10-Q

（以前的名称、以前的地址和以前的财年，如果自上次报告以来发生了变化）

通过勾选标记标明注册人是否（1）在过去12个月内（或在注册人被要求提交此类报告的较短期限内）提交了1934年证券交易法第13或15（d）条要求提交的所有报告，以及（2）在过去90天内是否遵守此类提交要求。是的 ☒ 没有 ☐

通过勾选来验证注册人是否已以电子方式提交了根据第S-t条第405条要求提交的所有互动数据文件（§232. 本章第405条）在过去12个月内（或登记人被要求提交此类文件的较短期限内）。是的 ☒ 没有 ☐

通过复选标记来确定注册人是大型加速申报人、加速申报人、非加速申报人、小型报告公司还是新兴成长型公司。请参阅《交易法》第120条第2条中「大型加速申报人」、「加速申报人」、「小型报告公司」和「新兴成长型公司」的定义。

如果是新兴成长型公司，请通过勾选标记表明注册人是否选择不利用延长的过渡期来遵守根据《交易法》第13（a）条规定的任何新的或修订的财务会计准则。 ☐

通过勾选标记检查注册人是否是空壳公司（定义见《交易法》第120条第2款）。是的 ☐ 没有 ☒

截至2024年11月1日，登记人已 65,457,648 普通股，每股面值0.001美金，已发行。

本季度10-Q表格报告包含1995年《私人证券诉讼改革法案》含义内的前瞻性陈述。我们希望此类前瞻性陈述受1933年证券法（经修订）第27 A条或《证券法》和1934年证券交易法（经修订）第21 E条或《交易法》所载前瞻性陈述的安全港条款的涵盖。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，包括但不限于有关以下方面的陈述：

这些陈述既不是承诺，也不是保证，而是涉及已知和未知的风险、不确定性和其他重要因素，可能导致我们的实际结果、业绩或成就与前瞻性陈述中表达或暗示的任何未来结果、业绩或成就存在重大差异。

在某些情况下，您可以通过“可能”、“将会”、“应该”、“预期”、“计划”、“预期”、“可能”、“打算”、“目标”、“专案”、“考虑”、“相信”、“估计”、“预测”、“潜在”、“将”或“继续”或这些术语的否定或其他类似表述来识别前瞻性陈述，尽管并非所有前瞻性陈述都包含这些词语或表述。本季度报告中关于Form 10-Q的前瞻性陈述仅为预测，主要基于我们目前对未来事件和财务趋势的预期和预测，我们认为这些事件和财务趋势可能会影响我们的业务、财务状况和运营结果。这些前瞻性陈述仅针对截至本Form 10-Q季度报告的日期发表，受许多已知和未知的风险、不确定性和假设的影响，包括在本Form 10-Q季度报告中题为“风险因素”和“管理层对财务状况和经营成果的讨论与分析”的章节以及本Form 10-Q季度报告的其他章节中描述的那些风险、不确定性和假设。由于前瞻性陈述本身就会受到风险和不确定性的影响，其中一些风险和不确定性是无法预测或量化的，有些是我们无法控制的，因此您不应依赖这些前瞻性陈述作为对未来事件的预测。我们的前瞻性陈述中反映的事件和情况可能无法实现或发生，实际结果可能与前瞻性陈述中预测的结果大不相同。

此外，我们在不断变化的环境中运营。新的风险因素和不确定性可能会不时出现，管理层不可能预测所有风险因素和不确定性。您应该完整阅读本10-Q表格季度报告以及我们在本10-Q表格季度报告中引用的文件，并了解我们的实际未来结果可能与我们的预期存在重大差异。我们通过这些警示性陈述来限制我们所有的前瞻性陈述。虽然我们可能会选择在未来的某个时候更新此类前瞻性陈述，但我们不承担任何这样做的义务，即使后续事件导致我们的观点发生变化。

除非上下文另有要求，否则我们在本10-Q表格季度报告中使用术语「Lyra」、「公司」、「我们」、「我们的」和类似名称来指代Lyra Therapeutics，Inc.及其全资子公司Lyra Therapeutics Securities Corporation。

我们的业务面临许多风险和不确定性，包括第二部分第1A项中描述的风险和不确定性。本季度报告中的「风险因素」表格10-Q。在投资我们的普通股时，您应该仔细考虑这些风险和不确定性。影响我们业务的主要风险和不确定性包括以下内容：

1.器官改制、重组、持续经营和列报基础

莱拉治疗公司(以下简称“莱拉治疗公司”)是一家临床阶段的生物技术公司，专注于慢性鼻窦炎(CRS)患者的局部治疗方法的开发和商业化。该公司的专利技术旨在通过一次给药，持续地将药物直接输送到受影响的组织。该公司的候选产品LYR-210和LYR-220是可生物吸收的鼻部植入物，旨在通过简单的办公室程式给药，旨在向鼻腔通道提供为期6个月的持续抗炎药物治疗，以治疗CRS。该公司于年注册为特拉华州的一家公司。2005年11月21日位于马萨诸塞州沃特敦。2018年7月16日，公司前身从480 Biomedical，Inc.更名为Lyra Treateutics，Inc.

该公司面临著与治疗和制药行业的公司相同的风险，包括但不限于：临床前研究和临床试验失败的风险；它可能确定和开发的任何候选药物需要获得市场批准的风险；对其候选产品成功商业化并获得市场认可的需要；对关键人员的依赖；对专有技术的保护；对政府法规的遵守；竞争对手对技术创新的开发；对第三方制造商的依赖；从试点生产过渡到大规模生产产品的能力；以及需要获得足够的额外融资来资助其候选产品的开发。

重组

2024年5月16日，该公司报告称，公司第三阶段启蒙1试验的TOPLINE结果评估了LYR-210，一种生物可吸收的鼻腔植入物(7500微克呋喃莫米松)，作为治疗慢性鼻窦炎(CRS)的六个月药物。在24周时，在CRS的三个主要症状(3CS)(鼻塞、流鼻水、面部疼痛/压力)的综合评分中，启蒙1没有达到其主要终点，即与假对照组相比，在统计学上有显著改善。启蒙1号是评估LYR-210的两个3期临床试验之一。启蒙1号试验为期52周的安全延长阶段最近结束，预计2024年第四季度将有数据。LYR-210在CRS的第二个关键3期试验--启蒙2号正在进行中，2024年10月完成登记。预计2025年第二季度将公布TOPLINE结果。

关于未能达到主要终点的启蒙1号审判，2024年5月16日，公司董事会(“董事会”)批准了一项影响公司裁员的决定87员工，发生在2024年5月和6月。随著兵力的减少，该公司停止了LYR-210的制造和商业化工作，以及LYR-220的开发工作，以努力减少运营费用。此外，该公司目前正在进行所有市场营销的ESS三将其租赁物业用于转租安排。

该公司已记录了一笔金额为#美元的重组费用。9.3截至2024年9月30日的9个月，主要与遣散费和留任费用有关，如附注4所述。公司还记录了财产和设备的减值费用#美元1.9百万和使用权资产，金额为#22.8百万美元，如附注5和6中进一步讨论的那样。

持续经营

该公司的第三阶段启蒙1试验未能达到其主要终点，导致该公司在2024年第二季度进行了重组，这给该公司满足其业务计划和进行未来运营的能力带来了重大不确定性。该公司自成立以来每年都出现经常性净营业亏损，累计亏损约为#美元。393.82024年9月30日时为100万人。该公司预计在可预见的未来将继续产生营业亏损。截至2024年9月30日，该公司约有23.8 百万现金和现金等值物以及美金27.8 数百万短期投资。这些情况对公司自简明综合财务报表发布之日起一年内持续经营的能力产生了重大怀疑。

自成立以来至2024年9月30日，该公司已筹集总计2024年9月30日424.8 万为其运营提供资金，其中美金162.1 百万美金是出售可赎回可转换优先股的总收益，美金96.3 百万是2022年4月融资的净收益，美金46.5 百万是2023年5月融资（定义如下）的净收益，美金57.3 百万美金是公司首次公开募股的净收益，美金23.9 百万美金是与公司日期为2023年9月1日的控制股权发行协议（「原始销售协议」）相关的净收益，美金16.8 万是总收益

该公司的现金流量表包括有限现金、现金和现金等价物，这些现金流量表上显示的期初和期末总额进行了核对。将资产负债表内报告的现金、现金等价物和限制性现金与现金流量表中所列相同数额的总额进行核对如下：


	9月30日，		12月31日，
	2024		2023
现金及现金等价物	$	23,800	$	22,353
受限制现金		1,992		1,392
总计	$	25,792	$	23,745

每股净亏损

该公司自成立以来一直报告亏损，并通过将普通股股东应占净亏损除以当期已发行普通股的加权平均数量来计算每股普通股基本净亏损，而不考虑潜在的稀释证券。本公司已将预付资金权证计入根据名义行权价计算的每股基本净亏损。

由于本公司已发行符合参与证券定义的股份，故本公司采用两类法计算其每股基本及摊薄净亏损。两级法是一种收益分配公式，它将参与证券视为拥有普通股股东本来可以获得的收益的权利。本公司的参与证券根据合约赋予该等股份持有人参与股息的权利，但并不根据合约要求该等股份的持有人分担本公司的亏损。因此，在公司报告净亏损的期间，此类损失不会分配给此类参与证券。此外，在公司报告净亏损的期间，稀释每股净亏损与每股基本净亏损相同，因为如果稀释普通股的效果是反稀释的，则不会假设它们已经发行。

下表列出了被排除在每股摊薄净亏损计算之外的潜在摊薄证券，因为在截至2024年9月30日和2023年9月30日的三个月和九个月内，将它们包括在内将是反摊薄的(在普通股等值股票中)：


	2024		2023
股票期权		6,387,089		5,838,677
普通股凭证		8,606,303		10,030,575
限制性股票单位		867,472		243,703
总计		15,860,864		16,112,955

最近发布的会计公告

新的会计声明不时由财务会计准则委员会或其他准则制定机构发布，并由公司自指定生效日期起采用。除非另有讨论，否则本公司认为，近期发布的尚未生效的准则的影响不会对本公司的综合财务状况、经营业绩或现金流产生实质性影响。

2023年11月，FASB发布了ASU 2023-07，分部报告(主题280)：对可报告分部披露的改进，旨在改善可报告分部披露。该指引扩大了我们年度和中期简明合并财务报表中对可报告分部的披露要求，主要是通过加强对重大分部费用的披露。该标准将从我们2024财年的年度报告开始以及之后的中期报告开始生效，并允许及早采用。我们目前正在评估这一标准对我们部门披露的影响。

本准则要求披露定期提供给首席运营决策者“CODM”的重大分部费用，幷包括在每次报告的分部损益计量中，为使其他分部专案与分部损益相一致的其他分部专案的金额和构成说明，以及实体CODM的名称和职位。

3.公平值计量

下表列出了有关公司经常性按公允价值计量的金融资产和负债的信息，并表明用于确定此类公允价值的公允价值层级的级别：


			报告日的公允价值计量使用
	9月30日，		相同资产在活跃市场中的报价（1级）		其他重要可观察输入（2级）		重大不可观察输入数据（3级）
	2024
资产：
现金等价物
货币市场基金	$	16,976	$	16,976	$	—	$	—
现金等值物总额	$	16,976	$	16,976	$	—	$	—
短期投资：
美国国库券	$	27,826	$	—	$	27,826	$	—
短期投资总额	$	27,826	$	—	$	27,826	$	—


			报告日的公允价值计量使用
	12月31日，		相同资产在活跃市场中的报价（1级）		其他重要可观察输入（2级）		重大不可观察输入数据（3级）
	2023
资产：

货币市场基金	$	11,167	$	11,167	$	—	$	—
美国国库券		8,980		—		8,980		—
现金等值物总额	$	20,147	$	11,167	$	8,980	$	—
短期投资：
美国国库券	$	76,918	$	—	$	76,918	$	—
美国政府机构和外国国家银行证券		3,482		—		3,482		—
短期投资总额	$	80,400	$	—	$	80,400	$	—

4.重组及其他有关收费

关于未能达到主要终点的INITTEN 1试验，董事会于2024年5月16日批准了公司裁员，影响了87员工，发生在2024年5月和6月。该公司主要在2024年第二季度发生了与员工离职福利相关的成本和与重组相关的其他成本，其余成本将发生到2025年5月1日。这些金额在我们的简明综合经营报表中作为重组和其他相关费用记录，并在发生时计入全面亏损。截至2024年9月30日的三个月，重组和其他相关费用为$2.8百万美元，其中包括$0.9百万美元的遣散费，1.8百万美元的保留成本，以及0.1上百万的其他成本。截至2024年9月30日的9个月，重组和其他相关费用为$9.3百万美元，其中包括$5.7百万美元的遣散费，2.6百万美元的保留成本，以及1.0上百万的其他成本。

截至2024年9月30日的9个月内重组负债活动(单位：千)：


	1月1日，							9月30日，
	2024		应计		现金支付			2024
2024年重组计划
遣散费	$	—	$	5,651	$	(3,435	)	$	2,216
留任成本		—		2,608	$	(74	)	$	2,534
其他费用		—		995		(890	)	$	105
总计	$	—	$	9,254	$	(4,399	)	$	4,855

5.财产和设备及相关损害

截至2024年9月30日和2023年12月31日，财产和设备包括以下内容（以千计）：


	9月30日，			12月31日，
	2024			2023
财产和设备：
实验室设备	$	4,158		$	2,736
计算机软体和设备		160			105
办公室家具和装置		934			662
租赁物业装修		485			461
总	$	5,737		$	3,964
减：累计折旧		(2,241	)		(1,921	)
减：损害		(1,883	)		—
财产和设备，净值	$	1,613		$	2,043

期间 2024年第二季度，由于公司的第三阶段ENLIGHTEN 1试验未能达到其主要终点，公司对其财产和设备进行了可回收性测试。该公司的结论是，与其财产和设备相关的未贴现现金流量低于财产和设备的公允价值。该公司将财产和设备的公允价值与其公允价值进行了比较，并记录了损失

协议，该公司已同意向坎托支付相当于3.0根据原始销售协定通过该公司出售的任何股份所得总收益的百分比。此外，本公司已同意偿还Cantor因原始销售协定而产生的若干费用。2024年2月14日，公司发布1,041,666公司自动柜员机协定下的股份，净收益为$4.8百万美元。

于2024年3月22日，本公司修订并重述与Cantor Fitzgerald&Co.(“Cantor”)的受控股权发售销售协定，根据该协定，本公司可不时透过Cantor发售及出售本公司普通股股份，总收益最高可达$75.0百万美元。提供和销售最高可达$75.0100万股普通股已根据#年证券法登记。根据本公司最初于2024年3月22日提交予证券交易委员会的S-3表格登记说明书(第333-278163号档案)(“注册说明书”)、载于注册说明书内的基本招股章程，以及于2024年3月22日提交予美国证券交易委员会的与股份有关的招股说明书补编(“招股说明书补编”)，经修订的证券法。

2023年5月融资

于2023年5月25日，本公司与买方订立购买协定，据此，本公司同意以私募方式向投资者出售证券(“私募”)。《购买协定》规定本公司出售和发行：

17,652,962公司普通股和配套认股权证最多可购买8,826,481公司普通股(认股权证)的股份，行使价为$2.67每股，总收益为$44.0 万每份认购权证于2023年11月30日生效，并于2028年11月30日到期。此外，该公司发行了预先出资的认股权证来购买2,408,188公司普通股(预融资权证)的股份，行使价为$0.001每股，以及随附的认购权证，以购买最多1,204,094公司普通股(认股权证)的股份，行使价为$2.673每股，总收益为$6.0百万美元。总计10,030,575已发出认购权证，并2,408,188发行了预先出资的认股权证。预筹资权证可立即行使，并于2028年5月31日到期。私募于2023年5月31日结束。

公司收到的总额为#美元。50.0总收入为百万美元，或$46.5扣除发行成本后的百万美元。本公司已就上述每项交易采用相对公允价值法在普通股、认购权证及预融资权证之间分配所得款项净额。该公司已拨出$30.5百万美元的普通股，$4.2百万美元到预先出资的认股权证和$12.0一百万美元到认购权证。

公司的已发行认股权证是独立的工具，由于认股权证与公司普通股挂钩并符合股本分类标准，因此被归类为股东权益。

总计1,424,272已行使与2023年5月融资有关的认购权证2024年9月30日以买入价$2.673 每股

2022年4月融资

2022年4月13日，该公司宣布结束其私募普通股(或代之以购买普通股的预融资权证)，所得总收入约为$100.5百万美元(“2022年4月融资”)。该公司收到了大约$96.3扣除估计发行成本$后的净收益4.2百万美元。根据证券购买协定，(I)若干投资者买入合共18,815,159普通股价格为$4.22每股收益为公司总收入$79.4百万美元；及(Ii)某些投资者购买了预先出资的权证，以购买总计5,000,000普通股，行使价为$0.001每股总收益为$21.1给公司一百万美元。这些认股权证可于2022年4月13日或之后行使，并于2027年4月12日到期。

的预筹资认股权证被分类为额外实收资本内股东权益的一部分，并于发行日期按相对公允价值分配法入账。预融资认股权证被归类为权益类，因为它们是独立的金融工具，可在法律上与权益工具分开行使，可立即行使，不体现本公司回购其股份的义务，允许持有人在行使时获得固定数量的普通股，与公司普通股挂钩，并符合股权分类标准。此外，这类预先出资的认股权证不提供任何价值或回报保证。该公司的价值

8.普通股授权令

下表为截至2011年尚未行使及可行使的认购权摘要 2024年9月30日，所有这些均为股票分类：


	普通凭证数量			平均行使价		加权平均剩余合同期限（年）		总内在价值		失效日期	预先融资授权证数量			加权平均行使价		加权平均剩余合同期限（年）		总内在价值		失效日期
截至2023年12月31日未偿还		10,030,575		$	2.673		4.90	$	25,700	2028年11月30日		5,756,349		$	0.001		3.92	$	30,200	2027年4月-2028年5月
行使		(1,424,272	)	$	2.673			$	5,052			(5,756,349	)	$	0.001			$	37,770
截至2024年9月30日未完成		8,606,303		$	2.673		4.15	$	—	2028年11月30日		—		$	—		—	$	—		—

9.基于股票的补偿费用

该公司目前根据2020年激励奖励计划（「2020年计划」）和2022年就业诱导奖励计划（「诱导奖励计划」）授予股权奖励。公司此前根据2005年股权激励计划（「2005年计划」）和2016年股权激励计划（「2016年计划」以及2020年计划、诱导奖励计划和2005年计划，统称为「计划」）授予了股权奖励。该公司还维持2020年员工股票购买计划（「ESPP」）。

计划下的限制性股票单位活动摘要截至2024年9月30日的九个月情况如下：


	股份			加权- 平均授予日期公允价值
截至2023年12月31日发行的限制性股票单位		105,048		$	3.20
授予		984,929		$	5.49
既得		(27,869	)	$	3.29
没收		(194,636	)	$	4.28
截至2024年9月30日已发行的限制性股票单位		867,472		$	5.56

计划下的股票期权活动摘要截至2024年9月30日的九个月情况如下：


	股份			加权- 平均行使价格		加权- 平均剩余合同生活 (in年）		骨料内在值 (in数千）
截至2023年12月31日未偿还		5,709,980		$	5.68		8.0	$	6,334
授予		2,605,002			4.89
行使		(1,002	)		3.96
取消		(1,926,891	)		4.83
截至2024年9月30日未完成		6,387,089		$	5.61		7.9	$	—

授予员工、董事和非员工的每份股票期权的公允价值是在授予日期使用Black-Scholes期权定价模型或在授予高管的某些期权的情况下使用蒙特卡洛模拟进行估计的，并采用以下加权平均假设截至2024年和2023年9月30日的三个月和九个月：


	止三个月 9月30日，						截至9月30日的九个月，
	2024			2023			2024			2023
无风险利率		0.0	%		4.3	%		4.2	%		3.7	%
预期股息收益率		—	%		—	%		—	%		—	%
预计期限（年）		—			6.1			6.0			6.0
预期波幅		0.0	%		80.0	%		80.5	%		82.9	%

权衡截至2023年9月30日的三个月内授予员工、董事和非员工的期权的年龄公允价值为美金2.57。有几个不是截至2024年9月30日的三个月内授予员工、董事或非员工的期权。不他对截至2024年9月30日的九个月内授予员工、董事和非员工的期权的加权平均公允价值 2023年为美金2.80 和$2.08，分别。

股票补偿费用包含在公司合并经营报表和全面亏损如下（单位：千）：


	止三个月 9月30日，				截至9月30日的九个月，
	2024		2023		2024		2023
研发	$	214	$	294	$	627	$	865
一般和行政		1,277		1,147		4,150		3,540
总计	$	1,491	$	1,441	$	4,777	$	4,405

截至2024年9月30日期间，约为$15,000 的股票补偿费用被记录为负债。截至2023年9月30日止期间，公司不是不要将任何基于股票的补偿费用记录为负债。

与股票期权相关的未确认股份薪酬金额O $6.6 万 2024年9月30日预计将在大约 2.86 年认不出来d与限制性股票单位相关的股份薪酬指定为美金2.0 万 2024年9月30日预计将在大约 2.4 年

2024年3月，公司授予购买期权 550,000 行使价为美金的普通股6.07 每股授予其执行长（「2024年绩效期权」）并授予 385,000 其执行主席的RSU（「2024年PSU」），每个RSU都根据2020年计划具有基于绩效的归属条件。 2024年绩效选项和2024年PSE的归属是基于在指定时期内实现各种临床和监管里程碑。

对于基于业绩的股票奖励，公司根据授予日奖励的公允价值计量股票补偿费用，然后在公司确定业绩标准有可能实现后确认

有不是交易价格的变化 2023年12月31日至2024年9月30日. 以下是ng表反映交易价格（以千计）：


	截至2024年9月30日
	里程碑后
综合绩效义务	$	11,862
开发活动绩效义务		5,138
总计	$	17,000

下表反映了与各项履行义务相关的确认收入和剩余递延收入（以千计）：


	截至2024年9月30日
	综合绩效义务		开发活动绩效义务			总计
截至2022年12月31日的递延收入	$	11,748	$	3,604		$	15,352
已确认收入		—		(1,558	)		(1,558	)
截至2023年12月31日的递延收入		11,748		2,046			13,794
已确认收入		—		(1,325	)		(1,325	)
截至2024年9月30日的递延收入	$	11,748	$	721		$	12,469

开发和监管里程碑费用是一种可变对价，在很可能不会发生重大逆转的情况下，被确认为收入。请注意，鉴于未来12个月内交付的潜在不确定性，与临床供应协定相关的已分配递延收入已被记录为长期递延收入。截至2024年9月30日，双方仍未完成临床供应协定谈判。在这一点上，这样的协定是否会完成还不确定。鉴于临床供应协定完成的不确定性，本公司可能决定将此类付款确认为加速时间表上的收入。

实体关联Ted with Perceptive Advisors，LLC是本公司和LianBio的股东。此外，该公司的两名董事是Perceptive Advisors LLC的常务董事，其中一名董事也是LianBio董事会的执行主席。

转租“由于本公司作为租户，根据现有租赁安排将空间分租，根据该安排，承租人同意根据分租协定将空间分租给本公司。

沃瑟姆租赁

2022年5月，该公司签署了一份位于马萨诸塞州沃尔瑟姆温特街880号的租赁协定。租赁的房产包括大约29,000平方米英尺的办公和实验室空间，租约最初规定的基本租金为#美元2.2每年100万美元，这一数位将会增加3在206月30日结束的不可取消期限内每年%。该公司有权将租约延长至一个额外的五年任期并负责其应承担的适用于租赁房屋的房地产税、维护和其他运营费用。该公司在计量使用权资产和租赁负债时，没有包括将租约再延长五年的选择权。

关于租约，一笔保证金以不可撤销备用信用证的形式交付给房东，抵押金额为#美元。1.1存放在金融机构的百万美元存款被记录为受限现金。

沃尔瑟姆转租

2023年12月，本公司签署了一份关于位于马萨诸塞州沃尔瑟姆温特街880号的额外实验室和办公空间的分租协定。转租房屋包括大约24,000平方米英尺，转租规定的基本租金为$1.8每年100万美元，这一数位将会增加3在2032年11月30日结束的不可取消期限内每年%。本公司亦须承担适用于转租物业的房地产税、维护费及其他营运费用。

于2024年1月3日开始转租时，本公司将转租记录为其经营租赁使用权资产和经营租赁负债的组成部分。关于转租，一笔押金以不可撤销备用信用证的形式交付给分地主，抵押金额为#美元。0.6存放在金融机构的百万美元存款被记录为受限现金。

本公司简明合并财务报表中记录的租赁成本构成如下(以千计)：


	止三个月 9月30日，				截至9月30日的九个月，
	2024		2023		2024		2023
租赁成本：
经营租赁成本	$	1,346	$	483	$	5,082	$	1,371
可变租赁成本		608		399		1,866		893
总租赁成本	$	1,954	$	882	$	6,948	$	2,264

可变租赁付款包括公司分配的业主在建筑物运营和管理中发生的成本和支出份额。

与公司经营租赁相关的加权平均剩余租期和贴现率如下：


	截至2024年9月30日
加权平均剩余租期（年）		7.7
加权平均折扣率		6.20	%

截至2024年9月30日，根据ASC 842，公司经营租赁负债的到期日如下（单位：千）：

以下对我们财务状况和经营运绩的讨论和分析应与我们未经审计的简明综合财务报表以及本季度报告中其他地方出现的相关注释一起阅读，表格10-Q。本讨论和分析中包含的部分信息或本季度报告10-Q表格其他地方列出的部分信息，包括有关我们业务计划和战略的信息，包括涉及风险和不确定性的前瞻性陈述。

我们的实际结果和某些事件的时间可能与任何前瞻性陈述中讨论、预测、预期或表明的结果存在重大差异。我们警告您，前瞻性陈述并不能保证未来业绩，我们的实际经营结果、财务状况和流动性以及我们经营所在行业的发展可能与本季度报告中包含的前瞻性陈述存在重大差异。表格10-Q。此外，即使我们的经营运绩、财务状况和流动性以及我们经营所在行业的发展与本季度报告中包含的前瞻性陈述一致，它们也可能无法预测未来时期的业绩或发展。

以下信息和任何前瞻性陈述应根据本季度报告10-Q表格中其他地方讨论的因素进行考虑，包括第二部分第1A项下识别的风险。危险因素

我们警告读者不要过度依赖我们做出的任何前瞻性陈述，这些陈述仅限于做出之日。除非法律和美国证券交易委员会规则特别要求，否则我们不承担任何公开更新或修改任何此类陈述的义务，以反映我们的预期或任何此类陈述可能基于的事件、条件或情况的任何变化，或者可能影响实际结果与前瞻性陈述中所述结果不同的可能性。

我们是一家临床阶段的生物技术公司，专注于创新抗炎疗法的开发和商业化，用于局部治疗慢性鼻窦炎（CRS）患者。我们的候选产品LY R-210和LY R-220是生物可吸收鼻植入物，旨在通过简单的办公室程式进行给药，旨在为鼻窦通道提供六个月的持续抗炎药物治疗，以治疗CRS一次给药。LY R-210和LY R-220中嵌入的药物是莫米松糠酸盐（MF），它是美国食品药品监督管理局（FDA）批准的各种药物中的活性成分，具有公认的功效和安全性。CRS是一种副鼻窦炎症性疾病，会导致衰弱症状和严重的发病率，影响美国约1400名鼻喉科患者。

LIR-210旨在治疗之前医疗管理失败的CRS患者。LY-210尺寸较小，适用于患有和不患有鼻息肉的患者。 2024年5月，我们宣布了公司3期ENLIGHTEN 1试验的总体结果，该试验评估了LyR-210治疗CRS的效果。ENLIGHTEN 1没有达到其主要终点，即与假对照组相比，第24周时CRS三种主要症状（3CS）（鼻塞、鼻涕、面部疼痛/压力）的综合评分有统计学显著改善。

第24周时，ENLIGHTEN 1试验与基线相比显示了以下结果，但未达到统计学意义：

LyR-210总体耐受性良好，未发生与产品相关的严重不良事件。研究人群中最常报告的不良事件是鼻出血、鼻臭、上呼吸道感染和鼻窦炎。ENLIGHTEN 1试验的52周扩展阶段已经完成，预计将于2024年第四季度发布数据。扩展阶段的LY-210的安全性数据总体与24周主要治疗阶段一致，包括接受重复给药的患者，导致治疗期为12个月。 LyR-210总体耐受性良好，未发生与产品相关的严重不良事件。研究人群中最常报告的不良事件是慢性鼻窦炎、鼻臭、鼻出血、鼻窦炎和口鼻炎。 ENLIGHTEN 2是第二项在CRS中进行的关键第三期试验，该试验正在进行中，招募工作已于2024年10月完成。 ENLIGHTEN 2试验的总体结果预计将于2025年第二季度公布。

我们的第二个候选流水线产品LYR-220专为CRS患者设计，这些患者之前的治疗失败，尽管接受了筛窦手术，但仍需要治疗来管理CRS症状。LYR-220采用了较大的植入物，专为鼻腔较大的患者设计，包括那些接受筛窦手术后鼻腔较大的患者。我们进行了名为Beacon的LYR-220第二阶段临床试验。Beacon试验是一项对照平行分组研究，旨在评估安全性、耐受性、药代动力学和疗效，比较LYR-220(7500微克MF)的两种设计，在24周内对大约70名曾接受过双侧鼻窦手术的有症状的成年CRS受试者进行对照。2023年9月，我们报告了Beacon的阳性背线结果，显示在24周时3CS和SNOT-22评分在统计上和临床上有显著改善。在2024年5月宣布的削减成本的努力中，该公司停止了LYR-220的开发工作。

我们的创新和专有药物输送技术旨在通过单次给药在持续的一段时间内将小分子药物局部持续输送到受影响的组织。该技术由三个相互关联的部分组成：

迄今为止，我们的业务仅限于组织公司和人员配备、业务规划、筹集资本、开发技术、建立智慧财产权组合以及开展研发活动，包括为我们候选产品的临床制造。我们没有任何获准销售的产品，也没有从产品销售中产生任何收入。

2020年5月5日，我们完成了首次公开募股，发行并出售了4，025，000股普通股（包括承销商完全行使购买额外普通股股份的选择权后发行的股份），公开发行价为每股16.00美金，面值0.001美金，总收益为6440日元。扣除我们支付的承保折扣和佣金以及发行费用后，我们收到了约5730美金的净收益。该股票于2020年5月1日开始在纳斯达克全球市场交易。IPO完成后，我们所有已发行的可转换优先股将转换为8，335，248股普通股，面值0.001美金。

自成立至2024年9月30日，我们已筹集了总计42480美元的万资金用于我们的运营，其中16210美元万是我们出售可赎回可转换优先股的总收益，9,630美元万是我们2022年4月融资的净收益，4,650美元万是我们2023年5月融资的净收益，5,730美元万是我们首次公开募股的净收益，2,390美元万是与我们2023年9月1日的受控股权发行协定(“原始销售协定”)相关的净收益，1,680美元万是政府合同的总收益，1,700美元万是联博许可协定的净收益，380美元万是行使普通股认股权证的总收益。此外，我们目前拥有于2024年3月22日提交给美国证券交易委员会的有效S-3表格(第333-278163号)(“S-3表格”)的有效搁置登记声明，根据该声明，S可以不时在一次或多次发行中提供普通股和优先股、债务证券、权证和单位的任意组合，总计高达30000美元的万。

自成立以来，我们每年都会产生经常性净运营亏损，预计在可预见的未来将继续产生巨额费用并增加运营亏损。我们的净亏损可能会因季度而大幅波动

年复一年，而且可能是巨大的。截至2024年9月30日，我们迄今为止的净亏损为39380卢比。截至2024年9月30日，我们拥有约2380便士的现金及现金等值物以及2780便士的短期投资。这些情况对我们自简明综合财务报表发布之日起一年内持续经营的能力产生了重大怀疑。

2024年5月，我们宣布裁员约75%，影响87名员工，此外还采取其他成本削减措施以保存资本，包括停止LY-210的制造和商业化工作以及暂停LY-220的开发工作。尽管如此，我们预计在继续进行两项正在进行的LY R-210 ENLIGHTEN 3期临床试验时，我们将继续产生费用。

除非我们成功完成临床开发并获得监管部门对候选产品的批准，否则我们预计不会从产品销售中获得收入。将来，如果我们获得融资并决定重新开始我们的制造活动，我们可能会聘请第三方合同制造商来生产我们的产品。我们还没有一个销售组织。如果我们的任何候选产品获得监管部门的批准，我们预计将产生与产品销售、营销、制造和分销相关的巨额商业化费用。此外，作为一家上市公司，我们将继续产生与运营相关的额外成本。因此，我们需要大量额外资金来支持我们的持续运营。在我们能够从产品销售中获得可观的收入之前，如果有的话，我们预计将通过公共或私人股本或债务融资或其他来源，包括战略合作和许可安排，为我们的运营提供资金。然而，我们可能无法在需要时以优惠条件或根本无法筹集额外资金或达成此类其他安排。我们未能在需要时筹集资金或达成其他安排，将对我们的财务状况和我们开发当前候选产品或任何额外候选产品的能力产生负面影响。

由于与治疗产品开发相关的众多风险和不确定性，我们无法准确预测费用增加的时间或金额，或者何时或是否能够实现或维持盈利能力。即使我们能够从产品销售中产生收入，我们也可能无法盈利。如果我们未能实现盈利或无法持续维持盈利能力，那么我们可能无法继续按计划水平运营，并被迫减少或终止运营。

根据我们目前的运营计划，管理层得出的结论是，我们作为一家持续经营的企业继续经营的能力存在很大疑问。截至2024年9月30日，我们拥有总计2,380美元万的现金和现金等价物，以及总计2,780美元万的短期投资。管理层相信，我们现有的现金、现金等价物和短期投资将使我们能够为2026年第一季度的运营费用和资本支出需求提供资金。我们基于的这些估计可能被证明是不准确或不正确的，我们可能会比目前预期的更早使用我们可用的资本资源。请参阅“流动性和资本资源”。由于与开发我们的候选产品以及任何未来的候选产品和技术相关的众多风险和不确定性，以及我们可能在多大程度上与第三方合作开发我们的候选产品，我们无法估计与完成候选产品的研究、开发和制造相关的增加的资本支出和运营费用。

如果我们通过与第三方的额外合作、战略联盟或许可安排筹集额外资金，我们可能不得不放弃对我们的技术、未来收入来源、研究项目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。如果我们无法在需要时通过股权或债务融资筹集额外资金，我们可能会被要求推迟、限制、减少或终止我们的产品开发计划或任何未来的商业化努力，或者授予开发和营销我们原本宁愿开发和营销自己的候选产品的权利。

2024年7月19日，我们收到书面通知纳斯达克证券市场有限责任公司（「通知」）（「纳斯达克」）通知我们，在过去连续30个工作日，我们普通股的出价，每股面值0.001美金，收盘价低于纳斯达克上市规则5450（a）规定的继续纳入纳斯达克全球市场的每股最低出价要求1.00美金（1）（「最低投标价格要求」）。该通知目前对我们普通股的上市没有任何影响，该普通股继续在纳斯达克全球市场交易，代码为「LY RA」。

根据纳斯达克上市规则5810（c）（3）（C），我们有180个日历日或直至2025年1月15日（「合规日期」）的期限来重新遵守最低出价要求。为了重新遵守最低出价要求，普通股在合规日期前至少连续10个工作日的收盘出价必须至少为每股1.00美金。

如果我们未能在合规日期之前重新遵守最低投标价格要求，我们可能有资格再申请180个日历日的合规期。要获得资格，我们必须提交普通股转移到纳斯达克资本市场上市的申请，这要求我们必须满足公开持有股票市值的持续上市要求以及纳斯达克资本市场的所有其他初始上市标准，但投标价格要求除外。我们还需要向纳斯达克支付申请费，并提供书面通知，说明其打算在额外的合规期内弥补不足之处。作为审查过程的一部分，纳斯达克将确定它是否相信我们能够弥补这一缺陷。如果公司不符合或未能在额外的合规期内重新获得合规，则纳斯达克将通知我们其决定将我们的普通股退市，届时我们将有机会向纳斯达克听证会小组上诉退市决定。不能保证，如果我们决定对任何除名决定提出上诉，这种上诉一定会成功。

我们打算积极监控普通股的收盘出价，并在适当的情况下考虑实施可用的期权以重新遵守最低出价要求。无法保证我们能够重新遵守最低出价要求或保持遵守任何其他上市要求。欲了解更多信息，请参阅本季度报告10-Q表格第二部分第1A项中的「风险因素-如果我们无法重新遵守纳斯达克的持续上市要求，我们的普通股可能会从纳斯达克全球市场退市，这可能会损害我们的业务、我们普通股的交易价格、我们筹集额外资本的能力以及我们普通股市场的流动性」。

由于ENLIGHTEN 1试验未能达到其主要终点，董事会于2024年5月16日批准裁员，影响了87名员工，该裁员发生在2024年5月和6月。此外，我们停止了LY R-210的制造和商业化工作，以及LY R-220的开发工作，以减少运营费用。

鉴于ENLIGHTEN 1试验未能达到其主要终点，我们目前正在考虑各种运营和战略选择，包括额外的临床试验、出售资产或战略业务合并。除了减少运营费用以管理其现金状况外，董事会尚未决定具体计划。此外，我们目前正在营销所有租赁物业以进行转售安排，并且我们还可能寻求与房东协商提前终止租赁。

迄今为止，我们尚未从产品销售中产生任何收入，并且预计在可预见的未来也不会从产品销售中产生任何收入。截至2024年9月30日，我们已从LianBio许可协议中确认了450美金的合作收入。

如果我们对候选产品的开发工作取得成功并获得监管批准和成功的商业化工作或额外的合作协议，那么我们未来可能会从产品销售、额外合作或我们可能与第三方签订的许可协议的付款或其任何组合中产生收入。我们无法预测我们是否、何时或在多大程度上从候选产品的商业化和销售中产生收入。我们的任何候选产品可能永远无法成功获得监管机构的批准。

我们预计未来几年的任何收入将主要来自我们与联生物的合作协议。我们无法保证LianBio未来里程碑或特许权使用费付款的时间，也无法保证我们将收到任何这些付款，特别是考虑到LianBio的逐步减少活动。

2022年9月26日，我们与联生物签订了修订后的联生物许可协议，在大中华区（中国大陆、香港、台湾和澳门）、韩国、新加坡和泰国开发和商业化LIR-210。根据LianBio许可协议的条款，我们收到了1200美金的预付款。2022年2月，该公司为美国首例患者提供了500美金的开发里程碑，相关现金金额已于2022年4月实现。根据指定的开发、监管和商业化里程碑的实现，该公司有资格在未来获得高达13500美金的付款。逐地区商业化后，我们将有权根据许可地区的LY-210净销售额获得较低的两位数特许权使用费。联生物将负责

在许可地区进行LY-210的临床开发和商业化，我们将保留所有其他地区对LY-210的所有权利。作为LianBio许可协议的一部分，LianBio还将拥有在许可地区获得我们的LY-220候选产品的开发和商业权的优先权。

我们根据ASC 606对这一安排进行了评估，并得出结论，合同对手方LianBio是客户。在安排开始时，我们确定了以下重大承诺：(1)开发和商业化LYR-210的许可证，(2)与临床供应LYR-210相关的制造活动，(3)生产LYR-210的非独家许可证，以及在供应中断的情况下转让制造技术的义务，以及(4)该公司执行与全球第三阶段临床试验相关的开发活动。我们确定，将LYR-210开发和商业化的许可证、与临床供应LYR-210相关的制造活动、生产LYR-210的非独家许可证以及在供应故障的情况下转让制造技术的义务是单一的履行义务，因为LYR-210制造过程的特殊性质，即许可证不能与与LYR-210供应相关的制造活动分开，并且只有在供应故障时才有制造LYR-210的权利。就ASC 606而言，我们确定有两项明确的履约义务：(1)开发和商业化LYR-210的许可、与临床供应LYR-210相关的制造活动、生产LYR-210的非独家许可以及在供应中断的情况下转让制造技术的义务，以及(2)公司履行与全球第三阶段临床试验相关的开发活动。

根据LianBio许可协议，为了评估ASC 606的交易价格，我们确定1200美金的预付款和LY-210临床供应的可报销成本构成了自安排开始时将包含在交易价格中的全部对价，该对价被分配给两项履行义务。我们有资格收到的潜在里程碑付款被排除在交易价格之外，因为所有里程碑金额都根据实现的可能性受到完全限制。

此外，我们确定LianBio在许可地区获得LIR-220的开发和商业权的优先拒绝权是一种选择，因为任何协议都将在公平的情况下谈判，因此不会为LianBio提供重大权利，因此，不被视为一种绩效义务。

我们将确认与开发和商业化LYR-210的许可相关的收入、与临床供应LYR-210相关的制造活动、制造LYR-210的非独家许可以及在供应失败的情况下转让制造技术的义务，以及在交付LYR-210临床供应时的履行义务。我们根据与全球第三期临床试验相关的开发活动所产生的成本以及未来为履行绩效义务而预期产生的成本，确认与全球第三阶段临床试验绩效义务相关的开发活动相关的收入，因为开发活动是使用输入法执行的。控制权的移交发生在这段时间内，在管理层看来，这是在履行履约义务方面取得进展的最佳衡量标准。收到的尚未确认为收入的金额将作为我们综合资产负债表上的合同负债递延，并将分别在交付LYR-210临床供应和进行全球3期临床试验的剩余时间内确认。

联生宣布，2023年10月，其董事会开始对其业务进行全面战略评估。LianBio董事会最终得出结论，出售资产和逐步结束业务是实现股东价值最大化的最佳方式。LianBio报告说，很大一部分逐步结束的活动，包括履行现有协定下的过渡服务义务，以及逐步停止目前正在进行的临床试验，将在2024年底之前完成。LianBio于2024年2月宣布，将进一步削减员工规模至约50人，并计划在2024年期间进一步削减这一数位。LianBio表示，它将保持一个必要的核心员工团队，以实施有序的清盘，并支持其努力最大化其剩余业务和资产的价值，包括与公司的合作。由于这些发展，随著LianBio继续逐步关闭，同时寻求第三方根据LianBio许可协定收购LianBio的权利，公司与LianBio的合作前景不确定。

自成立以来，我们的运营费用仅包括研发成本以及一般和行政成本。

研究和开发费用主要包括我们研究活动产生的成本，包括开发和寻求监管批准我们用于治疗CRS的最先进候选产品LY R-210，其中包括：

我们将研究和开发费用按发生时支付。我们根据使用临床研究中心激活、患者入组或供应商和临床研究中心向我们提供的信息等数据对特定任务完成进度的评估，确认某些开发活动（例如临床试验）的成本。这些活动的付款基于个别协议的条款，该条款可能与发生的成本模式不同，并可能在我们的合并财务报表中反映为预付或应计的研发费用。

我们的研究和开发费用主要包括与我们的临床前和临床开发活动相关的员工薪酬、咨询费、支付给CMO的费用以及CTO费用等成本。我们通常在开发计划中使用员工和基础设施资源，我们不会将人员成本和其他内部成本分配给特定候选产品或开发计划，但制造候选产品的成本除外。

临床开发后期的候选产品通常比临床开发早期阶段的候选产品的开发成本更高，这主要是由于后期临床试验规模和持续时间的增加。我们预计在可预见的未来，我们的研发费用将减少，因为我们于2024年5月裁员75%，并停止了大部分制造和CMS相关活动。研发费用将主要集中在继续两项正在进行的LILIGHTEN 3期临床试验。

LY-210和其他潜在未来候选产品的成功开发存在高度不确定性。因此，目前我们无法合理估计或了解完成这些候选产品开发所需的工作的性质、时间和成本。我们也无法预测何时（如果有的话）我们将从我们可能获得营销批准的任何候选产品的商业化和销售中产生收入和重大净现金流入。我们可能永远无法成功地获得任何候选产品的监管批准。临床前研究、临床试验和候选产品开发的持续时间、成本和时间将取决于多种因素，包括：

与我们任何候选产品的开发、制造或商业化支持活动相关的任何这些变量的结果发生变化，都会显着改变与该候选产品的开发相关的成本、时间和可行性。例如，如果FDA或其他监管机构要求我们进行超出我们预期完成候选产品临床开发所需的临床试验，或者如果我们因患者入组或其他原因而在临床试验中出现重大延误，我们可能需要花费大量额外的财务资源和时间来完成临床开发。

一般和行政费用主要包括执行、财务和行政职能人员的工资和其他相关费用，包括基于股票的报酬。一般和行政费用还包括与设施相关的直接和分配成本以及法律、专利、咨询、投资者、公共关系、会计、审计、税务服务和保险成本的专业费用。

我们预计未来的一般和行政费用将保持稳定，以支持现有的研发活动。此外，我们将继续承担与上市公司相关的费用，包括与遵守交易所上市和SEC要求相关的会计、审计、法律、监管和税务相关服务成本、董事和高级管理人员保险成本以及投资者和公共关系成本。

利息收入包括我们的现金和现金等值物以及短期投资赚取的利息收入。

所得税包括与公司马萨诸塞州安全公司相关的所得税。由于未来应税收入的不确定性，该公司尚未记录任何与其经营亏损相关的收益。

我们管理层对财务状况和经营结果的讨论和分析是以我们未经审计的简明综合财务报表为基础的，这些报表是根据美国公认的会计原则或GAAP编制的。在编制这些财务报表时，我们需要作出估计和判断，以影响报告期间资产、负债、收入和支出的报告金额、报告期内我们合并财务报表中或有资产和负债的披露，以及用于评估我们作为持续经营企业的能力的估计。我们对这些项目进行监测和分析，以了解事实和情况的变化，这些估计可能在未来发生重大变化。我们基于历史经验、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进行估计，这些因素的结果构成了对资产和负债账面价值的判断的基础，而这些资产和负债的账面价值从其他来源看起来并不明显。估计数的变化反映在已知期间的报告结果中。在不同的假设或条件下，实际结果可能与这些估计值大不相同。

与我们向美国证券交易委员会（SEC）提交的10-k表格年度报告中第二部分第7项“管理层对财务状况和运营结果的讨论和分析-关键会计估计”中所述的内容相比，我们的关键会计估计没有发生重大变化。2024年3月22日。

我们已审查了所有最近发布的准则，并确定，除了本季度10-Q表格报告其他地方包含的未经审计的简明综合财务报表中的注释2中披露的内容外，此类准则不会对我们的综合财务报表产生重大影响或不以其他方式适用于我们的运营。

下表总结了我们截至2024年9月30日和2023年9月30日三个月的经营业绩（以千计）：

截至2024年和2023年9月30日止三个月的合作收入是根据我们于2021年5月31日签订的LianBio许可协议确认的收入的结果。同比下降主要与ENLIGHTEN 1试验的主要研究阶段的完成有关，该试验用于收入确认。

与截至2023年9月30日的三个月相比，截至2024年9月30日的三个月的研发费用减少了650万美元，从1240万美元降至590万美元。截至2024年9月30日的三个月研发费用减少主要是由于我们完成了LyR-220的BEACON试验和LyR-210的ENLIGHTEN 1试验的主要阶段，临床相关成本减少了380万美元，员工相关成本减少了250万美元，主要是由于2024年5月发生的部队减少，专业和咨询成本减少40万美元，产品开发和制造成本减少4000万美元。成本的减少被分配成本和折旧60万美元的增加部分抵消。

与截至2023年9月30日的三个月相比，截至2024年9月30日的三个月的一般和行政费用减少了110万美元，从500万美元减少到390万美元。

截至2024年9月30日的三个月内一般和行政费用的减少主要是由于我们在2024年5月宣布ENLIGHTEN 1试验未达到其主要终点后缩减了活动，专业和咨询费用减少了100万美元。此外，主要由于2024年5月发生的部队减少，员工相关成本减少了50万美元。这些被分配和支持成本增加40万美元部分抵消，这主要是由于截至2024年9月30日的三个月与截至2023年9月30日的三个月相比，公司三个租赁设施的租金和设施费用增加。

与截至2023年9月30日的三个月相比，截至2024年9月30日的三个月的利息收入减少了60万美元。本期利息收入主要归因于公司短期投资的利息，减少主要是由于截至2024年9月30日止三个月短期投资余额较截至2023年9月30日止三个月减少。

截至2024年9月30日的三个月内，我们记录了7，000美元的所得税费用，而截至2023年9月30日的三个月期间为16，000美元。所得税费用的减少与我们的马萨诸塞证券公司有关。

截至2024年9月30日的三个月，该公司发生了价值280万美元的重组费用，主要与遣散费和保留费有关，而2023年同期没有此类费用。

下表总结了我们截至2024年9月30日和2023年9月30日的九个月的经营业绩（以千计）：

截至2024年和2023年9月30日止九个月的合作收入是根据我们于2021年5月31日签订的LianBio许可协议确认的收入的结果。截至2024年9月30日和2023年9月30日的九个月的协作收入与同期相比保持相对稳定。

与截至2023年9月30日的九个月相比，截至2024年9月30日的九个月的研发费用增加了160万美元，从3580万美元增至3740万美元。截至2024年9月30日的九个月研发费用增加主要是由于裁员前发生的人员分配和租金上涨，导致组织内共享活动的分配和支持成本增加了440万美元，以及专业和咨询费用增加了120万美元。这一增加被临床相关成本减少300万美元所抵消，因为我们完成了LyR-220的BEACON试验和LyR-210的ENLIGHTEN 1试验的主要研究阶段，以及员工相关成本减少110万美元。

截至2024年9月30日的九个月，一般和行政费用相对稳定，为1490万美元，而截至2023年9月30日的九个月为1470万美元。

截至2024年9月30日止九个月的利息收入减少了60万美元至250万美元，而截至2023年9月30日止九个月的利息收入为310万美元。利息收入减少主要是由于截至2024年9月30日止九个月短期投资余额较截至2023年9月30日止九个月减少，导致公司短期投资利息减少。

截至2024年9月30日的九个月内，公司发生的所得税费用为33，000美元，而截至2023年9月30日的九个月内，与我们的马萨诸塞州证券公司相关的所得税费用为42，000美元。

截至2024年9月30日止九个月，公司发生了与财产和设备相关的损失成本190万美元，而2023年同期为160万美元。

截至2024年9月30日止九个月，该公司发生了与使用权资产相关的损失成本2280万美元，而2023年同期没有此类费用。

截至2024年9月30日的九个月，该公司发生了930万美元的重组费用，主要与遣散费和保留费有关，而2023年同期没有此类费用。

从成立到2024年9月30日，我们已经筹集了总计42480美元的万来为我们的运营提供资金，其中16210美元万是我们出售可赎回可转换优先股的毛收入，9,630美元万是我们2022年4月融资的净收益，4,650美元万是我们2023年5月融资的净收益，5,730美元万是我们首次公开募股的净收益，2,390美元万是与我们2023年9月1日的原始销售协议相关的净收益，1,680美元万是政府合同的毛收入，1,700美元万是联博许可协议的毛收入，380美元万是行使普通股认股权证的毛收入。截至2024年9月30日，我们尚未出售任何S-3表格下的证券。于2024年3月22日，吾等与康托尔订立经修订及重订的受控股权发售协议，根据该协议，本公司可不时透过康托尔发售及出售本公司普通股股份，总收益最高可达7,500万美元。

下表提供了有关我们截至2024年9月30日和2023年12月31日的现金及现金等值项目以及短期投资总额的信息（单位：千）：

我们将大部分现金和现金等值物保存在主要评级高的跨国和地方金融机构的账户中，并且我们在这些机构的存款超过了保险限额。市场条件可能会影响这些机构的生存能力，任何无法获取或延迟获取这些资金的行为都可能会对我们的业务和财务状况产生不利影响。

下表提供了截至2024年9月30日和2023年9月30日止九个月现金流的信息（单位：千）：

经营活动中使用的现金主要来自我们根据非现金费用和营运资金组成部分变化进行调整的净亏损。

截至2024年9月30日止九个月，经营活动使用的净现金为5870万美元，主要是由于我们的净亏损8250万美元，以及我们的经营资产和负债变化提供的现金410万美元，部分被非现金调整2790万美元抵消。我们的净亏损主要归因于研究和开发活动、一般和行政费用以及重组费用和对我们长期资产的减损。截至2024年9月30日止九个月内，我们的非现金净费用主要包括2280万美元的使用权资产减损损失、480万美元的股份补偿费用、30万美元的折旧费用和190万美元的长期资产减损，这些费用被短期投资折扣净摊销200万美元部分抵消。

Net cash used in operating activities was $44.2 million for the nine months ended September 30, 2023, primarily resulting from our net loss of $47.5 million and cash used for changes in our operating assets and liabilities of $0.5 million, partially offset by non-cash adjustments of $3.8 million. Our net loss was primarily attributed to research and development activities and our general and administrative expenses. Net cash used for our operating assets and liabilities of $0.5 million during the nine months ended September 30, 2023 consisted primarily of an increase in prepaid expenses, other current assets, and other assets of $2.7 million and a decrease in deferred revenue of $1.4 million, partially offset by an increase of $3.4 million in accounts payable and accrued expenses and a $0.2 million decrease in net operating lease assets and lease liabilities. Our net non-cash charges during the nine months ended September 30, 2023 primarily consisted of $4.4 million of share-based compensation expense, $0.2 million of depreciation expense and $1.6 million of impairment of long-lived assets, which were partially offset by $2.4 million of net amortization of premiums on short-term investments.

截至2024年9月30日止九个月，投资活动提供的净现金为5220万美元，而截至2023年9月30日止九个月，投资活动使用的现金为1020万美元。投资活动提供的现金增加6240万美元，主要是由于短期投资到期的净收益。

截至2024年9月30日的九个月，融资活动提供的净现金为850万美元，而截至2023年9月30日的九个月为4680万美元，原因是2024年股权融资筹集的现金减少。

我们预计将继续因我们正在进行的活动而产生费用，主要是两项正在进行的评估LyR-210的ENLIGHTEN 3期试验。如果我们获得任何候选产品的营销批准，我们预计将产生与产品销售、营销、制造和分销相关的巨额商业化费用。此外，我们将继续承担与上市公司运营相关的额外成本。因此，我们需要获得与持续运营相关的大量额外资金。如果我们无法在需要时或以有吸引力的条件筹集资金，我们将被迫推迟、减少或取消我们的研发计划或未来的商业化工作。

尽管管理层得出的结论是，对我们持续经营的能力存在重大疑问，但这一结论是基于我们根据适用会计准则进行的分析。根据我们当前的业务计划，我们预计我们的现金、现金等值物和短期投资余额足以为我们到2026年第一季度的运营费用和资本支出提供资金。然而，我们的这一估计是基于可能被证明是错误的假设。如果出于任何原因，我们的费用与我们的假设存在重大差异，或者我们比预期更快地利用现金，或者如果我们无法及时获得资金，我们可能会被要求修改我们的业务计划和战略，这可能导致我们进一步削减、推迟或停止我们的一个或多个研究或开发计划。因此，我们的业务、财务状况和运营业绩可能会受到重大不利影响。

管理层为公司获取资源的计划包括通过出售其股权证券获得资本、达成战略合作伙伴关系安排以及从银行、股东或其他关联方（如果需要）获得短期借款。然而，管理层无法保证公司将成功实现其任何计划。

识别潜在的候选产品并进行临床前测试和临床试验是一个耗时、昂贵且不确定的过程，需要数年时间才能完成，而且我们可能永远不会产生获得上市批准和实现产品销售所需的必要数据或结果。此外，我们的候选产品如果获得批准，可能无法取得商业成功。我们的商业收入（如果有的话）将来自我们预计多年内不会上市（如果有的话）的产品的销售。因此，我们需要继续依赖额外融资来实现我们的业务目标。我们可能无法以可接受的条款或根本无法获得足够的额外融资。

此外，包括信贷和金融市场在内的全球经济周期性地经历极端波动和干扰，包括流动性和信贷可用性严重减少、利率和通胀率上升、消费者信心下降、经济增长下降、失业率上升和经济稳定的不确定性。所有这些因素都可能影响我们的流动性和未来融资需求，包括但不限于我们在需要时以可接受的条款筹集额外资本的能力（如果有的话）。任何经济放缓的持续时间都是不确定的，对我们业务的影响也很难预测。请参阅“风险因素-不稳定的全球政治或经济状况可能会对我们的业务、财务状况和股价产生严重的不利后果。

在此之前，如果我们能够产生可观的产品收入，我们预计将通过股权发行、债务融资、合作、战略联盟和许可安排的组合来满足我们的现金需求。我们没有任何承诺的外部资金来源。在我们通过出售股权或可转换债务证券筹集额外资本的情况下，您的所有权权益可能会被稀释，这些证券的条款可能包括清算或其他可能对您作为普通股股东的权利产生不利影响的优惠。如果LianBio许可协议下的开发活动成功，我们可能可以获得与该协议相关的额外资金。然而，鉴于LianBio的重大重组，这一合作的未来是不确定的，如本文所述。任何债务融资，如果可用，可能涉及包括限制性契约的协议，这些契约限制我们采取具体行动的能力，例如招致额外债务、进行资本支出或宣布股息，这些可能会对我们开展业务的能力产生不利影响。

If we raise funds through additional collaborations, strategic alliances, or licensing arrangements with third parties, we may have to relinquish valuable rights to our technologies, future revenue streams, research programs, or product candidates, or to grant licenses on terms that may not be favorable to us. If we are unable to raise additional funds through equity or debt financings when needed, we may be required to delay, limit, reduce, or terminate our product development or future commercialization efforts or grant rights to develop and market product candidates that we would otherwise prefer to develop and market ourselves.

The JOBS Act permits an “emerging growth company” such as us to take advantage of an extended transition period to comply with new or revised accounting standards applicable to public companies. We have elected to use this extended transition period under the JOBS Act. As a result, our financial statements may not be comparable to the financial statements of issuers who are required to comply with the effective dates for new or revised accounting standards that are applicable to public companies, which may make comparison of our financials to those of other public companies more difficult.

We will remain an emerging growth company until the earliest to occur of: (1) the last day of the fiscal year (a) following the fifth anniversary of the completion of our IPO, or December 31, 2025, (b) in which we have total annual gross revenues of $1.235 billion or more, or (c) in which we are deemed to be a large accelerated filer under the rules of the SEC, which means the market value of our outstanding common stock held by non-affiliates exceeds $700 million as of last business day of our most recently completed second fiscal quarter, and (2) the date on which we have issued more than $1.0 billion in nonconvertible debt during the previous three years.

We are a smaller reporting company as defined in Rule 12b-2 of the Exchange Act and are not required to provide the information otherwise required under this Item 3.

In designing and evaluating our disclosure controls and procedures, management recognizes that any controls and procedures, no matter how well designed and operated, can provide only reasonable assurance of achieving the desired control objectives. In addition, the design of disclosure controls and procedures must reflect the fact that there are resource constraints and that management is required to apply judgment in evaluating the benefits of possible controls and procedures relative to their costs.

Our management, with the participation of our Chief Executive Officer and Chief Financial Officer, evaluated, as of the end of the period covered by this Quarterly Report on Form 10-Q, the effectiveness of our disclosure controls and procedures (as defined in Rules 13a-15(e) and 15d-15(e) under the Exchange Act). Based on that evaluation, our Chief Executive Officer and Chief Financial Officer concluded that our disclosure controls and procedures were effective at the reasonable assurance level as of September 30, 2024.

There were no changes in our internal control over financial reporting identified in management’s evaluation pursuant to Rules 13a-15(f) or 15d-15(f) of the Exchange Act during the three months ended September 30, 2024 that materially affected, or are reasonably likely to materially affect, our internal control over financial reporting.

From time to time, we may become involved in litigation relating to claims arising from the ordinary course of business. Our management believes that there are currently no claims or actions pending against us, the ultimate disposition of which could have a material adverse effect on our results of operations or financial condition.

Investing in our common stock involves a high degree of risk. You should carefully consider the risks and uncertainties described below and the other information contained in this Quarterly Report on Form 10-Q before making an investment in our common stock. Our business, financial condition, results of operations, or prospects could be materially and adversely affected if any of these risks occurs, and as a result, the market price of our common stock could decline and you could lose all or part of your investment. This Quarterly Report on Form 10-Q also contains forward-looking statements that involve risks and uncertainties. See “Special Note Regarding Forward-Looking Statements.” Our actual results could differ materially and adversely from those anticipated in these forward-looking statements as a result of certain factors, including those set forth below.

Any potential financial or strategic option we pursue in an effort to maximize shareholder value may not result in the identification of a suitable transaction, or if one is identified and pursued, may not be completed on attractive terms, or at all.

In May 2024, in connection with the Company’s announcement that we failed to meet the primary endpoint of our ENLIGHTEN 1 Phase 3 clinical trial, we announced our interest in potential strategic alternatives. We have not yet engaged a financial adviser to assist us in this effort. Such alternatives may include a merger, sale, divestiture of assets, licensing, or other strategic transaction.

The process of continuing to evaluate these strategic options may be costly, time-consuming and complex and we may incur significant costs related to this continued evaluation, such as legal, accounting and advisory fees and expenses and other related charges. Moreover, any potential financial or strategic option we pursue may not result in the identification of a suitable transaction, or if one is identified and pursued, may not be completed on attractive terms, or at all. There can be no assurance of completion of any particular course of action or a defined timeline for completion, and we can provide no assurance that any strategic alternative we pursue will have a positive impact on our results of operations or financial condition.

We are attempting to sublease or assign our three leaseholds, which represent significant operating costs, and there can be no assurance that we will accomplish this effort on favorable terms, or at all, which could adversely affect our business, results of operations and financial condition.

The Company has three leaseholds including two in Waltham, Massachusetts and one in Watertown, Massachusetts. These leaseholds represent significant operating costs for the Company. The Company has retained a broker to sublease or assign all three of the leaseholds in connection with the Company’s capital preservation efforts. There can be no assurance that the Company will find third parties to enter into a sublease or assignment of these leaseholds at terms that are favorable to the Company, on a timetable that is advantageous to the Company, or at all.

The operating lease, as amended, for office and laboratory space in Watertown expires in April 2027 and comprises approximately 27,311 square feet. The lease provides for base rent of $2.0 million per year. The Company maintains a letter of credit of approximately $300,000 securing its obligations under the Watertown operating lease.

The Company has two leases for space at 880 Winter Street in Waltham. The first lease comprises approximately 29,000 square feet of office and lab space, and the lease provides for base rent of $2.2 million per year, which will increase 3% per year over the noncancellable term ending on June 30, 2033. In connection with the lease, a security deposit was delivered to the landlord in the form of an irrevocable standby letter of credit collateralized by $1.1 million of deposits with the financial institution.

In December 2023, the Company executed a sublease agreement for additional laboratory and office space located at 880 Winter Street in Waltham. The subleased premises comprise approximately 24,000 square feet, and the sublease provides for base rent of $1.8 million per year, which will increase 3% per year over the noncancellable term ending on November 30, 2032. The Company provided the landlord with a security deposit in the form of a letter of credit in the amount of approximately $600,000.

Under all three leases, the Company is responsible for its share of real estate taxes, maintenance, and other operating expenses applicable to the respective leased premises. An inability to successfully sublease or assign all three of the leaseholds will negatively impact our capital preservation efforts and could materially and adversely affect our business, financial condition and the results of operations.

We have incurred significant losses since inception and expect to incur significant additional losses for the foreseeable future. We may never achieve or maintain profitability.

We have incurred significant operating losses in each year since our inception, including operating losses of approximately $11.9 million and $15.6 million for the three months ended September 30, 2024 and 2023 respectively. In addition, we have not commercialized any products and have never generated any revenue from product sales. We have devoted almost all of our financial resources to research and development, including our pre-clinical development activities.

In May 2024, our Board approved a reduction in force by up to 87 employees, effective on or about May 21, 2024 with respect to approximately 80 employees and effective on or about June 20, 2024 with respect to approximately seven employees (the “May 2024 RIF”). The Board’s decision was based on the need to implement cost-reduction initiatives intended to reduce the Company’s ongoing operating expenses and maximize shareholder value. The Company incurred charges of approximately $9.5 million in connection with this workforce reduction, primarily consisting of severance payments, employee benefits and related costs. Certain of these expenses have been paid to former employees as of the date of these condensed consolidated financial statements and relate to the May 2024 reduction in force. The remaining expenses are included within accrued restructuring with anticipated payout at a later date, primarily pertaining to current employees.

We expect to continue to incur significant additional operating losses for the foreseeable future and we may not achieve or maintain profitability in the future. In order to obtain FDA approval of any product candidate, we must submit to the FDA an NDA demonstrating that the product candidate is safe for humans and effective for its intended use. This demonstration requires significant research and animal tests, which are referred to as non-clinical or pre-clinical studies, as well as human tests, which are referred to as clinical trials. Furthermore, the costs of advancing product candidates into each succeeding clinical phase tend to increase substantially over time. The total costs to advance any of our product candidates to marketing approval in even a single jurisdiction would be substantial. Because of the numerous risks and uncertainties associated with CRS treatment product development, we are unable to accurately predict the timing or amount of increased expenses or when, or if, we will be able to begin generating revenue from the commercialization of products or achieve or maintain profitability. Our expenses will also increase substantially if we:

Furthermore, our ability to successfully develop, commercialize, and license our products and generate product revenue is subject to substantial additional risks and uncertainties. Each of our product candidates will require additional pre-clinical and/or clinical development, potential regulatory approval in multiple jurisdictions, the development of or securing of manufacturing supply, capacity, and expertise, the use of external vendors, the building of a manufacturing and commercial organization, substantial

investment, and significant marketing efforts before we generate any revenue from product sales. As a result, we expect to continue to incur net losses and negative cash flows for the foreseeable future. These net losses and negative cash flows have had, and will continue to have, an adverse effect on our stockholders’ equity and working capital.

The amount of future losses and when, if ever, we will achieve profitability are uncertain. We have no products that have generated any commercial revenue, do not expect to generate revenues from the commercial sale of products in the foreseeable future, and might never generate revenues from the sale of products. Our ability to generate revenue and achieve profitability will depend on, among other things, successful completion of the clinical development of our product candidates; obtaining necessary regulatory approvals from the FDA and international regulatory agencies; establishing cost-effective manufacturing, generating sales, and achieving market acceptance of our products and marketing infrastructure to commercialize our product candidates for which we obtain approval; and raising sufficient funds to finance our activities. We might not succeed at any of these undertakings. If we are unsuccessful at some or all of these undertakings, our business, prospects, and results of operations may be materially adversely affected.

Our recurring losses from operations raise substantial doubt regarding our ability to continue as a going concern.

We continue to operate with limited resources. We have incurred significant losses since our inception and have never generated revenue or profit, and it is possible we will never generate revenue or profit. Based on our current operating plans, and without additional funding, there is substantial doubt about our ability to continue as a going concern. See Part I, Item 2. “Management’s Discussion and Analysis of Financial Condition and Results of Operations” of this Quarterly Report on Form 10-Q for a discussion of our expected cash runway. This cash runway estimate is based on assumptions that may prove to be wrong, and we could use our available capital resources sooner than we currently expect. Until such time as the Company can generate significant revenue from product sales, if ever, it plans to finance its operations through a combination of equity or debt financings, collaboration agreements, strategic alliances and licensing arrangements, but there can be no assurances that such financing will be available to us on satisfactory terms, or at all.

Securing additional financing may divert our management from our day-to-day activities, which may adversely affect our ability to develop and commercialize any of our product candidates. If we are unable to obtain funding, we would be forced to delay, reduce or eliminate our research and development programs, which would adversely affect our business prospects. In addition, if we are unable to raise capital, we will also need to implement additional cost reduction measures, and any failure to effectively do so will harm our business, results of operations and future prospects. The perception that we may not be able to continue as a going concern may cause others to choose not to deal with us due to concerns about our ability to meet our contractual obligations. If we are unable to continue as a going concern, investors could lose all or part of their investment in our Company.

We need significant additional funding in order to complete development of, manufacture, and obtain regulatory approval for our product candidates and commercialize our products, if approved. Moreover, the failure of our ENLIGHTEN 1 Phase 3 trial to meet its primary endpoint has made it more difficult for us to raise capital. If we are unable to raise capital when needed, we could be forced to delay, reduce, or eliminate our product development programs or commercialization efforts, and/or discontinue operations.

We continue to need additional capital, which we may raise through equity offerings, debt financings, marketing, and distribution arrangements and other collaborations, strategic alliances, and licensing arrangements or other sources. The failure to meet the primary endpoint of our ENLIGHTEN 1 Phase 3 clinical trial has made it significantly more difficult for us to raise more capital. Additional sources of financing might not be available on favorable terms, if at all. If we do not succeed in raising additional funds on acceptable terms, we might be unable to complete planned clinical trials or obtain approval of any of our product candidates from the FDA, or any foreign regulatory authorities, and could be forced to discontinue product development or reduce our operations.

We will require substantial funds to further develop, manufacture, obtain approval for, and commercialize our product candidates, including LYR-210, for which we initiated two pivotal Phase 3 clinical trials. In May 2024 we suspended further development of LYR-220. We would also require substantial additional funds to further develop, obtain approval for, and commercialize, LYR-220.

Our future funding requirements, both near and long-term, will depend on many factors, including, but not limited to:

Depending on our business performance, the economic climate, and market conditions, we may be unable to raise additional funds through any sources. Market volatility could also adversely impact our ability to access capital as and when needed.

We maintain our cash and cash equivalents in accounts with major U.S. and multi-national financial institutions, and U.S. treasury bills and our deposits at these institutions exceed insured limits. Market conditions can impact the viability of these institutions. In the event of failure of any of the financial institutions where we maintain our cash and cash equivalents, there can be no assurance that we would be able to access uninsured funds in a timely manner or at all. Any inability to access or delay in accessing these funds could adversely affect our business and financial position.

Raising additional capital may cause dilution to our stockholders, restrict our operations, or require us to relinquish rights to our technologies or product candidates.

Until such time, if ever, as we can generate substantial revenue, we may finance our cash needs through a combination of equity offerings, debt financings, marketing, and distribution arrangements and other collaborations, strategic alliances, and licensing arrangements. 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 equity or convertible debt securities, the ownership interests of our shareholders will be diluted, and the terms of these securities may include liquidation or other preferences that adversely affect the rights of our common stockholders. Debt financing and preferred equity financing, if available, may involve agreements that include covenants limiting or restricting our operations and our ability to take specific actions, such as incurring additional debt, making capital expenditures, declaring dividends, redeeming our stock, making certain investments, and engaging in certain merger, consolidation, or asset sale transactions, among other restrictions. If we raise additional funds through additional collaborations, strategic alliances, or marketing, distribution, or licensing arrangements with third parties, we may be required 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. If we are unable to raise additional funds through equity or debt financings when needed, we may be required to delay, limit, reduce, or terminate our product development or future commercialization efforts or grant rights to develop and market product candidates that we would otherwise prefer to develop and market ourselves.

To date, we have no approved product on the market and have generated no product revenues. Unless we receive approval from the FDA or other regulatory authorities for our product candidates, we will not have product revenues. Therefore, for the foreseeable future, we will have to fund all of our operations and capital expenditures from cash on hand and licensing fees and grants, if any.

LYR-210 is at a development stage and we have suspended further efforts on LYR-220.

We are a biotechnology company focused on the development and commercialization of novel integrated drug and drug delivery solutions for the localized treatment of patients with CRS. Our product candidates are in clinical development, and favorable results in early-stage clinical trials may not be predictive of success in later clinical trials and may not lead to commercially viable products for any of several reasons. For example, we failed to meet the primary endpoint in our ENLIGHTEN 1 Phase 3 trials for LYR-210 which has a material adverse effect on our development plans for LYR-210. In May 2024 we also suspended further development of LYR-220. LYR-210, as well as LYR-220 if in the future we decide to advance it, will require significant additional development, clinical trials, regulatory authorizations, and additional investment by us before it can be commercialized.

Our business is highly dependent on the success of our most advanced product candidate, LYR-210, which requires on-going clinical testing before we can seek regulatory approval and potentially launch our product. If LYR-210 does not receive regulatory approval or is not successfully commercialized, or is significantly delayed in doing so, our business will be harmed.

A substantial portion of our business and future success depends on our ability to develop, obtain regulatory approval for, and successfully commercialize our most advanced product candidate, LYR-210. We currently have no products that are approved for commercial sale and have not completed the development of any product candidates, and may never be able to develop marketable products. We expect that a substantial portion of our efforts and expenditures will be devoted to LYR-210, which will each require continued clinical development and potential additional pre-clinical development, management of clinical and medical affairs and manufacturing activities, regulatory approval in multiple jurisdictions, the securing of manufacturing supply, the building of a manufacturing and commercial organization, substantial investment, and significant marketing efforts before we can generate any revenues from any commercial sales. We cannot be certain that LYR-210 will be successful in ongoing or future clinical trials, receive regulatory approval, or be successfully commercialized even if we receive regulatory approval. Even if we receive approval to market LYR-210 from the FDA or other regulatory bodies, we cannot be certain that our product candidates will be successfully commercialized, profitable, widely accepted in the marketplace, or more effective than other commercially available alternatives. Nor can we be certain that, if and when approved, the safety and efficacy profile of LYR-210 and will be consistent with the profiles observed in clinical trials.

We advanced LYR-210 through our Phase 2 randomized, controlled, patient blinded LANTERN clinical trial, evaluating the safety and efficacy in surgically-naïve CRS patients who have failed previous medical management. The trial was designed to enroll 99 evaluable patients with the potential to increase to up to 150 patients and was initiated in May 2019 at sites in Australia, Austria, Czech Republic, New Zealand, and Poland. In December 2019, the FDA authorized our investigational new drug application, and, prior to the COVID-19 pandemic, we planned to enroll patients in the United States. However, in light of developments relating to the COVID-19 pandemic, as described below, we discontinued enrollment at 67 patients in our Phase 2 LANTERN clinical trial and did not enroll any patients in the United States.

On December 7, 2020, we reported top-line results from our Phase 2 LANTERN clinical trial, including that LYR-210 failed to meet the primary endpoint of the trial. We believe this was primarily due to the discontinuation of enrollment related to the COVID-19 pandemic. As a result of the decrease in the number of patients enrolled from planned (99 evaluable) to actually enrolled (67) patients in our Phase 2 LANTERN clinical trial, a greater magnitude of change in composite score of the seven-day average of four cardinal symptoms from baseline at week 4 and/or a smaller standard deviation associated with the change from baseline at week 4 was required in order for the trial to achieve statistical significance for the primary endpoint. On May 6, 2024, we reported top-line results from our Phase 3 ENLIGHTEN 1 clinical trial, including that LYR-210 failed to meet its primary endpoint of demonstrating statistically significant improvement compared to sham control in the composite score of the three cardinal symptoms of CRS (nasal obstruction, nasal discharge, facial pain/pressure) at 24 weeks. The 52-week extension phase of the ENLIGHTEN 1 trial is complete and full data are expected in Q4 2024. ENLIGHTEN 2, the second pivotal Phase 3 trial of LYR-210 in CRS, is ongoing and topline data is expected in the second quarter of 2025. There can be no assurance that we will achieve the primary endpoint or any other endpoints in the ENLIGHTEN 2 Phase 3 clinical trial for LYR-210.

If the required regulatory approvals for LYR-210 are not obtained or are significantly delayed, or any approved products are not commercially successful, our business, financial condition, and results of operations may be materially harmed. For example, the Company may need to revise its regulatory strategy for LYR-210 since the Company failed to meet the primary endpoint of the ENLIGHTEN 1 Phase 3 clinical trial.

Further, our competitors may be developing products with similar mechanisms of action and may experience problems with their products that could identify problems that would potentially harm our business.

If LianBio is unable to find a third party to acquire its rights under the LianBio License Agreement, it may materially harm our business, financial condition, results of operations and prospects.

LianBio announced that in October 2023 its board of directors commenced a comprehensive strategic review of its business. The LianBio Board ultimately concluded that selling off assets and winding down operations was the best way to realize maximum shareholder value. LianBio reported that a substantial portion of the wind down activities, including fulfillment of transition service obligations under its existing agreements and gradual cessation of currently active clinical trials, will be completed by the end of 2024. LianBio announced in 2024 that it was further reducing the size of its workforce to approximately 50 employees with plans to reduce that number further over the course of 2024. LianBio stated it will maintain a core group of employees necessary to implement an orderly wind down and support its efforts to maximize the value of its remaining business and assets including the collaboration with the Company. Due to these developments, the future of the Company’s collaboration with LianBio is uncertain as LianBio continues its wind down, while seeking a third party to acquire LianBio’s rights under the LianBio License Agreement. If LianBio is unable to find a third party to acquire LianBio’s rights under the LianBio License Agreement, it may materially harm our business, financial condition, results of operations and prospects.

Managing our obligations under our license and other strategic agreements may divert management time and attention, causing delays or disruptions to our business.

We are party to the LianBio License Agreement, as amended. The LianBio License Agreement grants an exclusive license to develop and commercialize LYR-210 in Greater China (mainland China, Hong Kong, Macau, and Taiwan), Singapore, South Korea, and Thailand, or the Territory. Furthermore, under the LianBio License Agreement, LianBio has the first right to obtain a license to develop and commercialize LYR-220.

Under the LianBio License Agreement, as amended, both parties agreed to negotiate prior to December 31, 2022 a clinical supply agreement to support clinical trials to be conducted by LianBio in the territory, i.e., PRC, Hong Kong, Macau, Taiwan, Singapore, South Korea, and Thailand. Subsequently, there was a side letter executed on December 27, 2022 which extended the negotiations of a supply agreement. Payments made by LianBio to the Company that have not yet been recognized as revenue are deferred as a contract liability on the Company’s consolidated balance sheet. The Company anticipated that the payments treated as a contract liability would be recognized as revenue as the clinical supply of LYR-210 was delivered and over the remaining time it takes to conduct the applicable trials. As of September 30, 2024, the parties still have not completed their negotiations of the clinical supply agreement. At this point, it is uncertain whether such an agreement will be completed. In view of the uncertainty around the completion of the clinical supply agreement, the Company may decide to recognize such payments as revenue on an accelerated schedule.

We also may in the future enter into license and strategic agreements, which, subject us to various obligations, including diligence obligations, reporting and notification obligations, payment obligations for achievement of certain milestone as well as other material obligations. We may need to devote substantial time and attention to ensuring that we successfully integrate these transactions into our existing operations and are compliant with our obligations under these agreements, which may divert management’s time and attention away from our research and development programs or other day-to-day activities.

Our license and strategic agreements are also complex and certain provisions in those agreements may be susceptible to multiple interpretations. In the event of any disagreement about the interpretation of these provisions, our management may need to devote a disproportionate amount of its attention to resolving these disagreements. Such disruptions may cause delays in our research and development programs and other business objectives.

Our operating activities may be restricted by certain covenants in our license and strategic agreements, which could limit our development and commercial opportunities.

In connection with our license and strategic agreements, we may agree to and be bound by negative covenants which may limit our development and commercial opportunities. For example, pursuant to the LianBio License Agreement, we made certain covenants to not commercialize a competing product anywhere in the Territory, nor collaborate with, enable, or otherwise authorize, license, or grant any right to any third party to commercialize a competing product anywhere in the Territory, subject to certain carve-outs. We also made certain covenants to grant an exclusive option to LianBio for the development and commercialization of LYR-220 in the Territory. These provisions may inhibit our development efforts, prevent us from forming strategic collaborations to develop and potentially commercialize any other product candidates and may materially harm our business, financial condition, results of operations and prospects.

Failure to obtain marketing approval in international jurisdictions would prevent our products from being marketed in such jurisdictions.

In order to market and sell our products in jurisdictions outside of the United States, we or our third-party collaborators must obtain separate marketing approvals and comply with numerous and varying regulatory requirements. The approval procedure varies among countries and can involve additional testing. The time required to obtain approval may differ substantially from that required to obtain FDA approval. The regulatory approval process outside the United States generally includes all the risks associated with obtaining FDA approval. In addition, in many countries outside the United States, it is required that the product be approved for reimbursement before the product can be approved for sale in that country. Additionally, we may be dependent on third-party collaborators to develop and commercialize our product candidates in certain international jurisdictions, such as in the case of our exclusive license agreement with LianBio for the development and commercialization of LYR-210 in the Territory. In the agreement with LianBio, while we have agreed that we must use commercially reasonable efforts to complete a global Phase 3 clinical trial for LR-210 and seek regulatory approval in the United States, LianBio must also use commercially reasonable efforts to develop, seek regulatory approval for, and commercialize LYR-210 in the Territory. We or these third parties may not obtain approvals from regulatory authorities outside the United States on a timely basis, if at all. Approval by the FDA does not ensure approval by regulatory authorities in other countries or jurisdictions, and approval by one regulatory authority outside the United States does not ensure approval by regulatory authorities in other countries or jurisdictions or by the FDA. However, the failure to obtain approval in one jurisdiction may negatively impact our ability to obtain approval in other jurisdictions. We and our third-party collaborators may not be able to file for marketing approvals, and even if we do, we may not obtain necessary approvals to commercialize our medicines in any market.

We are party to a collaboration agreement, and may enter into other collaborations, that place the development and commercialization of our product candidates outside our control, require us to relinquish important rights or may otherwise be on terms unfavorable to us, and if our collaborations are not successful, our product candidates may not reach their full market potential.

Our drug development programs and the potential commercialization of our drug candidates will require substantial additional cash to fund expenses. For some of our drug candidates, we may decide to collaborate with additional pharmaceutical and biotechnology companies for the development and potential commercialization of those drug candidates in selected geographic territories or for selected patient populations. For example, we are party to the LianBio License Agreement to develop and commercialize LYR-210 in the Territory. We face significant competition in seeking appropriate collaborators. Whether we reach a definitive agreement for a collaboration or successfully maintain a collaboration will depend, among other things, upon our assessment of the collaborator’s resources and expertise, the terms and conditions of the proposed or existing collaboration and the proposed or existing collaborator’s evaluation of a number of factors. Those factors may include the design or results of clinical trials, the likelihood of approval by the FDA or similar regulatory authorities outside the United States, the potential market for the subject drug candidate, the costs and complexities of manufacturing and delivering such drug candidate to patients, the potential of competing therapies, the existence of uncertainty with respect to our ownership of technology, which can exist if there is a challenge to such ownership without regard to the merits of the challenge and industry and market conditions generally. The collaborator may also consider alternative drug candidates or technologies for similar indications that may be available to collaborate on and whether such a collaboration could be more attractive than the one with us for our drug candidate. The terms of any existing or additional collaborations or other arrangements that we may establish may not be favorable to us.

We may in the future expend our limited resources to pursue a particular product candidate or indication and fail to capitalize on product candidates or indications that may be more profitable or for which there is a greater likelihood of success.

Because we have limited financial and managerial resources, we focus on research programs and product candidates that we identify for specific indications. As a result, we may forego or delay pursuit of opportunities with other product candidates or for other indications that later prove to have greater commercial potential. Our resource allocation decisions may cause us to fail to timely capitalize on viable commercial products or profitable market opportunities. Our spending on current and future research and development programs and product candidates for specific indications may not yield any commercially viable products. If we do not accurately evaluate the commercial potential or target market for a particular product candidate, we may relinquish valuable rights to that product candidate through collaboration, licensing, or other royalty arrangements in cases in which it would have been more advantageous for us to retain sole development and commercialization rights to such product candidate.

Risks Related to Discovery, Development, Clinical Testing, Manufacturing, and Regulatory Approval

Clinical trials required for our lead product candidate and any future product candidates are expensive and time-consuming, their outcome is uncertain, and if our clinical trials do not meet safety or efficacy endpoints in these evaluations, or if we experience significant delays in these trials, our ability to commercialize our product candidates and our financial position will be impaired.

We initiated the pivotal Phase 3 clinical trials for our most advanced product candidate, LYR-210. In May 2024 we suspended further clinical development on our other product candidate, LYR-220, in view of our failure to meet our primary endpoint in the ENLIGHTEN 1 Phase 3 clinical trial for LYR-210 and the need to preserve capital. It is impossible to predict if LYR-210 will prove effective and safe in humans or if we will receive regulatory approval, and the risk of failure through the development process is high. Given the similarities in the design of the ENLIGHTEN 1 and ENLIGHTEN 2 Phase 3 clinical trials, the risk that we fail to meet the primary endpoint in the ENLIGHTEN 2 Phase 3 clinical trial has increased since we failed to meet our primary endpoint in the ENLIGHTEN 1 Phase 3 clinical trial. Before obtaining marketing approval from regulatory authorities for the sale of any product candidate, we may need to complete pre-clinical development and then conduct extensive clinical trials to demonstrate the safety and efficacy of our product candidates in humans.

Clinical development is a long, expensive, and uncertain process that is subject to significant delays. Due to known or unknown circumstances beyond our control, it may take us several years to complete our testing, and failure can occur at any stage of testing. The outcome of pre-clinical testing and early clinical trials may not be predictive of the results of later clinical trials, and interim results of a clinical trial do not necessarily predict final results. We cannot assure you that any clinical trial that we are conducting, or may conduct in the future, will demonstrate consistent or adequate efficacy and safety to obtain regulatory approval to market our product candidates. Moreover, pre-clinical and clinical data are often susceptible to varying interpretations and analysis, and many companies that have believed their product candidates performed satisfactorily in pre-clinical studies and clinical trials have nonetheless failed to obtain marketing approval of their products.

Delays associated with products for which we are directly conducting pre-clinical studies or clinical trials may cause us to incur additional operating expenses. The commencement and rate of completion of pre-clinical studies or clinical trials may be delayed by, or terminated because of, many factors, including:

If we are required to extend the duration of current pre-clinical studies or clinical trials or to conduct additional pre-clinical studies or clinical trials or other testing of our product candidates beyond those that we currently contemplate, if we are unable to successfully complete pre-clinical studies or clinical trials of our product candidates or other testing, if the results of these trials, studies, or tests are not positive or are only modestly positive, if there are safety concerns, or if we determine that the observed safety or efficacy profile would not be competitive in the marketplace, we may:

We could encounter delays if a clinical trial is materially modified, suspended, or terminated by us, by the IRBs of the institutions in which such trials are being conducted, by the Data Safety Monitoring Board, or DSMB, for such trial, or by the FDA or other regulatory authorities. Such authorities may impose a material modification, suspension, or termination 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 for our product candidates, or other products or product candidates in the same drug class, 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. Furthermore, we may rely on CROs and clinical trial sites to ensure the proper and timely conduct of clinical trials and while we would have agreements governing their committed activities, we would have limited influence over their actual performance, as described in “—Risks Related to Our Dependence on Third Parties.”

Our most advanced product candidate, LYR-210, is in clinical development and will require the completion of clinical testing before we are prepared to submit an NDA for regulatory approval. We cannot predict if or when we might complete the development of LYR-210 and submit an NDA or whether any such NDA will be approved by the FDA. We may also seek feedback from the FDA or other regulatory authorities on our clinical development programs, and the FDA or such regulatory authorities may not provide such feedback on a timely basis, or such feedback may not be favorable, which could further delay our development programs. If the results of ongoing and future clinical trials for LYR-210 are positive, we plan to submit an NDA in the United States. However, no assurance can be given that we will be successful in the near term, obtain regulatory approval, or have any commercial sales of LYR-210.

Any clinical test may fail to produce results satisfactory to the FDA or foreign regulatory authorities. Pre-clinical and clinical data can be interpreted in different ways by different reviewers and regulators, which could delay, limit, or prevent regulatory approval. Drug-related adverse events during a pre-clinical study or clinical trial could cause us to repeat a trial or study, perform an additional trial or study, expand the size and/or duration of a trial or study, terminate a trial or study, or even cancel a pre-clinical or clinical program. The failure of pre-clinical studies or clinical trials to demonstrate safety and effectiveness for the desired indications could harm the development of that product candidate and other product candidates. This failure could cause us to abandon a product candidate and could delay development of other product candidates. Any delay in, or termination of, our clinical trials would delay the filing of our NDAs with the FDA and, ultimately, our ability to commercialize our product candidates and generate product revenues. A number of companies in the biotechnology and pharmaceutical industry have suffered significant setbacks in advanced clinical trials due to lack of efficacy or adverse safety profiles, notwithstanding promising results in earlier trials. Even if our future and ongoing pre-clinical studies and clinical trials are completed as planned, we cannot be certain that their results will support the safety and effectiveness of LYR-210, and/or any future product candidate.

If we experience delays in the commencement or completion of, or have to extend or expand, our pre-clinical studies or clinical trials, or if we terminate a pre-clinical study or clinical trial prior to completion, the commercial prospects of LYR-210, or any future product candidate could be harmed, and our ability to generate revenues from LYR-210, or any future product candidate may be delayed. In addition, any delays in our pre-clinical studies or clinical trials could increase our costs, slow down the development and approval process, and jeopardize our ability to commence product sales and generate revenues. Any of these occurrences may harm our business, financial condition, and results of operations. In addition, many of the factors that cause, or lead to, a delay in the commencement or completion of pre-clinical studies or clinical trials may also ultimately lead to the denial of regulatory approval of our product candidates.

We previously transitioned most of our clinical manufacturing from a contract manufacturing organization, or CMO, to an in-house manufacturing facility at our Watertown headquarters to produce LYR-210 and LYR-220. We never previously completed a

technical transfer process to an in-house facility, built, owned or operated a commercial manufacturing facility, and there is no guarantee that we will be successful doing so. Since the May 2024 RIF, we are no longer engaged in the manufacture of our product candidates and we no longer intend to build out a commercial manufacturing capability. We believe we have sufficient supply of LYR-210 to complete our ENLIGHTEN 1 and ENLIGHTEN 2 Phase 3 clinical trial. We are also engaged in an effort to sublease or assign our three leaseholds which include manufacturing space. Throughout Item 1A, we refer to manufacturers, CMOs and suppliers interchangeably.

Parts of our manufacturing process are still outsourced and we expect them to remain outsourced. Our CMOs provide multiple different types of services to us. For example, some CMOs provide raw materials for our in-house manufacturing effort; some CMOs perform analytical testing for our starting materials, intermediates, drug product, and stability studies; and some CMOs provide services like sterilizing, packaging, and labeling. Currently, our manufacturing activities are suspended and that suspension applies to third party CMOs that provide materials and services related to our manufacturing.

If we restart our in-house manufacturing, it is common that various aspects of the development program, such as manufacturing methods and equipment, are altered along the way in an effort to optimize cost of goods, processes and results. Such changes carry the risk that these manufacturing efforts will not achieve these successfully or in a cost-efficient manner, or that we will be subject to additional requirements by the FDA or other regulatory bodies. Slight deviations resulting from technology transfer, including those affecting quality attributes and stability, may result in unacceptable changes in the product that could result in lot failures or product recalls. Lot failures or product recalls could cause us to delay product launches or clinical trials, which could be costly to us and otherwise harm our business, financial condition, results of operations and prospects. Problems with our in-house manufacturing process could restrict our ability to meet our clinical and regulatory timelines, and market demand for our products.

As a result of the May 2024 RIF, we no longer have a sufficient number of experienced scientific, quality and manufacturing personnel needed to operate our clinical and commercial manufacturing processes, which in the event we restart our manufacturing efforts, could result in delays in production or difficulties in maintaining compliance with applicable regulatory requirements.

Any problems in our manufacturing process or facilities, or that of our CMOs, licensees and suppliers, could make us a less attractive collaborator for potential partners, including larger pharmaceutical companies and academic research institutions, which could limit our access to additional capital or capabilities.

Our pre-clinical studies and clinical trials may fail to demonstrate adequately the safety and efficacy of any of our product candidates and the development of our product candidates may be delayed or unsuccessful, which could prevent or delay regulatory approval and commercialization.

Currently LYR-210 is our only product candidate still in clinical development. Notwithstanding the data obtained to date with respect to LYR-210 and LYR-220 in CRS, LYR-210 will require additional clinical and non-clinical development, regulatory review and approval in multiple jurisdictions, substantial investment, access to sufficient commercial manufacturing capacity, and significant marketing efforts before we can generate any revenue from our product sales. In addition, if we encounter safety or efficacy problems, developmental delays or regulatory issues, delays caused by COVID-19, or other problems, our developmental plans and business could be significantly harmed.

If the development of LYR-210, or any other future product candidate is unsuccessful, our ability to generate revenues will be significantly and adversely affected. Our development of current and future product candidates is subject to the risks of failure and delay inherent in the development of new products and product candidates, including:

In addition, product candidates in later stages of clinical trials may fail to show the desired safety profiles and efficacy results despite having progressed through pre-clinical studies and initial clinical trials. A number of companies in the biotechnology industry have suffered significant setbacks in advanced clinical trials due to lack of efficacy or adverse safety profiles, notwithstanding promising results in earlier trials. Based upon negative or inconclusive results, we may decide, or regulators may require us, to conduct additional clinical trials or pre-clinical studies. In addition, data obtained from trials and studies are susceptible to varying interpretations, and regulators may not interpret our data as favorably as we do, which may delay, limit, or prevent regulatory approval.

Additionally, we have not conducted, nor do we believe we are required to conduct, any head-to-head trials comparing LYR-210 to other approved or experimental treatments for CRS. Any such head-to-head trial, if conducted, may show that LYR-210 is not more effective than any of such other drugs. Material adverse differences in the relative efficacy of LYR-210 could significantly harm the adoption of LYR-210 and our business prospects.

Because of these risks, our research and development efforts may not result in any commercially viable products. If a significant portion of these development efforts are not successfully completed, required regulatory approvals are not obtained, or any approved products are not commercially successful, our business, financial condition, and results of operations may be materially harmed.

Success in pre-clinical or earlier clinical trials may not be indicative of results in future clinical trials.

Success in pre-clinical studies and early clinical trials does not ensure that later clinical trials will generate the same results or otherwise provide adequate data to demonstrate the efficacy and safety of a product candidate. Pre-clinical studies and Phase 1 and Phase 2 clinical trials are primarily designed to test safety, study pharmacokinetics and pharmacodynamics, and understand the side effects of product candidates at various doses and schedules. Success in pre-clinical studies and early clinical trials does not ensure that later, large-scale efficacy trials will be successful nor does it predict final results. Our product candidates may fail to show the desired safety and efficacy in clinical development despite positive results in pre-clinical studies or having successfully advanced through initial clinical trials.

In addition, the design of a clinical trial can determine whether its results will support approval of a product, and flaws in the design of a clinical trial may not become apparent until the clinical trial is well advanced, or later. Many companies in the pharmaceutical and biotechnology industries have suffered significant setbacks in late-stage clinical trials even after achieving promising results in pre-clinical studies and earlier-stage clinical trials. Data obtained from pre-clinical and clinical activities are subject to varying interpretations, which may delay, limit, or prevent regulatory approval. In addition, we may experience regulatory delays or rejections as a result of many factors, including changes in regulatory policy during the period of our product candidate development. Any such delays could negatively impact our business, financial condition, results of operations, and prospects.

If the FDA does not conclude that LYR-210 satisfies the requirements for the Section 505(b)(2) regulatory approval pathway, or if the requirements for LYR-210 under Section 505(b)(2) are not as we expect, the approval pathway for LYR-210 may take significantly longer, cost significantly more, and entail significantly greater complications and risks than anticipated, and in either case may not be successful.

We intend to seek FDA approval for LYR-210 through the Section 505(b)(2) regulatory pathway. The Drug Price Competition and Patent Term Restoration Act of 1984, also known as the Hatch-Waxman Amendments, added Section 505(b)(2) to the Federal Food, Drug and Cosmetic Act, or FDCA. Section 505(b)(2) permits the filing of an NDA where at least some of the information required for approval comes from trials that were not conducted by or for the applicant and for which the applicant has not obtained a right of reference. Section 505(b)(2), if applicable to us under the FDCA, would allow an NDA we submit to the FDA to rely in part on data in the public domain or the FDA’s prior conclusions regarding the safety and effectiveness of approved drugs, which could expedite the development program for our product candidates by potentially decreasing the amount of clinical data that we would need to generate in order to obtain FDA approval. If the FDA does not allow us to pursue the Section 505(b)(2) regulatory pathway as we anticipate, we may need to conduct additional clinical trials, provide additional data and information, and meet additional standards for regulatory approval. If this were to occur, the time and financial resources required to obtain FDA approval for our product candidates, and complications and risks associated with the development of our product candidates, would likely substantially increase. Moreover, inability to pursue the Section 505(b)(2) regulatory pathway could result in competitive products reaching the market before our product candidates, which could impact our competitive position and prospects. Even if we are allowed to pursue the Section 505(b)(2) regulatory pathway, we cannot assure you that our product candidates will receive the requisite approvals for commercialization, or that a competitor would not obtain approval first along with subsequent market exclusivity from the FDA, thereby delaying potential approval of our product.

In addition, the pharmaceutical industry is highly competitive, and Section 505(b)(2) NDAs are subject to special requirements designed to protect the patent rights of sponsors of previously approved drugs that are referenced in a Section 505(b)(2) NDA. These requirements may give rise to patent litigation and mandatory delays in approval of our NDAs for up to 30 months or longer depending on the outcome of any litigation. It is not uncommon for a manufacturer of an approved product to file a citizen petition with the FDA seeking to delay approval of, or impose additional approval requirements for, pending competing products. If successful, such petitions can significantly delay, or even prevent, the approval of the new product. However, even if the FDA ultimately denies such a petition, the FDA may substantially delay approval while it considers and responds to the petition. In addition, even if we are able to utilize the Section 505(b)(2) regulatory pathway, there is no guarantee this would ultimately lead to accelerated product development or earlier approval.

Moreover, even if our product candidates are approved under Section 505(b)(2), the approval may be subject to limitations on the indicated uses for which the products may be marketed or to other conditions of approval, or may contain requirements for costly post-marketing testing and surveillance to monitor the safety or efficacy of the products.

We have conducted, are conducting, and, in the future, may conduct clinical trials for our product candidates in sites outside the United States, and the FDA may not accept data from trials conducted in foreign locations.

We have conducted and are conducting clinical trials for LYR-210 outside the United States, primarily in Europe, and we may in the future choose to conduct other clinical trials outside the United States for LYR-210, or any of our other future product candidates. Although the FDA may accept data from clinical trials conducted outside the United States, acceptance of this data is subject to certain conditions imposed by the FDA. For example, the clinical trial must be well designed and conducted and performed by qualified investigators in accordance with GCP, including review and approval by an IEC and receipt of informed consent from subjects. In general, the patient population for any clinical trials conducted outside of the United States must be representative of the population for which we intend to seek approval for the product in the United States. In addition, while these clinical trials are subject to the applicable local laws, FDA acceptance of the data will be dependent upon its determination that the trials also complied with all applicable U.S. laws and regulations. There can be no assurance the FDA will accept data from trials conducted outside of the United States. If the FDA does not accept the data from our clinical trials of our product candidates, it would likely result in the need for additional trials, which would be costly and time-consuming and delay or permanently halt our development of our product candidates.

In addition, there are risks inherent in conducting clinical trials in multiple jurisdictions, inside and outside of the United States, such as:

Interim 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 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. Interim or preliminary data 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. Differences between interim or preliminary data and final data could significantly harm our business prospects.

LYR-210 will be regulated as a drug-device combination products, which may result in additional regulatory and other risks.

LYR-210 is a drug-device combination products. We may experience delays in obtaining regulatory approval of LYR-210 given the increased complexity of the review process when approval of a combination product is sought under a single marketing application. LYR-210 will be regulated as drug-device combination products, which require coordination within the FDA and similar foreign regulatory agencies for review of the product candidates’ device and drug components. The determination whether a combination product requires a single marketing application or two separate marketing applications for each component is made by the FDA on a case-by-case basis. Although we believe a single marketing application for the approval of a combination product would be successful, there can be no assurance that the FDA will not determine that separate marketing applications are necessary. This determination could significantly increase the resources and time required to bring a particular combination product to market. Although the FDA and similar foreign regulatory agencies have systems in place for the review and approval of combination products such as ours, we may experience delays in the development and commercialization of our product candidates due to regulatory timing constraints and uncertainties in the product development and approval process, as well as coordination between two different centers within FDA responsible for review of the different components of the combination product.

Failure to successfully develop or supply the device component, delays in or failure of the studies conducted by us, our collaborators, or third-party providers, or failure of our Company, our collaborators, or third-party providers to obtain or maintain regulatory approval or clearance of the device component of LYR-210, as appropriate, could result in increased development costs, delays in or failure to obtain regulatory approval, and associated delays in these product candidates reaching the market. Further, failure to successfully develop or supply the device, or to gain or maintain its approval, could adversely affect sales of LYR-210.

If we fail to obtain the necessary U.S. regulatory approvals to commercialize any product candidate, we will not be able to generate revenue in the U.S. market.

We cannot assure you that we will receive the approvals necessary to commercialize our product candidates, or any product candidate we acquire or develop in the future. We will need FDA approval to commercialize our product candidates in the United States and approvals from equivalent regulatory authorities in foreign jurisdictions to commercialize our product candidates in those jurisdictions. Satisfaction of the FDA’s regulatory requirements typically takes many years, depends upon the type, complexity, and novelty of the product candidate, and requires substantial resources for research, development, and testing. We cannot predict whether our research and clinical efforts will result in drugs that the FDA will determine are safe for humans and effective for their intended uses. The FDA has substantial discretion in the drug approval process and may require us to conduct additional pre-clinical and clinical testing, perform post-marketing studies, address manufacturing concerns, or otherwise limit or impose conditions on any approval we obtain. The approval process may also be delayed by changes in government regulation, the impact of COVID-19, future legislation or administrative action, or changes in FDA policy that occur prior to or during our regulatory review. Delays in obtaining regulatory approvals may:

Even if we receive approval of an NDA or comparable foreign regulatory filing for our product candidates, the FDA or the applicable foreign regulatory body may approve our product candidates for a more limited indication than we originally requested, and the FDA may not approve the labeling that we believe is necessary or desirable for the successful commercialization of our product candidates.

Even if we comply with all FDA requests, the FDA may ultimately reject one or more of our NDAs. We cannot be sure that we will ever obtain regulatory clearance for our product candidates. Failure to obtain FDA approval of our product candidates will severely undermine our business by leaving us without a commercially available product, and therefore without any source of revenues, until another product candidate can be developed or obtained and ultimately approved. There is no guarantee that we will ever be able to develop or acquire another product candidate or that we will be able to obtain FDA approval to commercialize such product candidate.

Even if we obtain FDA approval for our product candidates in the United States, we may never obtain approval for or commercialize them in any other jurisdiction, which would limit our ability to realize their full market potential.

We intend, either on our own or through collaborations or partnerships, to market our products in international markets. In order to market any products in the European Union and many other foreign jurisdictions, we must establish and comply with numerous and varying regulatory requirements on a country-by-country basis regarding safety and efficacy. Approval by the FDA in the United States does not ensure approval by regulatory authorities in other countries or jurisdictions. However, the failure to obtain approval in one jurisdiction may negatively impact our ability to obtain approval elsewhere. In addition, clinical trials conducted in one country may not be accepted by regulatory authorities in other countries, and regulatory approval in one country does not guarantee regulatory approval in any other country.

Approval processes vary among countries and can involve additional product testing and validation and additional administrative review periods. Seeking foreign regulatory approval could result in difficulties and increased costs for us and require additional pre-clinical studies or clinical trials which could be costly and time consuming. Regulatory requirements can vary widely from country to country and could delay or prevent the introduction of our products in those countries. We do not have any product candidates approved for sale in any jurisdiction, including in international markets, and we do not have experience in obtaining regulatory approval in international markets. If we fail to comply with regulatory requirements in international markets or to obtain and maintain required approvals, or if regulatory approvals in international markets are delayed, our target market will be reduced and our ability to realize the full market potential of any product we develop will be unrealized.

The regulatory approval processes of the FDA and comparable foreign authorities are lengthy, costly, time-consuming, and inherently unpredictable, and if we are ultimately unable to obtain regulatory approval for our product candidates, our business will be substantially harmed. We cannot predict when or if, and in which territories, we, or any of our potential future collaborators, will obtain marketing approval to commercialize a product candidate.

The time required to obtain approval by the FDA and comparable foreign authorities is unpredictable but typically takes many years following the commencement of clinical trials and depends upon numerous factors, including substantial discretion of 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. We have not obtained regulatory approval for any product candidate and it is possible that neither LYR-210, nor any future product candidates we may seek to develop in the future will ever obtain regulatory approval. Neither we nor any future collaborator is permitted to market any of our product candidates in the United States until we receive regulatory approval of an NDA from the FDA. It is possible that the FDA may refuse to accept for substantive review any NDAs that we submit for our product candidates or may conclude after review of our data that our application is insufficient to obtain marketing approval of our product candidates.

Prior to obtaining approval to commercialize a product candidate in the United States or abroad, we or our collaborators must demonstrate with substantial evidence from well-controlled clinical trials, and to the satisfaction of the FDA or foreign regulatory agencies, that such product candidates are safe and effective for their intended uses in patients. Results from non-clinical studies and clinical trials can be interpreted in different ways. Even if we believe the non-clinical or clinical data for our product candidates are promising, such data may not be sufficient to support approval by the FDA and other regulatory authorities. The FDA may also require us to conduct additional pre-clinical studies or clinical trials for our product candidates either prior to or post-approval, or it may object to elements of our clinical development program. Depending on the extent of these or any other FDA-required studies, approval of any NDA or other application that we submit may be delayed by several years, or may require us to expend significantly more resources than we have available.

Of the large number of potential products in development, only a small percentage successfully complete the FDA or foreign regulatory approval processes and are commercialized. The lengthy and costly approval process as well as the unpredictability of future clinical trial results may result in our failing to obtain regulatory approval to market our product candidates, which would significantly harm our business, results of operations, and prospects.

Moreover, principal investigators for our clinical trials may serve as scientific advisors or consultants to us from time to time and receive compensation in connection with such services. Under certain circumstances, we may be required to report some of these relationships to the FDA or comparable foreign regulatory authorities. The FDA or comparable foreign regulatory authorities may conclude that a financial relationship between us and a principal investigator has created a conflict of interest or otherwise affected interpretation of the study. The FDA or comparable foreign regulatory authorities may therefore question the integrity of the data generated at the applicable clinical trial site and the utility of the clinical trial itself may be jeopardized. This could result in a delay in approval, or rejection, of our marketing applications by the FDA or comparable foreign regulatory authorities, as the case may be, and may ultimately lead to the denial of marketing approval of one or more of our product candidates.

Separately, in response to the COVID-19 pandemic the FDA postponed most inspections of domestic and foreign manufacturing facilities at various points. Even though the FDA has since resumed standard inspection operations of domestic facilities where feasible, the FDA has continued to monitor and implement changes to its inspectional activities to ensure the safety of its employees and those of the firms it regulates as it adapts any resurgence of the virus or emergence of new variants may lead to further inspectional delays. Regulatory authorities outside the United States may adopt similar restrictions or other policy measures in response to future COVID-19 related concerns, including providing guidance regarding the conduct of clinical trials. If global health concerns continue to prevent the FDA or other regulatory authorities from conducting their regular inspections, reviews, or other regulatory activities, it could significantly impact the ability of the FDA or other regulatory authorities to timely review and process our regulatory submissions, which could have a material adverse effect on our business.

If we encounter delays or difficulties enrolling patients in our clinical trials, our clinical development activities and receipt of regulatory approvals could be delayed or otherwise adversely affected.

The timely completion of clinical trials in accordance with their protocols depends, among other things, on our ability to enroll a sufficient number of patients who remain in the trial until its conclusion. For example, we were unable to enroll patients in our Phase 2 LANTERN clinical trial in the United States from whom we intended to collect certain additional pharmacokinetic data due to the COVID-19 pandemic, and, as a result, we initiated a separate characterization study in September 2020 as a follow-on to our Phase 2 LANTERN clinical trial in order to collect such data. Trials may be subject to delays as a result of patient enrollment taking longer than anticipated or patient withdrawal. We may encounter delays in enrolling, or be unable to enroll, a sufficient number of patients to complete any of our clinical trials, and even once enrolled we may be unable to retain a sufficient number of patients to complete any of our trials. We may not be able to initiate or continue clinical trials for our product candidates if we are unable to locate and enroll a sufficient number of eligible patients to participate in these trials as required by the FDA or similar regulatory authorities outside the United States. We cannot predict how successful we will be at enrolling subjects in future clinical trials. The enrollment of patients depends on many factors, including:

In addition, our clinical trials will compete with other clinical trials for product candidates that are in the same therapeutic areas as our product candidates, and this competition will reduce the number and types of patients available to us, because some patients who might have opted to enroll in our trials may instead opt to enroll in a trial being conducted by one of our competitors. Since the number of qualified clinical investigators is limited, we expect to conduct some of our clinical trials at the same clinical trial sites that some of our competitors use, which will reduce the number of patients who are available for our clinical trials in such clinical trial site.

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 LYR-210 and/or any other future product candidates, or could render further development impossible.

Our product candidates may cause serious adverse events or undesirable side effects including injury and death or have other properties which may delay or prevent their regulatory approval, limit the commercial profile of an approved label, or result in significant negative consequences following marketing approval. If any of our product candidates receives marketing approval and we, or others, later discover that the drug is less effective than previously believed or causes undesirable side effects that were not previously identified, our ability, or that of any potential future collaborators, to market the drug could be compromised.

Before obtaining regulatory approvals for the commercial sale of our product candidates, we must demonstrate through lengthy, complex, and expensive pre-clinical testing and clinical trials that our product candidates are both safe and effective for use in each target indication, and failures can occur at any stage of testing. Clinical trials often fail to demonstrate safety and efficacy of the product candidate studied for the target indication. Serious adverse events, or SAEs, or undesirable side effects caused by our product candidates could cause us or regulatory authorities to interrupt, delay, or halt clinical trials and could result in a more restrictive label or the delay or denial of regulatory approval by the FDA or other comparable foreign authorities. Results of our clinical trials or pre-clinical studies could reveal a high and unacceptable severity and prevalence of side effects, toxicities, or unexpected characteristics, including death. For example, in our Phase 1 clinical trial for our most advanced product candidate, LYR-210, there was one SAE in the active group (acute myocardial infarction), which was considered not related to LYR-210.

In addition, subjects treated with LYR-210 have experienced adverse events, including epistaxis, rhinitis, rhinorrhea, facial pain, nasopharyngitis, sinusitis, upper respiratory tract infection, procedural headache, nasal discomfort, and nasal odor, among others. In our Phase 2 LANTERN clinical trial, treatment-related adverse events were reported in 16 patients, and all treatment-related adverse events except one (increased viscosity of upper respiratory secretion) were mild or moderate in nature. In addition, there was one patient in the LYR-210 (2,500 µg) group who had a serious adverse event of acarodermatitis in our Phase 2 LANTERN clinical trial, which was deemed to be not related to treatment. In the 24-week treatment phase of the Phase 3 ENLIGHTEN 1 clinical trial, the most commonly reported adverse events in the study population were epistaxis, nasal odor, upper respiratory tract infection and sinusitis.

If unacceptable side effects arise in the development of our product candidates, we, the FDA, the IRBs at the institutions in which our studies are conducted, could materially modify, suspend, or terminate our clinical trials or the FDA or comparable foreign regulatory authorities could order us to cease pre-clinical studies or clinical trials, require us to conduct additional animal or human studies regarding the safety and efficacy of our product candidates which we have not planned or anticipated, or deny approval of our product candidates for any or all targeted indications. Many product candidates that initially showed promise in early-stage testing have later been found to cause side effects that prevented further development of the product candidate. Treatment-related side effects could also affect patient recruitment or the ability of enrolled patients to complete the trial or result in potential product liability claims. In addition, these side effects may not be appropriately recognized or managed by the treating medical staff. We have historically trained and may in the future have to train medical personnel using our product candidates to understand the side effect profiles for our clinical trials and upon any commercialization of any of our product candidates. Inadequate training in recognizing or managing the potential side effects of our product candidates could result in patient injury or death. Any of these occurrences may harm our business, financial condition, and prospects significantly.

If any of our product candidates receives marketing approval, and we or others later identify undesirable side effects caused by any such product, including during any long-term follow-up observation period recommended or required for patients who receive treatment using our products, a number of potentially significant negative consequences could result, including:

There can be no assurance that we will resolve any issues related to any product-related adverse events to the satisfaction of the FDA or any regulatory agency in a timely manner or at all. Any of these events could prevent us from achieving or maintaining market acceptance of the particular product candidate, if approved, and could significantly harm our business, results of operations, and prospects.

Our employees and independent contractors, including principal investigators, CROs, consultants, vendors, and any third parties we may engage in connection with research, development, regulatory, manufacturing, quality assurance, and other pharmaceutical functions and commercialization may engage in misconduct or other improper activities, including noncompliance with regulatory standards and requirements, which could have a material adverse effect on our business.

Misconduct by our employees and independent contractors, including principal investigators, CROs, consultants, vendors, and any third parties we may engage in connection with research, development, regulatory, manufacturing, quality assurance, and other pharmaceutical functions and commercialization, could include intentional, reckless, or negligent conduct or unauthorized activities that violate: (i) the laws and regulations of the FDA, the European Medicines Agency, or the EMA, and other similar regulatory authorities, including those laws that require the reporting of true, complete, and accurate information to such authorities; (ii) manufacturing standards; or (iii) data privacy, security, fraud and abuse, and other healthcare laws and regulations. Specifically, sales, marketing, and business arrangements in the healthcare industry are subject to extensive laws and regulations intended to prevent fraud, misconduct, kickbacks, self-dealing, and other abusive practices. These laws and regulations may restrict or prohibit a wide range of pricing, discounting, marketing and promotion, sales commission, customer incentive programs, and other business arrangements. Activities subject to these laws could also involve the improper use or misrepresentation of information obtained in the course of pre-clinical studies or clinical trials, creation of fraudulent data in pre-clinical studies or clinical trials, or illegal misappropriation of drug product, which could result in regulatory sanctions and cause serious harm to our reputation. It is not always possible to identify and deter misconduct by employees and other third parties, 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 comply with such laws 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 significant civil, criminal, and administrative penalties, damages, monetary fines, disgorgements, possible exclusion from participation in Medicare, Medicaid, other U.S. federal healthcare programs or healthcare programs in other jurisdictions, integrity oversight and reporting obligations to resolve allegations of non-compliance, individual imprisonment, other sanctions, contractual damages, reputational harm, diminished profits and future earnings, and curtailment of our operations.

Our computer systems, as well as those of our CROs and other contractors, vendors, suppliers, and consultants, are vulnerable to damage from computer viruses, unauthorized access, natural disasters (including the impacts of climate change), international terrorism and conflicts, and telecommunication and electrical failures. If such an event were to occur and cause interruptions in our operations, it could result in a material disruption of our product candidate development programs and our business. For example, the loss of pre-clinical studies or clinical trial data from completed, ongoing, or planned trials could result in delays in our regulatory approval efforts and significantly increase our costs to recover or reproduce the data. To the extent that any disruption or security breach were to result in a loss of or damage to our data or applications, or inappropriate disclosure of personal, confidential, or proprietary information, we could incur liability and the further development of LYR-210, or any other product candidate could be delayed.

In the ordinary course of our business, we directly or indirectly collect and store sensitive data, including intellectual property, confidential information, pre-clinical and clinical trial data, proprietary business information, personal data, and personally identifiable health information of our clinical trial subjects and employees, in our data centers and on our networks, or on those of third parties. The secure processing, maintenance, and transmission of this information is critical to our operations. Despite our security measures, our information technology and infrastructure has been and, from time to time, may be vulnerable to attacks by hackers or internal bad actors, or breached due to employee error, a technical vulnerability, malfeasance, or other disruptions. For example, companies have experienced an increase in phishing and social engineering attacks from third parties in connection with COVID-19. Although, to our knowledge, we have not experienced any material security breach, any such breach could compromise our networks and the information stored there could be accessed, publicly disclosed, lost, or stolen. Any such access, disclosure, or other loss of information could result in legal claims or proceedings (including class actions), liability under laws that protect the

privacy of personal information, or significant regulatory penalties, and such an event could disrupt our operations, damage our reputation, and cause a loss of confidence in us and our ability to conduct clinical trials, which could adversely affect our business reputation and delay our clinical development of our product candidates.

Product candidates employing our technology will be subject to extensive and rigorous domestic government regulation including regulation by the FDA, the Centers for Medicare and Medicaid Services, or CMS, other divisions of the United States Department of Health and Human Services, the United States Department of Justice, state and local governments, and their respective equivalents outside of the United States. The FDA regulates the research, development, pre-clinical and clinical testing, manufacture, safety, effectiveness, record-keeping, reporting, labeling, packaging, storage, approval, advertising, promotion, sale, distribution, import, and export of pharmaceutical products. If products employing our technologies are marketed abroad, they will also be subject to extensive regulation by foreign governments, whether or not they have obtained FDA approval for a given product and its uses. Such foreign regulation may be equally or more demanding than corresponding United States regulation.

Government regulation substantially increases the cost and risk of researching, developing, manufacturing, and selling our products. The regulatory review and approval process, which includes pre-clinical testing and clinical trials of each product candidate, is lengthy, expensive, and uncertain. We or our collaborators must obtain and maintain regulatory authorization to conduct pre-clinical studies and clinical trials. We or our collaborators must obtain regulatory approval for each product we intend to market, and the manufacturing facilities used for the products must be inspected and meet legal requirements. Securing regulatory approval requires the submission of extensive pre-clinical and clinical data and other supporting information for each proposed therapeutic indication in order to establish the product’s safety and efficacy, potency, and purity, for each intended use. The development and approval process takes many years, requires substantial resources, and may never lead to the approval of a product.

Even if we are able to obtain regulatory approval for a particular product, the approval may limit the indicated medical uses for the product, may otherwise limit our ability to promote, sell, and distribute the product, may require that we conduct costly post-marketing surveillance, and/or may require that we conduct ongoing post-marketing studies. Material changes to an approved product, such as, for example, manufacturing changes or revised labeling, may require further regulatory review and approval. Once obtained, any approvals may be withdrawn, including, for example, if there is a later discovery of previously unknown problems with the product, such as a previously unknown safety issue.

If we, our collaborators, consultants, contract manufacturers, CROs, or other vendors fail to comply with applicable regulatory requirements at any stage during the regulatory process, such noncompliance could result in, among other things, delays in the approval of applications or supplements to approved applications; refusal of a regulatory authority, including the FDA, to review pending market approval applications or supplements to approved applications; warning letters; fines; import and/or export restrictions; product recalls or seizures; injunctions; total or partial suspension of production; civil penalties; withdrawals of previously approved marketing applications or licenses; recommendations by the FDA or other regulatory authorities against governmental contracts; and/or criminal prosecutions.

Enacted and future healthcare legislation may increase the difficulty and cost for us to obtain marketing approval of and commercialize our product candidates and could adversely affect our business.

In the United States, the EU, and other jurisdictions, there have been, and we expect there will continue to be, a number of legislative and regulatory changes and proposed changes to the healthcare system that could prevent or delay marketing approval of our products in development, restrict or regulate post-approval activities involving any product candidates for which we obtain marketing approval, impact pricing and reimbursement, and impact our ability to sell any such products profitably. In particular, there have been and continue to be a number of initiatives at the U.S. federal and state levels that seek to reduce healthcare costs and improve the quality of healthcare. In addition, new regulations are frequently adopted and interpretations of existing healthcare statutes may change over time.

For instance, in August 2022, the Inflation Reduction Act of 2022, or IRA, was signed into law. The IRA includes several provisions that may impact our business to varying degrees, including provisions that establish a $2,000 out-of-pocket cap for Medicare Part D beneficiaries, impose new manufacturer financial liability on many drugs reimbursed under Medicare Part D, allow the U.S. government to negotiate Medicare Part B and Part D pricing for certain high-cost drugs and biologics without generic or biosimilar competition, and require companies to pay rebates to Medicare for drug prices that increase faster than inflation. The IRA permits the Secretary of the Department of Health and Human Services (“HHS”) to implement many of these provisions through guidance, as opposed to regulation, for the initial years. HHS has and will continue to issue and update guidance as these programs

are implemented. On August 29, 2023, HHS announced the list of the first ten drugs that will be subject to price negotiations, although the Medicare drug price negotiation program is currently subject to legal challenges. For that and other reasons, it is currently unclear how the IRA will be effectuated. In addition, in response to the Biden administration’s October 2022 executive order, on February 14, 2023, HHS released a report outlining three new models for testing by the Centers for Medicare and Medicaid Services (“CMS”) Innovation Center which will be evaluated on their ability to lower the cost of drugs, promote accessibility, and improve quality of care. It is unclear whether the models will be utilized in any health reform measures in the future.

In March 2010, the Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act, or collectively the ACA, was enacted, which substantially changed the way healthcare is financed by both governmental and private insurers. Among the provisions of the ACA, those of greatest importance to the pharmaceutical and biotechnology industries include the following:

Since its enactment, there have been judicial and Congressional challenges to certain aspects of the ACA, and we expect there will be additional challenges and amendments to the ACA in the future. On March 2, 2020, the U.S. Supreme Court granted the petitions for writs of certiorari to review the constitutionality of the ACA, although it is unclear when or how the Supreme Court will rule. It is also unclear how other efforts to challenge, repeal, or replace the ACA will impact the law and may impact our business or financial condition.

In addition, other legislative changes have been proposed and adopted in the United States since the ACA was enacted. In August 2011, the Budget Control Act of 2011 resulted in aggregate reductions of Medicare payments to providers of 2% per fiscal year, which went into effect in April 2013 and, due to subsequent legislative amendments to the statute, will remain in effect through 2030, unless additional action is taken by Congress. In January 2013, the American Taxpayer Relief Act of 2012 was signed into law, which, among other things, further reduced Medicare payments to several types of providers, including hospitals, imaging centers, and cancer treatment centers, and increased the statute of limitations period for the government to recover overpayments to providers from three to five years. These new laws or any other similar laws introduced in the future may result in additional reductions in Medicare and other healthcare funding, which could negatively affect our customers and accordingly, our financial operations.

Moreover, payment methodologies may be subject to changes in healthcare legislation and regulatory initiatives. For example, CMS may develop new payment and delivery models, such as bundled payment models. In addition, recently there has been heightened governmental scrutiny over the manner in which manufacturers set prices for their marketed products, which has resulted in several U.S. Congressional inquiries and proposed and enacted federal legislation designed to, among other things, bring more transparency to drug pricing, reduce the cost of prescription drugs under Medicare, and review the relationship between pricing and manufacturer patient programs. While any proposed measures will require authorization through additional legislation to become effective, Congress has indicated that it will continue to seek new legislative and/or administrative measures to control drug costs. We expect that additional U.S. federal healthcare reform measures will be adopted in the future, any of which could limit the amounts that the U.S. federal government will pay for healthcare products and services, which could result in reduced demand for our product candidates or additional pricing pressures.

Individual states in the United States have also increasingly passed legislation and implemented regulations designed to control pharmaceutical and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access, and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing. Legally-mandated price controls on payment amounts by third-party payors or other restrictions could harm our business, results of operations, financial condition, and prospects. In addition, regional healthcare authorities and individual hospitals are increasingly using bidding procedures to determine what pharmaceutical products and which suppliers will be included in their prescription drug and other healthcare programs. This could reduce the ultimate demand for our product candidates or put pressure on our product pricing.

In the EU, similar political, economic, and regulatory developments may affect our ability to profitably commercialize our product candidates, if approved. In addition to continuing pressure on prices and cost containment measures, legislative developments at the EU or member state level may result in significant additional requirements or obstacles that may increase our operating costs. The delivery of healthcare in the EU, including the establishment and operation of health services and the pricing and reimbursement of medicines, is almost exclusively a matter for national, rather than EU, law and policy. National governments and health service providers have different priorities and approaches to the delivery of healthcare and the pricing and reimbursement of products in that context. In general, however, the healthcare budgetary constraints in most EU member states have resulted in restrictions on the pricing and reimbursement of medicines by relevant health service providers. Coupled with ever-increasing EU and national regulatory burdens on those wishing to develop and market products, this could prevent or delay marketing approval of our product candidates, restrict or regulate post-approval activities, and affect our ability to commercialize our product candidates, if approved.

In markets outside of the United States and the EU, reimbursement and healthcare payment systems vary significantly by country, and many countries have instituted price ceilings on specific products and therapies.

此外，还提出了立法和监管提案，以扩大批准后要求并限制药品的销售和促销活动。我们无法确定是否会颁布额外的立法变更，或者FDA的法规、指南或解释是否会改变，或者这些变更对我们候选产品的上市批准（如果有的话）可能会产生什么影响。此外，美国国会对FDA批准过程加强审查可能会严重推迟或阻止上市批准，并使我们面临更严格的产品标签和上市后测试和其他要求。

我们无法预测美国、欧盟或任何其他司法管辖区未来的立法或行政行动可能产生的政府监管的可能性、性质或程度。如果我们或我们可能聘请的任何第三方行动缓慢或无法适应现有要求的变化或新要求或政策的采用，或者如果我们或此类第三方无法维持监管合规性，我们的候选产品可能会失去任何可能已获得的监管批准，并且我们可能无法实现或维持盈利能力。

即使我们的候选产品获得了监管机构的批准，我们也将受到持续的监管义务和持续的监管审查的约束，这可能会导致大量额外费用，如果我们没有遵守监管要求或我们的候选产品出现了意想不到的问题，我们可能会受到惩罚。

我们获得上市批准的任何候选产品，以及该产品的制造流程、批准后的临床数据、标签、包装、分销、不良事件报告、储存、记录保存、出口、进口以及广告和促销活动等，都将受到FDA、EMA和其他监管机构的广泛和持续的要求和审查。这些要求包括提交安全和其他上市后资讯和报告、机构注册和药品上市要求、继续遵守与制造、质量控制、品质保证和相应记录和文件维护相关的cGMP要求、关于向医生分发样品的要求，以及我们在批准后进行的任何临床试验的记录保存和GCP要求。此外，经批准的保密协定的赞助商还应接受定期检查和FDA的其他监督和报告

义务，包括监测和报告不良事件和其他信息的义务，例如产品不符合NDA中的规范。NDA申办者必须提交新的或补充申请，并获得FDA批准对已批准的产品、产品标签或制造工艺的某些变更。申请持有人还必须向FDA提交广告和其他宣传材料，并报告正在进行的临床试验。FDA可能要求更改已批准药品的标签，并要求申办者进行上市后研究。因此，我们和与我们合作的其他人必须继续在监管合规的所有领域（包括制造、生产和质量）投入时间、金钱和精力。

即使候选产品获得了上市批准，该批准也可能受到对产品上市指定用途的限制或批准条件的限制，包括实施REMS的要求，其中可能包括对药物指南、医生沟通计划或确保安全使用的其他要素的要求，例如限制的分销方法、患者登记、和其他风险缓解工具。如果我们的任何候选产品获得营销批准，随附标签可能会限制我们产品的批准使用，从而限制产品的销售。

FDA还可能要求进行昂贵的上市后研究或临床试验和监测，以监测我们批准产品的安全性或有效性。此外，广告和宣传材料必须遵守FDA规则以及其他可能适用的联邦和州法律。FDA严格监管药物的批准后营销和推广，以确保药物仅针对批准的适应症并按照批准的标签规定进行销售。FDA对制造商关于标签外使用的沟通实施了严格限制，如果我们在其批准的适应症之外销售我们的产品，我们可能会受到标签外营销的执法行动。违反FDA有关处方药推广的限制也可能导致调查，指控其违反联邦和州医疗保健欺诈和滥用法以及州消费者保护法。

向医生分发产品样本必须符合FDCA的要求。NDA申办者必须获得FDA对产品、制造和标签变更的批准，具体取决于变更的性质。根据具体情况，未能满足这些批准后要求可能会导致刑事起诉、罚款、禁令、永久禁令的同意令、召回或扣押产品、完全或部分暂停生产、拒绝或撤回上市前产品批准，或拒绝允许我们签订供应合同，包括政府合同。

此外，后来发现我们的产品或制造过程之前未知的不良事件或其他问题，包括意外严重程度或频率的不良事件或制造过程，或未能遵守监管要求，可能会产生各种结果，包括：

任何政府对涉嫌违法行为的调查都可能需要我们花费大量时间和资源来应对，并可能会产生负面宣传。任何不遵守持续监管要求的行为都可能会对我们商业化和创收的能力产生重大不利影响。如果实施监管制裁或拒绝或撤回监管批准，我们公司的价值和经营运绩将受到不利影响。

FDA的政策可能会发生变化，并且可能会颁布额外的政府法规，这可能会阻止、限制或推迟监管机构对LIR-210和/或任何其他未来候选产品的批准。如果我们行动缓慢或无法适应现有要求的变化或新要求或政策的采用，或者如果我们无法保持监管合规性，我们可能会失去我们可能获得的任何营销批准，这将对我们的业务、前景以及实现或维持盈利能力产生不利影响。

我们也无法预测美国或国外未来的立法或行政或行政行动可能产生的政府监管的可能性、性质或程度。此外，2024年7月美国最高法院的三项裁决可能会导致针对监管机构的诉讼增加，这可能会带来不确定性，从而对我们的业务产生负面影响。第一个裁决推翻了既定的先例，即法院必须服从监管机构对模棱两可的法定语言的解释。第二个决定推翻了监管机构在行政诉讼中实施民事处罚的能力。第三项裁决延长了诉讼时效，各实体可以在该时效内对机关的行为提出质疑。这些案件可能导致行业对监管机构提起更多诉讼，并影响这些机构选择采取执法和合规行动的方式。然而，这些裁决的具体和持久影响尚不清楚，这些裁决在不同的司法区和巡回法庭可能有所不同。我们也无法预测FDA和美国证券交易委员会的法规、政策和决定可能在多大程度上受到越来越多的法律挑战、延误和变化。

FDA和其他政府机构资金的变化可能会阻碍他们雇用和留住关键领导和其他人员的能力，或者以其他方式阻止新产品和服务及时开发、批准或商业化，甚至根本阻止新产品和服务的开发、批准或商业化，这可能会对我们的业务产生负面影响。

FDA审查和批准新产品的能力可能受到多种因素的影响，包括政府预算和资金水平、雇用和保留关键人员并接受用户费用支付的能力、法定、监管和政策变化，以及其他可能影响政府机构履行日常职能能力的事件。因此，近年来该机构的平均审查时间一直在波动。此外，政府对资助研发活动的其他政府机构的资助也受到政治进程的影响，政治进程本质上是不稳定且不可预测的。

FDA和其他机构的混乱也可能会减缓新药经过必要政府机构审查和/或批准所需的时间，这将对我们的业务产生不利影响。例如，在过去的几年里，美国政府多次关门，FDA等某些监管机构不得不让关键员工休假并停止关键活动。

如果政府长期关闭，或者全球健康问题阻止FDA或其他监管机构进行定期检查、审查或其他监管活动，可能会严重影响FDA或其他监管机构及时审查和处理我们监管提交的能力，这可能会对我们的业务产生重大不利影响。此外，未来的政府关闭或延误可能会影响我们进入公开市场和获得必要资本以适当资本化和继续运营的能力。

我们的业务运营以及与调查人员、医疗保健专业人员、顾问、第三方付款人、患者组织和客户的当前和未来关系将受到适用的医疗保健监管法的约束，这可能会使我们面临处罚。

我们的业务运营以及当前和未来与调查人员、医疗保健专业人员、顾问、第三方付款人、患者组织和客户的安排可能会使我们面临广泛适用的欺诈和滥用以及其他医疗保健法律和法规的风险。这些法律可能会限制我们开展运营所通过的业务或财务安排和关系，包括我们如何研究、营销、销售和分销我们的候选产品（如果获得批准）。此类法律包括：

确保我们的内部运营和未来与第三方的业务安排符合适用的医疗保健法律和法规将涉及巨额成本。政府当局可能会得出结论，我们的商业实践，包括我们与医生和其他医疗保健提供者的关系（其中一些人以提供咨询服务的股票期权形式获得补偿）可能不符合当前或未来的法规、法规、机构指南或涉及适用欺诈和滥用的案例法或其他医疗保健法律和法规。如果我们的运营被发现违反了上述任何法律或可能适用于我们的任何其他政府法律和法规，我们可能会受到重大影响

处罚，包括民事、刑事和行政处罚、损害赔偿、罚款、被排除在政府资助的医疗保健计划之外，如Medicare和Medicaid或其他国家或司法管辖区的类似计划，诚信监督和报告义务，以解决有关违规、交还、个人监禁、合同损害、声誉损害、利润减少以及削减或重组我们业务的指控。如果我们预期与之开展业务的任何医生或其他提供者或实体被发现不遵守适用法律，他们可能会受到刑事、民事或行政制裁，包括被排除在政府资助的医疗保健计划和监禁之外，这可能会影响我们的业务运营能力。此外，防御任何此类操作都可能成本高昂、耗时长，并且可能需要大量的人力资源。因此，即使我们成功地抵御了任何可能对我们提起的此类诉讼，我们的业务也可能受到损害。

如果发生信息技术系统故障、网络攻击、数据安全事件或网络安全缺陷，我们的业务、财务状况和运营结果可能会受到影响。

我们依靠我们的资讯技术系统和第三方服务提供商的系统进行对我们业务至关重要的内部和外部操作。我们面临许多不断变化的网路安全风险，这些风险威胁到我们和第三方提供商维护的资讯技术系统和数据的机密性、完整性和可用性，包括个人资讯、临床试验数据、机密和专有知识产权、金融资讯、商业秘密和其他商业资讯。我们的资讯技术系统和数据，以及我们的第三方服务提供商、承包商和顾问的系统和数据容易受到电脑病毒和恶意软体(如勒索软体)、错误、错误配置、恶意代码、自然灾害、恐怖主义、战争、电信和电气故障、黑客、网路攻击、网路钓鱼攻击和其他社会工程计划、员工窃盗或滥用、人为错误、欺诈、拒绝服务攻击或服务降级、复杂的民族国家和民族国家支持的行为者或组织内部人员或有权访问组织内部系统的人员的未经授权访问或使用的攻击、中断和破坏。对资讯技术系统和数据的攻击在频率、持续性、复杂性和强度方面都在增加--包括利用人工智慧进行的攻击--而且是由动机和专业知识广泛的复杂和有组织的团体和个人实施的。此外，由于用于未经授权访问或破坏系统和数据的技术经常变化，而且通常在针对目标启动之前不被识别，因此我们可能无法预测这些技术或实施足够的预防措施。我们还可能遇到可能在很长一段时间内未被发现的安全事件。即使被发现，我们也可能无法充分调查或补救事件，因为攻击者越来越多地使用旨在规避控制、避免检测以及移除或混淆法医证据的工具和技术。

也不能保证我们的网路安全风险管理计划和流程，包括我们的政策、控制或程式，将在保护我们的资讯技术系统和数据方面得到充分实施、遵守或有效。虽然我们不认为我们经历过任何重大的系统故障或事件，但我们和我们的第三方提供商不时成为网路安全攻击的目标，我们预计随著网路安全威胁的复杂性和数量迅速演变，攻击将继续下去。虽然我们不认为到目前为止任何事件对我们的运营或财务业绩产生了实质性影响，但我们不能保证未来不会发生重大事件。如果发生这样的事件并导致我们的运营中断，可能会导致我们的计划受到实质性的破坏。例如，我们候选产品的临床试验数据的丢失可能会导致我们的监管审批工作延迟，并显著增加我们恢复或复制数据的成本。我们还可能招致责任，我们候选产品的进一步开发可能会被推迟。此外，对我们的资讯技术系统或数据的可用性、完整性或保密性的任何不利影响都可能使我们面临法律索赔或诉讼(包括集体诉讼)、执法诉讼和监管当局的调查，并可能导致处罚、罚款和重大法律责任。我们还可能遇到负面声誉影响，导致信任受到侵蚀，和/或重大事件回应、系统恢复或补救以及未来的合规成本。上述任何或全部情况都可能对我们的业务、经营结果和财务状况产生重大不利影响。最后，我们坚持认为，网路保险可能不足以覆盖事件可能造成的财务、法律、商业或声誉损失，并且我们不能保证未来将以经济合理的条款或根本不提供适用的保险。

We are subject to governmental regulation and other legal obligations, particularly related to privacy, data protection, and information security, and we are subject to consumer protection laws that regulate our marketing practices and prohibit unfair or deceptive acts or practices. Our actual or perceived failure to comply with such obligations could harm our business.

We, and third parties on our behalf, receive, store, handle, transmit, use and otherwise process business information and information related to individuals, including from and about trial patients as well as our employees, business contacts, and service providers. We and our partners are subject to diverse state, federal, and international laws and regulations relating to data privacy and security, including, in the United States, the California Consumer Privacy Act, or the CCPA, and, in the EU and the European Economic Area, or EEA, the General Data Protection Regulation, or the GDPR. New privacy rules are being enacted in the United States and globally, and existing ones are being updated and strengthened, creating an ever evolving patchwork of privacy laws. For

example, the CCPA creates individual privacy rights for California consumers and increases the privacy and security obligations of entities handling certain personal information. The CCPA provides for civil penalties for violations, as well as a private right of action for certain data breaches. Complying with these numerous, complex, and often changing laws and regulations is expensive and difficult, and failure or perceived failure to comply with any privacy laws or data security laws or any security incident or breach involving the misappropriation, loss, or other unauthorized use or disclosure of personal information, whether by us or another third-party, could adversely affect our business, financial condition, and results of operations, including but not limited to: damage to our reputation, an erosion of trust, and negative media attention; investigation costs; material fines and penalties; compensatory, special, punitive, and statutory damages; litigation; consent orders regarding our privacy and security practices; requirements that we provide notices, credit monitoring services, and/or credit restoration services or other relevant services to impacted individuals; adverse actions against our licenses to do business; and injunctive relief.

In Europe, the GDPR requires us, among other things, to make detailed disclosures to data subjects, to disclose the legal basis on which we can process personal data, to obtain valid consent for processing, to appoint data protection officers when sensitive personal data, such as health data, is processed on a large scale, and provides robust rights for data subjects, introduces mandatory data breach notification, imposes additional obligations on us when contracting with service providers, and requires us to adopt appropriate privacy governance including policies, procedures, training, and data audit. In addition, the GDPR increases the scrutiny of transfers of personal data from clinical trial sites located in the EEA to the United States and other jurisdictions that the European Commission does not recognize as having “adequate” data protection laws, which could increase our costs and our ability to efficiently process personal data from the EEA. If we do not comply with our obligations under the GDPR, we could be exposed to fines of up to the greater of €20.0 million or up to 4% of our total global annual revenue in the event of a significant breach. In addition, we may be the subject of litigation and/or adverse publicity, which could adversely affect our business, results of operations, and financial condition. Additionally, following the United Kingdom’s withdrawal from the EEA and the EU, companies have to comply with the GDPR and the GDPR as incorporated into United Kingdom national law, the latter regime having the ability to separately fine up to the greater of £17.5 million or 4% of global turnover.

We cannot assure you that our third-party service providers with access to our or our customers’, suppliers’, trial patients’, and employees’ personal information and other sensitive or confidential information will not breach contractual obligations imposed by us, or that they will not experience data security breaches or attempts thereof, which could have a corresponding effect on our business, including putting us in breach of our obligations under privacy laws and regulations and/or which could in turn adversely affect our business, results of operations, and financial condition. We cannot assure you that our contractual measures and our own privacy and security-related safeguards will protect us from the risks associated with the third-party processing, storage, and transmission of such information.

We face potential liability related to the privacy of health information we obtain from clinical trials sponsored by us.

Most healthcare providers, including research institutions from which we obtain patient health information, are subject to privacy and security regulations promulgated under HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act, or the HITECH Act. We are not currently classified as a covered entity or business associate under HIPAA. However, any person may be prosecuted under HIPAA’s criminal provisions either directly or under aiding-and-abetting or conspiracy principles. Consequently, depending on the facts and circumstances, we could face substantial criminal penalties if we knowingly receive individually identifiable health information from a HIPAA-covered healthcare provider or research institution that has not satisfied HIPAA’s requirements for disclosure of individually identifiable health information. In addition, we may maintain sensitive personally identifiable information, including health information, that we receive throughout the clinical trial process, in the course of our research collaborations, and directly from individuals (or their healthcare providers) who enroll in our patient assistance programs. As such, we may be subject to state laws requiring notification of affected individuals and state regulators in the event of a breach of personal information, which is a broader class of information than the health information protected by HIPAA. Our clinical trial programs outside the United States may implicate international data protection laws, including the GDPR and legislation of the EU and EEA member states implementing it.

Our activities outside the United States impose additional compliance requirements and generate additional risks of enforcement for noncompliance. Failure by our CROs and other third-party contractors to comply with the strict rules on the transfer of personal data outside of the European Union into the United States may result in the imposition of criminal and administrative sanctions on such collaborators, which could adversely affect our business. Furthermore, certain health privacy laws, data breach notification laws, consumer protection laws, and genetic testing laws may apply directly to our operations and/or those of our collaborators and may impose restrictions on our collection, use, and dissemination of individuals’ health information. The GDPR provides that EU and EEA member states may establish their own laws and regulations limiting the processing of personal data, including genetic, biometric, or health data, which could limit our ability to use and share personal data or could cause our costs to increase. Moreover, patients about whom we or our collaborators obtain health information, as well as the providers who share this

向我们提供的信息可能拥有限制我们使用和披露信息能力的法定或合同权利。我们可能需要花费大量资本和其他资源来确保持续遵守适用的隐私和数据安全法。声称我们侵犯了个人隐私权或违反了我们的合同义务，即使我们没有被发现承担责任，辩护也可能昂贵且耗时，并且可能会导致不利宣传，从而损害我们的业务。

如果我们、我们的CROs或其他承包商或顾问未能遵守适用的联邦、州或地方监管要求，我们可能会受到一系列监管行动的约束，这些行动可能会影响我们或我们的承包商开发和商业化我们候选产品的能力，并可能损害或阻止我们能够商业化的任何受影响产品的销售。或者可能大幅增加开发、商业化和营销我们产品的成本和费用。任何威胁或实际的政府执法行动也可能会产生不利的宣传，并要求我们投入大量资源，否则这些资源本可以用于我们业务的其他方面。越来越多地使用社交媒体可能会导致责任、数据安全受到破坏或声誉损害。

我们受到环境、健康和安全法律法规的约束，我们可能会因环境合规或补救活动而承担责任和巨额费用。

我们的运营，包括开发、测试和制造活动，都受到众多环境、健康和安全法律法规的约束。这些法律和法规除其他外，规范危险材料和生物材料（例如化学溶剂、人体细胞、致癌化合物、致突变化合物以及对生殖、实验室程式和接触血液病原体有毒性影响的化合物）的受控使用、处理、释放和处置以及登记册的维护。如果我们未能遵守此类法律和法规，我们可能会受到罚款或其他制裁。

与从事与我们类似活动的其他公司一样，我们面临著当前和历史活动固有的环境责任风险，包括与危险或生物材料的释放或接触相关的责任。此外，某些环境法可能会规定责任，而不考虑行为发生时的过错或合法性。环境、健康和安全法律法规变得更加严格。我们可能需要为未来的环境合规或补救活动承担大量费用，在这种情况下，我们的开发工作可能会中断或延迟。

我们和我们的员工越来越多地利用社交媒体工具作为内部和外部的沟通手段。

尽管我们努力监控不断变化的社交媒体传播指南并遵守适用的规则，但我们或我们的员工使用社交媒体传播我们的候选产品或业务可能会导致我们被发现违反了适用的要求。此外，我们的员工可能会故意或无意地以不符合我们的政策和其他法律或合同要求的方式使用社交媒体，这可能会产生责任，导致商业秘密或其他知识产权的损失，或导致我们的员工、临床试验患者、客户和其他人的个人资讯公开。此外，社交媒体上关于我们或我们的候选产品的负面帖子或评论可能会严重损害我们的声誉、品牌形象和商誉，无论这些帖子的真实性如何。这些事件中的任何一个都可能对我们的业务、前景、经营结果和财务状况产生重大不利影响，并可能对我们普通股的价格产生不利影响。

竞争对手的开发可能会使我们的产品或技术过时或失去竞争力，或者可能会缩小我们的市场规模。

我们的行业一直以广泛的研发努力、快速的技术发展、激烈的竞争和对专有产品的高度重视为特征。我们面临著来自许多不同来源的潜在竞争，包括销售或开发治疗CRS的药物的制药、生物技术和专业制药公司。学术研究机构、政府机构以及公共和私营机构也是有竞争力的产品和技术的潜在来源。我们的竞争对手可能已经拥有或可能开发出先进的技术或方法，这可能会为他们提供竞争优势。我们的潜在产品可能不会成功竞争。如果这些竞争对手在我们推出更好或更便宜的疗法之前进入市场，我们的候选产品如果被批准商业化，可能不会有利可图，也不值得继续开发。制药行业的技术已经经历了快速而重大的变化，我们预计它将继续这样做。在我们收回与其开发相关的任何费用之前，我们开发的任何化合物、产品或工艺都可能变得过时或不经济。我们候选产品的成功将取决于产品的有效性、安全性、可靠性、可用性、时机、监管批准的范围、

接受度和价格等。我们成功的其他重要因素包括开发候选产品的速度、完成临床开发和实验室测试、获得监管机构批准以及制造和销售商业批量的潜在产品。

我们的候选产品旨在与现有产品和治疗直接或间接竞争。即使获得批准并商业化，我们的候选产品也可能无法获得医院、医生或患者的市场接受。医院、医生或患者可能会得出结论，认为我们的潜在产品比这些现有治疗方法不太安全、有效，或者吸引力较差。如果我们的候选产品因任何原因没有得到市场的认可，我们的收入潜力就会减弱，这将对我们的盈利能力产生重大不利影响。此外，医生可能更喜欢通过进行筛窦手术来治疗CRS患者，这一旦获得批准，可能会减少对我们候选产品的需求。

有许多公司正在开发或营销用于治疗和管理CRS的疗法，这些疗法可能与我们当前的候选产品竞争，其中包括许多主要的制药和生物技术公司。这些公司包括：赛诺菲、葛兰素史克、Regeneron、Optinose、美敦力、基因泰克和诺华。

我们的大多数竞争对手，包括上面列出的许多竞争对手，都比我们拥有更多的资本资源、强大的候选产品渠道、成熟的市场地位，以及在研发、制造、临床前和临床测试、获得监管批准和报销以及营销批准的产品方面的专业知识。因此，我们的竞争对手可能比我们更早实现产品商业化或专利保护。规模较小或处于初创阶段的公司也可能成为重要的竞争对手，特别是通过与大型和成熟公司的合作安排。这些竞争对手还在招聘和留住合格的临床、监管、科学、销售、营销和管理人员、建立临床试验场地和临床试验患者注册以及获取补充或必要的技术方面与我们展开竞争。如果我们的竞争对手开发和商业化的产品比我们可能开发的任何产品更安全、更有效、副作用更少或更不严重、更方便或更便宜，或者会使我们可能开发的任何产品过时或不具竞争力，我们的商业机会可能会减少或消失。

我们候选产品的成功商业化将在一定程度上取决于政府当局和健康保险公司建立覆盖范围、足够的报销水平和定价政策。如果获得或维持我们候选产品的覆盖范围和足够的报销（如果获得批准），可能会限制我们营销这些产品的能力并降低我们创收的能力。

如果FDA批准，政府医疗保健计划(如Medicare和Medicaid)、私人健康保险公司和其他第三方付款人提供的保险范围和报销充足，对于大多数患者能够负担得起医疗服务和药品(如我们的候选产品)至关重要。政府当局、私人健康保险公司和其他组织使用我们的产品或程式对我们的产品或程式实现可接受的承保和报销水准的能力，将影响我们成功将我们的候选产品商业化的能力。为我们的产品获得保险和足够的补偿可能特别困难，因为在医生监督下给药的价格往往较高。对于产品本身或使用我们产品的治疗或程式，可能不提供单独的报销。如果第三方付款人决定不为使用我们产品的产品或程式承保或单独报销，一旦获得批准，可能会减少医生对我们产品的使用。假设第三方付款人使用我们的产品候选产品或程式为我们的候选产品或程式提供保险，则由此产生的报销付款率可能不够高，或者可能需要患者认为不可接受的高共付额。患者不太可能使用我们的候选产品，除非提供保险，并且报销足以支付我们候选产品的很大一部分成本。

同样，我们的候选产品是医生管理的治疗，因此，产品本身可能会单独报销，也可能不会。相反，医院或主管医生可能只会因提供使用我们产品的治疗或程式而获得报销。在一定程度上，LYR-210应该可以单独承保和报销，我们预计它将以“先买后付”的方式出售给医生。购买和开具账单的产品必须由医疗保健提供者购买，然后才能对患者进行管理。医疗保健提供者随后必须向适用的第三方付款人(如联盟医疗保险或健康保险公司)寻求产品的报销。如果获得批准，医疗保健提供者可能不愿管理我们的候选产品，因为他们必须为购买产品提供资金，然后寻求报销，这可能低于他们的购买价格，或者因为他们不想要获得产品报销所需的额外管理负担。我们不知道医生使用我们的候选产品治疗CRS患者，或执行插入我们的候选产品的程式，或者此类医生认为这种补偿是否足够，是否或在什么水准上可以获得补偿。

此外，我们任何候选产品的报销代码状态，如果获得批准，也可能影响报销。J代码是由医疗保险和医疗补助服务中心(CMS)维护的报销代码，是医疗保健通用程式编码系统的一个组成部分，通常用于报告通常不能自行给药的注射药物。我们目前没有针对我们的任何候选产品的特定J-Code。如果我们的候选产品获得批准，我们可以申请一个，但不能保证J-Code会被批准。如果任何候选产品都可以单独承保或报销，如果获得批准，而特定的J-Code不可用，医生将需要使用非特定的杂项J-Code来向第三方付款人开具这些医生管理的药物的账单。由于各种各样的产品可能会使用各种J代码，健康计划可能更难确定患者实际使用的产品和账单。这些索赔通常必须提交附加资讯并手动处理，这可能会推迟索赔处理时间，并增加索赔拒绝和索赔错误的可能性。我们不能确定我们的候选产品或我们可能开发的任何产品是否可以在美国、欧盟或其他地方获得保险和报销，任何可能获得的报销可能不够充分，或者可能在未来减少或取消。

第三方付款人越来越多地对药品和服务的收费提出挑战，许多第三方付款人可能会拒绝为特定药物和生物制品提供保险和报销，因为有同等的仿制药、生物相似药物或更便宜的疗法可用。第三方付款人可能会认为我们的产品是可替代的，并只提出向患者报销价格较低的产品。即使我们对我们的候选产品表现出更好的疗效或更好的管理便利性，现有第三方疗法的定价可能会限制我们对我们的候选产品收取的费用。这些付款人可能会拒绝或撤销特定产品的报销状态，或将新产品或现有市场产品的价格设定在太低的水准，使我们无法从我们对候选产品的投资中实现适当的回报。如果无法获得报销或仅限量报销，我们可能无法成功地将我们的候选产品商业化，也可能无法为我们的候选产品获得满意的财务回报。

新批准产品的保险范围和报销存在重大不确定性。在美国，第三方支付者，包括私人和政府支付者，例如医疗保险和医疗补助计划，在确定新药和生物制品的覆盖程度方面发挥著重要作用。在美国，医疗保险和医疗补助计划越来越多地被用作私人支付者和其他政府支付者如何制定药物和生物制品的保险和报销政策的模式。一些第三方付款人可能需要预先批准新药或创新药物疗法的承保范围，然后才能向使用此类疗法的医疗保健提供者报销。目前我们无法预测第三方付款人将如何决定我们候选产品的承保范围和报销。

美国的第三方付款人之间没有统一的产品承保和报销政策。因此，付款人的产品覆盖范围和报销可能会有很大差异。因此，承保范围确定过程通常是一个耗时且成本高昂的过程，需要我们分别向每个付款人提供使用我们候选产品的科学和临床支持，而不能保证承保范围和足够的报销将一致适用或首先获得。此外，有关报销的规则和法规经常发生变化，在某些情况下是在短时间内发生变化的，我们相信这些规则和法规可能会发生变化。

在美国以外，国际业务通常受到广泛的政府价格管制和其他市场法规的约束，我们相信欧盟和其他司法管辖区对成本控制举措的日益重视已经并将继续对我们候选产品的定价和使用带来压力。在许多国家，作为国家卫生系统的一部分，医疗产品的价格受到不同的价格控制机制的约束。其他国家允许公司自行定价医疗产品，但监控和控制公司利润。额外的外国价格管制或定价监管的其他变化可能会限制我们能够为候选产品收取的费用。因此，在美国以外的市场，与美国相比，我们候选产品的报销可能会减少，并且可能不足以产生商业上合理的收入和利润。

此外，美国和国外的政府和第三方支付者加大力度限制或降低医疗保健成本，可能会导致此类组织限制新批准产品的覆盖范围和报销水平，因此，他们可能无法为我们的候选产品提供足够的付款。由于管理式医疗保健的趋势、健康维护组织的影响力不断增加以及额外的立法变化，我们预计将在销售候选产品时面临定价压力。总体医疗保健成本的下行压力，尤其是

处方药、生物制剂、外科手术和其他治疗方法的使用已经变得密集。结果，新产品的进入壁垒越来越高。

我们的临床研究旨在根据FDA要求证明LY R-210的安全性和有效性，并且可能不会被视为对医生或患者有吸引力。

我们的成功取决于医学界是否接受LYR-210作为CRS患者的治疗方法。LYR-210之前在纽西兰和澳大利亚的20名患者中进行了一项开放标签的第一阶段临床试验，在第4周达到了主要的安全终点。在第一阶段试验中，我们还观察到，患者在SNOT-22评分方面总体上经历了显著和迅速的、有临床意义和持久的改善。观察到鼻塞-22评分在第1周显著下降，这种下降持续到第25周，也就是试验结束。在我们的第二阶段Lantern临床试验中，我们报告了积极的顶线结果，但未能达到主要终点。尽管在第4周(主要终点)没有统计学意义，但在7500微克剂量下，根据第16、20和24周基线的变化，LYR-210在4css方面取得了统计上的显著改善，有利于治疗组。此外，在7,500微克剂量下，LYR-210在8周、16周、20周和24周的SNOT-22评分中取得了统计上的显著改善，有利于治疗组。即使这些临床试验的结果表明具有良好的安全性和有效性，研究设计和结果，以及我们进行的未来临床试验的设计和结果，可能对我们的医生客户或患者并不具有说服力。如果医生不认为我们的数据令人信服，即使LYR-210获得市场批准，他们也可以选择不使用我们的产品或限制其使用。我们的3期启蒙1临床试验未能达到其主要终点，即在24周时，与假对照组相比，CRS的三个主要症状(鼻塞、鼻分泌物、面部疼痛/压力)的综合评分在统计学上有显著改善。启蒙1号试验的52周延长阶段已经完成，预计2024年第四季度将有完整的数据。LYR-210在CRS的第二个关键3期试验--启蒙2号正在进行中，预计2025年第二季度将公布背线数据。不能保证我们将在LYR-210的启蒙2阶段3临床试验中实现主要终点或任何其他终点。我们也不能向您保证，可能收集的任何数据对医学界都是有说服力的，因为这些数据可能没有临床意义，也可能不能证明与替代疗法的数据相比，LYR-210是一种有吸引力的手术。

即使LY-210获得上市批准，它也可能无法获得医生、患者、第三方付款人或商业成功所需的医疗界其他人的市场接受。

如果LY-210获得上市批准，它可能仍无法获得医生、患者、第三方付款人和医疗界其他人的足够市场接受。如果它没有达到足够的接受程度，或者如果我们无法实现最佳的商品成本，我们可能无法产生可观的产品收入或盈利。如果批准商业销售，LIR-210的市场接受程度将取决于多种因素，包括但不限于：

如果我们的候选产品获得批准，但没有达到足够的商品成本或医生、医疗保健支付者和患者的接受程度，我们可能无法从这些产品中产生足够的收入，并且我们可能无法实现或维持盈利能力。我们向医疗界和第三方支付者宣传我们候选产品的好处的努力可能需要大量资源，并且可能永远不会成功。此外，我们成功商业化候选产品的能力将取决于我们以商业规模制造产品、将我们的产品与竞争产品区分开来以及保护我们产品智慧财产权的能力。

由于我们预计，如果获得批准，LIR-210的销售将在相当长的一段时间内产生我们几乎所有的产品收入，因此该产品未能获得市场接受将损害我们的业务，并可能需要我们寻求额外的融资。

如果医生或患者不愿意改变当前的做法并采用我们的LIR-210办公室给药程式，则可能无法获得市场接受，我们的业务将受到损害。

虽然我们相信，如果成功开发并获得批准，ENt医生将能够与内窥镜手术结合使用LY R-210，从而使放置与CRS患者的现有护理连续体保持一致，并消除了ENt医生安排单独手术时间的需要，但ENt医生可能不会采用我们的办公室手术有多种原因，包括：

如果ENt医生出于任何原因（包括上述原因）不采用放置程式，即使LyR-210获得上市批准，我们发展业务的能力也将受到损害。

我们相信著名ENt医生对我们产品的推荐和支持可能会影响市场的接受度和采用。如果我们没有得到有影响力的ENt医生的支持，我们的产品获得市场广泛接受的能力可能会受到损害。

此外，如果未来患者对ENt医生办公室环境中治疗的接受度变得不那么有利，这种转变可能会对我们产品的市场接受度产生负面影响。患者通过口碑或社交媒体向医生或其他患者报告，也可能加剧因患者接受性而产生的任何负面变化。

此外，虽然目前对于医疗保健系统来说，提供者在ENt医生办公室进行放置手术比在手术室进行内窥镜鼻窦手术更具成本效益，但医疗保健经济学可能会发生变化。如果由于报销经济学的变化，我们的产品的使用不再比内窥镜鼻窦手术更具成本效益，那么我们的产品可能无法获得市场的认可，我们的业务可能会受到不利影响。

如果我们无法独自或与第三方合作成功建立制造、销售、营销和分销能力，那么如果获得批准，我们可能无法成功地将LY-210商业化，并且我们可能无法产生任何收入。

我们没有用于所有产品的制造、销售、营销或分销的商业基础设施，建立和维护这样一个组织的成本可能会超过这样做的成本效益。ENLIGHTEN 1 3期试验未能达到主要终点也对公司的LyR-210商业化计划产生了不利影响。

我们预计在可预见的未来不会有资源分配给LY-210或美国以外市场的任何未来候选产品的销售和营销。因此，我们未来在这些市场的销售将在很大程度上取决于我们建立和维护此类能力协作关系的能力、合作者对产品的战略利益以及合作者成功营销和销售产品的能力。如果获得批准，我们打算在美国以外的某些市场选择性地寻求有关LY-210的销售和营销的合作安排;但是，我们无法保证我们能够建立或维持此类合作安排，或者如果能够这样做，他们将拥有有效的销售力量。

如果未来我们无法建立自己的销售队伍或就LY-210的商业化谈判合作关系，我们可能会被迫推迟LY-210的潜在商业化或缩小我们的销售或营销活动范围。如果我们选择增加支出来资助自己的商业化活动，我们将需要获得额外的资本，而我们可能无法以可接受的条件获得这些资本，或者根本无法获得这些资本。我们可以在比理想情况更早的阶段与合作伙伴达成安排，我们可能会被要求放弃对LIR-210的权利或以其他方式同意对我们不利的条款，其中任何条款都可能对我们的业务、经营运绩和前景产生不利影响。

如果我们无法单独或与第三方合作建立足够的销售、营销和分销能力，我们将无法成功地将LY-210商业化，并且可能无法盈利，并可能会招致重大额外损失。我们将与许多目前拥有广泛且资金充足的营销和销售业务的公司竞争。如果没有内部团队或第三方的支持来履行营销和销售职能，我们可能无法与这些更成熟的公司成功竞争。

我们业务的成功可能在一定程度上取决于我们渗透外国市场的能力，在那里我们将面临额外的监管负担以及其他风险和不确定性。

我们未来的盈利能力可能在一定程度上取决于我们将候选产品在国外市场商业化的能力，而我们可能依赖于与第三方的合作。我们正在评估我们的候选产品在国外市场的开发和商业化机会。在获得外国市场相关监管机构的监管批准之前，我们不被允许营销或推广我们的任何候选产品，我们可能永远不会获得任何候选产品的监管批准。为了在其他国家获得单独的监管批准，我们可能需要遵守这些国家/地区关于我们候选产品的安全性和有效性以及管理我们候选产品的临床试验和商业销售、定价和分销等方面的众多不同的监管要求，我们无法预测在这些司法管辖区是否会成功。如果我们的候选产品获得批准，并最终将我们的候选产品在国外市场商业化，我们将面临额外的风险和不确定性，包括：

我们候选产品的海外销售也可能受到政府控制、政治和经济不稳定、贸易限制以及关税变化的不利影响。

在一些国家，特别是欧洲国家，处方药的定价受到政府控制。在这些国家，在获得药物上市批准后，与政府当局的定价谈判可能需要相当长的时间。为了在某些国家/地区获得报销或定价批准，我们可能需要进行临床试验，将我们的候选产品与其他可用疗法的成本效益进行比较。如果我们的产品无法报销或范围或金额受到限制，或者定价设定在不令人满意的水平，我们的业务可能会受到损害，可能会受到严重损害。

我们的候选产品旨在治疗的患者人群规模尚未精确确定。如果我们候选产品的市场机会小于我们的估计，或者如果我们获得的任何批准是基于比我们预期更窄的患者群体定义，那么我们的收入和实现盈利能力可能会受到重大不利影响。

我们旨在通过我们的计划解决的疾病的确切发生率和患病率尚不清楚，也无法准确确定。我们对患有这些疾病的人数以及有可能从我们的候选产品治疗中受益的患有这些疾病的人数的预测是基于信念和估计的。这些估计来自多种来源，包括科学文献、诊所调查、患者基金会或市场研究，但可能被证明是不正确的。此外，新信息可能会改变这些疾病的估计发病率或患病率，并且这些疾病的发病率或患病率可能会发生变化。

我们所有候选产品的总可达市场最终将取决于候选产品获得批准和可能上市的适应症和使用条件、医学界的接受程度以及患者准入、药品定价和报销。我们的候选产品在美国、其他主要市场和其他地方旨在治疗的患者群体规模可能会小于预期，患者可能无法接受我们的候选产品治疗，或者新患者可能变得越来越难以识别或获得接触，所有这些都将对我们的运营结果和业务产生不利影响。此外，即使我们为候选产品获得了重要的市场份额，尽管获得了如此重要的市场份额，我们可能永远无法实现盈利。

如果我们无法与其他制药公司竞争市场份额，我们可能无法获得足够的产品收入，我们的业务就会受到影响。

如果我们的候选产品获得FDA批准，它们将与其他公司开发、制造和销售的许多现有和未来的药物和疗法竞争。现有或未来的竞争产品可能会为特定适应症提供比我们的产品更大的治疗便利性或临床或其他益处，或者可能以较低的价格提供相当的性能

成本如果我们的产品未能占领和维持市场份额，我们可能无法实现足够的产品收入，我们的业务就会受到影响。

我们将与完全整合的制药公司和与大型制药公司、学术机构、政府机构以及其他公共和私人研究组织合作的小型公司竞争。其中许多竞争对手可能已经在我们当前和未来候选产品的治疗类别中获得批准或正在开发的化合物。此外，许多竞争对手，无论是单独还是与合作伙伴一起，可能会运营更大的研发计划，或者拥有比我们更多的财务资源，以及在开发候选产品方面拥有更丰富的经验;制定和制造产品;以及推出、营销和销售产品等。

如果未来我们获得在美国境外商业化任何产品的批准，与国际业务相关的各种风险可能会对我们的业务产生重大不利影响。

如果LY-210获得商业化批准，我们可能会与第三方合作在美国以外的某些司法管辖区营销它。我们预计我们将面临与国际制药运营相关的额外风险，包括：

我们在这些领域没有经验。此外，欧盟和许多欧洲国家还规定了复杂的监管、税收、劳工和其他法律要求，我们需要遵守这些要求。许多美国-总部位于生物技术公司发现在欧洲营销自己的产品的过程非常具有挑战性。

针对我们的潜在产品责任诉讼可能会导致我们承担重大责任并限制我们可能开发的任何产品的商业化。

在临床试验中使用LYR-210，以及销售我们获得市场批准的任何产品，都会使我们面临产品责任索赔的风险。例如，LYR-210植入物在植入过程中产生的并发症，或植入后LYR-210植入物在鼻窦内降解或移位，或植入后鼻窦内异物生长引起的并发症，可能会导致对我们的产品责任索赔。消费者、医疗保健提供者、制药公司或销售或以其他方式接触我们产品的其他人可能会对我们提出产品责任索赔。有时，在基于具有意想不到的不利影响的产品的集体诉讼中，会做出大额判决。如果我们不能成功地对产品责任索赔进行辩护，我们可能会产生大量的责任和成本，而这些可能不在保险范围之内。此外，无论是非曲直或最终结果如何，产品责任索赔都可能导致重大后果，包括：

我们暂停了临床材料的内部生产。如果我们重新启动制造，我们可能会依赖第三方提供某些开发和制造相关服务，而且我们目前没有与其中任何一方签订长期合同。我们对第三方的持续依赖增加了我们没有足够数量此类材料的风险，

候选产品或我们可能开发和商业化的任何疗法，或者我们无法以可接受的成本提供此类供应，这可能会延迟、阻止或损害我们的开发或商业化努力。

我们之前在候选产品的临床开发过程中依赖第三方提供某些开发和制造相关服务，并且如果我们的任何候选产品获得营销批准，我们可能会依赖第三方提供某些制造相关服务。其中某些制造商对我们的生产至关重要，这些制造商流失给我们的竞争对手或其他人，或者无法以可接受的成本或质量获得数量，可能会延迟、阻止或损害我们及时进行临床前研究或临床试验的能力，并将对我们的开发和商业化工作产生重大不利影响。

在我们的候选产品或我们候选产品的元件的生产中涉及的某些第三方使用的设施可能需要FDA批准，检查可能在我们向FDA提交保密协定后进行。虽然我们可能能够通过我们的勤奋和承包过程来降低风险，但当我们利用第三方进行生产时，我们依赖他们遵守药品生产的cGMP要求和其他法律法规。如果这些第三方制造商不能成功地制造或供应符合我们的规格和FDA或其他机构的严格监管要求的材料，他们将无法确保和/或保持对其制造设施的监管批准。我们的一些合同制造商可能没有生产商业批准的产品，因此可能没有获得必要的FDA批准。此外，我们在确保第三方制造商保持足够的质量控制、品质保证和合格人员方面的能力有限。如果FDA或类似的外国监管机构不批准这些设施用于生产我们的候选产品，或者如果它在未来撤回任何此类批准，我们可能需要寻找替代制造设施，这将严重影响我们开发、获得监管批准或营销我们的候选产品的能力(如果获得批准)。

我们的第三方制造商未能遵守适用法规可能会导致我们受到制裁，包括临床搁置、罚款、禁令、民事处罚、延迟、暂停或撤回批准、扣押或召回候选产品或产品、运营限制和刑事起诉，其中任何一种都可能对我们产品的供应产生重大不利影响。此外，我们可能无法与第三方制造商达成任何协议或以可接受的条款达成协议。

即使我们能够与第三方制造商达成协议，对第三方制造商或供应商的依赖也会带来额外的风险，包括：

我们的候选产品和我们可能开发的任何产品都可能与其他候选产品和产品竞争制造设施。在cGMP法规下运营的制造商数量有限，可能有能力为我们制造产品。我们现有或未来的制造商的任何表现不佳都可能推迟临床开发或上市批准，任何相关的补救措施实施起来都可能是昂贵或耗时的。我们目前还没有安排为生产我们的候选产品所需的所有原材料提供多余的供应或第二个来源。地缘政治事件(如当前俄罗斯与乌克兰之间或中东的冲突)或其他事件(如不断演变的新冠肺炎大流行)对我们获得足够供应以开发产品和候选产品的能力的影响程度将取决于事件的严重性和持续时间，以及为遏制其负面影响而采取的行动，可能会导致延误。如果我们目前的第三方制造商不能按协定履行，我们可能会被要求更换这些制造商，我们可能无法及时或根本无法更换他们。我们目前和预期未来对他人生产我们的候选产品或产品的依赖可能会对我们未来的利润率和我们将任何及时和有竞争力地获得营销批准的产品商业化的能力产生不利影响。

我们依赖第三方进行临床前研究和临床试验。第三方未能根据GCP及时进行临床试验，可能会延迟或阻止我们为候选产品寻求或获得监管机构批准或商业化的能力。

我们依赖第三方进行临床前研究和临床试验，包括我们计划和正在进行的LY R-210临床试验。如果我们决定对LY-210或其他候选产品进行未来的临床试验，我们预计将依赖

第三方进行这些未来的临床试验和临床前研究。具体地说，我们一直使用和依赖，并打算继续使用和依赖医疗机构、临床研究人员、CRO和顾问，以根据我们的临床方案和法规要求进行临床试验。这些CRO、调查人员和其他第三方在这些试验的进行和时间安排以及随后的数据收集和分析方面发挥著重要作用。虽然我们有协定管理我们的第三方承包商的活动，但我们对他们的实际表现的影响有限。然而，我们有责任确保我们的每一项临床试验都是根据适用的方案以及法律、法规和科学标准进行的，我们对CRO和其他第三方的依赖不会免除我们的监管责任。我们和我们的CRO必须遵守GCP要求，这些要求是FDA和类似的外国监管机构对我们临床开发中的所有候选产品执行的法规和指导方针。监管机构通过定期检查试验赞助商、主要调查人员和试验地点来执行这些GCP。如果我们或我们的任何CRO或试验站点未能遵守适用的GCP，在我们的临床试验中产生的临床数据可能被认为是不可靠的，FDA或类似的外国监管机构可能会要求我们在批准我们的营销申请之前进行额外的临床试验。我们不能向您保证，在特定监管机构进行检查后，该监管机构将确定我们的任何临床试验是否符合GCP规定。此外，我们的临床试验必须使用根据cGMP法规生产的产品进行。我们不遵守这些规定可能需要我们重复临床试验，这将推迟监管部门的批准过程。

不能保证任何此类CRO、调查人员或其他第三方将投入足够的时间和资源进行此类试验或按合同要求履行。如果这些第三方中的任何一方未能在预期的最后期限内完成、遵守我们的临床方案、或满足法规要求、或以其他不符合标准的方式进行，我们的临床试验可能会被延长、推迟或终止。此外，与我们签约的许多第三方也可能与其他商业实体有关系，包括我们的竞争对手，他们可能还在为这些实体进行临床试验或其他药物开发活动，这可能会损害我们的竞争地位。此外，我们临床试验的首席研究人员可能会不时担任我们的科学顾问或顾问，并可能因此类服务而获得现金或股权补偿。如果这些关系和任何相关的赔偿导致感知或实际的利益冲突，或者FDA得出结论认为财务关系可能影响了试验的解释，则在适用的临床试验地点生成的数据的完整性可能会受到质疑，临床试验本身的效用可能会受到危害，这可能会导致我们向FDA提交的任何NDA被推迟或拒绝。任何这样的延迟或拒绝都可能阻止我们将候选产品商业化。

如果我们与这些第三方的任何关系终止，我们可能无法与其他第三方达成安排或以商业上合理的条款这样做。更换或增加CRO、调查人员和其他第三方涉及额外成本，并需要管理时间和重点。此外，当新的CRO开始工作时，有一个自然的过渡期。因此，会出现延迟，这可能会对我们满足期望的临床开发时间表的能力产生实质性影响。我们与这些第三方的关系也可能受到地缘政治事件的不利影响，例如当前俄罗斯与乌克兰和中东的冲突，或其他事件，如不断演变的新冠肺炎疫情。例如，新冠肺炎和政府采取的应对措施已经对我们的CRO产生了重大影响，我们预计它们将面临进一步的干扰，这可能会影响我们启动和完成临床前研究和临床试验的能力。尽管我们谨慎地处理与CRO、调查人员和其他第三方的关系，但不能保证我们在未来不会遇到挑战或延误，也不能保证这些延误或挑战不会对我们的业务、财务状况和前景产生实质性的不利影响。

我们可能会与第三方合作开发和商业化LIR-210以及我们未来的任何候选产品。我们可能无法成功地建立和维护协作关系，这可能会严重限制我们成功开发和商业化LY-210或未来候选产品（如果有的话）的能力。

我们可能会为LY-210或任何未来候选产品的开发和商业化寻求额外的合作关系。未能为LY-210或任何未来候选产品建立合作关系可能会严重损害这些候选产品的潜力。我们还可能需要建立合作关系，以提供资金来支持我们的其他研发项目。

如果我们寻求但无法建立合作，我们可能不得不改变我们的开发和商业化计划。

我们的产品开发计划和候选产品的潜在商业化将需要大量额外资本。我们可能会决定与制药和生物技术公司合作，开发我们的候选产品并实现潜在的商业化。

我们在寻找合适的合作者方面面临著巨大的竞争。我们可能无法及时、以可接受的条款或根本无法就合作进行谈判。如果我们做不到，我们可能不得不减少此类产品的开发

候选人，减少或推迟其开发计划或我们的一个或多个其他开发计划，推迟其潜在的商业化或缩小任何销售或营销活动的范围，或增加我们的支出并自费进行开发或商业化活动。如果我们选择增加支出来资助自己的开发或商业化活动，我们可能需要获得额外的资本，而我们可能无法以可接受的条件或根本无法获得这些资本。如果我们没有足够的资金，我们可能无法进一步开发我们的候选产品或将其推向市场并产生收入。

我们所依赖的合作者和其他人提供的未经独立验证的数据可能会被证明是错误的、误导性的或不完整的。

我们依赖第三方供应商，例如CROs、科学家和合作者，为我们提供与我们的项目、临床前研究或临床试验和我们的业务相关的重要数据和其他信息。如果此类第三方提供不准确、误导性或不完整的数据，我们的业务、前景和运营运绩可能会受到重大不利影响。

我们没有LIR-210中使用的一些零部件的多个供应来源，也没有长期供应合同，而且我们的某些供应商对我们的生产至关重要。如果我们失去供应商，可能会对我们完成LY-210开发的能力产生重大不利影响。如果我们获得LIR-210的监管批准，我们将需要扩大其组件的供应，以便将其商业化。

我们没有用于制造LIR-210的零部件的多个供应来源。我们也没有与任何供应商签订长期供应协议。我们可能无法为我们的候选产品建立额外的供应来源，或者可能无法以可接受的条款这样做。供应商须遵守GMP质量和监管要求，涵盖与我们候选产品相关的制造、测试、质量控制和记录保存，并接受监管机构的持续检查。我们的任何供应商未能遵守适用法规可能会导致供应长期延误和中断。制造供应商还受到地方、州和联邦法规和许可要求的约束。我们的任何供应商未能遵守所有适用的法规和要求可能会导致供应长期延误和中断。

我们候选产品原材料成分的供应商数量有限。如果有必要或希望从替代供应商获取供应，我们可能无法以商业上合理的条款获得它们（如果有的话）。重新设计我们的制造流程以与另一家公司合作还可能需要大量的时间和费用。此外，我们的某些供应商对我们的生产至关重要，这些供应商流失给我们的竞争对手之一或以其他方式将对我们的开发和商业化工作产生重大不利影响。

作为任何营销批准的一部分，监管机构进行检查，检查必须在产品批准之前成功。制造供应商未能成功完成这些监管检查将导致延误。如果批准供应商的供应中断，商业供应可能会出现重大中断。替代供应商需要通过NDA修正案或补充获得资格，这可能会导致进一步延迟。如果依赖新供应商进行商业生产，FDA或美国以外的其他监管机构也可能要求进行额外的研究。更换供应商可能涉及巨额成本，并且可能导致我们预期的临床和商业时间表的延迟。

如果我们无法以合理的价格或及时获得所需的供应，可能会对我们完成LY-210开发的能力产生重大不利影响，或者如果我们获得LY-210的监管批准，将其商业化的能力产生重大不利影响。

如果我们无法获得、维护或充分保护我们的智慧财产权，我们可能无法在市场中进行有效竞争。

我们依靠专利、商业秘密保护和保密协议的结合来保护我们的智慧财产权并防止其他人复制LY-210和任何未来的候选产品。

生物技术和制药领域的专利实力涉及复杂的法律、事实和科学问题，并且可能是不确定的。在获得专利保护之前，我们可能无法识别研发成果中可获得专利的方面。我们拥有的专利申请可能无法获得涵盖我们在美国或其他外国国家的候选产品的已发布专利。无法保证与我们的专利和专利申请相关的所有潜在相关的现有技术都已被发现，这可能会使专利无效或阻止专利的颁发

来自正在处理的专利申请。即使专利确实成功发布，即使此类专利涵盖了我们的候选产品，第三方也可能会对此类专利的发明人身份、所有权、有效性、可转让性或范围提出质疑，这可能导致此类专利被缩小或无效，或被认为无法执行。此外，即使我们的专利和专利申请没有受到质疑，也可能无法充分保护我们的智慧财产权、为我们的候选产品提供排他性，或阻止其他人围绕我们的主张进行设计。此外，无法保证第三方不会在不侵犯我们专利的情况下创造出实现类似结果的新产品或方法。任何这些结果都可能损害我们防止第三方竞争的能力，这可能会对我们的业务产生不利影响。

如果我们就我们的程式或候选产品持有的专利申请未能颁发，如果其保护的广度或强度受到威胁，或者如果它们未能为我们的候选产品提供有意义的排他性，那么可能会阻止公司与我们合作开发候选产品，并威胁我们将未来产品商业化的能力。最近提交了多项涵盖我们候选产品的专利申请。我们无法就将颁发哪些专利（如果有的话）、任何此类专利的广度，或者任何已颁发的专利是否会被发现无效或不可执行或受到第三方威胁提供任何保证。对这些专利或我们拥有的任何其他专利的任何成功反对都可能剥夺我们可能开发的任何候选产品成功商业化所需的权利。

此外，如果我们在监管审批方面遇到拖延，我们可以在专利保护下销售候选产品的时间段可能会缩短。由于美国和大多数其他国家的专利申请在申请后的一段时间内是保密的，有些专利申请在发布之前仍然是保密的，我们不能确定我们是第一个提交与候选产品有关的专利申请的公司。此外，如果第三方在2013年3月16日《莱希-史密斯法案》颁布之前提交了此类专利申请，第三方可以在美国启动干预程式，以确定谁是第一个发明我们申请的专利权利要求所涵盖的任何主题的人。此外，专利的寿命是有限的。在美国，专利的有效期一般是在申请后20年。可能会有各种延期；然而，专利的有效期及其提供的保护是有限的。即使获得了涵盖我们候选产品的专利，一旦涵盖某一产品的专利有效期到期，我们可能会面临来自非专利竞争产品的竞争。

专利的颁发对其发明人、所有权、范围、有效性或可转让性没有定论，我们的专利可能会在美国和国外的法院或专利局受到质疑。此外，专利的颁发并不赋予我们实施专利发明的权利。第三方可能拥有阻止专利，这可能会阻止我们营销我们的候选产品（如果获得批准）或实践我们自己的专利技术。因此，我们专利权的发放、范围、有效性、可转让性和商业价值具有高度不确定性。

除了专利提供的保护外，我们还依靠商业秘密保护和保密协定来保护不可申请专利或我们选择不申请专利的专有技术、难以实施专利的过程以及我们候选产品发现和开发过程中涉及专利未涵盖的专有技术、资讯或技术的任何其他要素。然而，商业秘密可能很难保护。我们寻求通过与我们的员工、顾问、科学顾问和承包商签订保密协定来保护我们的专有技术和工艺。此外，我们亦致力维护我们楼宇的实体安全，以及我们的资讯科技系统的实体和电子安全，以维护我们的资料和商业秘密的完整性和保密性。虽然我们对这些个人、组织和系统有信心，但协定或安全措施可能会被违反，我们可能没有足够的补救措施来应对任何违规行为。一旦被披露，我们很可能会失去商业秘密保护。

尽管我们要求我们的所有员工和顾问将他们的发明转让给我们，但如果员工或顾问在为我们工作时使用他人拥有的知识产权，可能会出现关于相关或由此产生的专有技术和发明的权利的争议。此外，尽管我们要求我们的所有员工、顾问、合作者、顾问和任何能够访问我们专有技术、资讯或技术的第三方签订保密协定，但我们不能保证我们的商业秘密和其他机密专有资讯不会被泄露，或者竞争对手不会以其他方式获取我们的商业秘密、独立发现我们的商业秘密或开发实质上同等的资讯和技术。这些各方中的任何一方都可能违反这些协定，而我们可能没有足够的补救措施来应对任何特定的违规行为。挪用或未经授权披露我们的商业秘密或其他机密专有资讯可能会损害我们的竞争地位，并可能对我们的业务产生重大不利影响。强制执行一方非法披露或挪用商业秘密的主张是困难、昂贵和耗时的，结果是不可预测的。此外，如果为维护我们的商业秘密或其他机密专有资讯而采取的步骤被认为不充分，我们可能没有足够的追索权来对抗第三方挪用商业秘密或其他机密专有资讯。

如果我们无法阻止向第三方实质性披露与我们的技术相关的非专利智慧财产权，并且无法保证我们将获得任何此类可强制执行的商业秘密保护，我们可能无法在我们的市场中建立或维持竞争优势，这可能会对我们的业务、经营运绩和财务状况产生重大不利影响。

第三方智慧财产权侵权索赔可能会阻止或推迟我们的开发和商业化努力。

我们的商业成功在一定程度上取决于我们避免侵犯或指控侵犯第三方的专利和其他专有权利。在美国国内外，有大量涉及生物技术和制药行业专利和其他知识产权的诉讼，包括专利侵权诉讼、干预、异议、复审和向美国专利商标局(USPTO)和相应的外国专利局提起的各方之间的审查程式。在我们正在寻求开发候选者的领域中，存在著大量由第三方拥有的美国和外国颁发的专利和未决的专利申请。许多依赖知识产权的行业的公司，包括生物技术和制药行业，都利用知识产权诉讼作为一种手段，以获得相对于竞争对手的优势。随著生物技术和制药行业的扩张和专利的颁发，以及我们作为一家上市公司获得更大的知名度和市场曝光率，我们的候选产品可能会受到侵犯第三方专利权的索赔的风险增加。一些索赔人可能拥有比我们多得多的资源，并可能比我们能够在更大程度上和更长时间内承受复杂的知识产权诉讼费用。此外，只专注于通过强制执行专利权来提取专利费和和解的专利控股公司可能会针对我们。

第三方可能会声称我们在未经授权的情况下使用他们的专有技术。可能存在第三方专利或专利申请，这些专利要求与我们候选产品的使用或制造相关的物质组成、药物输送、制造方法或治疗方法。我们不能保证我们的技术、产品、成分及其使用不会或不会侵犯第三方专利或其他知识产权。由于专利申请可能需要数年时间才能发布，因此可能存在当前正在处理的专利申请，这些申请可能会导致我们的候选产品可能会侵犯已颁发的专利。此外，第三方可能会在未来获得专利，并声称使用我们的技术侵犯了这些专利。已公布的待定专利申请可以在受到某些限制的情况下在以后进行修改，以涵盖我们的候选产品或对我们候选产品的使用。在专利发布后，专利权利要求的范围仍然取决于法律解释、专利中的书面披露和专利的起诉历史。我们对专利或待决申请的相关性或范围的解释可能是不正确的，这可能会对我们营销我们的候选产品的能力产生负面影响。如果有管辖权的法院持有任何第三方专利，涵盖我们任何候选产品的组成、我们候选产品的制造过程或我们候选产品的使用方法，则任何此类专利的持有者可能能够阻止我们将该候选产品商业化的能力，除非我们根据适用专利获得了许可，该许可可能不可用或可能无法以商业合理的条款获得，或者直到该专利到期。

对我们提出索赔的各方可能会获得禁令或其他公平救济，这可能会有效地阻止我们进一步开发和商业化我们的一个或多个候选产品和/或损害我们的声誉和财务业绩。对这些索赔的辩护，无论其是非曲直，都可能涉及巨额诉讼费用，并可能从我们的业务中大量转移管理层和员工资源。如果针对我们的侵权索赔成功，我们可能必须支付巨额损害赔偿，包括故意侵权的三倍损害赔偿金和律师费、支付特许权使用费、重新设计我们的侵权产品、在涉及注册商标的索赔中重新命名我们的产品候选产品，或者从第三方获得一个或多个许可证，这些可能需要大量的时间和金钱支出，并且可能是不可能的或在技术上不可行的。此外，我们可能无法以商业上合理的条款或根本无法获得任何所需的许可证。即使我们能够获得许可，它也可能是非排他性的，从而使我们的竞争对手能够访问向我们许可的相同技术；或者，或者另外，它可能包括阻碍或摧毁我们在商业市场上成功竞争的能力的条款。

我们可能会卷入保护或执行我们的专利或其他智慧财产权的诉讼，这可能会昂贵、耗时且不成功。

竞争对手可能会侵犯我们的专利、商标、版权或其他知识产权。可能很难检测到不宣传其产品中使用的元件的侵权者。此外，可能很难或不可能获得竞争对手或潜在竞争对手的产品侵权的证据。为了打击侵权或未经授权的使用，我们可能会被要求在每个国家的基础上提出侵权索赔，这可能既昂贵又耗时，并分散了我们的管理和科学人员的时间和注意力。我们不能保证我们将有足够的财政或其他资源来提起和追查此类侵权索赔，这些索赔通常会持续数年才能结案。除了声称我们的专利无效或不可执行，或两者兼而有之之外，我们对被认为侵权者提出的任何索赔也可能促使这些当事人对我们提出反索赔，声称我们侵犯了他们的专利。

此外，在侵权诉讼中，法院可能会裁定我们的专利无效、不可执行和/或未被侵权，或者可以狭隘地限制专利的权利要求或拒绝阻止对方使用有争议的技术，理由是我们的专利不涵盖有争议的技术。任何诉讼或辩护程式中的不利结果都可能导致

我们的一项或多项专利面临被无效、狭义解释或被视为无法执行的风险，可能会使我们的专利申请面临无法发布的风险，并可能限制我们针对这些当事人或其他竞争对手主张这些专利的能力，并限制或排除我们排除第三方制造和销售类似或竞争性产品的能力。同样，如果我们主张商标侵权索赔，法院可能会确定我们主张的标记无效或不可执行，或者我们主张商标侵权的一方对相关标记拥有优先权利。在这种情况下，我们最终可能被迫停止使用此类商标，这可能会对我们的业务造成重大损害，并对我们在市场上的地位产生负面影响。

即使我们确定侵权，法院也可能决定不对进一步的侵权活动发布禁令，而只判给金钱损害赔偿，这可能是也可能不是充分的补救措施。此外，由于智慧财产权诉讼需要大量发现，因此我们的一些机密信息存在在此类诉讼期间可能因披露而受到损害的风险。还可以公开宣布听证会、动议或其他临时程式或事态发展的结果。如果证券分析师或投资者认为这些结果为负面，可能会对我们普通股的价格产生重大不利影响。

最近的专利改革立法增加了我们专利申请起诉以及我们已发布专利的执行或辩护的不确定性和成本，并可能总体降低专利的价值。

与其他生物技术公司一样，我们的商业成功严重依赖于智慧财产权，尤其是专利。在生物技术行业获得和执行专利涉及技术和法律的复杂性，因此成本高昂、耗时且本质上不确定。美国最近广泛的专利改革立法，包括《莱希-史密斯美国发明法案》或《莱希-史密斯法案》，可能会增加这些不确定性和成本。

Leahy-Smith法案包括对美国专利法的一些重大修改，包括影响专利申请起诉方式的条款，也可能影响专利诉讼。根据《莱希-史密斯法案》，美国从“先发明”转变为“先申请”制度，用于在要求同一发明的不同当事人提交两项或更多专利申请时，决定哪一方应被授予专利。这将要求我们了解从发明到提交专利申请的时间，并勤奋地提交专利申请，但情况可能会阻止我们迅速提交关于我们发明的专利申请。Leahy-Smith法案还扩大了符合现有技术的披露范围，并扩大了第三方可以用来挑战美国专利的程式范围，包括授权后审查和各方之间审查程式。由于USPTO诉讼中的证据标准低于美国联盟法院宣布专利权利要求无效所需的证据标准，第三方可能会在USPTO程式中提供足以让USPTO裁定权利要求无效的证据，即使相同的证据如果首先在地区法院诉讼中提交将不足以使权利要求无效。Leahy-Smith法案及其实施可能会增加围绕我们专利申请的起诉以及我们已发布专利的执行或保护的不确定性和成本，所有这些都可能对我们的业务和财务状况产生实质性的不利影响。

此外，最近法院对分子病理学协会诉Myriad Genetics，Inc.等案件的裁决，BRCA 1-& BRCA 2-基于遗传性癌症测试专利诉讼和Promega Corp.诉Life Technology Corp.缩小了某些情况下可用的专利保护范围，并削弱了某些情况下专利所有者的权利。除了增加我们未来获得专利的能力的不确定性之外，这种事件的组合还对获得专利的价值产生了不确定性。根据美国国会、美国法院、USPTO和其他国家相关立法机构未来的行动，管理专利的法律和法规可能会以不可预测的方式发生变化，这将削弱我们获得新专利或执行现有专利和未来可能获得的专利的能力。

We may be subject to claims that our employees, consultants, or independent contractors have wrongfully used or disclosed confidential information of third parties or that our employees have wrongfully used or disclosed alleged trade secrets of their former employers.

We may employ individuals who were previously employed at universities or other biotechnology or pharmaceutical companies, including our competitors or potential competitors. Although we try to ensure that our employees, consultants, and independent contractors 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 our employees, consultants, or independent contractors have inadvertently or otherwise used or disclosed intellectual property, including trade secrets or other proprietary information, of any of our employee’s former employers or other third parties. Litigation may be necessary to defend against these claims. If we fail in defending any such claims, in addition to paying monetary damages, we may lose valuable intellectual property rights or personnel, or our ability to hire personnel, which, in any case of the foregoing, could adversely impact our business. Even if we are successful in defending against such claims, litigation could result in substantial costs and be a distraction to management and other employees.

Obtaining and maintaining our patent protection depends on compliance with various procedural, document submission, fee payment, and other requirements imposed by governmental patent agencies, and our patent protection could be reduced or eliminated for non-compliance with these requirements.

The USPTO, European, and other patent agencies require compliance with a number of procedural, documentary, fee payment, and other similar provisions during the patent application process. Periodic maintenance fees, renewal fees, annuity fees, and various other governmental fees on patents and/or applications will be due to be paid to the USPTO and various governmental patent agencies outside of the United States in several stages over the lifetime of the patents and/or applications. We have systems in place to remind us to pay these fees, and we employ an outside firm and rely on our outside counsel to pay these fees due to non-U.S. patent agencies. The USPTO and various non-U.S. governmental patent agencies require compliance with a number of procedural, documentary, fee payment, and other similar provisions during the patent application process. We employ law firms and other professionals to help us comply, and in many cases, an inadvertent lapse can be cured by payment of a late fee or by other means in accordance with the applicable rules. However, there are situations in which non-compliance can result in abandonment or lapse of the patent or patent application, resulting in partial or complete loss of patent rights in the relevant jurisdiction. In such an event, our competitors might be able to enter the market, which could have a material adverse effect on our business.

Issued patents covering our product candidates could be found invalid or unenforceable if challenged in court.

If we initiated legal proceedings against a third party to enforce a patent covering one of our product candidates, the defendant could counterclaim that the patent covering our product candidate is invalid and/or unenforceable. Grounds for a validity challenge could be an alleged failure to meet any of several statutory requirements, including lack of novelty, obviousness, or non-enablement. Grounds for an unenforceability assertion could be an allegation that someone connected with prosecution of the patent withheld relevant information from the USPTO, or made a misleading statement, during prosecution. Third parties may also raise similar claims before administrative bodies in the United States or abroad, even outside the context of litigation.

Such mechanisms include re-examination, post grant review, and equivalent proceedings in foreign jurisdictions (e.g., opposition proceedings). Such proceedings could result in revocation or amendment to our patents in such a way that they no longer cover our product candidates.

The outcome following legal assertions of invalidity and unenforceability is unpredictable. With respect to the validity question, for example, we cannot be certain that there is no invalidating prior art, of which we and the patent examiner were unaware during prosecution. If a defendant were to prevail on a legal assertion of invalidity and/or unenforceability, we would lose at least part, and perhaps all, of the patent protection on one or more of our product candidates. Such a loss of patent protection could have a material adverse impact on our business. A defendant could also challenge our ownership of patents assigned to us. We cannot be certain that a third party would not challenge our rights to these patents and patent applications. Any legal proceeding or enforcement action can also be expensive and time-consuming.

Patent terms may be inadequate to protect our competitive position on our products for an adequate amount of time.

The term of any individual patent depends on applicable law in the country where the patent is granted. In the United States, provided all maintenance fees are timely paid, a patent generally has a term of 20 years from its application filing date or earliest claimed non-provisional filing date. Extensions may be available under certain circumstances, but the life of a patent and, correspondingly, 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. For patents that are eligible for extension of patent term, we expect to seek extensions of patent terms in the United States and, if available, in other countries. In the United States, the Drug Price Competition and Patent Term Restoration Act of 1984 permits a patent term extension of up to five years beyond the normal expiration of the patent, which is limited to the approved indication (or any additional equivalent indications approved during the period of extension). 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 otherwise, or failure to satisfy any of the numerous applicable requirements. Moreover, the applicable authorities, including the FDA and the USPTO in the United States, 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 pre-clinical 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.

We may not be able to protect our intellectual property rights throughout the world.

Filing, prosecuting, and defending our intellectual property in countries throughout the world could be prohibitively expensive, and our intellectual property rights in some countries outside the United States can be less extensive than those in the United States. Therefore, we may choose not to pursue or maintain protection for certain intellectual property in certain jurisdictions. In addition, the laws of some foreign countries do not protect intellectual property rights to the same extent as federal and state laws in the United States. Consequently, we may not be able to prevent third parties from practicing our inventions in all countries outside the United States, or from selling or importing products made using our inventions in and into the United States or other jurisdictions. Competitors may use our technologies in jurisdictions where we have not obtained patent protection to develop their own products and further, may export otherwise infringing products to territories where we have patent protection, but enforcement is not as strong as that in the United States. These products may compete with our products and our patents or other intellectual property rights may not be effective or sufficient to prevent such competitors from competing.

Many companies have encountered significant problems in protecting and defending intellectual property rights in foreign jurisdictions. The legal systems of certain countries, particularly certain developing countries, do not favor the enforcement of patents, trade secrets, and other intellectual property protection, particularly those relating to biotechnology products, which could make it difficult for us to stop the infringement of our patents or marketing of competing products in violation of our proprietary rights generally. Proceedings to enforce our patent rights in foreign jurisdictions could result in substantial costs and divert our efforts and attention from other aspects of our business, could put our patents at risk of being invalidated or interpreted narrowly and our patent applications at risk of not issuing, and could provoke third parties to assert claims against us. We may not prevail in any lawsuit that we initiate and the damages or other remedies awarded, if any, may not be commercially meaningful. Accordingly, our efforts to enforce our intellectual property rights around the world may be inadequate to obtain a significant commercial advantage from the intellectual property that we develop or license. In addition, many countries have compulsory licensing laws under which a patent owner may be compelled to grant licenses to third parties (for example, the patent owner has failed to “work” the invention in that country, or the third party has patented improvements) or limit the enforceability of patents against government agencies or government contractors. In these countries, the patent owner may have limited remedies, which could materially diminish the value of the patent.

If our trademarks and trade names are not adequately protected, then we may not be able to build name recognition in our trademarks of interest and our business may be adversely affected.

While we seek to protect the trademarks we use in the United States and in other countries, we may be unsuccessful in obtaining registrations and/or otherwise protecting these trademarks. If that were to happen, we may be prevented from using our names, brands, and trademarks unless we enter into appropriate royalty, license, or coexistence agreements, which may not be available or may not be available on commercially reasonable terms. Over the long term, if we are unable to establish name recognition based on our trademarks, trade names, service marks, and domain names, then we may not be able to compete effectively, resulting in a material adverse effect on our business. Our registered or unregistered trademarks or trade names may be challenged, infringed, diluted, 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 to build name recognition among potential partners or customers in our markets of interest. At times, competitors may adopt trademarks and trade names similar to ours, thereby impeding our ability to build brand identity and possibly leading to market confusion. In addition, there could be potential trademark infringement claims brought by owners of other registered trademarks or trademarks that incorporate variations of our registered or unregistered trademarks. Over the long term, if we are unable to establish name recognition based on our trademarks, then we may not be able to compete effectively and our business may be adversely affected. 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. Effective trademark protection may not be available or may not be sought in every country in which our products are made available. Any name we propose to use for our products in the United States 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 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.

Our proprietary rights may not adequately protect our technologies and product candidates, and do not necessarily address all potential threats to our competitive advantage.

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:

The May 2024 RIF was undertaken to significantly reduce our ongoing operating expenses but it may not result in our intended outcomes and may yield unintended consequences and additional costs.

In connection with the May 2024 RIF, we incurred charges of approximately $4.1 million in connection with the reduction in force, primarily consisting of severance payments, employee benefits and related costs. We incurred an additional $5.2 million in

charges for the restructuring subsequent to the May 2024 RIF. This amount primarily relates to ongoing retention efforts for current employees and have been reflected within the financial statements as of September 30, 2024.

The reduction in force may result in unintended consequences and costs, such as the loss of institutional knowledge and expertise, attrition beyond the intended number of employees, decreased morale among our remaining employees, and the risk that we may not achieve the anticipated benefits of the reduction in force. In addition, while positions have been eliminated certain functions necessary to our operations remain, and we may be unsuccessful in distributing the duties and obligations of departed employees among our remaining employees. The reduction in workforce could also make it difficult for us to pursue, or prevent us from pursuing, new opportunities and initiatives due to insufficient personnel, or require us to incur additional and unanticipated costs to hire new personnel to pursue such opportunities or initiatives. If we are unable to realize the anticipated benefits from the reduction in force, or if we experience significant adverse consequences from the reduction in force, our business, financial condition, and results of operations may be materially adversely affected.

In the future, we may engage in acquisitions or strategic partnerships that could disrupt our business, cause dilution to our stockholders, reduce our financial resources, cause us to incur debt or assume contingent liabilities, and subject us to other risks.

In the future, we may enter into transactions to acquire other businesses, products, or technologies or enter into strategic partnerships, including licensing. If we do identify suitable acquisition or partnership candidates, we may not be able to make such acquisitions or partnerships on favorable terms, or at all. Any acquisitions or partnerships we make may not strengthen our competitive position, and these transactions may be viewed negatively by employees, customers or investors. We may decide to incur debt in connection with an acquisition or issue our common stock or other equity securities to the stockholders of the acquired company, which would reduce the percentage ownership of our existing stockholders. We could incur losses resulting from undiscovered liabilities of the acquired business or partnership that are not covered by the indemnification we may obtain from the seller or our partner. In addition, we may not be able to successfully integrate any acquired personnel, technologies, and operations into our existing business in an effective, timely, and non-disruptive manner. Acquisitions or partnerships may also divert management attention from day-to-day responsibilities, lead to a loss of key personnel, increase our expenses, and reduce our cash available for operations and other uses. We cannot predict the number, timing, or size of future acquisitions or partnerships or the effect that any such transactions might have on our operating results.

Our common stock may be delisted from The Nasdaq Global Market if we cannot regain compliance with Nasdaq’s continued listing requirements, which could harm our business, the trading price of our common stock, our ability to raise additional capital and the liquidity of the market for our common stock.

Our common stock is currently listed on The Nasdaq Global Market. To maintain the listing of our common stock on The Nasdaq Global Market, we are required to meet certain listing requirements, including related to the price of our common stock. On July 19, 2024, we received a Notice from Nasdaq notifying us that for the last 30 consecutive business days, the bid price for our common stock, par value $0.001 per share, had closed below the $1.00 per share minimum bid price requirement for continued inclusion on The Nasdaq Global Market as set forth in Nasdaq Listing Rule 5450(a)(1) (“the Minimum Bid Price Requirement”). The Notice has no effect at this time on the listing of our common stock, which continues to trade on The Nasdaq Global Market under the symbol “LYRA.”

In accordance with Nasdaq Listing Rule 5810(c)(3)(C), we have a period of 180 calendar days, or until January 15, 2025 (the “Compliance Date”) to regain compliance with the Minimum Bid Price Requirement. To regain compliance with the Minimum Bid Price Requirement, the closing bid price of the common stock must be at least $1.00 per share for a minimum of 10 consecutive business days prior to the Compliance Date.

In the event we do not regain compliance with the Minimum Bid Price Requirement by the Compliance Date, we may be eligible for a second 180 calendar day compliance period. To qualify, we must submit an application to transfer the listing of the common stock to The Nasdaq Capital Market, which requires us to meet the continued listing requirement for the market value of publicly held shares and all other initial listing standards for The Nasdaq Capital Market, with the exception of the bid price requirement. We would also need to pay an application fee to Nasdaq and to provide written notice of its intention to cure the deficiency during the additional compliance period. As part of its review process, Nasdaq will make a determination of whether it believes we will be able to cure this deficiency. If the Company does not qualify for or fails to regain compliance during the additional compliance period, then Nasdaq will notify us of its determination to delist our common stock, at which point we would have an opportunity to appeal the delisting determination to a Nasdaq hearings panel. There can be no assurance that, if we decide to appeal any delisting determination, such appeal would be successful.

We intend to actively monitor the closing bid price of our common stock and may, if appropriate, consider implementing available options to regain compliance with the Minimum Bid Price Requirement. There can be no assurance that we will be able to regain compliance with the Minimum Bid Price Requirement or maintain compliance with any other listing requirements.

Delisting from The Nasdaq Global Market or any Nasdaq market could make trading our common stock more difficult for investors, potentially leading to declines in our share price and liquidity. In addition, without a Nasdaq market listing, stockholders may have a difficult time getting a quote for the sale or purchase of our common stock, the sale or purchase of our common stock would likely be made more difficult and the trading volume and liquidity of our common stock could decline. Delisting from Nasdaq could also result in negative publicity and could also make it more difficult for us to raise additional capital. The absence of such a listing may adversely affect the acceptance of our common stock as currency or the value accorded by other parties. If our common stock is delisted by Nasdaq, our common stock may be eligible to trade on an over-the-counter quotation system, such as the OTCQB market, where an investor may find it more difficult to sell our common stock or obtain accurate quotations as to the market value of our common stock. We cannot assure you that our common stock, if delisted from Nasdaq, will be listed on another national securities exchange or quoted on an over-the counter quotation system.

The market price of our common stock may be volatile and fluctuate substantially, which could result in substantial losses for purchasers of our common stock.

Our stock price may be volatile. The stock market in general and the market for smaller biotechnology companies in particular have experienced extreme volatility that has often been unrelated to the operating performance of particular companies. As a result of this volatility, you may not be able to sell your common stock at or above your purchase price. The market price for our common stock may be influenced by many factors, including:

In addition, the trading prices for common stock of other biotechnology companies may become highly volatile as a result of geopolitical events such as the current conflicts between Russia and Ukraine and in the Middle East. The extent to which such events may impact our business, pre-clinical studies, and clinical trials will depend on future developments, which are highly uncertain and cannot be predicted with confidence.

A significant portion of our total outstanding shares are eligible to be sold into the market in the near future, which could cause the market price of our common stock to drop significantly, even if our business is doing well.

Sales of a substantial number of shares of our common stock in the public market, 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. Holders of approximately 60.1 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, until such shares can otherwise be sold without restriction under Rule 144 or until the rights terminate pursuant to the terms of the ninth amended and restated investor rights agreement between us and such holders. We have also registered all shares of common stock that we may issue under our equity compensation plans, which can be freely sold in the public market upon issuance, subject to volume limitations applicable to affiliates.

We are an “emerging growth company,” and the reduced disclosure requirements applicable to emerging growth companies may make our common stock less attractive to investors.

We are an “emerging growth company,” as defined in the JOBS Act, and may remain an emerging growth company until December 31, 2025. However, if certain events occur prior to such date, including if we become a “large accelerated filer,” our annual gross revenues exceed $1.235 billion, or we issue more than $1.0 billion of non-convertible debt in any three-year period, we will cease to be an emerging growth company prior to such date. For so long as we remain an emerging growth company, we are permitted and intend to rely on exemptions from certain disclosure requirements that are applicable to other public companies that are not emerging growth companies. These exemptions include:

We have taken advantage of reduced reporting burdens in our Annual Reports on Form 10-K and our Quarterly Reports on Form 10-Q including by providing only two years of audited financial statements and have not included all of the executive compensation related information that would be required if we were not an emerging growth company. We cannot predict whether investors will find our common stock less attractive if we rely on these exemptions. 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 reduced or more volatile. In addition, the JOBS Act provides that an emerging growth company can take advantage of an extended transition period for complying with new or revised accounting standards. This allows an emerging growth company to delay the adoption of these accounting standards until they would otherwise apply to private companies.

If securities or industry analysts do not publish research or reports about our business, or if they issue an adverse or misleading opinion regarding our stock, our stock price and trading volume could decline, even if our business is doing well.

The trading market for our common stock will be influenced by the research and reports that industry or securities analysts publish about us or our business. If any of the analysts who cover us issue an adverse or misleading opinion regarding us, our business model, our intellectual property, or our stock performance, or if our target pre-clinical studies or clinical trials and operating results fail to meet the expectations of analysts, our stock price would likely decline. If one or more of these analysts ceases coverage of us or fails to publish reports on us regularly, we could lose visibility in the financial markets, which in turn could cause our stock price or trading volume to decline.

We are a “smaller reporting company” and the reduced disclosure requirements applicable to smaller reporting companies may make our common stock less attractive to investors.

We are considered a “smaller reporting company.” We are therefore entitled to rely on certain reduced disclosure requirements, such as an exemption from disclosing certain executive compensation information and three years of financial statements. We are also exempt from the requirement to obtain an external audit on the effectiveness of internal control over financial reporting provided in Section 404(b) of the Sarbanes-Oxley Act. These exemptions and reduced disclosures in our SEC filings due to our status as a smaller reporting company may make it harder for investors to analyze our results of operations and financial prospects. 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 trading market for our common stock and our stock prices may be more volatile.

Provisions in our restated certificate of incorporation and amended and restated bylaws and under Delaware law could make an acquisition of our Company, which may be beneficial to our stockholders, more difficult and may prevent attempts by our stockholders to replace or remove our current management.

Provisions in our restated certificate of incorporation and our amended and restated bylaws may discourage, delay, or prevent a merger, acquisition, or other change in control of our Company that stockholders may consider favorable, including transactions in which you might otherwise receive a premium for your shares. These provisions could also limit the price that investors might be willing to pay in the future for shares of our common stock, thereby depressing the market price of our common stock. In addition, because our Board of Directors is responsible for appointing the members of our management team, these provisions may frustrate or prevent any attempts by our stockholders to replace or remove our current management by making it more difficult for stockholders to replace members of our Board of Directors. Among other things, these provisions include those establishing:

Moreover, because we are incorporated in Delaware, we are governed by the provisions of Section 203 of the General Corporation Law of the State of Delaware, which prohibits a person who owns in excess of 15% of our outstanding voting stock from merging or combining with us for a period of three years after the date of the transaction in which the person acquired in excess of 15% of our outstanding voting stock, unless the merger or combination is approved in a prescribed manner.

Our restated certificate of incorporation designates specific courts as the exclusive forum for certain litigation that may be initiated by our stockholders, which could limit our stockholders’ ability to obtain a favorable judicial forum for disputes with us.

Our restated certificate of incorporation specifies that, unless we consent in writing to the selection of an alternative forum, the Court of Chancery of the State of Delaware will be the sole and exclusive forum for most legal actions involving claims brought against us by stockholders; provided that, the exclusive forum provision will not apply to suits brought to enforce any liability or duty created by the Securities Act, the Exchange Act, the rules and regulations thereunder, or any other claim for which the federal courts have exclusive jurisdiction; and provided further that, if and only if the Court of Chancery of the State of Delaware dismisses any such action for lack of subject matter jurisdiction, such action may be brought in another state or federal court sitting in the State of Delaware. Our restated certificate of incorporation further provides that, unless we consent in writing to the selection of an alternative forum, the federal district courts of the United States of America shall, to the fullest extent permitted by law, be the sole and exclusive forum for the resolution of any complaint asserting a cause of action arising under the Securities Act. Any person or entity purchasing or otherwise acquiring any interest in shares of our capital stock shall be deemed to have notice of and to have consented to the provisions of our restated certificate of incorporation described above.

We believe these provisions benefit us by providing increased consistency in the application of Delaware law by chancellors particularly experienced in resolving corporate disputes and in the application of the Securities Act by federal judges, as applicable, efficient administration of cases on a more expedited schedule relative to other forums, and protection against the burdens of multi-forum litigation. However, the provision may have the effect of discouraging lawsuits against our directors, officers, employees, and agents as it may limit any stockholder’s ability to bring a claim in a judicial forum that such stockholder finds favorable for disputes with us or our directors, officers, employees, or agents. The enforceability of similar choice of forum provisions in other companies’ certificates of incorporation has been challenged in legal proceedings, and it is possible that, in connection with any applicable action brought against us, a court could find the choice of forum provisions contained in our restated certificate of incorporation to be inapplicable or unenforceable in such action. If a court were to find the choice of forum provision contained in our restated certificate of incorporation to be inapplicable or unenforceable in an action, we may incur additional costs associated with resolving such action in other jurisdictions, which could adversely affect our business, financial condition, or results of operations.

We have incurred and expect to continue to incur significant costs as a result of operating as a public company, and our management is required to devote substantial time to new compliance initiatives and corporate governance practices.

As a public company, we incur significant legal, accounting, and other expenses. The Sarbanes-Oxley Act of 2002, the Dodd-Frank Wall Street Reform and Consumer Protection Act, the listing requirements of The Nasdaq Global Market, and other applicable securities rules and regulations impose various requirements on public companies, including establishment and maintenance of effective disclosure and financial controls and corporate governance practices. Our management and other personnel devote a substantial amount of time to these compliance initiatives. Moreover, these rules and regulations have increased our legal and financial compliance costs and made some activities more time-consuming and costly. For example, we expect that these rules and regulations may make it more difficult and more expensive for us to obtain director and officer liability insurance, which in turn could make it more difficult for us to attract and retain qualified members of our Board of Directors.

We continue to evaluate these rules and regulations, and cannot predict or estimate the amount of additional costs we may incur or the timing of such costs. These rules and regulations are often subject to varying interpretations, in many cases due to their lack of specificity, and, as a result, their application in practice may evolve over time as new guidance is provided by regulatory and governing bodies. This could result in continuing uncertainty regarding compliance matters and higher costs necessitated by ongoing revisions to disclosure and governance practices.

Pursuant to Section 404 of the Sarbanes-Oxley Act of 2002, or Section 404, we are required to furnish a report by our management on our internal control over financial reporting. However, while we remain an emerging growth company, we will not be required to include an attestation report on internal control over financial reporting issued by our independent registered public accounting firm. To achieve compliance with Section 404 within the prescribed period, we are engaged in a process to document and evaluate our internal control over financial reporting, which is both costly and challenging. In this regard, we will need to continue to dedicate internal resources, engage outside consultants, adopt a detailed work plan to assess and document the adequacy of internal control over financial reporting, continue steps to improve control processes as appropriate, validate through testing whether such controls are functioning as documented, and implement a continuous reporting and improvement process for internal control over financial reporting. Despite our efforts, there is a risk that we will not be able to conclude, within the prescribed timeframe or at all, that our internal control over financial reporting is effective as required by Section 404. We may discover significant deficiencies or material weaknesses, which we may not successfully remediate on a timely basis or at all. Any failure to remediate any significant deficiencies or material weaknesses identified by us or to implement required new or improved controls, or difficulties encountered in their implementation, could cause us to fail to meet our reporting obligations or result in material misstatements in our financial statements. The identification of one or more material weaknesses could result in an adverse reaction in the financial markets due to a loss of confidence in the reliability of our financial statements.

Because we do not anticipate paying any cash dividends on our common shares in the foreseeable future, capital appreciation, if any, would be your sole source of gain.

On March 20, 2012, we declared and paid a special cash dividend of $0.2630467 per share of our common stock, par value $0.001, which we refer to as the Special Dividend, which totaled approximately $42,115 in the aggregate. Other than the Special Dividend, we have never declared or paid any cash dividends on our common shares. We currently anticipate that we will retain future earnings for the development, and operation of our business and do not anticipate declaring or paying any cash dividends for the foreseeable future. As a result, capital appreciation, if any, of our common shares would be your sole source of gain on an investment in our common shares for the foreseeable future.

Litigation could be costly and time-consuming and could result in additional liabilities.

We may from time to time be subject to legal proceedings and claims that arise in the ordinary course of business or otherwise, such as claims brought by us against, vendors or collaborators, and/or claims brought by our customers in connection with commercial disputes and employment claims made by our current or former employees. Claims may also be asserted by or on behalf of a variety of other parties, including government agencies, patients, or vendors of our customers, or stockholders.

Any litigation involving us may result in substantial costs, operationally restrict our business, and may divert management’s attention and resources, which may seriously harm our business, overall financial condition, and results of operations. Insurance may not cover existing or future claims, be sufficient to fully compensate us for one or more of such claims, or continue to be available on terms acceptable to us. A claim brought against us that is uninsured or under insured could result in unanticipated costs, thereby adversely impacting our results of operations and resulting in a reduction in the trading price of our stock.

In the past, 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 biotechnology companies have experienced significant stock price volatility in recent years. If we face such litigation, it could result in substantial costs and a diversion of management’s attention and resources, which could harm our business.

Our insurance policies are expensive and protect us only from some business risks, which leaves us exposed to significant uninsured liabilities.

We do not carry insurance for all categories of risk that our business may encounter. Some of the policies we currently maintain include general liability, employment practices liability, and property, auto, workers’ compensation, umbrella, and directors’

and officers’ insurance. Any additional product liability insurance coverage we acquire in the future may not be sufficient to reimburse us for any expenses or losses we may suffer.

Moreover, insurance coverage is becoming increasingly expensive and in the future we may not be able to maintain insurance coverage at a reasonable cost or in sufficient amounts to protect us against losses. If we obtain marketing approval for LYR-210, we intend to acquire insurance coverage to include the sale of commercial products; however, we may be unable to obtain product liability insurance on commercially reasonable terms or in adequate amounts. A successful product liability claim or series of claims brought against us could cause our share price to decline and, if judgments exceed our insurance coverage, could adversely affect our results of operations and business, including preventing or limiting the development and commercialization of any product candidates we develop. We do not carry specific biological or hazardous waste insurance coverage, and our property, casualty, and general liability insurance policies specifically exclude coverage for damages and fines arising from biological or hazardous waste exposure or contamination. Accordingly, in the event of contamination or injury, we could be held liable for damages or be penalized with fines in an amount exceeding our resources, and our clinical trials or regulatory approvals could be suspended.

Operating as a public company has made it more difficult and more expensive for us to obtain director and officer liability insurance, and in the future we may be required to accept reduced policy limits and coverage or incur substantially higher costs to obtain the same or similar coverage. As a result, it may be more difficult for us to attract and retain qualified people to serve on our Board of Directors, our board committees, or as executive officers. We do not know, however, if we will be able to maintain existing insurance with adequate levels of coverage. Any significant uninsured liability may require us to pay substantial amounts, which would adversely affect our cash position and results of operations.

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 the Company’s current and projected business operations and its financial condition and results of operations.

Actual 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. The Company maintains the majority of its cash and cash equivalents in accounts with major U.S. institutions, and our deposits at certain of these institutions exceed insured limits. Market conditions can impact the viability of these institutions. In the event of failure of any of the financial institutions where we maintain our cash and cash equivalents, there can be no assurance that we would be able to access uninsured funds in a timely manner or at all. Any inability to access or delay in accessing these funds could adversely affect our current and projected business operations, our financial condition and results of operations.

Our ability to use our 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 net operating loss carryforwards, or NOLs, of $128.3 million for federal income tax purposes and $48.3 million for state income tax purposes, which may be available to offset our future taxable income, if any, and begin to expire at various dates through 2043. As of December 31, 2023, we also had federal and state research and development credit carryforwards of $5.3 million, which begin to expire at various dates through 2043. In general, under Sections 382 and 383 of the Internal Revenue Code of 1986, or IRC, as amended, or the Code, a corporation that undergoes an “ownership change,” generally defined as a greater than 50% change by value in its equity ownership over a three-year period, is subject to limitations on its ability to utilize its pre-change NOLs and its research and development credit carryforwards to offset future taxable income. The Company had performed an IRC 382 study during the prior year which resulted in identifying three separate ownership changes that occurred on March 31, 2006, January 17, 2020, and April 13, 2022. We performed an update assessment to our 382 analysis in conjunction with the May 2023 financing noting no additional ownership change. For these reasons, in the event we experience a change of control, we may not be able to utilize a material portion of the NOLs or research and development credit carryforwards even if we attain profitability.

New tax legislation may impact our results of operations and financial condition.

The Inflation Reduction Act of 2022 introduced, among other changes, a 15% corporate minimum tax on certain United States corporations and a 1% excise tax on certain stock redemptions by United States corporations. The U.S. government may enact further significant changes to the taxation of business entities. The likelihood of these changes being enacted or implemented is unclear. We are currently unable to predict the ultimate impact of the Inflation Reduction Act or any such further changes on our business.

Unstable global, political or economic conditions may have serious adverse consequences on our business, financial condition and share price.

The global economy, including credit and financial markets, has experienced extreme volatility and disruptions, including severely diminished liquidity and credit availability, rising interest and inflation rates, declines in consumer confidence, declines in economic growth, increases in unemployment rates and uncertainty about economic stability. There can be no assurance that further deterioration in credit and financial markets and confidence in economic conditions will not occur. If the equity and credit markets continue to deteriorate, or the United States enters a recession, it may make any necessary debt or equity financing more difficult to obtain in a timely manner or on favorable terms, more costly or more dilutive. In addition, international terrorism and conflicts could disrupt or otherwise adversely impact our operations and those of third parties upon which we rely. Related sanctions, export controls or other actions have and may in the future be initiated by nations including the U.S., the EU or Russia (e.g., potential cyberattacks, disruption of energy flows, etc.), which could adversely affect our business and/or our supply chain, our CROs, CMOs and other third parties with which we conduct business. Any of the foregoing could harm our business, results of operations and price of our common stock may be adversely affected.

We or the third parties upon whom we depend may be adversely affected by natural disasters and our business continuity and disaster recovery plans may not adequately protect us from a serious disaster.

Natural disasters could severely disrupt our operations and have a material adverse effect on our business, results of operations, financial condition, and prospects. If a natural disaster, power outage, or other event occurred that prevented us from using all or a significant portion of our headquarters, that damaged critical infrastructure, such as the manufacturing facilities on which we rely, or that otherwise disrupted operations, it may be difficult or, in certain cases, impossible for us to continue our business for a substantial period of time. The disaster recovery and business continuity plans we have in place may prove inadequate in the event of a serious disaster or similar event. We may incur substantial expenses as a result of the limited nature of our disaster recovery and business continuity plans, which could have a material adverse effect on our business. For example, following Hurricane Maria, shortages in production and delays in a number of medical supplies produced in Puerto Rico resulted, and any similar interruption due to a natural disaster affecting us or any of our third-party manufacturers could materially delay our operations.

International terrorism, political unrest, and wars, or other events such as the COVID-19 pandemic have previously and could in the future adversely impact our business and operations, including our clinical trials.

International terrorism, political unrest and wars could delay or disrupt our business activity, and if any conflict escalates or spills over to or otherwise impacts additional regions, it could heighten many of the other risk factors described in this Item 1A. In addition, the COVID-19 global pandemic and government measures taken in response have had a significant impact, both direct and indirect, on businesses and commerce, as worker shortages have occurred; supply chains have been disrupted; facilities and production have been suspended; and demand for certain goods and services, such as medical services and supplies, has spiked, while demand for other goods and services, has fallen. If the COVID-19 pandemic resurges, our business and operations could be adversely affected again. Similarly, if another pandemic unfolds or if a geopolitical crisis escalates, our business and operations could be adversely affected.

(b) Material changes to the procedures by which security holders may recommended nominees to the board of directors.

During the three months ended September 30, 2024, no director or officer of the Company, as defined in Rule 16a-1(f) of the Exchange Act, adopted or terminated a “Rule 10b5-1 trading arrangement” intended to satisfy the affirmative defense of Rule 10b5-1(c) or “non-Rule 10b5-1 trading arrangement” as each term is defined in Item 408(a) of Regulation S-K.

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.


德拉瓦	84-1700838
（州或其他司法管辖区成立或组织）	（国税局雇主识别号）
阿森纳路480号水城, 马	02472
（主要行政办公室地址）	(Zip代码）


		页面
第一部分.	财务资料	2
项目1.	简明合并财务报表（未经审计）	2
	精简合并资产负债表	2
	简明合并经营报表和综合损失	3
	简明合并股东权益报表	4
	简明综合现金流量表	6
	公司简明综合财务报表附注	7
项目2.	管理层对财务状况和经营成果的讨论和分析	20
项目3.	关于市场风险的定量和定性披露	33
项目4.	控制和程式	33
第二部分.	其他信息	34
项目1.	法律诉讼	34
项目1A.	危险因素	34
项目2.	股权证券的未登记销售和收益的使用	84
项目3.	优先证券	84
项目4.	矿山安全披露	84
项目5.	其他信息	85
项目6.	展品	86
签名		87


	9月30日，			12月31日，
	2024			2023
资产
易变现资产：
现金及现金等价物	$	23,800		$	22,353
短期投资		27,826			80,400
预付费用和其他易变现资产		2,818			2,068
易变现资产总额		54,444			104,821
财产和设备，净值		1,613			2,043
经营租赁使用权资产		20,707			33,233
受限制现金		1,992			1,392
其他资产		—			1,111
总资产	$	78,756		$	142,600
负债和股东权益
流动负债：
应付帐款	$	2,292		$	3,131
重组责任		4,855			—
应计费用和其他流动负债		3,197			9,374
经营租赁负债		4,003			5,434
递延收入		607			1,658
流动负债总额		14,954			19,597
经营租赁负债，扣除流动部分		31,321			21,447
递延收入，扣除流动部分		11,862			12,136
总负债		58,137			53,180
承诺和意外情况 (Note 13）
股东权益：
优先股，美金0.001 面值， 10,000,000 2024年9月30日授权的股份和2023年12月31日; 不是截至2024年9月30日已发行和发行的股份以及 2023年12月31日		—			—
普通股，美金0.001 面值; 200,000,000 授权的股份 2024年9月30日和2023年12月31日; 65,456,735 和 57,214,550 发行股份并分别于2024年9月30日和2023年12月31日未偿还		65			57
借记资本公积		414,345			400,685
累计其他综合收益，扣除税		20			33
累计赤字		(393,811	)		(311,355	)
股东权益总额		20,619			89,420
负债和股东权益总额	$	78,756		$	142,600


	止三个月 9月30日，						截至9月30日的九个月，
	2024			2023			2024			2023
协作收入	$	195		$	544		$	1,325		$	1,412

运营费用：
研发		5,902			12,368			37,404			35,763
一般和行政		3,931			5,003			14,888			14,700
财产和设备损坏		—			—			1,883			1,592
使用权资产减损		—			—			22,836			—
重组和其他相关费用		2,804			—			9,254			—
总运营费用		12,637			17,371			86,265			52,055
经营亏损		(12,442	)		(16,827	)		(84,940	)		(50,643	)
其他收入：
利息收入		576			1,192			2,517			3,161
其他收入总额		576			1,192			2,517			3,161
除所得税开支前亏损		(11,866	)		(15,635	)		(82,423	)		(47,482	)
所得税开支		(7	)		(16	)		(33	)		(42	)
净亏损		(11,873	)		(15,651	)		(82,456	)		(47,524	)
其他综合损失：
短期投资未实现持有收益（损失），扣除税款		24			20			(13	)		(17	)
全面亏损	$	(11,849	)	$	(15,631	)	$	(82,469	)	$	(47,541	)
归属于普通股的每股净亏损股东-基本和稀释	$	(0.18	)	$	(0.27	)	$	(1.27	)	$	(1.04	)
加权平均流通普通股- 基本及摊薄		65,456,735			56,953,685			64,981,219			45,894,643


	截至9月30日的九个月，
	2024			2023
经营活动产生的现金流量：
净亏损	$	(82,456	)	$	(47,524	)
将净亏损与经营活动中使用的净现金进行调节的调整：
股票补偿		4,777			4,405
折旧费用		320			193
财产和设备损坏		1,883			1,592
递延融资成本冲销		140			—
使用权资产减损		22,836			—
短期投资溢价净摊销		(2,009	)		(2,408	)
经营资产和负债变化：
预付费用和其他易变现资产		(750	)		565
经营租赁使用权资产		570			1,080
其他资产		1,111			(3,240	)
应付帐款		(774	)		3,985
应计费用和其他流动负债		(5,400	)		(625	)
重组责任		4,855			—
经营租赁负债		(2,437	)		(857	)
递延收入		(1,325	)		(1,412	)
经营活动所用现金净额		(58,659	)		(44,246	)
投资活动产生的现金流量：
购买财产和设备		(2,396	)		(260	)
购买短期投资		(47,949	)		(72,765	)
短期投资的成熟度		102,519			62,800
投资活动提供（用于）的净现金		52,174			(10,225	)
融资活动产生的现金流量：
出售普通股、购买证和预先融资证的收益，扣除发行成本		8,819			50,000
支付延期发行成本		(290	)		(3,332	)
行使股票期权的收益		3			103
融资活动提供的净现金		8,532			46,771
现金、现金等值物和限制性现金净增加（减少）		2,047			(7,700	)
现金、现金等值物和受限制现金，期末		23,745			33,942
现金、现金等值物和限制现金，期末	$	25,792		$	26,242

非现金融资和投资活动补充披露：
财产和设备采购包括在应付帐款中	$	—		$	8
租赁协议修改	$	—		$	4,931
应付帐款、应计费用和其他流动负债中的发行成本	$	—		$	150
计入应付帐款和其他流动负债的其他资产	$	—		$	2,740
使用权资产换取租赁负债	$	13,667		$	—
递延发行成本包括在应付帐款和应计费用中	$	—		$	161


☒	根据1934年《证券交易法》第13或15（d）条的季度报告


☐	根据1934年《证券交易所法》第13或15（d）条提交的过渡报告


大型加速文件夹	☐	加速编报公司	☐

非加速归档	☒	小型上市公司	☒

		新兴成长型公司	☒


	普通股				额外实收			累积其他全面			积累			总计股东
	股份		量		资本			收入（损失），扣除税款			赤字			股权
2022年12月31日余额		31,827,659	$	32	$	329,387		$	10		$	(248,675	)	$	80,754
普通股期权的行使		2,115		—		4			—			—			4
RSU发行普通股归属		7,041		—		—			—			—			—
可供出售证券未实现损失		—		—		—			(22	)		—			(22	)
股票补偿		—		—		1,610			—			—			1,610
净亏损		—		—		—			—			(16,255	)		(16,255	)
2023年3月31日余额		31,836,815	$	32	$	331,001		$	(12	)	$	(264,930	)	$	66,091
发行普通股和预融资认购证，扣除发行成本美金3,332		17,652,962	$	18	$	46,650			—			—		$	46,668
普通股期权的行使		55,262		—		97			—			—			97
可供出售证券未实现损失		—		—		—			(15	)		—			(15	)
股票补偿		—		—		1,354			—			—			1,354
净亏损		—		—		—			—			(15,618	)		(15,618	)
2023年6月30日余额		49,545,039	$	50	$	379,102		$	(27	)	$	(280,548	)	$	98,577
发行成本		—		—	$	(150	)		—			—		$	(150	)
普通股期权的行使		520		—		2			—			—			2
可供出售证券的未实现收益		—		—		—			20			—			20
股票补偿		—		—		1,441			—			—			1,441
净亏损		—		—		—			—			(15,651	)		(15,651	)
2023年9月30日余额		49,545,559	$	50	$	380,395		$	(7	)	$	(296,199	)	$	84,239

	普通股				额外实收			累积其他全面			积累			总计股东
			量		资本			收入（损失），扣除税款			赤字			股权
2023年12月31日余额		57,214,550	$	57	$	400,685		$	33		$	(311,355	)	$	89,420
普通股期权的行使		918		—		3			—			—			3
ATM下发行的股份，扣除发行成本美金150		1,041,666		1		4,849			—			—			4,850
行使预先融资的认购权		1,255,500		1		1			—			—			2
普通股认购权的行使		1,424,272		2		3,806			—			—			3,808
RSU发行普通股归属		27,869		—		—			—			—			—
可供出售证券未实现损失		—		—		—			(8	)		—			(8	)
股票补偿		—		—		1,881			—			—			1,881
净亏损		—		—		—			—			(22,452	)		(22,452	)
2024年3月31日余额		60,964,775	$	61	$	411,225		$	25		$	(333,807	)	$	77,504
行使预先融资的认购权		4,490,876	$	4	$	4			—			—		$	8
普通股期权的行使		84		—		—			—			—			—
可供出售证券未实现损失		—		—		—			(29	)		—			(29	)
股票补偿		—		—		1,625			—			—			1,625
净亏损		—		—		—			—			(48,131	)		(48,131	)
2024年6月30日余额		65,455,735	$	65	$	412,854		$	(4	)	$	(381,938	)	$	30,977
ESPP下普通股发行		1,000		—		—			—			—			—
可供出售证券的未实现收益		—		—		—			24			—			24
股票补偿		—		—		1,491			—			—			1,491
净亏损		—		—		—			—			(11,873	)		(11,873	)
2024年9月30日余额		65,456,735	$	65	$	414,345		$	20		$	(393,811	)	$	20,619


贴现率	9.5-10.5%
任期（年）	2.96-9.13
预期分租租金增加		3.0	%


截至12月31日的期间，
2024年10月1日至2024年12月31日	$	1,546
2025		6,121
2026		6,494
2027		5,131
2028		4,507
此后		20,652
总期限	$	44,451
减：推定利息		(9,127	)
经营租赁负债现值	$	35,324
减：经营租赁负债的当前部分		(4,003	)
经营租赁负债总额，扣除流动部分	$	31,321


	截至9月30日的三个月，						美元
	2024			2023			变化
协作收入	$	195		$	544		$	(349	)

运营费用：
研发		5,902			12,368			(6,466	)
一般和行政		3,931			5,003			(1,072	)
财产和设备减值		—			—			—
使用权资产减值准备		—			—			—
重组和其他相关费用		2,804			—			2,804
总运营支出		12,637			17,371			(4,734	)
运营亏损		(12,442	)		(16,827	)		4,385
其他收入：
利息收入		576			1,192			(616	)
其他收入合计		576			1,192			(616	)
所得税费用前亏损		(11,866	)		(15,635	)		3,769
所得税费用		(7	)		(16	)		9
净亏损	$	(11,873	)	$	(15,651	)	$	3,778


	截至9月30日的9个月，						美元
	2024			2023			变化
协作收入	$	1,325		$	1,412		$	(87	)

运营费用：
研发		37,404			35,763			1,641
一般和行政		14,888			14,700			188
财产和设备减值		1,883			1,592			291
使用权资产减值准备		22,836			—			22,836
重组和其他相关费用		9,254			—			9,254
总运营支出		86,265			52,055			34,210
运营亏损		(84,940	)		(50,643	)		(34,297	)
其他收入：
利息收入		2,517			3,161			(644	)
其他收入合计		2,517			3,161			(644	)
所得税费用前亏损		(82,423	)		(47,482	)		(34,941	)
所得税费用		(33	)		(42	)		9
净亏损	$	(82,456	)	$	(47,524	)	$	(34,932	)


	截至		截至
	9月30日， 2024		十二月三十一日， 2023
现金及现金等价物	$	23,800	$	22,353
短期投资		27,826		80,400
*总计	$	51,626	$	102,753


Exhibit Number	Description	Form or Schedule	Exhibit No.	Filing Date with SEC	SEC File Number

3.1	Restated Certificate of Incorporation of the Registrant, dated May 5, 2020 and the Certificate of Amendment to the Restated Certificate of Incorporation of the Registrant, dated June 13, 2024.	8-K	3.1	June 18, 2024	001-39273

3.2	Amended and Restated Bylaws of the Registrant	8-K	3.1	December 18, 2023	001-39273

4.1	Specimen Stock Certificate evidencing the shares of Common Stock of the Registrant	S-1	4.2	April 27, 2020	333-236962

31.1*	Certification of Principal Executive Officer Pursuant to Rules 13a-14(a) and 15d-14(a) under the Securities Exchange Act of 1934, as Adopted Pursuant to Section 302 of the Sarbanes-Oxley Act of 2002

31.2*	Certification of Principal Financial Officer Pursuant to Rules 13a-14(a) and 15d-14(a) under the Securities Exchange Act of 1934, as Adopted Pursuant to Section 302 of the Sarbanes-Oxley Act of 2002

32.1+	Certification of Principal Executive Officer Pursuant to 18 U.S.C. Section 1350, as Adopted Pursuant to Section 906 of the Sarbanes-Oxley Act of 2002

32.2+	Certification of Principal Financial Officer pursuant to 18 U.S.C. Section 1350, as Adopted Pursuant to Section 906 of the Sarbanes-Oxley Act of 2002

101.INS*	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*	Inline XBRL Taxonomy Extension Schema Document

101.CAL*	Inline XBRL Taxonomy Extension Calculation Linkbase Document

101.DEF*	Inline XBRL Taxonomy Extension Definition Linkbase Document

101.LAB*	Inline XBRL Taxonomy Extension Label Linkbase Document

101.PRE*	Inline XBRL Taxonomy Extension Presentation Linkbase Document

104*	Cover Page Interactive Date File (embedded within the Inline XBRL document)


	截至2024年9月30日
普通股凭证		8,606,303
股票期权和限制性股票单位		10,075,165
员工股票购买计划		723,906
总计		19,405,374


	LYRA THERAPEUTICS, INC.

Date: November 12, 2024	By:	/s/ Maria Palasis, Ph.D.
		Maria Palasis, Ph.D.
		President and Chief Executive Officer (Principal Executive Officer)

Date: November 12, 2024	By:	/s/ Jason Cavalier
		Jason Cavalier
		Chief Financial Officer (Principal Financial Officer and Principal Accounting Officer)