美国
证券交易委员会
华盛顿特区20549
表格
截至2024年6月30日季度结束
或
委员会档案编号：
（依凭章程所载的完整登记名称）
| 编号 | |
(成立地或组织其他管辖区) | （联邦税号） |
(主要行政办公室的地址)（邮政编码）
(
(注册人电话号码，包括区号)
根据法案第12(b)条规定注册的证券：
请打勾表示登记人（1）在过去12个月内（或在过去必须提交这些报告的较短期间内），是否已按照1934年证券交易法第13条或15条的规定提交了所有需要提交的报告，（2）是否在过去90天内一直受到此提交要求的约束。
在前12个月内（或公司需要提交这些文件的较短时间内），公司是否已通过选中标记表明已阅读并提交了应根据S-t法规第405条规定（本章第232.405条）提交的所有互动式数据文件？
请打勾表示公司是否为大型加速发行人、加速发行人、非加速发行人、较小报告公司或新兴成长公司。请参阅《交易所法》第120亿2条中对「大型加速发行人」、「加速发行人」、「较小报告公司」和「新兴成长公司」的定义（只能选择一个）。
| 加速披露人☐ | |
非加速提交者☐ | 较小的报告公司 | |
新兴成长型公司 |
如果是新兴成长公司，请勾选指示，如果登记人已选择不遵守根据《交易所法》第13(a)条规定提供的任何新的或修订后的财务会计标准的扩展过渡期。☐
检查标记指示申报人是否为空壳公司（如Exchange Act第120亿2条的定义）。 是
截至2024年10月29日，
第一部分-财务信息
项目 1. 未经审核的基本报表
CELLDEX THERAPEUTICS, INC.
缩表合并资产负债表
(未经查核)
(以千为单位，股份和每股数据除外)
九月三十日 | 12月31日 | |||||
| 2024 |
| 2023 | |||
资产 | ||||||
流动资产: | ||||||
现金及现金等价物 | $ | | $ | | ||
有价证券 |
| |
| | ||
应收帐款和其他应收款 |
| |
| | ||
预付款及其他流动资产 |
| |
| | ||
流动资产总额 |
| |
| | ||
资产和设备净值 |
| |
| | ||
营运租赁权利资产，净额 | | | ||||
无形资产 |
| |
| | ||
其他资产 |
| |
| | ||
总资产 | $ | | $ | | ||
负债及股东权益 | ||||||
流动负债： | ||||||
应付账款 | $ | | $ | | ||
应计费用 |
| |
| | ||
营运租赁负债的流动部分 | | | ||||
其他长期负债的流动部分 |
| |
| | ||
流动负债合计 |
| |
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营业租赁负债长期部分 | | | ||||
其他长期负债 |
| |
| | ||
总负债 |
| |
| | ||
承诺和潜在负债 | ||||||
股东权益： | ||||||
2024年6月30日和2023年12月31日分别发行和流通的可转换优先股，分别为$125,292.00、$100,912.65和$93,890.20。清算优先权为$242,381、$187,780、$108,696和$96,106。 |
|
| ||||
0.01 |
| |
| | ||
资本公积额额外增资 |
| |
| | ||
其他综合收益累计额 |
| |
| | ||
累积亏损 |
| ( |
| ( | ||
股东权益总额 |
| |
| | ||
负债和股东权益总额 | $ | | $ | | ||
请参阅未经审核的简明综合财务报表附注
3
CELLDEX THERAPEUTICS, INC.
综合损益及综合亏损简明综合损益表
(未经查核)
(以千为单位，每股金额除外)
三个月结束了 | 三个月结束了 | 截至九个月 | 截至九个月 | |||||||||
| 2024年9月30日 |
| 2023年9月30日 |
| 2024年9月30日 |
| 2023年9月30日 | |||||
收入： | ||||||||||||
产品开发和许可协议 | $ | | $ | | $ | | $ | | ||||
合同与补助款 |
| |
| |
| |
| | ||||
总收益 |
| |
| |
| |
| | ||||
营业费用： |
|
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研发费用 |
| |
| |
| |
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总务与行政 |
| |
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营业费用总计 |
| |
| |
| |
| | ||||
营业亏损 |
| ( |
| ( |
| ( |
| ( | ||||
投资和其他收入净额 |
| |
| |
| |
| | ||||
净损失 | $ | ( | $ | ( | $ | ( | $ | ( | ||||
基本及稀释每股普通股净损失 | $ | ( | $ | ( | $ | ( | $ | ( | ||||
计算基本和稀释每股净亏损所使用的股份 |
| |
| |
| |
| | ||||
综合亏损： | ||||||||||||
净亏损 | $ | ( | $ | ( | $ | ( | $ | ( | ||||
其他综合损益： | ||||||||||||
持有有价证券未实现之利益 |
| |
| |
| |
| | ||||
全面损失 | $ | ( | $ | ( | $ | ( | $ | ( | ||||
请参阅未经审核的简明综合财务报表附注
4
CELLDEX THERAPEUTICS, INC.
现金流量表简明综合报表
(未经查核)
(以千为单位)
截至九个月 | 截至九个月 | |||||
| 2024年9月30日 |
| 2023年9月30日 | |||
经营活动现金流量： | ||||||
净损失 | $ | ( | $ | ( | ||
调整为使净亏损转化为经营活动所使用现金： | ||||||
折旧与摊提 |
| |
| | ||
偿还及金融工具净溢价 |
| ( |
| ( | ||
资产出售或处置损失 | | — | ||||
以股份为基础之报酬支出 |
| |
| | ||
营运资产和负债的变化： | ||||||
应收帐款和其他应收款 |
| |
| | ||
预付及其他流动资产 |
| ( |
| | ||
其他资产 | ( | ( | ||||
应付帐款和应计费用 |
| |
| | ||
其他负债 |
| ( |
| | ||
经营活动所使用之净现金流量 |
| ( |
| ( | ||
投资活动之现金流量: | ||||||
有价证券的销售和到期 |
| |
| | ||
可销售证券的购入 |
| ( |
| ( | ||
资产及设备的收购 | ( | ( | ||||
投资活动提供的净现金流量（使用） |
| ( |
| | ||
来自筹资活动的现金流量: | ||||||
股票发行的净收益 | | — | ||||
员工福利计划发行股份所得款项 |
| |
| | ||
筹资活动提供的净现金 |
| |
| | ||
现金及现金等价物的净增加（减少） |
| |
| ( | ||
期初现金及现金等价物余额 |
| |
| | ||
期末现金及现金等价物 | $ | | $ | | ||
非现金投资活动 | ||||||
在建工程应计 | $ | | $ | | ||
请参阅未经审核的简明综合财务报表附注
5
CELLDEX THERAPEUTICS, INC.
基本报表未经审核简明合并财务报表注脚
2024年9月30日
(1) 报告基础
随函附上之未经审核的简明综合基本报表已由Celldex Therapeutics, Inc. (以下简称"公司"或"Celldex") 根据美国普遍公认会计原则（"U.S. GAAP"）编制，并反映了公司及其全资子公司的业务。所有公司内部结余及交易均已在合并中消除。
这些暂行基本报表未包含美国总稽会（U.S. GAAP）对年度基本报表所需的所有信息和附注，应配合截至2023年12月31日年度基本报表的稽核基本报表一起阅读，该报表已纳入公司于2024年2月26日提交给证券交易委员会（SEC）的10-k表格。根据管理层的观点，这些暂行基本报表反映了为公平陈述公司截至报告期间的财务状况和经营成果所需的所有正常循环调整。为了比较目的呈现的年终简明资产负债表数据来自稽核基本报表，但未包含U.S. GAAP所要求的所有披露。
暂行期间的经营成果并不一定能反映出未来任何暂行期间或截至2024年12月31日的财政年度的预期经营成果。
截至2024年9月30日，公司现金、现金等价物和有市场性的证券总额为$
在未来的十二个月及更长时间内，本公司可能采取进一步措施筹集额外资金，以满足其长期流动性需求，包括但不限于以下一项或多项：与现有或新合作伙伴进行药物候选品授权、可能的业务组合、发行债务或透过私募或公开发行发行普通股或其他证券等。尽管本公司过去成功筹集资金，但无法保证额外融资将以可接受条件提供，甚至可能无法获得，且本公司在筹资过程中的谈判立场可能会因现有资源的使用而恶化。本公司亦无法保证能够进一步进入合作关系。额外的权益融资可能对公司股东造成稀释；如有的话，债务融资可能涉及重大现金支付义务及限制本公司营运能力的盟约；而授权或战略合作可能导致对正在开发的产品的经济潜力产生版税或其他降低影响。本公司继续资助其计划业务的能力，亦取决于对其前进一步里程碑在协议支付下的支付的时间和方式(详见附录14)，即使本公司实现了与该支付有关的里程碑。本公司可以选择以现金、其普通股股份或两者的组合支付该里程碑支付金额。如果本公司无法筹集所需资金以满足其长期流动性需求，则可能必须延迟或中止一个或多个方案的开发，中止或延迟正在进行或预期的临床试验，提早授权方案，以高价或其他不利条款(如果有的话)筹集资金，或卖出全部或部分本公司。
(2) 重大会计政策
截至2024年9月30日结束的三个月和九个月之内，用于编制本季度报告表格10-Q中的这些简明综合财务报表所使用的重大会计政策与公司截至2023年12月31日年终的年度报告中财务报表备注2中讨论的那些一致。
6
最近会计宣告
公司会在指定的生效日期起采纳由财务会计准则委员会（“FASB”）或其他标准设定机构发行的新会计准则。除非另有讨论，公司相信尚未生效的最近发行准则的采纳不会对公司的合并财务报表或披露产生实质影响。
在2023年11月，FASB发布了ASU 2023-07。 分部报告-改进可报告分部披露。ASU 2023-07改善了可报告部门的披露要求，主要通过增强重要部门支出的披露。ASU 2023-07的修订适用于包括仅有一个可报告部门的上市实体，并于2023年12月15日后开始的财政年度和2024年12月15日后开始的财政年度内的中期时段，可提前采纳。公司不认为采纳此准则会对其合并财务报表及相关披露产生实质影响。
2023年12月，FASB发布了ASU 2023-09「 所得税（主题740）：对所得税披露的改进，要求公开实体披露有效税率调解中的特定类别，以及为超出量化阈值的调解项目提供额外信息。ASU 2023-09还要求所有实体披露按联邦、州和外国税种加以区分支付的所得税，并进一步按特定超过总支付所得税5%的司法管辖区进行细分，除其他扩大的披露。ASU 2023-09将于2024年12月15日后开始的财政年度生效，允许提前适用。公司目前正在评估采用ASU 2023-09可能对其合并财务报表和相关披露产生的影响。 2024年3月，SEC采纳了最终规则，要求公开实体在其登记报表和年度报告中提供某些与气候相关的信息。规则要求披露，包括但不限于：重大与气候相关的风险；减轻或适应此类风险的活动；管理此类风险的治理；以及所拥有或控制的营运中的重大温室气体（GHG）排放（范围1）和/或购买的能源消耗所产生的间接排放（范围2）。此外，该规则要求在财务报表附注中披露严重天气事件和其他自然条件的影响，受到一定重要性阈值的限制。在2024年4月，由于未定的法律挑战，SEC自愿暂停了新规则。在未解决法律挑战的情况下，并取消暂停之后，规则将按阶段时间表生效，首个要求将于公司2025年开始的财政年度中实施。公司正在评估新规则对其合并财务报表和相关披露的影响。
2023年9月作出制订的所得税法之修改已生效，她要求公众实体披露有效税率调解的特定类别，以及超出一个特定数量的调解项目的额外信息。ASU 2023-09亦要求所有实体披露收入税款按联邦、州和外国税种分类支付，并进一步按特定超过总支付收入税5%的司法管辖区进行分类，除其他扩大的披露。ASU 2023-09于2024年12月15日或之后的财政年度起生效，并允许提前采用。公司目前正在评估公司的累计财务报表和有关披露中的所得税调解。
(3) 公允价值衡量
以下表格列出公司根据公允价值衡量的金融资产和负债：
截至日期 | ||||||||||||
| 2024年9月30日 |
| 一级 |
| 二级 |
| 三级 | |||||
（以千为单位） | ||||||||||||
资产： | ||||||||||||
货币市场基金和现金等值物 | $ | | — | $ | | — | ||||||
有价证券 | | — | | — | ||||||||
$ | | — | $ | | — | |||||||
截至日期 | ||||||||||||
| 2023年12月31日 |
| 一级 |
| 二级 |
| 三级 | |||||
（以千为单位） | ||||||||||||
资产： | ||||||||||||
货币市场基金和现金等值物 | $ | | — | $ | | — | ||||||
有价证券 | | — | | — | ||||||||
$ | | — | $ | | — | |||||||
7
公司的财务资产主要包括货币市场基金、货币等值物和有市场价值的证券，被归类为估值层次中的2级。公司通过独立价格服务来评估其有市场价值的证券，这些服务通常根据最近报告的相同或相似证券的交易价格进行定价，并根据重大可观察的交易进行调整。 每个资产负债表日，可观察到的市场输入可能包括交易信息、经纪商或经销商报价、竞价、要约或这些数据来源的组合。
根据3级输入测量的依据，截至2024年9月30日和2023年12月31日，公司的应变成货责任债务的公平价值为$
截至所有期间结束时，有短期负债未偿。
公司在三个月和九个月截至2024年9月30日没有任何转移进出第3级。 或 截至2024年9月30日的九个月结束了。
(4) 具有流动性的证券
以下是归类为可供出售的市场债务证券之摘要：
摊销后成本 | 未实现毛损 | 未实现毛损 | 公平 | |||||||||
| 成本 |
| 收益 |
| 亏损 |
| 价值 | |||||
（以千为单位） | ||||||||||||
2024年9月30日 | ||||||||||||
有价证券 | ||||||||||||
美国政府和市政债务 | ||||||||||||
一年或少于一年到期 | $ | | $ | | $ | — | $ | | ||||
一年到三年至期 | | | — | | ||||||||
总合美国政府和市政债务 | $ | | $ | | $ | — | $ | | ||||
公司债券 | ||||||||||||
在一年或一年以内到期 | $ | | $ | | $ | ( | $ | | ||||
在一年后至三年内到期 | | | ( | | ||||||||
总企业债券安防 | $ | | $ | | $ | ( | $ | | ||||
可销售证券总额 | $ | | $ | | $ | ( | $ | | ||||
摊销后成本 | 未实现毛损 | 未实现毛损 | 公平 | |||||||||
| 成本 |
| 收益 |
| 亏损 |
| 价值 | |||||
（以千为单位） | ||||||||||||
2023年12月31日 | ||||||||||||
有价证券 | ||||||||||||
美国政府和市政债务 | ||||||||||||
一年或以下到期 | $ | | $ | | $ | ( | $ | | ||||
一年至三年后到期 | | | — | | ||||||||
美国政府和市政债务总额 | $ | | $ | | $ | ( | $ | | ||||
企业债券 | ||||||||||||
在一年或更短的时间内到期 | $ | | $ | | $ | ( | $ | | ||||
一年至三年到期 | | | — | | ||||||||
总公司债证券 | $ | | $ | | $ | ( | $ | | ||||
可销售证券总额 | $ | | $ | | $ | ( | $ | | ||||
8
公司持有投资级别的有价证券。未实现亏损一般是由于利率的变动所造成。截至2024年9月30日和2023年12月31日，公司持有的有价证券集合公允价值处于未实现亏损的位置，金额分别为$。
有价证券包括截至2024年9月30日和2023年12月31日，分别为$。
(5) 无形资产
截至2024年9月30日和2023年12月31日，公司无限期无形资产的帐面价值为$
公司每年至少对IPR&D资产进行减损测试，或者如果事件或情况变更表明IPR&D资产可能受损，则更频繁地进行减损测试。由于IPR&D项目的性质，公司可能将来面临未来延迟或未能获得监管批准进行临床试验，该等临床试验失败或未能取得商业可行产品等失败，因此可能在未来认列进一步的减损亏损。
(6) 其他资产
公司记录在资产负债表日后一年内不会执行的服务预付款项作为其他资产。这些金额将在相关服务执行的期间认列为费用。反映在我们合并资产负债表中的其他资产中的预付款项为$
(7) 其他长期负债
其他长期负债包括以下:
| 九月三十日 |
| 12月31日， | |||
2024 | 2023 | |||||
（以千为单位） | ||||||
与IPR&D相关的净透支所得税负债（附注12） | $ | | $ | | ||
来自销售税务优惠的透支收入 |
| | | |||
透支收入（附注11） |
| | | |||
总计 |
| | | |||
扣除当期部分 |
| ( | ( | |||
长期部分 | $ | | $ | | ||
2022年3月，公司获得新泽西经济发展局的批准，同意出售新泽西税收优惠，金额为$
9
(8) 股东权益
在2023年11月，公司向SEC提交了一份自动架构登记声明，以登记销售在该登记声明中描述的各种证券类型，包括其普通股股份。同样在2023年11月，公司发行了
在2024年2月26日，公司与Cantor Fitzgerald ＆ Co.（“Cantor”）签署了一份控股权益发售协议（“ATm 协议”），以允许公司不时通过代理商Cantor 发行和销售普通股。同样在2024年2月26日，公司终止了其与Cantor签署的既有控股权益发售协议，日期为2016年5月19日。至2024年9月30日，公司已登记了
2024年3月，公司发行了
10
2024年和2023年截至9月30日三个月和九个月的股东权益变动摘要如下：
|
|
|
| 累计 |
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| |||||||||||
Common | Common | 额外的 | 其他 | 总计 | |||||||||||||
股票 | 股票分析 | 资本剩余 | 综合 | 累计 | 股东权益 | ||||||||||||
| 股份 |
| 价值 |
| 资本 |
| 收入 |
| 赤字累计 |
| 权益 | ||||||
(以千为单位，股份数除外) | |||||||||||||||||
2023年12月31日的综合资产负债表 |
| |
| $ | |
| $ | |
| $ | |
| $ | ( |
| $ | |
股票期权和员工股票购买计划下发行的股份 |
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| — |
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| | — |
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| — |
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在承销发行中发行的股份，净值 |
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| — |
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| — |
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股份报酬 |
| — |
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| — |
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| — |
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| — |
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持有市场证券的未实现亏损 |
| — |
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| — |
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| — |
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| ( |
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| — |
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| ( |
净损失 |
| — |
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| — |
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| — |
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| — |
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| ( |
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| ( |
2024年3月31日的合并资产负债表 |
| |
| $ | |
| $ | |
| $ | | $ | ( |
| $ | | |
股票期权和员工股票购买计划下发行的股份 | | — | | — | — | | |||||||||||
股份报酬 | — | — | | — | — | | |||||||||||
未实现的可销售证券损失 | — | — | — | ( | — | ( | |||||||||||
净损失 | — | — | — | — | ( | ( | |||||||||||
2024年6月30日的综合账户余额 | | $ | | $ | | $ | | $ | ( | $ | | ||||||
股票期权和员工股票购买计划下发行的股份 | | — | | — | — | | |||||||||||
股份报酬 | — | — | | — | — | | |||||||||||
持有有价证券未实现之利益 | — | — | — | | — | | |||||||||||
净损失 | — | — | — | — | ( | ( | |||||||||||
2024年9月30日的综合平衡表 | | $ | | $ | | $ | | $ | ( | $ | | ||||||
|
|
|
| 累计 |
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| |||||||||||
Common | Common | 额外的 | Total Fees Previously Paid | 总计 | |||||||||||||
股票 | 股票市场 | 实收 | 综合 | 累积 | 股东权益 | ||||||||||||
分享 | 价值 | 资本 | 收入 | 赤字累计 | 权益 | ||||||||||||
（单位：千元，股数除外） | |||||||||||||||||
2022年12月31日的综合账户余额 |
| | $ | | $ | | $ | | $ | ( | $ | | |||||
员工股票期权和员工股票购买计划下发行的股份 |
| |
| — |
| |
| — |
| — |
| | |||||
股份报酬 |
| — |
| — |
| |
| — |
| — |
| | |||||
持有有价证券未实现之利益 |
| — |
| — |
| — |
| |
| — |
| | |||||
净损失 |
| — |
| — |
| — |
| — |
| ( |
| ( | |||||
2023年3月31日的综合结余 |
| | $ | | $ | | $ | | $ | ( | $ | | |||||
根据股票期权和员工股票购买计划发行的股份 |
| |
| — |
| |
| — |
| — |
| | |||||
股份报酬 |
| — |
| — |
| |
| — |
| — |
| | |||||
可交易证券的未实现损失 |
| — |
| — |
| — |
| ( |
| — |
| ( | |||||
净损失 |
| — |
| — |
| — |
| — |
| ( |
| ( | |||||
2023年6月30日的综合账户余额 |
| | $ | | $ | | $ | | $ | ( | $ | | |||||
股票期权和员工股票购买计划下发行的股份 | | — | | — | — | | |||||||||||
股份报酬 | — | — | | — | — | | |||||||||||
持有有价证券未实现之利益 | — | — | — | | — | | |||||||||||
净损失 | — | — | — | — | ( | ( | |||||||||||
2023年9月30日的综合账户余额 | | $ | | $ | | $ | | $ | ( | $ | | ||||||
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(9) 股票期权酬劳
2024年9月30日结束之九个月股票期权活动摘要如下：
期权 | 期权 | ||||||
平均价格 | 平均价格 | ||||||
行使数量： | 仍未行使的期权数量： | ||||||
价钱 | 合约上的 | ||||||
| 股份 |
| 每股 |
| 期限（年） | ||
2023年12月31日的期权未行使数量 |
| | $ | | |||
已发放 |
| | $ | | |||
行使 |
| ( | $ | | |||
取消 |
| ( | $ | | |||
期权截至2024年9月30日仍持有 |
| | $ | | |||
2024年9月30日已授权以及预期授权的期权 |
| | $ | | |||
于2024年9月30日可行使的期权 |
| | $ | | |||
2021年Celldex Therapeutics, Inc.全权股权激励计划（经修订，自2024年6月13日生效）于2024年9月30日供授予的股份 |
| | |||||
截至2024年9月30日结束的三个月和九个月期间授予的期权的加权平均授予日公平价值为$
截至2024年9月30日，已授出并预期于当日实现的期权的合计内在价值为$
截至2024年9月30日和2023年结束的三个月和九个月内，基于股份的补偿费用记录如下：
截至 9 月 30 日止的三个月 | 截至九月三十日的九个月 | |||||||||||
| 2024 |
| 2023 |
| 2024 |
| 2023 | |||||
(以千为单位) | (以千为单位) | |||||||||||
研发 | $ | | $ | | $ | | $ | | ||||
总务及行政 |
| |
| |
| |
| | ||||
股票基于报酬的总费用 | $ | | $ | | $ | | $ | | ||||
在2024年和2023年截至9月30日的三个和九个月内授予的员工、顾问和非员工董事期权的公平价值是使用Black-Scholes期权定价模型估值，并假设如下：
截至 9 月 30 日止的三个月 | 截至九月三十日的九个月 | |||||||
|
| 2024 |
| 2023 |
| 2024 |
| 2023 |
预期股价波动性 |
|
| ||||||
预期选择权期限 |
|
| ||||||
无风险利率 |
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| ||||||
预期股息收益率 |
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| ||||||
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(10) 累积其他全面收入
2024年9月30日结束的九个月内，以股东权益组件报告的累积其他全面收入变动摘要如下：
未实现收益 | |||||||||
（收益）损失 | |||||||||
市场可流通证券 | 外国 | ||||||||
| 证券 |
| 货币项目 |
| 总计 | ||||
（以千为单位） | |||||||||
于2023年12月31日止之余额 | $ | | $ | | $ | | |||
其他全面损失 |
| |
| |
| | |||
2024年9月30日的余额 | $ | | $ | | $ | | |||
(11) 营业收入
合同和补助金收入
公司已与洛克菲勒大学（“洛克菲勒”）签订协议，根据该协议，公司以按工时和材料基础或经协商定价的方式提供制造和研发服务。公司在截至2024年9月30日的三个月和九个月内分别在与洛克菲勒的协议下认识了收入$
合约资产和负债
截至2024年9月30日和2023年12月31日，公司根据所有合同获取的权利被视为无条件，因此存在已记录的合同资产。
(12) 所得税
公司已评估对其净递延税资产实现性影响的正面和负面证据，并考虑其亏损历史，最终得出结论，「公司更有可能不会认可联邦、州和外国递延税资产的好处」，因此，截至2024年9月30日和2023年12月31日，公司对其递延税资产保持全额评估准备。
为$的净递延税负债
麻萨诸塞州、新泽西州、纽约州和康涅狄格州是公司主要经营或曾经营且具有所得税纳税地位的司法管辖区。目前公司未被这些或其他任何司法管辖区审查任何税年。
13
(13) 每股净损失
基本每股净损失乃基于本期活跃的普通股平均已发行未授权限制的股票数，不包括已发行但尚未授予的限制性股票。稀释每股净损失基于本期活跃的普通股平均已发行数额外加上本期活跃的额外稀释普通股的平均数，当该效应为稀释时。在公司有净损失的期间，基本和稀释每股净损失没有差别，因为稀释的普通股未假设已发行，因其效应具有反稀释性。尚未纳入每股净损失计算中的有潜力稀释普通股，因该效应为反稀释性而未计入的普通股如下：
截至九月三十日的九个月 | ||||
| 2024 |
| 2023 | |
股票期权 |
| |
| |
受限股票 |
| — |
| — |
| |
| | |
(14) Kolltan收购
2016年11月29日，公司收购了Kolltan的所有股权和债务利益，以交换公司的普通股加上最高为$百万的发展、监管批准和基于销售的里程碑条款（“Kolltan里程碑”），可以用现金支付，用Celldex的普通股支付，或者两者兼而有之，全由Celldex自行决定，并根据2016年11月1日签署的《合并协议及计划》（即“合并协议”）的条款规定。
在2019年10月，公司收到了SRS的函，SRS是Kolltan前股东的聘雇代表，通知公司反对公司对于与CDX-0158相关的开发、监管批准和销售里程碑的表述，指称该里程碑已被放弃，并主张Kolltan股东应由Celldex支付相关的里程碑款项。
2020年8月18日，Celldex在特拉华州特许法院对抗SRS（根据合并协议担任Kolltan前股东代表的角色）提起了经核实的申诉，就合并协议下与中止的CDX-0158计划相关的某些有条件的里程碑付款的权利和义务寻求宣告判决。
2022年7月15日，公司与SRS达成了一项确定性和解协议（“和解协议”），公司和SRS共同于2022年7月19日提交了一份具有抗辩力的撤销和解协议有关诉讼的和解协议书。
根据和解协议条款，合并协议所规定的所有里程碑付款均被以下款项整体取代，每笔仅支付一次：
| (i) | 公司支付了$。 |
| (ii) | 公司支付了$。 |
| (iii) | 该公司应支付$ |
以上付款义务完全取代了并购协议中包含的最高达＄的开发、监管批准和销售里程碑形式的有条件考量。
14
根据和解协议，公司和SRS各自提供广泛互相释放所有与并购协议相关或产生的索赔，包括但不限于在诉讼中提出的所有索赔或可能提出的索赔。
公司在2022年7月以现金支付了首期支付。公司在2023年11月以现金支付了barzolvolimab第2期第2期临床试验"成功完成"的里程碑。
与barzolvolimab计划有关的未来补助金支付，在涉及诉讼时，将根据ASC 450下的损耗凭证模型的损失之可能性和合理估计记录。与其余留存公司产品有关的未来里程碑支付将按公平价值衡量（请参阅附注3）。如果上述剩余支付的到期日确定，则应在公司唯一选择下，按照现金或股票（如并购协议所载）或其组合支付。
15
项目2。管理层对财务状况和业绩的讨论与分析
1995年根据《私人证券诉讼改革法》的安全港声明： 本第10-Q表格的季度报告包含根据1933年修订版的《证券法》第27A条和1934年修订版的《证券交易法》第21E条的安全港条款所作的前瞻性陈述。前瞻性陈述包括涉及我们信念、计划、目标、期望、预期、假设、估计、意图和未来表现的声明，涉及已知和未知风险、不确定性和其他超出我们控制范围的因素，这可能导致我们的实际结果、表现或成就与未来结果、表现或暗示的差异很大。除了历史事实的声明外，所有声明都可能是前瞻性陈述。您可以通过我们使用“可能”、“将”、“可”、“预测”、“假设”、“应”、“指示”、“将”、“相信”、“思考”、“期望”、“寻求”、“估计”、“持续”、“计划”、“指出”、“项目”、“预测”、“能”、“打算”、“目标”、“潜力”等类似的词语和表达未来的方式来识别这些前瞻性陈述。
有许多重要因素可能导致实际结果与我们所表达的任何前瞻性陈述有所不同。这些因素包括但不限于：
| ● | 我们对仍处于开发阶段的产品候选者的依赖； |
| ● | 我们成功完成研究和进一步发展的能力，包括临床前和临床研究； |
| ● | 我们预期的临床前发展、监管提交、临床试验的开始和完成，以及产品批准的时间； |
| ● | 我们洽谈战略合作伙伴关系的能力，如适当地为我们的药品候选者； |
| ● | 我们能够管理多个处于不同发展阶段的药品候选品的多个临床试验； |
| ● | 进行中的临床前和临床测试的成本、时间、范围和结果； |
| ● | 我们对我们的产品和开发候选品的属性（包括药品特性、效力、安全性和剂量方案）的期望； |
| ● | 为我们的药品候选品获得监管机构批准的成本、时间和不确定性； |
| ● | 我们的临床研究机构合作伙伴提供的临床管理服务的可用性、成本、交付和质量； |
| ● | 我们自己的制造设施生产的临床和商用级材料的可用性、成本、交付和质量，或者合同代工商、供应商和合作伙伴提供的材料； |
| ● | 我们将药品候选品商品化的能力以及该等药品候选品市场的增长； |
| ● | 我们开发和商品化优于竞争对手所开发替代方案的产品的能力； |
| ● | 我们有能力开发技术能力，包括确定新颖且临床重要的目标，利用现有的技术平台开发新的药品候选物，并将我们对现有靶向治疗药物的关注扩展到更广泛的市场； |
| ● | 支付根据我们收购Kolltan及相关和解协议所需支付的合规性批准里程碑成本； |
16
| ● | 我们能够筹集足够资金，用于支持我们的临床前和临床研究，满足我们的长期流动性需求，并且条款对我们可接受，或者完全符合。如果我们无法筹集必要的资金以满足我们的长期流动性需求，我们可能需要延迟或中止一个或多个计划的开发，停止或延迟进行中或预期的临床试验，停止或延迟我们的商业制造努力，中止或延迟我们拓展药物产品候选人用途领域的努力，提前许可计划，以远低于预期的价格筹措资金，或以其他不利条款筹款，如果有的话，卖出我们的业务全部或部分; |
| ● | 我们保护知识产权权利的能力，以及避免知识产权诉讼的能力，这可能成本高昂且分散管理队伍的时间和注意力; |
| ● | 我们开发和商业化产品的能力，而不侵犯第三方的知识产权权利; |
| ● | 基金风险因素已在本季度报告10-Q的其他地方设定，以及在我们截至2023年12月31日的年度报告10-k中标题为“业务”、“风险因素”和“管理层对财务状况和经营结果的讨论”下列出的因素，以及我们与SEC提交的其他报告。. |
所有前瞻性陈述在其整体上均受到本警语通知的明确限制。 我们警告您不要过度依赖任何仅于本报告日期或参照入本报告的文件日期发表的前瞻性陈述。 我们无义务，并明确放弃任何更新、修订或纠正任何前瞻性陈述的义务，无论是出于新信息、未来事件或其他原因。 我们以诚信表达了我们的期望、信念和预测，我们相信它们具有合理基础。 然而，我们无法保证我们的期望、信念或预测将会实现或达成。
概观
我们是一家专注于探索肥大细胞生物学并开发治疗性抗体的生物制药公司，这些抗体能够促使人体免疫系统参与和/或直接影响关键途径，以改善患有严重炎症、过敏、自体免疫和其他毁灭性疾病的患者的生活。 我们的药物候选包括单克隆和双特异性抗体，旨在应对肥大细胞介导的疾病，对其现有治疗不足。
我们把努力和资源集中在持续研究和开发中
| ● | Barzolvolimab（也称为CDX-0159），这是一种特异性结合KIt受体并有效抑制其活性的单克隆抗体，目前正在多种肥大细胞驱动疾病中进行研究，包括 |
| - | 慢性寻常性荨麻疹：我们于2024年7月开始慢性自发性荨麻疹（CSU）的3期试验。 2023年11月，我们宣布我们在CSU的2期研究达到了主要的疗效终点（与安慰剂相比，从基线到第12周的荨麻疹活动评分的平均变化在统计上有显著差异），并且耐受良好。 研究中的患者继续接受Barzolvolimab，并且我们于2024年9月发布了52周治疗的数据—显示持续和深化的疾病疗效和良好的长期安全性档案。 我们于2024年7月宣布，我们在慢性诱发性荨麻疹（CIndU）中的2期研究达到了主要的疗效终点（与安慰剂相比，第12周负激发试验病人百分比之差异具有统计显著性），并且耐受良好。 CIndU研究的12周数据于2024年10月公布，该研究的所有次要终点也达到了并且在统计上高度明显且在临床上具有意义。 研究中的患者继续接受Barzolvolimab治疗20周； |
| - | 皮疹结节性疮（PN）：2024年4月，我们在PN开展了一项2期研究，并且招募工作正在进行中；2023年11月，我们正在进行PN的10亿研究中获得了积极的数据； |
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| - | 食道嗜酸白细胞增多症（EoE）：EoE的2期研究于2023年6月启动，目前仍在招募中；并且 |
| - | 异位性皮肤炎（AD）：异位性皮肤炎已被选为barzolvolimab研究的下一个指示。我们目前正在计划在这个指示中进行2期研究的设计，包括接受过先前生物制品治疗的患者，并计划在2024年年底前开始这项研究。 |
| ● | 我们的下一代双特异性抗体平台用于支持管道扩张，提供额外的候选人用于炎症性疾病。目标是基于新科学选择，以及它们与我们现有抗体计划相容，使其可以用于具有双特异性抗体格式的开发。开发集中于控制炎症性疾病的新兴重要途径。 |
有关这些计划的更多细节请参见临床开发计划部分。
我们的目标是建立一家完全集成的、商业阶段的生物制剂公司，为那些医疗需求未被满足的患者开发重要的治疗方法。我们认为我们的计划资产为我们提供了策略选择，可以选择保留我们创新治疗方法的完全经济权或通过有利的商业合作伙伴关系寻求有利的经济条件。这种方法使我们能够最大限度地发挥我们的技术和产品组合的整体价值，同时最好地确保每个产品的迅速开发。
执行我们业务计划所需的支出存在许多不确定性。临床试验的完成可能需要数年或更长时间，一般来说，根据药物候选物的类型、复杂性、新颖性和预期使用，所需时间会大幅变化。有很多这类药物候选物的临床开发要花费五年甚至更长时间，每种药物候选物的总开发成本可能超过数亿美元。我们估计我们一般进行的临床试验通常在以下时间表上完成：
| 估价 | |
| 完成 | |
临床阶段 |
| 周期 |
第一阶段 |
| 1 - 2 年 |
第二阶段 |
| 1 - 5 年 |
第三阶段 |
| 1 - 5 年 |
在项目的整个生命周期中，临床试验的持续时间和成本可能会因临床试验方案期间出现的差异而大幅变化，其中包括但不限于以下情况：
| ● | 最终参与试验的患者人数； |
| ● | 根据结果看来适当的患者后续随访的时间。 |
| ● | 临床试验中包括的临床研究中心数量； |
| ● | 招募合适病患受试者所需的时间长短；以及 |
| ● | 药物候选品的有效性和安全性概况。 |
我们对潜在药物候选品进行多项预临床研究，包括安全性、毒理学和免疫原性。我们之后可能为每个药物候选品进行多个临床试验。当我们从试验获得结果时，我们可能选择中止或延迟某些药物候选品的临床试验，以便将资源集中在更有潜力的药物候选品上。
我们业务策略的一个元素是追求广泛组合的药物候选品的发现、研究和开发。这旨在使我们能够分散与研究开发支出相关的风险。在无法维持广泛范围的药物候选品时，我们对一个或几个药物候选品成功的依赖程度将增加。
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在我们能够将我们的药物候选品作为治疗产品推向市场之前，需要获得监管机构的批准。为了能够进行后续的临床试验阶段并最终获得监管机构的批准，监管机构必须得出我们的临床数据证明我们的产品候选品是安全和有效的结论。从历史上看，从前临床试验和早期临床试验（达到第2期）中得出的结果通常无法预测后期临床试验中获得的结果。许多新药物和生物制品在早期临床试验中展示出有希望的结果，但后来未能建立足够的安全性和有效性数据以获得必要的监管批准。
此外，我们的业务策略包括与第三方进行合作安排，以完成我们药物候选品的开发和商业化。如果第三方负责我们药物候选品之一的临床试验过程，预计完成日期将主要由该第三方控制，而非我们。我们无法确定将来哪些专有产品（如果有的话）将受到未来合作安排的影响，以及这些安排将如何影响我们的开发计划或资本需求。我们的计划也可能受益于补助金、资助、合同或政府或机构赞助的研究，这可能会降低我们的开发成本。
由于上述不确定性等因素的影响，很难准确估计我们研究和开发项目的持续时间和完成成本，以及我们将何时（如果有的话）以及在何种程度上从产品的商业化和销售中获得现金流入。我们无法及时完成研究和开发项目或者在适当时进行合作协议可能会显著增加我们的资本需求并可能对我们的流动性造成不利影响。这些不确定性可能迫使我们不时寻求额外的外部融资来继续我们的业务策略。我们无法筹集到额外资本，或者以我们能够接受的条件进行筹集，将危及我们业务的未来成功。
过去五年中，至2023年12月31日，我们在研究和开发方面总共遭遇到33880万美元的支出。以下表格显示了在截至2024年9月30日及2013年9月30日九个月中，我们为每个重要研究计划和其他明确研究和开发活动所遭遇到的金额。表格中披露的金额反映了直接的研究和开发成本，与技术相关的许可费以及将间接的研究和开发成本分配给每个计划。
九个月 | 九个月 | |||||
结束 | 结束 | |||||
| 2024年9月30日 |
| 2023年9月30日 | |||
| （以千为单位） | |||||
Barzolvolimab/Anti-KIt计划 | $ | 88,643 | $ | 59,009 | ||
CDX-585 |
| 2,213 |
| 5,499 | ||
CDX-622 | 10,175 | 12,696 | ||||
其他项目 |
| 15,580 |
| 10,381 | ||
研发总费用 | $ | 116,611 | $ | 87,585 | ||
临床发展计划
Barzolvolimab（也称为CDX-0159）
Barzolvolimab是一种人源化单克隆抗体，专门结合受体酪氨酸激酶KIt并强效抑制其活性。KIt在各种细胞中表达，包括肥大细胞，其被配体SCF激活调控肥大细胞的生长、分化、存活、趋化和脱颗粒。Barzolvolimab旨在通过破坏SCF结合和KIt二聚化来阻断KIt的活化。通过作用于KIt，Barzolvolimab已被证明能抑制肥大细胞活性并减少肥大细胞数量，我们认为这可能在肥大细胞相关疾病中提供潜在的临床益处。
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Barzolvolimab最初是在慢性特发性荨麻疹（CSU）和慢性诱发性荨麻疹（CIndU）中进行研究，这些疾病中肥大细胞脱颗可能在疾病的发病和进展中起著核心作用。2024年7月，我们在CSU中展开了两项第3期研究。在CSU和CIndU中的第1期研究已成功完成，第2期研究正在进行中。2023年7月，我们宣布正在进行的CSU第2期研究已完成招募。2023年11月，我们报告Barzolvolimab在这项研究中达到了主要疗效终点，在周12的UAS7（每周荨麻疹活动评分）的平均变化与安慰剂相比具有统计学意义，并且耐受性良好。2024年4月，我们宣布正在进行的CIndU第2期研究已完成招募。2024年7月，我们报告Barzolvolimab在这项研究中达到了主要疗效终点，在周12负责任测试的患者百分比与安慰剂相比具有统计学意义，并且耐受性良好。我们计划在2024年下半年发布CSU研究的52周上线数据和CIndU研究的完整12周主要终点数据。
根据在荨麻疹中报告的正面结果，我们将Barzolvolimab的开发扩展到其他肥大细胞被认为发挥重要作用的领域。我们正在对嗜酸性食道炎（EoE）进行进行中的第2期研究，并在2024年4月在报告了2023年底PN第10亿研究的正面数据后，启动了PN的第2期研究。我们将过敏性皮肤炎选择为Barzolvolimab研究的下一个领域，目前正在规划该领域的第2期研究设计，包括接受过先前生物制品治疗的患者，并计划在2024年年底前开始进行此研究。我们继续评估Barzolvolimab在其他肥大细胞发挥重要作用的疾病中的潜在机会，例如皮肤科、呼吸道、过敏、胃肠和眼科疾病。
慢性特发性荨麻疹（CSU）
CSU表现为至少六周长的瘙痒性荨麻疹、血管水肿或两者，没有特定诱因；多次发作可能持续数年甚至数十年。这是最常见的皮肤病之一，在美国总人口中的盛行率为0.5-1.0％，大约有300万患者（Weller等人，2010年，Hautarzt. 61（8），Bartlett等人，2018年，DermNet.Org）。大约有50％的CSU患者通过抗组织胺剂实现症状控制。 IgE抑制剂奥玛班（Omalizumab）对于剩下的一半抗组织胺剂耐受患者提供了缓解。因此，需要其他的治疗方法。
我们已完成了一项第10亿阶段的随机、双盲、安慰剂对照、多中心的barzolvolimab在CSU中的研究。该研究旨在评估在使用抗组织胺治疗后症状仍持续的CSU患者中，barzolvolimab多剂量的安全性。次要和探索性目标包括药动学和药效评估、临床活性结果和生活质量评估。 Barzolvolimab通过静脉注射作为H1-抗组织胺的附加治疗，可单独使用，也可以与H2-抗组织胺和/或白三烯受体激动剂组合使用。有45名中度至严重的CSU抗组织胺无效的患者参加了治疗（35名barzolvolimab（0.5 mg / kg的9名，1.5 mg / kg的8名，3.0 mg / kg的9名，4.5 mg / kg的9名）和10名安慰剂）。
在饱和剂量（1.5 mg / kg及以上）下，barzolvolimab对试图抗组织胺治疗仍有症状的中度至严重CSU患者呈现出快速、明显且持久的反应。1.5 mg / kg，3.0 mg / kg和4.5 mg / kg剂量组显示出类似明显改善的荨麻疹症状，包括快速的反应开始（首剂后最早在1周后）以及长期的疾病控制，持续耐用度长达24周。之前使用过奥玛班疗法的患者也和所有患者一样有类似的症状改善。
| ● | 在第12周，1.5 mg/kg剂量组（n=8）的周鼻疽活动评分（UAS7）平均基线降幅为67%，3.0 mg/kg剂量组为67%，4.5 mg/kg剂量组为82%。 在第24周，1.5 mg/kg剂量组（n=7）的UAS7平均基线降幅为80%，3.0 mg/kg剂量组为70%，4.5 mg/kg剂量组为77%。 |
| ● | 在第12周，1.5 mg/kg剂量组的完整反应（UAS7=0）为57%，3.0 mg/kg剂量组为44%，4.5 mg/kg剂量组为67%。在第24周，1.5 mg/kg剂量组的完整反应为57%，3.0 mg/kg剂量组为67%，4.5 mg/kg剂量组为43%。 |
| ● | 在第12周时，1.5毫克/公斤剂量组的控制良好疾病率（UCT≥12）为75％，3.0毫克/公斤剂量组为63％，4.5毫克/公斤剂量组为89％。在第24周时，1.5毫克/公斤剂量组的控制良好疾病率（UCT≥12）为75％，3.0毫克/公斤剂量组为67％，4.5毫克/公斤剂量组为67％。 |
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| ● | During post-treatment follow up, 71% (10 of 14) of patients who had been treated with doses greater than or equal to 1.5 mg/kg and had a complete response (UAS7=0) at week 12, remained urticaria free at week 24 (patients received last dose of barzolvolimab at week 8). |
| ● | Profound and durable improvement in angioedema symptoms as measured through the weekly angioedema activity score (AAS7) was achieved across all dose levels evaluated with sustained activity observed with the 1.5 mg/kg and greater dose levels. |
| ● | Patients also reported improvements in quality of life outcomes as assessed by the Dermatology Life Quality Index (DLQI) which surveys patients’ perceptions of symptoms and feelings, daily activities, leisure, work and school performance, personal relationships and treatment. |
| ● | Tryptase suppression, indicative of mast cell depletion, paralleled symptom improvement, demonstrating the impact of mast cell depletion on CSU disease activity. |
| ● | Barzolvolimab was well tolerated. Most adverse events were mild or moderate in severity and resolved while on study. The most common treatment emergent adverse events were hair color changes, COVID-19, headache, neutropenia and urinary tract infections (UTIs). UTIs and COVID-19 were reported as unrelated to treatment. Generally transient, asymptomatic and mild changes in hematologic parameters were observed, consistent with observations from prior studies. No pattern of further decrease was observed with multiple dose administration. |
Data from this study were reported across multiple medical meetings, including the American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting in February 2023, the European Academy of Allergy and Clinical Immunology (EAACI) Annual Congress in June 2023 and the European Academy of Dermatology & Venereology (EADV) Congress in October 2023.
In June 2022, we initiated dosing in a Phase 2 study in patients with CSU who remained symptomatic despite antihistamine therapy; in July 2023, we announced that enrollment was complete. The study is being conducted at approximately 75 sites across 9 countries. The study is a randomized, double-blind, placebo-controlled, parallel group Phase 2 study evaluating the efficacy and safety profile of multiple dose regimens of barzolvolimab to determine the optimal dosing strategy. 208 patients have been randomly assigned on a 1:1:1:1 ratio to receive subcutaneous injections of barzolvolimab at 75 mg every 4 weeks, 150 mg every 4 weeks, 300 mg every 8 weeks or placebo during a 16-week placebo-controlled treatment phase. After 16 weeks, patients then enter a 36-week active treatment period, in which patients receiving placebo or the 75 mg dose are randomized to receive barzolvolimab 150 mg every 4 weeks or 300 mg every 8 weeks; patients already randomized to the 150 mg and 300 mg treatment arms remain on the same regimen as during the placebo-controlled treatment period. After 52 weeks, patients then enter a follow-up period for an additional 24 weeks. The primary endpoint of the study is mean change in baseline to week 12 in UAS7 (weekly urticaria activity score). Secondary endpoints include safety and other assessments of clinical activity including ISS7 (weekly itch severity score), HSS7 (weekly hive severity score) and AAS7 (weekly angioedema activity score).
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Topline data from this study were presented in November of 2023 and 12 week treatment results were presented at the American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting in February 2024. Data from the 208 patients randomized in the study showed that barzolvolimab achieved the primary efficacy endpoint, with a statistically significant mean change from baseline to week 12 in UAS7 compared to placebo at all dose levels. Secondary and exploratory endpoints in the study were also achieved at week 12 and strongly support the primary endpoint results, including changes in ISS7 and HSS7 and responder analyses. Importantly, barzolvolimab demonstrated rapid, durable and clinically meaningful responses in patients with moderate to severe CSU refractory to antihistamines, including patients with prior omalizumab treatment. Demographics and baseline disease characteristics were well balanced across treatment groups. The majority of patients on study had severe disease (UAS7≥28).
Summary of Clinical Activity Assessments at Week 12 | ||||
300 mg Q8W | 150 mg Q4W | 75 mg Q4W | Placebo | |
UAS7 Changes | ||||
Baseline UAS7 (mean) | 31.33 | 30.75 | 30.30 | 30.09 |
LS Mean change at Week 12 | -23.87 | -23.02 | -17.06 | -10.47 |
LS Mean difference from placebo (Confidence Interval, p value) | -13.41 | -12.55 | -6.60 | |
HSS7 Changes | ||||
Baseline HSS7 (mean) | 14.92 | 15.05 | 14.86 | 14.47 |
LS Mean change at Week 12 | -12.19 | -11.19 | -8.25 | -4.95 |
LS Mean difference from placebo (Confidence Interval, p value) | -7.24 | -6.24 | -3.31 | |
ISS7 Changes | ||||
Baseline ISS7 (mean) | 16.42 | 15.70 | 15.44 | 15.61 |
LS Mean change at Week 12 | -11.79 | -11.68 | -8.62 | -5.47 |
LS Mean difference from placebo (Confidence Interval, p value) | -6.32 | -6.21 | -3.16 | |
Responder Analyses/Clinical Responses | ||||
UAS7=0 (Complete Control) | 37.5% | 51.1% | 22.9% | 6.4% |
UAS7≤6 (Well-controlled) | 62.5% | 59.6% | 41.7% | 12.8% |
UAS7, HSS7 and ISS7 data were analyzed using ANCOVA model and multiple imputation.
Barzolvolimab demonstrated strong improvement in UAS7 independent of omalizumab status at week 12. Approximately 20% (n=41) of enrolled patients received prior treatment with omalizumab and more than half of these patients had omalizumab-refractory disease. These patients experienced a similar clinical benefit as the overall treated population within their individual dosing groups consistent with the barzolvolimab mechanism of action.
Barzolvolimab was well tolerated with a favorable safety profile. Most adverse events were mild to moderate in severity; through 12 weeks, the most common treatment emergent adverse events in barzolvolimab treated patients were urticaria/CSU (10%), hair color changes (9%), and neutropenia/ANC decrease (8%). The rate of infections was similar between barzolvolimab treated patients and placebo with no association between neutropenia and infections.
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In June 2024, data on a secondary endpoint from the study, angioedema activity, and additional measures of angioedema control, were presented at the EAACI 2024 Congress. Approximately 72% of patients on study had angioedema at baseline. Barzolvolimab demonstrated significant improvements in AAS7 in patients with angioedema across all doses at week 12. This improvement was rapid (within 2 weeks) and durable (continued through 12 weeks). Barzolvolimab demonstrated strong improvement in AAS7 independent of omalizumab status at Week 12. Patients on barzolvolimab experienced a > 8 point improvement in AAS7 (considered a clinically meaningful result) across all doses compared to placebo (p<0.05). Barzolvolimab increased angioedema free days compared to placebo through 12 weeks. Patients in the 300 mg cohort were angioedema free 77% of the time over the 12 week period.
Patients on study continued to receive barzolvolimab for up to 52 weeks and these long term treatment data were presented in September at the European Academy of Dermatology & Venereology (EADV) Congress 2024. The data demonstrated a sustained and deepening disease efficacy and a well tolerated safety profile over a 52 week treatment period. Key highlighted included:
| ● | Improvements in UAS7 (weekly urticaria activity score), previously shown to be statistically significantly vs placebo at Week 12, were noted as early as week 1 and were sustained or deepened at Week 52. |
| ● | At Week 16, patients receiving low dose barzolvolimab (75 mg) or placebo were transitioned to barzolvolimab 150 mg or 300 mg; after crossover, these patients experienced similar clinically meaningful disease response as the rest of the study population. |
| ● | 71% of patients treated with barzolvolimab 150 mg Q4W and 52% of patients treated with 300 mg Q8W had a complete response (no itch/hives; UAS7=0) at Week 52. These responses were observed early and sustained through 52 weeks. |
| ● | 74% of patients treated with barzolvolimab 150 mg Q4W and 68% of patients treated with 300 mg Q8W had well controlled (UAS7<6) disease at Week 52. |
| ● | These robust responses were observed regardless of prior omalizumab experience. |
| ● | Barzolvolimab was well tolerated with a favorable safety profile through 52 weeks of treatment. Most adverse events were grade 1 (mild), mechanism related (KIT) and expected to be reversible. The most common treatment emergent adverse events occurring in greater than 10% of barzolvolimab treated patients were hair color changes, neutropenia, urticaria, skin hypopigmentation (areas of skin lightening) and nasopharyngitis (common cold). Neutrophil counts did not decline further with continued dosing and there was no association between infections and neutropenia. The hypopigmentation was observed with longer term exposure and did not lead to treatment discontinuation. Adverse events were not dose dependent. |
We believe these results strongly support the further development of barzolvolimab in CSU. In July 2024, we initiated two Phase 3 studies of barzolvolimab in CSU. The studies, EMBARQ-CSU1 and EMBARQ-CSU2, are designed to establish the efficacy and safety of barzolvolimab in adult patients with CSU who remain symptomatic despite H1 antihistamine treatment. Both Phase 3 trials are randomized, double-blind, placebo-controlled, parallel group, global studies ( approximately 40 countries; 250 sites per study) where approximately 915 patients per trial will be randomized evenly to barzolvolimab 150 mg every 4 weeks (following 300 mg loading dose), barzolvolimab 300 mg every 8 weeks (following 450 mg loading dose) or placebo for 52 weeks. At 24 weeks, patients on placebo will be re-randomized to active treatment across both dosing groups. The primary endpoint of the studies will evaluate the clinical effect of barzolvolimab in reducing urticaria activity (weekly urticaria activity score; UAS7) at week 12. The studies are designed to detect a clinically meaningful difference between each of the active arms versus placebo in the overall population as well as in the subpopulation of omalizumab refractory participants. Enrollment is ongoing.
Chronic Inducible Urticaria (CIndU)
CIndUs are forms of urticaria that have an attributable cause or trigger associated with them, typically resulting in hives or wheals. The prevalence of CIndU is estimated at 0.5% of the total population and is reported to overlap in up to 36% of CSU patients (Weller et al. 2010. Hautarzt. 61(8), Bartlett et al. 2018. DermNet.Org). There are currently no approved therapies for chronic inducible urticarias other than antihistamines and patients attempt to manage symptoms associated with their disease through avoidance of triggers. We are currently exploring cold-induced and dermographism (scratch-induced) urticarias in an ongoing Phase 2 study.
23
We completed a Phase 1b open label clinical trial in patients with CIndU refractory to antihistamines, conducted in Germany. This study was designed to evaluate the safety of a single intravenous dose (3 mg/kg) of barzolvolimab in patients with cold urticaria (ColdU) or symptomatic dermographism (SD). The study was expanded to include a cohort (single dose, 3 mg/kg) in patients with cholinergic urticaria (“CholU”) and a cohort at a lower dose (single dose, 1.5 mg/kg) in ColdU. Patient’s symptoms were induced via provocation testing that resembles real life triggering situations. Secondary and exploratory objectives included pharmacokinetic and pharmacodynamic assessments, including changes from baseline provocation thresholds, measurement of tryptase and stem cell factor levels, clinical activity outcomes, quality of life assessments and measurement of tissue mast cells through skin biopsies.
Generally patients on study had high disease activity at baseline that was poorly controlled and marked impairment in quality of life. At 3 mg/kg in the ColdU and SD cohorts, safety results were reported for 21 patients and activity results were reported for the 20 patients who received a full dose of barzolvolimab. At 1.5 mg/kg in the ColdU cohort, safety results were reported for 10 patients and activity results were reported for the 9 patients who received a full dose of barzolvolimab. At 3 mg/kg in the cholinergic cohort, safety results were reported for 21 patients and activity results were reported for the 20 patients who received a full dose of barzolvolimab.
Rapid (as early as 1 week) and durable responses were observed in patients as assessed by provocation testing.
| ● | A complete response was achieved in 95% (n=19/20) of patients with ColdU and SD treated with a single dose at 3 mg/kg (n=10/10 ColdU; n=9/10 SD), including 3 patients who experienced insufficient response to prior omalizumab treatment. The median duration (range) of complete response through the 12-week observation period was 77+ days (29–86; n=10) for patients with ColdU and 57+ days (16–70; n=9) for patients with SD. A UCT score of ≥12 (well controlled) was achieved by 80% (n=16/20) of the patients within week 4 post-treatment. By week 8, all patients (100%; n=20/20) achieved well-controlled urticaria, which was sustained to week 12 post-dose by 80% (n=16/20) of patients. Complete urticaria control (UCT=16) was achieved by 35% (n=7/20), 65% (n=13/20), and 40% (n=8/20) at weeks 4, 8, and 12, respectively. |
| ● | A complete response was achieved in 100% (n=9 of 9) patients with ColdU treated with a single dose at 1.5 mg/kg, including 4 patients with disease refractory to omalizumab. The median duration of complete response through the 12-week observation period was 51+ days (7+ weeks). Following barzolvolimab administration, all patients achieved well controlled disease (UCT>12) with 7 of 9 achieving complete control (UCT=16). |
| ● | A complete response was achieved in 56% (n=5 of 9) patients with cholinergic urticaria treated with a single dose at 3 mg/kg. Most responses remained durable through to week 12. 63% (5/8) patients reported well controlled disease (UCT ≥12) at week 8 and 50% (4/8) at week 12, respectively. |
| ● | Patients also reported improvements in quality of life outcomes as assessed by the Dermatology Life Quality Index (DLQI) which surveys patients’ perceptions of symptoms and feelings, daily activities, leisure, work and school performance, personal relationships and treatment. |
| ● | A single dose of barzolvolimab led to marked decreases in tryptase and in skin mast cells. The kinetics correlated with improvements in provocation testing and clinical activity, consistent with a central role for mast cells in the pathogenesis of ColdU and SD. This confirmed that serum tryptase level is a robust pharmacodynamic biomarker for assessing mast cell burden and clinical activity in inducible urticaria and potentially in other diseases with mast cell driven involvement. |
| ● | Barzolvolimab was well tolerated across all cohorts. In the 3 mg/kg ColdU and SD cohorts, most adverse events were mild, and the most common (≥3 patients) were hair color changes (76%; n=16/21), infusion reactions (43%; n=9/21), taste changes (38%; n=8/21), nasopharyngitis (24%; n=5/21), malaise (24%; n=5/21), and headache (19%; n=4/21). Hair color changes (generally small areas of hair color lightening) and taste disorders (generally partial changes of ability to taste salt or umami) are consistent with inhibiting KIT signaling in other cell types and completely resolved over time during follow-up. One patient with a history of fainting experienced loss of consciousness during infusion. The patient rapidly recovered. Importantly, no evidence of mast cell activation as measured by serum tryptase monitoring was observed in this patient. Barzolvolimab was also generally well tolerated by patients in the 1.5 mg/kg ColdU cohort and the 3.0 mg/kg cholinergic cohort with a similar safety profile to that reported previously. Across the Phase 1b inducible urticaria study, mean hematology parameters generally remained within the normal ranges—an important finding for a KIT inhibitor. Mild, transient, and asymptomatic decreases in hemoglobin and white blood cell parameters occurred for some patients. |
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| ● | Long term follow up data was collected from the 3.0 mg/kg cohorts in cold urticaria and symptomatic dermographism. 14 patients consented to the optional evaluation (6 cold, 8 symptomatic dermographism); 10 of the 14 still had complete control of their disease as assessed by provocation testing at week 12. Data were collected at one or more timepoints beyond week 12 through week 36. Most patients had return of symptoms and/or loss of urticaria control between 12 and 36 weeks. Remarkably, two patients remained provocation negative at 36 weeks, and four had well controlled disease (UCT ≥12) 36 weeks post dosing. Serum tryptase exhibits a similar rate of recovery as clinical symptoms, while skin mast cells return at a slower rate. Tissue KIT signaling, as approximated by SCF levels, was rapidly inhibited after dose administration and fully reactivated approximately 18 weeks after dosing. Tryptase levels return to pretreatment levels during follow up, while mast cells continue to recover. Drug related adverse events noted during the study all resolved. |
Data from this study were reported in Allergy (Nov 2022) and across multiple medical meetings, including the GA²LEN Global Urticaria Forum (GUF) in December and the European Academy of Allergy and Clinical Immunology (EAACI) Annual Congress in June 2022.
In July 2022, we announced that the first patient had been dosed in a Phase 2 study in patients with CIndU who remain symptomatic despite antihistamine therapy; in April 2024, we announced that enrollment was complete. The study is being conducted at approximately 85 sites across approximately 12 countries. The randomized, double-blind, placebo-controlled, parallel group Phase 2 study is evaluating the efficacy and safety profile of multiple dose regimens of barzolvolimab in patients with CIndU to determine the optimal dosing strategy. 196 patients in 2 cohorts (differentiated by CIndU subtype) including 97 patients with cold urticaria and 99 patients with symptomatic dermographism were randomly assigned on a 1:1:1 ratio to receive subcutaneous injections of barzolvolimab at 150 mg every 4 weeks, 300 mg every 8 weeks or placebo during a 20-week treatment phase. Patients then enter a follow-up phase for an additional 24 weeks. In addition, the study includes the option for patients who have symptoms following the treatment phase, including patients who were on placebo, to enroll in an open label extension where all patients receive 300 mg of barzolvolimab every 8 weeks. The primary endpoint of the study is the percentage of patients with a negative provocation test at week 12. Secondary endpoints include safety and other assessments of clinical activity including CTT (Critical Temperature Threshold), CFT (Critical Friction Threshold) and WI-NRS (Worst itch numeric rating scale).
25
Topline primary endpoint data from this study were reported in July 2024 and 12 week treatment results were presented at the American College of Allergy, Asthma & Immunology's Annual Scientific Meeting. Data from the 193 patients randomized and treated in the study showed that barzolvolimab achieved the primary efficacy endpoint, a statistically significant difference between the percent of patients with a negative provocation test compared to placebo at week 12 as assessed by the TempTest® in ColdU and the FricTest® in SD. Secondary and exploratory endpoints in the study were also achieved at week 12 and strongly support the primary endpoint results, including responder analyses, improvements in Critical Temperature and Critical Friction Thresholds (CFT and CFT), changes in WI-NRSprovo (itch associated with provocation test) and Urticaria Control Test. Demographics and baseline disease characteristics were well balanced across treatment groups. In cold urticaria, patients presented with a mean baseline critical temperature threshold of approximately 19°C or 66°F on the TempTest on initial provocation testing. In patients with symptomatic dermographism baseline FricTest thresholds were an average of 3.6 out of 4 pins. UCT scores at baseline reflect poorly controlled disease.
Summary of Clinical Assessments at Week 12 | |||||||
Cold Urticaria |
| Symptomatic Dermographism | |||||
All measurements at | 150 mg | 300 mg | Placebo | 150 mg | 300 mg | Placebo | |
Primary endpoint: | 46.9% | 53.1% | 12.5% | 57.6% | 42.4% | 3.2% | |
% of patients with complete or partial response per provocation test | 62.5% | 75% | 31.3% | 66.6% | 57.5% | 12.9% | |
Improvement in Critical Temperature (CTT) and Critical Friction (CFT) Thresholds | -8.82°C | -9.61°C | -0.30°C | -2.46 pins | -2.27 pins | -0.82 pins | |
% of patients with Urticaria Control Test >12 | 58.6% | 68.8% | 31.0% | 54.8% | 65.5% | 32.0% | |
Patients experienced rapid disease improvement as early as two weeks (the first assessment) after receiving the initial dose of barzolvolimab as demonstrated by reductions in critical temperature and friction thresholds resulting in hives and rapid reduction in itch at the time of provocation testing (WI-NRSprovo).
Barzolvolimab was well tolerated with a favorable safety profile consistent with prior studies. Most adverse events were grade 1 (mild). Through 12 weeks, the most common treatment emergent adverse events in barzolvolimab treated patients were hair color changes (13%; Grade 1, n=15 / Grade 2, n=2) and neutropenia (10%; Grade 1, n=7 / Grade 2, n=6), which are mechanism related (KIT) and expected to be reversible. The rate of infections was similar between barzolvolimab-treated patients and placebo with no association between neutropenia and infections.
We believe these results strongly support the further development of barzolvolimab in CIndU and plan to advance CIndU into Phase 3 registrational development.
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Prurigo Nodularis (PN)
We have expanded clinical development of barzolvolimab into prurigo nodularis (PN). PN is a chronic skin disease characterized by the development of hard, intensely itchy (pruritic) nodules on the skin. Mast cells through their interactions with sensory neurons and other immune cells are believed to play an important role in amplifying chronic itch and neuroinflammation, both of which are a hallmark of PN. There is currently only one FDA approved therapy for PN, representing an area of significant unmet need. Industry sources estimate there are approximately 154,000 patients in the United States with PN who have undergone treatment within the last 12 months and, of these, approximately 75,000 would be biologic-eligible.
We have completed a Phase 1b multi-center, randomized, double-blind, placebo-controlled intravenous study in PN. Data from the study, including 24 weeks of follow-up, were presented at the 12th World Congress on Itch (WCI) held in November 2023. 24 adults (evaluable: n=23 safety; n=22 efficacy) with moderate to severe PN were randomized across three arms: (1) barzolvolimab 3.0 mg/kg (n=9), barzolvolimab 1.5 mg/kg (n=7) and placebo (n=8). The primary endpoint of the study was safety; key secondary endpoints include changes from baseline in Worst Itch-Numerical Rating Scale (WI-NRS) & Investigator Global Assessment (IGA). The primary timepoint for evaluation of clinical activity was 8 weeks; patients were followed for safety and efficacy endpoints to 24 weeks. Patients on study generally had moderate to severe disease with mean baselines scores across all arms of 8.6 for WI-NRS and 3.3 for IGA.
A single IV dose of 3.0 mg/kg barzolvolimab resulted in rapid and durable reductions in itch and healing of skin lesions in patients with moderate to severe PN and that barzolvolimab was generally well tolerated.
| ● | At week 8, the percentage of patients with ≥4-point decrease in WI-NRS was 57% and 43% for the single dose 3.0 or 1.5 mg/kg barzolvolimab arms, respectively, and 25% for the placebo arm; this level of response generally persisted out to week 16. In the 3.0 mg/kg arm, a ≥4-point decrease in WI-NRS reduction was seen as early as the first week and reached a high of 71% of patients at week six which was distinct from both the 1.5 mg/kg barzolvolimab and placebo arms. |
% of Subjects with ≥4-point decrease in WI-NRS | |||||||||
Dose | Week 1 | Week 2 | Week 3 | Week 4 | Week 5 | Week 6 | Week 7 | Week 8 | |
1.5 mg/kg | 0 | 14 | 29 | 14 | 29 | 29 | 29 | 43 | |
3.0 mg/kg | 14 | 29 | 29 | 29 | 57 | 71 | 57 | 57 | |
placebo | 0 | 0 | 13 | 13 | 25 | 38 | 38 | 25 | |
| ● | At week 8, 29% of patients achieved clear or almost clear skin according to IGA following a single dose of barzolvolimab 3.0 mg/kg. This effect was noted as early as week 2 (the first clinic visit) and was maintained out to week 12/16. No patients treated at 1.5 mg/kg barzolvolimab or placebo achieved clear or almost clear skin according to IGA through week 8. 2 additional patients in the 1.5 mg/kg arm, 2 additional patients in the 3.0 mg/kg arm and 1 patient on placebo had IGA 0/1 at timepoints between weeks 8 and 24. |
% of Subjects with IGA 0/1 | ||||
Dose | Baseline | Week 2 | Week 4 | Week 8 |
1.5 mg/kg | 0 | 0 | 0 | 0 |
3.0 mg/kg | 0 | 14 | 14 | 29 |
Placebo | 0 | 0 | 0 | 0 |
| ● | Clinical activity was associated with profound serum tryptase reduction. At the 3.0 mg/kg dose, tryptase was profoundly reduced to, or below, the level of quantification and this level of reduction was maintained at least through 8 weeks. Tryptase reduction was observed in the 1.5 mg/kg arm but to a lesser extent. |
| ● | Adverse Events were generally mild to moderate in intensity and considered unrelated to treatment. During the initial 8 week observation period in the 3.0 mg/kg dosing arm, an anaphylactic reaction occurred in a complicated patient with multiple comorbidities; the event fully resolved without sequelae. Generally, adverse events seen during the 24-week follow-up period were consistent with comorbidities commonly observed in the PN population. |
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In April 2024, we initiated a Phase 2 subcutaneous study in PN. This randomized, double-blind, placebo-controlled, parallel group study is evaluating the efficacy and safety profile of 2 dose levels of barzolvolimab compared to placebo in approximately 120 patients with moderate to severe PN who had inadequate response to prescription topical medications, or for whom topical medications are medically inadvisable (such as concerns for safety). Patients are randomly assigned on a 1:1:1 ratio to receive barzolvolimab injections of 150 mg Q4W after an initial loading dose of 450 mg, 300 mg Q4W after an initial loading dose of 450 mg, or placebo during a 24‑week Treatment Phase. Participants then enter a follow-up phase with no study treatment for an additional 16 weeks through week 40. The primary objective of this study is to evaluate the clinical effect of barzolvolimab, compared to placebo, on itch response as measured by the proportion of participants with ≥ 4-point improvement in the worst intensity itch per a numeric rating scale (WI-NRS). Secondary objectives include but are not limited to additional measures of itch response from baseline compared to different timepoints, the assessment of skin lesions as measured by the Investigator Global Assessment (IGA), QoL outcomes and safety. The study will include approximately 50 clinical trial centers worldwide, including the United States. Enrollment is ongoing.
Eosinophilic Esophagitis (EoE)
In July of 2023, we announced that the first patient had been dosed in a Phase 2 study of eosinophilic esophagitis (EoE). EoE, the most common type of eosinophilic gastrointestinal disease, is a chronic inflammatory disease of the esophagus characterized by the infiltration of eosinophils. This chronic inflammation can result in trouble swallowing, chest pain, vomiting and impaction of food in the esophagus, a medical emergency. Several studies have suggested that mast cells may be an important driver in the disease, demonstrating that the number and activation state of mast cells are greatly increased in EoE biopsies and that mast cell signatures correlate with markers of inflammation, fibrosis, pain and disease severity. Currently, there is only one FDA approved therapy for EoE, representing an area of significant unmet need. Industry sources estimate there are approximately 160,000 patients in the United States with EoE who have undergone treatment within the last 12 months and, of these, approximately 48,000 would be biologic-eligible. Given the lack of effective therapies for EoE and barzolvolimab’s potential as a mast cell depleting agent, we believe EoE is an important indication for future study.
The randomized, double-blind, placebo-controlled, parallel group Phase 2 study is evaluating the efficacy and safety profile of subcutaneous barzolvolimab in patients with active EoE. To optimize potential efficacy signal in this difficult to treat indication, we have recently amended the protocol to dose 300 mg every 4 weeks rather than 8 weeks. Approximately 75 patients will be enrolled in total. In the revised protocol, patients will be randomly assigned on a 1:1 ratio to receive subcutaneous injections of barzolvolimab at 300 mg every 4 weeks or placebo during a 16-week placebo-controlled treatment phase. Patients then enter a 12-week active treatment phase, in which all patients will receive barzolvolimab 300 mg every 4 weeks. Patients then enter a follow-up phase for an additional 16 weeks. The primary endpoint of the study is reducing esophageal intraepithelial infiltration of mast cells as assessed by peak esophageal intraepithelial mast cell count. Secondary endpoints include the reduction of symptoms of dysphagia and esophageal intraepithelial infiltration of eosinophils and safety. The study includes approximately 60 clinical trial centers across 8 countries, including the United States. Enrollment is ongoing.
Additional Barzolvolimab Development Activities
In 2023, we completed the transfer of our current barzolvolimab manufacturing process to a CMO and successfully scaled up the drug substance manufacturing process to produce larger cGMP batches in support of late-stage trials and to prepare for potential commercialization. Drug product manufacturing into 1 mL pre-filled syringes has been completed and are actively being used in the ongoing Phase 3 CSU trials.
In February 2022, we reported interim data after completing the in-life dosing portion of our six-month chronic toxicology study in non-human primates. The only clinically adverse finding at the completion of dosing was a profound impact on spermatogenesis, an expected and well understood effect of KIT inhibition. As a standard part of toxicology studies, some animals from each group continued to be observed through a recovery period to understand the reversibility of any adverse findings. Due to the very high concentrations of barzolvolimab at the end of dosing, the recovery period was approximately one year. As we expected, and consistent with previous findings with KIT blocking antibodies, we were pleased to report in December 2022, that during this recovery period spermatogenesis fully recovered in all male animals as measured by both sperm count and motility. The final histologic analysis and study report were completed in early 2023 and were consistent with previously reported results. We are encouraged with these findings and believe these data strongly support continued development of barzolvolimab.
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Bispecific Platform
Our next generation bispecific antibody platform is supporting the expansion of our pipeline with additional candidates for inflammatory diseases. Targets are being selected based on new science as well as their compatibility to be used in bispecific antibody formats with our existing antibody programs. Development is focused on emerging, important pathways controlling inflammatory diseases.
CDX-622
CDX-622 is a bispecific antibody that targets two complementary pathways that drive chronic inflammation, potently neutralizing the alarmin thymic stromal lymphopoietin (TSLP) and depleting mast cells via stem cell factor (SCF) starvation. TSLP has been directly implicated in several respiratory and dermatological disorders, such as asthma, chronic obstructive pulmonary disease (COPD), eosinophilic esophagitis, atopic dermatitis and chronic spontaneous urticaria, and in fibrotic diseases such as systemic sclerosis and idiopathic pulmonary fibrosis. In these disorders, TSLP is often upregulated and associated with disease severity. Similarly, mast cells drive or contribute to the pathophysiology of allergic, inflammatory, autoimmune and fibrotic disorders and CDX-622 contains a unique SCF neutralizing function that is expected to inhibit and deplete mast cells. Combined neutralization of SCF and TSLP with CDX-622 is expected to simultaneously reduce tissue mast cells and inhibit Type 2 inflammatory responses to potentially offer enhanced therapeutic benefit in inflammatory and fibrotic disorders. In preclinical studies, CDX-622 inhibits TSLP and SCF with similar potency to both its respective parental mAbs and comparator mAbs in vitro. CDX-622 was well tolerated in a multi-dose 8 week toxicology study in non-human primates. The No Adverse Event Level (NOAEL) was established to be 75 mg/kg, the highest dose level tested. We have completed manufacturing and IND-enabling activities and plan to initiate a Phase 1 study of CDX-622 in healthy volunteers by the end of 2024.
CDX-585
CDX-585 combines our proprietary highly active PD-1 blockade and anti-ILT4 blockade to overcome immunosuppressive signals in T cells and myeloid cells, respectively. The concept behind CDX-585 is to simultaneously inhibit both T cell and myeloid suppressive signals to potentiate the anti-tumor activity of both cell types, and potentially overcome PD-1 resistance. We began dosing patients in May 2023 in a Phase 1 open-label, multi-center, multi-dose study in patients with advanced or metastatic solid tumors that have progressed during or after standard of care therapy. The dose-escalation phase of the study has been completed and we have decided not to advance CDX-585 given our expanding clinical development program in the inflammatory space, including barzolvolimab, which will enter studies in its fifth indication by year end 2024 and the near term advancement of CDX-622 into the clinic.
CRITICAL ACCOUNTING POLICIES AND ESTIMATES
See Note 2 to the unaudited condensed consolidated financial statements included elsewhere in this Quarterly Report on Form 10-Q for information regarding newly adopted and recent accounting pronouncements. See also Note 2 to our financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2023 for a discussion of our critical accounting policies and estimates. There have been no material changes to such critical accounting policies or estimates. We believe our most critical accounting policies include accounting for contingent consideration, revenue recognition, intangible and long-lived assets, research and development expenses and stock-based compensation expense.
29
RESULTS OF OPERATIONS
Three Months Ended September 30, 2024 Compared with Three Months Ended September 30, 2023
Three Months Ended | Increase/ | Increase/ |
| |||||||||
September 30, | (Decrease) | (Decrease) |
| |||||||||
| 2024 |
| 2023 |
| $ |
| % |
| ||||
| (In thousands) | |||||||||||
Revenues: | ||||||||||||
Product development and licensing agreements | $ | 3 |
| $ | 2 | $ | 1 | 50 | % | |||
Contracts and grants |
| 3,188 |
|
| 1,515 |
| 1,673 | 110 | % | |||
Total revenues | $ | 3,191 |
| $ | 1,517 | $ | 1,674 | 110 | % | |||
Operating expenses: |
|
|
|
|
| |||||||
Research and development |
| 45,263 |
|
| 34,535 |
| 10,728 | 31 | % | |||
General and administrative |
| 10,054 |
|
| 8,221 |
| 1,833 | 22 | % | |||
Total operating expenses |
| 55,317 |
|
| 42,756 |
| 12,561 | 29 | % | |||
Operating loss |
| (52,126) |
| (41,239) |
| 10,887 | 26 | % | ||||
Investment and other income, net |
| 10,005 |
|
| 2,979 |
| 7,026 | 236 | % | |||
Net loss | $ | (42,121) | $ | (38,260) | $ | 3,861 | 10 | % | ||||
Net Loss
The $3.9 million increase in net loss for the three months ended September 30, 2024, as compared to the three months ended September 30, 2023, was primarily due to an increase in research and development expenses, partially offset by an increase in investment and other income, net.
Revenue
Revenue from product development and licensing agreements for the three months ended September 30, 2024 was relatively consistent with the three months ended September 30, 2023. The $1.7 million increase in contracts and grants revenue for the three months ended September 30, 2024, as compared to the three months ended September 30, 2023, was primarily due to an increase in revenue from our contract manufacturing and research and development agreements with Rockefeller University. We expect revenue to decrease over the next twelve months primarily due to a decrease in services expected to be performed under our contract manufacturing and research and development agreements with Rockefeller University.
Research and Development Expense
Research and development expenses consist primarily of (i) personnel expenses, (ii) laboratory supply expenses relating to the development of our technology, (iii) facility expenses and (iv) product development expenses associated with our drug candidates as follows:
Three Months Ended | Increase/ |
| ||||||||||
September 30, | (Decrease) |
| ||||||||||
| 2024 |
| 2023 |
| $ |
| % |
| ||||
| (In thousands) | |||||||||||
Personnel | $ | 13,855 | $ | 10,532 | $ | 3,323 | 32 | % | ||||
Laboratory supplies |
| 1,074 |
| 1,249 |
| (175) | (14) | % | ||||
Facility |
| 1,263 |
| 1,282 |
| (19) | (1) | % | ||||
Product development |
| 26,539 |
| 19,457 |
| 7,082 | 36 | % | ||||
Personnel expenses primarily include salary, benefits, stock-based compensation and payroll taxes. The $3.3 million increase in personnel expenses for the three months ended September 30, 2024, as compared to the three months ended September 30, 2023, was primarily due to higher stock-based compensation expense and an increase in employee headcount. We expect personnel expenses to increase over the next twelve months as a result of additional headcount to support the expanded development of barzolvolimab.
30
Laboratory supplies expenses include laboratory materials and supplies, services, and other related expenses incurred in the development of our technology. Laboratory supply expenses for the three months ended September 30, 2024 were relatively consistent with the three months ended September 30, 2023. We expect laboratory supplies expenses to remain relatively consistent over the next twelve months, although there may be fluctuations on a quarterly basis.
Facility expenses include depreciation, amortization, utilities, rent, maintenance and other related expenses incurred at our facilities. Facility expenses for the three months ended September 30, 2024 were relatively consistent with the three months ended September 30, 2023. We expect facility expenses to remain relatively consistent over the next twelve months, although there may be fluctuations on a quarterly basis.
Product development expenses include clinical investigator site fees, external trial monitoring costs, data accumulation costs, contracted research and outside clinical drug product manufacturing. The $7.1 million increase in product development expenses for the three months ended September 30, 2024, as compared to the three months ended September 30, 2023, was primarily due to an increase in barzolvolimab clinical trial expenses, partially offset by a decrease in barzolvolimab contract manufacturing expenses. We expect product development expenses to increase over the next twelve months as a result of the expanded development of barzolvolimab, although there may be fluctuations on a quarterly basis.
General and Administrative Expense
The $1.8 million increase in general and administrative expenses for the three months ended September 30, 2024, as compared to the three months ended September 30, 2023, was primarily due to higher stock-based compensation and barzolvolimab commercial planning expenses. We expect general and administrative expenses to increase over the next twelve months as a result of the expanded development of barzolvolimab and an increase in commercial planning efforts, although there may be fluctuations on a quarterly basis.
Investment and Other Income, Net
The $7.0 million increase in investment and other income, net for the three months ended September 30, 2024, as compared to the three months ended September 30, 2023, was primarily due to higher levels of cash as a result of our November 2023 and March 2024 underwritten public offerings. We expect investment and other income to remain relatively consistent over the next twelve months, although there may be fluctuations on a quarterly basis.
Nine Months Ended September 30, 2024 Compared with Nine Months Ended September 30, 2023
Nine Months Ended | Increase/ | Increase/ |
| |||||||||
September 30, | (Decrease) | (Decrease) |
| |||||||||
| 2024 |
| 2023 |
| $ |
| % |
| ||||
| (In thousands) | |||||||||||
Revenues: |
| |||||||||||
Product development and licensing agreements | $ | 5 |
| $ | 19 | $ | (14) | (74) | % | |||
Contracts and grants |
| 5,840 |
|
| 2,733 |
| 3,107 | 114 | % | |||
Total revenues | $ | 5,845 |
| $ | 2,752 | $ | 3,093 | 112 | % | |||
Operating expenses: |
|
|
|
|
| |||||||
Research and development |
| 116,611 |
|
| 87,585 |
| 29,026 | 33 | % | |||
General and administrative |
| 28,285 |
|
| 22,082 |
| 6,203 | 28 | % | |||
Total operating expenses |
| 144,896 |
| 109,667 |
| 35,229 | 32 | % | ||||
Operating loss |
| (139,051) |
|
| (106,915) |
| 32,136 | 30 | % | |||
Investment and other income, net | 28,280 | 8,792 | 19,488 | 222 | % | |||||||
Net loss | $ | (110,771) | $ | (98,123) | $ | 12,648 | 13 | % | ||||
Net Loss
The $12.6 million increase in net loss for the nine months ended September 30, 2024, as compared to the nine months ended September 30, 2023, was primarily due to increases in research and development and general and administrative expenses, partially offset by an increase in investment and other income, net.
31
Revenue
Revenue from product development and licensing agreements for the nine months ended September 30, 2024 was relatively consistent with the nine months ended September 30, 2023. The $3.1 million increase in contracts and grants revenue for the nine months ended September 30, 2024, as compared to the nine months ended September 30, 2023, was primarily due to an increase in revenue from our contract manufacturing and research and development agreements with Rockefeller University.
Research and Development Expense
Research and development expenses consist primarily of (i) personnel expenses, (ii) laboratory supply expenses relating to the development of our technology, (iii) facility expenses and (iv) product development expenses associated with our drug candidates as follows:
Nine Months Ended | Increase/ |
| ||||||||||
September 30, | (Decrease) |
| ||||||||||
| 2024 |
| 2023 |
| $ |
| % |
| ||||
| (In thousands) | |||||||||||
Personnel | $ | 37,176 | $ | 28,559 | $ | 8,617 | 30 | % | ||||
Laboratory supplies |
| 3,997 | 4,167 | (170) | (4) | % | ||||||
Facility |
| 3,799 | 3,699 | 100 | 3 | % | ||||||
Product development |
| 64,732 | 45,348 | 19,384 | 43 | % | ||||||
Personnel expenses primarily include salary, benefits, stock-based compensation and payroll taxes. The $8.6 million increase in personnel expenses for the nine months ended September 30, 2024, as compared to the nine months ended September 30, 2023, was primarily due to higher stock-based compensation expense and an increase in employee headcount.
Laboratory supplies expenses include laboratory materials and supplies, services, and other related expenses incurred in the development of our technology. Laboratory supply expenses for the nine months ended September 30, 2024 were relatively consistent with the nine months ended September 30, 2023.
Facility expenses include depreciation, amortization, utilities, rent, maintenance and other related expenses incurred at our facilities. Facility expenses for the nine months ended September 30, 2024 were relatively consistent with the nine months ended September 30, 2023.
Product development expenses include clinical investigator site fees, external trial monitoring costs, data accumulation costs, contracted research and outside clinical drug product manufacturing. The $19.4 million increase in product development expenses for the nine months ended September 30, 2024, as compared to the nine months ended September 30, 2023, was primarily due to an increase in barzolvolimab clinical trial expenses, partially offset by a decrease in barzolvolimab contract manufacturing expenses.
General and Administrative Expense
The $6.2 million increase in general and administrative expenses for the nine months ended September 30, 2024, as compared to the nine months ended September 30, 2023, was primarily due to higher stock-based compensation and barzolvolimab commercial planning expenses.
Investment and Other Income, Net
The $19.5 million increase in investment and other income, net for the nine months ended September 30, 2024, as compared to the nine months ended September 30, 2023, was primarily due to higher levels of cash as a result of our November 2023 and March 2024 underwritten public offerings.
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LIQUIDITY AND CAPITAL RESOURCES
Our cash equivalents are highly liquid investments with a maturity of three months or less at the date of purchase and consist primarily of investments in money market mutual funds with commercial banks and financial institutions. We maintain cash balances with financial institutions in excess of insured limits. We do not anticipate any losses with respect to such cash balances. We invest our excess cash balances in marketable securities, including municipal bond securities, U.S. government agency securities and high-grade corporate bonds that meet high credit quality standards, as specified in our investment policy. Our investment policy seeks to manage these assets to achieve our goals of preserving principal and maintaining adequate liquidity.
The use of our cash flows for operations has primarily consisted of salaries and wages for our employees; facility and facility-related costs for our offices, laboratories and manufacturing facility; fees paid in connection with preclinical studies, clinical studies, contract manufacturing, laboratory supplies and services; and consulting, legal and other professional fees. We anticipate that our cash flows from operations will continue to be focused in these areas as we progress our current drug candidates through the clinical trial process and develop additional drug candidates. To date, the primary sources of cash flows from operations have been payments received from our collaborative partners and from government entities and payments received for contract manufacturing and research and development services provided by us. The timing of any new contract manufacturing and research and development agreements, collaboration agreements, government contracts or grants and any payments under these agreements, contracts or grants cannot be easily predicted and may vary significantly from quarter to quarter.
At September 30, 2024, our principal sources of liquidity consisted of cash, cash equivalents and marketable securities of $756.0 million. We have had recurring losses and incurred a loss of $110.8 million for the nine months ended September 30, 2024. Net cash used in operations for the nine months ended September 30, 2024 was $125.3 million. We believe that the cash, cash equivalents and marketable securities at September 30, 2024 are sufficient to meet estimated working capital requirements and fund current planned operations through 2027. This could be impacted if we elect to pay the future milestone under the Settlement Agreement with SRS in cash, in the event that we achieve the milestone related to that payment.
During the next twelve months, we may take further steps to raise additional capital to meet our long-term liquidity needs including, but not limited to, one or more of the following: the licensing of drug candidates with existing or new collaborative partners, possible business combinations, issuance of debt, or the issuance of common stock or other securities via private placements or public offerings. Although we have been successful in raising capital in the past, there can be no assurance that additional financing will be available on acceptable terms, if at all, and our negotiating position in capital raising efforts may worsen as existing resources are used. There is also no assurance that we will be able to enter into further collaborative relationships. Additional equity financings may be dilutive to our stockholders; debt financings, if available, may involve significant cash payment obligations and covenants that restrict our ability to operate as a business; and licensing or strategic collaborations may result in royalties or other terms which reduce our economic potential from products under development. Our ability to continue funding our planned operations into and beyond twelve months from the issuance date is also dependent on the timing and manner of payment of the future milestone under the Settlement Agreement with SRS, in the event that we achieve the milestone related to that payment. We may decide to pay that milestone payment in cash, shares of our common stock or a combination thereof. If we are unable to raise the funds necessary to meet our long-term liquidity needs, we may have to delay or discontinue the development of one or more programs, discontinue or delay ongoing or anticipated clinical trials, license out programs earlier than expected, raise funds at a significant discount or on other unfavorable terms, if at all, or sell all or a part of our business.
Operating Activities
Net cash used in operating activities was $125.3 million for the nine months ended September 30, 2024 as compared to $74.8 million for the nine months ended September 30, 2023. The increase in net cash used in operating activities was primarily due to increases in research and development and general and administrative expenses and an increase in advance payments to clinical research and contract manufacturing organizations, partially offset by an increase in investment income as a result of higher levels of cash. We expect that cash used in operating activities will increase over the next twelve months as a result of the expanded development of barzolvolimab.
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We have incurred and will continue to incur significant costs in the area of research and development, including preclinical and clinical trials and clinical drug product manufacturing as our drug candidates are developed. We plan to spend significant amounts to progress our current drug candidates through the clinical trial process as well as to develop additional drug candidates. As our drug candidates progress through the clinical trial process, we may be obligated to make significant milestone payments, pursuant to our existing arrangements and arrangements we may enter in the future.
Investing Activities
Net cash used in investing activities was $314.2 million for the nine months ended September 30, 2024 compared to net cash provided by investing activities of $65.4 million for the nine months ended September 30, 2023. The increase in net cash used in investing activities was primarily due to net purchases of marketable securities of $313.0 million for the nine months ended September 30, 2024 as compared to net sales and maturities of marketable securities of $66.5 million for the nine months ended September 30, 2023.
Financing Activities
Net cash provided by financing activities was $441.1 million for the nine months ended September 30, 2024 as compared to $1.1 million for the nine months ended September 30, 2023. The increase in net cash provided by financing activities was primarily due to an increase in net proceeds from stock issuances.
In March 2024, we issued 9,798,000 shares of common stock in an underwritten public offering, resulting in net proceeds of $432.3 million, after deducting underwriting fees and offering expenses.
Item 3. Quantitative and Qualitative Disclosures about Market Risk
We own financial instruments that are sensitive to market risk as part of our investment portfolio. Our investment portfolio is used to preserve our capital until it is used to fund operations, including our research and development activities. None of these market-risk sensitive instruments are held for trading purposes. We invest our cash primarily in money market mutual funds. These investments are evaluated quarterly to determine the fair value of the portfolio. From time to time, we invest our excess cash balances in marketable securities including municipal bond securities, U.S. government agency securities and high-grade corporate bonds that meet high credit quality standards, as specified in our investment policy. Our investment policy seeks to manage these assets to achieve our goals of preserving principal and maintaining adequate liquidity. Because of the short-term nature of these investments, we do not believe we have material exposure due to market risk. The impact to our financial position and results of operations from likely changes in interest rates is not material.
We do not utilize derivative financial instruments. The carrying amounts reflected in the consolidated balance sheet of cash and cash equivalents, accounts receivables and accounts payable approximate fair value at September 30, 2024 due to the short-term maturities of these instruments.
Item 4. Controls and Procedures
Evaluation of Disclosure Controls and Procedures.
As of September 30, 2024, we evaluated, with the participation of our Chief Executive Officer and Chief Financial Officer, the effectiveness of our disclosure controls and procedures (as defined in Rules 13a-15(e) and 15d-15(e) under the Securities Exchange Act of 1934, as amended (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. Our disclosure controls and procedures are designed to provide reasonable assurance that information required to be disclosed in the reports that we file or submit under the Exchange Act is recorded, processed, summarized and reported within time periods specified by the SEC’s rules and forms, and that such information is accumulated and communicated to our management, including our Chief Executive Officer and Chief Financial Officer, as appropriate to allow timely decisions regarding required disclosure.
Changes in Internal Control Over Financial Reporting.
There were no changes in our internal control over financial reporting during the quarter ended September 30, 2024 that have materially affected, or are reasonably likely to materially affect, our internal control over financial reporting.
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PART II — OTHER INFORMATION
Item 1A. Risk Factors
In addition to the other information set forth in this report, you should carefully consider the factors discussed in Part I, “Item 1A. Risk Factors” in our Annual Report on Form 10-K for the year ended December 31, 2023, which could materially affect our business, financial condition or future results. The risks described in our Annual Report on Form 10-K may not be the only risks facing us. Additional risks and uncertainties not currently known to us or that we currently deem to be immaterial also may materially adversely affect our business, financial condition and/or operating results.
There were no material changes to the risk factors previously disclosed in our Annual Report on Form 10-K filed with the SEC on February 26, 2024.
Item 5. Other Information
During the period covered by this Quarterly Report on Form 10-Q, no director or officer of the Company
Item 6. Exhibits
The exhibits filed as part of this Quarterly Report on Form 10-Q are listed in the exhibit index included herewith and are incorporated by reference herein.
EXHIBIT INDEX
Exhibit |
| Description |
*31.1 | ||
*31.2 | Certification of Senior Vice President and Chief Financial Officer. | |
**32.1 | ||
*101.INS | Inline XBRL Instance Document – the instance document does not appear in the Interactive Data File because its 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 Data File (formatted as Inline XBRL with applicable taxonomy extension information contained in Exhibits 101). |
* | Filed herewith. |
** | Furnished herewith. |
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SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned thereunto duly authorized.
| CELLDEX THERAPEUTICS, INC. |
|
|
| BY: |
|
|
| /s/ ANTHONY S. MARUCCI |
Dated: November 6, 2024 | Anthony S. Marucci |
| President and Chief Executive Officer |
| (Principal Executive Officer) |
|
|
| /s/ SAM MARTIN |
Dated: November 6, 2024 | Sam Martin |
| Senior Vice President and Chief Financial Officer |
| (Principal Financial and Accounting Officer) |
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