision from the European Commission, which may lead to additional compliance costs for us and could increase our overall risk. It is unclear how UK data protection laws and regulations will develop in the medium to longer term, and how data transfers to and from the UK will be regulated in the long term. Although the EU GDPR and the EU GDPR currently impose substantially similar obligations, it is possible that over the time the UK GDPR could become less aligned with the EU GDPR. In addition, EU member states have adopted national laws to supplement the EU GDPR, which may partially deviate from the EU GDPR, and the competent authorities in the EU Member States may interpret EU GDPR obligations slightly differently from country to country, such that we do not expect to operate in a uniform legal landscape in the EEA with respect to data protection regulations. The potential of the respective provisions and enforcement of the EU GDPR and UK GDPR further diverging in the future creates additional regulatory challenges and uncertainties for us. The lack of clarity on future UK laws and regulations and their interaction with EU laws and regulations could add legal risk, uncertainty, complexity and cost to the handling of European personal data and our privacy and data security compliance programs could require us to implement different compliance measures for the UK and EEA.
Similar legal requirements are either in place or are being proposed in the U.S. There are a broad variety of data protection laws that are applicable to our activities, and a wide range of enforcement agencies at both the state and federal levels that can review companies for privacy and data security concerns based on general consumer protection laws. The Federal Trade Commission and state Attorneys General are all aggressive in reviewing consumers’ privacy and data security protections. New laws also are being considered at both the state and federal levels. For example, the California Consumer Privacy Act—which went into effect on January 1, 2020 and which was recently amended by the California Privacy Rights Act —is creating similar risks and obligations as those created by GDPR. Though the Act does exempt certain information collected as part of a clinical trial subject to the Federal Policy for the Protection of Human Subjects, or the Common Rule, it does apply to other personal information that we may otherwise handle, such as personal information collected in a business to business context and personal information collected from employees, applicants and retirees residing in California. Similar broad consumer privacy laws have already been passed in numerous states, and laws in Virginia, Colorado and Connecticut already have entered into force. In addition, bills for broad consumer privacy laws are being considered in numerous other states and at the federal level.
Compliance with the above requirements and any other data privacy and data security laws and regulations is a rigorous and time-intensive process and requires significant resources and an ongoing review of our technologies, systems and practices, as well as those of any third-party collaborators, service providers, contractors or consultants that process or transfer personal data. The GDPR and other changes in laws or regulations associated with the enhanced protection of certain types of sensitive data, such as healthcare data or other personal information from our clinical trials, could require us to change our business practices and put in place additional compliance mechanisms, may interrupt or delay our development, regulatory and commercialization activities and increase our cost of doing business, and could lead to government enforcement actions, private litigation and significant fines and penalties against us and could have a material adverse effect on our business, financial condition or results of operations.
Artificial intelligence presents risks and challenges that can impact our business including by posing security risks to our confidential information, proprietary information, and personal data.
Issues in the development and use of artificial intelligence, combined with an uncertain regulatory environment, may result in reputational harm, liability, or other adverse consequences to our business operations. As with many technological innovations, artificial intelligence presents risks and challenges that could impact our business. We may adopt and integrate generative artificial intelligence tools into our systems for specific use cases reviewed by legal and information security. Our vendors may incorporate generative artificial intelligence tools into their offerings without disclosing this use to us, and the providers of these generative artificial intelligence tools may not meet existing or rapidly evolving regulatory or industry standards with respect to privacy and data protection and may inhibit our or our vendors’ ability to maintain an adequate level of service and experience. If we, our vendors, or our third-party partners experience an actual or perceived breach or privacy or security incident because of the use of generative artificial intelligence, we may lose valuable intellectual property and confidential information and our reputation and the public perception of the effectiveness of our security measures could be harmed. Further, bad actors around the world use increasingly sophisticated methods, including the use of artificial intelligence, to engage in illegal activities involving the theft and misuse of
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personal information, confidential information, and intellectual property. Any of these outcomes could damage our reputation, result in the loss of valuable property and information, and adversely impact our business.
Risks Related to Our Intellectual Property
Our commercial success depends on our ability to protect our intellectual property and proprietary technology.
Our commercial success depends in large part on our ability to obtain and maintain intellectual property rights protection through patents, trademarks and trade secrets in the U.S. and other countries with respect to our proprietary product candidates, AMX0035, AMX0114, avexitide, and any future proprietary product candidates. If we do not adequately protect our intellectual property rights, competitors may be able to erode, negate or preempt any competitive advantage we may have, which could harm our business and ability to sustain profitability. To protect our proprietary position, we have filed patent applications and may file other patent applications in the U.S. or abroad related to AMX0035, AMX0114, or any other current or future product candidates that are important to our business; we may also license or purchase patents or patent applications filed by others. With respect to protection of our intellectual property rights in avexitide, our acquisition of that product candidate from Eiger includes acquisition of all of Eiger’s owned and co-owned patents and applications directed to avexitide, as well as assuming Eiger’s licenses to patents and applications directed to avexitide and owned and co-owned by other entities. The patent application process is expensive and time-consuming. We may not be able to file and prosecute all necessary or desirable patent applications at a reasonable cost or in a timely manner.
If the scope of the patent protection we obtain is not sufficiently broad, we may not be able to prevent others from developing and commercializing technology and products similar or identical to ours. The degree of patent protection we require to successfully compete in the marketplace may be unavailable or severely limited in some cases and may not adequately protect our rights or permit us to gain or keep any competitive advantage. We cannot provide any assurances that any of our patents have, or that any of our pending owned patent applications that mature into issued patents will include claims with a scope sufficient to protect our proprietary therapeutics or otherwise provide any competitive advantage. Other parties have developed or may develop technologies that may be related or competitive with our approach, and may have filed or may file patent applications and may have been issued or may be issued patents with claims that overlap or conflict with our patent applications, either by claiming the same compounds, formulations or methods or by claiming subject matter that could dominate our patent position. In addition, the laws of foreign countries may not protect our rights to the same extent as the laws of the U.S. Furthermore, patents have a limited lifespan. In the U.S., the natural expiration of a patent is generally twenty years after it is filed. Various extensions may be available; however, the life of a patent, and the protection it affords, is limited. Given the amount of time required for the development, testing and regulatory review of new product candidates, patents protecting such candidates might expire before or shortly after such candidates are commercialized. As a result, our patent portfolio may not provide us with adequate and continuing patent protection sufficient to exclude others from commercializing products similar to AMX0035, AMX0114, avexitide or any other current or future product candidates. In the event that an alternative combination of AMX0035, or TURSO as a single drug product, is developed and approved for use in indications for which we may seek approval and falls outside the scope of our patent claims, the marketability and commercial success of AMX0035 could be materially harmed.
Even if they are unchallenged, our owned patents and pending patent applications, if issued, may not provide us with any meaningful protection or prevent competitors from designing around our patent claims to circumvent our patents by developing similar or alternative therapeutics in a non-infringing manner. For example, a third party may develop a competitive therapy that provides benefits similar to our product candidate but falls outside the scope of our patent protection or license rights. If the patent protection provided by the patent and patent applications we hold or pursue with respect to AMX0035, AMX0114, avexitide or any other current or future product candidates is not sufficiently broad to impede such competition, our ability to successfully commercialize our product candidate could be negatively affected, which would harm our business.
We, or any future partners, collaborators, or licensees, may fail to identify patentable aspects of inventions made in the course of development and commercialization activities before it is too late to obtain patent protection on them. Therefore, we may miss potential opportunities to strengthen our patent position.
It is possible that defects of form in the preparation or filing of our patent or patent applications may exist, or may arise in the future, for example with respect to proper priority claims, inventorship, claim scope, or requests for patent term adjustments. If we or our partners, collaborators, or licensees whether current or future, fail to establish, maintain or protect such patents and other intellectual property rights, such rights may be reduced or eliminated. If our partners, collaborators, or licensees are not fully cooperative or disagree with us as to the prosecution, maintenance or enforcement of any patent rights, such patent rights could be compromised. If there are material defects in the form, preparation, prosecution, or enforcement of our patents or patent applications, such patents may be invalid and/or unenforceable, and such applications may never result in valid, enforceable patents. Any of these outcomes could impair our ability to prevent competition from third parties, which may have an adverse impact on our business.
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The patent position of biotechnology and pharmaceutical companies carries uncertainty. In addition, the determination of patent rights with respect to pharmaceutical compounds commonly involves complex legal and factual questions, which are dependent upon the current legal and intellectual property context, extant legal precedent and interpretations of the law by individuals. As a result, the issuance, scope, validity, enforceability and commercial value of our patent rights are characterized by uncertainty.
Pending patent applications cannot be enforced against third parties practicing the technology claimed in such applications unless and until a patent issues from such applications. Assuming the other requirements for patentability are met, currently, the first to file a patent application is generally entitled to the patent. However, prior to March 16, 2013, in the U.S., the first to invent was entitled to the patent. Publications of discoveries in the scientific literature often lag behind the actual discoveries, and patent applications in the U.S. and other jurisdictions are not published until 18 months after filing, or in some cases not at all. Therefore, we cannot be certain that we were the first to make the inventions claimed in our patent or pending patent applications, or that we were the first to file for patent protection of such inventions. If third parties have filed prior patent applications on inventions claimed in our patents or applications that were filed on or before March 15, 2013, an interference proceeding in the U.S. can be initiated by such third parties to determine who was the first to invent any of the subject matter covered by the patent claims of our applications. If third parties have filed such prior applications after March 15, 2013, a derivation proceeding in the U.S. can be initiated by such third parties to determine whether our invention was derived from theirs.
Moreover, because the issuance of a patent is not conclusive as to its inventorship, scope, validity or enforceability, our patents may be challenged in the courts or patent offices in the U.S. and abroad. Also, while we believe that we have disclosed all potentially relevant prior art relating to our patents and patent applications, there is no assurance that we have found all such prior art or disclosed it in every relevant jurisdiction. Publications of discoveries in the scientific literature often lag behind the actual discoveries, and patent applications in the U.S. and other jurisdictions are typically not published until 18 months after filing or, in some cases, not at all.
Therefore, we cannot know with certainty whether we were the first to make the inventions claimed in our patents or pending patent applications, or that we were the first to file for patent protection of such inventions. If such prior art exists, it may be used to invalidate a patent, or may prevent a patent from issuing from a pending patent application. For example, such patent filings may be subject to a third-party submission of prior art to the U.S. Patent and Trademark Office, or USPTO, or to other patent offices around the world. Alternately or additionally, we may become involved in post-grant review procedures, oppositions, derivation proceedings, ex parte reexaminations, inter partes review, supplemental examinations, or interference proceedings or challenges in district court, in the U.S. or in various foreign patent offices, including both national and regional, challenging patents or patent applications in which we have rights, including patents on which we rely to protect our business. An adverse determination in any such challenges may result in loss of the patent or in patent or patent application claims being narrowed, invalidated or held unenforceable, in whole or in part, or in denial of the patent application or loss or reduction in the scope of one or more claims of the patent or patent application, any of which could limit our ability to stop others from using or commercializing similar or identical technology and products, or limit the duration of the patent protection of our technology and products.
Pending and future patent applications may not result in patents being issued that protect our business, in whole or in part, or which effectively prevent others from commercializing competitive products. Competitors may also be able to design around our patents. Changes in either the patent laws or interpretation of the patent laws in the U.S. and other countries may diminish the value of our patents or narrow the scope of our patent protection. In addition, the laws of foreign countries may not protect our rights to the same extent or in the same manner as the laws of the U.S. For example, patent laws in various jurisdictions, including jurisdictions covering significant commercial markets, such as the European Patent Office, or EPO, China and Japan, restrict the patentability of methods of treatment of the human body more than U.S. law does. If these developments were to occur, they could have a material adverse effect on our ability to generate revenue.
The patent application process is subject to numerous risks and uncertainties, and there can be no assurance that we or any of our future development partners will be successful in protecting AMX0035, AMX0114, avexitide or any other current or future product candidates by obtaining and defending patents. These risks and uncertainties include the following:
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Issued patents that we have or may obtain or license may not provide us with any meaningful protection, prevent competitors from competing with us or otherwise provide us with any competitive advantage. Our competitors may be able to circumvent our patents by developing similar or alternative technologies or products in a non-infringing manner. Our competitors may also seek approval to market their own products similar to or otherwise competitive with our products. Alternatively, our competitors may seek to market generic versions of any approved products by submitting ANDAs to the FDA in which they claim that patents owned or licensed by us are invalid, unenforceable or not infringed. In these circumstances, we may need to defend or assert our patents, or both, including by filing lawsuits alleging patent infringement. In any of these types of proceedings, a court or other agency with jurisdiction may find our patents invalid or unenforceable, or that our competitors do not infringe our patents. Thus, even if we have valid and enforceable patents, these patents still may not provide protection against competing products or processes sufficient to achieve our business objectives.
In addition, we rely on the protection of our trade secrets and proprietary, unpatented know-how. Although we have taken steps to protect our trade secrets and unpatented know-how, including entering into confidentiality agreements with third parties, and confidential information and invention assignment agreements with employees, consultants, collaborators, vendors, and advisors, we cannot provide any assurances that all such agreements have been duly executed, and third parties may still obtain this information or may come upon this or similar information independently. It is possible that technology relevant to our business will be independently developed by a person who is not a party to such a confidentiality or invention assignment agreement. We may not be able to prevent the unauthorized disclosure or use of our technical knowledge or trade secrets by consultants, collaborators, vendors, advisors, former employees and current employees. Furthermore, if the parties to our confidentiality agreements breach or violate the terms of these agreements, we may not have adequate remedies for any such breach or violation, and we could lose our trade secrets as a consequence of such breaches or violations. Our trade secrets could otherwise become known or be independently discovered by our competitors. Additionally, if the steps taken to maintain our trade secrets are deemed inadequate, we may have insufficient recourse against third parties for misappropriating our trade secrets. If any of these events occurs or if we otherwise lose protection for our trade secrets or proprietary know-how, our business may be harmed.
It is difficult and costly to protect our intellectual property and our proprietary technologies, and we may not be able to ensure their protection.
Our commercial success will depend in part on obtaining and maintaining patent protection and trade secret protection for our proprietary product candidates, AMX0035, AMX0114, and our newly acquired product candidate, avexitide, as well as on successfully defending these patents against potential third-party challenges. Our ability to protect our product candidate from unauthorized making, using, selling, offering to sell or importing by third parties is dependent on the extent to which we have rights under valid and enforceable patents that cover these activities.
The patent positions of pharmaceutical, biotechnology and other life sciences companies can be highly uncertain and involve complex legal and factual questions for which important legal principles remain unresolved and have in recent years been the subject of much litigation. Changes in either the patent laws or in interpretations of patent laws in the U.S. and other countries may diminish the value of our intellectual property. Over the past decade, U.S. federal courts have increasingly invalidated pharmaceutical and biotechnology patents during litigation often based on changing interpretations of patent law. Further, the determination that a patent application or patent claim meets all of the requirements for patentability is a subjective determination based on the application of law and jurisprudence. The ultimate determination by the U.S. Patent and Trademark Office, or USPTO, or by a court or other trier of fact in the U.S., or corresponding foreign national patent offices or courts, on whether a claim meets all requirements of patentability cannot be assured. Accordingly, we cannot predict the breadth of claims that may be allowed or enforced in our owned patents or patent applications.
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We cannot provide assurances that any of our patent applications will be found to be patentable, including over our own prior art publications or patent literature, or will issue as patents. Neither can we make assurances as to the scope of any claims that may issue from our pending and future patent applications nor to the outcome of any proceedings by any potential third parties that could challenge the patentability, validity or enforceability of our patents and patent applications in the U.S. or foreign jurisdictions. Any such challenge, if successful, could limit patent protection for our products and current or future product candidates and/or materially harm our business.
In addition to challenges during litigation, third parties can challenge the validity of our patents in the U.S. using post-grant review and inter partes review proceedings, which some third parties have been using to cause the cancellation of selected or all claims of issued patents of competitors. For a patent filed March 16, 2013 or later, a petition for post-grant review can be filed by a third party in a nine-month window from issuance of the patent. A petition for inter partes review can be filed immediately following the issuance of a patent if the patent has an effective filing date prior to March 16, 2013. A petition for inter partes review can be filed after the nine-month period for filing a post-grant review petition has expired for a patent with an effective filing date of March 16, 2013 or later. Post-grant review proceedings can be brought on any ground of invalidity, whereas inter partes review proceedings can only raise an invalidity challenge based on published prior art and patents. These adversarial actions at the USPTO review patent claims without the presumption of validity afforded to U.S. patents in lawsuits in U.S. federal courts, and use a lower burden of proof than used in litigation in U.S. federal courts. Therefore, it is generally considered easier for a competitor or third party to have a U.S. patent invalidated in a USPTO post-grant review or inter partes review proceeding than invalidated in a litigation in a U.S. federal court. If any of our patents are challenged by a third party in such a USPTO proceeding, there is no guarantee that we will be successful in defending the patent, which may result in a loss of the challenged patent right to us.
In the EU, third parties can challenge the validity of our patents by filing an Opposition before the EPO. An adverse determination by the Opposition Board can result in the narrowing or invalidation of a European patent. If any of our European patents are challenged by a third party in such an opposition proceeding, there is no guarantee that we will be successful in defending the patent, which may result in a loss of the challenged patent right to us.
The degree of future protection for our proprietary rights is uncertain because legal means afford only limited protection and may not adequately protect our rights or permit us to gain or keep our competitive advantage. For example:
In addition, to the extent that we are unable to obtain and maintain patent protection for AMX0035, AMX0114, or avexitide or any other current or future product candidates or in the event that such patent protection expires, it may no longer be cost-effective to extend our portfolio by pursuing additional development of a product or product candidate for follow-on indications.
If we are unable to protect the confidentiality of our trade secrets, the value of our technology could be materially adversely affected and our business would be harmed.
In addition to patents, we also may rely on trade secrets to protect our proprietary product candidate, especially where we do not believe patent protection is appropriate or obtainable. Trade secrets are difficult to protect. We seek to protect our confidential proprietary information, in part, by confidentiality agreements and invention assignment agreements with our employees, consultants, scientific advisors, contractors and collaborators. These agreements are designed to protect our proprietary information. However, we cannot be certain that such agreements have been entered into with all relevant parties, and we cannot be certain that our trade secrets and other confidential proprietary information will not be disclosed or that competitors will not otherwise gain access to our trade secrets or independently develop substantially equivalent information and techniques. For example, our employees, consultants, contractors, outside scientific collaborators and other advisers may unintentionally or willfully disclose our information to competitors. Enforcing a claim that a third-party entity illegally obtained and is using any of our trade secrets is expensive and time-consuming, and the outcome is unpredictable, and we may not be able to obtain adequate remedies for such breaches. We also seek to
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preserve the integrity and confidentiality of our confidential proprietary information by maintaining physical security of our premises and physical and electronic security of our IT systems, but it is possible that these security measures could be breached. In addition, courts outside the U.S. are sometimes less willing to protect trade secrets. Moreover, our competitors may independently develop equivalent knowledge, methods and know-how. Notably, proprietary technology protected by a trade secret does not preempt the patenting of independently developed equivalent technology, even if such equivalent technology is invented subsequent to the technology protected by a trade secret. If any of our confidential proprietary information were to be lawfully obtained or independently developed by a competitor, we would have no right to prevent such competitor from using that technology or information to compete with us, which could harm our competitive position.
Patent terms and market exclusivities, if obtained, may be inadequate to protect our competitive position on our products for an adequate amount of time.
Patents have a limited lifespan. In the U.S., if all maintenance fees are timely paid, the natural expiration of a patent is generally 20 years from its earliest U.S. non-provisional filing date. The patent term of a U.S. patent may be lengthened by patent term adjustment, which compensates a patentee for administrative delays by the U.S. Patent and Trademark Office in granting a patent, or may be shortened if a patent is terminally disclaimed over an earlier-filed patent.
Various extensions may be available, but the life of a patent, and the protection it affords, is limited. Given the amount of time required for the development, testing and regulatory review of new product candidates, patents protecting such candidates might expire before or shortly after such candidates are commercialized.
In the U.S., the Drug Price Competition and Patent Term Restoration Act of 1984 permits a Patent Term Extension, or PTE, of up to five years beyond the normal expiration of the patent to compensate patent owners for loss of enforceable patent term due to the lengthy regulatory approval process. PTE is limited to the approved indication (or any additional indications approved during the period of extension). We anticipate applying for PTE in the U.S. Similar extensions may be available in other countries where we are prosecuting patents and we likewise anticipate applying for such extensions.
The granting of such patent term extensions is not guaranteed and is subject to numerous requirements. We might not be granted an extension because of, for example, failure to apply within applicable periods, failure to apply prior to the expiration of relevant patents or failure to otherwise satisfy any of the numerous applicable requirements. Moreover, the applicable authorities, including the FDA and the USPTO in the U.S., and any equivalent regulatory authority in other countries, may not agree with our assessment of whether such extensions are available, and may refuse to grant extensions to our patents, or may grant more limited extensions than we request. If this occurs, our competitors may be able to obtain approval of competing products following our patent expiration by referencing our clinical and preclinical data and launch their product earlier than might otherwise be the case. If this were to occur, it could have a material adverse effect on our ability to generate revenue.
In addition, market exclusivities may be available for our product candidates and indications. If any product we develop does not receive five years of NCE exclusivity, the FDA may approve generic versions of such product three years after its date of approval, subject to the requirement that the ANDA applicant certifies to the invalidity or non-infringement of any patents listed for our products in the Orange Book. If an infringement suit is timely filed by the NDA or patent holder, the FDA cannot finally approve the ANDA for 30 months unless a court decision in favor of the generic manufacturer is issued earlier. Three-year exclusivity is given to a drug if it contains an active moiety that has previously been approved, and the NDA includes reports of one or more new clinical investigations, other than bioavailability or bioequivalence studies, that were conducted by or for the applicant and are determined by the FDA to be essential to the approval of the NDA. This form of data exclusivity is known as New Clinical Investigation, or NCI, exclusivity. If AMX0035 is approved for future uses, such as Wolfram syndrome or PSP, and if avexitide is approved for future uses, or if current and future candidates, such as AMX0114, are approved with only NCI exclusivity, generic manufacturers may file their ANDAs anytime following approval of AMX0035, AMX0114, or avexitide and seek to launch their generic products following the expiration of the three year market exclusivity period, even if we still have patent protection for our product.
In addition, in the U.S. the FDCA provides a period of seven years of orphan drug exclusivity for drugs that treat small patient populations less than 200,000 patients or for which there are more than 200,000 patients but there is no reasonable expectation that the cost of developing and making the drug for such disease or condition will be recovered from sales in the U.S. of such drug.
In the EU, innovative medicinal products (including both small molecules and biological medicinal products), sometimes referred to as new active substances, or NAS, qualify for eight years of data exclusivity upon marketing authorization and an additional two years of market exclusivity. The data exclusivity, if granted, prevents generic or biosimilar applicants from referencing the innovator’s preclinical and clinical trial data contained in the dossier of the reference product when applying for a generic or biosimilar marketing authorization, for a period of eight years from the date on which the reference product was first authorized in the EU. During the additional two-year period of market exclusivity, a generic or biosimilar marketing authorization can be submitted, and the innovator’s
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data may be referenced, but no generic or biosimilar product can be marketed until the expiration of the market exclusivity period. This 10-year market exclusivity period may be extended to 11 years if, during the first eight of those 10 years, the marketing authorization holder obtains an approval for one or more new therapeutic indications that bring significant clinical benefits compared with existing therapies. However, even if an innovative medicinal product gains the prescribed period of data exclusivity, another company may market another version of the product if such company obtained a marketing authorization based on an application with a complete and independent data package of pharmaceutical tests, preclinical tests and clinical trials. The current orphan medicines regime in the EU entitles an orphan medicine to a 10-year period of market exclusivity, which can be extended to 12 years if the sponsor complies with an agreed upon paediatric investigation plan. However, the European Commission introduced a legislative proposal in April 2023 that, if implemented, could reduce the current exclusivity period for certain orphan medicines.
Competition that AMX0035, AMX0114, avexitide or any future products, if approved, may face from generic versions of such products could negatively impact our future revenue, profitability and cash flows and substantially limit our ability to obtain a return on our investments in those product candidates.
Changes in the interpretation of patent law in the U.S. and other jurisdictions could diminish the value of patents in general, thereby impairing our ability to protect our products.
The U.S. Congress is responsible for passing laws establishing patentability standards. As with any laws, implementation is left to federal agencies and the federal courts based on their interpretations of the laws. Interpretation of patent standards can vary significantly within the U.S. Patent and Trademark Office, and across the various federal courts, including the Supreme Court. Recently, the Supreme Court has ruled on several patent cases, generally limiting the types of inventions that can be patented. Further, there are open questions regarding interpretation of patentability standards that the Supreme Court has yet to decisively address. Absent clear guidance from the Supreme Court, the USPTO has become increasingly conservative in its interpretation of patent laws and standards.
In addition to increasing uncertainty with regard to our ability to obtain patents in the future, the legal landscape in the U.S. has created uncertainty with respect to the value of patents. Depending on any actions by Congress, and future decisions by the lower federal courts and the Supreme Court, along with interpretations by the USPTO, the laws and regulations governing patents could change in unpredictable ways and could weaken our ability to obtain new patents or to enforce our existing patents and patents that we might obtain in the future.
We may not be able to enforce our intellectual property rights throughout the world.
Filing, prosecuting, enforcing and defending patents on our product candidate in all countries throughout the world would be prohibitively expensive, and our intellectual property rights in some countries outside the U.S. can be less extensive than those in the U.S. The requirements for patentability may differ in certain countries, particularly in developing countries; thus, even in countries where we do pursue patent protection, there can be no assurance that any patents will issue with claims that cover our products.
Moreover, our ability to protect and enforce our intellectual property rights may be adversely affected by unforeseen changes in foreign intellectual property laws. Additionally, laws of some countries outside of the U.S. and the EU do not afford intellectual property protection to the same extent as the laws of the U.S. and the EU. Many companies have encountered significant problems in protecting and defending intellectual property rights in certain foreign jurisdictions. This could make it difficult for us to stop the infringement of our patents or the misappropriation of our other intellectual property rights. For example, many foreign countries have compulsory licensing laws under which a patent owner must grant licenses to third parties. Consequently, we may not be able to prevent third parties from practicing our inventions in certain countries outside the U.S. and the EU or from selling or importing products made from our inventions in and into the U.S. or other jurisdictions. Competitors may use our technologies in jurisdictions where we have not obtained patent protection to develop and market their own products and, further, may export otherwise infringing products to territories where we have patent protection if our ability to enforce our patents to stop infringing activities is inadequate. These products may compete with our products, and our patents or other intellectual property rights may not be effective or sufficient to prevent them from competing.
Proceedings to enforce our patent rights, whether or not successful, could result in substantial costs and divert our efforts and resources from other aspects of our business. Moreover, such proceedings could put our patents at risk of being invalidated or held unenforceable, or interpreted narrowly, and our pending patent applications at risk of not issuing, and could provoke third parties to assert claims against us. We may not prevail in any lawsuits that we initiate and the damages or other remedies awarded, if any, may not be commercially meaningful. Furthermore, while we intend to protect our intellectual property rights in major markets for our products, we cannot ensure that we will be able to initiate or maintain similar efforts in all jurisdictions in which we may wish to market our products, if approved. Accordingly, our efforts to protect our intellectual property rights in such countries may be inadequate.
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Others may challenge inventorship or claim an ownership interest in our intellectual property which could expose it to litigation and have a significant adverse effect on its prospects.
A third party or former employee or collaborator may claim an inventorship or ownership interest in one or more of our or our licensors’ patents or other proprietary or intellectual property rights. A third party could bring legal actions against us and seek monetary damages and/or enjoin clinical testing, manufacturing and marketing of the affected product or products. While we are presently unaware of any claims or assertions by third-parties with respect to inventorship or ownership of our patents or other intellectual property, we cannot guarantee that a third party will not assert a claim or an interest in any of such patents or intellectual property. If we fail in defending any such claims, in addition to paying monetary damages, we may lose valuable intellectual property rights, such as exclusive ownership of, or right to use, intellectual property that is important to AMX0035, AMX0114, avexitide, or any other current or future product candidates. Further, regardless of the outcome, if we become involved in any litigation, it could consume a substantial portion of our resources, and cause a significant diversion of effort by our technical and management personnel.
If we are sued for infringing intellectual property rights of third parties, such litigation could be costly and time consuming and could prevent or delay us from developing or commercializing AMX0035, AMX0114, avexitide, or any other current or future product candidates.
Our commercial success depends, in part, on our ability to develop, manufacture, market and sell our product candidate without infringing the intellectual property and other proprietary rights of third parties. However, our research, development and commercialization activities may be subject to claims that we infringe or otherwise violate patents or other intellectual property rights owned or controlled by third parties. Third parties may have U.S. and non-U.S. issued patents and pending patent applications relating to compounds, methods of manufacturing compounds and/or methods of use for the treatment of the disease indications for which we are developing AMX0035, AMX0114, avexitide, or any other current or future product candidates. If any third-party patents or patent applications are found to cover AMX0035, AMX0114, avexitide, or any other current or future product candidates or their methods of use or manufacture, we may not be free to manufacture or market such product candidates as planned without obtaining a license, which may not be available on commercially reasonable terms, or at all.
There is a substantial amount of intellectual property litigation in the biotechnology and pharmaceutical industries, and we may become party to, or threatened with, litigation or other adversarial proceedings regarding intellectual property rights with respect to our products candidates, including patent infringement lawsuits in the U.S. or abroad. There may be third-party patents or patent applications with claims to materials, formulations, methods of manufacture or methods for treatment related to the composition, use or manufacture of AMX0035, AMX0114, avexitide or any other current or future product candidates. While we perform periodic searches for relevant patents and patent applications with respect to our proprietary drug candidates, AMX0035, AMX0114, and our newly acquired product candidate, avexitide, we cannot guarantee that any of our patent searches or analyses including, but not limited to, the identification of relevant patents, the scope of patent claims or the expiration of relevant patents are complete or thorough, nor can we be certain that we have identified each and every patent and pending application in the U.S. and abroad that is relevant to or necessary for the commercialization of AMX0035, AMX0114, avexitide, or any other current or future product candidates in any jurisdiction. Because patent applications can take many years to issue, there may be currently pending patent applications which may later result in issued patents that AMX0035, AMX0114, avexitide, or any other current or future product candidates may be accused of infringing. In addition, third parties may obtain patents in the future and claim that use of our technologies infringes upon these patents. Accordingly, third parties may assert infringement claims against us based on intellectual property rights that exist now or arise in the future. The outcome of intellectual property litigation is subject to uncertainties that cannot be adequately quantified in advance. The pharmaceutical and biotechnology industries have produced a significant number of patents, and it may not always be clear to industry participants, including us, which patents cover various types of products or methods of use or manufacture. The scope of protection afforded by a patent is subject to interpretation by the courts, and the interpretation is not always uniform. If we were sued for patent infringement, we would need to demonstrate that our product candidate, product or method either do not infringe the patent claims of the relevant patent or that the patent claims are invalid or unenforceable, and we may not be able to do this. Proving invalidity is difficult. For example, in the U.S., proving invalidity requires a showing of clear and convincing evidence to overcome the presumption of validity enjoyed by issued patents. Even if we are successful in these proceedings, we may incur substantial costs and the time and attention of our management and scientific personnel could be diverted in pursuing these proceedings, which could significantly harm our business and operating results. In addition, parties making claims against us may be able to sustain the costs of complex patent litigation more effectively than we can because they have substantially greater resources, and we may not have sufficient resources to bring these actions to a successful conclusion.
If we are found to infringe a third party’s intellectual property rights, we could be forced, including by court order, to cease developing, manufacturing or commercializing the infringing product candidate or product. Alternatively, we may be required to obtain a license from such third party in order to use the infringing technology and continue developing, manufacturing or marketing the infringing product candidate or product. If we were required to obtain a license to continue to manufacture or market the affected
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product, we may be required to pay substantial royalties or grant cross-licenses to our patents. We cannot, however, assure you that any such license will be available on acceptable terms, if at all. Ultimately, we could be prevented from commercializing a product, or be forced to cease some aspect of our business operations as a result of claims of patent infringement or violation of other intellectual property rights. Further, the outcome of intellectual property litigation is subject to uncertainties that cannot be adequately quantified in advance, including the demeanor and credibility of witnesses and the identity of any adverse party. This is especially true in intellectual property cases that may turn on the testimony of experts as to technical facts upon which experts may reasonably disagree. Furthermore, we may not be able to obtain any required license on commercially reasonable terms or at all. Even if we were able to obtain a license, it could be non-exclusive, thereby giving our competitors access to the same technologies licensed to us; alternatively or additionally it could include terms that impede or destroy our ability to compete successfully in the commercial marketplace. In addition, we could be found liable for significant monetary damages, including treble damages and attorneys’ fees if we are found to have willfully infringed a patent. A finding of infringement could prevent us from commercializing AMX0035, AMX0114, avexitide, or any other current or future product candidates or force us to cease some of our business operations, which could harm our business. Claims that we have misappropriated the confidential information or trade secrets of third parties could have a similar negative impact on our business. Furthermore, because of the substantial amount of discovery required in connection with intellectual property litigation or administrative proceedings, there is a risk that some of our confidential information could be compromised by disclosure. In addition, any uncertainties resulting from the initiation and continuation of any litigation could have a material adverse effect on our ability to raise additional funds or otherwise have a material adverse effect on our business, results of operations, financial condition and prospects.
We may be subject to claims by third parties asserting that our employees or we have misappropriated their intellectual property, or claiming ownership of what we regard as our own intellectual property.
Many of our current and former employees and our licensors’ current and former employees, including our senior management, were previously employed at universities or at other biotechnology or pharmaceutical companies, including some which may be competitors or potential competitors. Some of these employees, including members of our senior management, may have executed proprietary rights, non-disclosure and non-competition agreements, or similar agreements, in connection with such previous employment. Although we try to ensure that our employees do not use the proprietary information or know-how of others in their work for us, we may be subject to claims that we or these employees have used or disclosed intellectual property, including trade secrets or other proprietary information, of any such third party. Litigation may be necessary to defend against such claims. If we fail in defending any such claims, in addition to paying monetary damages, we may sustain damages or lose key personnel, valuable intellectual property rights or the personnel’s work product, which could hamper or prevent commercialization of our technology, which in turn could materially affect our commercial development efforts. Such intellectual property rights could be awarded to a third party, and we could be required to obtain a license from such third party to commercialize our technology or products. Such a license may not be available on commercially reasonable terms or at all. Even if we are successful in defending against such claims, litigation could result in substantial costs and be a distraction to management.
In addition, while we typically require our employees, consultants and contractors who may be involved in the development of intellectual property to execute agreements assigning such intellectual property to us, we may be unsuccessful in executing such an agreement with each party who in fact develops intellectual property that we regard as our own, which may result in claims by or against us related to the ownership of such intellectual property. If we fail in prosecuting or defending any such claims, in addition to paying monetary damages, we may lose valuable intellectual property rights. Even if we are successful in prosecuting or defending against such claims, litigation could result in substantial costs and be a distraction to our senior management and scientific personnel.
If our trademarks and trade names are not adequately protected, then we may not be able to build name recognition in our trademarks and our business may be adversely affected.
Our trademarks or trade names may be challenged, infringed, circumvented or declared generic or determined to be infringing on other marks. We rely on both registration and common law protection for our trademarks. We may not be able to protect our rights to these trademarks and trade names or may be forced to stop using these names, which we need for name recognition by potential partners or customers in our markets of interest. During trademark registration proceedings, we may receive rejections. Although we would be given an opportunity to respond to those rejections, we may be unable to overcome such rejections. In addition, in the USPTO and in comparable agencies in many foreign jurisdictions, third parties are given an opportunity to oppose pending trademark applications and to seek to cancel registered trademarks. Opposition or cancellation proceedings may be filed against our trademarks, and our trademarks may not survive such proceedings. Moreover, any name we propose to use for our products in the U.S. must be approved by the FDA, regardless of whether we have registered it, or applied to register it, as a trademark. The FDA typically conducts a review of proposed product names, including an evaluation of potential for confusion with other product names. If the FDA objects to any of our proposed product names, we may be required to expend significant additional resources in an effort to identify a usable substitute name that would qualify under applicable trademark laws, not infringe the existing rights of third parties and be
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acceptable to the FDA. If we are unable to establish name recognition based on our trademarks and trade names, we may not be able to compete effectively and our business may be adversely affected.
Intellectual property rights do not necessarily address all potential threats to our business.
The degree of future protection afforded by our intellectual property rights is uncertain because intellectual property rights have limitations, and may not adequately protect our business, or permit us to maintain our competitive advantage. The following examples are illustrative:
Our reliance on third parties for research and development and manufacturing requires us to share our trade secrets, which increases the possibility that our trade secrets will be misappropriated or disclosed, and confidentiality agreements with employees and third parties may not adequately prevent disclosure of trade secrets and protect other proprietary information.
We consider proprietary trade secrets or confidential know-how and unpatented know-how to be important to our business. We may rely on trade secrets or confidential know-how to protect our technology, especially where patent protection is believed by us to be of limited value. We rely on third parties for research and development work, and expect to rely on third parties for future manufacturing of our proprietary product candidate, AMX0035, AMX0114, and our newly acquired product candidate, avexitide, and any other current or future product candidates. We also expect to collaborate with third parties on the development of AMX0035, AMX0114, avexitide, and any other current or future product candidates. As a result of the aforementioned collaborations, we must, at times, share trade secrets with our collaborators.
Trade secrets or confidential know-how can be difficult to maintain as confidential. To protect this type of information against disclosure or appropriation by competitors, our policy is to require our employees, consultants, contractors and advisors to enter into confidentiality agreements and, if applicable, material transfer agreements, consulting agreements or other similar agreements with us prior to beginning research or disclosing proprietary information. These agreements typically limit the rights of the third parties to use or disclose our confidential information, including our trade secrets. However, current or former employees, consultants, contractors and advisers may unintentionally or willfully disclose our confidential information to competitors, and confidentiality agreements may not provide an adequate remedy in the event of unauthorized disclosure of confidential information. The need to share trade secrets and other confidential information increases the risk that such trade secrets become known by our competitors, are inadvertently incorporated into the technology of others, or are disclosed or used in violation of these agreements. Given that our proprietary position is based, in part, on our know-how and trade secrets, a competitor’s discovery of our trade secrets or other unauthorized use or disclosure would impair our competitive position and may have an adverse effect on our business and results of operations. Enforcing a claim that a third party obtained illegally and is using trade secrets or confidential know-how is expensive, time consuming and unpredictable. Moreover, the enforceability of confidentiality agreements may vary from jurisdiction to jurisdiction.
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In addition, these agreements typically restrict the ability of our advisors, employees, third-party contractors and consultants to publish data potentially relating to our trade secrets, although our agreements may contain certain limited publication rights. Despite our efforts to protect our trade secrets, our competitors may discover our trade secrets, either through breach of our agreements with third parties, independent development or publication of information by any of our third-party collaborators. A competitor’s discovery of our trade secrets would impair our competitive position and have an adverse impact on our business.
We may need to acquire or license intellectual property from third parties, and such licenses may not be available or may not be available on commercially reasonable terms.
A third party may hold intellectual property, including patent rights that are important or necessary to the development of additional future product candidates. It may be necessary for us to use the patented or proprietary technology of one or more third parties to commercialize our current and future product candidates. If we are unable to acquire such intellectual property outright, or obtain licenses to such intellectual property from such third parties when needed or on commercially reasonable terms, our ability to commercialize additional future product candidates, if approved, would likely be delayed.
The risks described elsewhere pertaining to our intellectual property rights also apply to the intellectual property rights that we may in-license, and any failure by us or our licensors to obtain, maintain, defend and enforce these rights could have an adverse effect on our business. In some cases we may not have control over the prosecution, maintenance or enforcement of the patents that we license, and may not have sufficient ability to provide input into the patent prosecution, maintenance and defense process with respect to such patents, and potential future licensors may fail to take the steps that we believe are necessary or desirable in order to obtain, maintain, defend and enforce the licensed patents.
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Risks Related to Our Business Operations and Employee Matters
Our Restructuring Plan and associated organizational changes may not adequately reduce our operating costs or improve operating margins, may lead to additional workforce attrition, and may cause operational disruptions.
We implemented our Restructuring Plan that is designed to focus our resources on key clinical and preclinical programs in April 2024. The Restructuring Plan reduced our workforce by approximately 70% and a decreased external financial commitments outside of our priority areas.
The long-term effects of the Restructuring Plan may yield unintended consequences and costs, such as the loss of institutional knowledge and expertise, employee attrition beyond our intended reduction in force, a reduction in morale among our remaining employees, greater-than-anticipated costs incurred in connection with implementing the Restructuring Plan, and the risk that we may not achieve the benefits from the Restructuring Plan to the extent or as quickly as we anticipate, all of which may have a material adverse effect on our results of operations or financial condition. These restructuring initiatives could place substantial demands on our management and employees, which could lead to the diversion of our management’s and employees’ attention from other business priorities. In addition, while certain positions have been eliminated in connection with the Restructuring Plan, certain functions necessary to our reduced operations remain, and we may be unsuccessful in distributing the duties and obligations of departed employees among our remaining employees or to external service providers, which could result in disruptions to our operations. We may also discover that the workforce reduction and other restructuring efforts will make it difficult for us to pursue new opportunities and initiatives and require us to hire qualified replacement personnel, which may require us to incur additional and unanticipated costs and expenses. We may further discover that, despite the implementation of our Restructuring Plan, we may require additional capital to continue expanding our business, and we may be unable to obtain such capital on acceptable terms, if at all. Our failure to successfully accomplish any of the above activities and goals may have a material adverse impact on our business, financial condition, and results of operations. Finally, we have received and may receive additional lawsuits from employees relating to their separation from the Company. These lawsuits may result in increased costs and reputational risk to the Company.
We are continuously evaluating and pursuing strategic transactions, and may pursue strategic transactions in the future that are aligned with our mission in to improve our underlying business performance. For example, we have recently completed the acquisition of avexitide, and may in the future seek to acquire additional assets.
We anticipate completing acquisitions and business combinations in the future, especially given the discontinuation of the marketing authorizations for RELYVRIO/ALBRIOZA (AMX0035) for ALS and its withdrawal from the commercial market in the U.S. and Canada. For example, we recently completed the acquisition of substantially all of the rights, title and interests in, to and under those assets and interests used by Eiger in the development, manufacture and commercialization of avexitide. Our ability to complete future acquisitions and business combinations will depend, in part, on the availability of suitable candidates at acceptable prices, terms, and conditions; our ability to compete effectively for acquisition candidates; and the availability of capital and personnel to complete such acquisitions and run the acquired business effectively. Any acquisition or business combination could impair our business, reputation, operating results and financial condition. The benefits of an acquisition or business combination may take more time than expected to develop or integrate into our operations, and we cannot guarantee that previous or future acquisitions or business combinations will, in fact, produce any benefits. For example, we may not receive the anticipated benefits of the acquisition of avexitide for some time. Acquisitions and business combinations may involve a number of risks, the occurrence of which could adversely affect our business, reputation, operating results and financial condition, including:
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In addition, effective internal controls are necessary for us to provide reliable and accurate financial reports and to effectively prevent fraud. The integration of acquired businesses may result in our systems and controls becoming increasingly complex and more difficult to manage. We devote significant resources and time to comply with the internal control over financial reporting requirements of the Sarbanes-Oxley Act. However, we cannot be certain that these measures will ensure that we design, implement, and maintain adequate control over our financial processes and reporting in the future, especially in the context of acquisitions of other businesses, regardless of whether such acquired business was previously privately or publicly held. Any difficulties in the assimilation of acquired businesses into our control system could harm our operating results or cause us to fail to meet our financial reporting obligations. These risks, among others, could be heightened if we complete a large acquisition or other business combination or multiple transactions within a relatively short period of time.
We are currently operating in a period of economic uncertainty and capital markets disruption, which has been significantly impacted by geopolitical instability, ongoing military conflicts, including the ongoing war between Russia and Ukraine, the Israel-Hamas war and escalating conflict in the Middle East, U.S. presidential elections, events related thereto, such as changes to candidates or political unrest or otherwise, and high inflation and interest rates, any of which could have a material adverse effect on our business, financial condition and results of operations.
U.S. and global markets have recently been experiencing volatility and disruption caused by economic uncertainty, including as a result of the ongoing Russia-Ukraine war and the effects of sanctions imposed on Russia as a result of the conflict, as well as the Israel-Hamas war and escalating conflict in the Middle East. Although the length and impact of the ongoing military conflict is highly unpredictable, the conflict in Ukraine has led to market disruptions, including significant volatility in commodity prices, credit and capital markets, as well as supply chain interruptions, which contributed to record inflation globally. In addition, global markets may experience additional disruptions as a result of the current Israel-Hamas war and the escalating conflict in the Middle East. We are continuing to monitor inflation, the situations in Ukraine and Israel and global capital markets and assessing their potential impact on our business, including the impact on the supply chains we rely on for the manufacture of AMX0035, avexitide or any other current or future product candidates.
Although, to date, our business has not been materially impacted by the events described above, geopolitical tensions, or record inflation, it is impossible to predict the extent to which our operations will be impacted in the short and long term, or the ways in which such matters may impact our business. The extent and duration of the conflicts in Ukraine and Israel, geopolitical tensions, record inflation and resulting market disruptions are impossible to predict but could be substantial. Any such disruptions may also magnify the impact of other risks we face.
Inadequate funding for the FDA, the SEC and other government agencies, including from government shutdowns, or other disruptions to these agencies’ operations, could hinder their ability to hire and retain key leadership and other personnel, prevent new products and services from being developed or commercialized in a timely manner or otherwise prevent those agencies from performing normal business functions on which the operation of our business may rely, which could negatively impact our business.
The ability of the FDA to review and approve new products can be affected by a variety of factors, including government budget and funding levels, the ability to hire and retain key personnel and accept the payment of user fees, and statutory, regulatory and policy changes. Average review times at the agency have fluctuated in recent years as a result. In addition, government funding of the SEC
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and other government agencies on which our operations may rely, including those that fund research and development activities, is subject to the political process, which is inherently fluid and unpredictable.
Disruptions at the FDA and other agencies may also slow the time necessary for new product candidates to be reviewed and/or approved by necessary government agencies, which would adversely affect our business. If a prolonged government shutdown occurs, it could significantly impact the ability of the FDA to timely review and process our regulatory submissions, which could have a material adverse effect on our business. Further, future government shutdowns could impact our ability to access the public markets and obtain necessary capital in order to properly capitalize and continue our operations.
We depend heavily on our executive officers, principal consultants and others, and the loss of their services would materially harm our business.
Our success depends, and will likely continue to depend, upon our ability to hire and retain the services of our current executive officers, principal consultants and others. We have entered into employment agreements with our current executive officers, but they may terminate their employment with us at any time. The loss of their services might impede the achievement of our research, development and commercialization objectives.
Our ability to compete in the biotechnology and pharmaceuticals industries depends upon our ability to attract and retain highly qualified managerial, scientific and medical personnel. Our industry has experienced a high rate of turnover of management personnel in recent years, which has also impacted our company. For example, in February 2024, our then Chief Human Resource Officer, Debra Canner, was replaced by Linda Arsenault as our current Chief Human Resource Officer. Replacing executive officers or other key employees may be difficult and may take an extended period of time because of the limited number of individuals in our industry with the breadth of skills and experience required to develop, gain regulatory approval of and commercialize products successfully.
Competition to hire from this limited pool is intense, and we may be unable to hire, train, retain or motivate these additional key employees on acceptable terms given the competition among numerous pharmaceutical and biotechnology companies for similar personnel. We also experience competition for the hiring of scientific and clinical personnel from universities and research institutions.
We rely on consultants and advisors, including scientific and clinical advisors, to assist us in formulating our research and development and commercialization strategy. Our consultants and advisors may be employed by other entities and may have commitments under consulting or advisory contracts with those entities that may limit their availability to us. If we are unable to continue to attract and retain highly qualified personnel, our ability to develop AMX0035, avexitide or any other current or future product candidates will be limited.
We only have a limited number of employees to manage and operate our business.
We implemented a Restructuring Plan to reduce our workforce by 70% in April 2024. Our Restructuring Plan and our focus on research and the development of our product candidates requires us to optimize cash utilization and to manage and operate our business in a highly efficient manner. We cannot assure you that we will be able to hire and/or retain adequate staffing levels to develop our product candidates or to run our operations and/or to accomplish all of the objectives that we otherwise would seek to accomplish.
Our employees, independent contractors, consultants, collaborators and CROs may engage in misconduct or other improper activities, including non-compliance with regulatory standards and requirements, which could cause significant liability for us and harm our reputation.
We are exposed to the risk that our employees, independent contractors, consultants, collaborators and CROs may engage in fraudulent conduct or other illegal activity. Misconduct by those parties could include intentional, reckless and/or negligent conduct or disclosure of unauthorized activities to us that violates:
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Activities subject to these laws also involve the improper marketing, use or misrepresentation of information obtained in the course of clinical trials, creating fraudulent data in our preclinical studies or clinical trials or illegal misappropriation of product materials, which could result in regulatory sanctions and serious harm to our reputation. It is not always possible to identify and deter misconduct, and the precautions we take to detect and prevent this activity may not be effective in controlling unknown or unmanaged risks or losses or in protecting us from governmental investigations or other actions or lawsuits stemming from a failure to be in compliance with such laws, standards or regulations. Additionally, we are subject to the risk that a person or government could allege such fraud or other misconduct, even if none occurred. If any such actions are instituted against us, and we are not successful in defending ourselves or asserting our rights, those actions could have a significant impact on our business and results of operations, including the imposition of civil, criminal and administrative penalties, damages, monetary fines, disgorgement, integrity oversight and reporting obligations, possible exclusion from participation in Medicare, Medicaid and other federal healthcare programs, contractual damages, reputational harm, diminished profits and future earnings, and curtailment of our operations, any of which could have a material adverse effect on our ability to operate our business and our results of operations.
A pandemic, epidemic, or outbreak of an infectious disease may materially and adversely affect our business, including our preclinical studies, clinical trials, third parties on whom we rely, our supply chain, our ability to raise capital, our ability to conduct regular business and our financial results.
We are subject to risks related to public health crises. For instance, from 2020 through 2022, we experienced certain impacts from the COVID-19 pandemic, including alterations to our preclinical and clinical trial activities, such as scheduling certain work off-site and performing off-site assessments. There can be no guarantee we will not experience other impacts in the future, such as being forced to further delay or pause enrollment, experiencing potential interruptions to our supply chain, facing difficulties or additional costs in enrolling patients in future clinical trials or being able to achieve full enrollment of our studies within the timeframes we anticipate, or at all.
Any negative impact any future pandemic or similar disruption has on patient enrollment or treatment, or the development of AMX0035, avexitide and any other current or future product candidates, could cause costly delays to clinical trial activities, which could adversely affect our ability to obtain regulatory approval for and to commercialize AMX0035, avexitide and any other current or future product candidates, if approved, increase our operating expenses, which could have a material adverse effect on our financial results. The COVID-19 pandemic and other global macroeconomic factors have also caused significant volatility in public equity markets and disruptions to the U.S. and global economies and any future pandemic or similar disruption could lead to further market dislocation. Any such increased volatility and economic dislocation may make it more difficult for us to raise capital on favorable terms, or at all. If we or any of the third parties with whom we engage were to experience business disruptions, our ability to conduct our business in the manner and on the timelines presently planned could be materially and negatively affected, which could have a material adverse impact on our business and our results of operations and financial conditions. To the extent any future pandemic or similar disruption adversely affects our business and financial results, it may also heighten many of the other risks described in this ‘‘Risk Factors’’ section, such as those relating to the timing and completion of our clinical trials and our ability to obtain future financing.
Risks Related to Our Common Stock
The price of our stock may be volatile, and you could lose all or part of your investment.
The trading price of our common stock may be highly volatile and could be subject to wide fluctuations in response to various factors, some of which are beyond our control, including limited trading volume. For example, from January 7, 2022, the first day that our stock traded on the Nasdaq Global Select Market, through September 30, 2024, our stock has traded within a range of a high price of $41.93 and a low price of $1.58 per share. In addition to the factors discussed in this “Risk Factors” section and elsewhere in this Quarterly Report, these factors include:
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In addition, the stock market in general, and pharmaceutical companies in particular, have experienced extreme price and volume fluctuations that have often been unrelated or disproportionate to the operating performance of these companies. Broad market and industry factors may negatively affect the market price of our common stock, regardless of our actual operating performance.
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Unstable market, economic, political and geographical conditions may have serious adverse consequences on our business, financial condition and stock price.
As widely reported, global credit and financial markets have experienced extreme volatility and disruptions in the past several years, including severely diminished liquidity and credit availability, declines in consumer confidence, increases in the rate of inflation and interest rates and uncertainty about economic stability, including most recently in connection with the wars in Ukraine and Israel and the U.S. presidential election. There can be no assurance that further deterioration in credit and financial markets and confidence in economic conditions will not occur. Our general business strategy may be adversely affected by any such economic downturn, volatile business environment or continued unpredictable and unstable market conditions. Our business could also be impacted by volatility caused by geopolitical events such as the wars in Ukraine and Israel. If the current equity and credit markets deteriorate, or do not improve, it may make any necessary debt or equity financing more difficult, more costly, and more dilutive. Furthermore, our stock price may decline due in part to the volatility of the stock market and the general economic downturn.
Failure to secure any necessary financing in a timely manner and on favorable terms could have a material adverse effect on our growth strategy, financial performance and stock price and could require us to delay, scale back or discontinue the development and commercialization of one or more of our product candidates or delay our pursuit of potential in-licenses or acquisitions. In addition, there is a risk that one or more of our current service providers, manufacturers and other partners may not survive these difficult economic times, which could directly affect our ability to attain our operating goals on schedule and on budget.
We are no longer an emerging growth company and the reduced compliance requirements applicable to emerging growth companies no longer apply to us.
We no longer qualify as an emerging growth company as defined in the Jumpstart Our Business Startups Act of 2012, or the JOBS Act, and as such we no longer are entitled to rely on exemptions from certain compliance requirements that are applicable to companies that are emerging growth companies. As a result, subject to certain grace periods, we are now required to:
We are no longer able to take advantage of cost savings associated with the JOBS Act. Furthermore, if the additional requirements applicable to non-emerging growth companies divert the attention of our management and personnel from other business concerns, they could have a material adverse effect on our business, financial condition and results of operations. The increased costs will decrease our net income or increase our net loss and may require us to reduce costs in other areas of our business. We cannot predict or estimate the amount or timing of additional costs we may incur to respond to these requirements. Furthermore, if we are unable to satisfy our obligations as a non-emerging growth company, we could be subject to delisting of our common stock, fines, sanctions and other regulatory action and potentially civil litigation.
Commencing December 31, 2024, we will be a smaller reporting company due to our requalification at June 30, 2024 and we will become an accelerated filer, rather than a large accelerated filer due to our status at June 30, 2024. We cannot be certain if the reduced reporting requirements applicable to smaller reporting companies will make our common stock less attractive to investors.
As of June 30, 2023, the market value of our common stock that was held by non-affiliates exceeded $700 million, and therefore, effective as of January 1, 2024, we became a large accelerated filer. We also were no longer qualified as an emerging growth company or smaller reporting company and were no longer able to avail ourselves of the reduced disclosure requirements available to smaller reporting companies. However, based on the market value of our common stock that was held by non-affiliates as of June 30, 2024, we will regain smaller reporting company status effective as of December 31, 2024 and will be able to avail ourselves of the reduced disclosure requirements. As a smaller reporting company, we will be permitted and intend to rely on reduced disclosure requirements that are applicable to other public companies that are smaller reporting companies. Smaller reporting companies are able to provide simplified executive compensation disclosure and have certain other reduced disclosure obligations, including, among other things, being required to provide only two years of audited financial statements and not being required to provide supplemental financial information or risk factors. Despite status effectiveness at December 31, 2024, due to requalification we are able to rely on these reduced requirements beginning after June 30, 2024. We cannot predict if investors will find our common stock less attractive because we may rely on these exemptions. If some investors find our common stock less attractive as a result, there may be a less active
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trading market for our common stock and our stock price may be more volatile. As of June 30, 2024, we are also an accelerated filer and are still required to have our independent auditors annually attest to our evaluation, as well as issue their own opinion on our internal control over financial reporting.
A significant portion of our total outstanding shares may be sold into the market, which could cause the market price of our common stock to decline significantly, even if our business is doing well.
Sales of a substantial number of shares of our common stock in the public market could occur at any time. These sales, or the perception in the market that the holders of a large number of shares intend to sell shares, could reduce the market price of our common stock. As of October 31, 2024, we had outstanding 68,547,860 shares of common stock, which may be resold in the public market immediately without restriction, unless held by our affiliates. Moreover, holders of approximately 11.9 million shares of our common stock have rights, subject to specified conditions, to require us to file registration statements covering their shares or to include their shares in registration statements that we may file for ourselves or other stockholders.
We do not anticipate paying any cash dividends on our capital stock in the foreseeable future. Accordingly, stockholders must rely on capital appreciation, if any, for any return on their investment.
We have never declared nor paid cash dividends on our capital stock. We currently plan to retain all of our recent or any future earnings, if any, to finance the operation, development and growth of our business. In addition, the terms of any future debt or credit agreements may preclude us from paying dividends. As a result, capital appreciation, if any, of our common stock will be your sole source of gain for the foreseeable future.
Concentration of ownership of our common stock among our existing executive officers, directors and principal stockholders may prevent new investors from influencing significant corporate decisions.
Our executive officers and directors, combined with our stockholders who own more than 5% of our outstanding common stock, own a significant portion of our common stock. As a result, these stockholders acting together, could be able to significantly influence all matters submitted to our stockholders for approval, as well as our management and affairs. For example, these stockholders, if they choose to act together, could significantly influence the election of directors and approval of any merger, consolidation or sale of all or substantially all of our assets. This may prevent or discourage unsolicited acquisition proposals or offers for our common stock that our stockholders may feel are in their best interest.
Delaware law and provisions in our amended and restated certificate of incorporation, or our certificate of incorporation, and amended and restated bylaws, or our bylaws, could make a merger, tender offer or proxy contest difficult, thereby depressing the trading price of our common stock.
Provisions of our certificate of incorporation and bylaws may delay or discourage transactions involving an actual or potential change in our control or change in our management, including transactions in which stockholders might otherwise receive a premium for their shares or transactions that our stockholders might otherwise deem to be in their best interests. Therefore, these provisions could adversely affect the price of our common stock. Among other things, our certificate of incorporation and bylaws:
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The amendment of any of these provisions, with the exception of the ability of our board of directors to issue shares of preferred stock and designate any rights, preferences and privileges thereto, would require approval by the holders of at least 66-2/3% of our then-outstanding common stock.
In addition, as a Delaware corporation, we are subject to Section 203 of the Delaware General Corporation Law. These provisions may prohibit large stockholders, in particular those owning 15% or more of our outstanding voting stock, from merging or combining with us for a certain period of time. A Delaware corporation may opt out of this provision by express provision in its original certificate of incorporation or by amendment to its certificate of incorporation or bylaws approved by its stockholders. However, we have not opted out of this provision.
These and other provisions in our certificate of incorporation, bylaws and Delaware law could make it more difficult for stockholders or potential acquirors to obtain control of our board of directors or initiate actions that are opposed by our then-current board of directors, including delay or impede a merger, tender offer or proxy contest involving our company. The existence of these provisions could negatively affect the price of our common stock and limit opportunities for you to realize value in a corporate transaction.
If we fail to maintain proper and effective internal control over financial reporting, our ability to produce accurate and timely financial statements could be impaired, which could harm our operating results, investors' views of us and, as a result, the value of our common stock.
Pursuant to Section 404, our management is required to assess and report annually on the effectiveness of our internal control over financial reporting and to identify any material weaknesses in our internal control over financial reporting. As a result of no longer qualifying as an emerging growth company as defined in the JOBS Act and becoming a large accelerated filer, we were also required to comply with, among other requirements, the auditor attestation requirements of Section 404(b), and as an accelerated filer will be required to continue to comply with such requirements. Preparing such attestation report and the cost of compliance with reporting requirements that we had not previously implemented has and will continue to increase our expenses and require significant management time. Investors may find our common stock less attractive because of the additional compliance costs. If some investors find our common stock less attractive as a result, there may be a less active trading market for our common stock and our stock price may be more volatile.
The rules governing the standards that must be met for management and our independent registered public accounting firm to assess our internal control over financial reporting are complex and require significant documentation, testing, and possible remediation. In connection with our and our independent registered public accounting firm's evaluations of our internal control over financial reporting, we may need to upgrade systems, including information technology, implement additional financial and management controls, reporting systems, and procedures, and hire additional accounting and finance staff.
Any failure to implement required new or improved controls, or difficulties encountered in their implementation, could cause us to fail to meet our reporting obligations. In addition, any testing by us or our independent registered public accounting firm conducted in connection with Section 404 may reveal deficiencies in our internal control over financial reporting that are deemed to be material
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weaknesses or that may require prospective or retroactive changes to our financial statements or identify other areas for further attention or improvement. Inferior internal controls could also cause investors to lose confidence in our reported financial information, which could have a negative effect on the trading price of our common stock. Internal control deficiencies could also result in a restatement of our financial results in the future. We could become subject to stockholder or other third-party litigation, as well as investigations by the SEC, the Nasdaq Global Select Market, or other regulatory authorities, which could require additional financial and management resources and could result in fines, trading suspensions, payment of damages or other remedies. Further, any delay in compliance with the auditor attestation provisions of Section 404 could subject us to a variety of administrative sanctions, including ineligibility for short-form resale registration, action by the SEC and the suspension or delisting of our common stock, which could reduce the trading price of our common stock and could harm our business.
Our bylaws provide that the Court of Chancery of the State of Delaware and the federal district courts of the U.S. will be the exclusive forums for substantially all disputes between us and our stockholders, which could limit our stockholders’ ability to obtain a favorable judicial forum for disputes with us or our directors, officers, or employees.
Our bylaws provide that, to the fullest extent permitted by law and subject to the court’s having personal jurisdiction over the indispensable parties named as defendants, the Court of Chancery of the State of Delaware is the exclusive forum for the following types of actions or proceedings under Delaware statutory or common law:
This provision would not apply to suits brought to enforce a duty or liability created by the Exchange Act. Furthermore, Section 22 of the Securities Act creates concurrent jurisdiction for federal and state courts over all such Securities Act actions. Accordingly, both state and federal courts have jurisdiction to entertain such claims. To prevent having to litigate claims in multiple jurisdictions and the threat of inconsistent or contrary rulings by different courts, among other considerations, our certificate of incorporation further provides that the federal district courts of the U.S. will be the exclusive forum for resolving any complaint asserting a cause of action arising under the Securities Act. While the Delaware courts have determined that such choice of forum provisions are facially valid, a stockholder may nevertheless seek to bring a claim in a venue other than those designated in the exclusive forum provisions. In such instance, we would expect to vigorously assert the validity and enforceability of the exclusive forum provisions of our certificate of incorporation. This may require significant additional costs associated with resolving such action in other jurisdictions and there can be no assurance that the provisions will be enforced by a court in those other jurisdictions.
These exclusive forum provisions may limit a stockholder’s ability to bring a claim in a judicial forum that it finds favorable for disputes with us or our directors, officers, or other employees, which may discourage lawsuits against us and our directors, officers and other employees. If a court were to find either exclusive forum provision in our certificate of incorporation to be inapplicable or unenforceable in an action, we may incur further significant additional costs associated with resolving the dispute in other jurisdictions, all of which could seriously harm our business.
Future sales and issuances of our common stock or rights to purchase common stock, including pursuant to our equity incentive plans, could result in additional dilution of the percentage ownership of our stockholders and could cause our stock price to fall.
We expect that we will need significant additional capital in the future to continue our planned operations, including conducting clinical trials, commercialization efforts if we are able to obtain marketing approval of any of AMX0035, avexitide or any other current or future product candidates, research and development activities, and costs associated with operating a public company. To raise capital, we may sell common stock, convertible securities or other equity securities in one or more transactions at prices and in a manner we determine from time to time. If we sell common stock, convertible securities or other equity securities, investors may be materially diluted by subsequent sales. Such sales may also result in material dilution to our existing stockholders, and new investors
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could gain rights, preferences and privileges senior to the holders of our common stock, including shares of common stock sold in our public offerings.
Pursuant to our 2022 Stock Option and Incentive Plan, or the 2022 Plan, our management is authorized to grant stock options to our employees, directors and consultants. Additionally, the number of shares of our common stock reserved for issuance under our 2022 Plan will automatically increase on January 1 of each year, beginning on January 1, 2023 and continuing through and including January 1, 2032, by 5.0% of the total number of shares of our capital stock outstanding on December 31 of the preceding calendar year, or a lesser number of shares determined by our board of directors. In addition, pursuant to our ESPP, the number of shares of our common stock reserved for issuance will automatically increase on January 1 of each calendar year, beginning on January 1, 2023 (through January 1, 2032), by the lesser of (i) 1.0% of the total number of shares of our common stock outstanding on the last day of the calendar month before the date of the automatic increase, and (ii) 1,210,000 shares; provided that before the date of any such increase, our board of directors may determine that such increase will be less than the amount set forth in clauses (i) and (ii). Unless our board of directors elects not to increase the number of shares available for future grant each year, our stockholders may experience additional dilution, which could cause our stock price to fall.
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General Risk Factors
We incur significant costs as a result of operating as a public company, and our management is required to devote substantial time to compliance initiatives.
As a public company, we incur significant and ongoing legal, accounting, and other expenses, particularly now that we are no longer an emerging growth company. We are subject to the reporting requirements of the Exchange Act, which require, among other things, that we file with the SEC annual, quarterly, and current reports with respect to our business and financial condition. In addition, the Sarbanes-Oxley Act, as well as rules subsequently adopted by the SEC and the Nasdaq Global Select Market to implement provisions of the Sarbanes-Oxley Act, impose significant requirements on public companies, including requiring maintenance of effective disclosure and financial controls and changes in corporate governance practices. Further, in July 2010, the Dodd-Frank Wall Street Reform and Consumer Protection Act, or the Dodd-Frank Act, was enacted. There are significant corporate governance and executive compensation related provisions in the Dodd-Frank Act that require the SEC to adopt additional rules and regulations in these areas such as “say on pay” and proxy access. Stockholder activism, the current political environment and the current high level of government intervention and regulatory reform may lead to substantial new regulations and disclosure obligations, which may lead to additional compliance costs and impact the manner in which we operate our business in ways we cannot currently anticipate.
Moreover, since we ceased to be an emerging growth company, we may no longer take advantage of certain exemptions from various reporting requirements that are applicable to public companies. This increase in reporting requirements will further increase our compliance burden. We expect to continue to incur substantial costs to comply with the rules and regulations applicable to public companies. If these requirements divert the attention of our management and personnel from other business concerns, they could have a material adverse effect on our business, financial condition, and results of operations. The increased costs will decrease our net income or increase our net loss, and may require us to reduce costs in other areas of our business or increase the prices of our products or services. We cannot predict or estimate the amount or timing of additional costs we may incur to respond to these requirements. The impact of these requirements could also make it more difficult for us to attract and retain qualified persons to serve on our board of directors, our board committees or as executive officers.
Cyber-attacks or other failures in our telecommunications or IT systems, or those of our collaborators, CROs, third-party logistics providers, distributors or other contractors or consultants, could result in information theft, data corruption and significant disruption of our business operations.
We, our collaborators, our CROs, third-party logistics providers, distributors and other contractors and consultants utilize IT systems and networks to process, transmit and store electronic information in connection with our business activities. As use of digital technologies has increased, cyber incidents, including third parties gaining access to employee accounts using stolen or inferred credentials, computer malware, viruses, social engineering, spamming or other means, and deliberate attacks and attempts to gain unauthorized access to computer systems and networks, have generally been increasing in frequency and sophistication. Cyber-attacks also could include phishing attempts or e-mail fraud to, for example, cause payments or information to be transmitted to an unintended recipient. We and some of our third-party collaborators have in the past and may in the future experience cyber security attacks. These threats pose a risk to the security of our, our collaborators’, our CROs’, third-party logistics providers’, distributors’ and other contractors’ and consultants’ systems and networks, and the confidentiality, availability and integrity of our data. There can be no assurance that we will be successful in preventing cyber-attacks or successfully mitigating their effects. Similarly, there can be no assurance that our collaborators, CROs, third-party logistics providers, distributors and other contractors and consultants will be successful in protecting our clinical and other data that is stored on their systems or to which they have access. Any cyber-attack, data breach, security incident or destruction, misuse, or loss of data could result in a violation of applicable U.S. and international privacy, data protection and other laws, and subject us to litigation and governmental investigations and proceedings by federal, state and local regulatory entities in the U.S. and by international regulatory entities, resulting in exposure to material civil and/or criminal liability. Further, our general liability insurance and corporate risk program may not cover all potential claims to which we are exposed and may not be adequate to indemnify us for all liability that maybe imposed and could have a material adverse effect on our business and prospects. For example, the loss of clinical trial data from completed, ongoing or future clinical trials for AMX0035, avexitide or any of our future product candidates could result in delays in our development and regulatory approval efforts and significantly increase our costs to recover or reproduce the data. In addition, we may suffer reputational harm or face litigation or adverse regulatory action as a result of cyber-attacks or other data security breaches or incidents and may incur reputational harm and significant additional expense, including to implement further data protection or remedial measures, from fines and penalties or other liability, and from loss of existing and future business.
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Our ability to use net operating losses and research and development credits to offset future taxable income may be subject to certain limitations.
As of December 31, 2023, we had U.S. federal net operating loss, or NOL, carryforwards of $69.8 million that carry forward indefinitely. The amount of annual utilization of these NOL carryforwards may be limited based on provisions of the Tax Cuts and Jobs Act of 2017, or TCJA. As of December 31, 2023, we also had U.S. federal research and development tax credit carryforwards of $6.8 million and we have additionally recorded deferred tax assets for U.S. state NOL and research and development tax credit carryforwards of $9.8 million. These U.S. federal research and development tax credit and U.S. state carryforwards could begin to expire if unused in 2042 and 2035, respectively. Utilization of all NOL and research and development tax credit carryforwards is conditioned upon us generating U.S. federal and state taxable income.
Ownership changes occurred in the years ended December 31, 2016 and 2023. In general, under Sections 382 and 383 of the Internal Revenue Code of 1986, as amended, or the IRC, and corresponding provisions of state law, a corporation that undergoes an ownership change is subject to limitations on its ability to utilize its pre-change NOL or tax credit carryforwards to offset future taxable income. For these purposes, an ownership change generally occurs where the aggregate stock ownership of one or more stockholders or groups of stockholders who owns at least five percent of a corporation’s stock increases its ownership by more than 50 percentage points over its lowest ownership percentage within a specified testing period. Future changes in our stock ownership, many of which are outside of our control, could result in an ownership change under Sections 382 and 383 of the IRC. Our existing federal and state NOL and research and development tax credit carryforwards may be subject to limitations arising from these future ownership changes. Accordingly, we may not be able to utilize a material portion of these carryforwards.
We are currently involved in securities class action litigation and could be subject to additional securities class action litigation in the future.
On February 9, 2024, a putative class action lawsuit was filed in the U.S. District Court for the Southern District of New York against the Company and certain of its current and former officers (Shih v. Amylyx Pharmaceuticals, Inc., et al., Case Number 1:24-CV-00988, or the Shih Complaint). Plaintiff filed an amended complaint on June 24, 2024. The Shih Complaint asserts a claim against all defendants for alleged violations of Section 10(b) of the Exchange Act and Rule 10b-5 promulgated thereunder and a claim under Section 20(a) against certain current and former officers as alleged controlling persons. The Shih Complaint alleges that defendants made materially false and misleading statements related to the commercial results and prospects for RELYVRIO. The Shih Complaint seeks unspecified damages, interest, costs and attorneys’ fees, and other unspecified relief that the court deems appropriate.
On August 12, 2024, the case was transferred from the U.S. District Court for the Southern District of New York to the U.S. District Court for the District of Massachusetts, or the Court, and assigned docket number 1:24-CV-12068. Following the transfer, on September 6, 2024, defendants moved to dismiss the Shih Complaint. Plaintiff filed his opposition to Defendants’ motion to dismiss on October 21, 2024 and defendants’ response is due on or before November 20, 2024. On October 2, 2024, a derivative complaint was filed in the U.S. District Court for the District of Massachusetts against certain current and former director and officer defendants, naming the Company as nominal defendant (Jones v. Cohen, et al., 1:24-CV-12527, or the Derivative Complaint). The substantive allegations mirror those of the Shih Complaint but also include claims for alleged violations of Section 14(a) of the Exchange Act, breach of fiduciary duty, insider trading, and unjust enrichment. The Derivative Complaint seeks unspecified damages to be awarded to the Company along with interest, costs, and attorneys’ fees, restitution, and unspecified corporate governance and internal procedural reforms and improvements. On October 31, 2024, the Court entered an order staying the action until the earlier of the dismissal of the Shih Complaint with prejudice, including the exhaustion of all appeals, or defendants file an answer to the Shih Complaint.
The Company intends to defend against the Shih Complaint and Derivative Complaint vigorously. At this time, an estimate of the impact, if any, of the claims made in the Shih Complaint and Derivative Complaint cannot be made.
We may also become subject to additional securities class action lawsuits in the future. Securities class action litigation has often been brought against a company following a decline in the market price of its securities. This risk is especially relevant for us because pharmaceutical companies have experienced significant stock price volatility in recent years. Such litigation could result in substantial costs and a diversion of management’s attention and resources, which could harm our business.
Our failure to meet Nasdaq’s continued listing requirements could result in a delisting of our common stock.
If we fail to satisfy the continued listing requirements of the Nasdaq Global Select Market, such as the corporate governance requirements or the minimum closing bid price requirement, Nasdaq may take steps to delist our common stock. Such a delisting would likely have a negative effect on the price of our common stock and would impair your ability to sell or purchase our common stock when you wish to do so. In the event of a delisting, we can provide no assurance that any action taken by us to restore
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compliance with listing requirements would allow our common stock to become listed again, stabilize the market price or improve the liquidity of our common stock, prevent our common stock from dropping below the minimum bid price requirement or prevent future non-compliance with the listing requirements of the Nasdaq Global Select Market.
If securities analysts publish negative evaluations of our stock, the price of our stock could decline.
The trading market for our common stock depends in part on the research and reports that industry or securities analysts publish about us or our business. If one or more of the analysts who may cover us issues an adverse opinion about our company, our stock price would likely decline. If one or more of these analysts ceases research coverage of us or fails to regularly publish reports on us, we could lose visibility in the financial markets, which in turn could cause our stock price or trading volume to decline.
Item 2. Unregistered Sales of Equity Securities, Use of Proceeds and Issuer Purchases of Equity Securities
None.
Item 3. Defaults Upon Senior Securities.
None.
Item 4. Mine Safety Disclosures.
Not applicable.
Item 5. Other Information.
(c)
During the three months ended September 30, 2024, no officers or directors of the Company (as defined in Rule 16a-1(f))
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Item 6. Exhibits.
Exhibit Number |
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Description |
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3.1 |
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3.2 |
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31.1* |
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31.2* |
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31.3* |
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32.1+ |
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32.2+ |
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32.3+ |
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101.INS |
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Inline XBRL Instance Document – the instance document does not appear in the Interactive Data File because XBRL tags are embedded within the Inline XBRL document. |
101.SCH |
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Inline XBRL Taxonomy Extension Schema With Embedded Linkbase Documents |
104 |
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Cover Page Interactive Data File (embedded within the Inline XBRL document) |
* Filed herewith.
+ This certification will not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended, or otherwise subject to the liability of that section. Such certification will not be deemed to be incorporated by reference into any filing under the Securities Act of 1933, as amended, except to the extent specifically incorporated by reference into such filing.
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SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned thereunto duly authorized.
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AMYLYX PHARMACEUTICALS, INC. |
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Date: November 7, 2024 |
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By: |
/s/ Joshua B. Cohen |
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Joshua B. Cohen |
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Co-Chief Executive Officer |
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By: |
/s/ Justin Klee |
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Justin Klee |
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Co-Chief Executive Officer |
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By: |
/s/ James M. Frates |
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James M. Frates |
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Chief Financial Officer |
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