10-Q

用复选标记表示注册人(1)是否在过去12个月内(或注册人被要求提交此类报告的较短时间内)提交了1934年《证券交易法》第13条或15(D)节要求提交的所有报告，以及(2)在过去90天内是否符合此类提交要求。是 ☒ 没有预设

用复选标记表示注册人是否在过去12个月内(或在注册人被要求提交此类文件的较短时间内)以电子方式提交了根据S-T规则第405条(本章232.405节)要求提交的每个交互数据文件。是 ☒ 没有预设

用复选标记表示注册人是大型加速申报公司、加速申报公司、非加速申报公司、较小的报告公司或新兴成长型公司。请参阅《交易法》第12b-2条规则中“大型加速申报公司”、“加速申报公司”、“较小申报公司”和“新兴成长型公司”的定义。

如果是一家新兴的成长型公司，用复选标记表示注册人是否已选择不使用延长的过渡期来遵守根据《交易所法》第13(A)节提供的任何新的或修订的财务会计准则。☐

用复选标记表示注册人是否是空壳公司(如《交易法》第12b-2条所定义)。是，☐不是☒

截至2024年10月29日，登记人已 84,663,840 普通股，每股面值0.001美元，已发行。

这份Form 10-Q季度报告包括涉及重大风险和不确定性的前瞻性陈述。除有关历史事实的陈述外，本10-Q表格季度报告中包含的所有陈述，包括有关我们的战略、未来运营、未来财务状况、未来收入、预计成本、前景、计划和管理目标的陈述，均为前瞻性陈述。“预期”、“相信”、“考虑”、“继续”、“可能”、“估计”、“预期”、“打算”、“可能”、“可能”、“计划”、“潜在”、“预测”、“项目”、“应该”、“目标”、“将会”、“将会”或这些词语的否定或其他类似表述旨在识别前瞻性陈述。尽管并不是所有的前瞻性陈述都包含这些识别词语。

本季度报表10—Q表中的前瞻性陈述包括，除其他事项外，关于：

我们可能无法实际实现我们的前瞻性声明中披露的计划、意图或预期，您不应过度依赖我们的前瞻性声明。实际结果或事件可能与我们在前瞻性陈述中披露的计划、意图和预期大不相同。我们在这份Form 10-Q季度报告中的警示性声明中包含了重要因素，特别是在“风险因素”部分，我们认为这些因素可能会导致实际结果或事件与我们所作的前瞻性声明大不相同。我们的前瞻性陈述不反映我们可能进行或进行的任何未来收购、合并、处置、合作、合资或投资的潜在影响。

您应该阅读本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，并已作为我们向美国证券交易委员会提交的其他文件的证据完整提交，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。本季度报告（Form 10-Q）中包含的前瞻性陈述于本季度报告（Form 10-Q）之日做出，我们不承担任何更新任何前瞻性陈述的义务，无论是由于新信息、未来事件还是其他原因，适用法律要求的除外。

除文意另有所指或另有指示外，本季度报告中的“我们”、“我们的公司”、“公司”和“我们的业务”是指Verve Treateutics公司及其合并子公司。

我们的业务面临着许多风险，在做出投资决定之前，您应该意识到这些风险。以下我们总结了我们认为我们的业务面临的主要风险，以及本报告中包含的本季度报告第二部分关于Form 10-Q的“风险因素”和其他信息中更全面地描述的风险。下面描述的风险和不确定性并不是我们面临的唯一风险和不确定性。我们目前不知道或我们目前认为不太重要的其他风险和不确定性也可能损害我们的业务运营。

如果发生以下任何风险，我们的业务、财务状况和经营结果以及未来的增长前景可能会受到重大不利影响，本报告中作出的前瞻性陈述的实际结果可能与此类前瞻性陈述中预期的结果大不相同：

1. 业务性质和列报依据

组织

Verve治疗公司(“公司”或“Verve”)是一家临床阶段的公司，开发一种治疗心血管疾病的新型基因药物，有可能将治疗从慢性治疗转变为单疗程基因编辑药物。该公司于2018年3月9日成立，名为Endcadia，Inc.，是特拉华州的一家公司，此后不久开始运营。2019年1月，公司修改了公司注册证书，更名为Verve Treateutics，Inc.。公司的主要办事处位于马萨诸塞州波士顿。

流动资金和资本资源

自成立以来，公司主要致力于研究开发和筹集资金。该公司受到生物技术行业早期公司常见的风险和不确定因素的影响，这些风险和不确定因素包括但不限于与候选产品的成功研究、开发和制造有关的技术风险、竞争对手对新技术创新的开发、对关键人员的依赖、对专有技术的保护、对政府法规的遵守以及获得额外资本以资助运营的能力。目前和未来的项目将需要大量的研究和开发努力，包括广泛的临床前和临床测试以及商业化之前的监管批准。这些努力需要大量额外资本、充足的人员和基础设施以及广泛的合规报告能力。即使该公司的开发努力取得了成功，该公司何时(如果有的话)将从产品销售中获得可观的收入也是不确定的。

随附的简明综合财务报表乃以持续经营为基础编制，考虑在正常业务过程中变现资产及清偿负债及承担。本公司预期其现金、现金等价物及有价证券$539.9 万截至2024年9月30日，将足以为自这些财务报表发布之日起未来12个月内的运营和资本支出需求提供资金。该公司将需要额外的资金来支持其持续运营和实施其增长战略。在该公司能够从产品销售中获得可观的收入之前，如果有的话，它预计将通过股权发行、债务融资、合作、战略联盟以及营销、分销或许可安排来为其运营提供资金。公司可能无法在需要时以优惠条款或根本无法筹集额外资金或签订此类其他协议。无法在需要时筹集资金，可能会对公司的财务状况和实施其业务战略的能力产生负面影响。该公司将需要创造大量收入来实现盈利，而且它可能永远不会这样做。

陈述的基础

随附的简明综合财务报表乃根据美国公认会计原则(“公认会计原则”)及美国证券交易委员会(“美国证券交易委员会”)的规则及规定编制。本附注内对适用指引的任何提及均指财务会计准则委员会(“FASB”)的会计准则编纂(“ASC”)及“会计准则更新”(“ASU”)所载的权威公认会计原则。按照“公认会计原则”编制的财务报表中通常包含的某些信息和脚注披露已根据这些规则和条例予以精简或省略。

未经审核简明综合财务报表已按经审核综合财务报表的相同基准编制。公司管理层认为，随附的未经审计的简明综合财务报表包含所有必要的调整，以公平地反映公司截至2024年9月30日的财务状况、截至2024年和2023年9月30日的三个月和九个月的运营结果和其他全面亏损、截至2024年和2023年9月30日的三个月和九个月的股东权益以及截至2024年和2023年9月30日的九个月的现金流量。这样的调整是正常的和反复出现的。截至2024年9月30日的三个月和九个月的业绩不一定代表截至2024年12月31日的一年或任何未来时期的业绩。这些中期财务报表应与截至及截至该年度的经审计综合财务报表一并阅读

3.有价证券

按证券类型划分的有价证券包括以下内容：


	2024年9月30日
(单位：千)	摊销成本		毛收入未实现利得		毛收入未实现损失			公平值
美国国库券和票据	$	179,012	$	673	$	(1	)	$	179,684
美国机构证券		201,056		486		(15	)		201,527
总	$	380,068	$	1,159	$	(16	)	$	381,211


	2023年12月31日
(单位：千)	摊销成本		毛收入未实现利得		毛收入未实现损失			公平值
美国国库券和票据	$	147,978	$	144	$	(15	)	$	148,107
美国机构证券		269,520		277		(134	)		269,663
总	$	417,498	$	421	$	(149	)	$	417,770

截至2024年9月30日，所有有价证券的剩余合同期限均不到18个月，截至2023年12月31日，其余合同期限均不到24个月。截至2024年9月30日，公司有价证券的未实现毛额损失为极低。公司有价证券的未实现毛额损失 $0.1 万截至2023年12月31日，是由于利率上升导致这些证券的市值下降。由于公允价值下降是由于利率变化而不是信贷质量变化，并且由于公司无意出售投资，并且公司不太可能被要求在收回其摊销成本基础（可能到期）之前出售投资，因此公司不认为该有价证券于9月30日出现了损失，2024年或2023年12月31日.该公司的有价证券均未处于持续未实现亏损状态 12个月或更大截至 2024年9月30日或2023年12月31日.

4. P性能和设备，网络

财产和设备净额由下列部分组成：


(单位：千)	2024年9月30日			2023年12月31日
实验室设备	$	30,937		$	28,851
租赁权改进		776			726
家具和固定装置		2,323			2,323
计算机设备		997			997
总资产和设备		35,033			32,897
减去累计折旧		(15,408	)		(10,392	)
财产和设备，净额	$	19,625		$	22,505

下表总结了发生的折旧费用：


	截至9月30日的三个月，				截至9月30日的9个月，
(单位：千)	2024		2023		2024		2023
折旧费用	$	1,754	$	1,474	$	5,053	$	3,938

5. f金融工具的空气价值

根据公司与哈佛学院（“哈佛”）院长和研究员签订的许可协议，公司按经常性公平价值计量的金融工具包括货币市场基金、有价证券和衍生负债（成功付款负债）。（“Broad”），该许可协议在本文中称为《哈佛/Broad许可协议》。

下表列出了公司金融工具按公允价值等级内的公允价值：


	截至2024年9月30日
(单位：千)	公平值		1级		2级		3级
资产
货币市场基金	$	72,489	$	72,489	$	—	$	—
有价证券：
美国国库券和票据		179,684		—		179,684		—
美国机构证券		201,527		—		201,527		—
总资产	$	453,700	$	72,489	$	381,211	$	—
负债
成功付款责任	$	977	$	—	$	—	$	977
总负债	$	977	$	—	$	—	$	977


	截至2023年12月31日
(单位：千)	公平值		1级		2级		3级
资产
货币市场基金	$	120,987	$	120,987	$	—	$	—
有价证券：
美国国库券和票据		148,107		—		148,107		—
美国机构证券		269,663		—		269,663		—
总资产	$	538,757	$	120,987	$	417,770	$	—
负债
成功付款责任	$	2,720	$	—	$	—	$	2,720
总负债	$	2,720	$	—	$	—	$	2,720

现金等价物-现金等价物$72.5 万和 $121.0 万截至2024年9月30日和2023年12月31日，分别由货币市场基金组成，并被归类为公允价值层级的第一级，因为它们使用活跃市场的市场报价进行估值。

有价证券-该公司以公允价值经常性地计量其有价证券，并将这些工具归类在公允价值等级的第二级。有价证券被归类于公允价值等级的第二级，因为定价投入不同于活跃市场的报价，于报告日期可直接或间接观察到，而公允价值是通过使用模型或其他估值方法来确定的。

成功付款责任-如果公司的平均市值在指定的一段时间内超过指定的门槛，从十位数的中位数美元金额上升到美元，公司有义务向哈佛和远大分级成功付款10.0 亿美元，或以超过这些门槛的对价出售公司。如果控制权发生变更或出售公司，公司必须在事件发生后的指定期限内以现金支付成功付款。否则，成功付款可以由公司选择以现金或普通股股份，或现金和普通股股份的组合结算。公司可支付的最高成功付款总额为美元31.3 百万，其中美元25.0 公司仍需支付百万美元。

成功付款负债按公允价值列报，并被归类于公允价值层次的第3级，因为其公允价值计量部分基于市场上未观察到的重大投入。该公司使用蒙特卡洛模拟模型，该模型根据几个关键变量对负债价值进行建模，这些变量包括事件发生的概率、事件发生的时间以及公司普通股的价值。

公司按公允价值重新计量负债，截至2024年9月30日止三个月的其他费用小幅增加，并减少美元1.7 万截至2024年9月30日止九个月计入其他收入并减少 $0.8 万和 $0.9 万截至2023年9月30日的三个月和九个月分别计入其他收入。

用于评估成功付款负债的主要输入 2024年9月30日和2023年12月31日如下：


	在… 2024年9月30日			在 2023年12月31日
普通股公允价值(每股)	$	4.84		$	13.94
股票波动性		85	%		83	%

基于第三级输入的金融工具公允价值变化对账截至2024年9月30日的九个月如下：


(单位：千)	成功支付责任
2023年12月31日的余额	$	2,720
公允价值变动		(1,743	)
2024年9月30日余额	$	977

截至2023年9月30日止九个月基于第三级输入的金融工具公允价值变化对账如下：


(单位：千)	成功支付责任
2022年12月31日的余额	$	2,885
公允价值变动		(878	)
2023年9月30日的余额	$	2,007

7. 租契

该公司的经营租赁活动包括马萨诸塞州波士顿办公室和实验室空间的不可取消设施租赁。

该公司还与第三方签订了多项合同研究和合同制造服务协议，其中包含ASC主题842“租赁”范围内的嵌入式租赁。嵌入式租赁被视为短期租赁，因为合同期限为12个月或更短。因此，未记录租赁负债或使用权资产。公司已认识到 $0.7 万和 $2.8 万截至2024年9月30日的三个月和九个月内与嵌入式租赁相关的短期租赁成本，分别。公司已认可美元0.4 亿和$0.9 数百万美元的短期租赁成本associ分别在截至2023年9月30日的三个月和九个月内与嵌入式租赁一起到期。

经营租赁费用的构成如下：


	截至9月30日的三个月，				截至9月30日的9个月，
(单位：千)	2024		2023		2024		2023
经营租赁成本	$	3,234	$	3,234	$	9,702	$	9,702
可变租赁成本		1,064		1,127		3,143		2,775
总	$	4,298	$	4,361	$	12,845	$	12,477

与经营租赁有关的补充现金流量信息如下：


	截至9月30日的9个月，
(单位：千)	2024		2023
为计量租赁负债所包括的金额支付的现金：
与经营租赁相关的经营现金流	$	7,922	$	9,983

截至2024年9月30日，公司的经营租赁采用加权平均增量借款利率为 7.89加权平均剩余租期为%8.3 年

不可撤销租约下的未来最低承诺额2024年9月30日如下：


截至12月31日止的年度，	量
	(单位：千)
2024年剩余时间	$	2,668
2025		10,894
2026		11,210
2027		11,534
2028		11,868
此后		49,881
租赁付款总额	$	98,055
减去：利息		(26,800	)
经营租赁负债现值	$	71,255

向公司员工、董事、顾问和外部顾问授予单位、绩效奖励和其他以股份为基础的奖励。根据2021年计划保留发行的股份将在2031年1月1日之前每年增加。

2024年1月1日，4,098,485 公司普通股股份已计入2021年计划下预留的发行金额。截至2024年9月30日，公司已预留 14,242,655 用于发行股票期权、限制性股票和限制性股票单位的公司普通股股份，其中 3,119,785 根据2021年计划，股票仍可用于未来的授予。自2021年计划生效后，本公司停止根据2018年计划授予额外奖励。

2024年2月，董事会通过了《2024年激励股票激励计划》(简称《激励计划》)。这个

激励计划规定授予非法定股票期权、股票增值权、限制性股票奖励、

对以下人员的限制性股票单位和其他基于股票的奖励：(A)以前不是董事的员工或(B)

在任何一种情况下，在一段真正的非受雇期间后开始受雇于公司，作为

该人按照要求进入公司工作的诱因材料

纳斯达克股票市场规则5635（c）（4）的规定。截至2024年9月30日，公司已预留4,000,000 用于发行非法定股票期权和限制性股票单位奖励的公司普通股股份，其中 3,432,320 根据诱导计划，股份仍可供未来授予。

在公司简明合并经营报表和综合亏损中计入的股票补偿费用如下：


	截至9月30日的三个月，				截至9月30日的9个月，
(单位：千)	2024		2023		2024		2023
研发	$	5,404	$	4,895	$	17,512	$	14,232
一般和行政		5,414		3,930		15,294		11,630
基于股票的薪酬总支出	$	10,818	$	8,825	$	32,806	$	25,862

股票期权

下表提供了年内股票期权活动的摘要截至2024年9月30日的九个月：


	数量选项			加权平均值锻炼单价分享		加权平均值剩余合同寿命(以年为单位)		集料固有的值(2) (单位：千)
截至2023年12月31日的未偿还债务		9,924,878		$	16.98
授与		4,282,316			9.85
已锻炼		(602,114	)		1.89
被没收		(838,259	)		20.23
截至2024年9月30日未完成		12,766,821		$	15.08		7.7	$	4,284
可于2024年9月30日取消		6,136,725		$	15.52		6.3	$	4,279
预计于2024年9月30日之后归属(1)		6,630,096		$	14.68		8.9	$	5

(1)

这代表截至2011年未归属期权的数量 2024年9月30日预计将在未来归属。

(2)

总内在价值计算为标的期权的行使价与截至2011年以货币计价的期权的普通股公允价值之间的差额 2024年9月30日.

截至2024年9月30日，已有 $62.6 万与未归属股票期权相关的未确认股票补偿费用，预计将在大约 2.4 年

限制性股票单位

截至2024年9月30日止九个月内，公司授予 1,421,880 2021年计划和诱导计划下的限制性股票单位。这些限制性股票单位每年在一年内归属四年制期

截至年未归属限制性股票单位的状况和变化摘要 2024年9月30日情况如下：


	股份			加权的- 平均补助金约会集市每股价值
截至2023年12月31日的未归属限制性股票单位		964,511		$	19.92
已批出的限制性股票单位		1,421,880		$	11.58
归属的限制性股票单位		(193,186	)	$	20.98
被没收的限制性股票单位		(195,585	)	$	15.47
截至2024年9月30日未归属的限制性股票单位		1,997,620		$	14.32

截至2024年9月30日，已有 $23.9 万与预期归属的限制性股票单位相关的未确认的股票补偿费用。这些成本预计将在加权平均剩余归属期内确认 3.2 好几年了。

2021年修订和重述员工股票购买计划

2021年6月，董事会通过并获得公司股东批准了经修订和重述的2021年员工股票购买计划（“ESPP”），该计划于2021年6月16日生效。根据ESPP保留发行的股份将在2031年1月1日之前每年增加。2024年1月1日， 819,697 普通股被添加到e ESPP下保留出售的金额。截至2024年9月30日， 1,989,903根据ESPP，股票仍可供发行。

以下对我们财务状况和经营结果的讨论和分析应与我们的精简综合财务报表以及本季度报告中其他部分包括的10-Q表格和我们于2024年2月27日提交给美国证券交易委员会(美国证券交易委员会)的10-k表格年度报告中包含的这些陈述的相关注释一起阅读。除历史财务信息外，以下讨论和分析包含涉及风险、不确定性和假设的前瞻性陈述。由于许多因素，包括第二部分第1A项“风险因素”中讨论的因素，我们的实际结果可能与这些前瞻性陈述中预期的结果大不相同。您应该仔细阅读题为“风险因素”的部分，以了解可能导致实际结果与我们的前瞻性陈述大不相同的重要因素。

我们是一家临床阶段的公司，正在开发一种治疗心血管疾病或CVD的新型基因药物，有可能将治疗从慢性治疗转变为单疗程基因编辑药物。尽管过去50年在治疗方面取得了进展，但心血管疾病仍然是全球主要的死亡原因。目前的慢性护理模式是脆弱的--需要严格的患者依从性、广泛的医疗基础设施和定期的医疗保健服务--并使许多患者得不到适当的护理。我们正在开发一系列基因编辑程序，针对导致动脉粥样硬化性心血管疾病(ASCVD)的三种脂蛋白途径，即最常见的心血管疾病形式：低密度脂蛋白(LDL)、富含甘油三酯的脂蛋白和脂蛋白(A)，或Lp(A)。我们的主要计划针对的是PCSK9和Angptl3 这些基因已被广泛验证为降低低密度脂蛋白胆固醇（LDL-C）的目标。我们相信，编辑这些基因可以在患有ASCVD或有ASCVD风险的患者的整个一生中有效且持久地降低LDL-C。

我们的方法利用21世纪的多个突破世纪生物医学--人类遗传分析、基因编辑、信使核糖核酸或信使核糖核酸--以治疗和脂质纳米粒(或LNP)为基础的疗法--靶向主要在肝脏中表达的基因，以干扰可导致ASCVD的蛋白质的产生。我们正在推进一条单道课程的管道体内基因编辑程序，每个程序旨在模拟自然抗病突变并关闭特定基因以降低血脂，从而降低ASCVD的风险。我们打算首先开发治疗家族性高胆固醇血症（FH）患者的主导项目，这是一种遗传性疾病，会导致血液LDL-C终生严重升高，导致早发性ASCVD的风险增加。如果我们的项目在FH中取得成功，我们相信它们还可以为更广泛的确诊ASCVD患者群体提供潜在的治疗方法，这些患者继续受到高LDL-C水平的影响。最终，我们相信这些治疗方法有可能被开发用于治疗有ASCVD风险的人，作为一种预防措施。

我们于2018年3月注册成立，此后不久开始运营。自我们成立以来，我们将几乎所有的资源都投入到构建我们的基因编辑和LNP技术，推进我们的项目组合的发展，建立和保护我们的知识产权，进行研究和开发活动，组织和配备我们的公司，业务规划，筹集资金，并为这些业务提供一般和行政支持。到目前为止，我们主要通过出售我们的优先股，通过出售我们的首次公开募股(IPO)普通股，我们的后续公开募股，我们的在市场上(或ATM)的股权发行计划，以及通过我们与Vertex制药公司(Vertex)和礼来公司(Lilly)的战略合作，为我们的运营提供资金。

截至2024年9月30日，我们通过私募出售优先股和普通股以及公开发行普通股，筹集了总计11亿美元的总收益。

我们是一家临床阶段公司。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收入。自成立以来，我们已经出现了重大的运营损失。截至2024年9月30日的三个月和九个月，我们的净亏损分别为5010万美元和14870万美元。截至2024年9月30日，我们累计赤字69300万美元。

我们预计，随着我们正在进行的VERVE-102候选产品的心脏2期10亿临床试验，与我们的计划组合相关的正在进行的开发活动将继续产生巨额费用和不断增加的运营亏损PCSK9，以及我们正在进行的针对VERVE-201的Pulse-1期10亿临床试验，我们的候选产品瞄准 Angptl3，每个都利用我们专有的GalNAc-LNP递送技术；确定我们的心脏-1期10亿VERVE-101临床试验的下一步；进一步开发碱基编辑和新的基因编辑技术、递送技术和制造能力；寻求发现和开发更多的候选产品；维持、扩大执法、捍卫和保护我们的知识产权组合；聘请研究和

我们的目标是帮助我们的研发和临床人员；最终建立销售、营销和分销基础设施，将我们可能获得上市批准的任何产品商业化；建立商业制造来源和安全供应链能力，足以提供我们可能获得监管批准的任何候选产品的商业数量；增加运营、法律、合规、财务和管理信息系统和人员，以支持我们作为一家上市公司的研究、产品开发、未来的商业化努力和运营。

因此，我们将需要大量额外资金来支持我们的持续运营和实施我们的战略。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，我们预计将通过股票发行、债务融资和其他资本来源的组合为我们的运营提供资金，其中可能包括与其他公司的合作、战略联盟和营销、分销或许可安排或其他战略交易。如果我们无法在需要时或在可接受的条件下筹集资金或获得足够的资金，我们可能会被迫推迟、限制、减少或终止我们的研发计划或任何未来的商业化努力，或授予开发和营销我们原本更愿意自己开发和营销的候选产品的权利。

由于与产品开发相关的许多风险和不确定性，我们无法预测增加费用的时间或金额，也无法预测我们何时或是否能够实现盈利。即使我们能够从产品销售中获得收入，我们也可能无法盈利。如果我们无法实现盈利或无法持续盈利，那么我们可能无法继续按计划运营，并被迫减少或终止我们的运营。

截至2024年9月30日，我们拥有现金、现金等值物和有价证券53990万美元。我们相信，我们现有的现金、现金等值物和有价证券将使我们能够为2026年之前的运营费用和资本支出需求提供资金。我们的这一估计是基于可能被证明是错误的假设，我们可能会比预期更早耗尽可用的资本资源。为了在此之后为我们的运营提供资金，我们需要从现有合作中实现里程碑或筹集额外资本，但这无法保证。请参阅“流动性和资本资源”。

Verve-101和Verve-102，我们的候选产品PCSK9, 被设计为永久关闭PCSK9肝脏中的基因。PCSK9是一个高度有效的靶点，通过调节低密度脂蛋白受体(LDLR)在控制血液低密度脂蛋白-C方面发挥关键作用。血液中PCSK9蛋白的减少提高了肝脏从血液中清除低密度脂蛋白-C的能力。VERVE-101和VERVE-102利用LNP介导的递送来定位肝脏，并利用碱基编辑技术在PCSK9基因，以扰乱PCSK9蛋白的生产。Verve-101和Verve-102使用相同的基本编辑器和指南RNAPCSK9然而，VERVE-102是使用一种不同的、专有的GalNAc-LNP递送技术交付的，该技术旨在允许LNP使用去唾液酸糖蛋白受体或ASGPR或低密度脂蛋白受体访问肝细胞，而VERVE-101‘S LNP旨在使用低密度脂蛋白受体访问肝细胞。

VERVE-102正在Heart-2试验中接受评估，这是一项开放标签的10亿期临床试验，旨在评估VERVE-102在患有杂合家族性高胆固醇血症（HeFH）和/或早发性冠状动脉疾病（CAD）的成年患者中的安全性和耐受性，这些患者需要额外降低LDL-C，并对药代动力学以及血液PCSK 9蛋白和LDL-C水平的变化进行额外分析。该试验是一项单次剂量给药剂量递减研究，具有适应性设计，预计将包括四个剂量队列，每个队列由三至九名HeFH或过早CAD患者组成。

在Heart-2临床试验中，前两个队列的7名参与者已完成给药，剂量为0.3毫克/公斤和0.45毫克/公斤。截至2024年10月29日，VERVE-102耐受良好，未发生严重不良事件，也未观察到具有临床意义的实验室异常。在独立数据和安全性监测委员会进行标准审查后，我们预计将继续进行Heart-2试验的剂量升级部分。

我们已获得英国、加拿大、澳大利亚、新西兰和以色列进行的VERVE-102 Heart-2试验的监管许可。我们预计将在2025年上半年提供Heart-2试验的初始数据和PCSK 9计划的更新。我们计划于2025年下半年启动PCSK 9项目的第二期临床试验。

VERVE-101正在Heart-1试验中接受评估，这是一项开放标签的10亿期临床试验，其试验终点为安全性和耐受性以及HeFH患者血液PCSK 9蛋白和LDL-C水平的变化，已建立ASCVD

和不受控制的高胆固醇血症。新西兰和英国共有13名参与者参加了该试验。

在两个较高剂量队列（0.45毫克/公斤和0.6毫克/公斤）中观察到平均时间平均PCSK 9蛋白下降超过60%。观察到0.45毫克/公斤（n=6）剂量下平均LDL-C降低了42%，0.6毫克/公斤（n=1）剂量下平均LDL-C降低了57%。LDL-C和PCSK 9蛋白的平均降幅基于从第28天到最后一次可用随访（截至数据截止日期2024年10月3日）的时间平均降幅。一名接受0.45毫克/公斤剂量给药的参与者的LDL-C和PCSK 9蛋白观察结果未纳入该时间平均分析中。在最高剂量队列的单个参与者中，单剂后LDL-C下降持续了18个月。

2024年4月，我们宣布暂停了心脏1号试验的登记，因为在试验中服用的第13名患者观察到了短暂的无症状实验室异常--3级药物引起的血清丙氨酸氨基转移酶瞬时升高以及3级药物引起的血小板减少的严重不良事件。自此公告以来，未发生新的与治疗相关的不良事件。我们已经完成了一系列非临床研究，作为对观察到的实验室异常的调查的一部分。为了分离LNP的作用并确定在心脏1号试验中观察到的实验室异常是否是由于LNP递送系统造成的，这些研究使用了带有非靶向引导RNA的VERVE-101版本，该RNA旨在阻止碱基编辑。这些研究的数据继续支持我们的理解，即VERVE-101中的LNP可能是观察到的实验室异常的主要驱动因素。在心脏-2试验的剂量升级部分，心脏-1试验的登记预计将保持暂停状态。VERVE-101研究性新药申请和其他临床试验申请仍然活跃。

Verve-201，我们的产品候选目标Angptl3，旨在永久关闭Angptl3肝脏中的基因可降低导致疾病的LDL-C以及残留胆固醇。我们计划开发该计划最初用于治疗患有难治性高胆固醇血症的ASCVD患者（尽管接受了最大耐受的标准护理疗法（可能包括PCSK 9抑制剂）治疗，但仍存在高LDL-C），以及患有纯合家族性高胆固醇血症（HoFH）的患者，HoFH是一种罕见且通常是致命的过早ASCVD的遗传原因，其特征是血液LDL-C极高。

对于Verve-201，我们正在利用我们内部开发的GalNAc-LNP技术来提供一个针对Angptl3基因到肝脏。在HoFH患者中，由于LDLR缺乏（已知介导LNP吸收的LDLR），将具有标准LNP的碱基编辑器输送到肝脏具有挑战性。我们的GalNAc-LNP旨在与肝脏中的ASGPT或LDLR结合，从而使HoFH患者的肝脏吸收。

Pulse-1试验正在对VERVE-201进行评估，这是一项开放标签的10亿期临床试验，旨在评估VERVE-201在患有难治性高胆固醇血症的成年患者中的安全性和耐受性，并对药代动力学和血液ANGPTL 3蛋白和LDL-C水平的变化进行额外分析。Pulse-1试验是一项单次剂量给药剂量增加研究，具有适应性设计，预计将包括四个剂量队列，每个队列由三至九名难治性高胆固醇血症患者组成。

我们最近获得了在澳大利亚、加拿大和英国启动Pulse-1试验的监管许可，并于2024年第四季度在难治性高胆固醇血症患者中启动了Pulse-1试验。

根据各种许可和合作协议，我们有义务在未来支付潜在的重大里程碑和成功付款，并为这些协议涵盖的最终获得监管批准和商业化的任何候选产品的销售支付特许权使用费。有关这些协议的信息，请参阅本季度报告10-Q表格中包含的简明合并财务报表的注释9“许可协议”和注释10“合作和许可协议”。

截至2024年9月30日的三个月和九个月内，我们根据战略合作和许可协议（即Vertex协议）以及研究和合作协议（即礼来协议）分别确认了690万美元和1930万美元的合作收入。我们预计，随着合作努力的继续，与这些合作相关的收入将会增加。我们预计不会从产品销售中产生任何收入

在不久的将来，除非和直到我们成功完成开发并获得一个或多个候选产品的监管批准。如果我们对候选产品的开发工作成功并获得监管机构批准，或者我们成功与第三方签订了许可或合作协议，除了Vertex协议和Lilly协议之外，我们未来可能会从产品销售、此类额外第三方合作或许可协议的付款中产生收入，或其任何组合。

研究和开发费用包括进行研究和开发活动所产生的成本，其中包括：

我们按所发生的费用来支付研究和开发费用。我们为将来收到的用于研发活动的商品或服务支付的不可退还的预付款被记录为预付费用。预付金额随着福利的消耗而支出。

在开发的早期阶段，我们的研发成本通常用于概念验证研究，这些研究不一定可以分配给特定的目标；因此，我们尚未开始逐个计划地跟踪我们的费用。

研发活动是我们商业模式的核心。我们预计，在可预见的未来，随着我们将我们的计划和候选产品推向临床开发，以及我们继续：(I)开发更多的候选产品；(Ii)建立我们的制造能力；以及(Iii)发展我们的基因编辑和LNP技术，我们的研究和开发费用将继续增加。我们还预计我们的发现研究工作和相关的人员成本将增加，因此，我们预计我们的研究和开发费用，包括与股票薪酬相关的成本，将增加到历史水平以上。此外，我们可能会产生与向第三方支付里程碑和特许权使用费相关的额外费用，我们可能会与这些第三方签订许可、收购和期权协议，以获得未来候选产品的权利。

目前，我们无法合理估计或知道完成我们的任何候选产品或计划的临床前和临床开发并获得监管部门批准所需努力的性质、时间和成本。我们的候选产品能否成功开发具有很大的不确定性。这是由于与产品开发相关的许多风险和不确定性，包括：

对于我们当前或未来的任何候选产品而言，这些变量中的任何一个的变化都可能显著改变与该候选产品开发相关的成本、时机和生存能力。我们可能永远不会成功地获得监管部门对我们可能开发的任何候选产品的批准。

一般和行政费用主要包括与人事有关的费用，包括高管、知识产权、业务发展和行政职能人员的工资、福利和基于股票的薪酬。一般和行政费用还包括与知识产权和公司事务有关的法律费用、会计、审计、税务和咨询服务的专业费用、保险费、差旅费、与设施有关的直接和分配费用以及其他运营成本。

我们预计，未来我们的一般和行政费用将增加，以支持更多的研发活动。我们还预计与上市公司相关的成本将继续增加，包括与遵守纳斯达克和美国证券交易委员会要求相关的会计、审计、法律、监管和税务相关服务的成本，董事和高管保险成本，以及投资者和公关成本。

如果我们的平均市值超过了指定的门槛，从十位数的中位数美元金额上升到$100亿，或者出售我们的公司，以换取超过这些门槛的代价，我们有义务向哈佛和宽泛分级成功付款。如本公司控制权发生变更或本公司被出售，本公司须在事件发生后的指定期间内以现金支付任何相关的成功付款。否则，成功付款可以根据我们的选择以现金或我们普通股的股票或现金和我们普通股的股票的组合来支付。我们可能支付的剩余潜在成功付款为2,500美元万。于协议开始时，成功付款负债按公允价值入账，而成本则记为研究及发展费用，并于每个报告期重新计量，并于未清偿票据时于其他收入中记入费用。

根据我们的估值，成功付款负债的公允价值，以及我们在经营报表中记录的公允价值相应变化，可能会在不同时期大幅波动。

利息和其他收入主要包括有价证券赚取的利息以及与我们的核心业务无关的其他杂项收入和费用。

截至2024年9月30日的三个月和九个月的所得税拨备分别为10万美元和30万美元。截至2023年9月30日的三个月和九个月的所得税拨备分别为10万美元和20万美元。所得税拨备主要与基于总利息收入的州所得税有关。

下表总结了截至2024年9月30日和2023年9月30日三个月的经营业绩：

截至2024年9月30日和2023年9月30日的三个月，协作收入分别为690万美元和310万美元。截至2024年9月30日的三个月内，合作收入包括与Vertex协议中的研究服务相关的270万美元和与礼来协议中的研究服务相关的420万美元。截至2023年9月30日的三个月内，合作收入包括与Vertex协议的研究服务和成本报销相关的240万美元，以及与礼来协议的研究服务和成本报销相关的70万美元。截至2024年9月30日的三个月合作收入的增加主要是由于与2023年7月开始的礼来协议相关的努力。

下表总结了截至2024年9月30日和2023年9月30日三个月的研发费用：

截至2024年9月30日的三个月，研发费用为4990万美元，而截至2023年9月30日的三个月为4380万美元。增加约620万美元主要是由于以下原因：

我们预计，在可预见的未来，随着我们将我们的计划和候选产品推进到临床开发并通过临床开发，以及我们继续开发更多的候选产品，包括我们合作的产品，建设我们的制造能力，开发我们的基因编辑和LNP交付技术，我们的研究和开发费用将继续增加。

截至2024年9月30日的三个月，一般和行政费用为1380万美元，而截至2023年9月30日的三个月为1170万美元。增加约220万美元主要归因于以下原因：

截至2024年9月30日的三个月内，成功付款负债的公允价值变化为极低。截至2023年9月30日的三个月内，成功付款负债公允价值发生80万美元变化主要是由于我们普通股公允价值下降，并被记录为其他收入。

与截至2023年9月30日的三个月相比，截至2024年9月30日的三个月的利息和其他收入净增加100万美元，主要是由于有价证券余额增加和利率上升。

下表总结了截至2024年9月30日和2023年9月30日止九个月的经营业绩：

截至2024年9月30日和2023年9月30日的九个月，协作收入分别为1930万美元和660万美元。截至2024年9月30日的九个月内，合作收入包括与Vertex协议研究服务相关的870万美元和与礼来协议研究服务相关的1060万美元。截至2023年9月30日的九个月内，合作收入包括与Vertex协议的研究服务和成本报销相关的590万美元，以及与礼来协议的研究服务和成本报销相关的70万美元。截至2024年9月30日的九个月内合作收入的增加主要是由于与2023年7月开始的礼来协议相关的努力。

截至2024年9月30日的九个月，研发费用为14930万美元，而截至2023年9月30日的九个月为13810万美元。增加1120万美元主要是由于以下原因：

截至2024年9月30日的九个月，一般和行政费用为4250万美元，而截至2023年9月30日的九个月为3770万美元。增加约490万美元主要归因于以下原因：

截至2024年9月30日的九个月内，成功付款负债公允价值发生170万美元变化主要是由于我们普通股公允价值下降，并计入其他收入。截至2023年9月30日的九个月内，成功付款负债公允价值发生90万美元变化主要是由于我们普通股公允价值下降，并计入其他收入。

与截至2023年9月30日止九个月相比，截至2024年9月30日止九个月的利息和其他收入净增加560万美元，主要归因于有价证券余额增加和利率上升。

自2018年成立以来，我们已经出现了巨额运营亏损。随着我们推进项目的临床前和临床开发，我们预计在可预见的未来将产生巨额费用和运营损失。迄今为止，我们主要通过股票发行以及战略合作和相关私募为我们的运营提供资金。截至2024年9月30日，我们通过私募出售优先股和普通股以及首次公开募股、后续公开募股和ATM股票发行计划中的普通股，筹集了总计11亿美元的总收益。截至2024年9月30日，我们拥有53990万美元现金、现金等值物和有价证券。

除了我们现有的现金、现金等价物和有价证券外，我们还有资格获得里程碑和其他

根据我们与礼来和Vertex的合作协议付款。在截至2024年9月30日的九个月内，由于礼来协议项下实现了研发里程碑，我们从礼来获得了500万美元。我们根据合作协议赚取其他里程碑或其他付款的能力以及赚取这些金额的时间取决于我们开发、监管和商业活动的时间和结果，因此目前尚不确定。

2023年7月，我们以私募方式向礼来公司出售并发行了1，552，795股普通股，总购买价格为3000万美元，即礼来公司私募。

2023年8月，根据礼来协议，我们从礼来公司收到了3,000美元万作为预付款。

2023年12月，我们发行并出售了14，375，000股普通股，其中包括根据完全行使承销商购买额外股份的选择权以公开发行价格出售的1，875，000股普通股

每股10.00美元。扣除承销折扣和发行费用约900万美元后，我们收到的净收益约为13470万美元。

2023年12月，在与2023年12月承销发行同时进行的私募中，我们以每股10.00美元的价格向礼来发行并出售了2，296，317股普通股，总购买价格为2300万美元。

2022年7月，我们与Jefferies LLC或Jefferies作为代理签订了公开市场销售协议，根据该协议，我们有权不时以现行市场价格提供和出售我们普通股的股票，总发行价最高可达20000美元万。我们同意向Jefferies支付最高3.0%的佣金，该佣金为Jefferies根据销售协议出售的任何股票的总销售收益的3.0%。销售协议项下的任何销售将根据我们于2022年9月23日生效的S-3表格中的登记声明(文件编号333-267578)进行。于截至2024年9月30日止三个月内，吾等并无根据销售协议作出任何销售。在截至2024年9月30日的9个月内，我们根据销售协议出售了1,766,835股普通股，扣除佣金和我们应支付的发售费用后，净收益总额为2,240美元万。截至2024年9月30日，我们已根据销售协议出售了总计4,547,688股普通股，扣除佣金和我们应支付的发售费用后，净收益总额为8,600美元万。

截至2024年9月30日的九个月，经营活动使用的净现金为11680万美元，主要包括我们对非现金项目进行调整的净亏损14870万美元，其中包括与成功付款负债公允价值变化相关的170万美元和与投资溢价摊销相关的1030万美元。这些金额被3280万美元的股票补偿、540万美元的非现金租赁费用、510万美元的折旧费用以及运营资产和负债变动净增加60万美元的部分抵消。

截至2023年9月30日的九个月，经营活动中使用的净现金为10890万美元，主要包括净亏损15170万美元，并根据非现金项目进行调整，包括与投资溢价摊销相关的1100万美元和与成功付款负债公允价值变动相关的90万美元。这些金额被非现金费用部分抵消，包括股票补偿2590万美元、折旧费用390万美元、非现金租赁费用500万美元以及我们的运营资产和负债净变化1990万美元。

截至2024年9月30日的九个月，投资活动提供的净现金为4530万美元，包括到期的有价证券39860万美元，部分被购买有价证券35090万美元以及购买230万美元的财产和设备所抵消，主要与实验室设备相关。

截至2023年9月30日的九个月，投资活动提供的净现金为3660万美元，包括到期的有价证券43850万美元，部分被购买有价证券39480万美元以及购买财产和设备710万美元（主要与实验室设备相关）所抵消。

截至2024年9月30日的九个月，融资活动提供的净现金为2400万美元，主要包括根据销售协议出售我们普通股的净收益2240万美元、行使股票期权的收益110万美元以及通过我们的员工股票购买计划发行股票的收益50万美元。

截至2023年9月30日的九个月内，融资活动提供的净现金为3520万美元，主要包括礼来私募的净收益3170万美元、出售我们的普通股的净收益

销售协议下的股票190万美元、行使股票期权的收益90万美元以及通过我们的员工股票购买计划发行股票的收益70万美元。

随着我们继续推进我们的项目组合，我们的运营费用和未来的资金需求预计将大幅增加。

截至2024年9月30日，我们拥有现金、现金等值物和有价证券53990万美元。我们相信，我们现有的现金、现金等值物和有价证券将使我们能够为2026年之前的运营费用和资本支出需求提供资金。我们的这一估计是基于可能被证明是错误的假设，我们可能会比预期更早耗尽可用的资本资源。

确定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、昂贵和不确定的过程，需要数年时间才能完成，而且我们可能永远无法生成获得市场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，可能不会获得商业成功。我们的商业收入，如果有的话，将来自我们预计在几年内不能投入商业使用的产品的销售。因此，我们将需要获得大量额外资金来实现我们的业务目标。

我们对我们为目前计划的业务提供资金的能力的预期是基于受风险和不确定性影响的估计。由于管理层目前未知的许多因素，我们的运营计划可能会发生变化，而且不能保证目前的运营计划将在我们预期的时间框架内实现，我们可能需要比计划更早地寻求额外资金。

在可接受的条件下，我们可能无法获得足够的额外资金，或者根本没有。我们没有任何承诺的外部资金来源。市场波动也可能对我们在需要时获得资本的能力产生不利影响。通过出售股权或可转换债务证券筹集的额外资本可能包括清算或其他优惠。债务融资和优先股融资可能涉及的协议包括限制或限制我们采取具体行动的能力的契约，例如产生额外债务、出售或许可我们的资产、进行资本支出或宣布股息，并可能需要发行认股权证。

如果我们通过与第三方的合作、战略联盟或营销、分销或许可安排来筹集更多资金，我们可能不得不放弃对我们的技术、未来收入来源、研究计划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或在我们可接受的条件下通过股权或债务融资或其他安排筹集额外资金，我们可能被要求推迟、限制、减少或终止我们的产品开发或未来的商业化努力，或授予开发和营销我们本来更愿意自己开发和营销的候选产品的权利。

在截至2024年9月30日的三个月和九个月内，我们的合同义务和承诺与我们于2024年2月27日向SEC提交的10-k表格年度报告中“管理层对财务状况和运营结果的讨论和分析-合同义务”标题下描述的义务和承诺没有重大变化。有关我们租赁义务的更多信息，请参阅本10-Q表格季度报告第一部分第1项的简明合并财务报表注释7“租赁”，并请参阅截至12月31日的年度经审计合并财务报表注释8“许可协议”，2023年包含在我们于2024年2月27日向SEC提交的10-k表格年度报告中，以获取有关我们在许可协议下潜在付款义务的更多信息。

管理层对我们财务状况和经营结果的讨论和分析是以我们的合并财务报表为基础的，我们是按照美国公认会计原则编制的。编制这些财务报表和相关披露要求我们作出估计、判断和假设，这些估计、判断和假设会影响我们合并财务报表中资产、负债和费用的报告金额以及或有资产和负债的披露。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并不是从其他来源很容易看出的。我们在持续的基础上评估我们的估计和假设。在不同的假设或条件下，我们的实际结果可能与这些估计不同。

在截至2024年9月30日的三个月和九个月内，我们的关键会计估计与2024年2月27日向SEC提交的10-k表格年度报告中所述的估计没有重大变化。

参见我们于2024年2月27日提交给美国证券交易委员会的Form 10-k年报中包含的合并财务报表附注2《重大会计政策摘要-最近通过的会计公告》。

我们面临与利率变化相关的市场风险。截至2024年9月30日，我们拥有现金和现金等值物15870万美元，其中包括主要投资于美国政府支持证券和国债的标准支票账户和货币市场基金。此外，截至2024年9月30日，我们还拥有约38120万美元的有价证券，其中包括美国国债和机构证券。然而，由于短期到期，利息收入对总体利率水平的变化很敏感

由于我们的现金等同物和有价证券的低风险，利率立即变化10%不会对我们的现金等同物和有价证券的公平市场价值产生重大影响。

我们目前没有面临与外币汇率变化相关的重大市场风险；然而，我们确实与美国以外的供应商签订了合同，这些供应商可能会受到外币汇率波动的影响。我们未来可能会与美国以外的供应商签订额外的合同，这可能会增加我们的外汇兑换风险。

通货膨胀通常通过增加我们的劳动力成本和目标开发成本来影响我们。我们认为，截至2024年9月30日的三个月和九个月内，通货膨胀对我们的业务、财务状况或经营业绩没有产生重大影响。

在我们首席执行官和首席财务官的参与下，我们的管理层在本季度报告10-Q表格所涵盖的期间结束时评估了我们的披露控制和程序的有效性，这些控制和程序符合《交易法》规则13a-15(E)和15d-15(E)的规定。《交易法》规则13a-15(E)和15d-15(E)中定义的术语“披露控制和程序”是指公司的控制和其他程序，旨在确保公司在根据交易法提交或提交的报告中要求披露的信息在美国证券交易委员会规则和表格指定的时间段内得到记录、处理、汇总和报告。披露控制和程序包括但不限于旨在确保公司根据《交易法》提交或提交的报告中要求披露的信息被积累并传达给公司管理层，包括其主要高管和主要财务官，或酌情履行类似职能的人员的控制和程序，以便及时做出关于所需披露的决定。管理层认识到，任何控制和程序，无论设计和操作得多么好，都只能为实现其目标提供合理的保证，管理部门在评估可能的控制和程序的成本-效益关系时必须运用其判断。

根据对截至2024年9月30日披露控制和程序的评估，我们的首席执行官和首席财务官得出的结论是，截至该日期，我们的披露控制和程序在合理保证水平上有效。

截至2024年9月30日的季度，我们对财务报告的内部控制（定义见《交易法》第13 a-15（f）条和第15 d-15（f）条）没有发生对我们对财务报告的内部控制产生重大影响或合理可能产生重大影响的变化。

2024年8月27日，一起推定的证券集体诉讼标题为Oldroyd诉Verve治疗公司等艾尔，案件号1：24-CV-12218，已在美国马萨诸塞州地区地方法院针对我们和我们的某些官员提起诉讼。该投诉指控违反了《交易法》第10（b）条和第20（a）条以及据此颁布的100亿.5条规则，理由是有关该公司暂停参加Heart-1试验的据称存在重大虚假和误导性陈述和遗漏。除其他外，该投诉寻求未具体说明的损害赔偿、利息、律师费、专家费和其他费用。2024年10月28日，原告Thomas Oldroyd提出了一项无人反对的动议，要求任命为主要原告并批准宾夕法尼亚州罗森律师事务所作为首席律师。

我们相信我们拥有强大的防御，我们打算大力防御这一行动。该诉讼正处于早期阶段，目前无法评估可能的结果或结果对我们是否重要。

此外，我们可能会不时卷入正常业务过程中产生的诉讼或其他法律程序。无论结果如何，由于辩护和和解成本、管理资源的转移和其他因素，诉讼都可能对我们的业务、财务状况、运营业绩和前景产生不利影响。

由于下面描述的风险和不确定性，我们未来的经营结果可能与本季度报告中所述的10-Q表格中描述的结果有很大的不同。在评估我们的业务时，您应该仔细考虑以下有关风险的信息。如果实际发生以下任何风险，我们的业务、财务状况、经营业绩和未来增长前景都可能受到重大不利影响。在这种情况下，我们普通股的市场价格可能会下跌。此外，我们不能向投资者保证我们的假设和预期将被证明是正确的。重要因素可能导致我们的实际结果与前瞻性陈述中表明或暗示的结果大不相同。有关受这些风险因素限制的一些前瞻性陈述的讨论，请参阅本季度报告的第一页Form 10-Q。可能导致或促成这种差异的因素包括下文讨论的那些因素。

自成立以来，我们遭受了重大损失，没有任何产品获准销售。我们预计在可预见的未来会出现亏损，可能永远不会实现或保持盈利。

自成立以来，我们将几乎所有的财务资源和精力投入到研究和开发，包括临床前研究和临床试验，但却出现了重大的经营损失。截至2024年9月30日止九个月，我们的净亏损为14870万美元，截至2023年12月31日止一年为20010万美元。截至2024年9月30日，我们累计赤字69300万美元。我们没有批准的产品，也没有从产品销售中产生任何收入。我们主要通过私募优先股和普通股以及公开募股中普通股的出售以及与2022年7月Vertex Pharmaceuticals Incorporated或Vertex签订的战略合作和许可协议或Vertex协议相关的付款为我们的运营提供资金，以及与研究和合作协议或礼来协议有关的付款，与礼来公司（Eli Lilly and Company）或礼来公司（Lilly）合作，于2023年7月生效。

在可预见的未来，我们预计将继续产生巨额运营费用和净亏损。我们的运营费用和净亏损可能会在不同季度和年度之间大幅波动。我们预计我们的费用将大幅增加，如果我们：

即使我们获得了一个或多个候选产品的营销批准，并成功地将其商业化，我们预计也会产生大量额外的研发和其他支出，以开发和营销更多的候选产品和/或扩大任何上市产品的批准适应症。我们可能会遇到不可预见的费用、困难、并发症、延误和其他可能对我们的业务产生不利影响的未知因素。我们未来净亏损的规模将在一定程度上取决于我们未来支出的增长率和我们创造收入的能力。

我们从未从产品销售中获得收入，也可能永远不会实现或保持盈利。

我们在2022年开始了我们的第一个候选产品的临床开发，预计还需要很多年，如果有的话，我们才能有一个准备好商业化的候选产品。为了实现并保持盈利，我们必须成功地开发、获得必要的监管批准，并最终将产生大量收入的一个或多个产品商业化。实现这一成功的能力将要求我们在一系列具有挑战性的活动中保持有效，包括：

不能保证我们会在这些活动中取得成功，即使我们成功了，也可能永远不会产生足够大的收入来实现盈利。我们还没有完成任何候选产品的临床试验。由于与药品开发相关的众多风险和不确定性，我们无法准确预测增加费用的时间或金额，或者我们何时或是否能够产生收入或实现盈利。

即使我们能够从销售任何经批准的产品中获得收入，我们也可能无法盈利，可能需要获得额外的资金才能继续运营。我们的收入将在一定程度上取决于我们获得监管批准的地区的市场规模、产品的可接受价格、获得保险和补偿的能力，以及我们是否拥有该地区的商业权。如果我们的潜在患者数量没有我们估计的那么多，监管部门批准的适应症比我们预期的要窄，或者治疗人群因竞争、医生选择或治疗指南而缩小，即使获得批准，我们也可能无法从此类产品的销售中获得大量收入。

我们将需要大量额外资金。如果我们无法在需要时筹集资金，我们可能会被迫推迟、减少或取消我们的产品开发计划或商业化工作。

我们预计将投入大量财政资源用于我们正在进行和计划中的活动，特别是我们启动和进行临床试验；继续研究、开发和临床前测试；并可能为我们可能开发的任何候选产品寻求市场批准。我们预计，与我们正在进行和计划中的活动相关的费用将大幅增加，特别是在我们推进临床前活动以及正在进行和计划中的临床试验时。此外，如果我们的任何候选产品获得市场批准，我们预计将产生与产品制造、销售、营销和分销相关的巨额商业化费用。此外，我们预计继续产生与上市公司运营相关的额外成本。因此，我们将需要获得与我们的持续业务有关的大量额外资金。我们目前没有信贷安排，也没有任何承诺的资金来源。如果我们无法在需要时或在可接受的条件下筹集资金或获得足够的资金，我们可能会被迫推迟、限制、减少或终止我们的研发计划或任何未来的商业化努力，或授予开发和营销我们原本更愿意自己开发和营销的候选产品的权利。

确定潜在的候选产品以及进行临床前测试和临床试验是一个耗时、昂贵和不确定的过程，需要数年时间才能完成，而且我们可能永远无法生成获得市场批准和实现产品销售所需的必要数据或结果。此外，即使我们成功地确定和开发了候选产品并获得批准，我们也可能不会取得商业成功。我们的商业收入，如果有的话，可能不足以维持我们的运营。因此，我们将需要继续依靠额外的融资来实现我们的业务目标。

截至2024年9月30日，我们拥有现金、现金等值物和有价证券约53990万美元。我们相信，我们现有的现金、现金等值物和有价证券将使我们能够为2026年之前的运营费用和资本支出需求提供资金。然而，我们的这一估计是基于可能被证明是错误的假设，并且我们的运营计划可能会因我们目前未知的许多因素而改变。因此，我们的资本资源可能会比目前预期更早耗尽，并可能被迫比计划更早寻求额外资金。

任何额外的筹款努力可能会转移我们的管理层对他们日常活动的注意力，这可能会对我们开发和商业化任何候选产品的能力产生不利影响。我们不能确定是否会在可接受的条件下提供额外资金，或者根本不能。例如，经济和其他因素最近对全球金融市场造成了重大干扰，这种情况可能会持续下去，并会降低我们获得资本的能力，这可能会在未来对我们的流动性产生负面影响。我们没有额外资本或外部资金的承诺来源，如果我们无法筹集足够的额外资本或按我们可以接受的条款筹集额外资本，我们可能不得不大幅推迟、缩减或停止我们候选产品或其他研发计划的开发或商业化。我们可能被要求为我们可能开发的候选产品寻找合作伙伴，而不是在其他情况下是可取的，或者以比其他方式更不利的条款寻找合作伙伴，或者放弃或以不利条款许可我们可能开发的候选产品的权利，否则我们可能会寻求自己寻求开发或商业化的市场。

上述任何事件都可能严重损害我们的业务、前景、财务状况和经营结果，并导致我们的普通股价格下跌。

筹集额外资本可能会对我们的股东造成稀释，限制我们的运营，或者要求我们放弃对我们的技术或候选产品的权利。

在此之前，如果我们能够从产品销售中获得可观的收入，我们预计将通过股权发行、债务融资、合作、战略联盟和营销、分销或许可安排的组合来满足我们的现金需求。我们没有任何承诺资本或外部资金的来源。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，我们的股东利益将被稀释，这些证券的条款可能包括清算或其他优惠，对我们作为普通股股东的权利产生不利影响。任何债务融资和优先股融资可能涉及的协议包括限制或限制我们采取特定行动的能力的契约，例如产生额外债务、出售或许可我们的资产、进行资本支出、宣布股息或扣押我们的资产以确保未来的债务。

如果我们通过与第三方的合作、战略联盟或营销、分销或许可安排来筹集更多资金，我们可能不得不放弃对我们的技术、未来收入来源、研究计划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或在我们接受的条件下通过股权或债务融资或其他安排筹集额外资金，我们将被要求推迟、限制、减少或终止我们的产品开发或未来的商业化努力，或授予开发和营销我们本来更愿意自己开发和营销的候选产品的权利。

我们有限的经营历史可能会使股东难以评估我们业务迄今的成功程度，也难以评估我们未来的生存能力。

我们于2018年开始运营，是一家临床阶段的公司。迄今为止，我们的业务仅限于组织和配备我们的公司、业务规划、筹集资金、开发我们的技术、识别潜在的候选产品、保护知识产权以及进行临床前研究和临床试验。我们于2022年7月启动了第一项临床试验，即针对VERVE-101的Heart-1试验，于2024年第二季度启动了第二项临床试验，即针对VERVE-102的Heart-2试验，并于2024年第四季度启动了第三项临床试验，即针对VERVE-201的Pulse-1试验。我们的其他研究项目仍处于研究开发阶段，失败的风险很高。我们尚未证明我们有能力完成任何临床试验、获得上市批准、制造临床试验

开发或商业规模产品或安排第三方代表我们这样做，或进行成功产品商业化所需的销售和营销活动。部分由于缺乏经验，我们无法确定正在进行的临床前研究和临床试验是否会按时完成，或者计划的临床前研究和临床试验是否会按时开始或完成（如果有的话）。因此，如果我们有更长的运营历史或成功开发和商业化基因编辑产品的历史，股东对我们未来的成功或生存能力的任何预测可能不会那么准确。

我们有限的运营历史，特别是考虑到快速发展的遗传药物领域，可能会使我们难以评估我们的技术和行业并预测我们未来的表现。作为一家运营公司，我们有限的历史使我们对未来成功或生存能力的任何评估都受到重大不确定性的影响。我们将在快速发展的领域遇到初创公司经常遇到的风险和困难。如果我们不成功应对这些风险，我们的业务将受到影响。

此外，随着业务的增长，我们可能会遇到不可预见的费用、限制、困难、复杂情况、延误和其他已知和未知的因素。我们需要在某个时候从一家专注于研发的公司转型为一家能够支持商业活动的公司。在这样的过渡中，我们可能不会成功。

我们使用我们的净营业亏损和研发税收抵免结转来抵消未来应纳税收入或税款的能力可能会受到某些限制。

我们有累计亏损的历史，并预计在可预见的未来我们将继续产生重大亏损；因此，我们不知道我们是否或何时将产生必要的应税收入，以利用我们的净运营亏损、NOL或研发税收抵免结转。截至2023年12月31日，我们有联邦NOL结转18820美元万和州NOL结转18610美元万。

一般而言，根据修订后的1986年《国税法》第382和383条，或该法典以及州法律的相应条款，公司经历了“所有权变更”，一般定义为某些股东在三年内其股权所有权变化超过50个百分点(按价值计算)，其利用变更前的NOL和研发税收抵免结转以抵消变更后的应纳税所得额或税款的能力受到限制。我们还没有进行一项研究，以评估是否发生了此类所有权变更。我们过去可能经历过这样的所有权变化，未来可能会因为我们股票所有权的后续变化(这可能不是我们所能控制的)而经历这种所有权变化。因此，如果我们赚取了应纳税所得额净额，我们使用变动前的NOL和研发税收结转抵销此类应税收入的能力可能会受到限制。根据州法律，我们的NOL或研发税收抵免也可能受到损害。

还有一种风险是，由于法规变化，如暂停使用NOL或其他不可预见的原因，我们现有的NOL和研发税收抵免结转可能到期或无法用于抵消未来的所得税负债。如下文所述，税法或其实施或解释的变化可能对我们的业务和财务状况产生不利影响，减税和就业法案，或经冠状病毒援助、救济和经济安全法案或CARE法案修订的税法，包括美国联邦税率和NOL结转管理规则的变化，这可能会显著影响我们未来利用NOL抵消应税收入的能力。出于这些原因，即使我们实现了盈利，我们也可能无法使用我们的NOL和其他税收属性的很大一部分。

我们的临床开发工作还处于早期阶段，我们还没有完成任何候选产品的临床试验。因此，我们预计，如果我们将任何候选产品商业化，也需要很多年时间。如果我们无法通过临床试验推进我们当前或未来的候选产品，无法获得营销批准，并最终将我们的候选产品商业化，或者在这样做的过程中遇到重大延误，我们的业务将受到实质性损害。

我们正处于临床开发工作的早期阶段，尚未完成任何候选产品的临床试验。2024年4月，我们宣布，在观察到短暂的无症状实验室异常（3级药物诱导的血清谷丙氨转移酶（ALt）短暂升高，以及3级药物诱导的血小板减少症的严重不良事件）后，我们暂停了Heart-1试验的入组。Heart-1试验预计将在评估VERVE-102的Heart-2试验的剂量增加部分期间保持暂停。我们创造产品收入的能力（如果有的话）将在很大程度上取决于我们候选产品的成功开发、营销批准和最终商业化，

这可能永远不会发生。我们尚未从产品销售中产生收入，而且我们可能永远无法开发或商业化可销售的产品。

在美国开始临床试验需要FDA接受研究性新药（IND）申请，并根据与FDA和其他监管机构的讨论最终确定试验设计。FDA过去并可能在未来再次要求我们完成额外的临床前研究并满足临床试验的其他要求，导致此类试验的开始或进展被推迟。例如，2022年11月，FDA暂停了我们在美国进行评价VERVE-101的临床试验的IND，并要求提供解决搁置所需的各种信息，包括临床前和临床数据。2023年10月，我们宣布FDA已解除临床搁置并批准了我们的IND。我们尚未在美国启动VERVE-101的临床试验中心，并且无法确定我们的VERVE-101 IND将来不会再次被置于临床搁置状态。

即使我们收到并纳入了这些监管机构的指导意见，FDA或其他监管机构仍可能确定我们没有满足他们开始临床试验的要求，或者改变他们对我们的试验设计或所选临床终点的可接受性的立场，这可能需要我们完成更多的临床前研究或临床试验，推迟我们的临床试验的登记，或施加比我们目前预期更严格的批准条件。在其他国家，包括加拿大、澳大利亚、新西兰和欧洲国家，临床试验申请也有同样的过程和风险。

我们可能开发的任何候选产品的商业化将需要临床前和临床开发；需要在多个司法管辖区获得监管和营销批准，包括FDA、药品和保健产品监管机构或MHRA和EMA；制造供应、能力和专业知识；商业组织；以及重大的营销努力。VERVE-101、VERVE-102、VERVE-201和我们可能确定和开发的任何其他候选产品的成功将取决于许多因素，包括以下因素：

如果我们不能及时或根本地在这些因素中的一个或多个方面取得成功，我们可能会遇到重大延误或无法成功地将我们可能开发的任何候选产品商业化，这将对我们的业务造成实质性损害。如果我们无法通过临床开发推进我们的候选产品，无法获得监管部门的批准，并最终将我们的候选产品商业化，或者在这样做的过程中遇到重大延误，我们的业务将受到实质性损害。

体内基因编辑，包括碱基编辑，是一种新的技术，尚未被临床验证为安全和有效的人类治疗用途。我们正在采取的发现和开发新疗法的方法是未经验证的，可能永远不会产生适销对路的产品。

我们专注于开发药物利用体内基因编辑技术，这是一种新技术，而且在很大程度上未经证实。我们已获得许可并与VERVE-101、VERVE-102和VERVE-201一起使用的基础编辑技术尚未在任何已完成的临床试验中进行评估，我们也不知道第三方使用我们的基础编辑或类似技术完成了任何安全性或有效性临床试验。支持基于基因编辑技术开发候选产品可行性的科学证据既初步又有限。候选产品的成功开发需要我们安全地将基因编辑器输送到靶细胞中，优化此类候选产品的效率和特异性，并确保此类候选产品的治疗选择性。无法保证碱基编辑技术或其他基因编辑技术将导致遗传药物的开发，也无法保证我们将成功解决任何或所有这些问题。

我们未来的成功高度依赖于基因编辑技术、传递技术方法和该技术的治疗应用的成功开发。我们可能会决定改变或放弃我们最初的计划，因为有了新的数据，我们在开发基因编辑疗法方面获得了经验。我们不能确定我们的技术将产生令人满意的产品，在我们的初始适应症或我们追求的任何其他适应症中，这些产品是安全有效、可扩展或有利可图的。我们不能保证基于基因编辑技术开发任何特定候选产品的进展或成功将转化为其他候选产品。其他基因编辑技术公司的临床开发工作的不利发展也可能对我们的努力或投资者对我们候选产品的看法产生不利影响。

同样，其他尚未被发现的新基因编辑技术可能是由第三方开发的，可能被确定为比基础编辑更具吸引力，因为我们正在使用基础编辑技术追求基因靶标。

我们还在寻求开发新的基因编辑开发候选方案，作为我们与Vertex和礼来公司合作的一部分，包括寻求识别和设计针对感兴趣目标的特定基因编辑系统和输送系统。我们可能会寻求为未来的程序开发新的基因编辑技术。我们以前没有自己开发过新的基因编辑技术，也没有从第三方获得许可的基因编辑技术。根据我们与Vertex和礼来公司的协议，我们不能确定我们是否能够成功地为目标开发新的基因编辑系统，或者为任何其他目标开发新的基因编辑系统。

此外，我们不能确定我们是否能够获得开发其他基因编辑技术所需的任何权利。尽管我们目前在基础编辑技术领域向我们提供咨询和咨询服务的所有创始人都就他们为我们提供的服务向我们转让了发明义务，但这些发明义务的转让受到限制，不适用于他们在其他领域的工作，也不适用于他们受雇于各自的学术和研究机构所产生的知识产权。为了获得这些创始人分配给这些机构的知识产权，我们需要与这些机构签订许可协议，这些协议可能无法以商业上合理的条款获得，或者根本无法获得。这些因素中的任何一个都可能减少或消除我们的商业机会，并可能对我们的业务、财务状况、运营结果和前景产生重大不利影响。

基因编辑领域的开发活动目前面临与某些知识产权的所有权和使用有关的一些风险，这些风险在美国受到专利干涉程序的影响，在欧洲受到反对程序的影响。有关可能适用于我们和我们的许可人知识产权的风险的更多信息，请参阅标题为“-与我们的知识产权相关的风险”一节以了解更多信息。

此外，与采用新疗法或新的治疗方法有关的公众看法和相关媒体报道，以及与基因编辑特别相关的伦理关切，可能会对受试者参与临床试验的意愿产生不利影响，或者如果任何治疗方法获得批准，医生和患者可能会接受这些新的和个性化的治疗。医生、医疗保健提供者和第三方付款人采用新产品、新技术和新治疗方法的速度往往很慢，特别是那些可能还需要额外的前期成本和培训的产品、技术和治疗方法。医生可能不愿意接受采用这些新颖的和潜在的个性化疗法的培训，可能会认为特定的疗法太复杂或可能有风险，不能在没有适当的培训的情况下采用，并且可能选择不实施该疗法。此外，由于健康状况、基因特征或其他原因，某些患者可能不适合接受治疗。此外，联邦和州机构、国会委员会和外国政府对公众的负面看法、道德关切或财务考虑的反应可能会导致新的立法、法规或医疗标准，可能会限制我们开发或商业化任何候选产品、获得或维持监管批准或以其他方式实现盈利的能力。可能会制定新的政府要求，推迟或阻止监管部门批准我们正在开发的候选产品。不可能预测立法是否会改变，法规、政策或指导方针是否会改变，或者

机构或法院的解释发生了变化，或者此类变化（如果有的话）可能会产生什么影响。基于这些和其他因素，医疗保健提供者和支付者可能会决定这些新疗法的好处不会或不会超过其成本。

基因编辑领域相对较新，并且发展迅速。我们的主要候选产品的研发工作重点是使用碱基编辑技术的基因编辑，但可能会发现其他基因编辑技术比碱基编辑提供显着优势，这可能会对我们的业务造成重大损害。

到目前为止，我们的主要候选产品主要集中在使用碱基编辑的基因编辑技术上。其他公司此前曾使用锌指核酸酶、工程巨核酸酶和转录激活物样效应核酸酶进行基因编辑技术的研究和开发，但到目前为止，还没有一家公司获得候选产品的上市批准。不能肯定碱基编辑技术将导致基因药物的开发，或者其他基因编辑技术不会被认为对药物开发更好或更具吸引力。例如，麻省理工学院的张峰和布罗德，以及哥伦比亚大学的塞缪尔·斯特恩伯格分别宣布发现了转座子的使用，即“跳跃基因”。转座子可以将自己插入基因组的不同位置，并可以被编程为将特定的DNA序列携带到特定的位置，而不需要在DNA中造成双链断裂。Prime Medicine，Inc.和Beam Treateutics Inc.使用Prime编辑技术，该技术利用CRISPR蛋白质靶向DNA中的突变位置，并切割目标DNA的单链。引导RNA允许CRISPR蛋白质识别与引导RNA互补的DNA序列，并携带用于反转录的引物和替换模板。逆转录酶复制缺口部位的模板序列，安装编辑。

其他公司正在开发一些替代方法，例如，Intellia Treateutics，Intellia，Inc.，它已经启动了NTLA-2001的3期试验，一种基于CRISPR/Cas9的基因编辑产品候选方案，用于治疗遗传性甲状腺激素过敏症，即伴有多发性神经病的淀粉样变性，以及用于治疗伴有心肌病的ATTR，以及NTLA-2002的3期试验，以及体内基于CRISPR/Cas9的用于治疗遗传性血管性水肿的候选基因编辑产品。Chroma Medicine，Inc.和Tune Treateutics，Inc.使用表观遗传编辑，旨在通过将DNA结合区域与表观遗传效应区域偶联来针对基因和控制染色质构象。同样，其他尚未被发现的新基因编辑技术可能比碱基编辑更具吸引力。此外，我们不能确定我们是否能够获得开发或使用其他基因编辑技术的权利。这些因素中的任何一个都可能减少或消除我们的商业机会，并可能对我们的业务、财务状况、运营结果和前景产生实质性的不利影响。

我们在寻找和开发潜在候选产品的努力中可能不会成功。如果这些努力不成功，我们可能永远不会成为一家商业舞台公司，也不会产生任何收入。

我们业务的成功主要取决于我们使用基因编辑技术识别、开发和商业化候选产品的能力。由于多种原因，我们的研究计划可能无法确定临床开发的潜在候选产品。我们的研究方法可能不能成功识别其他潜在的候选产品，我们的潜在候选产品可能被证明在临床前有有害的副作用。体外培养在实验或动物模型研究中，它们可能不会在此类实验或研究中显示出有希望的治疗效果信号，或者它们可能具有其他特征，可能使候选产品不切实际、无法上市或不太可能获得上市批准。

公共卫生流行病或大流行可能会影响我们启动和完成当前或未来临床前研究和临床试验的能力，扰乱监管活动，或对我们的业务和运营产生其他不利影响。此外，公共卫生流行病或大流行可能会对世界各地的经济产生不利影响，这可能会对我们的业务、运营和前景产生不利影响。

我们的业务和运营可能会受到公共卫生流行病或流行病的不利影响，包括最近的新冠肺炎疫情，影响到我们和我们的合作者经营的市场和行业。我们和我们的合同制造组织(CMO)和合同研究组织(CRO)已经经历了进行研究规模生产和执行一些临床前研究的能力的下降，我们已经并可能在未来面临影响我们启动和完成临床前研究和临床试验的能力的中断，以及对我们的研发活动至关重要的项目采购的中断，包括：

我们和我们的CRO和CMO未来可能面临与获得必要的机构审查委员会(IRB)、机构生物安全委员会(IBC)或其他必要的现场批准的能力相关的制造中断和中断，以及临床试验地点的其他延误。

此外，拜登政府于2023年5月终止了与新冠肺炎疫情相关的公共卫生紧急声明，FDA也终止了多项与新冠肺炎相关的政策。FDA保留了一些与COVID相关的政策，但在适用的情况下进行了适当的修改。目前还不清楚这些政策将如何影响我们开发和商业化我们的候选产品的努力。

我们未来可能会因任何大流行措施而面临监管会议和批准的障碍或延误。我们不能确定此类疫情对我们业务的整体影响，尽管由于上述原因，此类疫情有可能对我们的业务、财务状况、运营结果和前景产生不利影响。

临床药物开发涉及一个漫长而昂贵的过程，结果不确定。如果我们最终无法获得监管部门对我们的候选产品的批准，我们的业务将受到严重损害。

我们每个候选产品的失败风险都很高。我们无法预测我们的候选产品何时或是否会在人体上证明有效或安全，或者是否会获得上市批准。从FDA、EMA或其他类似的外国监管机构获得批准所需的时间是不可预测的，但通常需要在临床试验开始后多年，并取决于许多因素，包括监管机构的重大自由裁量权。在获得监管部门批准销售任何候选产品之前，我们必须完成临床前开发，然后进行广泛的临床试验，以证明我们的候选产品在人体上的安全性和有效性。我们还没有完成任何临床试验。临床试验可能无法证明我们的候选产品对人类是安全的，并对指定用途有效。即使我们可能开发的任何候选产品的初始临床试验都是成功的，我们可能开发的这些候选产品可能无法在临床开发的后期阶段显示出预期的安全性和有效性，尽管已经成功地通过了临床前研究和初步临床试验。正在进行临床试验的药物和生物制品的失败率很高。制药和生物技术行业的一些公司在后期临床试验中遭遇重大挫折，即使在早期临床试验中取得了令人振奋的结果。此外，即使临床试验成功，开发期间上市审批政策的变化、额外法规、法规或指南的制定或颁布的变化，或对每一项提交的产品申请的监管审查的变化，都可能导致申请的批准或拒绝的延迟。

在我们可以开始候选产品的临床试验之前，我们必须完成广泛的临床前测试和研究，以支持我们计划在美国和国外提交的IND和其他监管文件。我们不能确定我们的临床前测试和研究的及时完成或结果，也不能预测我们的临床前测试和研究的结果是否最终将支持我们当前或未来候选产品的进一步开发，或者监管机构是否会接受我们提议的临床计划。因此，我们可能无法在我们预期的时间内提交美国的IND或类似的外国申请来启动临床开发，并且这些申请的提交可能不会导致监管机构允许临床试验开始。

例如，2022年11月，FDA要求我们的IND在美国暂停评估VERVE-101的临床试验，并要求提供解决暂停所需的各种信息，包括临床前和临床数据。2023年10月，我们宣布FDA已经解除了临床限制，并批准了我们的IND使用VERVE-101。

此外，候选产品还需要接受持续的非临床安全性研究，这些研究可能与我们的临床测试同时进行。这些安全性研究的结果可能会推迟未来临床试验的启动或登记，并可能影响我们继续进行临床试验的能力。

临床测试费用昂贵，难以设计和实施，可能需要数年时间才能完成，而且结果还不确定。我们不能保证我们的任何临床试验都将按计划进行或按计划完成，或者根本不能。一项或多项临床试验的失败可能发生在测试的任何阶段，这可能是由多种因素造成的，包括但不限于研究设计的缺陷、剂量选择问题、安慰剂效应、患者登记标准以及未能证明良好的安全性或有效性特征。例如，在2024年4月，我们宣布，在观察到试验中第13名患者的暂时性无症状实验室异常--3级药物引起的一过性ALT升高以及3级药物引起的严重不良事件--之后，我们暂停了心脏1号试验的登记。在心脏-2试验的剂量升级部分，心脏-1试验预计将保持暂停状态。

临床前和临床数据往往容易受到不同解释和分析的影响，许多公司认为他们的候选产品在临床前研究和临床试验中表现令人满意，但仍未能获得其产品的营销批准。此外，如果我们的任何候选产品未能在任何临床试验中证明安全性和有效性，可能会对我们其他候选产品的观感产生负面影响，和/或导致FDA、EMA或其他监管机构在批准我们的任何候选产品之前要求进行额外的测试。

我们当前和未来的候选产品可能会因为许多原因而无法获得监管部门的批准，包括以下原因：

这一漫长的审批过程以及临床试验结果的不可预测性可能会导致我们无法获得监管部门的批准，无法将我们开发的任何候选产品推向市场，这将严重损害我们的业务、财务状况、运营结果和前景。

FDA、EMA和其他类似的外国监管机构在审批过程中拥有相当大的自由裁量权，并决定我们开发的任何候选产品何时或是否获得监管批准。即使我们相信从我们正在进行的或未来的候选产品临床试验中收集的数据是有希望的，这些数据可能也不足以支持FDA、EMA或任何其他类似的外国监管机构的批准。

即使我们获得批准，监管机构也可能批准我们的任何候选产品，其适应症比我们要求的更少或更有限，可能会根据昂贵的上市后临床试验的表现而批准，或者可能批准其标签不包括该候选产品成功商业化所必需或需要的标签声明。此外，在美国以外，监管机构可能不会批准我们打算对我们的产品收取的价格。上述任何一种情况都可能对我们的候选产品的商业前景造成实质性损害。

临床前研究和早期临床试验的结果可能不能预测未来的结果或后来的临床前研究和临床试验的成功。

我们从2022年开始才启动并开始进行临床试验。因此，我们对我们项目的潜在能力的信念主要基于研究和临床前研究。然而，临床前研究的结果可能不能预测后来的临床前研究或临床试验的结果，任何早期临床试验的结果也可能不能预测后来的临床试验的结果。此外，临床试验的初步成功可能并不代表这些试验完成后所取得的结果。此外，临床前和临床数据往往容易受到不同解释和分析的影响，许多公司认为他们的候选产品在临床前研究和临床试验中表现令人满意，但仍未能获得其产品的营销批准。我们已经对我们的候选产品在非人类灵长类动物身上进行了几次临床前研究，但我们不能确定在这些研究中观察到的结果是否会在我们的候选产品在人类身上的临床试验中转化为类似的结果。我们正在进行的或未来的临床试验可能最终不会成功，也不会支持我们可能开发的任何候选产品的进一步临床开发。通过临床试验的候选产品有很高的失败率。制药和生物技术行业的一些公司在临床开发方面遭遇了重大挫折，即使在早期的研究中取得了令人鼓舞的结果。我们临床开发中的任何这样的挫折都可能对我们的业务和运营结果造成实质性的损害。

我们可能会在完成或最终无法完成我们候选产品的开发和商业化过程中产生意外成本或遇到延迟。

在临床试验期间或临床试验的结果中，我们可能会遇到许多不可预见的事件，这些事件可能会推迟或阻止我们获得上市批准或将我们的候选产品商业化，包括：

如果临床试验被我们、进行此类试验的机构的IRBs或其伦理委员会、此类试验的数据审查委员会或数据安全监测委员会或FDA、EMA或其他外国监管机构暂停或终止，我们可能会遇到延迟。例如，在咨询了我们的心脏一号试验的独立数据和安全监测委员会后，我们暂停了心脏一号试验的登记，因为在试验中服用的第13名患者观察到了暂时性的无症状实验室异常--3级药物引起的一过性ALT升高以及3级药物引起的血小板减少的严重不良事件。监管机构可能会因多种因素而暂停或终止临床试验，这些因素包括未能按照监管要求或我们的临床规程进行临床试验、FDA、EMA或其他外国监管机构对临床试验操作或试验地点的检查导致实施临床暂停、不可预见的安全问题或不良副作用，包括与我们的候选产品所属产品类别相关的问题。

如果我们被要求对我们的候选产品进行超出我们目前预期的额外临床试验或其他测试，如果我们无法成功完成我们候选产品的临床试验或其他测试，如果这些试验或测试的结果不呈阳性或仅为轻微阳性，或者如果存在安全问题，我们可能会：

如果我们在临床前研究或临床试验或在获得上市批准方面遇到延误，我们的开发成本也会增加。我们不知道我们的任何临床前研究或临床试验是否会按计划开始，是否需要重组，或是否会如期完成，或者根本不知道。我们还可能决定更改一个或多个临床试验的设计或方案，包括增加更多的患者或手臂，这可能会导致成本和费用的增加和/或延迟。重大的临床前研究或临床试验延迟也可能缩短我们拥有将候选产品商业化的独家权利的任何期限，或允许我们的竞争对手在我们之前将产品推向市场，并削弱我们成功将候选产品商业化的能力，并可能损害我们的业务和运营结果。

临床前药物的开发是不确定的。我们的部分或全部临床前计划可能会延迟或可能永远不会进入临床试验，这将对我们及时获得市场批准或将这些候选产品商业化的能力产生不利影响，这将对我们的业务产生不利影响。

为了获得FDA批准销售一种新的生物制品，我们必须证明产品的纯度(或产品质量)以及对人体的安全性和效力或功效的证明。为了满足这些要求，我们将必须进行充分和良好控制的临床试验。在我们可以开始候选产品的临床试验之前，我们必须完成广泛的临床前测试和研究，以支持美国的IND。我们不能确定我们的临床前测试和研究的及时完成或结果，我们也不能预测FDA是否会接受我们提出的临床计划，或者我们的临床前测试和研究的结果是否最终将支持这些候选产品的进一步开发。因此，我们不能确保我们能够在我们预期的时间表上提交IND或类似的临床前计划申请，我们也不能确保IND或类似申请的提交将导致FDA或其他监管机构允许临床试验开始。

进行临床前试验是一个漫长、耗时和昂贵的过程。根据候选产品的类型、复杂性、新颖性和预期用途，时间长度可能会有很大不同，并且每个候选产品通常可以是几年或更长时间。与我们自己进行临床前测试和研究的候选产品相关的延迟可能会导致我们产生额外的运营费用。此外，我们可能会受到与我们的潜在合作者对某些候选产品进行的临床前测试和研究相关的延迟的影响，而我们对此无法控制。候选产品的临床前研究和临床试验的开始和完成速度可能会因许多因素而延迟，例如：

此外，即使我们确实启动了其他候选产品的临床试验，我们的开发工作也可能不会成功，我们或第三方代表我们进行的临床试验可能无法证明产品纯度(或质量)以及为我们的任何候选产品或使用我们技术的候选产品获得必要的营销批准所需的安全性和有效性或有效性证明。即使我们从临床前研究或初步临床试验中获得了积极的结果，我们也可能不会在未来的试验中取得同样的成功。

如果我们在临床试验的患者登记过程中遇到延迟或困难，我们收到必要的监管批准可能会被推迟或阻止。

确定并使患者有资格参与我们的候选产品的临床试验对我们的成功至关重要。成功和及时地完成临床试验将需要我们招募足够数量的患者留在试验中，直到试验结束。如果我们无法根据FDA或美国以外的类似监管机构的要求找到并招募足够数量的合格患者参加这些试验，我们可能无法为我们的候选产品启动或继续进行额外的临床试验。鉴于动脉粥样硬化性心血管疾病或ASCVD的患者人数众多，如果我们扩大用于治疗已确诊的ASCVD患者的VERVE-101或VERVE-102的临床开发，为获得监管机构对该适应症的批准而进行临床试验所需的患者数量可能非常高，我们可能无法招募足够数量的患者，因此我们可能无法启动或完成用于治疗已确诊的ASCVD患者的VERVE-101或VERVE-102的临床试验。由于纯合子家族性高胆固醇血症(HoFH)的患者人数较少，我们可能难以招募患者，我们可能无法启动或完成VERVE-201治疗HoFH的临床试验。

我们无法找到并招募足够数量的患者参加我们的临床试验，将导致重大延误，可能需要我们完全放弃一项或多项临床试验，并可能推迟或阻止我们获得必要的监管批准。我们临床试验的登记延迟可能会导致我们候选产品的开发成本增加，减慢或停止我们的候选产品开发和审批过程，并危及我们寻求和获得开始产品销售和创造收入所需的营销批准的能力，这将导致我们公司的价值下降，并限制我们获得额外融资的能力。

即使我们能够为我们未来的临床试验招募足够数量的患者，我们也可能难以在我们的临床试验中维持患者。许多最终接受安慰剂治疗的患者可能会意识到他们没有接受接受测试的候选产品，他们可能会决定退出我们的临床试验，以寻求替代疗法，而不是继续试验。如果我们难以招募或维持足够数量的患者进行临床试验，我们可能需要推迟、限制或终止临床试验，其中任何一项都会损害我们的业务、财务状况、运营结果和前景。

如果我们开发的任何候选产品或我们管理它们所依赖的交付模式导致严重的不良事件、不良副作用或意外特征，这些不良事件、副作用或特征可能会推迟或阻止监管部门对候选产品的批准，限制商业潜力或在任何潜在的上市批准后导致重大负面后果。

我们的开发工作还处于早期阶段，尚未完成临床试验。涉及使用基因编辑技术的临床试验数量有限，还没有完成的临床试验涉及碱基编辑技术，类似于我们在VERVE-101、VERVE-102和VERVE-201中使用的基因编辑技术。此外，还没有任何体内已获得监管机构批准用于人类的候选基因编辑产品。无法预测我们可能开发的任何候选产品何时或是否会证明对人类是安全的。无法保证基因编辑技术不会造成不良副作用，因为对患者DNA的不当编辑可能会导致淋巴瘤、白血病或其他癌症或其他功能异常的细胞。

任何候选基因编辑产品的一个重大风险是可能发生“非目标”编辑，这可能导致严重的不良事件、不良副作用或意想不到的特征。我们不能确定我们正在进行的或未来的任何临床试验中都不会发生非靶标编辑，临床前研究中缺乏观察到的副作用并不能保证这种副作用不会在人类临床试验中发生。由于DNA编辑的潜在永久性或用于携带遗传物质的候选产品的其他成分，还存在暴露于基因编辑人员后延迟或延迟呈现不良事件的潜在风险。此外，因为基因编辑可以永久改变，所以即使在观察到副作用之后，治疗也不能撤销。

我们正在使用LNP将我们的基因编辑器传递到肝脏。LNP最近被用于在人体中递送mRNA，包括辉瑞公司开发的COVID-19疫苗，或辉瑞、BioNTech SE以及Moderna，Inc.，LNP被用于在临床试验中递送mRNA以进行治疗。LNP有可能诱导肝损伤和/或引发全身炎症反应，其中任何一种都可能是致命的。虽然我们的目标是继续优化我们的LNP，但不能保证我们的LNP不会产生不希望的影响。2024年4月，我们宣布

在观察到短暂的无症状实验室异常（3级药物诱导的ALt短暂增加以及3级药物诱导的血小板减少症的严重不良事件）后，暂停了Heart-1试验的入组。作为对这些观察到的实验室异常调查的一部分，我们完成了一系列非临床研究，旨在隔离LNP在实验室异常中的潜在作用。这些研究的数据继续支持我们的理解，即VERVE-101中的LNP可能是观察到的实验室异常的主要驱动因素。

我们的LNP可能全部或部分导致以下一项或多项：肝损伤、免疫反应、输注反应、补充反应、调节反应、抗体反应（包括Igm、Igm、IE或Igg或其某种组合），或对聚乙二醇或聚乙二醇或聚乙二醇的反应（来自与LNP相关的一些脂质或聚乙二醇）。我们研究药物的某些方面可能会引发mRNA或脂质的免疫反应，以及肝脏途径内的不良反应或mRNA或LNP的降解，其中任何一种都可能导致我们正在进行的一项或多项临床试验中出现重大不良事件。其他LNP也观察到了其中一些类型的不良反应。任何此类不良反应的根本原因可能存在不确定性，这将使临床试验中的副作用难以准确预测，并导致我们的项目严重延迟。

我们专有的GalNAc-LNP（我们正在VERVE-102和VERVE-201中使用）是一种将基因编辑器递送到肝脏的新型递送机制，此前尚未在人体中进行过研究。因此，我们无法确定我们在Heart-1试验中观察到的实验室异常或其他不良事件不会发生在我们正在进行或未来利用新型递送机制的临床试验中。

如果我们开发的任何候选产品与严重不良事件、不良副作用或意想不到的特征相关，我们可能需要放弃其开发，或将其开发限制在严重不良事件、不良副作用或其他特征不太普遍、不太严重或从风险效益角度来看更容易接受的特定用途或人群中，任何这些都会对我们的业务、财务状况、运营结果和前景产生实质性的不利影响。

如果将来我们无法证明上述任何不良事件是由我们的候选产品以外的因素引起的，FDA、EMA或其他监管机构可以命令我们停止进一步开发或拒绝批准我们能够针对任何或所有目标适应症开发的任何候选产品。如果在任何上市后的后续研究中发现了严重的安全问题，他们也可以撤销营销授权。即使我们能够证明所有未来的严重不良事件都不是与产品相关的，此类事件也可能影响患者招募或入选患者完成试验的能力。此外，如果我们选择或被要求推迟、暂停或终止我们可能开发的任何候选产品的临床试验，该候选产品的商业前景可能会受到损害，我们从任何这些候选产品产生产品收入的能力可能会被推迟或取消。这些情况中的任何一种都可能损害我们识别和开发候选产品的能力，并可能严重损害我们的业务、财务状况、运营结果和前景。

公众对基因药物的负面看法，尤其是基因编辑和碱基编辑，可能会对我们潜在产品的需求产生负面影响，而加强对基因药物的监管审查可能会对我们为候选产品获得监管批准的能力产生不利影响。

我们的计划包括编辑人类基因组。我们候选产品的临床和商业成功将在一定程度上取决于公众对使用基因编辑和基因监管预防或治疗人类疾病的理解和接受。公众的态度可能会受到这样的说法的影响，即基因编辑和基因监管是不安全、不道德或不道德的，因此，我们的候选产品可能无法获得公众或医学界的接受。公众的不良态度可能会对我们招募临床试验的能力产生不利影响。此外，我们的成功将取决于医生开出的处方以及他们的患者愿意接受的治疗，这些治疗涉及使用我们可能开发的候选产品来替代或补充他们已经熟悉的现有治疗方法，并且可能获得更多的临床数据。

此外，美国、州或外国政府对公众负面看法或道德关切的反应可能会导致新的法律或法规，可能会限制我们开发或商业化任何候选产品、获得或维持监管批准或以其他方式实现盈利的能力。

更严格的政府法规或负面的公众舆论将对我们的业务或财务状况产生负面影响，并可能推迟或损害我们候选产品的开发和商业化或对任何产品获得批准后的需求。我们的临床前研究或临床试验中或我们的许可方、合作伙伴或竞争对手或利用基因编辑技术的学术研究人员的临床前研究或临床试验中的不良事件，即使最终不是归因于我们可能识别和开发的候选产品，并且由此产生的宣传可能会导致政府监管加强、不利的公众看法、潜在的监管延迟测试或批准我们的候选产品，对获得批准的候选产品提出更严格的标签要求，并减少对任何此类产品的需求

候选人第三方或政府利用基因编辑技术开发威胁美国国家安全的生物制剂或产品，同样可能对我们造成如此负面影响。

我们不时宣布或公布的临床试验的中期、初步或主要结果可能会随着更多参与者数据的获得而发生变化，并受到审计和验证程序的约束，这可能会导致最终数据发生重大变化。

有时，我们可能会公布或报告我们临床试验的中期、初步或主要结果。我们可能完成的临床试验的中期结果，例如我们在2023年11月、2024年4月和2024年10月报告的我们的心脏1号VERVE-101试验的中期数据，可能会随着参与者登记的继续和更多参与者数据的获得而面临一个或多个临床结果可能发生实质性变化的风险。作为数据分析的一部分，我们也会做出假设、估计、计算和结论，而我们可能没有收到或没有机会完全评估所有数据。初步、中期或顶线数据也仍需接受审计和核实程序，这可能会导致最终数据与我们之前公布的初步或中期数据大不相同。因此，在最终数据可用之前，应谨慎看待初步、中期或主要数据。初步或中期数据与最终数据之间的不利差异可能是实质性的，可能会严重损害我们的声誉和业务前景，并可能导致我们普通股的交易价格大幅波动。

基因药物很复杂，很难制造。我们可能会遇到满足监管机构要求的延迟或生产问题，这些问题会导致我们的开发计划延迟，限制我们可能开发的候选产品的供应，或者以其他方式损害我们的业务。

我们可能开发的任何候选产品都可能需要比大多数化学药物所需的加工步骤更复杂的加工步骤。此外，与化学药物不同，生物的物理和化学性质，如我们打算开发的候选产品，通常不能完全表征。因此，对候选成品的分析可能不足以确保候选产品将以预期的方式运行。制造过程的问题，即使是与正常过程的微小偏差，都可能导致产品缺陷或制造失败，从而导致批量故障、产品召回、产品责任索赔或库存不足，或可能延误我们潜在的IND申报的进展。如果我们成功地开发了候选产品，我们可能会遇到问题，无法获得足够数量和质量的临床级材料，这些材料符合FDA、EMA或其他类似的适用外国标准或规范，并具有一致和可接受的生产产量和成本。此外，我们可能开发的候选产品将需要复杂的交付模式，例如LNPs，这将在制造过程中引入额外的复杂性。

此外，FDA、EMA和其他监管机构可能会要求我们在任何时间提交任何批次经批准的产品的样品以及显示适用测试结果的协议。在某些情况下，FDA、EMA或其他监管机构可能会要求我们在机构授权发布之前不要分发大量产品。制造过程中的微小偏差，包括那些影响质量属性和稳定性的偏差，可能会导致产品发生不可接受的变化，从而导致批量故障或产品召回。批次失败或产品召回可能会导致我们推迟临床试验或产品发布，这可能会让我们付出高昂的代价，否则会损害我们的业务、财务状况、运营结果和前景。

我们还可能在聘用和留住管理我们的制造流程所需的经验丰富的科学、质量控制和制造人员方面遇到问题，这可能会导致我们的生产延迟或难以保持遵守适用的法规要求。

鉴于生物制品生产的性质，在生产过程中存在污染风险。任何污染都可能严重损害我们按计划生产候选产品的能力，并可能损害我们的运营结果，并造成声誉损害。我们预计制造过程中需要的一些原材料来自生物来源。这种原材料很难获得，可能会受到污染或召回。在我们可能开发的任何候选产品的制造中使用生物衍生物质的材料短缺、污染、召回或限制可能会对商业制造或临床材料的生产产生不利影响或中断，这可能会对我们的开发时间表以及我们的业务、财务状况、运营结果和前景造成实质性损害。

我们的制造流程或与我们签约的设施中的任何问题都可能使我们成为潜在合作伙伴(包括较大的制药公司和学术研究机构)的吸引力较低的合作伙伴，这可能会限制我们获得更多有吸引力的开发项目。第三方制造工艺或设施中的问题也可能限制我们确保为我们正在进行或计划进行的任何临床试验提供足够的临床材料的能力，并满足我们开发和商业化的任何候选产品的市场需求。

如果我们的任何候选产品获得了上市批准，而我们或其他人后来发现该药物的效果不如之前认为的那样有效，或者导致了以前没有发现的不良副作用，我们销售该药物的能力可能会受到影响。

我们候选产品的临床试验是在精心定义的同意进入临床试验的患者子集中进行的。因此，我们的临床试验可能会显示候选产品的明显正面效果大于实际正面效果(如果有的话)，或者无法识别不良副作用。如果我们的一个或多个候选产品获得了监管部门的批准，而我们或其他人后来发现它们的效果不如之前认为的那样有效，或者造成了不良的副作用，可能会导致许多潜在的重大负面后果，包括：

这些事件中的任何一种都可能阻止我们实现或保持市场对特定候选产品的接受程度，如果获得批准，可能会严重损害我们的业务、财务状况和运营结果。

我们可能会花费有限的资源来追求特定的候选产品或适应症，而无法利用可能更有利可图或成功可能性更大的候选产品或适应症。

由于我们的财务和管理资源有限，我们可能会放弃或推迟寻找其他候选产品或后来被证明具有更大商业潜力的其他迹象的机会。我们的资源分配决策可能会导致我们无法利用可行的商业产品或有利可图的市场机会。我们在当前和未来研发计划以及特定适应症候选产品上的支出可能不会产生任何商业上可行的产品。如果我们没有准确评估特定候选产品的商业潜力或目标市场，我们可能会通过合作、许可或其他版税安排放弃对该候选产品有价值的权利，而在这种情况下，保留该候选产品的独家开发权和商业化权利对我们更有利。如果不能成功地分配资源或利用战略，将对我们的业务、财务状况和运营结果产生不利影响。

我们一直在进行临床试验，并计划在美国以外的地点进行更多的临床试验。FDA可能不接受在这些地点进行的试验的数据，在美国以外的地方进行试验可能会使我们面临额外的延迟和费用。

我们一直在并计划在美国以外的一个或多个试验地点进行更多的临床试验，包括已经在新西兰和英国的试验地点进行的VERVE-101的心脏1号试验，以及VERVE-102的心脏2号试验和VERVE-201的脉冲1号试验。尽管FDA可能会接受在美国以外的地点进行的临床试验的数据，但这些数据的接受取决于FDA施加的条件。例如，如果来自外国临床试验地点的数据不打算作为在美国批准的唯一依据，FDA将不会接受这些数据作为营销申请的支持，除非临床试验是按照GCP要求良好地设计和进行的。如果有必要，FDA还必须能够通过现场检查来验证试验数据。如果外国临床试验的数据打算作为在美国上市批准的唯一依据，FDA通常不会仅根据外国数据批准申请，除非(I)数据适用于美国人口和美国医疗实践；(Ii)试验是由具有公认能力并符合GCP的临床研究人员进行的

法规;和（iii）无需FDA现场检查即可认为数据有效，或者如果FDA认为有必要进行此类检查，FDA能够通过现场检查或其他适当方式验证数据。此外，这些临床试验须遵守进行试验的司法管辖区的适用当地法律。无法保证FDA会接受在美国境外进行的试验的数据。如果FDA不接受我们在美国境外进行的任何试验的数据，可能会导致需要进行额外的试验，这将是昂贵且耗时的，并且可能会延迟或永久停止我们对适用候选产品的开发。

此外，在美国以外进行临床试验可能会对我们产生重大不利影响。进行国际临床试验所固有的风险包括：

我们依赖，并预计将继续依赖第三方进行我们产品制造、研究以及临床前和临床测试的部分或全部方面，这些第三方的表现可能不令人满意。

我们不希望独立进行我们产品制造、研究以及临床前和临床测试的所有方面。我们目前依赖并预计将继续依赖第三方进行其中的许多活动，包括制造我们在临床前或临床开发中测试的任何候选产品的CMO，以及进行临床试验、动物试验和研究的CRO。这些第三方中的任何一方可能随时终止与我们的合作，或可能面临供应链短缺，或无法获得必要的资源，例如用于我们的临床前试验的动物，以支持我们计划的开发活动。如果我们需要修改我们的开发计划或达成替代安排，这可能会推迟我们的产品开发活动。我们对这些第三方的研发活动的依赖将减少我们对这些活动的控制，但不会免除我们确保遵守所有必需的法规和研究方案的责任。例如，对于我们自己开发和商业化的候选产品，我们将继续负责确保我们的每一项启用IND的研究和临床试验都按照研究计划和协议进行。

尽管我们打算为我们可能开发的任何候选产品设计临床试验，但CROs将进行部分或全部临床试验。因此，我们开发计划的许多重要方面，包括其行为和时机，将超出我们的直接控制范围。与完全依赖自己的员工相比，我们依赖第三方进行正在进行的和未来的临床前研究和临床试验也将导致对通过临床前研究和临床试验开发的数据管理的直接控制减少。与外部方沟通也可能具有挑战性，可能导致错误以及协调活动的困难。外部各方可以：

这些因素可能会对第三方进行我们的临床前研究和临床试验的意愿或能力产生重大不利影响，并可能使我们面临超出我们控制范围的意外成本增加。如果CRO和其他第三方没有以令人满意的方式进行临床前研究以及正在进行的和未来的临床试验，违反他们对我们的义务或未能遵守监管要求，我们可能开发的任何候选产品的开发、监管批准和商业化可能会延迟，我们可能无法获得监管部门的批准并将我们的候选产品商业化，或者我们的开发计划可能受到实质性和不可逆转的损害。如果我们不能依赖我们的CRO和其他第三方收集的临床前和临床数据，我们可能会

需要重复、延长或增加我们进行的任何临床前研究或临床试验的规模，这可能会显著推迟商业化并需要更大的支出。

如果第三方未按照法规要求或我们声明的研究计划和方案成功履行其合同职责、在预期期限内完成或进行我们的研究，我们将无法完成或可能延迟完成支持未来IND提交和批准我们可能开发的任何候选产品所需的临床前研究和临床试验。

生物产品的制造是复杂的，由于各种原因容易造成产品损失。我们与第三方签订合同，生产我们的候选产品，用于临床前和临床测试，并预计将继续这样做以实现商业化。这种对第三方的依赖增加了我们无法以可接受的成本或质量获得足够数量的候选产品或产品或此类数量的风险，这可能会推迟、阻止或损害我们的开发或商业化努力。

我们不拥有或经营，目前也没有建立任何制造设施的计划。我们依赖，并预计将继续依赖第三方生产我们的候选产品，用于临床前和临床测试，以及用于商业生产(如果我们的任何候选产品获得市场批准)。我们还依赖这些第三方进行包装、贴标签、杀菌、储存、配送和其他生产物流。这种对第三方的依赖增加了我们无法以可接受的成本或质量获得足够数量的候选产品或产品或此类数量的风险，这可能会推迟、阻止或损害我们的开发或商业化努力。我们可能无法与第三方制造商达成任何协议，也无法以可接受的条款这样做。即使我们能够与第三方制造商达成协议，依赖第三方制造商也会带来额外的风险，包括：

由于产能限制或原料或原料药市场的延迟或中断，我们或我们的第三方制造商可能会遇到生产我们的候选产品所需的原材料或活性药物成分或原料药的短缺，这些原料或原料药的数量需要我们的临床试验所需的数量，或者，如果我们的候选产品获得批准，足够的数量用于商业化或满足需求的增加，包括我们的竞争对手或其他公司购买该等原材料或原料药造成的短缺。如果我们或我们的第三方制造商无法获得生产足够数量的候选产品所需的原材料或原料药，可能会对我们的业务产生重大不利影响。

被批准用于商业销售或用于晚期临床试验的成品治疗产品的成分必须按照cGMP生产。我们的第三方制造商在我们可以开始制造和销售我们的任何候选产品之前，都要接受监管机构的检查和批准，之后还要接受不定期的检查。第三方制造商可能无法遵守cGMP法规或美国以外的类似法规要求。我们或我们的第三方制造商未能遵守适用的法规可能会导致监管行动，例如发布FDA Form 483的观察通知、警告信或对我们施加的制裁，包括临床持有、罚款、禁令、民事处罚、延迟、暂停或撤回批准、吊销许可证、扣押或召回候选产品或产品、运营限制和刑事起诉，其中任何一项都可能对我们的产品供应产生重大不利影响。

VERVE-101、VERVE-102和VERVE-201等生物制品的生产是复杂的，尤其是大量生产。生物产品必须始终如一地生产，并符合明确定义的制造工艺。因此，必须能够验证和控制制造过程，以确保其可重现性。生物制品的生产极易因污染、设备故障或设备安装或操作不当、供应商或操作员错误、产量不一致、产品特性变化以及产品工艺难以规模化而造成产品损失。我们还没有为我们的任何潜在商业化候选产品扩大制造工艺。即使与正常制造流程的微小偏差也可能导致产量下降、产品缺陷和其他供应中断。如果在我们的候选产品中或在制造我们候选产品的制造设施中发现微生物、病毒或其他污染，可能需要关闭此类制造设施很长一段时间以调查和补救污染，这可能会损害我们的运营结果并造成潜在的声誉损害。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。因此，我们可能无法优先使用这些设施，甚至根本无法使用。

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。

我们现有或未来制造商的任何业绩失败都可能推迟临床开发或营销批准。我们目前没有为大量药物物质提供多余供应或来源的安排，也没有与第三方制造商就长期商业供应达成任何协议。如果我们未来的合同制造商不能按约定履行合同，我们可能会被要求更换这些制造商。尽管我们相信有几个潜在的替代制造商可以生产我们的候选产品，但我们在确定和鉴定任何此类替代产品时可能会产生额外的成本和延误，或者无法与替代制造商达成协议。

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。

如果我们候选产品的任何第三方制造商无法扩大我们候选产品的生产规模，和/或提高其制造的产品良率，那么我们制造候选产品的成本可能会增加，商业化可能会推迟。

为了生产足够的数量来满足临床试验的需求，如果获得批准，我们可能开发的任何当前或未来的候选产品随后将实现商业化，我们的第三方制造商将被要求在保持产品质量的同时增加产量和优化制造工艺。向更大规模生产的过渡可能会被证明是困难的。此外，如果我们的第三方制造商不能优化他们的制造流程来提高我们候选产品的产品产量，或者如果他们无法在保持产品质量的同时增加我们候选产品的产量，那么我们可能无法满足我们正在进行的或未来的临床试验或市场需求，这可能会降低我们创造利润的能力，并对我们的业务和运营结果产生实质性的不利影响。

我们已经与第三方就项目或候选产品的研究、开发、制造和商业化进行了合作，并可能进行更多的合作。如果这些合作不成功，我们的业务可能会受到不利影响。

作为我们战略的一部分，我们已经达成合作，并打算寻求与第三方就我们的一个或多个计划或候选产品达成更多合作。例如，2019年4月，我们与比姆签订了原始合作和许可协议，或原始比姆协议，独家许可比姆的某些碱基编辑、基因编辑和针对某些心血管靶的交付技术用于我们的候选产品，该协议于2022年7月修订和重述，根据该协议，比姆于2023年10月将其某些权利和义务转让给礼来公司；2020年10月，我们签订了Acuitas协议，从Acuitas获得许可，许可我们在VERVE-101中使用的LNP交付技术；2021年10月，我们签署了诺华协议，从诺华公司获得了我们正在VERVE-102和VERVE-201中使用的某些脂质技术的许可；2022年7月，我们签署了Vertex协议，进行为期四年的全球研究合作，重点是开发体内基因编辑候选者瞄准治疗单一肝脏疾病的未公开目标; 2023年6月，我们签署了《礼来协议》，进行为期五年的全球研究合作，最初重点是推进我们的发现阶段体内基因编辑脂蛋白（a）程序。我们可能参与任何其他合作安排的合作者包括大中型制药公司、区域和国家制药公司以及生物技术公司。根据ARCLA，以及根据我们可能与任何第三方达成的任何其他安排，我们对合作者致力于我们候选产品的开发或商业化的资源数量和时间有有限的控制权。我们从这些安排中产生收入的能力可能取决于我们的合作者成功履行这些安排中分配给他们的职能的能力。

我们参与的合作可能不会成功，任何成功都将在很大程度上取决于这些合作者的努力和活动。协作会带来许多风险，包括以下风险：

协作协议可能不会以最有效的方式导致候选产品的开发或商业化，或者根本不会。如果当前或未来的任何合作没有成功开发产品并将其商业化，或者如果我们的一个协作者终止了与我们的协议，我们可能不会收到任何未来的研究资金或合作下的里程碑或特许权使用费付款。如果我们没有收到我们根据这些协议预期的资金，我们候选产品的开发可能会被推迟，我们可能需要额外的资源来开发我们的候选产品。本“风险因素”一节中描述的与产品开发、监管审批和商业化相关的所有风险也适用于我们的合作者的活动。

合作协议可能要求我们产生非经常性费用和其他费用，增加我们的短期和长期支出，发行稀释现有股东的证券，或扰乱我们的管理和业务。例如，于执行原来的Beam协议时，我们向Beam发行了276,075股普通股；就执行Vertex协议而言，我们完成了与Vertex的私募，据此，我们向Vertex发行了1,519,756股普通股；就礼来协议的效力而言，我们完成了与礼来的私募，根据该协议，我们向礼来公司发行了1,552,795股普通股。此外，根据Cas9许可协议，我们向布罗德和哈佛发行了138,037股普通股。远大和哈佛也拥有反稀释权利，据此，我们在完成优先股融资后，向远大和哈佛额外发行了309,278股普通股。我们还根据Cas9许可协议在IPO结束时向远大和哈佛额外发行了878,098股普通股。如果我们的平均市值超过了指定的门槛，从十位数的中位数美元金额上升到$100亿，或者如果我们的公司发生控制权变更或出售，以超过这些门槛作为代价，我们也有义务向哈佛和宽泛分级成功付款。如本公司控制权发生变更或本公司被出售，本公司须在事件发生后的指定期间内以现金支付任何相关的成功付款。否则，成功付款可以根据我们的选择以现金或我们普通股的股票或现金和我们普通股的股票的组合来支付。到目前为止，我们已经根据CAS9许可协议以现金支付了大约630万的成功付款。

在寻找合适的合作者方面，我们可能面临激烈的竞争，谈判过程既耗时又复杂。我们达成最终协作协议的能力将取决于我们对协作者的资源和专业知识的评估、拟议协作的条款和条件以及提议的协作者对几个因素的评估。如果我们许可我们或我们的合作者可能开发的任何候选产品的权利，如果我们无法成功地将这些交易与我们现有的运营和公司文化相结合，我们可能无法实现此类交易的好处。

此外，在其对我们的合同义务的约束下，如果我们的合作者参与业务合并，则该合作者可能会淡化或终止经我们许可的任何候选产品的开发或商业化。如果我们的一个合作者终止了与我们的协议，我们可能会发现更难吸引新的合作者，我们在商业和金融界的看法可能会受到不利影响。

如果我们不能在商业上合理的条件下建立或维持合作，我们可能不得不改变我们的开发和商业化计划，我们的业务可能会受到不利影响。

我们在吸引合适的合作者方面面临着激烈的竞争，一些更成熟的公司可能也在寻求授权或获得我们认为有吸引力的第三方知识产权的战略。这些老牌公司由于其规模、财务资源以及更强的临床开发和商业化能力，可能比我们具有竞争优势。此外，将我们视为竞争对手的公司可能不愿将权利转让或许可给我们。我们是否就合作达成最终协议，除其他外，将取决于我们对合作伙伴的资源和专长的评估、拟议合作的条款和条件以及拟议合作伙伴对若干因素的评价。这些因素可能包括临床试验的设计或结果，FDA、EMA或其他监管机构批准的可能性，候选产品的潜在市场，制造和向患者交付此类候选产品的成本和复杂性，竞争产品的潜力，我们对技术所有权的不确定性，如果在不考虑挑战的优点、任何现有合作协议的条款以及一般的行业和市场条件的情况下对这种所有权提出挑战，则可能存在这种不确定性。协作者还可能有机会就类似适应症的其他候选产品或技术进行协作，并将不得不评估对于我们的候选产品而言，这样的协作是否会比与我们的协作更具吸引力。

根据现有或未来的许可协议，我们也可能受到限制，不能与潜在的合作者签订特定条款的协议。

协作是复杂且耗时的谈判、记录和执行。此外，大型制药和生物技术公司之间的整合减少了未来潜在合作者的数量。

我们可能无法及时、以可接受的条款或根本无法就更多合作进行谈判。如果我们无法做到这一点，我们可能不得不减少我们正在寻求合作的候选产品的开发，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，或者增加我们的支出并自费进行开发或商业化活动。如果我们选择自己资助和从事开发或商业化活动，我们可能需要获得更多的专业知识和额外的资本，而这些可能是我们无法接受的条件或根本无法获得的。如果我们未能达成合作，并且没有足够的资金或专业知识来开展必要的开发和商业化活动，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。

我们的候选产品中使用的一些零部件和材料依赖于单一来源的供应商。

我们的候选产品中使用的一些零部件和材料依赖于单一来源的供应商。我们不能确保这些供应商或服务提供商将继续经营，有足够的能力或供应来满足我们的需求，也不能确保它们不会被我们的竞争对手或其他对继续与我们合作感兴趣的公司收购。我们使用原材料、零部件、关键工序和成品的单一来源供应商，使我们面临几个风险，包括供应中断、价格上涨或延迟交货。一般来说，替代部件的替代供应来源相对较少。这些供应商可能无法或不愿意满足我们未来对临床试验或商业销售的需求。为这些部件、材料和工艺建立额外的或替代供应商可能需要大量时间，而且可能很难建立符合监管要求的替代供应商。任何单一来源供应商或服务提供商的任何供应中断都可能导致供应延迟或中断，这将损害我们的业务、财务状况、运营结果和前景。

如果我们不得不更换供应商，我们可能开发的任何候选产品的制造和交付可能会中断很长一段时间，这可能会对我们的业务造成不利影响。建立其他或

如果需要更换供应商，可能不会很快完成。如果我们能够找到替代供应商，替代供应商将需要合格，并可能需要额外的监管机构批准，这可能会导致进一步的延误。虽然我们寻求保持产品中使用的单一来源组件和材料的充足库存，但组件或材料供应的任何中断或延迟，或我们无法以可接受的价格从替代来源获得组件或材料，都可能会削弱我们满足候选产品需求的能力。

如果我们或我们的许可人无法获得、维护、捍卫和执行涵盖我们的基因编辑技术和候选产品的专利权，或者如果获得的专利保护范围不够广泛，我们的竞争对手可能会开发和商业化与我们相似或相同的技术和产品，我们成功开发和商业化我们的技术和候选产品的能力可能会受到不利影响。

我们的成功在很大程度上取决于我们是否有能力获得、维护、捍卫和加强对我们可能单独和与他人共同拥有的知识产权的保护，或者可能就我们开发的专有技术和候选产品从美国和其他国家/地区的其他人那里获得许可，特别是专利。保护我们的基因编辑技术和候选产品是困难和昂贵的，我们可能无法确保它们的保护。我们阻止未经授权的第三方制造、使用、销售、提供销售、进口或以其他方式商业化我们可能开发的候选产品或运营上类似的产品的能力，取决于我们在涵盖这些活动的有效和可执行的专利或商业秘密下拥有的权利的程度。

We seek to protect our proprietary position by filing patent applications in the United States and abroad related to our product candidates that are important to our business and by in-licensing intellectual property related to our technologies and product candidates. If we are unable to obtain or maintain patent protection with respect to any proprietary technology or product candidate, our business, financial condition, results of operations and prospects could be materially harmed. Failure to obtain protection including patent protection, may be a result of specific legal and factual circumstances that may preclude the availability of protection for our product candidates in the United States or any given country. For example, inadequate, faulty or erroneous patent prosecution may result in diminution, loss or unavailability of patent rights that adequately cover our products. Patent disclosures and claims that are intended to cover our product candidates that are sufficient or allowable in one country may not be sufficient or allowable in another country. The requirements for filing a patent application in the United States may not be sufficient to support a patent filing in a country or region outside the United States.

The patent prosecution process is expensive, time-consuming and complex, and we may not be able to file, prosecute, maintain, defend or license all necessary or desirable patent applications at a reasonable cost or in a timely manner. In addition, our ability to obtain and maintain valid and enforceable patents depends on whether the differences between our inventions and the prior art allow our inventions to be patentable over the prior art. It is also possible that we will fail to identify patentable aspects of our research and development output before it is too late to obtain patent protection. Moreover, in some circumstances, we do not have the right to control the preparation, filing and prosecution of patent applications, or to maintain, enforce and defend the patents, covering technology that we license from third parties. Therefore, these in-licensed patents and applications may not be prepared, filed, prosecuted, maintained, defended and enforced in a manner consistent with the best interests of our business.

The patent position of pharmaceutical and biotechnology companies generally is highly uncertain, involves complex legal and factual questions and has in recent years been the subject of much litigation. The field of gene editing especially has been the subject of extensive patenting activity and litigation. In addition, the scope of patent protection outside of the United States is uncertain and laws of foreign countries may not protect our rights to the same extent as the laws of the United States or vice versa. For example, European patent law restricts the patentability of methods of treatment of the human body more than United States law does. Further, as of June 2023, European applications have the option, upon grant of a patent, of becoming a Unitary Patent which is subject to the jurisdiction of the Unitary Patent Court, or the UPC. This is a significant change in European patent practice. As the UPC is a new court system, there is no precedent for the court, increasing the uncertainty of any litigation.

With respect to both owned and in-licensed patent rights, we cannot predict whether the patent applications we and our licensors are currently pursuing will issue as patents in any particular jurisdiction or whether the claims of any issued patents will provide sufficient protection from competitors. Further, we may not be aware of all third-party intellectual property rights potentially relating to our product candidates.

In addition, publications of discoveries in the scientific literature often lag behind the actual discoveries, and patent applications in the United States and other jurisdictions are typically not published until 18 months after filing, or in some cases not published at all. Therefore, neither we nor our licensors can know with certainty whether either we or our

licensors were the first to make the inventions claimed in the patents and patent applications we own or in-license now or in the future, or that either we or our licensors were the first to file for patent protection of such inventions. As a result, the issuance, scope, validity, enforceability and commercial value of our owned and in-licensed patent rights are highly uncertain. Moreover, our owned and in-licensed pending and future patent applications may not result in patents being issued which protect our technology and product candidates, in whole or in part, or which effectively prevent others from commercializing competitive technologies and products. Changes in either the patent laws or interpretation of the patent laws in the United States and other countries may diminish the value of our patents and our ability to obtain, protect, maintain, defend and enforce our patent rights, narrow the scope of our patent protection and, more generally, could affect the value or narrow the scope of our patent rights.

Moreover, we or our licensors may be subject to a third-party preissuance submission of prior art to the United States Patent and Trademark Office, or USPTO, or become involved in opposition, derivation, revocation, reexamination, inter partes review, post-grant review or interference proceedings challenging our patent rights or the patent rights of others. An adverse determination in any such submission, proceeding or litigation could reduce the scope of, or invalidate, our patent rights, allow third parties to commercialize our technology or product candidates and compete directly with us, without payment to us, or result in our inability to manufacture or commercialize drugs without infringing third-party patent rights. If the breadth or strength of protection provided by our patents and patent applications is threatened, regardless of the outcome, it could dissuade companies from collaborating with us to license, develop or commercialize current or future product candidates.

Additionally, the coverage claimed in a patent application can be significantly reduced before the patent is issued, and its scope can be reinterpreted after issuance. Even if our owned and in-licensed patent applications issue as patents, they may not issue in a form that will provide us with any meaningful protection, prevent competitors from competing with us or otherwise provide us with any competitive advantage. The issuance of a patent is not conclusive as to its inventorship, scope, validity or enforceability, and our owned and in-licensed patents may be challenged in the courts or patent offices in the United States and abroad. Such challenges may result in loss of exclusivity or freedom to operate or in patent claims being narrowed, invalidated or held unenforceable, in whole or in part, which could limit our ability to stop others from using or commercializing similar or identical technology and products, or limit the duration of the patent protection of our technology and product candidates. Such proceedings also may result in substantial cost and require significant time from our management and employees, even if the eventual outcome is favorable to us. 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. Furthermore, our competitors may be able to circumvent our owned or in-licensed patents by developing similar or alternative technologies or products in a non-infringing manner. As a result, our owned and in-licensed patent portfolio may not provide us with sufficient rights to exclude others from commercializing technology and products similar or identical to any of our technology and product candidates.

Our rights to develop and commercialize our gene editing technology and product candidates are subject, in part, to the terms and conditions of licenses granted to us by others.

We depend on intellectual property licensed from third parties, and our licensors may not always act in our best interest. If we fail to comply with our obligations under our intellectual property licenses, if the licenses are terminated, or if disputes regarding these licenses arise, we could lose significant rights that are important to our business.

We have licensed and are dependent on certain patent rights and proprietary technology from third parties that are important or necessary to the development of our gene editing technology and product candidates. For example, we are a party to the ARCLA, the Cas9 License Agreement, the Acuitas Agreement, the Novartis Agreement, and other license agreements, pursuant to which we in-license and have acquired key patents and patent applications for our gene editing technology, LNP technology and product candidates. These license agreements impose various diligence, milestone payment, royalty, insurance and other obligations on us. If we fail to comply with these obligations, our licensors may have the right to terminate our license, in which event we may not be able to develop or market our gene editing technology or product candidates covered by the intellectual property licensed under these agreements.

These and other licenses may not provide exclusive rights to use such intellectual property and technology in all relevant fields of use and in all territories in which we may wish to develop or commercialize our gene editing technology and product candidates in the future. Some licenses and acquired patents granted to us are expressly subject to certain preexisting rights held by the licensor or certain third parties. As a result, we may not be able to prevent competitors from developing and commercializing competitive products in certain territories or fields. If we determine that rights to such excluded fields are necessary to commercialize our product candidates or maintain our competitive advantage, we may need to obtain a license from such third party in order to continue developing, manufacturing or marketing our product candidates. We may not be able to obtain such a license on an exclusive basis, on commercially reasonable terms, or at

all, which could prevent us from commercializing our product candidates or allow our competitors or others the chance to access technology that is important to our business.

In addition, pursuant to the Cas9 License Agreement, under certain specific circumstances, Harvard and Broad may grant a license to the patents that are the subject of such license agreements to a third party in the same field as such patents are licensed to us. Such third party may then have full rights that are the subject of the Cas9 License Agreement, which could impact our competitive position and enable a third party to commercialize products similar to our potential future product candidates and technology. Any grant of rights to a third party in this scenario would narrow the scope of our rights to the patents and patent applications we have in-licensed from Harvard and Broad.

We do not have complete control in the preparation, filing, prosecution, maintenance, enforcement and defense of patents and patent applications covering the technology that we license or have acquired from third parties. It is possible that our licensors’ enforcement of patents against infringers or defense of such patents against challenges of validity or claims of enforceability may be less vigorous than if we had conducted them ourselves, or may not be conducted in accordance with our best interests. We cannot be certain that these patents and patent applications will be prepared, filed, prosecuted, maintained, enforced and defended in a manner consistent with the best interests of our business. If our licensors fail to prosecute, maintain, enforce and defend such patents, or lose rights to those patents or patent applications, the rights we have licensed may be reduced or eliminated, our right to develop and commercialize any of our product candidates we may develop that are the subject of such licensed rights could be adversely affected and we may not be able to prevent competitors from making, using and selling competing products.

Our licensors may have relied on third-party consultants or collaborators or on funds from third parties such that our licensors are not the sole and exclusive owners of the patents we in-licensed. If other third parties have ownership rights to our in-licensed patents, the license granted to us in jurisdictions where the consent of a co-owner is necessary to grant such a license may not be valid and such co-owners may be able to license such patents to our competitors, and our competitors could market competing products and technology. In addition, our rights to our in-licensed patents and patent applications are dependent, in part, on inter-institutional or other operating agreements between the joint owners of such in-licensed patents and patent applications. If one or more of such joint owners breaches such inter-institutional or operating agreements, our rights to such in-licensed patents and patent applications may be adversely affected. Any of these events could have a material adverse effect on our competitive position, business, financial conditions, results of operations and prospects.

Furthermore, inventions contained within some of our in-licensed patents and patent applications were made using U.S. government funding. We rely on our licensors to ensure compliance with applicable obligations arising from such funding, such as timely reporting, an obligation associated with our in-licensed patents and patent applications. The failure of our licensors to meet their obligations may lead to a loss of rights or the unenforceability of relevant patents. For example, the U.S. government could have certain rights in such in-licensed patents, including a non-exclusive license authorizing the U.S. government to use the invention or to have others use the invention on its behalf. If the U.S. government decides to exercise these rights, it is not required to engage us as its contractor in connection with doing so. The U.S. government’s rights may also permit it to disclose the funded inventions and technology to third parties and to exercise march-in rights to use or allow third parties to use the technology we have licensed that was developed using U.S. government funding. The U.S. government may also exercise its march-in rights if it determines that action is necessary because we or our licensors failed to achieve practical application of the U.S. government-funded technology, because action is necessary to alleviate health or safety needs, to meet requirements of federal regulations or to give preference to U.S. industry. In addition, our rights in such in-licensed U.S. government-funded inventions may be subject to certain requirements to manufacture product candidates embodying such inventions in the United States. Any of the foregoing could harm our business, financial condition, results of operations and prospects significantly.

In the event any of our third-party licensors determine that, in spite of our efforts, we have materially breached a license agreement or have failed to meet certain obligations thereunder, it may elect to terminate the applicable license agreement or, in some cases, one or more license(s) under the applicable license agreement, and such termination would result in us no longer having the ability to develop and commercialize product candidates and technology covered by that license agreement or license. In the event of such termination of a third-party in-license, or if the underlying patents under a third-party in-license fail to provide the intended exclusivity, competitors would have the freedom to seek regulatory approval of, and to market, products identical to ours. Any of these events could have a material adverse effect on our competitive position, business, financial conditions, results of operations and prospects.

Our owned and in-licensed patents and patent applications and other intellectual property may be subject to priority or inventorship disputes, interferences and similar proceedings. If we or our licensors are unsuccessful in any of these proceedings, we may be required to obtain licenses from third parties, which may not be available on commercially reasonable terms or at all, or to cease the development, manufacture, and commercialization of

我们可能开发的一个或多个候选产品，这可能会对我们的业务产生实质性的不利影响。

我们拥有选择权的某些美国专利和一项美国专利申请由布罗德和麻省理工学院共同拥有，在某些情况下由布罗德、麻省理工学院和哈佛共同拥有，我们统称为波士顿许可方，并参与了美国干扰编号106,048与加州大学、维也纳大学和Emmanuelle Charpentier共同拥有的一项美国专利申请，我们统称为CVC。2018年9月10日，联邦巡回上诉法院(CAFC)确认了美国专利商标局(PTAB)的专利审判和上诉委员会，认为没有事实干预。干扰是美国专利商标局内的一种程序，目的是确定由不同当事人提出的专利权利要求的标的的发明优先权。

2019年6月24日，PTAB宣布CVC共同拥有的14项美国专利申请与波士顿许可方共同拥有的13项美国专利和1项美国专利申请之间存在第二次干扰(美国干扰编号106,115)。在已宣布的干预中，CVC被指定为初级当事人，波士顿许可方被指定为高级当事人。2022年2月28日，PTAB裁定，波士顿许可方在干扰的第1项方面优先于CVC：在真核细胞中发挥作用的单个RNA CRISPR-Cas9系统。因此，CVC涉及这一干扰的专利申请被认为是不可申请专利的。2022年9月，CVC对PTAB的决定向CAFC提出上诉，上诉仍在进行中。

2020年12月20日，PTAB宣布，ToolGen，Inc.拥有的一项美国专利申请与波士顿许可方共同拥有的14项美国专利和两项美国专利申请之间存在干扰(美国干扰编号106,126)。在声明的干预中，波士顿许可方被指定为初级方，而ToolGen，Inc.被指定为高级方。

On June 21, 2021, the PTAB declared an interference (U.S. Interference No. 106,133) between one U.S. patent application owned by Sigma-Aldrich Co., LLC and 14 U.S. patents and two U.S. patent applications that are co-owned by the Boston Licensing Parties. In the declared interference, Boston Licensing Parties have been designated as the junior party and Sigma-Aldrich Co., LLC has been designated as the senior party.

The PTAB has currently suspended these subsequent interference proceedings with Toolgen and Sigma-Aldrich, pending the CAFC’s decision of the appeal between the CVC and the Boston Licensing Parties over the outcome of the second interference.

As a result of the declaration of interference, an adversarial proceeding in the USPTO before the PTAB has been initiated, which is declared to ultimately determine priority, specifically and which party was first to invent the claimed subject matter. An interference is typically divided into two phases. The first phase is referred to as the motions or preliminary motions phase while the second is referred to as the priority phase. In the first phase, each party may raise issues including but not limited to those relating to the patentability of a party’s claims based on prior art, written description, and enablement. A party also may seek an earlier priority benefit or may challenge whether the declaration of interference was proper in the first place. Priority, or a determination of who first invented the commonly claimed invention, is determined in the second phase of an interference. Although we cannot predict with any certainty how long each phase will actually take, each phase may take approximately a year or longer before a decision is made by the PTAB. It is possible for motions filed in the preliminary motions phase to be dispositive of the interference proceeding, such that the second priority phase is not reached.

We or our licensors are subject to and may in the future become a party to similar proceedings or priority disputes in Europe or other foreign jurisdictions. For example, certain European patents that we have in-licensed from Broad were previously revoked in their entirety by the European Patent Office Opposition Division, or the Opposition Division. The Broad subsequently appealed and in March 2024, the Board of Appeals of the European Patent Office rendered a decision which overturned the prior revocations and remanded the cases back to the Opposition Division for further proceedings in connection with any remaining challenges. It is uncertain when or in what manner the Opposition Division will act on the remanded cases involving the in-licensed European patents.

There can be no assurance that the current appeal or these pending U.S. interference proceedings or the European proceedings will be ultimately resolved in favor of the Boston Licensing Parties. If the appeal in the second interference favors CVC, or 106,126, or 106,133 interference resolves in favor of Toolgen, Inc. or Sigma-Aldrich Co., LLC, respectively, or if the Boston Licensing Parties’ patents and patent application are narrowed, invalidated, or held unenforceable, we will lose the ability to license the optioned patents and patent application and our ability to commercialize our product candidates may be adversely affected if we cannot obtain a license to relevant third-party patents that cover our product candidates. We may not be able to obtain any required license on commercially reasonable terms or at all. Even if we were able to obtain a license, it could be nonexclusive, thereby giving our competitors and other third parties access to the same technologies licensed to us, and it could require us to make substantial licensing and royalty payments. If we are unable to obtain a necessary license to a third-party patent on commercially reasonable terms,

we may be unable to commercialize our gene editing technology or product candidates or such commercialization efforts may be significantly delayed, which could in turn significantly harm our business.

We or our licensors may also be subject to claims that former employees, collaborators, or other third parties have an interest in our owned patent applications or in-licensed patents or patent applications or other intellectual property as an inventor or co-inventor. If we are unable to obtain an exclusive license to any such third-party co-owners’ interest in such patent applications, such co-owners rights may be subject, or in the future subject, to assignment or license to other third parties, including our competitors. In addition, we may need the cooperation of any such co-owners to enforce any patents that issue from such patent applications against third parties, and such cooperation may not be provided to us.

If we or our licensors are unsuccessful in any interference proceedings or other priority, validity (including any patent oppositions) or inventorship disputes to which we or they are subject, we may lose valuable intellectual property rights through the loss of one or more of our owned, licensed or optioned patents, or such patent claims may be narrowed, invalidated or held unenforceable, or through loss of exclusive ownership of or the exclusive right to use our owned or in-licensed patents. In the event of loss of patent rights as a result of any of these disputes, we may be required to obtain and maintain licenses from third parties, including parties involved in any such interference proceedings or other priority or inventorship disputes. Such licenses may not be available on commercially reasonable terms or at all, or may be non-exclusive. If we are unable to obtain and maintain such licenses, we may need to cease the development, manufacture and commercialization of one or more of the product candidates we may develop. The loss of exclusivity or the narrowing of our patent claims could limit our ability to stop others from using or commercializing similar or identical technology and product candidates. Even if we or our licensors are successful in an interference proceeding, other similar priority disputes, or inventorship or ownership disputes, it could result in substantial costs and be a distraction to management and other employees. Any of the foregoing could result in a material adverse effect on our business, financial condition, results of operations or prospects.

If we fail to comply with our obligations in our intellectual property licensing arrangements with third parties, or otherwise experience disruptions to our business relationships with our licensors, we could lose intellectual property rights that are important to our business.

We are party to agreements, and we may enter into additional arrangements, with third parties that may impose diligence, development and commercialization timelines, milestone payment, royalty, insurance and other obligations on us. We have existing agreements, pursuant to which we are obligated to pay royalties on net product sales of product candidates or related technologies to the extent they are covered by the agreements. If we fail to comply with such obligations under current or future agreements, our counterparties may have the right to terminate these agreements or require us to grant them certain rights. Such an occurrence could materially adversely affect the value of any product candidate being developed under any such agreement. Termination of these agreements or reduction or elimination of our rights under these agreements may result in our having to negotiate new or reinstated agreements with less favorable terms, or cause us to lose our rights under these agreements, including our rights to important intellectual property or technology, which would have a material adverse effect on our business, financial condition, results of operations and prospects. While we still face all of the risks described herein with respect to those agreements, we cannot prevent third parties from also accessing those technologies. In addition, our licenses may place restrictions on our future business opportunities.

Disputes may arise regarding intellectual property subject to a licensing agreement, including:

In addition, the agreements under which we currently license intellectual property or technology from third parties are complex, and certain provisions in such agreements may be susceptible to multiple interpretations. The resolution of any contract interpretation disagreement that may arise could narrow what we believe to be the scope of our rights to the relevant intellectual property or technology, or increase what we believe to be our financial or other obligations under the relevant agreement, either of which could have a material adverse effect on our business, financial condition, results of operations and prospects. Moreover, if disputes over intellectual property that we have licensed prevent or impair our ability to maintain our current licensing arrangements on commercially acceptable terms, we may be unable to

successfully develop and commercialize the affected technology and product candidates, which could have a material adverse effect on our business, financial conditions, results of operations and prospects.

Our current or future licensors may have relied on third-party consultants or collaborators or on funds from third parties such that our licensors are not the sole and exclusive owners of the intellectual property or intellectual property rights we in-license. If other third parties have ownership rights to intellectual property or intellectual property rights we in-license, they may be able to license such intellectual property or intellectual property rights to our competitors, and our competitors could market competing products and technology. This could have a material adverse effect on our competitive position, business, financial conditions, results of operations and prospects.

In spite of our best efforts, our licensors might conclude that we have materially breached our license agreements and might therefore terminate the license agreements, thereby removing our ability to develop and commercialize product candidates and technology covered by these license agreements. If these in-licenses are terminated, or if the underlying intellectual property fails to provide the intended exclusivity, competitors would have the freedom to seek regulatory approval of, and to market, products and technologies identical to ours. This could have a material adverse effect on our competitive position, business, financial condition, results of operations and prospects.

If we are unable to obtain licenses from third parties on commercially reasonable terms or fail to comply with our obligations under such agreements, our business could be harmed.

We currently have rights to intellectual property, through licenses from third parties, to identify and develop product candidates, and we expect to seek to expand our product candidate pipeline in part by in-licensing the rights to key technologies. Although we have succeeded in licensing technologies from third-party licensors including Harvard, Broad, Beam, Acuitas, and Novartis in the past, we cannot assure our stockholders that we will be able to in-license or acquire the rights to any product candidates or technologies from third parties on acceptable terms or at all.

Various third parties practice in competitive technology areas and may have issued patents or patent applications that will issue as patents in the future, which could impede or preclude our ability to commercialize our product candidates. For any third-party patents that could be relevant to our product candidates, we rely in part on the “safe harbor” or research exemption under 35 U.S.C. § 271(e)(1), which exempts from patent infringement activities related to pursuing FDA approval for a drug product. However, while U.S. patent law provides such a “safe harbor” to our clinical product candidates under this provision, that exemption may expire when a BLA is submitted. Given the uncertainty of clinical trials, we cannot be certain of the timing of their completion and it is possible that we may submit a BLA for one of our product candidates at a time when one or more relevant third-party patents is in force.

It may therefore be necessary for us to use the patented or proprietary technology of third parties to commercialize our products, in which case we would be required to obtain a license from these third parties. If we are unable to license such technology, or if we are forced to license such technology on unfavorable terms, our business could be materially harmed. If we are unable to obtain a necessary license, we may be unable to develop or commercialize the affected product candidates, which could materially harm our business and the third parties owning such intellectual property rights could seek either an injunction prohibiting our sales or an obligation on our part to pay royalties and/or other forms of compensation. Even if we are able to obtain a license, it may be non-exclusive, thereby giving our competitors access to the same technologies licensed to us.

Furthermore, there has been extensive patenting activity in the field of gene editing, and pharmaceutical companies, biotechnology companies, and academic institutions are competing with us or are expected to compete with us in the field of gene editing technology and filing patent applications potentially relevant to our business, and there may be third-party patent applications that, if issued, may allow the third party to circumvent our patent rights. Because of the large number of patents issued and patent applications filed in our field, these and other third parties could allege they have patent rights encompassing our product candidates, technologies or methods. In order to market our product candidates, we may find it necessary or prudent to obtain licenses from such third-party intellectual property holders. However, we may be unable to secure such licenses or otherwise acquire or in-license any compositions, methods of use, processes, or other intellectual property rights from third parties that we identify as necessary for product candidates and gene editing technology we may develop. We may also require licenses from third parties for certain gene editing technologies including certain delivery and gene editing compositions and methods that we are evaluating, or may in the future evaluate, for use with product candidates we may develop. In addition, some of our owned patent applications and in-licensed patents and patent applications may be determined to be co-owned with third parties. With respect to any patents co-owned with third parties, we may require licenses to such co-owners’ interest to such patents. If we are unable to obtain an exclusive license to any such third-party co-owners’ interest in such patents or patent applications, such co-owners may be able to license their rights to other third parties, including our competitors, and our competitors could market competing products and technology. In addition, we may need the cooperation of any such co-owners of our patents in order to enforce such patents against third parties, and such cooperation may not be provided to us.

Additionally, we may collaborate with academic institutions to accelerate our preclinical research or development under written agreements with these institutions. In certain cases, these institutions provide us with an option to negotiate a license to any of the institution’s rights in technology resulting from the collaboration. Even if we hold such an option, we may be unable to negotiate a license from the institution within the specified timeframe or under terms that are acceptable to us. If we are unable to do so, the institution may offer the intellectual property rights to others, potentially blocking our ability to pursue our program.

In addition, the licensing or acquisition of third-party intellectual property rights is a highly competitive area, and a number of more established companies are also pursuing strategies to license or acquire third party intellectual property rights that we may consider attractive or necessary. These established companies may have a competitive advantage over us due to their size, capital resources and greater clinical development and commercialization capabilities. In addition, companies that perceive us to be a competitor may be unwilling to assign or license rights to us. We also may be unable to license or acquire third party intellectual property rights on terms that would allow us to make an appropriate return on our investment or at all. If we are unable to successfully obtain rights to required third party intellectual property rights or maintain the existing intellectual property rights we have, we may have to abandon development of the relevant program or product candidate, which could have a material adverse effect on our business, financial condition, results of operations, and prospects.

If we are unable to obtain rights to required third-party intellectual property rights or maintain the existing intellectual property rights we have, we may be required to expend significant time and resources to redesign our technology, product candidates, or the methods for manufacturing them or to develop or license replacement technology, all of which may not be feasible on a technical or commercial basis. If we are unable to do so, we may be unable to develop or commercialize the affected technology and product candidates, which could harm our business, financial condition, results of operations and prospects significantly.

Additionally, if we fail to comply with our obligations under license agreements, our counterparties may have the right to terminate these agreements, in which event we might not be able to develop, manufacture or market, or may be forced to cease developing, manufacturing or marketing, any product that is covered by these agreements or may face other penalties under such agreements. Such an occurrence could materially adversely affect the value of the product candidate being developed under any such agreement. Termination of these agreements or reduction or elimination of our rights under these agreements, or restrictions on our ability to freely assign or sublicense our rights under such agreements when it is in the interest of our business to do so, may result in our having to negotiate new or reinstated agreements with less favorable terms, cause us to lose our rights under these agreements, including our rights to important intellectual property or technology or impede, or delay or prohibit the further development or commercialization of one or more product candidates that rely on such agreements.

The intellectual property landscape around genome editing technology, including base editing and delivery, is highly dynamic, and third parties may initiate legal proceedings alleging that we are infringing, misappropriating, or otherwise violating their intellectual property rights, the outcome of which would be uncertain and may prevent, delay or otherwise interfere with our product discovery and development efforts.

Our commercial success depends upon our ability and the ability of our collaborators to research, develop, manufacture, market and sell our product candidates and use our proprietary technologies without infringing, misappropriating or otherwise violating the intellectual property rights of third parties. The field of genome editing, especially in the area of in vivo gene editing technology, including base editing and delivery technology, is still new, and no such product candidates utilizing in vivo gene editing have been approved. Due to the intense research and development that is taking place by several companies, including us and our competitors, in this field, the intellectual property landscape is evolving and in flux, and it may remain uncertain for the coming years. The biotechnology and pharmaceutical industries are characterized by extensive and complex litigation regarding patents and other intellectual property rights as well as administrative proceedings for challenging patents, including interference, derivation, inter partes review, post grant review, and reexamination proceedings before the USPTO or oppositions and other comparable proceedings in foreign jurisdictions. There may be significant intellectual property related litigation and proceedings relating to our owned and in-licensed, and other third party, intellectual property and proprietary rights in the future. We may be subject to and may in the future become party to, or threatened with, adversarial proceedings or litigation regarding intellectual property rights with respect to our gene editing platform technology and any product candidates we may develop, including interference proceedings, post-grant review, inter partes review, and derivation proceedings before the USPTO and similar proceedings in foreign jurisdictions such as oppositions before the European Patent Office. Numerous U.S. and foreign issued patents and pending patent applications that are owned by third parties exist in the fields in which we are developing our product candidates and they may assert infringement claims against us based on existing patents or patents that may be granted in the future, regardless of their merit.

As the biotechnology and pharmaceutical industries expand and more patents are issued, the risk increases that our gene editing technology and product candidates may give rise to claims of infringement of the patent rights of others. Moreover, it is not always clear to industry participants, including us, which patents cover various types of therapies, products or their methods of use or manufacture. We are aware of certain third-party patent applications that, if issued, may be construed to cover our gene editing technology and product candidates. There may also be third-party patents of which we are currently unaware with claims to technologies, methods of manufacture or methods for treatment related to the use or manufacture of our product candidates. Because patent applications can take many years to issue, there may be currently pending patent applications that may later result in issued patents that our product candidates may infringe. In addition, third parties may obtain patents in the future and claim that use of our technologies infringes upon these patents.

It is possible that we have failed to identify relevant third-party patents or applications that our product candidates and programs may infringe. Because patent applications can take many years to issue, may be confidential for 18 months or more after filing and can be revised before issuance, there may be applications now pending which may later result in issued patents that may be infringed by the manufacture, use, sale or importation of any product candidates we may develop or our technology, and we may not be aware of such patents. Furthermore, applications filed before November 29, 2000 and certain applications filed after that date that will not be filed outside the United States may remain confidential until a patent issues. Moreover, it is difficult for industry participants, including us, to identify all third-party patent rights that may be relevant to any product candidates we may develop and our technologies because patent searching is imperfect due to differences in terminology among patents, incomplete databases and the difficulty in assessing the meaning of patent claims. We may fail to identify relevant patents or patent applications or may identify pending patent applications of potential interest but incorrectly predict the likelihood that such patent applications may issue with claims of relevance to our technology. In addition, we may incorrectly conclude that a third-party patent is invalid, unenforceable or not infringed by our activities. Additionally, pending patent applications that have been published can, subject to certain limitations, be later amended in a manner that could cover our technologies, any product candidates we may develop or the use of any product candidates we may develop.

Third parties may assert infringement claims against us based on existing patents or patents that may be granted in the future, regardless of their merit. There is a risk that third parties may choose to engage in litigation with us to enforce or to otherwise assert their patent rights against us. Even if we believe such claims are without merit, a court of competent jurisdiction could hold that these third-party patents are valid, enforceable and infringed, which could adversely affect our ability to commercialize our product candidates or any other of our product candidates or technologies covered by the asserted third-party patents. In order to successfully challenge the validity of any such U.S. patent in federal court, we would need to overcome a presumption of validity. As this burden is a high one requiring us to present clear and convincing evidence as to the invalidity of any such U.S. patent claim, there is no assurance that a court of competent jurisdiction would invalidate the claims of any such U.S. patent.

Numerous third-party U.S. and foreign issued patents and pending patent applications exist in the fields in which we are developing product candidates. Our product candidates make use of CRISPR-based gene editing technology, which is a field that is highly active for patent filings. The extensive patent filings related to CRISPR and Cas make it difficult for us to assess the full extent of relevant patents and pending applications that may cover our gene editing technology and product candidates and their use or manufacture. There may be third-party patents or patent applications, including patents held or controlled by our competitors with claims to materials, formulations, methods of manufacture or methods for treatment related to the use or manufacture of our gene editing technology and product candidates.

If we are found to infringe, misappropriate or otherwise violate a third party’s valid and enforceable intellectual property rights, we could be required to obtain a license from such third party to continue developing, manufacturing and marketing our product candidates and technology. However, we may not be able to obtain any required license on commercially reasonable terms or at all. Even if we were able to obtain a license, it could be non-exclusive, thereby giving our competitors and other third parties access to the same technologies licensed to us, and it could require us to make substantial licensing and royalty payments. We may be forced, including by court order, to cease developing, manufacturing and commercializing the infringing technology or product candidates. In addition, we could be found liable for monetary damages, including treble damages and attorneys’ fees, if we are found to have willfully infringed a patent or other intellectual property right. A finding of infringement may prevent us from manufacturing and commercializing our product candidates or force us to cease some of our business operations, which could harm our business. Claims that we have misappropriated the confidential information or trade secrets of third parties could have a similar negative impact on our business, financial condition, results of operations and prospects.

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

Patents have a limited lifespan. The terms of individual patents depend upon the legal term for patents in the countries in which they are granted. In most countries, including the United States, if all maintenance fees are timely paid, the natural

expiration of a patent is generally 20 years from its earliest non-provisional filing date in the applicable country. However, the actual protection afforded by a patent varies from country to country, and depends upon many factors, including the type of patent, the scope of its coverage, the availability of regulatory-related extensions, the availability of legal remedies in a particular country and the validity and enforceability of the patent. Various extensions may be available, but the life of a patent, and the protection it affords, is limited. Even if patents covering our product candidates are obtained, once the patent life has expired, we may be open to competition from competitive products, including biosimilars. Given the amount of time required for the development, testing and regulatory review of new product candidates, patents protecting such candidates might expire before or shortly after such candidates are commercialized. As a result, our owned and licensed patent portfolio may not provide us with sufficient rights to exclude others from commercializing products similar or identical to ours.

Our product candidates may face competition from biosimilars approved through an abbreviated regulatory pathway.

The Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act of 2010, or collectively the PPACA, includes a subtitle called the Biologics Price Competition and Innovation Act of 2009, or BPCIA, which created an abbreviated approval pathway for biological products that are biosimilar to or interchangeable with an FDA-approved reference biological product. Under the BPCIA, an application for a biosimilar product may not be submitted to the FDA until four years following the date that the reference product was first approved by the FDA. In addition, the approval of a biosimilar product may not be made effective by the FDA until 12 years from the date on which the reference product was first approved. During this 12-year period of regulatory exclusivity, another company may still market a competing version of the reference product if the FDA approves a full BLA for the competing product containing the sponsor’s own preclinical data and data from adequate and well-controlled clinical trials to demonstrate the safety, purity and potency of the competing product.

In December 2022, Congress clarified through the Food and Drug Omnibus Reform Act that the FDA may approve multiple first interchangeable biosimilar biological products so long as the products are all approved on the same first day on which such a product is approved as interchangeable with the reference product and the exclusivity period may be shared amongst multiple first interchangeable products. More recently, in October 2023, the FDA issued its first interchangeable exclusivity determination under the BPCIA.

We believe that any of our product candidates approved as a biological product under a BLA should qualify for the 12-year period of exclusivity. Nonetheless, the approval of biosimilar products referencing any of our product candidates would have a material adverse impact on our business due to increased competition and pricing pressures. Moreover, there is a risk that any exclusivity we do receive could be shortened due to Congressional action or otherwise, or that the FDA will not consider our product candidates to be reference products for competing products, potentially creating the opportunity for biosimilar competition sooner than anticipated. Other aspects of the BPCIA, some of which may impact the BPCIA exclusivity provisions, have also been the subject of recent litigation. The extent to which a biosimilar, once approved, will be substituted for any one of our reference products in a way that is similar to traditional generic substitution for non-biological products is not yet clear, and will depend on a number of marketplace and regulatory factors that are still developing. The ultimate impact, implementation, and meaning of the BPCIA are subject to uncertainty, and any new regulations, guidance, policies or processes adopted by the FDA to implement the law could have a material adverse effect on the future commercial prospects for our biological products.

If we do not obtain patent term extension in the United States under the Hatch-Waxman Act and in foreign countries under similar legislation, thereby potentially extending the term of our marketing exclusivity for any product candidates we may develop, our business may be materially harmed.

In the United States, the patent term of a patent that covers an FDA-approved drug may be eligible for limited patent term extension, which permits patent term restoration as compensation for the patent term lost during the FDA regulatory review process. The Drug Price Competition and Patent Term Restoration Act of 1984, also known as the Hatch-Waxman Act, permits a patent term extension of up to five years beyond the expiration of the patent. The length of the patent term extension is related to the length of time the drug is under clinical development and regulatory review. Patent extension cannot extend the remaining term of a patent beyond a total of 14 years from the date of product approval, and only one patent applicable to and that covers an approved drug may be extended. Similar provisions are available in Europe, such as supplementary protection certificates, and certain other non-United States jurisdictions to extend the term of a patent that covers an approved drug. While, in the future, if and when our product candidates receive FDA approval, we expect to apply for patent term extensions on patents covering those product candidates, there is no guarantee that the applicable authorities will agree with our assessment of whether such extensions should be granted, and even if granted, the length of such extensions. We may not be granted patent term extension either in the United States or in any foreign country because of, for example, failing to exercise due diligence during the testing phase or regulatory review process,

failing to apply within applicable deadlines, failing to apply prior to expiration of relevant patents or otherwise failing to satisfy applicable requirements. Moreover, the term of extension, as well as the scope of patent protection during any such extension, afforded by the governmental authority could be less than we request. If we are unable to obtain any patent term extension or the term of any such extension is less than we request, our competitors may obtain approval of competing products following the expiration of our patent rights, and our business, financial condition, results of operations and prospects could be materially harmed.

It is possible that we will not obtain patent term extension under the Hatch-Waxman Act for a U.S. patent covering any of our product candidates that we may identify even where that patent is eligible for patent term extension, or if we obtain such an extension, it may be for a shorter period than we had sought.

Changes to patent laws in the United States and other jurisdictions could diminish the value of patents in general, thereby impairing our ability to protect our gene editing platform technology and product candidates.

As is the case with other biotech and pharmaceutical companies, our success is heavily dependent on intellectual property, particularly patents. Obtaining and enforcing patents in the biopharmaceutical industry involve both technological and legal complexity, and is therefore costly, time-consuming and inherently uncertain.

Changes in either the patent laws or interpretation of patent laws in the United States, including patent reform legislation such as the Leahy-Smith America Invents Act, or the Leahy-Smith Act, could increase the uncertainties and costs surrounding the prosecution of our owned and in-licensed patent applications and the maintenance, enforcement or defense of our owned and in-licensed issued patents. The Leahy-Smith Act includes a number of significant changes to United States patent law. These changes include provisions that affect the way patent applications are prosecuted, redefine prior art, provide more efficient and cost-effective avenues for competitors to challenge the validity of patents, and enable third-party submission of prior art to the USPTO during patent prosecution and additional procedures to attack the validity of a patent at USPTO-administered post-grant proceedings, including post-grant review, inter partes review, and derivation proceedings. Because of a lower evidentiary standard in USPTO proceedings compared to the evidentiary standard in United States federal courts necessary to invalidate a patent claim, a third party could potentially provide evidence in a USPTO proceeding sufficient for the USPTO to hold a claim invalid even though the same evidence would be insufficient to invalidate the claim if first presented in a district court action. Accordingly, a third party may attempt to use the USPTO procedures to invalidate our patent claims that would not have been invalidated if first challenged by the third party as a defendant in a district court action.

Assuming that other requirements for patentability are met, prior to March 2013, in the United States, the first to invent the claimed invention was entitled to the patent, while outside the United States, the first to file a patent application was entitled to the patent. After March 2013, under the Leahy-Smith Act, the United States transitioned to a first-to-file system in which, assuming that the other statutory requirements for patentability are met, the first inventor to file a patent application will be entitled to the patent on an invention regardless of whether a third party was the first to invent the claimed invention. As such, the Leahy-Smith Act and its implementation could increase the uncertainties and costs surrounding the prosecution of our patent applications and the enforcement or defense of our issued patents, all of which could have a material adverse effect on our business, financial condition, results of operations and prospects.

In addition, the patent positions of companies in the development and commercialization of biologics and pharmaceuticals are particularly uncertain. Past U.S. Supreme Court rulings have narrowed the scope of patent protection available in certain circumstances and weakened the rights of patent owners in certain situations. This combination of events has created uncertainty with respect to the validity and enforceability of patents once obtained. Depending on future actions by the U.S. Congress, the federal courts, and the USPTO, the laws and regulations governing patents could change in unpredictable ways that could have a material adverse effect on our patent rights and our ability to protect, defend and enforce our patent rights in the future. For example, in the case, Assoc. for Molecular Pathology v. Myriad Genetics, Inc., the U.S. Supreme Court held that claims to certain DNA molecules are not patentable. More recently, in Amgen Inc. v. Sanofi, the U.S. Supreme Court affirmed the Federal Circuit’s holding that claims with functional language may pose high hurdles in fulfilling the enablement requirement for claims with broad functional language. We cannot predict how this and future decisions by the courts, the U.S. Congress or the USPTO may impact the value of our patents. Any similar adverse changes in the patent laws of other jurisdictions could also have a material adverse effect on our business, financial condition, results of operations and prospects.

Issued patents covering our product candidates could be found invalid or unenforceable if challenged in court. We may not be able to protect our trade secrets in court.

If we or one of our licensing partners initiates 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 or unenforceable. In patent litigation in the United States, defendant counterclaims alleging invalidity or unenforceability are

commonplace. Grounds for a validity challenge could be an alleged failure to meet any of several statutory requirements, including unpatentable subject matter, lack of novelty, obviousness, inadequate written description or non-enablement. In addition, patent validity challenges may, under certain circumstances, be based upon non-statutory obviousness-type double patenting, which, if successful, could result in a finding that the claims are invalid for obviousness-type double patenting or the loss of patent term, including a patent term adjustment granted by the USPTO, if a terminal disclaimer is filed to obviate a finding of obviousness-type double patenting. Grounds for an unenforceability assertion could be an allegation that someone connected with prosecution of the patent withheld information material to patentability from the USPTO, or made a misleading statement, during prosecution. Third parties also may 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, inter partes review and equivalent proceedings in foreign jurisdictions. Such proceedings could result in the revocation or cancellation of 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 the patent examiner and we or our licensing partners were unaware during prosecution. If a defendant were to prevail on a legal assertion of invalidity or unenforceability, we could 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.

In addition to the protection afforded by patents, we rely on trade secret protection and confidentiality agreements to protect proprietary know-how that is not patentable or that we elect not to patent, processes for which patents are difficult to enforce and any other elements of our product candidate discovery and development processes that involve proprietary know-how, information or technology that is not covered by patents. However, trade secrets can be difficult to protect, and some courts inside and outside the United States are less willing or unwilling to protect trade secrets. We seek to protect our proprietary technology and processes, in part, by entering into confidentiality agreements with our employees, consultants, scientific advisors and contractors. We cannot guarantee that we have entered into such agreements with each party that may have or have had access to our trade secrets or proprietary technology and processes. We also seek to preserve the integrity and confidentiality of our data and trade secrets by maintaining physical security of our premises and physical and electronic security of our information technology systems. While we have confidence in these individuals, organizations and systems, agreements or security measures may be breached, and we may not have adequate remedies for any breach. In addition, our trade secrets may otherwise become known or be independently discovered by competitors.

Intellectual property litigation or other legal proceedings relating to intellectual property could cause us to spend substantial resources and distract our personnel from their normal responsibilities.

Even if resolved in our favor, litigation or other legal proceedings relating to intellectual property claims may cause us to incur significant expenses and could distract our technical and management personnel from their normal responsibilities. In addition, there could be public announcements of the results of hearings, motions or other interim proceedings or developments and if securities analysts or investors perceive these results to be negative, it could have a substantial adverse effect on the price of our common stock. Such litigation or proceedings could substantially increase our operating losses and reduce the resources available for development activities or any future sales, marketing or distribution activities. We may not have sufficient financial or other resources to conduct such litigation or proceedings adequately. Some of our competitors may be able to sustain the costs of such litigation or proceedings more effectively than we can because of their greater financial resources and may also have an advantage in such proceedings due to their more mature and developed intellectual property portfolios. Uncertainties resulting from the initiation and continuation of intellectual property litigation or other proceedings could compromise our ability to compete in the marketplace.

Obtaining and maintaining 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.

Periodic maintenance, renewal and annuity fees and various other government fees on any issued patent and pending patent application must be paid to the USPTO and foreign patent agencies in several stages or annually over the lifetime of our owned and in-licensed patents and patent applications. The USPTO and various foreign governmental patent agencies require compliance with a number of procedural, documentary, fee payment and other similar provisions during the patent application process. In certain circumstances, we may rely on our licensing partners to pay these fees to, or comply with the procedural and documentary rules of, the relevant patent agency. With respect to our patents, we rely on outside firms and outside counsel to remind us of the due dates and to make payment after we instruct them to do so. While an inadvertent lapse can in many cases be cured by payment of a late fee or by other means in accordance with the applicable rules, there are situations in which noncompliance 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. Non-compliance events that could result in abandonment or lapse of a patent or patent application include failure to respond to official actions

within prescribed time limits, non-payment of fees and failure to properly legalize and submit formal documents. In such an event, potential competitors might be able to enter the market with similar or identical products or technology. If we or our licensors fail to maintain the patents and patent applications covering our product candidates, it would have a material adverse effect on our business, financial condition, results of operations and prospects.

We have limited foreign intellectual property rights and may not be able to protect our intellectual property and proprietary rights throughout the world.

We have limited intellectual property rights outside the United States. Filing, prosecuting and defending patents on product candidates in all countries throughout the world would be prohibitively expensive, and the laws of foreign countries may not protect our rights to the same extent as the laws of the United States. 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, and even where such protection is nominally available, judicial and governmental enforcement of such intellectual property rights may be lacking. 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 or licenses 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 them 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 intellectual property and proprietary rights generally. In addition, certain jurisdictions do not protect to the same extent or at all inventions that constitute new methods of treatment.

Proceedings to enforce our intellectual property and proprietary 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, could put our patent applications at risk of not issuing, and could provoke third parties to assert claims against us. We may not prevail in any lawsuits that we initiate, and the damages or other remedies awarded, if any, may not be commercially meaningful. Accordingly, our efforts to enforce our intellectual property and proprietary rights around the world may be inadequate to obtain a significant commercial advantage from the intellectual property that we develop or license.

Many countries have compulsory licensing laws under which a patent owner may be compelled to grant licenses to third parties. In addition, many countries 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 such patent. If we or any of our licensors are forced to grant a license to third parties with respect to any patents relevant to our business, our competitive position may be impaired, and our business, financial condition, results of operations and prospects may be adversely affected.

Furthermore, geo-political actions in the United States and in foreign countries could increase the uncertainties and costs surrounding the prosecution or maintenance of our patent applications or those of any current or future licensors and the maintenance, enforcement or defense of our issued patents or those of any current or future licensors. For example, the United States and foreign government actions related to Russia’s invasion of Ukraine may limit or prevent filing, prosecution and maintenance of patent applications in Russia. Government actions may also prevent maintenance of issued patents in Russia. These actions could result in abandonment or lapse of our licensed patents or patent applications, resulting in partial or complete loss of patent rights in Russia. If such an event were to occur, it could have a material adverse effect on our business. In addition, a decree was adopted by the Russian government in March 2022, allowing Russian companies and individuals to exploit inventions owned by patentees that have citizenship or nationality in, are registered in, or have a predominantly primary place of business or profit-making activities in the United States and other countries that Russia has deemed unfriendly without consent or compensation. Consequently, we would not be able to prevent third parties from practicing our inventions in Russia or from selling or importing products made using our inventions in and into Russia. Accordingly, our competitive position may be impaired, and our business, financial condition, results of operations and prospects may be adversely affected.

We may be subject to claims by third parties asserting that our employees, consultants or contractors have wrongfully used or disclosed confidential information of third parties, or we have wrongfully used or disclosed

alleged trade secrets of their current or former employers or claims asserting we have misappropriated their intellectual property, or claiming ownership of what we regard as our own intellectual property.

Many of our employees, consultants and contractors were previously employed at universities or other pharmaceutical or biotechnology companies, including our competitors or potential competitors. Although we try to ensure that our employees, consultants and contractors do not use the proprietary information or know-how of others in their work for us, we may be subject to claims that these individuals or we have used or disclosed intellectual property, including trade secrets or other proprietary information, of any such individual’s current or former employer. Litigation may be necessary to defend against these claims.

In addition, while it is our policy to require our employees, consultants and contractors who may be involved in the development of intellectual property to execute agreements assigning such intellectual property to us, we may be unsuccessful in executing such an agreement with each party who in fact develops intellectual property that we regard as our own. Our intellectual property assignment agreements with them may not be self-executing or may be breached, and we may be forced to bring claims against third parties, or defend claims they may bring against us, to determine the ownership of what we regard as our intellectual property. Such claims could have a material adverse effect on our business, financial conditions, results of operations and prospects.

If we fail in prosecuting or defending any such claims, in addition to paying monetary damages, we may lose valuable intellectual property rights or personnel, which could have a material adverse effect on our competitive business position and prospects. Such intellectual property rights could be awarded to a third party, and we could be required to obtain a license from such third party to commercialize our technology or products, which license may not be available on commercially reasonable terms, or at all, or such license may be non-exclusive. Even if we are successful in prosecuting or defending against such claims, litigation could result in substantial costs and be a distraction to our management and employees.

If we are unable to protect the confidentiality of our trade secrets, our business and competitive position would be harmed.

In addition to seeking patents for some of our technology and product candidates, we also rely on trade secrets and confidentiality agreements to protect our unpatented know-how, technology and other proprietary information, to maintain our competitive position. We seek to protect our trade secrets and other proprietary technology, in part, by entering into non-disclosure and confidentiality agreements with parties who have access to them, such as our employees, corporate collaborators, outside scientific collaborators, CROs, CMOs, consultants, advisors and other third parties. We also enter into confidentiality and invention or patent assignment agreements with our employees and consultants, but we cannot guarantee that we have entered into such agreements with each party that may have or has had access to our trade secrets or proprietary technology. Despite these efforts, any of these parties may breach the agreements and disclose our proprietary information, including our trade secrets, and we may not be able to obtain adequate remedies for such breaches. Detecting the disclosure or misappropriation of a trade secret and enforcing a claim that a party illegally disclosed or misappropriated a trade secret is difficult, expensive and time-consuming, and the outcome is unpredictable.

In addition to contractual measures, we try to protect the confidential nature of our proprietary information through other appropriate precautions, such as physical and technological security measures. However, trade secrets and know-how can be difficult to protect. These measures may not, for example, in the case of misappropriation of a trade secret by an employee or third party with authorized access, provide adequate protection for our proprietary information. Our security measures may not prevent an employee or consultant from misappropriating our trade secrets and providing them to a competitor, and any recourse we might take against this type of misconduct may not provide an adequate remedy to protect our interests fully. In addition, trade secrets may be independently developed by others in a manner that could prevent us from receiving legal recourse. If any of our confidential or proprietary information, such as our trade secrets, were to be disclosed or misappropriated, or if any of that information was independently developed by a competitor, our competitive position could be harmed.

In addition, some courts inside and outside of the United States are less willing or unwilling to protect trade secrets. If any of our trade secrets were to be lawfully obtained or independently developed by a competitor or other third party, we would have no right to prevent them, or those to whom they communicate it, from using that technology or information to compete with us. If any of our trade secrets were to be disclosed to or independently developed by a competitor or other third party, our competitive position would be materially and adversely harmed.

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

Any registered trademarks or trade names may be challenged, circumvented or declared generic or determined to be infringing on other marks. We may not be able to protect our rights to these trademarks and trade names, which we need

to build name recognition among potential partners or customers in our markets of interest. At times, competitors may adopt trade names or trademarks similar to ours, thereby impeding our ability to build brand identity and possibly leading to market confusion. In addition, there could be potential trade name or trademark infringement claims brought by owners of other registered trademarks or trademarks that incorporate variations of our registered or unregistered trademarks or trade names. Over the long term, if we are unable to establish name recognition based on our trademarks and trade names, then we may not be able to compete effectively and our business may be adversely affected. Our efforts to enforce or protect our proprietary rights related to trademarks, trade secrets, domain names, copyrights or other intellectual property may be ineffective and could result in substantial costs and diversion of resources and could adversely impact our financial condition or results of operations.

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. For example:

Should any of these events occur, they could have a material adverse effect on our business, financial condition, results of operations and prospects.

Even if any of our current or future product candidates receives marketing approval, it may fail to achieve the degree of market acceptance by physicians, patients, third-party payors and others in the medical community necessary for commercial success, and the market opportunity for any of such product candidates, if approved, may be smaller than we estimate.

If any of our current or future product candidates receives marketing approval, it may nonetheless fail to gain sufficient market acceptance by physicians, patients, third-party payors and others in the medical community. For example, current CVD treatments such as statins, ezetimibe, bempedoic acid, lomitapide, mipomersen and icosapent ethyl are well-established in the medical community, and physicians may continue to rely on these treatments.

Even if VERVE-101, VERVE-102, VERVE-201 or any other product candidate we develop meets its safety and efficacy endpoints in clinical trials, we cannot be certain that success in clinical trials will ensure success as a commercial product. For example, in September 2022, AstraZeneca and Ionis Pharmaceuticals, Inc. determined not to advance an antisense oligonucleotide PCSK9 inhibitor dosed once monthly via subcutaneous administration into Phase 3 clinical development for the treatment of hypercholesterolemia following a Phase 2b clinical trial that met its primary endpoint and achieved a statistically significant 62.3% reduction in low density lipoprotein cholesterol, or LDL-C, after 28 weeks compared to placebo on the basis that the results did not meet AstraZeneca’s target product profile criteria to invest in a broad Phase 3 development program.

Efforts to educate the medical community and third-party payors on the benefits of our product candidates may require significant resources and may not be successful. If our current or future product candidates do not achieve an adequate level of acceptance, we may not generate significant product revenues and we may not become profitable. The degree of market acceptance of our current or future product candidates, if approved for commercial sale, will depend on a number of factors, including:

Our assessment of the potential market opportunity for our current or future product candidates is based on industry and market data that we obtained from industry publications, research, surveys and studies conducted by third parties and our analysis of these data, research, surveys and studies. Industry publications and third-party research, surveys and studies generally indicate that their information has been obtained from sources believed to be reliable, although they do not guarantee the accuracy or completeness of such information. While we believe these industry publications and third-party research, surveys and studies are reliable, we have not independently verified such data. Our estimates of the potential market opportunities for our product candidates include a number of key assumptions based on our industry knowledge, industry publications and third-party research, surveys and studies, which may be based on a small sample size and fail

to accurately reflect market opportunities. While we believe that our internal assumptions are reasonable, no independent source has verified such assumptions. If any of our assumptions or estimates, or these publications, research, surveys or studies prove to be inaccurate, then the actual market for any of our product candidates may be smaller than we expect, and as a result our revenues from product sales may be limited and it may be more difficult for us to achieve or maintain profitability.

We face substantial competition, which may result in others discovering, developing or commercializing products before us or more successfully than we do.

The development and commercialization of new drug or biologic products is highly competitive. It is particularly competitive with respect to new products for CVD, for which the standard of care is well-established. We face competition with respect to our current product candidates, and will face competition with respect to any product candidates that we may seek to develop or commercialize in the future, from major pharmaceutical companies, specialty pharmaceutical companies and biotechnology companies worldwide. There are a number of large pharmaceutical and biotechnology companies that currently market and sell products or are pursuing the development of products for the treatment of many of the disease indications for which we are developing our product candidates. Some of these competitive products and therapies are based on scientific approaches that are similar to our approach, and others are based on entirely different approaches. Potential competitors also include academic institutions, government agencies and other public and private research organizations that conduct research, seek patent protection and establish collaborative arrangements for research, development, manufacturing and commercialization.

There are several approved products for LDL-C lowering or cardiovascular risk reduction, such as statins, ezetimibe, bempedoic acid, lomitapide, mipomersen and icosapent ethyl.

There are several approved products that target PCSK9 protein as a mechanism to lower LDL-C and reduce the risk of ASCVD. Evolocumab, which is a monoclonal antibody, or mAb, marketed as Repatha® by Amgen Inc., is approved by the FDA for the treatment of patients with heterozygous familial hypercholesterolemia, or HeFH, patients with HoFH and patients with ASCVD. Alirocumab, which is a mAb marketed as PRALUENT® by both Sanofi and Regeneron Pharmaceuticals, Inc., or Regeneron, is approved by the FDA for the treatment of patients with ASCVD and for the treatment of patients with primary hyperlipidemia, including HeFH. The approved mAb treatments act through extracellular inhibition of the PCSK9 protein. Inclisiran, which is a small interfering RNA, or siRNA, marketed as Leqvio® by Novartis, is approved in the United States for the treatment of patients with ASCVD, HeFH or elevated LDL-C who are at high risk of CVD and in Europe for the treatment of patients with hypercholesterolemia, including HeFH, or mixed dyslipidemia. Inclisiran acts by inhibiting the synthesis of PCSK9 within liver cells, which is distinct from extracellular protein inhibition. We are also aware of two orally administered small molecule product candidates that target the PCSK9 protein as a mechanism to lower LDL-C and reduce the risk of ASCVD in various stages of clinical development. These consist of MK-0616 from Merck & Co., Inc, for which Merck released data from a completed Phase 2b trial of adult patients with hypercholesterolemia and initiated a Phase 3 pivotal trial of adult patients with hypercholesterolemia in August 2023; and AZD0780 from AstraZeneca which is being evaluated in an ongoing Phase 2 clinical trial.

We are aware of other gene editing and epigenetic editing programs targeting the PCSK9 gene in preclinical development. Precision Biosciences, Inc., or Precision, has published preclinical data showing long-term stable reduction of PCSK9 and LDL-C levels in non-human primates following in vivo gene editing of the PCSK9 gene using its gene editing platform. In September 2021, Precision entered into a collaboration with iECURE under which iECURE plans to advance Precision’s PCSK9 directed nuclease product candidate into Phase 1 clinical trials for the treatment of FH in 2022. In January 2023, Precision announced that it had decided to cease pursuit of this program with iECURE as a partner, with plans to provide additional guidance on whether and when this medicine will advance into clinical testing in the future. Additionally, in 2022, CRISPR Therapeutics, or CRISPR, announced CTX330, its research stage in vivo gene editing program targeting PCSK9. In 2023, both Tune Therapeutics and Chroma Medicine, Inc. announced preclinical data for each of their preclinical stage epigenetic editing programs targeting PCSK9.

Evinacumab, which is a mAb targeting ANGPTL3 protein that is marketed by Regeneron, is approved by the FDA for the treatment of patients with HoFH and has additionally been evaluated in Phase 2 studies of patients with refractory hypercholesterolemia and either ASCVD or HeFH, and severe hypertriglyceridemia.

We are aware of several product candidates in clinical development that target ANGPTL3 as a mechanism to lower LDL-C and reduce the risk of ASCVD, including zodasiran, a siRNA targeting ANGPTL3 that was evaluated by Arrowhead Pharmaceuticals, Inc., or Arrowhead, in Phase 2 clinical trials of patients with HoFH and patients with mixed dyslipidemia but for which Arrowhead announced in June 2024 it would deprioritize development. In addition, Lilly is evaluating a siRNA targeting ANGPTL3 protein in a Phase 2 clinical trial in adults with mixed dyslipidemia, and in 2023, CRISPR initiated a Phase 1 clinical trial for CTX310, its gene editing program targeting ANGPTL3.

Several investigational medicines designed to reduce lipoprotein(a), or Lp(a), are currently in development. These include pelacarsen, an antisense oligonucleotide licensed by Novartis from Ionis Pharmaceuticals in 2019, which is being evaluated in the Phase 3 Lp(a) HORIZON cardiovascular outcomes study in patients with elevated Lp(a) and CVD, with topline results expected in 2025. Olpasiran is an investigational siRNA medicine targeting LPA licensed by Amgen from Arrowhead, which was shown to lower Lp(a) concentrations in patients with established ASCVD and elevated Lp(a) concentrations. The potential for olpasiran to reduce cardiovascular events in patients with existing ASCVD and elevated Lp(a) is being evaluated in the Phase 3 OCEAN(a) trial, which was initiated in 2022 with plans for study completion in 2026. Lepodisiran is a GalNAc-conjugated siRNA being evaluated by Lilly in a Phase 3 clinical trial. In addition, zerlasiran is an investigational siRNA medicine that Silence Therapeutics plc, or Silence Therapeutics, is evaluating in an ongoing Phase 2 trial of patients with elevated Lp(a) concentrations and high risk for ASCVD events, for which Silence Therapeutics announced topline results in June 2024. In 2024, CRISPR initiated a Phase 1 clinical trial for CTX320, its gene editing program targeting LPA.

Our commercial opportunity could be reduced or eliminated if our competitors develop and commercialize products that are safer, more effective, have fewer or less severe side effects, are more convenient or are less expensive than any products that we may develop. Our competitors also may obtain FDA or other regulatory approval for their products more rapidly than we may obtain approval for ours, which could result in our competitors establishing a strong market position before we are able to enter the market. In addition, our ability to compete may be affected in many cases by insurers or other third-party payors seeking to encourage the use of generic products. If our product candidates achieve marketing approval, we expect that they will be priced at a significant premium to competitive biosimilar generic products.

Many of the companies against which we are competing or against which we may compete in the future have significantly greater financial resources and expertise in research and development, manufacturing, preclinical testing, conducting clinical trials, obtaining regulatory approvals and marketing approved products than we do.

Mergers and acquisitions in the pharmaceutical and biotechnology industry may result in even more resources being concentrated among a smaller number of our competitors. Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies. These competitors also compete with us in recruiting and retaining qualified scientific and management personnel and establishing clinical trial sites and patient registration for clinical trials, as well as in acquiring technologies complementary to, or necessary for, our programs.

If we are unable to establish sales, marketing and distribution capabilities or enter into sales, marketing and distribution agreements with third parties, we may not be successful in commercializing our current and future product candidates if and when they are approved.

We do not have a sales or marketing infrastructure and have no experience as a company with the commercialization of products. To achieve commercial success for any product for which we have obtained marketing approval, we will need to establish a sales, marketing and distribution organization, either ourselves or through collaborations or other arrangements with third parties.

In the future, we expect to build a sales and marketing infrastructure to market some of our product candidates in the United States, if and when they are approved. There are risks involved with establishing our own sales, marketing and distribution capabilities. For example, recruiting and training a sales force is expensive and time-consuming and could delay any product launch. If the commercial launch of a product candidate for which we recruit a sales force and establish marketing capabilities is delayed or does not occur for any reason, we would have prematurely or unnecessarily incurred these commercialization expenses. These efforts may be costly, and our investment would be lost if we cannot retain or reposition our sales and marketing personnel.

Factors that may inhibit our efforts to commercialize our products on our own include:

If we are unable to establish our own sales, marketing and distribution capabilities and we enter into arrangements with third parties to perform these services, our product revenues and our profitability, if any, are likely to be lower than if we were to market, sell and distribute any products that we develop ourselves. In addition, we may not be successful in entering into arrangements with third parties to sell, market and distribute our product candidates or may be unable to do so on terms that are acceptable to us. We likely will have little control over such third parties, and any of them may fail to devote the necessary resources and attention to sell and market our products effectively. If we do not establish sales, marketing and distribution capabilities successfully, either on our own or in collaboration with third parties, we will not be successful in commercializing our product candidates.

We currently rely, and expect to continue to rely, on CMOs to manufacture our product candidates. If we are unable to enter into such arrangements as expected or if such organizations do not meet our supply requirements, development and/or commercialization of our product candidates may be delayed.

We currently rely, and expect to continue to rely, on third parties to manufacture clinical supplies of our product candidates and commercial supplies of our products, if and when approved for marketing by applicable regulatory authorities, as well as for packaging, sterilization, storage, distribution and other production logistics. If we are unable to enter into such arrangements on the terms or timeline we expect, development and/or commercialization of our product candidates may be delayed. If these third parties do not successfully carry out their contractual duties, meet expected deadlines or manufacture our product candidates in accordance with regulatory requirements, if there are disagreements between us and such parties or if such parties are unable to expand capacities to support commercialization of any of our product candidates for which we obtain marketing approval, we may not be able to fulfill, or may be delayed in producing sufficient product candidates to meet, our supply requirements. These facilities may also be affected by catastrophic events, including public health epidemics or pandemics, including the COVID-19 pandemic, terrorist attacks, wars or other armed conflicts, geopolitical tensions, such as the ongoing war between Israel and Hamas and ongoing war between Russia and Ukraine, natural disasters, such as floods or fire, or such facilities could face manufacturing issues, such as contamination or regulatory concerns following a regulatory inspection of such facility. In such instances, we may need to locate an appropriate replacement third-party facility and establish a contractual relationship, which may not be readily available or on acceptable terms, which would cause additional delay and increased expense, including as a result of additional required FDA approvals, and may have a material adverse effect on our business.

Our third-party manufacturers will be subject to inspection and approval by the FDA before we can commence the manufacture and sale of any of our product candidates, and thereafter subject to FDA inspection from time to time. Failure by our third-party manufacturers to pass such inspections and otherwise satisfactorily complete the FDA approval regimen with respect to our product candidates may result in regulatory actions such as the issuance of FDA Form 483 notices of observations, warning letters or injunctions or the loss of operating licenses.

We or our third-party manufacturers may also encounter shortages in the raw materials or API necessary to produce our product candidates in the quantities needed for our clinical trials or, if our product candidates are approved, in sufficient quantities for commercialization or to meet an increase in demand, as a result of capacity constraints or delays or disruptions in the market for the raw materials or API, including shortages caused by the purchase of such raw materials or API by our competitors or others. The failure of us or our third-party manufacturers to obtain the raw materials or API necessary to manufacture sufficient quantities of our product candidates may have a material adverse effect on our business.

In addition, we currently rely on foreign third-party manufacturers, including those in China. Foreign third-party manufacturers may be subject to U.S. legislation, including sanctions, trade restrictions and other foreign regulatory requirements which could increase the cost or reduce the supply of material or services available to us, delay the procurement or supply of such material or services or have an adverse effect on our ability to secure significant commitments from governments to purchase our potential therapies. Moreover, in September 2024, the U.S. House of Representatives passed the BIOSECURE Act (H.R. 7085) and the Senate has advanced a substantially similar bill, which legislation, if passed by the Senate and enacted into law, would restrict the ability of U.S. biopharmaceutical companies like us to purchase services or products from, or otherwise collaborate with, specifically named Chinese biotechnology companies and authorizes the U.S. government to impose such restrictions on entities transacting with additional Chinese biotechnology companies as a condition of U.S. government contracts, grants and loan funding. The legislation passed by the House of Representatives contains a grandfathering provision that would prevent disruption to the provision of services or products furnished under contracts with the targeted biotechnology companies entered into before the

effective date of the legislation until January 2032. It is possible some of our contractual counterparties could be impacted by this legislation.

Even if we are able to commercialize any product candidates, the products may become subject to unfavorable pricing regulations, third-party coverage or reimbursement practices or healthcare reform initiatives, which could harm our business.

The regulations that govern marketing approvals, pricing, coverage and reimbursement for new drug products vary widely from country to country. Current and future legislation may significantly change the approval requirements in ways that could involve additional costs and cause delays in obtaining approvals. Some countries require approval of the sale price of a drug before it can be marketed. In many countries, the pricing review period begins after marketing or product licensing approval is granted. In some foreign markets, prescription pharmaceutical pricing remains subject to continuing governmental control even after initial approval is granted. As a result, we might obtain marketing approval for a product in a particular country, but then be subject to price regulations that delay our commercial launch of the product, possibly for lengthy time periods, and negatively impact the revenues we are able to generate from the sale of the product in that country. Adverse pricing limitations may hinder our ability to recoup our investment in one or more product candidates, even if our product candidates obtain marketing approval.

Our ability to commercialize any product candidates successfully also will depend in part on the extent to which coverage and adequate reimbursement for these products and related treatments will be available from government health administration authorities, private health insurers and other organizations. Government authorities and other third-party payors, such as private health insurers and health maintenance organizations, decide which medications they will pay for and establish reimbursement levels. Coverage and reimbursement by a third-party payor may depend upon a number of factors, including the third-party payor’s determination that use of a product is:

In the United States, there is no uniform policy of coverage and reimbursement for products exists among third-party payors. As a result, obtaining coverage and reimbursement approval of a product from a government or other third-party payor is a time-consuming and costly process that could require us to provide to each payor supporting scientific, clinical and cost-effectiveness data for the use of our products on a payor-by-payor basis, with no assurance that coverage and adequate reimbursement will be obtained. The availability and adequacy of coverage and reimbursement by governmental healthcare programs such as Medicare and Medicaid, private health insurers and other third-party payors are essential for most patients to be able to afford our product candidates, if approved. Our ability to achieve acceptable levels of coverage and reimbursement for our product candidates, if approved, by governmental authorities, private health insurers and other organizations will have an effect on our ability to successfully commercialize, our product candidates. Assuming we obtain coverage for a given product by a third-party payor, the resulting reimbursement payment rates may not be adequate or may require patient out-of-pocket costs that patients find unacceptably high.

A primary trend in the U.S. healthcare industry and elsewhere is cost containment. Government authorities and third-party payors have attempted to control costs by limiting coverage and the amount of reimbursement for particular medications. Increasingly, third-party payors are requiring that drug companies provide them with predetermined discounts from list prices and are challenging the prices charged for medical products. Coverage and reimbursement may not be available for any product that we commercialize and, even if these are available, the level of reimbursement may not be satisfactory. Reimbursement may affect the demand for, or the price of, any product candidate for which we obtain marketing approval. Obtaining and maintaining adequate reimbursement for our products may be difficult. We may be required to conduct expensive pharmacoeconomic studies to justify coverage and reimbursement or the level of reimbursement relative to other therapies. If coverage and adequate reimbursement are not available or reimbursement is available only to limited levels, we may not be able to successfully commercialize any product candidate for which we obtain marketing approval.

There may be significant delays in obtaining coverage and reimbursement for newly approved drugs, and coverage may be more limited than the purposes for which the drug is approved by the FDA or similar regulatory authorities outside of the United States. Reimbursement agencies in Europe may be more conservative than the Centers for Medicare & Medicaid Services, or CMS, in the United States. For example, a number of cancer drugs have been approved for reimbursement in the United States and have not been approved for reimbursement in certain European countries.

Moreover, eligibility for coverage and reimbursement does not imply that a drug will be paid for in all cases or at a rate that covers our costs, including research, development, manufacture, sale and distribution expenses. Interim reimbursement levels for new drugs, if applicable, may also not be sufficient to cover our costs and may not be made permanent. Reimbursement rates may vary according to the use of the drug and the clinical setting in which it is used, may be based on reimbursement levels already set for lower cost drugs and may be incorporated into existing payments for other services. Net prices for drugs may be reduced by mandatory discounts or rebates required by government healthcare programs or private payors and by any future relaxation of laws that presently restrict imports of drugs from countries where they may be sold at lower prices than in the United States. Third-party payors often rely upon Medicare coverage policy and payment limitations in setting their own reimbursement policies. Our inability to promptly obtain coverage and adequate reimbursement rates from both government-funded and private payors for any approved products that we develop could have a material adverse effect on our operating results, our ability to raise capital needed to commercialize products and our overall financial condition.

There can be no assurance that our product candidates, even if they are approved for sale in the United States or in other countries, will be considered medically reasonable and necessary for a specific indication or cost-effective by third-party payors, or that coverage and an adequate level of reimbursement will be available or that third-party payors’ reimbursement policies will not adversely affect our ability to sell our product candidates profitably.

Our future growth depends, in part, on our ability to penetrate foreign markets, where we would be subject to additional regulatory burdens and other risks and uncertainties that, if they materialize, could harm our business.

Our future profitability will depend, in part, on our ability to commercialize our product candidates in markets outside of the United States. If we commercialize our product candidates in foreign markets, we will be subject to additional risks and uncertainties, including:

If risks related to any of these uncertainties materializes, it could have a material adverse effect on our business.

Clinical trial and product liability lawsuits against us could divert our resources and could cause us to incur substantial liabilities and to limit commercialization of any products that we may develop.

We will face an inherent risk of clinical trial and product liability exposure related to the testing of our product candidates in human clinical trials, and we will face an even greater risk if we commercially sell any products that we may develop. While we currently have no products that have been approved for commercial sale, the ongoing, planned and future use of product candidates by us in clinical trials, and the sale of any approved products in the future, may expose us to liability claims. These claims might be made by patients that use the product, healthcare providers, pharmaceutical companies or others selling such products. If we cannot successfully defend ourselves against claims that our product candidates or

products caused injuries, we will incur substantial liabilities. Regardless of merit or eventual outcome, liability claims may result in:

We may need to obtain additional insurance coverage as we expand our clinical trials or if we commence commercialization of our product candidates. Insurance coverage is increasingly expensive. We may not be able to obtain and maintain insurance coverage at a reasonable cost or in an amount adequate to satisfy any liability that may arise. If a successful clinical trial or product liability claim or series of claims is brought against us for uninsured liabilities or in excess of insured liabilities, our assets may not be sufficient to cover such claims and our business operations could be impaired.

Gene editing is novel and the regulatory landscape that will govern any product candidates we may develop is uncertain and may change. As a result, we cannot predict the time and cost of obtaining regulatory approval, if we receive it at all, for any product candidates we may develop.

The regulatory requirements that will govern any novel gene editing product candidates we develop are not entirely clear and may change. Within the broader genetic medicines field, we are aware of a limited number of gene therapy products that have received marketing authorization from the FDA and the EMA. Even with respect to more established products that fit into the categories of gene therapies or cell therapies, the regulatory landscape is still developing. Regulatory requirements governing gene therapy products and cell therapy products have changed frequently and will likely continue to change in the future. Moreover, there is substantial, and sometimes uncoordinated, overlap in those responsible for regulation of existing gene therapy products and cell therapy products. For example, in the United States, the FDA has established the Office of Therapeutic Products within its Center for Biologics Evaluation and Research, or CBER, to consolidate the review of gene therapy and related products, and the Cellular, Tissue and Gene Therapies Advisory Committee to advise CBER on its review. Gene therapy clinical trials may also be subject to review and oversight by an IBC, a local institutional committee that reviews and oversees basic and clinical research conducted at the institution participating in the clinical trial. Although the FDA decides whether individual gene therapy protocols may proceed, the review process and determinations of other reviewing bodies can impede or delay the initiation of a clinical trial, even if the FDA has reviewed the trial and approved its initiation.

In the European Union, the development and evaluation of a gene therapy medicinal product must be considered in the context of the relevant EU guidelines. The EMA may issue new guidelines concerning the development and marketing authorization for gene therapy medicinal products and require that we comply with these new guidelines. Additionally, for advanced therapy medicinal products, a marketing application authorization undergoes review by the EMA’s Committee for Advanced Therapies, or CAT, in addition to review by the Committee for Medicinal Products for Human Use, or CHMP. As a result, the procedures and standards applied to gene therapy products and cell therapy products may be applied to any product candidates we may develop, but that remains uncertain at this point.

Adverse developments in post-marketing experience or in clinical trials conducted by others of gene therapy products, cell therapy products, or products developed through the application of a base editing or other gene editing technology may cause the FDA, the EMA, and other regulatory bodies to revise the requirements for development or approval of any product candidates we may develop or limit the use of products utilizing base editing technologies, either of which could materially harm our business. In addition, the clinical trial requirements of the FDA, the EMA, and other regulatory authorities and the criteria these regulators use to determine the safety and efficacy of a product candidate vary substantially according to the type, complexity, novelty, and intended use and market of the potential products. The regulatory approval process for novel product candidates such as the product candidates we may develop can be more expensive and take longer than for other, better known, or more extensively studied pharmaceutical or other product candidates. Regulatory agencies administering existing or future regulations or legislation may not allow production and

marketing of products utilizing base editing technology in a timely manner or under technically or commercially feasible conditions. In addition, regulatory action or private litigation could result in expenses, delays, or other impediments to our research programs or the commercialization of resulting products.

The regulatory review committees and advisory groups described above and the new guidelines they promulgate may lengthen the regulatory review process, require us to perform additional studies or trials, increase our development costs, lead to changes in regulatory positions and interpretations, delay or prevent approval and commercialization of these treatment candidates, or lead to significant post-approval limitations or restrictions. As we advance our research programs and develop future product candidates, we will be required to consult with these regulatory and advisory groups and to comply with applicable guidelines. If we fail to do so, we may be required to delay or discontinue development of any product candidates we identify and develop.

Because we are developing product candidates in the field of genetic medicines, a field that includes gene therapy and gene editing, in which there is little clinical experience, there is increased risk that the FDA, the EMA, or other regulatory authorities may not consider the endpoints of our clinical trials to provide clinically meaningful results and that these results may be difficult to analyze.

During the regulatory review process, we will need to identify success criteria and endpoints such that the FDA, the EMA, or other regulatory authorities will be able to determine the clinical efficacy and safety profile of any product candidates we may develop. As we are seeking to identify and develop product candidates to treat diseases in which there is no clinical experience using a gene editing approach, there is heightened risk that the FDA, the EMA, or other regulatory authorities may not consider the clinical trial endpoints that we propose to provide clinically meaningful results (reflecting a tangible benefit to patients). In addition, the resulting clinical data and results may be difficult to analyze. Even if the FDA does find our success criteria to be sufficiently validated and clinically meaningful, we may not achieve the pre-specified endpoints to a degree of statistical significance. Further, even if we do achieve the pre-specified criteria, we may produce results that are unpredictable or inconsistent with the results of the non-primary endpoints or other relevant data. The FDA also weighs the benefits of a product against its risks, and the FDA may view the efficacy results in the context of safety as not being supportive of regulatory approval. Other regulatory authorities in the European Union and other countries may make similar comments with respect to these endpoints and data. Any product candidates we may develop will be based on a novel technology that makes it difficult to predict the time and cost of development and of subsequently obtaining regulatory approval. The FDA has only recently approved the first ex vivo gene editing therapeutic product, CASGEVYTM for the treatment of sickle cell disease.

Even if we complete the necessary preclinical studies and clinical trials, the marketing approval process is expensive, time-consuming and uncertain and may prevent us from obtaining approvals for the commercialization of any product candidates we develop. If we are not able to obtain, or if there are delays in obtaining, required regulatory approvals, we will not be able to commercialize, or will be delayed in commercializing, product candidates we develop, and our ability to generate revenue will be materially impaired.

Any product candidates we develop and the activities associated with their development and commercialization, including their design, testing, manufacture, safety, efficacy, recordkeeping, labeling, storage, approval, advertising, promotion, sale and distribution, are subject to comprehensive regulation by the FDA and other regulatory authorities in the United States and by comparable authorities in other countries. Failure to obtain marketing approval for a product candidate will prevent us from commercializing the product candidate in a given jurisdiction. We have not received approval to market any product candidates from regulatory authorities in any jurisdiction. We have no experience as a company in filing and supporting the applications necessary to gain marketing approvals and expect to rely on third-party CROs to assist us in this process. Securing regulatory approval requires the submission of extensive preclinical and clinical data and supporting information, including manufacturing information, to the various regulatory authorities for each therapeutic indication to establish the biologic product candidate’s safety, purity and potency. Securing regulatory approval also requires the submission of information about the product manufacturing process to, and inspection of manufacturing facilities by, the relevant regulatory authority. Any product candidates we develop may not be effective, may be only moderately effective or may prove to have undesirable or unintended side effects, toxicities or other characteristics that may preclude our obtaining marketing approval or prevent or limit commercial use.

The process of obtaining marketing approvals, both in the United States and abroad, is expensive, may take many years if additional clinical trials are required, if approval is obtained at all, and can vary substantially based upon a variety of factors, including the type, complexity and novelty of the product candidates involved and the specific disease or condition to be treated. Of the large number of products in development, only a small percentage successfully complete the FDA or foreign regulatory approval processes and are commercialized. Even if any product candidates we may develop demonstrate safety and efficacy in clinical trials, the regulatory agencies may not complete their review processes in a timely manner, or we may not be able to obtain regulatory approval. Additional delays may result if an FDA Advisory

Committee or other regulatory authority recommends non-approval or restrictions on approval. Changes in marketing approval policies during the development period, changes in or the enactment of additional statutes or regulations, or changes in regulatory review for each submitted product application, may cause delays in the approval or rejection of an application. The FDA and comparable authorities in other countries have substantial discretion in the approval process and may refuse to accept any application or may decide that our data is insufficient for approval and require additional preclinical, clinical or other studies. In addition, varying interpretations of the data obtained from preclinical and clinical testing could delay, limit or prevent marketing approval of a product candidate. Any marketing approval we ultimately obtain may be limited or subject to restrictions or post-approval commitments that render the approved product not commercially viable.

In addition, we could be adversely affected by several significant administrative law cases decided by the U.S. Supreme Court in 2024. In Loper Bright Enterprises v. Raimondo, for example, the court overruled Chevron U.S.A., Inc. v. Natural Resources Defense Council, Inc., which for 40 years required federal courts to defer to permissible agency interpretations of statutes that are silent or ambiguous on a particular topic. The U.S. Supreme Court stripped federal agencies of this presumptive deference and held that courts must exercise their independent judgment when deciding whether an agency such as the FDA acted within its statutory authority under the Administrative Procedure Act, or the APA. Additionally, in Corner Post, Inc. v. Board of Governors of the Federal Reserve System, the court held that actions to challenge a federal regulation under the APA can be initiated within six years of the date of injury to the plaintiff, rather than the date the rule is finalized. The decision appears to give prospective plaintiffs a personal statute of limitations to challenge longstanding agency regulations. These decisions could introduce additional uncertainty into the regulatory process and may result in additional legal challenges to actions taken by federal regulatory agencies, including the FDA and CMS, that we rely on. In addition to potential changes to regulations as a result of legal challenges, these decisions may result in increased regulatory uncertainty and delays and other impacts, any of which could adversely impact our business and operations.

Further, our ability to develop and market new products may be impacted by ongoing litigation challenging the FDA's approval of mifepristone. Specifically, in April 2023, the U.S. District Court for the Northern District of Texas stayed the approval by the FDA of mifepristone, a drug product which was originally approved in 2000 and whose distribution is governed by various conditions adopted under a REMS. The Court of Appeals for the Fifth Circuit declined to order the removal of mifepristone from the market, but did hold that plaintiffs were likely to prevail in their claim that changes allowing for expanded access of mifepristone that the FDA authorized in 2016 and 2021 were arbitrary and capricious. In June 2024, the U.S. Supreme Court reversed and remanded that decision after unanimously finding that the plaintiffs did not have standing to bring this legal action against the FDA. Depending on the outcome of this litigation, if it continues, our ability to develop new drug product candidates and to maintain approval of existing drug products and measures adopted under a REMS is at risk and our efforts to develop and market new drug products could be delayed, undermined or subject to protracted litigation.

If we experience delays in obtaining approval or if we fail to obtain approval of any product candidates we develop, the commercial prospects for those product candidates may be harmed and our ability to generate revenues will be materially impaired.

Obtaining and maintaining marketing approval or commercialization of our product candidates in the United States does not mean that we will be successful in obtaining marketing approval of our product candidates in other jurisdictions. Failure to obtain marketing approval in foreign jurisdictions would prevent any product candidates we develop from being marketed in such jurisdictions, which, in turn, would materially impair our ability to generate revenue.

In order to market and sell any product candidates we may develop in the European Union and many other foreign jurisdictions, we or our collaborators must obtain separate marketing approvals and comply with numerous and varying local 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 of 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. We or our collaborators 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. We may not be able to file for marketing approvals and may not receive necessary approvals to commercialize our product candidates in any jurisdiction, which would materially impair our ability to generate revenue.

We could face heightened risks with respect to obtaining marketing authorization in the United Kingdom as a result of the United Kingdom's withdrawal from the European Union, or Brexit. As of January 2021, the MHRA is now the sole decision maker for marketing authorizations of pharmaceutical products in the United Kingdom, except for Northern Ireland, which

is subject to EU rules under the Northern Ireland Protocol. The United Kingdom and the European Union have however agreed to the Windsor Framework which fundamentally changes the existing system under the Northern Ireland Protocol, including with respect to the regulation of medicinal products in the United Kingdom. Once implemented, the changes introduced by the Windsor Framework will result in the MHRA being responsible for approving all medicinal products destined for the United Kingdom market (including Northern Ireland), and the EMA will no longer have any role in approving medicinal products destined for Northern Ireland. Any delay in obtaining, or an inability to obtain, any marketing approvals, as a result of Brexit or otherwise, may force us to restrict or delay efforts to seek regulatory approval in the United Kingdom for our product candidates, which could significantly and materially harm our business. As a result of Brexit, we expect we will need to submit a separate application to the MHRA for marketing approval in the United Kingdom, in addition to any planned marketing authorization applications for the EMA.

In addition, foreign regulatory authorities may change their approval policies and new regulations may be enacted. For instance, the European Union pharmaceutical legislation is currently undergoing a complete review process, in the context of the Pharmaceutical Strategy for Europe initiative, launched by the European Commission in November 2020. The European Commission's proposal for revision of several legislative instruments related to medicinal products (including potentially reducing the duration of regulatory data protection and revising the eligibility for expedited pathways) was published in April 2023, and the European Parliament has requested several amendments. The proposed revisions remain to be agreed and adopted by the European Parliament and European Council and the proposals may therefore be substantially revised before adoption, which is not anticipated before early 2026. The revisions may however have a significant impact on the pharmaceutical industry and our business in the long term.

We do not have any experience commercializing products outside of the United States. We expect that we will be subject to additional risks in commercializing any of our product candidates that receive marketing approval outside the United States, including tariffs, trade barriers and regulatory requirements; economic weakness, including inflation, or political instability in particular foreign economies and markets; compliance with tax, employment, immigration and labor laws for employees living or traveling abroad; foreign currency fluctuations, which could result in increased operating expenses and reduced revenue, and other obligations incident to doing business in another country; and workforce uncertainty in countries where labor unrest is more common than in the United States.

We may seek certain designations for our product candidates, including Fast Track, Breakthrough Therapy, Regenerative Medicine Advanced Therapy and Priority Review designations in the United States, Innovative Licensing and Access Pathway designation in the United Kingdom, and PRIME Designation in the European Union, but we might not receive such designations, and even if we do, such designations may not lead to a faster development or regulatory review or approval process.

If a product candidate is intended for the treatment of a serious or life-threatening condition and the product candidate demonstrates the potential to address unmet medical need for this condition, the sponsor may apply to the FDA for Fast Track designation. For Fast Track products, sponsors may have greater interactions with the FDA and the FDA may initiate review of sections of a Fast Track product’s application before the application is complete. This rolling review may be available if the FDA determines, after preliminary evaluation of clinical data submitted by the sponsor, that a Fast Track product may be effective.

In addition, an applicant may seek designation of its product as a breakthrough therapy, which is a drug that is intended, alone or in combination with one or more other drugs, to treat a serious or life-threatening disease or condition, and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development. For drugs and biologics that have been designated as breakthrough therapies, interaction and communication between the FDA and the sponsor of the trial can help to identify the most efficient path for clinical development while minimizing the number of patients placed in ineffective control regimens.

Additionally, a product is eligible for Regenerative Medicine Advanced Therapy, or RMAT, designation if it is intended to treat, modify, reverse or cure a serious or life-threatening disease or condition and preliminary clinical evidence indicates that the product candidate has the potential to address unmet medical needs for such disease or condition. The benefits of an RMAT designation are similar to a breakthrough therapy designation, and include early interactions with the FDA to expedite development and review, potential eligibility for priority review and accelerated approval based on surrogate or intermediate endpoints.

Further, if the FDA determines that a product candidate offers major advances in treatment or provides a treatment where no adequate therapy exists, the FDA may designate the product candidate for priority review. Significant improvement may be illustrated by evidence of increased effectiveness in the treatment of a condition, elimination or substantial reduction of a treatment-limiting product reaction, documented enhancement of patient compliance that may lead to improvement in serious outcomes, and evidence of safety and effectiveness in a new subpopulation. A priority review

designation means that the goal for the FDA to review an application is six months, rather than the standard review period of ten months.

We may seek these and other designations for our product candidates. The FDA has broad discretion with respect to whether or not to grant these designations to a product candidate, so even if we believe a particular product candidate is eligible for such designation or status, the FDA may decide not to grant it. Moreover, a Fast Track, breakthrough therapy, or RMAT designation does not necessarily mean a faster regulatory review process or necessarily confer any advantage with respect to approval compared to conventional FDA procedures. As a result, while we may seek and receive these designations for our product candidates, we may not experience a faster development process, review or approval compared to conventional FDA procedures. In addition, the FDA may withdraw these designations if it believes that the designation is no longer supported by data from our clinical development program.

在欧盟，我们可能会在未来为我们的一些候选产品寻求优质称号。PRIME是一项自愿计划，旨在加强EMA的作用，以加强科学和监管支持，以优化开发，并能够加快对具有解决未满足的医疗需求的潜力的重大公共卫生利益的新药的评估。该计划的重点是针对欧盟没有令人满意的治疗方法的疾病的药物，或者即使存在这种方法，它也可能提供比现有治疗方法更大的治疗优势。Prime仅限于正在开发且未在欧洲联盟获得授权的药品，申请人打算通过集中程序申请初步上市授权申请。要被接受为Prime，候选产品必须符合其主要公共健康利益和治疗创新方面的资格标准，该标准基于能够证实声明的信息。Prime指定的好处包括任命一名CHMP报告员在营销授权申请之前提供持续支持和帮助积累知识，在关键开发里程碑进行早期对话和科学建议，以及有可能对产品进行加速审查，这意味着减少审查时间，以便在申请过程中更早发布关于批准程度的意见。Prime还鼓励申请者同时请求EMA科学建议和卫生技术评估建议，以促进及时进入市场。即使我们获得了任何候选产品的优质认证，与传统的EMA程序相比，该认证可能不会带来实质性更快的开发过程、审查或批准。此外，获得Prime称号并不保证或增加EMA授予营销授权的可能性。

我们可能同样会遵循英国退欧后MHRA的一些程序，以优先获得将使患者受益的新药，例如150天评估、滚动审查程序和创新的许可和获取途径，或ILAP。ILAP旨在加快上市时间，并便利患者获得药物，包括新的化学实体、生物药物、新的适应症和重新调整用途的药物。我们于2023年2月从MHRA获得了创新护照，这是进入ILAP的起点。受益于ILAP的产品开发商将获得临床试验设计方面的建议，以确保为监管批准和卫生技术评估提供最佳的数据生成。

我们可能无法获得我们可能开发的任何候选产品的孤立药物排他性，即使我们这样做了，这种排他性也可能不会阻止FDA或EMA批准其他竞争产品。

根据《孤儿药品法》，如果一种产品是用于治疗罕见疾病或疾病的药物或生物制剂，FDA可以将该产品指定为孤儿药物。欧盟EMA对孤儿产品的审批也有类似的监管制度。一般来说，如果具有孤儿药物指定的候选产品随后获得了其具有该指定的适应症的第一次上市批准，则该产品有权在一段时间内获得市场排他期，这使得FDA或EMA不能在该时间段内批准同一产品的同一治疗适应症的另一营销申请。适用期限在美国为七年，目前在欧盟为十年。如果一种产品不再符合指定孤儿药物的标准，特别是如果该产品的利润足够高，以至于市场排他性不再合理，那么欧盟的排他性期限可以缩短到六年。

为了让FDA批准我们的一种产品获得孤儿药物独家经营权，该机构必须发现该产品被指定用于治疗美国每年患者人数少于20万人的疾病或疾病。FDA可能会得出结论，我们寻求孤儿药物排他性的条件或疾病不符合这一标准。即使我们获得了一种产品的孤儿药物排他性，这种排他性也可能无法有效地保护该产品免受竞争，因为不同的产品可以针对相同的条件获得批准。特别是，在基因疗法的背景下，在孤儿药物排他性的目的下，什么构成“同一药物”的概念仍然在变化，FDA最近发布了最终指导意见，表明它不会仅仅因为转基因或载体的微小差异而认为两种遗传药物产品是不同的药物。此外，即使在一种孤儿药物获得批准后，如果FDA得出结论认为，后一种产品在临床上更优越，因为它被证明更安全、更有效或对患者护理做出了重大贡献，则FDA随后可以针对相同的疾病批准相同的产品。如果FDA或EMA确定

指定存在重大缺陷，或者制造商无法确保足够数量的产品来满足罕见疾病或病症患者的需求。

2017年，国会通过了2017年FDA再授权法案（FDARA）。FDARA除其他外，将FDA现有的监管解释编入法典，要求药物申办者证明孤儿药的临床优越性，该药物与之前批准的用于相同罕见疾病的药物相同，以获得孤儿药的排他性。根据特朗普总统2020年12月签署的综合立法，产品表现出临床优越性的要求适用于在2017年FDARA颁布之前获得孤儿药认定但尚未获得FDA批准或许可的药物和生物制品。

FDA和国会可能会进一步重新评估《孤儿药物法案》及其法规和政策。鉴于上诉法院对11人的裁决，这一点可能尤其正确这是 2021年9月巡回调查发现，为了确定排他性范围，“相同疾病或病症”一词是指指定的“罕见疾病或病症”，FDA不能解释为指“适应症或用途”。尽管有立法提案推翻这一决定，但尚未成为法律。2023年1月，FDA宣布，在该法院命令范围之外的事务中，FDA将继续适用其现有法规，将孤儿药排他性与孤儿药获得批准的用途或适应症挂钩。我们不知道FDA或国会未来是否、何时或如何改变孤儿药法规和政策，也不确定任何变化会如何影响我们的业务。根据FDA或国会可能对其孤儿药法规和政策做出哪些改变，我们的业务可能会受到不利影响。

即使我们或我们可能拥有的任何合作伙伴为我们开发的任何候选产品获得营销批准，批准条款和对我们产品的持续监管可能需要大量资源支出，并可能限制我们或他们制造和营销我们的产品的方式，这可能会严重削弱我们的创收能力。

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、广告和促销活动，都将受到FDA和其他监管机构的持续要求和审查。这些要求包括提交安全和其他上市后信息和报告、注册和上市要求、与质量控制和制造有关的cGMP要求、记录和文件的质量保证和相应维护，以及关于向医生分发样本和保存记录的要求。例如，批准的BLA的持有者有义务监测和报告不良事件以及产品不符合BLA中的规格的任何故障。FDA通常建议接受基因药物治疗的患者接受长达15年的潜在不良事件的跟踪观察。经批准的BLA的持有者还必须提交新的或补充的申请，并获得FDA的批准，以对经批准的产品、产品标签或制造过程进行某些更改。即使批准了候选产品的上市，批准也可能受到对产品可能上市的指定用途的限制或批准条件的限制，或者包含对昂贵的上市后测试和监督的要求，以监测产品的安全性或有效性，包括实施可再生能源管理系统的要求。

因此，假设我们或我们可能拥有的任何合作者获得了我们开发的一个或多个候选产品的营销批准，我们和这样的合作者以及我们和他们的合同制造商将继续在所有合规领域花费时间、金钱和精力，包括制造、生产、产品监控和质量控制。如果我们和这样的合作者不能遵守批准后的监管要求，我们和这样的合作者可能会被监管机构撤回对我们产品的营销批准，并且我们或这样的合作者营销任何未来产品的能力可能会受到限制，这可能会对我们实现或维持盈利的能力产生不利影响。此外，遵守审批后法规的成本可能会对我们的业务、经营业绩、财务状况和前景产生负面影响。

我们获得上市批准的任何候选产品都可能受到限制或退出市场，如果我们没有遵守监管要求，或者如果我们的产品遇到了意想不到的问题，当其中任何产品获得批准时，我们可能会受到重大处罚。

FDA和其他监管机构密切监管药品的批准后销售和促销，以确保它们只针对批准的适应症并根据批准的标签的规定进行销售。2021年9月，FDA公布了最终规定，描述了FDA在确定药物或生物的预期用途时将考虑的证据类型。尽管医生在他们的专业医疗判断中可能会开出产品的标签上没有描述的用途，即所谓的标签外用途，但FDA和其他监管机构对制造商关于标签外使用的沟通施加了严格的限制，如果我们以与其批准的标签不符的方式销售我们的产品，我们可能会受到FDA和其他联邦和州执法机构(包括司法部或司法部)的标签外营销执法行动的影响。违反联邦食品、产品和化妆品法案和其他法规，包括

与处方药促销和广告有关的《虚假索赔法》也可能导致对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的调查或指控。

尽管对标签外促销有监管限制，但FDA和其他监管机构允许公司在某些情况下就其产品进行真实、非误导性和非促销的科学交流。例如，2023年10月，FDA发布了指导草案，概述了该机构管理向医疗保健提供者分发有关未经批准的用途的科学信息的不具约束力的政策。本指南草案要求此类通信真实、无误导性、事实和不偏不倚，并包括医疗保健提供者解释有关未经批准使用的信息的优点和缺点以及有效性和实用性所需的所有信息。此外，根据作为2023年综合拨款法案的一部分签署成为法律的《审批前信息交换法》，公司还可以推广与处方信息一致的信息，并主动与付款人的处方委员会成员就未经批准的药物或已批准药物的未批准用途的数据进行交谈。我们将需要仔细考虑FDA的各种法规、指导方针和政策，以及最近颁布的立法，以确保遵守有关我们产品推广的限制。

此外，后来发现我们的候选产品、制造商或制造工艺存在以前未知的问题，或未能遵守法规要求，可能会产生各种结果，包括：

政府对涉嫌违法的任何调查都可能需要我们花费大量时间和资源来回应，并可能产生负面宣传。发生上述任何事件或处罚可能会抑制我们将开发的任何候选产品商业化的能力，并对我们的业务、财务状况、运营结果和前景产生不利影响。

FDA、SEC和其他政府机构的资金不足，包括政府关闭或这些机构运营的其他干扰，可能会阻碍他们雇用和留住关键领导和其他人员的能力，阻止新产品和服务及时开发或商业化，或以其他方式阻止这些机构履行我们业务运营可能会的正常业务职能依赖，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各种因素的影响，包括政府预算和资金水平、雇用和留住关键人员以及接受用户费用支付的能力，以及法定、监管和政策变化。因此，该机构的平均审查时间近年来一直在波动。FDA和其他机构的中断也可能会减缓新产品候选产品被必要的政府机构审查和/或批准所需的时间，这将对我们的业务产生不利影响。此外，政府为美国证券交易委员会(Securities and Exchange Commission，简称美国证券交易委员会)以及我们的业务可能依赖的其他政府机构提供资金，包括那些为研发活动提供资金的机构，都会受到政治过程的影响，而政治过程本身就是不稳定和不可预测的。

FDA和其他机构的混乱也可能会减缓新候选产品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，某些监管机构，例如FDA和SEC，不得不让关键员工休假并停止关键活动。此外，FDA和其他机构可能会

经历公共卫生流行病或大流行造成的干扰，例如FDA在COVID-19大流行期间延迟国内外检查。如果政府长期关闭或出现其他干扰，可能会严重影响FDA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。

我们与客户、医疗保健提供者和专业人员以及第三方付款人等之间的任何关系都将受到适用的反回扣、欺诈和滥用以及其他医疗法律法规的约束，这可能会使我们面临惩罚，包括刑事制裁、民事处罚、合同损害、声誉损害、罚款、返还、被排除在政府医疗保健计划之外、削减或限制我们的业务，以及利润和未来收益的减少。

医疗保健提供者、医生和第三方付款人将在我们能够获得市场批准的任何产品的推荐和处方中发挥主要作用。我们与医疗保健提供者、第三方付款人和客户达成的任何安排都将使我们受到广泛适用的欺诈和滥用以及其他医疗保健法律法规的影响。法律和法规可能会约束我们进行临床研究、营销、销售和分销我们获得市场批准的任何产品的业务或财务安排和关系。这些措施包括：

努力确保我们与第三方达成的任何业务安排以及我们的业务总体上都符合适用的医疗法律和法规，这将涉及大量成本。政府当局可能会得出结论，我们的业务实践可能不符合当前或未来涉及适用欺诈和滥用或其他医疗保健法律和法规的现行或未来法规、法规或判例法。如果我们的运营被发现违反了这些法律或任何其他可能适用于我们的政府法规，我们可能面临重大的民事、刑事和行政处罚、损害赔偿、罚款、个人监禁、额外的报告要求和监督，如果我们受到公司诚信协议或类似协议的约束，以解决以下指控：不遵守这些法律、将产品排除在政府资助的医疗保健计划(如Medicare和Medicaid)之外、返还、合同损害、声誉损害，以及我们业务的削减或重组。防御任何此类行动都可能是昂贵、耗时的，可能需要大量的财政和人力资源。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。此外，如果我们预期与之开展业务的任何医生或其他医疗保健提供者或实体被发现不符合适用法律，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之外。

Current and future legislation may increase the difficulty and cost for us and any collaborators to obtain marketing approval and commercialize our product candidates and affect the prices we, or they, may obtain.

In the United States and some foreign jurisdictions, there have been a number of legislative and regulatory changes and proposed changes regarding the healthcare system that could, among other things, prevent or delay marketing approval of our product candidates, restrict or regulate post-approval activities and affect our ability, or the ability of any collaborators, to profitably sell or commercialize any product candidate for which we, or they, obtain marketing approval. We expect that current laws, as well as other healthcare reform measures that may be adopted in the future, may result in more rigorous coverage criteria and in additional downward pressure on the price that we, or any collaborators, may receive for any approved products.

2010年3月，总裁·奥巴马签署了PPACA，使之成为法律。此外，自PPACA颁布以来，还提出并通过了其他立法修改。2011年8月，《2011年预算控制法案》(Budget Control Act Of 2011)等法案为国会制定了削减开支的措施。一个赤字削减联合特别委员会的任务是建议在2013年至2021年期间有针对性地削减至少1.2亿美元的万亿赤字，但该委员会无法达到所需的目标，从而触发了立法自动削减到几个政府项目。这些变化包括每个财年向提供商支付的联邦医疗保险总额减少高达2%，这将一直有效到2032年上半年。2012年的《美国纳税人救济法》减少了向几家医疗服务提供者支付的联邦医疗保险，并将政府向提供者追回多付款项的诉讼时效从三年延长到五年。这些法律可能会导致联邦医疗保险和其他医疗保健资金的进一步减少，并以其他方式影响我们可能获得监管批准的任何候选产品的价格，或者任何此类候选产品的处方或使用频率。

事实上，根据目前的立法，医疗保险支出的实际减幅可能高达4%。综合拨款法案于2022年12月由总裁·拜登签署成为法律，对医疗保险计划的自动减支做出了几项修改。综合拨款法案第1001条将2010年4%的法定现收现付法(PAYGO)自动减支推迟两年，至2024年底。由《2021年美国救援计划法案》的颁布引发的，将医疗保险计划削减4%的计划将于2023年1月生效。综合拨款法案的医疗补偿标题包括第4163条，该条款将2011年联邦医疗保险自动减支的2%预算控制法案延长6个月至2032年，并降低2030年和2031年的支付减免百分比。

自PPACA颁布以来，已经并将继续有许多法律挑战和国会行动，以废除和取代该法律的条款。例如，税法废除了“个人强制令”。这项要求大多数美国人购买最低水平医疗保险的条款于2019年生效。此外，2018年12月，德克萨斯州北区的一名美国地区法院法官裁定，PPACA的个人授权部分是PPACA的一个基本且不可分割的特征，因此，由于该授权作为税法的一部分被废除，PPACA的其余条款也无效。然而，2021年6月，美国最高法院驳回了该案，维持了PPACA。围绕PPACA的诉讼和立法可能会继续，结果是不可预测和不确定的。

前特朗普总统政府还采取行政行动破坏或推迟PPACA的实施，包括指示根据PPACA拥有权力和责任的联邦机构放弃、推迟、拨款

豁免或推迟实施PPACA中任何会给州、个人、医疗保健提供者、健康保险公司或药品或医疗器械制造商带来财政或监管负担的条款。然而，2021年1月，总裁·拜登撤销了这些命令，并发布了一项行政命令，指示联邦机构重新考虑限制美国人获得医疗保健的规则和其他政策，并考虑采取行动保护和加强这种获得。根据这项行政命令，联邦机构将被指示重新审查：削弱对患有先前疾病的人的保护的政策，包括与新冠肺炎有关的并发症；根据联邦医疗补助和《泛美政治行动计划》的示威和豁免可能减少覆盖范围或破坏计划的政策，包括工作要求；破坏健康保险市场或其他医疗保险市场的政策；增加参加联邦医疗补助计划和泛美政治行动计划的难度的政策；以及降低保险或经济援助的可负担性，包括对受扶养人的负担能力的政策。这项行政命令还指示卫生与公众服务部为健康保险市场设立一个特别的投保期，以应对2023年6月结束的新冠肺炎大流行。

In the European Union in December 2021, Regulation No 2021/2282 on Health Technology Assessment, or HTA, amending Directive 2011/24/EU, was adopted. While the HTA entered into force in January 2022, it will only begin to apply from January 2025 onwards, with preparatory and implementation-related steps to take place in the interim. Once applicable, it will have a phased implementation depending on the concerned products. The HTA intends to boost cooperation among EU member states in assessing health technologies, including new medicinal products as well as certain high-risk medical devices, and provide the basis for cooperation at the EU level for joint clinical assessments in these areas. It will permit EU member states to use common HTA tools, methodologies, and procedures across the European Union, working together in four main areas, including joint clinical assessment of the innovative health technologies with the highest potential impact for patients, joint scientific consultations whereby developers can seek advice from HTA authorities, identification of emerging health technologies to identify promising technologies early, and continuing voluntary cooperation in other areas. Individual EU member states will continue to be responsible for assessing non-clinical (e.g., economic, social, ethical) aspects of health technology, and making decisions on pricing and reimbursement.

We expect that these healthcare reform measures, as well as other healthcare reform measures that may be adopted in the future, may result in additional reductions in Medicare and other healthcare funding, more rigorous coverage criteria, new payment methodologies and additional downward pressure on the price that we receive for any approved product and/or the level of reimbursement physicians receive for administering any approved product we might bring to market. Reductions in reimbursement levels may negatively impact the prices we receive or the frequency with which our products are prescribed or administered. Any reduction in reimbursement from Medicare or other government programs may result in a similar reduction in payments from private payors. Accordingly, such reforms, if enacted, could have an adverse effect on anticipated revenue from product candidates that we may successfully develop and for which we may obtain marketing approval and may affect our overall financial condition and ability to develop or commercialize product candidates.

The prices of prescription pharmaceuticals in the United States and foreign jurisdictions are subject to considerable legislative and executive actions and such actions could impact the prices we obtain for our products, if and when licensed.

The prices of prescription pharmaceuticals have also been the subject of considerable discussion in the United States. There have been several recent U.S. congressional inquiries, as well as proposed and enacted state and federal legislation designed to, among other things, bring more transparency to pharmaceutical pricing, review the relationship between pricing and manufacturer patient programs, and reduce the costs of pharmaceuticals under Medicare and Medicaid. In 2020, President Trump issued several executive orders intended to lower the costs of prescription products and certain provisions in these orders have been incorporated into regulations. These regulations include an interim final rule implementing a most favored nation model for prices that would tie Medicare Part B payments for certain physician-administered pharmaceuticals to the lowest price paid in other economically advanced countries, effective January 1, 2021. That rule, however, has been subject to a nationwide preliminary injunction and, in December 2021, CMS issued a final rule to rescind it. With issuance of this rule, CMS stated that it will explore all options to incorporate value into payments for Medicare Part B pharmaceuticals and improve beneficiaries’ access to evidence-based care.

In addition, in October 2020, HHS and the FDA published a final rule allowing states and other entities to develop a Section 804 Importation Program to import certain prescription drugs from Canada into the United States. That regulation was challenged in a lawsuit by the Pharmaceutical Research and Manufacturers of America, or PhRMA, but the case was dismissed by a federal district court in February 2023 after the court found that PhRMA did not have standing to sue HHS. Nine states have passed laws allowing for the importation of drugs from Canada. Certain of these states have submitted Section 804 Importation Program proposals and are awaiting FDA approval. In January 2024, the FDA authorized the importation of mass medications from Canada into Florida. Further, on November 20, 2020, HHS finalized a regulation removing safe harbor protection for price reductions from pharmaceutical manufacturers to plan sponsors under Part D,

either directly or through pharmacy benefit managers, unless the price reduction is required by law. The rule also creates a new safe harbor for price reductions reflected at the point-of-sale, as well as a new safe harbor for certain fixed fee arrangements between pharmacy benefit managers and manufacturers, the implementation of which has been delayed until January 1, 2032 by the Inflation Reduction Act, or IRA.

The IRA has implications for Medicare Part D, which is a program available to individuals who are entitled to Medicare Part A or enrolled in Medicare Part B to give them the option of paying a monthly premium for outpatient prescription drug coverage. Among other things, the IRA requires manufacturers of certain drugs to engage in price negotiations with Medicare (beginning in 2026), with prices that can be negotiated subject to a cap; imposes rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace inflation (which were first due in 2023); and replaces the Part D coverage gap discount program with a new discounting program (beginning in 2025). The IRA permits the Secretary of HHS to implement many of these provisions through guidance, as opposed to regulation, for the initial years.

Specifically, with respect to price negotiations, Congress authorized Medicare to negotiate lower prices for certain costly single-source drug and biologic products that do not have competing generics or biosimilars and are reimbursed under Medicare Part B and Part D. CMS may negotiate prices for ten high-cost drugs paid for by Medicare Part D starting in 2026, followed by 15 Part D drugs in 2027, 15 Part B or Part D drugs in 2028, and 20 Part B or Part D drugs in 2029 and beyond. This provision applies to drug products that have been approved for at least nine years and biologics that have been licensed for 13 years, but it does not apply to drugs and biologics that have been approved for a single rare disease or condition. Nonetheless, since CMS may establish a maximum price for these products in price negotiations, we would be fully at risk of government action if our products are the subject of Medicare price negotiations. Moreover, given the risk that could be the case, these provisions of the IRA may also further heighten the risk that we would not be able to achieve the expected return on our drug products or full value of our patents protecting our products if prices are set after such products have been on the market for nine years.

Further, the legislation subjects drug manufacturers to civil monetary penalties and a potential excise tax for failing to comply with the legislation by offering a price that is not equal to or less than the negotiated “maximum fair price” under the law or for taking price increases that exceed inflation. The legislation also requires manufacturers to pay rebates for drugs in Medicare Part D whose price increases exceed inflation. The law also caps Medicare out-of-pocket drug costs at an estimated $4,000 a year in 2024 and, thereafter beginning in 2025, at $2,000 a year. In addition, the IRA potentially raises legal risks with respect to individuals participating in a Medicare Part D prescription drug plan who may experience a gap in coverage if they required coverage above their initial annual coverage limit before they reached the higher threshold, or “catastrophic period” of the plan. Individuals requiring services exceeding the initial annual coverage limit and below the catastrophic period must pay 100% of the cost of their prescriptions until they reach the catastrophic period. Among other things, the IRA contains many provisions aimed at reducing this financial burden on individuals by reducing the co-insurance and co-payment costs, expanding eligibility for lower income subsidy plans, and adding price caps on annual out-of-pocket expenses, any of which could have potential pricing and reporting implications. Accordingly, while it is currently unclear how the IRA will be effectuated, we cannot predict with certainty what impact any federal or state health reforms will have on us, but such changes could impose new or more stringent regulatory requirements on our activities or result in reduced reimbursement for our products, any of which could adversely affect our business, results of operations and financial condition. In June 2023, Merck & Co. filed a lawsuit against the HHS and CMS asserting that, among other things, the IRA's Drug Price Negotiation Program for Medicare constitutes an uncompensated taking in violation of the Fifth Amendment of the Constitution. Subsequently, a number of other parties, including the U.S. Chamber of Commerce and pharmaceutical companies, have also filed lawsuits in various courts with similar constitutional claims against HHS and CMS. There have been various decisions by the courts considering these cases since they were filed. HHS has generally won substantive disputes in these cases, and various federal district court judges have expressed skepticism regarding the merits of the legal arguments being pursued by the pharmaceutical industry. Certain of these cases are now on appeal, with oral arguments held in October 2024. We expect that litigation involving these and other provisions of the IRA will continue, with unpredictable and uncertain results.

At the state level, individual states are increasingly aggressive in passing legislation and implementing 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. In addition, health care organizations 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 health care programs. These measures could reduce the ultimate demand for our products, once approved, or put pressure on our product pricing. We expect that additional state and federal healthcare reform measures will be adopted in the future, any of which could limit the amounts that federal and state governments will pay for healthcare products and services, which could result in reduced demand for our product candidates or additional pricing pressures.

In the European Union, similar political, economic and regulatory developments may affect our ability to profitably commercialize our product candidates, if approved. In markets outside of the United States and the European Union, reimbursement and healthcare payment systems vary significantly by country, and many countries have instituted price ceilings on specific products and therapies. In some countries, particularly the countries of the European Union, the pricing of prescription pharmaceuticals is subject to governmental control and access. In these countries, pricing negotiations with governmental authorities can take considerable time after the receipt of marketing approval for a product. To obtain reimbursement or pricing approval in some countries, we may be required to conduct a clinical trial that compares the cost-effectiveness of our product candidate to other available therapies. If reimbursement of our products is unavailable or limited in scope or amount, or if pricing is set at unsatisfactory levels, our business could be harmed, possibly materially.

Compliance with global privacy and data security requirements could result in additional costs and liabilities to us or inhibit our ability to collect and process data globally, and the failure to comply with such requirements could subject us to significant fines and penalties, which may have a material adverse effect on our business, financial condition or results of operations.

We are subject to data privacy and protection laws and regulations that apply to the collection, transmission, storage and use of personally-identifying information, which among other things, impose certain requirements relating to the privacy, security and transmission of personal information, including comprehensive regulatory systems in the United States, European Union and United Kingdom. The legislative and regulatory landscape for privacy and data protection continues to evolve in jurisdictions worldwide, and there has been an increasing focus on privacy and data protection issues with the potential to affect our business. Failure to comply with any of these laws and regulations could result in enforcement action against us, including fines, claims for damages by affected individuals, damage to our reputation and loss of goodwill, any of which could have a material adverse effect on our business, financial condition, results of operations or prospects.

There are numerous U.S. federal and state laws and regulations related to the privacy and security of personal information. In particular, regulations promulgated pursuant to HIPAA establish privacy and security standards that limit the use and disclosure of individually identifiable health information, or protected health information, and require the implementation of administrative, physical and technological safeguards to protect the privacy of protected health information and ensure the confidentiality, integrity and availability of electronic protected health information. Determining whether protected health information has been handled in compliance with applicable privacy standards and our contractual obligations can be complex and may be subject to changing interpretation. These obligations may be applicable to some or all of our business activities now or in the future.

If we are unable to properly protect the privacy and security of protected health information, we could be found to have breached certain contracts with our business partners. Further, if we fail to comply with applicable privacy laws, including applicable HIPAA privacy and security standards, we could face civil and criminal penalties. HHS enforcement activity can result in financial liability and reputational harm, and responses to such enforcement activity can consume significant internal resources. In addition, state attorneys general are authorized to bring civil actions seeking either injunctions or damages in response to violations that threaten the privacy of state residents. We cannot be sure how these regulations will be interpreted, enforced or applied to our operations. In addition to the risks associated with enforcement activities and potential contractual liabilities, our ongoing efforts to comply with evolving laws and regulations at the federal and state level may be costly and require ongoing modifications to our policies, procedures and systems.

In addition to potential enforcement by HHS, we are also potentially subject to privacy enforcement from the Federal Trade Commission, or FTC. The FTC has been particularly focused on the unpermitted processing of health and genetic data through its recent enforcement actions and is expanding the types of privacy violations that it interprets to be “unfair” under Section 5 of the FTC Act, as well as the types of activities it views to trigger the Health Breach Notification Rule (which the FTC also has the authority to enforce). The agency is also in the process of developing rules related to commercial surveillance and data security that may impact our business. We will need to account for the FTC’s evolving rules and guidance for proper privacy and data security practices in order to mitigate our risk for a potential enforcement action, which may be costly. If we are subject to a potential FTC enforcement action, we may be subject to a settlement order that requires us to adhere to very specific privacy and data security practices, which may impact our business. We may also be required to pay fines as part of a settlement (depending on the nature of the alleged violations). If we violate any consent order that we reach with the FTC, we may be subject to additional fines and compliance requirements.

States are also active in creating specific rules relating to the processing of personal information. In 2018, California passed into law the California Consumer Privacy Act, or the CCPA, which took effect on January 1, 2020 and imposed many requirements on businesses that process the personal information of California residents. Many of the CCPA’s requirements are similar to those found in the General Data Protection Regulation, or the GDPR, including requiring businesses to provide notice to data subjects regarding the information collected about them and how such information is

used and shared, and providing data subjects the right to request access to such personal information and, in certain cases, request the erasure of such personal information. The CCPA also affords California residents the right to opt-out of “sales” of their personal information. The CCPA contains significant penalties for companies that violate its requirements. In November 2020, California voters passed a ballot initiative for the California Privacy Rights Act, or the CPRA, which went into effect on January 1, 2023, and significantly expanded the CCPA to incorporate additional GDPR-like provisions including requiring that the use, retention, and sharing of personal information of California residents be reasonably necessary and proportionate to the purposes of collection or processing, granting additional protections for sensitive personal information, and requiring greater disclosures related to notice to residents regarding retention of information. The CPRA also created a new enforcement agency—the California Privacy Protection Agency—whose sole responsibility is to enforce the CPRA, which will further increase compliance risk. The provisions in the CPRA may apply to some of our business activities.

In addition to California, a number of other states have passed comprehensive privacy laws similar to the CCPA and CPRA. These laws are either in effect or will go into effect sometime over the next several years. Like the CCPA and CPRA, these laws create obligations related to the processing of personal information, as well as special obligations for the processing of “sensitive” data (which includes health data in some cases). Some of the provisions of these laws may apply to our business activities. These laws may impact our business activities, including our identification of research subjects, relationships with business partners and ultimately the marketing and distribution of our products.

Plaintiffs' lawyers are also increasingly using privacy-related statutes at both the state and federal level to bring lawsuits against companies for their data-related practices. In particular, there have been a significant number of cases filed against companies for their use of pixels and other web trackers. These cases often allege violations of the California Invasion of Privacy Act and other state laws regulating wiretapping, as well as the federal Video Privacy Protection Act. The rise in these types of lawsuits creates potential risk for our business.

Similar to the laws in the United States, there are significant privacy and data security laws that apply in Europe and other countries. The collection, use, disclosure, transfer, or other processing of personal data, including personal health data, regarding individuals who are located in the European Economic Area, or EEA, and the processing of personal data that takes place in the EEA, is regulated by the GDPR, which went into effect in May 2018 and imposes obligations on companies that operate in our industry with respect to the processing of personal data and the cross-border transfer of such data. The GDPR imposes onerous accountability obligations requiring data controllers and processors to maintain a record of their data processing and policies. If our or our partners’ or service providers’ privacy or data security measures fail to comply with the GDPR requirements, we may be subject to litigation, regulatory investigations, enforcement notices requiring us to change the way we use personal data and/or fines of up to 20 million Euros or up to 4% of the total worldwide annual turnover of the group of companies of the preceding financial year, whichever is higher, as well as compensation claims by affected individuals, negative publicity, reputational harm and a potential loss of business and goodwill.

The GDPR places restrictions on the cross-border transfer of personal data from the European Union to countries that have not been found by the European Commission to offer adequate data protection legislation, such as the United States. There are ongoing concerns about the ability of companies to transfer personal data from the European Union to other countries. In July 2020, the Court of Justice of the European Union, or CJEU, invalidated the EU-U.S. Privacy Shield, one of the mechanisms used to legitimize the transfer of personal data from the EEA to the United States. The CJEU’s decision also drew into question the long-term viability of an alternative means of data transfer, the standard contractual clauses, for transfers of personal data from the EEA to the United States. This CJEU decision has resulted in increased scrutiny on data transfers generally and may increase our costs of compliance with data privacy legislation as well as our costs of negotiating appropriate privacy and security agreements with our vendors and business partners.

Additionally, in October 2022, President Biden signed an executive order to implement the EU-U.S. Data Privacy Framework, which serves as a replacement to the EU-U.S. Privacy Shield. The European Commission adopted the adequacy decision in July 2023. The adequacy decision permits U.S. companies who self-certify to the EU-U.S. Data Privacy Framework to rely on it as a valid data transfer mechanism for data transfers from the European Union to the United States. However, some privacy advocacy groups have already suggested that they will be challenging the EU-U.S. Data Privacy Framework. If these challenges are successful, they may not only impact the EU-U.S. Data Privacy Framework, but also further limit the viability of the standard contractual clauses and other data transfer mechanisms. The uncertainty around this issue has the potential to impact our business internationally.

Following the withdrawal of the United Kingdom from the European Union, the United Kingdom’s Data Protection Act 2018 applies to the processing of personal data that takes place in the United Kingdom and includes parallel obligations to those set forth by GDPR. In relation to data transfers, both the United Kingdom and the European Union have determined, through separate “adequacy” decisions, that data transfers between the two jurisdictions are in compliance with the U.K.’s Data Protection Act 2018 and the GDPR, respectively. In October 2023, the United Kingdom and the United States

implemented a "U.S.-U.K. data bridge,” which functions similarly to the EU-U.S. Data Privacy Framework and provides an additional legal mechanism for companies to transfer data from the United Kingdom to the United States. Any changes or updates to these developments have the potential to impact our business.

Beyond GDPR, there are privacy and data security laws in a growing number of countries around the world. While many loosely follow GDPR as a model, other laws contain different or conflicting provisions. These laws will impact our ability to conduct our business activities, including both our clinical trials and the sale and distribution of commercial products, through increased compliance costs, costs associated with contracting and potential enforcement actions.

While we continue to address the implications of the recent changes to data privacy regulations, data privacy remains an evolving landscape at both the domestic and international level, with new regulations coming into effect and continued legal challenges, and our efforts to comply with the evolving data protection rules may be unsuccessful. It is possible that these laws may be interpreted and applied in a manner that is inconsistent with our practices. We must devote significant resources to understanding and complying with this changing landscape. Failure to comply with laws regarding data protection would expose us to risk of enforcement actions taken by data protection authorities in the EEA and elsewhere and carries with it the potential for significant penalties if we are found to be non-compliant. Similarly, failure to comply with federal and state laws in the United States regarding privacy and security of personal information could expose us to penalties under such laws. Any such failure to comply with data protection and privacy laws could result in government-imposed fines or orders requiring that we change our practices, claims for damages or other liabilities, regulatory investigations and enforcement action, litigation and significant costs for remediation, any of which could adversely affect our business. Even if we are not determined to have violated these laws, government investigations into these issues typically require the expenditure of significant resources and generate negative publicity, which could harm our reputation and our business, financial condition, results of operations or prospects.

Our employees, principal investigators, consultants and commercial partners may engage in misconduct or other improper activities, including non-compliance with regulatory standards and requirements and insider trading.

We are exposed to the risk of fraud or other misconduct by our employees, vendors, consultants and partners, and, for our clinical trials, our principal investigators and CROs. Misconduct by these parties could include intentional failures to comply with FDA regulations or the regulations applicable in the European Union and other jurisdictions, provide accurate information to the FDA, the European Commission, and other regulatory authorities, comply with healthcare fraud and abuse laws and regulations in the United States and abroad, report financial information or data accurately, or disclose unauthorized activities to us. In particular, 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 restrict or prohibit a wide range of pricing, discounting, marketing and promotion, sales commission, customer incentive programs, and other business arrangements. Such misconduct also could involve the improper use of information obtained in the course of clinical trials or interactions with the FDA or other regulatory authorities, which could result in regulatory sanctions and cause serious harm to our reputation. We have adopted a code of conduct applicable to all of our employees, but it is not always possible to identify and deter employee misconduct, and the precautions we take to detect and prevent this activity may not be effective in controlling unknown or unmanaged risks or losses or in protecting us from government investigations or other actions or lawsuits stemming from a failure to comply with these laws or regulations. 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, financial condition, results of operations and prospects, including the imposition of significant fines or other sanctions.

Laws and regulations governing any international operations we may have in the future may preclude us from developing, manufacturing and selling certain product candidates outside of the United States and require us to develop and implement costly compliance programs.

We are subject to numerous laws and regulations in each jurisdiction outside the United States in which we operate. The creation, implementation and maintenance of international business practices compliance programs is costly and such programs are difficult to enforce, particularly where reliance on third parties is required.

The Foreign Corrupt Practices Act, or FCPA, prohibits any U.S. individual or business from paying, offering, authorizing payment or offering of anything of value, directly or indirectly, to any foreign official, political party, or candidate for the purpose of influencing any act or decision of the foreign entity in order to assist the individual or business in obtaining or retaining business. The FCPA also obligates companies whose securities are listed in the United States to comply with certain accounting provisions requiring the company to maintain books and records that accurately and fairly reflect all transactions of the corporation, including international subsidiaries, and to devise and maintain an adequate system of internal accounting controls for international operations. The anti-bribery provisions of the FCPA are enforced primarily by the DOJ. The SEC is involved with enforcement of the books and records provisions of the FCPA.

Compliance with the FCPA and other anti-corruption laws potentially applicable to our business is expensive and difficult, particularly in countries in which corruption is a recognized problem. In addition, the compliance with the FCPA and other anti-corruption laws presents particular challenges in the pharmaceutical industry, because, in many countries, hospitals are operated by the government, and doctors and other hospital employees are considered foreign officials. Certain payments to hospitals in connection with clinical trials and other work have been deemed to be improper payments to government officials and have led to FCPA enforcement actions.

我们还受制于管理我们国际业务的其他法律和法规，包括适用的出口管制法律、对国家和个人的经济制裁以及海关要求。此外，各种法律、法规和行政命令还限制在美国境外使用和传播，或与某些非美国国民共享出于国家安全目的而保密的信息，以及某些产品和与这些产品有关的技术数据。我们在美国以外的扩张已经并将继续要求我们投入更多的资源来遵守这些法律，这些法律可能会阻止我们在美国以外的地方开发、制造或销售某些药物和候选药物，这可能会限制我们的增长潜力并增加我们的开发成本。

不能保证我们将完全有效地确保我们遵守《反海外腐败法》和其他适用的反腐败、出口、制裁和海关法律。如果不遵守管理国际商业惯例的法律，可能会受到重大处罚，包括暂停或取消政府合同的资格。违反这些法律，包括《反海外腐败法》，可能会导致重大的民事和刑事处罚。仅根据《反海外腐败法》提起诉讼就可能导致暂停与美国政府做生意的权利，直到悬而未决的索赔得到解决。违反《反海外腐败法》的定罪可能会导致长期取消政府承包商的资格。由于我们未能根据国际商业惯例法律履行我们的任何义务而导致政府合同或关系的终止，将对我们的运营产生负面影响，并损害我们的声誉和获得政府合同的能力。美国证券交易委员会还可能因发行人违反《反海外腐败法》的会计规定而暂停或禁止发行人在美国交易所交易证券。

如果我们或我们现在或将来雇佣的任何第三方制造商未能遵守环境、健康和安全法律法规，我们可能会受到罚款或罚款，或者产生可能对我们的业务产生重大不利影响的成本或责任。

我们现在和我们雇佣的第三方制造商，以及我们未来可能雇佣的任何第三方制造商，都将受到众多环境、健康和安全法律法规的约束，包括那些管理实验室程序以及危险材料和废物的处理、使用、储存、处理和处置的法律法规。我们的行动涉及使用危险和易燃材料，包括化学品和生物材料。我们的业务还会产生危险废物产品。我们通常与第三方签订合同，处理这些材料和废物。我们不能消除这些材料造成污染或伤害的风险。如果我们使用危险材料造成污染或伤害，我们可能要对由此造成的任何损害负责，任何责任都可能超出我们的资源范围。我们还可能产生与民事或刑事罚款和处罚相关的巨额费用。

尽管我们购买了一般责任保险和工伤保险，以保障我们因使用有害材料导致员工受伤而可能产生的成本和费用，但该保险可能无法为潜在责任提供足够的保障。我们不为可能因我们储存或处置生物、危险或放射性材料而对我们提出的环境责任或有毒侵权索赔投保。

此外，为了遵守当前或未来的环境、健康和安全法律法规，我们可能会产生巨额成本。这些现行或未来的法律法规可能会损害我们的研究、开发或商业化努力。不遵守这些法律法规也可能导致巨额罚款、处罚或其他制裁。

此外，对于我们目前和任何未来的第三方合同制造商的运营，如果他们未能遵守适用的环境，健康和安全法律法规或妥善处理与我们产品相关的废物，我们可能会对任何由此造成的损害负责，在我们的候选产品或产品的制造和供应过程中遭受声誉损害或中断。此外，倘我们的任何第三方合约制造商因不遵守环境、健康及安全法律及法规而受到禁制令或其他制裁，则我们的供应链可能受到不利影响。

我们未来的成功取决于我们留住关键高管的能力，以及吸引、留住和激励合格人才的能力。

我们高度依赖首席执行官Sekar Kathiresan万.D.、首席运营官兼总法律顾问总裁、首席财务官Allison Dorval、首席医疗官Frederick Fiedorek万.D.、首席科学官Troy Lister博士以及我们管理、科学和临床团队的其他主要成员的研发、临床、财务、运营和其他业务专长。虽然我们已经与我们的高管签订了雇佣协议，但他们中的每一位都可以随时终止与我们的雇佣关系。我们不为我们的任何高管或其他员工提供“关键人物”保险。招聘和留住合格的科学、临床、制造、会计、法律以及销售和营销人员也将是我们成功的关键。

失去高管或其他关键员工的服务可能会阻碍我们研发和商业化目标的实现，并严重损害我们成功实施业务战略的能力。此外，更换高管和关键员工可能很困难，而且可能需要较长的时间，因为我们行业中拥有成功开发、获得营销批准和产品商业化所需的技能和经验的个人数量有限。从这个有限的人才库中招聘的竞争非常激烈，鉴于众多制药和生物技术公司之间对类似人员的竞争，我们可能无法以可接受的条件聘用、培训、留住或激励这些关键人员。我们还面临着从大学和研究机构招聘科学和临床人员的竞争。此外，我们依靠顾问和顾问，包括科学和临床顾问，帮助我们制定我们的研发和商业化战略。我们的顾问和顾问可能受雇于我们以外的雇主，并可能根据与其他实体签订的咨询或咨询合同作出承诺，这可能会限制我们获得他们的机会。我们的成功还取决于实施和维持内部控制以及我们财务报告的准确性和及时性。如果我们不能继续吸引和留住高素质的人才，我们推行增长战略的能力将受到限制。

我们预计将扩大我们的开发和监管能力，并可能实施销售，营销和分销能力，因此，我们可能会在管理我们的增长方面遇到困难，这可能会扰乱我们的运营。

随着我们的发展，我们预计我们的员工数量和业务范围将大幅增长，特别是在药物开发、临床、监管事务、制造和质量控制领域，如果我们的任何候选产品获得营销批准、销售、营销和分销的话。为了管理我们预期的未来增长，我们必须继续实施和改进我们的管理、运营和财务系统，扩大我们的设施，并继续招聘和培训更多合格的人员。由于我们的财务资源有限，以及我们的管理团队在管理一家具有如此预期增长的公司方面的经验有限，我们可能无法有效地管理我们业务的扩张，或招聘和培训更多合格的人员。我们业务的扩张可能会导致巨大的成本，并可能转移我们的管理和业务发展资源。任何无法管理增长的情况都可能推迟我们业务计划的执行或扰乱我们的运营。

未来的收购或战略联盟可能会扰乱我们的业务，损害我们的财务状况和运营结果。

我们可能会收购更多的业务、技术或资产，与第三方结成战略联盟或创建合资企业，我们相信这些将补充或扩大我们现有的业务。如果我们收购具有前景的市场或技术的业务，如果我们不能成功地将它们与我们现有的运营和公司文化相结合，我们可能无法实现收购这些业务的好处。我们在开发、制造和营销因战略联盟或收购而产生的任何新产品或候选产品时，可能会遇到许多困难，可能会推迟或阻止我们实现预期的好处或增强我们的业务。我们不能向我们的股东保证，在任何此类收购之后，我们将实现预期的协同效应，以证明交易是合理的。我们在收购方面面临的风险包括：

我们未能解决这些风险或在过去或未来的收购或战略联盟中遇到的其他问题，可能会导致我们无法实现这些交易的预期好处，导致我们产生意想不到的债务，并总体上损害业务。还有一种风险是，未来的收购将导致债务、或有负债、摊销费用或增量运营费用，任何这些都可能损害我们的财务状况或运营结果。

我们的内部信息技术系统，或我们的合作者、供应商或其他承包商或顾问的系统，可能会出现故障或遭受安全漏洞、数据丢失和其他中断，这可能会导致我们的产品开发计划严重中断，危及与我们业务相关的敏感信息，或阻止我们访问关键信息，触发合同和法律义务，可能使我们承担责任、声誉损害或以其他方式对我们的业务和财务业绩产生不利影响。

我们依赖信息技术系统、基础设施和数据来运营我们的业务。在正常业务过程中，我们收集、存储和传输机密信息，包括但不限于知识产权、专有业务信息和个人信息。至关重要的是，我们、我们的供应商、协作者或其他承包商或顾问必须以安全的方式这样做，以维护此类机密信息的可用性、安全性、保密性、隐私性和完整性。

尽管实施了安全措施，我们以及任何合作者、供应商、承包商或顾问的内部信息技术系统很容易受到计算机病毒、计算机黑客、恶意代码、员工错误、盗窃或滥用、拒绝服务攻击、复杂的民族国家和民族国家支持的行为者的损害或中断，未经授权的访问、自然灾害、恐怖主义、战争或其他武装冲突，电信和电气故障或其他损害。由于俄罗斯和乌克兰之间持续的战争以及美国和欧洲各国政府由此实施的制裁，以及他们未来采取的任何额外制裁或其他行动，网络安全攻击总体上可能会增加。

网络攻击的频率、复杂性和强度都在增加，而且越来越难被发现。网络攻击可能包括部署有害的恶意软件、勒索软件、拒绝服务攻击、未经授权访问或删除文件、社会工程和其他手段，以影响服务可靠性并威胁信息的机密性、完整性和可用性。网络攻击还可能包括网络钓鱼或电子邮件欺诈，导致付款或信息被传输给非预期的收件人，还可能包括使用人工智能和机器学习对目标发动更自动化、有针对性和有组织的攻击。我们可能无法预见所有类型的安全威胁，也可能无法针对所有这些安全威胁采取有效的预防措施。网络犯罪分子使用的技术经常变化，可能在启动之前不会被认识到，而且可能来自各种各样的来源，包括外部服务提供商、有组织犯罪分支机构、恐怖组织或敌对的外国政府或机构等外部团体。

虽然我们没有经历过任何与网络攻击或安全漏洞有关的重大损失，但我们一直受到黑客攻击的攻击，导致我们的系统受到有限的破坏。我们不能保证我们迄今采取的措施以及我们未来可能采取的行动足以防止未来的任何网络攻击或安全漏洞。

在我们经历重大系统故障、事故、网络攻击或安全漏洞的程度上，它可能导致我们的开发计划和业务运营的重大中断，无论是由于我们的商业机密或其他专有或机密信息的损失，还是由于其他中断。例如，我们正在进行或计划进行的临床试验中的临床试验数据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。如果我们不分配和有效管理建立和维持适当的技术和网络安全基础设施所需的资源，我们可能会遭受严重的业务中断，包括交易错误、供应链或制造中断、处理效率低下、数据丢失或知识产权或其他专有信息的丢失或损坏。

如果任何中断或安全漏洞导致我们或我们的供应商、合作者或其他承包商或顾问的数据或应用程序丢失或损坏，或者不适当地披露机密或专有信息，我们可能会招致责任，包括诉讼曝光、处罚和罚款，我们可能成为监管行动或调查的对象，我们的竞争地位和声誉可能会受到损害，我们候选产品的进一步开发和商业化可能会被推迟。由于这样的事件，我们可能会违反我们的合同义务。此外，任何此类导致未经授权访问、使用或泄露个人信息(包括有关我们客户或员工的个人信息)的事件都可能损害我们的声誉，迫使我们遵守联邦和/或州的违规通知法和外国同等法律，强制我们采取纠正措施，否则我们将根据保护个人信息隐私和安全的法律和法规承担责任，这可能导致重大的法律和经济风险以及声誉损害。以上任何一项都可能对我们的业务、财务状况、运营结果或前景产生重大不利影响。

上述事件的财务风险可能无法通过我们维持的任何保险进行保险或不能完全覆盖，并可能对我们的业务、财务状况、运营结果或前景产生重大不利影响。此外，我们不能确保我们现有的保险范围将继续以可接受的条款提供，或者我们的保险公司不会拒绝承保任何未来的索赔。不能保证我们合同中的责任限制是可强制执行的或充分的，或以其他方式保护我们免受上述事件造成的责任或损害。

我们的高管、董事及其附属公司，如果他们选择共同行动，将有能力对提交给股东批准的所有事项产生重大影响。

截至2024年10月29日，我们的执行官和董事及其关联公司总共受益拥有约占我们普通股19.5%的股份。因此，如果这些股东选择共同行动，他们将有效地影响提交给股东批准的所有事项以及我们的管理和事务。例如，如果这些人选择共同行动，可能会对董事的选举以及我们所有或几乎所有资产的任何合并、合并或出售的批准产生重大影响。

我们公司章程文件和特拉华州法律中的条款可能会使对我们公司的收购变得更加困难，这可能对我们的股东有利，并可能阻止我们的股东试图更换或罢免我们目前的董事和管理层成员。

我们重述的公司注册证书以及修订和重述的章程中的条款可能会阻止、推迟或阻止股东可能认为有利的我们公司的合并、收购或其他控制权变更，包括我们的股东可能会获得其股票溢价的交易。这些条款还可能限制投资者未来可能愿意为我们普通股支付的价格，从而压低我们普通股的市场价格。此外，由于我们的董事会负责任命我们管理团队的成员，因此这些规定可能会挫败或阻止我们的股东更换或罢免我们现任管理层的任何企图，使股东更难更换我们的董事会成员。除其他外，这些规定：

此外，由于我们是在特拉华州注册成立的，我们受特拉华州公司法第203条的规定管辖，该条款禁止持有我们已发行有表决权股票超过15%的人在交易日期后三年内与我们合并或合并，除非合并或合并以规定的方式获得批准。

我们的普通股于2021年6月17日在纳斯达克全球精选市场开始交易。鉴于我们普通股的交易历史有限，我们股票的活跃交易市场可能无法持续下去。因此，我们的股东可能很难在不压低股票市场价格的情况下出售他们的股票，或者根本就很难。

如果证券分析师不发布或停止发布研究或报告，或者发布有关我们业务的误导性、不准确或不利的研究，或者如果他们发布对我们股票的负面评价，我们股票的价格和交易量可能会下降。

我们普通股的交易市场在一定程度上依赖于行业或金融分析师发布的关于我们或我们业务的研究和报告。不能保证现有的分析师将继续跟踪我们，也不能保证新的分析师将开始跟踪我们。也不能保证任何报道分析师会提供有利的报道。尽管我们已经获得了分析师的报道，但如果一名或多名跟踪我们业务的分析师下调了他们对我们股票的评估，或者发表了关于我们业务的不准确或不利的研究报告，或者提供了关于我们竞争对手的更有利的相对建议，我们的股票价格可能会下跌。如果这些分析师中的一位或多位不再跟踪我们的股票，我们可能会失去我们股票在市场上的可见度，这反过来可能会导致我们的股价和交易量下降。

我们普通股的价格一直不稳定，可能会大幅波动，这可能会给我们的股东带来重大损失。

我们的股价一直在波动，而且很可能会继续波动。股票市场，特别是较小的生物制药公司的市场经历了极端的波动，这种波动往往与某些公司的经营业绩无关。由于这种波动，我们的股东可能无法以或高于他们购买股票的价格出售他们的普通股。我们普通股的市场价格可能受到许多因素的影响，包括：

过去，在公司证券市场价格波动一段时间后，通常会对该公司提起证券集体诉讼。例如，我们和我们的某些官员在所谓的集体诉讼中被列为被告。该诉讼和我们作为一方当事人的其他类似诉讼，无论是否有法律依据，都可能导致不利的判决。我们还可能决定以不利的条件解决诉讼。任何此类负面结果都可能导致支付巨额损害赔偿或罚款、损害我们的声誉或对我们的产品或商业实践造成不利变化。此类诉讼还可能导致我们承担其他巨额费用来捍卫此类索赔并转移管理层的注意力和资源。此外，听证会、动议或其他临时程序或事态发展结果的负面公告可能会对我们普通股的市场价格产生负面影响。

我们和我们的某些官员已被列为一场所谓的证券集体诉讼的被告。该诉讼以及潜在的类似或相关诉讼或调查可能会导致重大损失，分散管理层对我们业务的时间和注意力，并对我们的运营业绩产生重大不利影响。该诉讼以及我们面临的任何其他诉讼或调查，辩护或遵守的成本将很高，并且结果不确定。

2024年8月27日，一起推定的证券集体诉讼标题为Oldroyd诉Verve治疗公司等艾尔，案件号1：24-CV-12218，已在美国马萨诸塞州地区地方法院针对我们和我们的某些官员提起诉讼。该投诉指控违反了《交易法》第10（b）和20（a）条以及据此颁布的100亿.5条规则，其依据是有关暂停招募我们的Heart-1试验的据称存在重大虚假和误导性陈述和遗漏。除其他外，该投诉寻求未具体说明的损害赔偿、利息、律师费、专家费和其他费用。

我们无法预测此事的结果，我们打算对这一行动进行有力辩护。然而，无论索赔是否成功，诉讼往往代价高昂，并且可能会转移管理层的注意力和资源对其他业务问题的注意力和资源，这可能会对我们的业务产生不利影响。

我们目前无法估计这一行动可能给我们带来的成本，因为悬而未决的诉讼目前处于早期阶段，我们无法确定需要多长时间才能解决悬而未决的诉讼，也无法确定我们可能需要支付的任何损害赔偿金额。如果我们最终被要求支付巨额辩护费用、损害赔偿或和解金额，此类付款可能会对我们的运营产生不利影响。

未来我们可能会成为类似诉讼或调查的目标。我们普通股的市场价格已经经历并可能继续经历波动，过去，股票市场价格经历波动的公司曾受到证券诉讼。未来的任何诉讼或调查都可能导致巨额成本，并转移我们管理层对其他业务问题的注意力，这可能会严重损害我们的业务。我们维持责任保险;然而，如果与未决诉讼或任何其他诉讼或调查相关的任何成本或费用超出了我们的保险范围，我们可能被迫直接承担部分或所有成本和费用，这可能会对我们的业务、财务状况、运营业绩或股价产生不利影响。

我们在使用现金、现金等值物和有价证券方面拥有广泛的自由裁量权，并且可能无法有效使用它们。

我们的管理层在运用我们的现金、现金等价物和有价证券方面拥有广泛的自由裁量权，可以在不改善我们的经营业绩或提高我们普通股价值的情况下使用这些资金。如果我们的管理层未能有效地使用这些资金，可能会导致财务损失，这可能会对我们的业务产生实质性的不利影响，导致我们的普通股价格下跌，并推迟我们候选产品的开发。在它们使用之前，我们可能会以不产生收入或贬值的方式投资这些资金。

即使我们的业务表现良好，出售大量普通股也可能导致我们普通股的市场价格显着下跌。

在公开市场上出售大量普通股，或者市场认为大量股票的持有者打算出售股票，可能会降低我们普通股的市场价格。人

在我们首次公开募股之前是我们的股东的人继续持有我们大量普通股股票。如果这些人在公开市场出售或表示有意出售我们大量普通股，我们普通股的交易价格可能会下跌。

此外，我们的某些高管、董事和与我们董事有关联的股东已经或可能加入规则10b5-1，规定不时出售我们的普通股。根据规则10b5-1计划，经纪商根据高管、董事或关联股东在进入计划时建立的参数执行交易，而无需高管、董事或关联股东的进一步指示。规则10b5-1计划可能在某些情况下被修改或终止。我们的高管、董事和与我们董事有关联的股东也可以在不掌握重大、非公开信息的情况下购买或出售规则10b5-1计划之外的股票。

此外，在符合特定条件的情况下，持有相当数量普通股的持有者有权要求我们提交关于他们股票的登记声明，或将他们的股票包括在我们可能为自己或其他股东提交的登记声明中。我们还提交了S-8表格的登记声明，登记了我们根据股权补偿计划能够发行的所有普通股。以S-8表格形式登记的股票在发行时可在公开市场自由出售，但受适用于关联公司、归属安排和行使期权的数量限制。

由于作为上市公司运营，我们已经并将继续产生增加的成本，我们的管理层已经投入并将继续被要求投入大量时间用于新的合规举措和公司治理实践。

作为一家上市公司，我们正在招致巨额的法律、会计和其他费用，这是我们以前作为私人公司没有招致的。2002年萨班斯-奥克斯利法案、多德-弗兰克华尔街改革和消费者保护法、纳斯达克全球精选市场的上市要求以及其他适用的证券规则和法规对上市公司提出了各种要求，包括建立和维持有效的披露、财务控制和公司治理做法。我们的管理层和其他人员致力于并将需要继续投入大量时间来实施这些合规倡议。此外，这些规则和法规将增加我们的法律和财务合规成本，特别是在我们雇用额外的财务和会计员工以满足上市公司内部控制和财务报告要求的情况下，并将使一些活动与我们还是私人公司时相比更加耗时和成本更高。例如，我们预计这些规章制度可能会使我们获得董事和高级管理人员责任保险变得更加困难和昂贵，这反过来可能会使我们更难吸引和留住合格的董事会成员。

我们正在评估这些规则和法规，无法预测或估计我们可能产生的额外成本金额或此类成本的时间。这些规则和法规往往有不同的解释，在许多情况下是由于它们缺乏具体性，因此，随着监管和理事机构提供新的指导，它们在实践中的应用可能会随着时间的推移而变化。这可能会导致合规问题持续存在不确定性，并因持续修改披露和治理实践而导致成本上升。

根据《萨班斯-奥克斯利法案》第404条，我们必须由我们的管理层提交一份关于我们的财务报告内部控制的报告，我们的独立注册会计师事务所必须证明我们的财务报告内部控制的有效性。对于我们的管理层来说，遵守第404条一直是并将继续是昂贵和耗时的。如果我们有一个无法弥补的重大弱点，我们将收到我们的独立注册会计师事务所对我们的财务报告内部控制的负面意见。如果我们发现我们对财务报告的内部控制存在一个或多个重大弱点，可能会导致金融市场因对我们财务报表的可靠性失去信心而产生不良反应。

由于我们预计在可预见的未来不会对我们的股本支付任何现金股息，因此资本增值(如果有的话)将是我们股东唯一的收益来源。

我们从未宣布或支付过我们股本的现金股息。我们目前打算保留我们未来的所有收益，如果有的话，为我们业务的增长和发展提供资金。因此，我们普通股的资本增值(如果有的话)将是我们股东在可预见的未来唯一的收益来源。

我们重述的公司注册证书指定特拉华州大法官法院和美利坚合众国联邦地区法院为某些类型诉讼的唯一和独家法庭

以及我们的股东可能发起的诉讼，这可能会限制我们的股东获得有利的司法论坛来解决与我们或我们的董事、高级管理人员和员工的纠纷的能力。

我们重述的公司注册证书规定，除非我们书面同意选择其他法院，否则特拉华州衡平法院（或者，如果特拉华州衡平法院没有管辖权，根据特拉华州成文法或普通法，以下类型的诉讼或程序将由特拉华州联邦地区法院（即特拉华州联邦地区法院）作为唯一和排他性的法院：

这些对法院条款的选择将不适用于为执行《交易法》规定的义务或责任而提起的诉讼。此外，《证券法》第22条规定，联邦法院和州法院对所有此类《证券法》诉讼拥有同时管辖权。因此，州法院和联邦法院都有管辖权受理此类索赔。为了避免不得不在多个司法管辖区对索赔提起诉讼，以及不同法院做出不一致或相反裁决的威胁等考虑因素，我们重述的公司注册证书规定，除非我们书面同意选择替代法院，否则在法律允许的最大范围内，美利坚合众国联邦地区法院应是解决根据证券法产生的任何索赔的唯一和独家法院。虽然特拉华州法院已经确定这种选择的法院条款在事实上是有效的，但股东仍然可以寻求在专属法院条款指定的地点以外的地点提出索赔。在这种情况下，我们预计将大力主张我们重述的公司注册证书的独家论坛条款的有效性和可执行性。这可能需要与在其他法域解决这类诉讼相关的大量额外费用，而且不能保证这些规定将由这些其他法域的法院执行。

这些排他性论坛条款可能会限制我们的股东在司法论坛上提出他们认为有利于与我们或我们的董事、高级管理人员或员工发生纠纷的索赔的能力，这可能会阻止针对我们和我们的董事、高级管理人员和员工的此类诉讼。如果法院发现我们重述的公司注册证书中包含的任何一项独家法院条款在诉讼中不适用或不可执行，我们可能会在其他司法管辖区产生与解决此类诉讼相关的进一步重大额外费用，所有这些都可能对我们的业务、财务状况和运营结果产生重大不利影响。

我们的披露控制和程序可能无法阻止或检测所有错误或欺诈行为。

我们必须遵守《交易法》的某些报告要求。我们的披露控制和程序旨在合理地确保我们根据交易所法案提交或提交的报告中要求我们披露的信息得到积累，并在美国证券交易委员会规则和表格中指定的时间段内传达给管理层、记录、处理、汇总和报告。我们相信，任何披露控制和程序或内部控制和程序，无论构思和运作如何完善，都只能提供合理的、而不是绝对的保证，确保控制系统的目标得以实现。这些固有的局限性包括这样的现实，即决策过程中的判断可能是错误的，故障可能因为简单的错误或错误而发生。此外，某些人的个人行为、两个或两个以上人的串通或未经授权超越控制，都可以规避控制。因此，由于我们的控制系统的固有限制，由于错误或欺诈而导致的错误陈述或披露不足的情况可能会发生，而不会被发现。

税法或其实施或解释的变化可能会对我们的业务和财务状况产生不利影响。

税法的变化可能会对我们的业务或财务状况产生不利影响。2017年12月22日，美国政府颁布了《税法》，对该法进行了重大改革。经CARE法案等修订的税法包含了对公司税的重大变化，包括将公司税率从35%的最高边际税率降至21%的统一税率，并将2017年12月31日后开始的纳税年度产生的NOL的扣除额限制在本年度应税收入的80%。此外，从2022年开始，税法取消了目前扣除研发支出的选择，一般要求公司在五年或15年内将其资本化和摊销(用于可归因于外国研究的支出)。

除了CARE法案，作为国会应对新冠肺炎疫情的一部分，2020年和2021年颁布了包含税收条款的经济救济立法，引入了一些新税收条款的爱尔兰共和军于2022年8月签署成为法律。爱尔兰共和军特别对上市公司的某些股票回购征收1%的消费税，这通常适用于上市公司(或其某些附属公司)为换取金钱或其他财产(公司本身的股票除外)而收购上市公司的股票，但有极低限度的例外情况。因此，消费税可能适用于非传统股票回购的某些交易。根据税法、爱尔兰共和军和这类额外立法提供的监管指导正在并将继续，这种指导最终可能会增加或减少它们对我们的业务和财务状况的影响。此外，目前还不确定各州是否以及在多大程度上将遵守税法、爱尔兰共和军和其他税收立法。我们敦促我们普通股的潜在投资者就最近颁布的任何税法或拟议的法律变化以及投资或持有我们普通股的潜在税收后果咨询他们的法律和税务顾问。

不利的全球经济状况可能对我们的业务、财务状况、股价和经营业绩产生不利影响。

我们的经营业绩可能会受到全球经济和全球金融市场总体状况以及经济稳定性不确定性的不利影响。全球经济和金融市场也可能受到军事冲突当前或预期影响的不利影响，包括以色列和哈马斯之间正在进行的战争、俄罗斯和乌克兰之间正在进行的战争、恐怖主义或其他地缘政治事件。美国和其他国家为应对这种冲突而实施的制裁，包括与俄罗斯有关的制裁，也可能对金融市场和全球经济造成不利影响，受影响国家或其他国家的经济对策可能会加剧市场和经济的不稳定。不能保证信贷和金融市场的进一步恶化以及对经济状况的信心不会发生。严重或长期的经济低迷可能会给我们的业务带来各种风险，包括对我们可能开发的任何候选产品的需求减弱，以及我们在需要时以可接受的条件筹集额外资本的能力(如果有的话)。经济疲软或下滑也可能给我们的供应商带来压力，可能导致供应中断。如果股市和信贷市场恶化，可能会使任何必要的债务或股权融资变得更加困难、成本更高、稀释程度更高。如果不能及时以有利的条件获得任何必要的融资，可能会削弱我们实现增长战略的能力，可能会损害我们的财务业绩和股价，并可能要求我们推迟或放弃临床开发计划。此外，我们目前或未来的服务提供商、制造商或其他合作伙伴可能无法挺过经济困难时期，这可能直接影响我们按时和按预算实现运营目标的能力。我们无法预测当前的经济气候和金融市场状况可能对我们的业务产生不利影响的所有方式。

Item 2. Unregistered sales of equity securities, use of proceeds, and issuer purchases of equity securities

在本Form 10-Q季度报告所涵盖的期间内，本公司并无发行任何非注册股本证券，但根据本公司目前的Form 8-k报告所披露的交易除外。

2021年6月21日，我们根据美国证券交易委员会于2021年6月16日宣布生效的S-1表格注册书(第333-256608号文件)和根据证券法第462(B)条提交、美国证券交易委员会于2021年6月16日宣布生效的S-1表格注册书(第333-257158号文件)完成了首次公开募股。

扣除承保折扣和我们应付的发行费用2510万美元后，我们的发行净收益为28160万美元。截至2024年9月30日，我们尚未使用IPO的任何净收益。我们已将此次发行的净收益投资于货币市场基金和有价证券。正如我们根据第424（b）条向美国证券交易委员会提交的日期为2021年6月16日的最终招股说明书中所述，我们IPO净收益的计划用途没有重大变化。

我们的董事或高级职员通过或已终止本报告涵盖的季度期间，规则10 b5 -1交易安排或非规则10 b5 -1交易安排（定义见S-K法规第408（c）项）。

根据1934年《证券交易法》的要求，注册人已正式促使本报告由正式授权的签署人代表其签署。


特拉华州	82-4800132
(述明或其他司法管辖权公司或组织)	(税务局雇主识别号码)

布鲁克莱恩大道201号, 一座601室波士顿, 马萨诸塞州	02215
（主要行政办公室地址）	(邮政编码)


		页面
第一部分：	财务信息	1
第1项。	财务报表(未经审计)	1
	简明综合资产负债表	1
	简明合并经营报表和全面亏损	2
	股东权益简明合并报表	3
	现金流量表简明合并报表	4
	简明合并财务报表附注(未经审计)	5
第二项。	管理层对财务状况和经营成果的探讨与分析	14
第三项。	关于市场风险的定量和定性披露	25
第四项。	控制和程序	26

第二部分。	其他信息	27
第1项。	法律诉讼	27
第1A项。	风险因素	27
第二项。	股权证券的未登记销售、所得款项的使用和发行人购买股权证券	91
第五项。	其他信息	91
第六项。	陈列品	92
签名		93


(单位为千，不包括每股和每股金额) (未经审计)	9月30日， 2024			十二月三十一日， 2023
资产
流动资产：
现金及现金等价物	$	158,709		$	206,180
有价证券		381,211			417,770
应收合作		2,628			5,897
预付费用和其他流动资产		13,911			8,102
流动资产总额		556,459			637,949
财产和设备，净额		19,625			22,505
受限现金		4,774			4,774
经营性租赁使用权资产		79,921			85,295
其他长期资产		3,127			2,165
总资产	$	663,906		$	752,688
负债和股东权益
流动负债：
应付帐款	$	4,637		$	6,636
应计费用		21,918			20,178
递延收入，当期		5,719			—
租赁负债，流动		10,368			10,192
流动负债总额		42,642			37,006
长期租赁负债		60,887			64,715
成功付款责任		977			2,720
递延收入，非流动		50,731			48,556
其他长期负债		118			189
总负债		155,355			153,186
承诺和或有事项（见注7、注8和注9）
股东权益：
优先股，$0.001票面价值；5,000,000授权股份；不是已发行和已发行的股份		—			—
普通股，$0.001票面价值；200,000,000授权的股份，84,638,814和81,969,693 分别于2024年9月30日和2023年12月31日发行和发行的股票		85			82
额外实收资本		1,200,302			1,143,453
累计其他综合收益		1,143			272
累计赤字		(692,979	)		(544,305	)
股东权益总额		508,551			599,502
总负债和股东权益	$	663,906		$	752,688


	截至9月30日的三个月，						截至9月30日的9个月，
(in千，份额和每股金额除外）（未经审计）	2024			2023			2024			2023
协作收入	$	6,865		$	3,117		$	19,252		$	6,614
运营费用：
研发		49,938			43,765			149,299			138,135
一般和行政		13,837			11,686			42,546			37,655
总运营支出		63,775			55,451			191,845			175,790
运营亏损		(56,910	)		(52,334	)		(172,593	)		(169,176	)
其他收入(支出)：
成功付款负债公允价值变化		(6	)		802			1,743			878
利息和其他收入，净额		6,887			5,841			22,452			16,825
其他收入合计，净额		6,881			6,643			24,195			17,703
扣除所得税准备前的亏损		(50,029	)		(45,691	)		(148,398	)		(151,473	)
所得税拨备		(104	)		(67	)		(276	)		(243	)
净亏损	$	(50,133	)	$	(45,758	)	$	(148,674	)	$	(151,716	)
每股普通股基本亏损和摊薄后净亏损	$	(0.59	)	$	(0.72	)	$	(1.77	)	$	(2.43	)
用于每股净亏损的加权平均普通股，基本和稀释		84,632,952			63,211,849			83,999,797			62,322,965
综合损失：
净亏损	$	(50,133	)	$	(45,758	)	$	(148,674	)	$	(151,716	)
其他全面亏损：
有价证券的未实现收益		1,758			157			871			97
综合损失	$	(48,375	)	$	(45,601	)	$	(147,803	)	$	(151,619	)


	普通股
(单位为千，不包括份额) (未经审计)	股份		量		其他内容已缴费资本		累计其他综合损失			累计赤字			总股东的股权
2022年12月31日的余额		61,730,816	$	62	$	895,801	$	(694	)	$	(344,237	)	$	550,932
股票期权的行使		29,010		-		116		-			-			116
通过市价发行普通股，扣除发行成本美元126		103,184		-		1,922		-			-			1,922
有价证券的未实现收益		-		-		-		457			-			457
基于股票的薪酬		-		-		8,024		-			-			8,024
净亏损		-		-		-		-			(51,975	)		(51,975	)
2023年3月31日的余额		61,863,010		62		905,863		(237	)		(396,212	)		509,476
股票期权的行使		98,598		-		548		-			-			548
有限制股份单位的归属		50,537		-		-		-			-			-
员工购股计划下普通股的发行		52,134		-		685		-			-			685
有价证券未实现亏损		-		-		-		(517	)		-			(517	)
基于股票的薪酬		-		-		9,013		-			-			9,013
净亏损		-		-		-		-			(53,983	)		(53,983	)
2023年6月30日的余额		62,064,279		62		916,109		(754	)		(450,195	)		465,222
股票期权的行使		43,429		-		213		-			-			213
有限制股份单位的归属		76,586		-		-		-			-			-
与礼来协议相关的普通股发行		1,552,795		2		31,708		-			-			31,710
有价证券的未实现收益		-		-		-		157			-			157
基于股票的薪酬		-		-		8,825		-			-			8,825
净亏损		-		-		-		-			(45,758	)		(45,758	)
2023年9月30日的余额		63,737,089	$	64	$	956,855	$	(597	)	$	(495,953	)	$	460,369

2023年12月31日的余额		81,969,693	$	82	$	1,143,453	$	272		$	(544,305	)	$	599,502
股票期权的行使		76,044		-		301		-			-			301
有限制股份单位的归属		7,290		-		-		-			-			-
通过市价发行普通股，扣除发行成本美元747		1,766,835		2		22,431		-			-			22,433
有价证券未实现亏损		-		-		-		(772	)		-			(772	)
基于股票的薪酬		-		-		10,341		-			-			10,341
净亏损		-		-		-		-			(48,736	)		(48,736	)
2024年3月31日的余额		83,819,862		84		1,176,526		(500	)		(593,041	)		583,069
股票期权的行使		520,995		1		825		-			-			826
有限制股份单位的归属		104,426		-		-		-			-			-
员工购股计划下普通股的发行		106,986		-		472		-			-			472
有价证券未实现损失		-		-		-		(115	)		-			(115	)
基于股票的薪酬		-		-		11,647		-			-			11,647
净亏损		-		-		-		-			(49,805	)		(49,805	)
2024年6月30日的余额		84,552,269		85		1,189,470		(615	)		(642,846	)		546,094
股票期权的行使		5,075		-		14		-			-			14
有限制股份单位的归属		81,470		-		-		-			-			-
有价证券的未实现收益		-		-		-		1,758			-			1,758
基于股票的薪酬		-		-		10,818		-			-			10,818
净亏损		-		-		-		-			(50,133	)		(50,133	)
2024年9月30日余额		84,638,814	$	85	$	1,200,302	$	1,143		$	(692,979	)	$	508,551


☒	根据1934年《证券交易法》第13或15(D)条规定的季度报告


☐	根据1934年证券交易法第13或15（d）条提交的过渡报告


大型加速文件服务器	☒	加速文件管理器	☐
非加速文件服务器	☐	规模较小的报告公司	☐
		新兴成长型公司	☐


	截至9月30日的9个月，
(未经审计，以千计)	2024			2023
经营活动的现金流：
净亏损	$	(148,674	)	$	(151,716	)
对净亏损与经营活动中使用的现金净额进行的调整：
折旧		5,053			3,938
非现金租赁费用		5,374			5,046
有价证券折价净增量		(10,250	)		(11,044	)
基于股票的薪酬		32,806			25,862
成功付款负债公允价值变化		(1,743	)		(878	)
经营资产和负债变化：
应收合作		3,264			(3,117	)
预付费用和其他资产		(6,765	)		(2,587	)
应付帐款		(2,321	)		(589	)
应计费用和其他负债		2,167			2,996
经营租赁负债		(3,653	)		(5,320	)
递延收入		7,895			28,540
用于经营活动的现金净额		(116,847	)		(108,869	)
投资活动产生的现金流：
购置财产和设备		(2,349	)		(7,098	)
购买有价证券		(350,928	)		(394,817	)
有价证券的到期日		398,607			438,498
投资活动提供的现金净额		45,330			36,583
融资活动的现金流：
与合作协议相关的普通股发行收益		—			31,710
行使股票期权所得收益		1,141			877
发行普通股所得收益，扣除发行成本		22,433			1,922
员工购股计划下普通股的发行		472			685
融资活动提供的现金净额		24,046			35,194
现金、现金等价物和限制性现金减少		(47,471	)		(37,092	)
现金、现金等价物和限制性现金--期初		210,954			120,236
现金、现金等价物和受限现金--期末	$	163,483		$	83,144
补充披露非现金投资和融资活动：
应付账款和应计费用中包括的财产和设备增加	$	757		$	495


	9月30日，		9月30日，
(单位：千)	2024		2023
现金及现金等价物	$	158,709	$	78,370
受限现金		4,774		4,774
现金总额、现金等价物和限制性现金	$	163,483	$	83,144


	截至9月30日，
	2024		2023
未归属的限制性股票单位		1,997,620		883,693
购买普通股的未偿还期权		12,766,821		9,942,213
总		14,764,441		10,825,906


	截至三个月 9月30日，
(单位：千)	2024			2023			变化
协作收入	$	6,865		$	3,117		$	3,748
运营费用：
研发		49,938			43,765			6,173
一般和行政		13,837			11,686			2,151
总运营支出		63,775			55,451			8,324
运营亏损		(56,910	)		(52,334	)		(4,576	)
其他收入(支出)：
成功付款负债公允价值变化		(6	)		802			(808	)
利息和其他收入，净额		6,887			5,841			1,046
其他收入合计，净额		6,881			6,643			238
扣除所得税准备前的亏损		(50,029	)		(45,691	)		(4,338	)
所得税拨备		(104	)		(67	)		(37	)
净亏损	$	(50,133	)	$	(45,758	)	$	(4,375	)


	九个月结束 9月30日，
(单位：千)	2024			2023			变化
协作收入	$	19,252		$	6,614		$	12,638
运营费用：
研发		149,299			138,135			11,164
一般和行政		42,546			37,655			4,891
总运营支出		191,845			175,790			16,055
运营亏损		(172,593	)		(169,176	)		(3,417	)
其他收入：
成功付款负债公允价值变化		1,743			878			865
利息和其他收入，净额		22,452			16,825			5,627
其他收入合计，净额		24,195			17,703			6,492
扣除所得税准备前的亏损		(148,398	)		(151,473	)		3,075
所得税拨备		(276	)		(243	)		(33	)
净亏损	$	(148,674	)	$	(151,716	)	$	3,042


展品数		描述

3.1		重述Verve Treateutics，Inc.的注册证书(通过引用注册人于2021年6月21日提交给美国证券交易委员会的当前8-k表报告的附件3.1并入)。

3.2		第二次修订和重新修订了Verve Treateutics，Inc.的章程(通过参考注册人于2023年2月17日提交给美国证券交易委员会的当前8-k表格报告的附件3.1并入)。

31.1*		根据根据2002年《萨班斯-奥克斯利法案》第302节通过的1934年《证券交易法》第13a-14(A)和15d-14(A)条颁发的首席执行干事证书。

31.2*		根据依照2002年萨班斯-奥克斯利法案第302节通过的1934年《证券交易法》第13a-14(A)和15d-14(A)条认证首席财务干事。

32.1+		根据2002年《萨班斯-奥克斯利法案》第906条通过的《美国法典》第18编第1350条规定的首席执行官证书。

32.2+		根据2002年《萨班斯-奥克斯利法案》第906节通过的《美国法典》第18编第1350条对首席财务官的认证。

101.INS		内联XBRL实例文档-实例文档不显示在交互数据文件中，因为其XBRL标记嵌入在内联XBRL文档中

101.SCH		内联XBRL分类扩展架构文档

101.CAL		内联XBRL分类扩展计算链接库文档

101.DEF		内联XBRL分类扩展定义Linkbase文档

101.LAB		内联XBRL分类扩展标签Linkbase文档

101.PRE		内联XBRL分类扩展演示文稿Linkbase文档

104		封面交互数据文件(嵌入内联XBRL文档中)


	VERVE THERAPETICS，Inc.

日期：2024年11月5日	作者：	/s/ Sekar Kathiresan
		Sekar Kathiresan万. D.
		首席执行官
		首席行政主任

日期：2024年11月5日	作者：	/s/艾莉森·多瓦尔
		艾莉森·多瓦尔
		首席财务官
		首席财务和会计干事


(单位：千)	9月30日， 2024		十二月三十一日， 2023
雇员补偿及相关福利	$	11,724	$	12,342
应计外部研发费用		7,366		4,856
专业费用		2,358		1,492
许可证和里程碑付款		120		500
其他		350		988
总	$	21,918	$	20,178


	截至三个月 9月30日，
(单位：千)	2024		2023		变化
与工作有关的费用	$	20,413	$	17,346	$	3,067
与制造活动相关的原材料成本和外部费用，包括第三方CMO		9,308		8,105		1,203
设施相关成本（包括折旧）		5,403		5,101		302
与外部顾问（包括第三方CROs）进行的临床前研究相关的外部费用		4,284		4,954		(670	)
临床试验成本		4,124		1,911		2,213
实验室用品		3,554		3,967		(413	)
其他研究和开发成本		2,852		2,381		471
研发费用总额	$	49,938	$	43,765	$	6,173


	九个月结束 9月30日，
(单位：千)	2024		2023		变化
与工作有关的费用	$	63,322	$	50,799	$	12,523
与制造活动相关的原材料成本和外部费用，包括第三方CMO		27,663		30,851		(3,188	)
设施相关成本（包括折旧）		15,862		14,120		1,742
实验室用品		12,623		13,614		(991	)
临床试验成本		10,805		4,343		6,462
与外部咨询服务(包括第三方CRO)进行的临床前研究相关的外部费用		10,640		18,394		(7,754	)
其他研究和开发成本		8,384		6,014		2,370
研发费用总额	$	149,299	$	138,135	$	11,164