10-Q

请勾选以下项目，以判定在过去12个月(或更短期间，该注册人被要求提交报告)内所有根据1934年证券交易法第13条或第15(d)条要求提供报告的报告是否已经提交，并且该注册人在过去90天中是否受到提交报告的要求。是 ☒ 否 ☐

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如果是新兴成长型企业，在符合任何依据证券交易法第13(a)条所提供的任何新的或修改的财务会计准则的遵循的延伸过渡期方面，是否选择不使用核准记号进行指示。☐

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截至2024年11月1日，登记公司普通股的流通股数： 101,848,572 股。

经过简化的综合损益表（未经审核）运营和综合损失（未经审计）

1. 概述和报告基础

Intellia Therapeutics，Inc.（“Intellia”或“公司”）是一家领先的临床阶段基因编辑公司，专注于利用CRISPR/Cas9技术开发潜在治愈性治疗药物。CRISPR/Cas9是基因组编辑的技术，全称“clustered，regularly interspaced short palindromic repeats（CRISPR）/CRISPR associated 9（Cas9）”。 Clustered， Regularly Interspaced Short Palindromic Repeats（“CRISPR”）/CRISPR associated 9（Cas9）是一种基因编辑技术，用于改变选择的基因组脱氧核糖核酸（“DNA”）序列。为了充分实现CRISPR/Cas9技术的革命潜力，Intellia正在构建一个全谱基因编辑公司，通过利用其模块化平台来推动，为抑郁症、焦虑症和其他沉思性障碍提供了有前景的新疗法。和体外通过两种主要方法来治疗需求量大的疾病。针对，为抑郁症、焦虑症和其他沉思性障碍提供了有前景的新疗法。应用于治疗遗传疾病，公司采用CRISPR/Cas9技术。公司的，为抑郁症、焦虑症和其他沉思性障碍提供了有前景的新疗法。项目利用CRISPR技术在人体内直接精准编辑致病基因。此外，公司正在推进体外应用于免疫肿瘤学和自身免疫疾病的应用中，该公司使用CRISPR/Cas9作为工具来创建工程化的细胞治疗。对于其体外计划，CRISPR/Cas9被用于体外工程人类细胞。公司深厚的科学、技术和临床开发经验，以及其强大的知识产权（“IP”）组合，使其能够开发CRISPR/Cas9和相关技术的广泛治疗应用，创造新的基因药物类别。

公司在此所包含的简明综合财务报表是根据美国证券交易委员会（“SEC”）的规则和法规编制的，未经审计。根据这些规则和法规的规定，按照美国通用会计准则（“U.S. GAAP”）编制的年度财务报表中通常包含的某些信息和脚注披露已经被省略或简化。因此，应阅读这些简明综合财务报表与公司在2023年12月31日止年度报告中包含的财务报表和附注一起阅读。

未经审计的简明综合财务报表包括Intellia Therapeutics, Inc.及其全资子公司Intellia Securities Corp.的账目。所有公司间余额和交易在合并时已经被消除。综合损失包括净损失、标记为市场证券的未实现收益/损失以及来自权益法投资的其他综合收益/损失。

按照美国通用会计准则编制财务报表要求管理层做出影响财务报表及附注中报告金额的估计、判断和假设。在这些简明综合财务报表中，与收入计算、研发费用、股权和公平价值法投资、附带条件款项和股权补偿费用的估计相关的重要估计是基于管理层认为在估计时合理的历史经验和其他各种假设。实际结果可能与这些估计有所不同。公司会定期根据情况、事实和经验变化复审其估计。

如有任何估计的材料修订效应，将从估计变更日期起在简明一体财务报表中前瞻性地体现。

据管理层意见，所提供的信息反映了为报告的中期时段结果进行公平呈现所需的所有调整，这些调整包括一切属于正常和经常性质的，公司认为发生于资产负债表日之后但财务报表发布之前的事件或交易，可提供与某些估计相关的额外证据，或者确认需要额外披露的事项。中期时段的运营结果未必能反映全年或任何其他中期时段可预期的结果。

流动性

自成立之初至2024年9月30日，公司已共计筹集了 $2,758.3百万用于支持其运营，通过其首次公开募股（“IPO”）和同时的私人定向配售，跟进公开招股，根据市场情况招股及发行可转换优先股，以及通过其合作协议。公司预计其现金、现金等价物和可市场折算证券截至2024年9月30日将使公司能够支持其持续营业费用和资本支出需求，至少在发布这些简明一体财务报表后的十二个月内。

3. 可变现证券

以下表格总结了公司可供出售的有价证券:


	2024年9月30日
	分期偿还的成本		未实现总额收益		未实现总额损失			估计公允数值
	（以千计）
可转换证券:
美国国债和其他政府支持的证券	$	432,997	$	1,345	$	(53	)	$	434,289
金融机构债务证券		248,197		1,437		(27	)		249,607
企业债券		104,174		584		(19	)		104,739
其他资产支持证券		35,521		30		-			35,551
总计	$	820,889	$	3,396	$	(99	)	$	824,186

	2023年12月31日
	分期偿还的成本		未实现总额收益		未实现总额损失			估计公允数值
	（以千计）
可转换证券:
美国国债和其他政府支持的证券	$	382,260	$	302	$	(254	)	$	382,308
金融机构债务证券		246,270		92		(243	)		246,119
企业债券		97,490		53		(135	)		97,408
其他资产支持证券		59,453		75		(24	)		59,504
总计	$	785,473	$	522	$	(656	)	$	785,339

可供出售证券的摊销成本已调整，以考虑预付款的摊销和折现以到期日。 no 在截至2024年9月30日的九个月内或截至2023年12月31日的年度中，出现了重大实现收益或亏损。公司一般并不打算在未收回其摊销成本基础的任何投资或处于未实现亏损位置的投资之前出售该投资。因此，公司已将这些亏损归类为暂时性。

公司在简明合并资产负债表中被归类为短期可交易证券的可供出售证券在资产负债表日期之日起一年内到期。在简明合并资产负债表中被归类为非流动资产的可供出售证券是那些在资产负债表日期之后到期的证券。一年但是在...之内月内。2023年和2022年的三个和九个月期权授予均以授予日公司普通股的公允价值相等的行权价格授予，并且是非法定股票期权。从资产负债表日期开始，并且公司在接下来的十二个月内不打算处置。在 2024年9月30日和

4. 公允价值计量

公司利用三级层次分类基于公允价值的衡量方法，以优先考虑用于衡量公允值的输入。此层次结构要求实体最大化利用可观察的输入并最小化使用不可观察的输入。用于衡量公允价值的三个级别的输入如下：第一级，活跃市场中的报价市价（未经调整）适用于相同资产或负债；第二级，除第一级中包括的报价市价外的可观察输入，例如用于非活跃市场的市场的报价市价或其他可观察或可通过可观察市场数据证实的输入；第三级，几乎没有市场活动支持的不可观察输入，对资产或负债的公允价值具有重大影响，包括某些定价模型、贴现现金流量方法和使用重要不可观察输入的类似技术。

公司的重复计量公允值的财务资产包括以下资产：


	2024年9月30日
	总计		一级		二级		Level 3
	(以千为单位)
资产
现金等价物和受限现金等价物	$	93,355	$	93,355	$	-	$	-
可转换证券:
美国国债和其他政府支持的证券		434,289		199,705		234,584		-
金融机构债务证券		249,607		-		249,607		-
企业债券		104,739		-		104,739		-
其他资产支持证券		35,551		-		35,551		-
所有基金类型投资		824,186		199,705		624,481		-
投资Kyverna Therapeutics, Inc。		5,740		5,740		-		-
总资产	$	923,281	$	298,800	$	624,481	$	-

	2023年12月31日
	总计		一级		二级		Level 3
	(以千为单位)
资产
现金及现金等价物和受限制的现金等价物	$	136,254	$	136,254	$	-	$	-
可转换证券:
美国国债和其他政府支持的证券		382,308		120,556		261,752		-
金融机构债务证券		246,119		-		246,119		-
企业债券		97,408		-		97,408		-
其他资产支持证券		59,504		-		59,504		-
所有基金类型投资		785,339		120,556		664,783		-
总资产	$	921,593	$	256,810	$	664,783	$	-

公司的某些资产，包括现金等价物、受限现金等价物和可交易证券，最初以交易价格价值，并在每个报告期末重新估价，利用第三方定价服务或其他可观察市场数据。这些定价服务利用行业标准估值模型和可观察市场输入来判断价值。

其他金融工具，包括应收账款、应付账款和预提费用，按成本计量，由于短期性和到期期限接近，近似于公允价值。

公司已判断其投资于Kyverna Therapeutics, Inc.（“Kyverna”）的估计公允价值为一级，因为它是根据活跃市场中的报价市场价值估算。对Kyverna的投资被分类在“投资和其他资产”中的简化合并资产负债表中。更多详情请参阅附注8。

CRISPR/Cas9技术的领导地位在治疗方面万亿。截至2024年9月30日，公司的应收账款与再生元制药公司、SparingVision和AvenCell的合作相关，公司的合同负债与再生元制药公司和SparingVision的合作相关。截至2023年12月31日，公司的应收账款与再生元制药公司、SparingVision、AvenCell和Kyverna的合作相关，公司的合同负债与再生元制药公司和SparingVision的合作相关。

下表显示了公司应收账款和合同负债的变动情况（单位：千美元）：


	期末余额本期开始期间		增加		减项			期末余额期间
2024年9月30日结束的九个月
应收账款	$	36,456	$	19,422	$	(47,024	)	$	8,854
合同责任 - 预收营业收入	$	60,993	$	-	$	(16,231	)	$	44,762

	期末余额本期开始期间		增加		减项			期末余额期间
截至2023年9月30日的九个月中，
应收账款	$	3,768	$	15,287	$	(12,564	)	$	6,491
合同负债-递延收入	$	63,771	$	-	$	(37,705	)	$	26,066

在2024年和2023年9月30日止九个月，公司根据合同负债余额变化确认了以下营业收入（以千美元计）：


	截至9月30日的九个月
本期来自的营业收入：	2024		2023
合同负债中包含的金额在期初	$	16,231	$	31,081

公司未发生重大支出以获取合作协议和履行这些合同的成本不会产生或增加公司的资源。因此， no 获取或履行合同的成本在任何期间均已资本化。

再生元制药公司（NASDAQ：REGN）之间的合作

2016年4月，公司与再生元制药公司签订了一项许可和合作协议（随时修订，称为“2016年再生元协议”）。2023年10月，再生元行使了其一次性延长科技合作期限的选择。作为额外的发生, 直到，实际利率，以非退款方式支付$30.0 百万美元，该款项于2024年4月收到。 2023年9月，再生元制药公司和Intellia进一步扩大了研究合作（“2023年再生元修正案”），以开发更多，为抑郁症、焦虑症和其他沉思性障碍提供了有前景的新疗法。基于CRISPR的基因编辑疗法主要关注神经系统和肌肉疾病。

2018年，公司与再生元制药公司签署了一项关于甲状腺激素转运蛋白(AATTR)淀粉样变性病(AL)的共同开发和共同推广（Co/Co）协议（“ATTR Co/Co”）。2020年5月，公司签署了有关治疗血友病A和血友病B的共同开发和共同资助协议（“血友病 Co/Co”协议）。2024年3月，公司通知再生元制药公司退出了血友病B的共同开发和共同推广协议（Co/Co协议）。公司继续承担血友病B Co/Co协议下的义务，直至2024年9月协议结束。公司将继续支持再生元制药公司开发针对血友病B的基因编辑产品，适用2020年再生元协议下的规定。该协议将控制各方开发和商业化针对血友病B的基因编辑产品的义务。根据2020年再生元协议，公司可能有资格在高个位数至低十位数的里程碑支付和版税中获得高达$*百万的收入，这些版税可能会受到各种降低、抵消和上游支付义务的影响。320.0 净营业收入。这些版税可能会受到各种降低、抵消和上游支付义务的影响。

截至2023年12月31日，2016年再生元协议，ATTR共同开发和共同推广协议，血友病共同开发和共同推广协议或2023年再生元协议（“再生元协议”）的关键条款没有发生重大变化，除非如上所述。

公司识别了与Regeneron协议相关的合作营业收入 $8.3 百万和$22.1 $百万，直至期满的 2024年9月30日结束的三个季度，$9.3 百万美元和百万美元23.5 百万美元的期间 2023年9月30日结束的三个月和九个月在压缩的综合损益表中分别为。这包括约$6.4 百万美元和$16.1 百万美元在 2024年9月30日结束的三个和九个月内，分别为，分别为$5.5 百万美元和$14.2 百万美元在 2023年9月30日结束的三个和九个月内，分别为分别主要代表因瑞生医药根据ATTR合作的款项到期而应收的营业收入。这些营业收入部分被血友病合作协议相关的逆向收入抵消，金额约为$4.0 百万美元和$11.6 百万美元 2024年9月30日结束的三个月和九个月，分别为$百万美元和$1.8 百万美元7.6 百万美元分别是2023年9月30日结束的三个月和九个月。

截至2024年9月30日，有$元。31.6 截至2026年4月，2016年Regeneron协议剩余交易价格的百万美元将被确认，剩余期限。截至2024年9月30日和2023年12月31日公司应收账款为$8.1 百万美元和$35.7 百万美元，分别为$31.6 百万美元和$47.1 分别与再生元公司达成的协议相关的金额分别为。

SparingVision SAS

2021年10月，公司与发展眼科疾病视力挽救治疗的基因医学公司SparingVision签署了许可和合作协议（以下简称“SparingVision LCA”），以开发利用CRISPR/Cas9技术治疗眼科疾病的新型基因药物。

自2023年12月31日以来，SparingVision LCA协议的关键条款未发生重大变化。

公司确认与SparingVision LCA相关的合作收入约为$0.6 百万和$1.7 分别与前期付款和临床里程碑相关的研究和开发费用为50万美元和90万美元。截至2024年9月30日结束的三个月和九个月的时间。和$0.4 百万美元和$1.3 分别为截至2023年9月30日的三个月和九个月的压缩综合损益表中的截至2023年9月30日和2023年12月31日1,500万美元的美国联邦净营业亏损（NOL）结转。0.3 百万美元和$0.5 分别为与SparingVision LCA相关的应收账款截至2024年9月30日和2023年12月31日公司推迟认定的营业收入为$13.2 百万和$13.9 百万分别与SparingVision LCA相关，预计从协议签署后的六至九年内确认。

ReCode Therapeutics, Inc.（“ReCode”）

2024年2月14日，公司与临床阶段基因药公司ReCode（“ReCode”）签订了许可、合作和期权协议（“ReCode LCA”），旨在开发用于治疗囊性纤维化（“CF”）的新型基因组药物。ReCode LCA利用了公司拥有的专有CRISPR基因编辑平台，包括其DNA写入技术，以及ReCode的专有Selective Organ Targeting（“SORT”）脂质纳米粒递送平台，精准校正一个或多个引起CF疾病的基因突变。作为协议的一部分，公司将专注于针对那些治疗选择有限或无治疗选择的CF患者的初期研究工作，并有机会在后期阶段扩大合作范围。公司将负责设计编辑策略和治疗调查疗法的研究级元件。ReCode将领导后续的临床前和临床开发，并全球商业化合作项目中产生的某些项目。公司还有选择在美国领导某些项目的商业化的权利（“Co/Co option”）。

ReCode LCA未包括各方之间的预付考虑交易。公司有资格获得高达$262.0 百万的特定开发和商业化里程碑付款，以及潜在销售额的一位数百分点的提成。如果公司行使Co/Co 期权，某些里程碑和提成支付可能会被取消或减少。公司在2024年9月30日结束的三个或九个月内未从ReCode LCA中确认任何营业收入。

其他协议

公司已与AvenCell、Kyverna和ONk Therapeutics, Ltd.（“ONK”）签订了现有许可和合作协议。自2023年12月31日以来，AvenCell、Kyverna和ONk许可和合作协议的关键条款未发生重大变化。截至2024年9月30日的三个月和九个月期间董事会委任了Related的执行副总裁Bryan Cho担任公司的三类董事。Cho先生的任命是根据咨询协议作出的，该协议规定顾问有权指定一名董事担任董事会成员，但顾问及其关联人须继续满足一些条件，包括顾问及其关联方持有至少一定数量的A类普通股。作为公司的董事，Cho先生的薪酬与公司的其他非雇员董事相同。0.2 百万美元相关的材料已按照AvenCell许可和合作协议（“AvenCell LCA”）出货，以及$21.0百万美元与AvenCell LCA相关的以前消除的企业内利润在简明综合公司（condensed consolidated）中为

8. 投资和其他资产

投资和其他资产包括以下内容：


	9月30日,		12月31日,
	2024		2023
	(以千为单位)
对 Kyverna 的投资	$	5,740	$	10,000
其他投资		24,213		14,760
长期限制性现金等价物		13,605		13,605
预付费用和其他资产，长期		3,230		4,518
投资和其他资产的总计	$	46,788	$	42,883

Kyverna Therapeutics，Inc。

2024年2月，Kyverna完成了其普通股的首次公开发行（“Kyverna IPO”）。在Kyverna IPO之前，由于Kyverna是一家私人公司，没有明显可观察的交易价格，公司对其对Kyverna的投资采用了替代计量方法，并且该投资在2023年12月31日时评估为$10.0 百万。截至2024年9月30日，公司对Kyverna的投资の价值为。公司确认了一项未实现损失 $5.7百万 $3.1百万 and $4.3百万，分别记录在2024年9月30日结束的三个和九个月的综合损益简明合并利润表内的“投资公平价值变动净额”中，与Kyverna普通股公允价值变动有关。

AvenCell Therapeutics, Inc.

截至2024年9月30日和2023年12月31日，公司持有 33.33%的AvenCell股权。截至2013年12月31日，公司按权益法会计处理其投资，因为公司对AvenCell具有重大影响力，但并未控制其，该投资价值为$11.8百万美元。2024年第一季度，与债务融资的完成相结合，AvenCell扩大了董事会规模，一位投资者控制了AvenCell的运营和财务决策。从那时起，公司不再能够对AvenCell施加重大影响，因此公司对AvenCell的投资按照ASC 321的规定来计算，AvenCell不再被视为关联方。

从权益法会计转变为ASC 321要求公司重新分类$2.1 百万美元，从之前因对AvenCell的投资而确认的其他综合损失累计金额移到AvenCell的投资账面价值，并在2024年第一季度的综合损益简明合并报表中，将之前取消的跨实体利润$21.0 百万美元作为“合作收入”予以确认。公司还考虑到投资是否存在减值迹象，并在那一期的综合损益简明合并报表中的“投资公允价值变动净额”中记录了一笔25.3 百万美元的减值。这种减值是由AvenCell的财务状况、根据债务融资的完成而出现的公允价值指标以及关于进一步融资的签署项条款所引起的，这些暗示表明投资的公允价值低于其账面价值。公司采用市场方法对投资进行估值，这是公允价值层次中的第3级测量。

除了合并协议条款规定的百万美元现金收购对价外，我们还产生了百万美元的直接交易成本，这些成本已纳入待分配给收购净资产的总对价中。21.0 上述已确认的被取消的跨实体利润中的百万美元在上述期间的综合损益报表中予以确认。公司已发行2019 ESPP下的股票，截至董事会委任了Related的执行副总裁Bryan Cho担任公司的三类董事。Cho先生的任命是根据咨询协议作出的，该协议规定顾问有权指定一名董事担任董事会成员，但顾问及其关联人须继续满足一些条件，包括顾问及其关联方持有至少一定数量的A类普通股。作为公司的董事，Cho先生的薪酬与公司的其他非雇员董事相同。0.2 百万美元相关于在AvenCell LCA期间按照规定运输的材料。在此期间内， 2023年9月30日结束的三个月和九个月公司分别认定了$1.9 百万和$12.7 百万美元的营业收入，与AvenCell LCA相关。截至0.4 百万和$0.2 分别有$百万美元的应收账款。 2024年9月30日截至2023年12月31日，公司资产总额也为$1.0 百万美元，与AvenCell协议相关的应计费用分别截至 2024年9月30日和2023年12月31日。

我们根据实际发生的股权奖励放弃而不是估计预期的放弃进行核算。截至2024年6月30日，与尚未确认的股票期权有关的总补偿成本（仅涉及2022年首席执行官期权授予）为$百万，在加权平均期限内确认，期限为年。与未发行的受限制股票单元相关的未确认补偿成本总额约为$百万，在加权平均期限内确认，期限为年。

股权激励费用按照以下方式在简明综合损益表中分类：


	截至9月30日的三个月				截至9月30日的九个月
	2024		2023		2024		2023
	(以千为单位)
研发费用	$	24,224	$	21,235	$	69,824	$	60,517
一般行政		15,395		14,117		44,832		38,490
总计	$	39,619	$	35,352	$	114,656	$	99,007

股票期权和激励计划

2016年4月，公司通过了经修订的2015年股票期权和激励计划（“2015计划”）。2015计划规定了授予激励股票期权、非合格股票期权、股票升值权、限制性股票奖励（“RSAs”）、限制性股票单位（“RSUs”）和其他基于股票的奖励。获得激励股票期权和非合格股票期权的收件人有权以行权价购买公司普通股，行权价等于授予日该股票的公允价值。截至2024年9月30日，2015年计划下有另外期权可供发行。根据2015年计划，每年1月1日，发行股票的数量将以上年12月31日已发行和流通股票的数量的百分比累积增加。 4,808,720 股票期权和激励计划中有可发行的股数。根据2015年计划，用于发行的股数将在每年1月1日逐年累增，等于上一年12月31日已发行和流通股数的百分之日通过四个股票期权和激励计划将根据上一年12月31日已发行和流通的股数的百分之日或者由董事会决定的同等或更少数量的股份。

2024年6月，公司通过了2024年诱导计划（“诱导计划”）。诱导计划允许向非公司雇员授予非合格期权、股票增值权、普通股奖、受限股票奖赏、无限制的股票奖赏和股息等同权。非合格期权的受赠人有资格以行权价格购买公司的普通股，该价格等于授予日期的股票公允价值。根据诱导计划的规定， 850,000 股份已被保留以供未来发行；截至2024年9月30日，诱导计划尚有 500,826 股可用于未来发行。

受限股票单位

以下表格总结了公司的RSU活动公司已发行2019 ESPP下的股票，截至:


	数量股份			已授予和预期于2021年1月2日授予股份平均授予和奖励公允日期价值每股
2023年12月31日尚未归属的受限股票单位		4,041,753		$	50.40
已批准		3,326,772			33.89
34,105		(1,335,350	)		51.56
已取消		(582,581	)		43.50
2024年9月30日尚未归属的受限股票单位		5,450,594		$	40.77

受限股票单位-服务奖励

公司在员工入职时和作为年度授予的一部分向所有员工授予带有服务条件的RSU。根据2015年计划在2024年和2023年以及2024年的诱因计划下授予的带有服务条件的RSU，通常在原始获权日期的首个周年日成为可行使的三分之一，其余部分在接下来的两年内逐年成为可行使的。

2024年3月，公司授予了期权，其中包括根据公司董事会薪酬委员会设定的一定递增的股价门槛的市场条件的限制性股票单位。股票单位平均在实现达到$ 2,157,921 员工年度授予的具有服务条件的RSUs，可能在一段时间内获得三年。这些RSUs的加权平均授予日公允价值为$32.66 ，这些RSUs的归属开始日期为2024年1月1日。

2023年3月，公司向高管授予了 2,195,135 员工年度授予的具有服务条件的RSUs，可能在一段时间内获得三年这些RSUs的加权平均授予日公允价值为$40.75 这些RSUs的认股起始日期为2023年1月1日。

截至2024年9月30日，上表中的未发股限制股单位包括 4,464,378 基于服务的RSUs。

受限制股单位 - 市场奖励

2024年、2023年和2022年，市场为高级管理人员授予了基于市场的RSUs。这些RSUs有可能在经过一段时间后获得。三年，控件开始日期分别为2024年1月1日、2023年和2022年，要交付的股份数量将取决于公司’s总股东回报率（“ TSR”），相对于一组生物技术公司的这一时期。截至2024年、2023年和2022年九个月结束的市场RSU授予数量分别为 286,084, 181,743 and 55,144，分别是。使用蒙特卡洛估值模型计算的市场RSU授予日期公允价值为$51.12, $68.55 和$126.49，分别是。用于确定三年授予日期公平价值的假设如下：无风险利率： 4.28%, 4.60%和1.44；预期波动率： 77.2%, 84.34%和82.53。所有授予的预期期限约为 3.0 年；预期股息率为 0.0%.

2024年9月30日的未实现限制性股票单位包括上述表格中的市值 RSU。 488,555 基于市值的 RSU。

限制性股票单位 - 按绩效评估的奖励和 TSR 倍增器

此外，还在2024年向高管授予了相对 TSR 修改器的绩效 RSU（“PSU”）。在截至2024年9月30日的九个月中，相对TSR修饰符授予的PSU数量是 486,617这些PSU（如被赋予），将于2027年1月1日获得，交付的股份数量将根据实现某些绩效目标来确定，区间可从 0可以降低至0.75%每年200。在确定绩效标准达成后，奖励的股份数量将根据TSR修饰符的应用而进行调整，区间可从 75可以降低至0.75%每年125。这些PSU的授予日公允价值，使用蒙特卡洛估值模型计算，为$36.16。用于确定授予日公允价值的假设如下：无风险利率： 4.28%；预期波动率： 77.2%; 预期期限约为 3.0 年；预期股息率： 0.0%. 公司根据其对将根据实现绩效目标的概率而准予的股票数量的估计，在规定服务期内按比例确认补偿费用。

2024年9月30日上述表格中的未获授之受限制股份单位包括 453,243 具有TSR乘数的PSU。

限制性股票单位-基于绩效的奖励

2022年3月，公司授予了 66,296 部分非执行员工的基于绩效的RSUs，这些RSUs将在达到某些科学里程碑后获得。总共有两个三个分阶段，每个阶段附属于不同的里程碑集合。第一个阶段的里程碑，由 21,878 个RSUs组成，在2023年第一季度实现，并获得了这些RSUs。其他绩效里程碑被认为到2024年9月30日时无法实现，并因此在该期间未记录任何相关的股票补偿费用。 2024年9月30日的未获授予限制性股票单位如上表所示

Unvested restricted stock units as of September 30, 2024 in the table above includes 44,418 基于绩效的限制性股票单位。

2024年9月30日结束的三个月和九个月内授予的所有限制性股票单位加权平均授予日期公允价值为$30.63 和$33.89，分别。限制性股票单位的总公允价值（按授予日期计量）截至2024年9月30日结束的三个月和九个月的时间。为$2.8 百万和$38.3 百万美元、分别。授予的RSUs的加权平均授予日期公允价值为 2023年9月30日结束的三个和九个月内，分别为为$39.14 和美元42.36、分别。RSUs的总公允价值（在归属日期测量）为 2023年9月30日结束的三个和九个月内，分别为为$4.2 百万和$22.5 百万。

截至2024年9月30日，有$元。133.3 百万美元的未认可的与所有即将归属的RSUs相关的股票补偿费用。这些成本预计将在加权平均剩余归属期内确认。 1.7 年.

股票期权

期权的加权平均授予日公允价值，估算截至授予日使用Black-Scholes期权定价模型。 $16.98 和$21.21 每份期权适用于2024年9月30日及2014年三个月内授予的期权分别为每份期权适用于2024年9月30日，以及2023年9月30日结束的九个月内授予的期权，并 $28.92 每份期权适用于2023年9月30日结束的九个月内授予的期权。在截至2023年3月31日的三个月内，公司回购和注销了no 适用于2023年9月30日结束的三个月内授予的期权。用于应用此定价模型的加权平均假设如下：


	截至9月30日的三个月		截至9月30日的九个月
	2024	2023	2024	2023
无风险利率	4.0%	n/a	4.2%	4.4%
预期期限	6.0 年	n/a	6.0 年	6.0 年
标的股票预期波动率	75.8%	n/a	76.3%	78.7%
预期股息收益	0.0%	n/a	0.0%	0.0%

无风险利率。无风险利率基于授予时的美国国债收益率曲线，到期期限大致与期权的预期期限相等。

预期期限。预期期限代表期权奖励预计有效的期间。对于被视为常规的期权授予，公司使用简化方法确定预期期限。简化方法将期限视为距离解除限制时间和期权合同生命周期的平均值。公司采用简化方法是因为其没有足够的历史期权行权数据，无法为估计预期期限提供合理依据。

预期波动性。预期波动率是基于公司股价在最近历史时期的实际波动估算的，以及期限内股票期权授予的预期波动率。

预期股息率。公司未支付现金分红，并且未来也没有意向支付现金分红。

股票期权通常在原始归属日期一周年时解禁三分之一，余额在接下来两年中每月解禁，除非它们包含特定的解禁规定。2015年计划和引入计划下授予的股票期权的最长期限为十年。

以下是股票期权活动摘要公司已发行2019 ESPP下的股票，截至:


	数量 Options			已授予和预期于2021年1月2日授予股份平均数行权每股价格分享		已授予和预期于2021年1月2日授予股份平均数剩余加权术语		总计截至2023年7月29日的余额值
						(年)		(以千为单位)
2023年12月31日未行使的股票期权		5,458,999		$	50.38		6.65	$	35,922
已批准		918,161			30.72
行使		(371,736	)		15.69
被取消		(526,473	)		71.23
截至2024年9月30日应收款项		5,478,951		$	47.43		6.52	$	11,250
2024年9月30日可行使		4,096,828		$	47.42		5.76	$	11,250

2024年9月30日结束的三个月和九个月期间行权的股票期权的总固有价值（即公允市值超过行权价的金额）。为$1.1 百万和$3.1百万美元。2023年9月30日结束的三个月和九个月期间行权的股票期权的总固有价值。为$4.8 百万和$6.62024年4月30日和2023年4月30日的六个月内的外汇重新计量净收益分别为$百万。

截至2024年9月30日，有$元。34.5 百万美元未确认的与尚未获得的股票期权有关的补偿成本，预计将在加权平均剩余归属期内确认 1.16年。

员工股票购买计划

2016年5月，公司通过了2016年员工股票购买计划（"2016计划"）。 2016计划允许符合条件的员工在每个预定的六个月购股期最后一天购买公司普通股 85期权期间开始或结束时每股的公平市值的较低百分比。 2016年计划规定每年1月和7月开始的六个月期权期间。

截至2024年9月30日 989,736 2016年计划下未来发行的股份。2016年计划下发行的股份数量将在每年1月1日累计增加。日按照上一年12月31日发行并正在流通的普通股数量的百分之一的较低者日, b) 500,000 普通股份、或者由董事会确定的较少数量的普通股份。

截至2024年和2023年9月30日的九个月内公司发行了87,751 and 69,631 分别在2016计划下发行的普通股份。根据2016计划发行的股份的加权平均购买价格为$19.02 和$29.45每股基本收益（$）（1） 0.03 (0.11) nm nm分别为2024年和2023年截至9月30日的九个月。

2016年计划下股票的公允价值是在发行期初使用Black-Scholes期权定价模型估计的，估计依据如下：


	截至9月30日的三个月		截至9月30日的九个月
	2024	2023	2024	2023
无风险利率	5.37%	5.53%	5.24%-5.37%	4.7%-5.53%
预期期限	0.5 年	0.5 年	0.5 年	0.5 年
标的股票预期波动率	59.0%	60.4%	56.7%-59.0%	60.4%-69.2%
预期股息收益	0.0%	0.0%	0.0%	0.0%

11. 每股亏损

公司通过将各自期间的净亏损除以各自期间的普通股加权平均流通量来计算基本每股亏损。公司在计算摊薄每股亏损时，考虑了期间内优先股期权和未归属的限制性股票单位的摊薄效应，除非这些证券具有抗稀释性。

基本每股亏损和摊薄每股亏损的计算如下：


	截至9月30日的三个月						截至9月30日的九个月
	2024			2023			2024			2023
	(以千为单位)
Net loss	$	(135,712	)	$	(122,224	)	$	(390,123	)	$	(349,031	)
基本及摊薄加权平均股本		101,002			88,645			97,842			88,204
基本和稀释每股净亏损	$	(1.34	)	$	(1.38	)	$	(3.99	)	$	(3.96	)

由于包含这些普通股等价物会对减少每股亏损的计算产生抵消作用，因此它们被排除在稀释每股亏损的计算之外：


	截至9月30日的三个月和九个月
	2024		2023
	(以千为单位)
未获授限制性股票单位		5,451		3,925
股票期权		5,479		5,591
		10,930		9,516

本季度10-Q表格中包含前瞻性陈述，该陈述根据1933年证券法修正案第27A条和1934年证券交易法修正案第21E条的安全港条款进行。这些陈述可能通过前瞻性术语如"可能"，"应当"，"预计"，"打算"，"计划"，"预期"，"相信"，"估计"，"预测"，"潜在"，"继续"或这些术语的否定形式或其他类似术语来识别。我们的前瞻性陈述基于一系列关于我们公司的期望、假设、估计和投影，不保证未来业绩或表现，并涉及重大风险和不确定性。我们实际上可能无法实现这些前瞻性陈述中披露的计划、意图或期望。实际结果或事件与在这些前瞻性陈述中披露的计划、意图和期望可能有重大差异。我们的业务和前瞻性陈述涉及大量已知和未知风险和不确定性，包括我们关于的风险和不确定性：

所有板块关于未来展望的陈述，均属于本季度10-Q表格的日期。在每种情况下，实际结果可能与此类展望信息有实质性差异。我们无法保证此类期望或展望性陈述将被证明是正确的。在本季度10-Q表格中提到的任何风险因素或风险和不确定性的出现，或其中的任何重大不利变化，或者包含在我们的其他公开披露或其他定期报告或其他文件或提交给证券交易委员会（“SEC”）的文件，可能会对我们的业务、前景、财务状况和经营业绩造成重大不利影响。除非法律要求，我们不打算或计划更新或修订任何此类展望性陈述，以反映实际结果、计划变更、假设、估计或投影，或影响此类展望性陈述的其他情况，即使这些结果、变更或情况明确表明任何未来信息将不会实现，这也适用于本季度10-Q表格日期之后发生的任何展望性陈述。我们在本季度10-Q表格之后发布的任何公开声明或披露，修改或影响本季度10-Q表格中包含的任何展望性陈述的，将被视为修改或取代本季度10-Q表格中的这些陈述。

Intellia Therapeutics, Inc.（“我们”，“我们”，“我们”，“Intellia”或“公司”）是一家领先的临床阶段基因编辑公司，专注于利用CRISPR/Cas9技术开发潜在的治疗性药物。CRISPR/Cas9是基因组编辑的技术，即改变选择性基因组脱氧核糖核酸（“DNA”）序列的过程。为了充分实现CRISPR/Cas9技术的变革潜力，我们正在通过利用我们的模块化平台来打造一家全方位的基因编辑公司，以推动 Clustered， Regularly Interspaced Short Palindromic R重复（“CRISPR”）/ CRISPR相关蛋白质9（“Cas9”）是一种基因组编辑技术，用于修改基因组脱氧核糖核酸（“DNA”）的选择性序列。为了充分实现CRISPR/Cas9技术的变革潜力，我们正在构建一家全方位的基因编辑公司，通过发展我们的模块化平台，以推动体内和体外通过两种主要方法来治疗需求量大的疾病。针对，为抑郁症、焦虑症和其他沉思性障碍提供了有前景的新疗法。为了治疗遗传疾病，我们采用CRISPR/Cas9技术。我们的，为抑郁症、焦虑症和其他沉思性障碍提供了有前景的新疗法。项目使用CRISPR技术，在人体内直接精确编辑致病基因。此外，我们正在推进我们建立了一个多元化的产品候选管道，包括旨在恢复Tregs的抑制和免疫调节功能的体外方法。我们的产品候选管道基于我们的三种不同潜在治疗方式：Treg增强生物制品、Treg衍生外泌体和自体Treg细胞疗法。“自体”意味着使用来源于患者本身的人类细胞治疗患者，而“同种异体”意味着使用来源于与患者基因不同的捐赠者的人类细胞治疗患者。我们的核心重点是开发这些疗法以针对Treg功能失调，这已被确定为神经退行性、自身免疫和代谢性疾病的重要病理生理组成部分，在这些领域迫切需要新的有效疗法。应用于解决免疫肿瘤学和自身免疫性疾病的应用程序，在这些应用中，我们使用CRISPR/Cas9作为工具来创建基因编辑细胞疗法。对于我们的体外项目，CRISPR/Cas9用于在体外改造人类细胞。我们深厚的科学、技术和临床开发经验，以及强大的知识产权（IP）组合，使我们能够解锁CRISPR/Cas9和相关技术的广泛治疗应用，创造新型遗传药物类别。

我们对财务状况和运营业绩的管理层讨论和分析是基于我们未经审计的压缩综合财务报表，这些报表包含在本季度报告的表格10-Q中，根据美国通用会计准则（“U.S. GAAP”）和1934年修订的证券交易法规S-X编制。本讨论和分析应当与本季度报告中其他地方包含的未经审计的压缩综合财务报表及其附注以及与年度报告中包含的经审计财务报表和附注一起阅读，年度报告截至2023年12月31日。

治疗和潜在治愈广泛区间的严重疾病将需要多种基因编辑方法。作为我们平台核心的专有CRISPR/Cas9技术，我们不断增加新的能力，扩展目前解决多种重大疾病的解决方案。这些新增内容包括我们专有的碱基编辑器和DNA写入技术，以及新型CRISPR酶，这些使我们能够实现多种编辑策略。

我们继续推进平台的模块化解决方案和对基因组编辑技术以及递送和电芯工程能力的研究工作，以产生更多的发展候选者。

我们的使命是通过开发潜在治愈基因编辑疗法，改变重疾患者的生活。我们相信，通过专注于四个关键要素，我们可以实现我们的使命，为所有利益相关者提供长期收益：

我们的策略是推进全面的基因编辑公司，专注于开发和商业化治愈性的CRISPR/Cas9基础疗法，利用我们的模块化平台。至今，所有板块的营业收入均为合作收入。自创立以来，直到2024年9月30日，我们已筹集约275830万美元的资金，以支持我们的运营，包括通过首次公开募股（“IPO”）和同时进行的私人配售、后续公开发行、市场发售以及可转换优先股的销售，以及通过我们的合作协议。

我们的首选候选人，为抑郁症、焦虑症和其他沉思性障碍提供了有前景的新疗法。 NTLA-2001 用于治疗甲状腺激素转运蛋白（ATTR）淀粉样变性和NTLA-2002 用于治疗遗传性血管性水肿（HAE）的候选治疗药物是首批以静脉输注方式在人类体内精确编辑靶组织基因的CRISPR/Cas9基因编辑疗法候选人。此外，我们正推进多个项目，完全由我们拥有并与合作伙伴合作，以治疗免疫肿瘤学和自身免疫性疾病。体外的多项项目正在推进，完全拥有并与合作伙伴合作，用于治疗免疫肿瘤和自身免疫性疾病。

我们的选择标准包括识别源自肝脏的疾病；具有明确定义的突变，可以通过敲除或插入方法处理；具有可观测的临床治疗终点，并且针对这些疾病，有效的治疗方法要么不存在，要么有限，要么过于繁重。我们最初的，为抑郁症、焦虑症和其他沉思性障碍提供了有前景的新疗法。指示针对遗传性肝脏疾病，包括我们的ATTR淀粉样变性疾病、HAE和α-1抗胰蛋白酶缺乏症（“AATD”）开发项目。我们目前的工作重点在于，为抑郁症、焦虑症和其他沉思性障碍提供了有前景的新疗法。递送重点在于使用脂质纳米颗粒（“LNPs”）将CRISPR/Cas9复合物输送至肝脏。

NTLA-2001，现在称为nexiguran ziclumeran（“nex-z”），是一种用于研究的CRISPR基因治疗，旨在在肝细胞中失活甲状腺素运载蛋白（TTR）基因，从而防止TTR蛋白的产生，用于治疗ATTR淀粉样变。 Nex-z提供通过一剂后，驱动TTR蛋白深度、一致且潜在终身减少的可能性，从而停止和逆转该疾病。，为抑郁症、焦虑症和其他沉思性障碍提供了有前景的新疗法。 CRISPR基因治疗的一个设计，旨在在肝细胞中失活甲状腺素运载蛋白（“TTR”) 基因，从而防止TTR蛋白的产生，用于治疗ATTR淀粉样变。 Nex-z提供通过一剂后，驱动TTR蛋白深度、一致且潜在终身减少的可能性，从而停止和逆转该疾病。

MAGNITUDE关键的3期试验是一项随机、双盲、安慰剂对照研究，旨在评估NTLA-2001对ATTR-Cm成人的疗效和安全性。该研究的主要终点是心血管相关死亡和事件的组合。患者将被2:1随机分组为NTLA-2001：安慰剂，其中将注射一次55毫克的NTLA-2001。2024年3月，在美国和全球范围内首批患者接受了剂量。该试验目前正在招募患者，并继续超前于我们的目标招募预测。在第二季度，我们获得了新欧盟临床试验法规下的申请批准，该法规使得第3期试验得以在丹麦、德国、法国、意大利、西班牙和瑞典进行。

具有多发性神经病的遗传性ATTR淀粉样蛋白沉积症（“ATTRv-PN”）：

2024年11月，我们宣布美国食品和药物管理局（“FDA”）已批准我们的nex-z调查新药（“IND”）申请，以启动ATTRv-PN的MAGNITUDE-2关键性3期试验。MAGNITUDE-2是一项国际性、随机化、双盲、安慰剂对照研究，旨在评估50名ATTRv-PN患者中nex-z的疗效和安全性。患者将以1:1的比例进行随机分组，接受单次55毫克的nex-z输注或安慰剂。分配至安慰剂组的患者有资格选择交叉使用nex-z。主要终点是月份18处和第29天血清TTR时的mNIS + 7改变。mNIS + 7量表是一种经过验证的措施，专门设计用于评估和量化多发性神经病变，包括肌无力、肌肉伸展。

反射、感觉丧失和自主神经障碍。我们预计将在年底前在美国以外的地点启动MAGNITUDE-2研究的患者招募。

我们将在进行中的第1期研究中展示新数据 2024年11月在美国心脏协会（“AHA”）科学会议上，我们将向ATTR-Cm患者展示。演示将包括ATTR-Cm患者的安全性、血清TTR的降低以及疾病进展和功能能力数据的生物标志物。

NTLA-2001是再生元制药公司（Regeneron Pharmaceuticals, Inc.）合作开发和共同推广（“合作/共同推广”）协议的主题，ATTR（“ATTR合作/共同推广”），我们是ATTR项目的临床和商业主导方，再生元公司是参与方。再生元公司将分担约25%的全球开发成本和ATTR项目的商业利润。有关我们与再生元公司合作的更多信息，请参阅我们在本季度报告的基本报表中的附注7“合作和其他安排”。

NTLA-2002 is a wholly owned, investigational ，为抑郁症、焦虑症和其他沉思性障碍提供了有前景的新疗法。 CRISPR-based therapy designed to knock out the 卡利克雷因B1（“KLKB1”） gene in the liver, with the goal of lifelong control of HAE attacks after a single dose.

2024年10月，我们宣布启动了NTLA-2002的HAELO第3期研究。HAELO是一项全球范围内的、随机的、双盲的、安慰剂对照研究，旨在评估NTLA-2002在60名患有I型或II型HAE的成年患者中的疗效和安全性。患者将被2:1随机分配，接受一次50毫克的NTLA-2002或安慰剂输入。随机分配至安慰剂组的患者将有资格在第28周选择转换至NTLA-2002。主要终点是从第5周到第28周HAE发作次数的变化。我们正在积极筛选HAELO第3期研究中的患者，并计划在2026年提交生物制品许可申请（“BLA”）或类似的营销申请。

我们对NTLA-2002的1/2期试验评估了安全性、耐受性、活性、药代动力学和药效动力学。研究的第1阶段是开放标签的、单剂量逐渐增加的设计。NTLA-2002的两个剂量水平从第1阶段确定，用于进一步评估在第2阶段研究的随机、双盲、安慰剂对照部分。

2024年1月，我们宣布完成了研究第2阶段的招募和给药。2024年8月，我们公布了NTLA-2002在HAE患者中第2阶段研究的积极的阶段性结果。在为期16周的初步观察期内，临床试验达到了其主要疗效和所有次要终点，单次25毫克或50毫克的剂量导致了严重的发作减少。没有观察到任何新的安全发现。根据与第2阶段研究中观察到的25毫克剂量相比，完全消除发作的患者数量更多且胰激肽酶蛋白减少更大，我们选择50毫克剂量进行全球关键的第3阶段研究进一步评估，这与先前报告的第1阶段结果一致。

2024年6月，我们向持续进行的第1期研究展示了积极的长期数据。在16周的初步观察期后，10名患者中有8名完全没有发作。这些患者接受了一次性治疗后持续没有发作的时间长达18个月以上，其中个别最长持续没有发作的时间已超过26个月。在所有患者中，与基线相比，NTLA-2002导致了HAE每月发作率的平均减少率达到了98%。与先前报道的结果一致，NTLA-2002耐受性良好，大多数不良事件在最新的随访中均为轻度。这些中期数据在2024年在西班牙瓦伦西亚举办的欧洲过敏和临床免疫学学会(EAACI)大会上进行了展示。

2024年8月，我们还宣布成功完成了与FDA的第2阶段结束会议，支持我们关于NTLA-2002第3阶段计划的执行。

2024年10月，我们发布了正在进行的第1/2期研究中的正面2期数据，结果继续支持NTLA-2002作为HAE功能性治愈的潜力。在使用一剂NTLA-2002后，11名中的8名患者中的50毫克组患者在16周的初次观察期内停止了任何发作。这八名患者在最新的随访期内继续没有发作，也没有需要进一步治疗。NTLA-2002的耐受性良好。最常见的不良事件（“AEs”）是头痛、疲劳和鼻咽炎。没有发生过严重的不良事件，所有不良事件都是1级或2级。这些临时数据已发表在《新英格兰医学杂志》上，并在2024年美国过敏、哮喘和免疫学学会（“ACAAI”）在马萨诸塞州波士顿举行的科学会议上进行了宣布。

NTLA-3001是一种首创CRISPR介导的，为抑郁症、焦虑症和其他沉思性障碍提供了有前景的新疗法。靶向基因插入是治疗AATD相关肺部疾病的开发候选药物，也是我们首个完全自有的基因插入项目。它被设计用于精确插入野生型 SERPINA1 基因，该基因编码α-1抗胰蛋白酶（“AAT”）蛋白，有潜力在单剂后恢复永久表达正常水平的完全功能AAt蛋白。

2024年7月，我们宣布获得英国药品和医疗保健产品监管局（“MHRA”）授权，以启动NTLA-3001的首次人体研究。我们预计将在年底对NTLA-3001的第一阶段1/2研究中给首位患者进行剂量。第1/2阶段研究将是一项两部分、开放标签、多中心研究，最多涉及30名患者，以评估NTLA-3001的安全性、耐受性、药代动力学和药效动力学。

2024年6月，我们展示了使用CRISPR重新投药的积极临床概念板块数据，在我们专有的非病毒LNP基础递送平台上，能够产生叠加药效。在NTLA-2001相位1剂量递增研究中之前接受最低剂量0.1 mg/kg的三名患者中，后续用量为55 mg的NTLA-2001导致蛋白质减少更显著。重新投药后第28天的血清TTR中位减少了90%。与原始基线水平相比，血清TTR中位减少了95%。在接受后续剂量后，NTLA-2001在所有患者中通常耐受良好。尽管不计划在ATTR淀粉样变中对NTLA-2001项目进行重新投药，但在未来追求目标叠加效应的调查疗法中，重新投药选择可能是我们基于LNP递送平台的重要优势。这些数据是在加拿大蒙特利尔举行的周围神经学会（“PNS”）年会上展示的。

我们正在通过部署新的编辑和递送创新技术，拓展了可以用我们基于CRISPR技术瞄准的疾病范围。这包括在与合作伙伴独立或合作的情况下，推进五种不同从肝脏之外的组织中的基因编辑项目。这些研究和临床前项目旨在瞄准起源于骨髓、大脑、肌肉、肺部和眼睛的疾病，如果成功，将极大地扩大CRISPR治疗的机会。

我们正在推进多个项目，完全拥有并与合作伙伴合作，利用我们的异基因平台治疗免疫肿瘤和自身免疫性疾病。我们的专有异基因细胞工程平台避免了前临床模型中t细胞和自然杀伤细胞介导的排斥反应，这是其他研究型异基因方法尚未解决的关键挑战。利用我们的异基因平台工程化的细胞疗法，结合增强细胞功能的修改，提供了一种针对血液和实体肿瘤的新方法。

我们经常签订合作和其他类似的安排，以开发和商业化药物候选。合作活动可能包括研究和开发、市场营销和销售（包括宣传活动和医生推销）、制造和分销。这些安排通常需要里程碑以及基于资产在开发中的成功与否的某些未来事件相关联的版税或利润分享支付，以及从合作伙伴那里的费用报销或支付。参见注2，以获取这些类型安排所实现的合作和其他收入金额。

为加速在多个治疗领域CRISPR/Cas9基因组编辑产品的开发和商业化，我们已经成立，并打算寻求其他合作机会，与可以增强我们在CRISPR/Cas9治疗开发领域领先地位的合作伙伴建立战略联盟。我们已与Regeneron、AvenCell Therapeutics, Inc.（“AvenCell”）、SparingVision SAS（“SparingVision”）、Kyverna Therapeutics, Inc.（“Kyverna”）、ONk Therapeutics, Ltd（“ONK”）和ReCode Therapeutics, Inc.（“ReCode”）签订了合作协议。有关我们与合作伙伴之间协议条款的更多信息，请参阅本季度报告的基本财务报表中出现的“合作伙伴关系和其他安排”注释。

我们的营业收入包括合作收入，包括与许可证有关的预付科技使用费、科技接入费、已发货的研究材料、研究资金以及根据我们的许可和合作协议赚取的里程碑付款。

迄今为止，我们的研究和开发费用与AV-101的开发有关。研究和开发费用按照发生的原则确认，并将在收到将用于研究和开发的货物或服务之前支付的款项资本化，直至收到这些货物或服务。

研发费用包括执行研究和开发活动所发生的费用，如全职研发员工的薪酬和福利（包括股票补偿），分配的与设施相关的费用、一般费用、许可和里程碑费用、合同研究、开发和制造服务、临床试验费用和其他相关费用。

一般和行政性费用主要包括对我们的高管、财务、法律、人力资源、业务拓展和压力位职能人员的薪酬和福利，包括基于股票的薪酬。一般和行政性费用还包括分配的与设施相关的成本，未包括在研发费用中的旅行费用，以及审计、税务和法律服务的专业费用，包括与知识产权相关的法律服务，以及其他咨询费用和开支。

在2024年9月30日结束的三个月和九个月期间，其他收入（费用），净额包括我们现金、现金等价物、受限现金等价物和可交易证券所赚取的利息收入以及投资公允价值的变动。在2023年9月30日结束的三个月期间，其他收入（费用），净额包括我们现金、现金等价物、受限现金等价物和可交易证券所赚取的利息收入，以及我们权益法投资的损失。在2023年9月30日结束的九个月期间，其他收入（费用），净额包括我们现金、现金等价物、受限现金等价物和可交易证券所赚取的利息收入，我们权益法投资的损失，以及应计考虑的公允价值变动。

有关财务状况和经营业绩的讨论应与附表中的简明合并基本报表及相关附注一起阅读。

合作收入在截至2024年9月30日的三个月内减少了290万美元，比截至2023年9月30日的三个月减少。合作收入减少主要是由于AvenCell许可和合作协议（“AvenCell LCA”）下的收入减少。

截至2024年9月30日的三个月内，研发费用比截至2023年9月30日的三个月增加了970万美元。

以下表格总结了我们的研发费用，以及这些项目的变化金额和相应的变化百分比：

2024年9月30日结束的三个月的研发费用增加，与2023年9月30日结束的三个月相比，主要是由于：

General and administrative expenses increased by $1.1 million during the three months ended September 30, 2024, as compared to the three months ended September 30, 2023. This increase was primarily related to an increase in stock-based compensation of $1.3 million.

The increase in other income, net of $0.2 million is primarily related to a $3.9 million change related to our equity method loss recorded in the third quarter of 2023, offset in part by $3.1 million in expense due to the change in fair value of our investment in Kyverna and a $0.6 million decrease in interest income.

Collaboration revenue increased by $6.8 million to $45.0 million during the nine months ended September 30, 2024, as compared to $38.2 million during the nine months ended September 30, 2023. The increase in collaboration revenue during the nine months ended September 30, 2024 is primarily due to the recognition of $21.0 million of previously eliminated intra-entity profit under the AvenCell LCA, offset in part by a $12.4 million reduction in revenue related to the AvenCell LCA. Refer to Note 7 to our condensed consolidated financial statements appearing elsewhere in this Quarterly Report on Form 10-Q for further details.

Research and development expenses increased by $23.3 million to $349.4 million during the nine months ended September 30, 2024, as compared to $326.1 million during the nine months ended September 30, 2023.

The following table summarizes our research and development expenses, together with the changes in those items in dollars and the respective percentages of change:

The increase in research and development expenses for the nine months ended September 30, 2024 compared to the nine months ended September 30, 2023 was primarily attributable to:

General and administrative expenses increased by $5.9 million to $93.4 million during the nine months ended September 30, 2024, compared to $87.5 million during the nine months ended September 30, 2023. This increase was primarily related to an increase in stock-based compensation of $6.3 million.

The decrease in other income, net of $18.7 million is primarily related to $29.5 million in expense due to the change in fair value of our investments in Kyverna and AvenCell and a $0.2 million decrease in interest income, offset in part by a $10.9 million change related to our equity method loss recorded in the nine months ended September 30, 2023.

Since our inception through September 30, 2024, we have raised an aggregate of $2,758.3 million to fund our operations through our collaboration agreements, our initial public offering and concurrent private placements, follow-on public offerings, at-the-market offerings and the sale of convertible preferred stock.

As of September 30, 2024, we had $944.7 million in cash, cash equivalents and marketable securities.

In March 2022, we entered into an Open Market Sale Agreement (the “2022 Sale Agreement”) with Jefferies LLC (“Jefferies”), under which Jefferies is able to offer and sell, from time to time in “at-the-market” offerings, shares of our common stock having aggregate gross proceeds of up to $400.0 million. In February 2024, we entered into an amendment to the 2022 Sale Agreement (the “2022 Sale Agreement, as amended”) to increase the size of the at-the-market offering program from $400.0 million to $750.0 million. We agreed to pay cash commissions of up to 3.0% of the gross proceeds of sales of common stock under the 2022 Sale Agreement, as amended. Through September 30, 2024 we have issued 14,522,533 shares of our common stock under the 2022 Sale Agreement, as amended.

During the nine months ended September 30, 2024, we issued 7,004,370 shares of our common stock, in a series of sales, at an average price of $25.68 per share, in accordance with the 2022 Sale Agreement, as amended, for aggregate net proceeds of $174.9 million, after payment of cash commissions and approximately $0.2 million related to legal, accounting and other fees in connection with the sales.

As of September 30, 2024, $249.1 million in shares of common stock remain eligible for sale under the 2022 Sale Agreement, as amended.

Our primary uses of capital are, and we expect will continue to be, research and development research materials and contracted services, clinical trial costs, compensation and related expenses, laboratory and office facilities, research supplies, legal and regulatory expenses, patent prosecution filing and maintenance costs for our licensed IP, milestone and royalty payments and general overhead costs. During the remainder of 2024, we expect our expenses to increase compared to prior periods in connection with our ongoing activities as we continue to develop our clinical programs and advance additional programs into clinical development.

Because our lead programs are in the clinical stage and the outcome of these efforts is uncertain, we cannot estimate the actual amounts necessary to successfully complete the development and commercialization of any future product candidates or whether, or when, we may achieve profitability. Until such time as we can generate substantial product revenues, if ever, we expect to fund our ongoing cash needs through equity financings and collaboration arrangements. We receive cost reimbursements from Regeneron related to our collaboration agreements with them. Additionally, we are eligible to earn milestone payments and royalties, in each case, on a per-product basis under our collaborations with SparingVision, ONK and ReCode, on a per-target basis under our collaboration with Regeneron, and upon achievement of certain events with Kyverna, subject to the provisions of our agreements with each of them. Except for these sources of funding, we will not have any committed external source of liquidity. To the extent that we raise additional capital through the future sale of equity, the ownership interest of our stockholders will be diluted, and the terms of these securities may include liquidation or other preferences that adversely affect the rights of our existing stockholders. If we raise additional funds through collaboration arrangements in the future, we may have to relinquish valuable rights to our technologies, future revenue streams or product candidates or grant licenses on terms that may not be favorable to us. If we are unable to raise additional funds through equity financings when needed, we may be required to delay, limit, reduce or terminate our product development or future commercialization efforts or grant rights to develop and market product candidates that we would otherwise prefer to develop and market ourselves.

Based on our research and development plans and our expectations related to the progress of our programs, we expect that our cash, cash equivalents and marketable securities as of September 30, 2024, as well as research and cost reimbursement funding from our collaboration agreements, will enable us to fund our ongoing operating expenses and capital expenditure requirements into late 2026, excluding any potential milestone payments or extension fees that could be earned and distributed under our collaboration agreements or any strategic use of capital not currently in the base case planning assumptions. We have based this estimate on current assumptions that may prove to be wrong, and we could use our capital resources sooner than we expect.

Our ability to generate revenue and achieve profitability depends significantly on our success in many areas, including: developing our delivery technologies and our CRISPR/Cas9 technology platform; selecting appropriate product candidates to develop; completing research and preclinical and clinical development of selected product candidates; obtaining regulatory approvals and marketing authorizations for product candidates for which we complete clinical trials; developing a sustainable and scalable manufacturing process for product candidates; launching and commercializing product candidates for which we obtain regulatory approvals and marketing authorizations, either directly or with a collaborator or distributor; obtaining market acceptance of our product candidates; addressing any competing technological and market developments; negotiating favorable terms in any collaboration, licensing, or other arrangements into which we may enter; maintaining good relationships with our collaborators and licensors; maintaining, protecting, and expanding our portfolio of IP rights, including patents, trade secrets, and know-how; and attracting, hiring, and retaining qualified personnel.

Net cash used in operating activities of $263.7 million during the nine months ended September 30, 2024 primarily consists of a net loss of $390.1 million, further reduced by the non-cash recognition of $21.0 million of previously eliminated intra-entity profit recorded within “collaboration revenue” and accretion of investment discounts and premiums of $14.2 million. These decreases are offset in part by stock-based compensation of $114.7 million, $29.5 million in net adjustments to the fair value of our investments in Kyverna and AvenCell, net changes in operating assets and liabilities of $9.8 million and depreciation of $7.7 million.

Net cash used in operating activities of $301.0 million during the nine months ended September 30, 2023 primarily consists of a net loss of $349.0 million, further reduced by changes in operating assets and liabilities of $55.6 million, including the receipt of $12.6 million in payments from our collaboration partners during that period and offset in part by non-cash charges of stock-based compensation of $99.0 million, loss on equity method investment of $17.5 million and depreciation of $6.5 million.

During the nine months ended September 30, 2024, we used $26.0 million of net cash in investing activities. The decrease in the nine months ended September 30, 2024 is primarily due to $21.2 million in marketable securities purchased (net of maturities) and $4.8 million in cash for the purchase of property and equipment.

During the nine months ended September 30, 2023 we used cash of $77.3 million in investing activities. The decrease in the nine months ended September 30, 2023 is primarily due to $64.8 million in marketable securities purchased (net of maturities) and $12.5 million in cash for the purchase of property and equipment.

Net cash provided by financing activities of $183.4 million during the nine months ended September 30, 2024 includes $176.9 million in net proceeds from at-the-market offerings, $4.8 million in cash received from the exercise of stock options and $1.7 million in cash received from the issuance of shares through our employee stock purchase plan.

Net cash provided by financing activities of $23.8 million during the nine months ended September 30, 2023 includes $16.2 million in net proceeds from at-the-market offerings, $5.6 million in cash received from the exercise of stock options and $2.1 million in cash received from the issuance of shares through our employee stock purchase plan.

Our critical accounting policies require the most significant judgments and estimates in the preparation of our condensed consolidated financial statements. Management has determined that our most critical accounting policies are those relating to revenue recognition, accrued research and development expenses and stock-based compensation. There have been no changes to our critical accounting policies from those which were discussed in our Annual Report for the year ended December 31, 2023.

Please read Note 2, “Summary of Significant Accounting Policies,” to our condensed consolidated financial statements included in Part I, Item 1, “Notes to Condensed Consolidated Financial Statements,” of this Quarterly Report on Form 10-Q for a description of recent accounting pronouncements applicable to our business.

There were no material changes to our contractual obligations during the three months ended September 30, 2024. For a complete discussion of our contractual obligations, please refer to our Management’s Discussion and Analysis of Financial Condition and Results of Operations in our Annual Report for the year ended December 31, 2023.

The market risk inherent in our financial instruments and in our financial position represents the potential loss arising from adverse changes in interest rates. As of September 30, 2024, we had cash equivalents, restricted cash equivalents and marketable securities of $917.5 million consisting of interest-bearing money market accounts, corporate and financial institution debt securities, U.S. Treasury and other government-backed securities and asset-backed securities. Our primary exposure to market

risk is interest rate sensitivity, which is affected by changes in the general level of U.S. interest rates, particularly because our investments are primarily in marketable securities. Due to the short-term duration of our investment portfolios and the low risk profile of our investments, we do not believe an immediate change of 100 basis points, or one percentage point, would have a material effect on the fair market value of our investment portfolio. Declines in interest rates, however, would reduce future investment income.

We do not have any foreign currency or derivative financial instruments. Inflation generally affects us by increasing our cost of labor and program costs. We do not believe that inflation had a material effect on our results of operations during the nine months ended September 30, 2024.

We have established disclosure controls and procedures designed to ensure that information required to be disclosed in the reports that we file or submit under the Exchange Act is recorded, processed, summarized and reported within the time periods specified in the SEC’s rules and forms and is accumulated and communicated to management, including the principal executive officer (our Chief Executive Officer) and principal financial officer (our Chief Financial Officer), to allow timely decisions regarding required disclosure.

Our management, under the supervision and with the participation of our Chief Executive Officer and Chief Financial Officer, has evaluated the effectiveness of our disclosure controls and procedures (as defined in Rules 13a-15(e) and 15d-15(e) under the Exchange Act) as of the end of the period covered by this Quarterly Report on Form 10-Q. Management recognizes that any disclosure controls and procedures, no matter how well designed and operated, can provide only reasonable assurance of achieving their objectives. Our disclosure controls and procedures have been designed to provide reasonable assurance of achieving their objectives. Based on such evaluation, our Chief Executive Officer and Chief Financial Officer concluded that our disclosure controls and procedures were effective at the reasonable assurance level as of September 30, 2024.

No change in our internal control over financial reporting (as defined in Rules 13a-15(f) and 15d-15(f) under the Exchange Act) occurred during the three months ended September 30, 2024 that has materially affected, or is reasonably likely to materially affect, our internal control over financial reporting.

In the ordinary course of business, we are from time to time involved in lawsuits, claims, investigations, proceedings, and threats of litigation related to intellectual property (“IP”), commercial arrangements and other matters. The outcome of any such legal proceedings, regardless of the merits, is inherently uncertain. In addition, litigation and related matters are costly and may divert the attention of our management and other resources that would otherwise be engaged in other activities. If we were unable to prevail in any such legal proceedings, our business, results of operations, liquidity and financial condition could be adversely affected.

On July 8, 2024, BlueAllele Corp. (“BlueAllele”) filed a complaint alleging infringement by Intellia of various patents in the U.S. District Court for the District of Delaware. Specifically, BlueAllele alleges that our experimentation, basic research, identification, optimization, manufacturing and/or use of bi-directional insertion template technology infringes the asserted patents and seeks, inter alia, unspecified compensatory damages and an injunction against the alleged infringing activities. On September 12, 2024, we filed a motion to dismiss the complaint. On October 23, 2024, BlueAllele responded to the motion to dismiss.

Investing in our common stock involves a high degree of risk. In evaluating us and our business, careful consideration should be given to the following risk factors, in addition to the other information set forth in this Quarterly Report on Form 10-Q, our Annual Report on Form 10-K for the year ended December 31, 2023, and in other documents that we file with the Securities and Exchange Commission (“SEC”). If any of the following risks and uncertainties actually occurs, our business, prospects, financial condition and results of operations could be materially and adversely affected. The risks summarized and described below are not intended to be exhaustive and are not the only risks facing us. New risk factors can emerge from time to time, and we cannot predict the impact that any factor or combination of factors may have on our business, prospects, financial condition and results of operations.

The risk factors denoted with a “*”, if any, are newly added or have been materially updated from our Annual Report on Form 10-K for the year ended December 31, 2023.

CRISPR/Cas9 genome editing technology has only recently been clinically validated for human therapeutic use. The approaches we are taking to discover and develop novel therapeutics using CRISPR/Cas9 systems are unproven and may never lead to marketable products. If we are unable to develop viable product candidates, achieve regulatory approval for any such product candidate or market and sell any product candidates, we may never achieve profitability.

We are focused on developing curative medicines utilizing CRISPR/Cas9 genome editing technology, including in vivo therapies and ex vivo engineered cell therapies. Although there have been significant advances in recent years in the fields of gene therapy and genome editing, in vivo CRISPR-based genome editing technologies are relatively new and their therapeutic utility is largely unproven. Our approach to developing therapies centers on using CRISPR/Cas9 technology to alter, introduce or remove genetic

information in vivo to treat various disorders, or to engineer human cells ex vivo to create therapeutic cells that can be introduced into the human body to address the underlying disease.

Successful development of products by us will require solving a number of issues, including developing or obtaining technologies to safely deliver a therapeutic agent into target cells within the human body or engineer human cells while outside of the body such that the modified cells can have a therapeutic effect when delivered to the patient, optimizing the efficacy and specificity of such products, and ensuring and demonstrating the therapeutic selectivity, efficacy, potency, purity and safety of such products. There can be no assurance we will be successful in solving any or all of these issues. With regards to CRISPR/Cas9-based therapies specifically, we are in clinical-stage development for NTLA-2001, NTLA-2002 and NTLA-3001, and advancing towards clinical testing for our other in vivo and ex vivo product candidates. Although one CRISPR/Cas9-edited ex vivo therapy has been recently approved in the United States (“U.S.”) and European Union (“EU”), no genome editing in vivo therapy has been approved in the U.S., EU countries or other key jurisdictions, and the potential to successfully obtain approval for any of our CRISPR/Cas9 product candidates remains unproven.

Our future success also is highly dependent on the successful development of CRISPR-based genome editing technologies, cellular delivery methods and therapeutic applications for the indications on which we have focused our ongoing research and development efforts. We may decide to alter or abandon these programs as new data become available and we gain experience in developing CRISPR/Cas9-based therapeutics. We cannot be sure that our CRISPR/Cas9 efforts and technologies will yield satisfactory products that are safe and effective, sufficiently pure or potent, manufacturable, scalable or profitable in our selected indications or any other indication we pursue. We cannot guarantee that progress or success in developing any particular CRISPR/Cas9-based therapeutic product will translate to other CRISPR/Cas9-based products.

Public perception and related media coverage of potential therapy-related efficacy or safety issues, including adoption of new therapeutics or novel approaches to treatment, as well as ethical concerns related specifically to genome editing and CRISPR/Cas9, may adversely influence the willingness of subjects to participate in clinical trials, or if any therapeutic is approved, of physicians and patients to accept these novel and personalized treatments. Physicians, healthcare providers and third party payors often are slow to adopt new products, technologies and treatment practices, particularly those that may also require additional upfront costs and training. Physicians may not be willing to undergo training to adopt these novel and potentially personalized therapies, may decide the particular therapy is too complex or potentially risky to adopt without appropriate training, and may choose not to administer the therapy. Further, due to health conditions, genetic profile or other reasons, certain patients may not be candidates for the therapies. In addition, responses by federal and state agencies, congressional committees and foreign governments to negative public perception, ethical concerns or financial considerations may result in new legislation, regulations, or medical standards that could limit our ability to develop or commercialize any product candidates, obtain or maintain regulatory approval or otherwise achieve profitability. New government requirements may be established that could delay or prevent regulatory approval of our product candidates under development. It is impossible to predict whether legislative changes will be enacted, regulations, policies or guidance changed, or interpretations by agencies or courts changed, or what the impact of such changes, if any, may be. Based on these and other factors, healthcare providers and payors may decide that the benefits of these new therapies do not or will not outweigh their costs.

Clinical development involves a lengthy and expensive process, with an uncertain outcome. We may incur additional costs or experience delays in completing, or ultimately be unable to complete, the development and commercialization of any product candidates.*

All of our programs are still in the discovery, preclinical or clinical stage. Our current and future product candidates will require preclinical and clinical activities and studies, regulatory review and approval in each jurisdiction in which we intend to market the products, substantial investment, establishing manufacturing capabilities, access to sufficient commercial manufacturing capacity and significant marketing efforts before we can generate any revenue from product sales. Before obtaining marketing approval from regulatory authorities for the sale of a product candidate, we must conduct extensive clinical trials to demonstrate the safety, purity, potency and efficacy of the product in humans. It is impossible to predict when or if any of our programs will prove effective and safe in humans or will receive regulatory approval. Preclinical and clinical testing is expensive, difficult to design and implement, can take many years to complete and is uncertain as to outcome. We may be unable to establish clinical endpoints that regulatory authorities consider clinically meaningful, and a clinical trial can fail at any stage. The outcome of preclinical testing and clinical trials may not be predictive of the success of later clinical trials, and interim results of a clinical trial do not necessarily predict final results. Moreover, preclinical and clinical data are often susceptible to varying interpretations and analyses, and many companies that have believed their product candidates performed satisfactorily in preclinical studies and clinical trials have nonetheless failed to obtain approval of their products.

Successful completion of clinical trials is a prerequisite to submitting a Biologics License Application (“BLA”) to the FDA, and similar applications to comparable foreign regulatory authorities, for each product candidate and, consequently, the ultimate approval and commercial marketing of any product candidates. We do not know whether any of our clinical trials will begin or be completed on schedule, if at all. In addition, the regulatory requirements for later phase clinical trials, such as pivotal trials, are generally more stringent than earlier phase clinical trials, such as Phase 1 trials. We may not meet the requirements of regulatory authorities, such as the FDA, for initiating later phase clinical trials for our product candidates, which could delay the development of our product candidates, including the submission of a BLA or comparable marketing application.

Because these are new therapeutic approaches, discovering, developing, manufacturing and commercializing our product candidates may subject us to a number of challenges or delays in completing our preclinical studies and initiating or completing clinical trials. We also may experience numerous unforeseen events during, or as a result of, any current or future clinical trials that we conduct, which could delay or prevent our ability to receive marketing approval or commercialize our product candidates, including:

We could also encounter delays if a clinical trial is suspended or terminated by us, the IRBs of the institutions in which such trials are being conducted, the relevant ethics committee or the FDA or other relevant regulatory authorities, or if the Data Monitoring Committee (“DMC”) for such trial recommends such suspension or termination. Such authorities may impose or recommend such a suspension or termination due to a number of factors, including failure to conduct the clinical trial in accordance with regulatory requirements or our clinical protocols, inspection of the clinical trial operations or trial site by the FDA or other regulatory authorities, resulting in the imposition of a clinical hold, manufacturing or quality control issues, unforeseen safety issues or adverse side effects, failure to demonstrate a benefit from using a product or treatment, failure to establish or achieve clinically meaningful trial endpoints, changes in governmental regulations or administrative actions or lack of adequate funding to continue the clinical trial. Many of the factors that cause, or lead to, a delay in the commencement or completion of clinical trials may also lead to a delay in submitting a BLA or comparable marketing application or ultimately lead to the denial of regulatory approval of our product candidates. Further, the FDA or other regulatory authorities may disagree with our clinical trial design and our interpretation of data from clinical trials or may change the requirements for approval even after they have reviewed and commented on the design for our clinical trials.

Additionally, because our in vivo technology potentially involves genome editing across multiple cell and tissue types, we are subject to many of the challenges and risks that other genome editing therapeutics and gene therapies face, including:

Further, because our ex vivo product candidates involve editing human cells and then delivering modified cells to patients, we are subject to many of the challenges and risks that engineered cell therapies face. For example, patients treated with engineered cell-based gene therapies may experience an allogeneic response leading to allograft rejection and potential local and systemic toxicities, which could be severe or life-threatening.

To date, most human clinical trials utilizing either in vivo or ex vivo CRISPR-based therapeutics, including our clinical trials for NTLA-2001 for transthyretin (“ATTR”) amyloidosis, NTLA-2002 for hereditary angioedema (“HAE”) and NTLA-3001 for alpha-1 antitrypsin deficiency (“AATD”)-associated lung disease, are still at a clinical stage, with only one ex vivo CRISPR-based therapeutic product approved in December 2023 in the U.S. and EU. We have ongoing clinical trials in various countries for NTLA-2001 and NTLA-2002 for patients with ATTR amyloidosis and HAE, respectively. There is no certainty that the FDA or other similar agencies will continue to apply to all our CRISPR/Cas9 product candidates the same regulatory pathway and requirements it is applying to other in vivo therapies or ex vivo engineered therapeutics.

In addition, if any product candidates encounter safety or efficacy problems, development delays, regulatory issues or other problems, our development plans and business could be significantly harmed. For the reasons described above, among others, regulatory bodies, particularly the FDA, have requested, and may request in the future, additional preclinical studies for genome editing products, such as additional studies related to toxicology, biodistribution or reproductive health, and/or preclinical studies earlier in clinical development compared to other therapeutic modalities. Although the FDA cleared the INDs that we have submitted, it is possible that the FDA may impose requirements that result in a delay of any of our programs, including our submission of a BLA or comparable marketing application, or their regulatory approval. For example, following the March 2023 IND clearance for NTLA-2002, the FDA requested supplemental preclinical data related to the inclusion of female patients of child-bearing potential, which we have since provided to the FDA in advance of the planned Phase 3 study and have received written feedback from the FDA that the data provided support inclusion of female patients of child-bearing potential in the Phase 3 study. If we are unable to complete the required studies satisfactorily, the FDA or other regulatory bodies could require that we exclude certain patient populations from clinical studies, place our clinical studies on hold, or require us to cease further clinical studies or deny approval of such product candidates. Further, competitors that are developing in vivo or ex vivo products with similar technology may experience problems with their product candidates or programs that could in turn cause us to identify problems with our product candidates and programs, or cause the FDA or other regulatory bodies to impose additional requirements, that could cause us to delay or pause development of our product candidates. Any of these occurrences may harm our ability to identify and develop product candidates, and may harm our business, financial condition, results of operations and prospects significantly.

We may experience manufacturing delays or other issues that prevent us from executing the clinical trials for NTLA-2001, NTLA-2002, NTLA-3001 or our other product candidates on the timeline we expect. Moreover, we cannot guarantee that the FDA, MHRA, the New Zealand Medicines and Medical Devices Safety Authority, or other regulatory authorities will not change their requirements in the future or approve amendments to our INDs or equivalent regulatory filings, including for NTLA-2001, NTLA-2002, NTLA-3001 or our other product candidates on the timeline we expect.

Results, including data from our preclinical and clinical studies, are not necessarily predictive of our other ongoing and future preclinical and clinical studies, and they do not guarantee or indicate the likelihood of approval of any potential product candidate by the FDA or any other regulatory agency. If we cannot replicate positive results from any of our preclinical or clinical activities and studies, we may be unable to successfully develop, obtain regulatory approval for and commercialize any potential product candidate.

From time to time, we may disclose interim data from our clinical trials, such as the interim results of our ongoing Phase 1 study of NTLA-2001 or Phase 1/2 study of NTLA-2002 or planned Phase 1/2 study of NTLA-3001. Interim data from clinical trials that have not been completed are subject to the risk that one or more of the clinical outcomes may materially change as patient

enrollment continues and more patient data become available or as patients from our clinical trials continue other treatments for their disease. We also make assumptions, estimations, calculations and conclusions as part of our analyses of data, and we may not have received or had the opportunity to fully and carefully evaluate all data. As a result, results that we report may differ from future results of the same studies, or different conclusions or considerations may qualify such results, once additional data have been received and fully evaluated. Consequently, interim data should be viewed with caution until we make the final data and analysis available.

In addition, there is a high failure rate, as well as potential substantial and unanticipated delays, for product candidates progressing through preclinical and clinical studies. Even if we are able to successfully complete our ongoing and future preclinical and clinical activities and studies for any potential product candidate, we may not be able to replicate, or may have to engage in significant efforts and resource and time investments to replicate, any positive results from these or any other studies in any of our future preclinical and clinical trials, and they do not guarantee approval of any potential product candidate by the FDA or any other necessary regulatory authorities in a timely manner or at all. For more information regarding these risks, see also the remainder of this risk factor section.

Negative public opinion and increased regulatory scrutiny of CRISPR/Cas9 use, genome editing or gene therapy generally may damage public perception of the safety of any product candidates that we develop and adversely affect our ability to conduct our business or obtain regulatory approvals for such product candidates.

Gene therapy in general, and genome editing in particular, remain novel technologies, with only a limited number of gene therapy products, and only one ex vivo genome editing product, approved to date in the U.S. and EU. Public perception may be influenced by claims that gene therapy or genome editing, including the use of CRISPR/Cas9, is unsafe or unethical, or carries an undue risk of side effects, such as improper modification of a gene sequence in a patient’s chromosome that could lead to cancer, and gene therapy or genome editing may not gain the acceptance of the public or the medical community. In particular, our success will depend upon physicians who specialize in the treatment of diseases targeted by our product candidates prescribing treatments that involve the use of our product candidates in lieu of, or in addition to, existing treatments with which they are more familiar and for which greater clinical data may be available. In addition, responses by the U.S., state or foreign governments to negative public perception or ethical concerns may result in new legislation or regulations that could limit our ability to develop or commercialize any product candidates, obtain or maintain regulatory approval or otherwise achieve profitability. More restrictive statutory regimes, government regulations or negative public opinion could have an adverse effect on our business, financial condition and results of operations and prospects, and may delay or impair the development and commercialization of our product candidates or demand for any products we may develop. For example, certain gene therapy trials led to several well-publicized adverse events, including cases of leukemia and death. Serious adverse events, such as these, in our clinical trials, or other clinical trials involving gene therapy or genome editing products or our competitors’ products, even if not ultimately attributable to the relevant product candidates, and the resulting publicity could result in increased government regulation, unfavorable public perception, potential regulatory delays in the testing or approval of our product candidates, stricter labeling requirements for those product candidates that are approved and a decrease in demand for any such product candidate. In addition, the use of the technology by third parties in areas that are not being pursued by us, such as for targeting and editing of embryonic cells, could adversely impact public and governmental perceptions regarding the ethics and risks of the CRISPR/Cas9 technology and lead to social or legal changes that could limit our ability to apply the technology to develop human therapies addressing disease. For example, reports of the use of CRISPR/Cas9 in China and Russia to edit embryos in utero have generated, and may continue to generate, negative public perception about the use of the technology in humans. Negative public and governmental perception of the technology, or additional governmental regulation of our technologies, could also adversely affect our stock price or our ability to enter into revenue generating collaborations or obtain additional funding from the public markets.

Inconclusive results, lack of efficacy, adverse events or additional safety concerns in clinical trials that we or others conduct may impede the regulatory approval process or overall market acceptance of our product candidates.

Therapeutic applications of genome editing technologies, and CRISPR/Cas9 in particular, for both in vivo products and ex vivo products, are unproven and must undergo rigorous clinical trials and regulatory review before receiving marketing authorization. If the results of our clinical studies or those of any other third parties, including with respect to genome editing technology or engineered cell therapies, are inconclusive or fail to show efficacy or if such clinical trials give rise to safety concerns or adverse events, we may:

Additionally, our product candidates could potentially cause other adverse events that have not yet been predicted and the potentially permanent nature of genome editing effects, including CRISPR/Cas9’s effects, on genes or novel cell therapies in the organs of the human body may make these adverse events irreversible. The inclusion of critically ill patients in our clinical studies or those of our competitors may result in deaths or other adverse medical events, including those due to other therapies or medications that such patients may be using. Any of these events could prevent us from achieving or maintaining regulatory approval or market acceptance of our product candidates and impair our ability to achieve profitability.

Research and development of biopharmaceutical products is inherently risky. We may not be successful in our efforts to use and enhance our genome editing technology to create a pipeline of product candidates, establish the necessary manufacturing capabilities, obtain regulatory approval and develop commercially successful products, or we may expend our limited resources on programs that do not yield a successful product candidate and fail to capitalize on potential product candidates or diseases that may be more profitable or for which there is a greater likelihood of success. If we fail to develop product candidates, our commercial opportunity, if any, will be limited.

We are at a clinical stage of development and our technology and approach has not yet led, and may never lead, to the approval or commercialization of any of our product candidates, including NTLA-2001 for ATTR amyloidosis, NTLA-2002 for HAE, or NTLA-3001 for AATD, or to our other product candidates being deemed appropriate for clinical development and ultimately approval by a regulatory agency. Even if we are successful in building our pipeline of product candidates, completing clinical development, establishing the necessary manufacturing processes and capabilities, obtaining regulatory approvals and commercializing product candidates will require substantial additional funding and are subject to the risks of failure inherent in therapeutic product development. Investment in biopharmaceutical product development involves significant risk that any potential product candidate will fail to demonstrate acceptable safety and efficacy profiles, gain regulatory approval, or become commercially viable.

We cannot provide any assurance that we will be able to successfully advance any of our product candidates, including NTLA-2001, NTLA-2002, NTLA-3001 or product candidates developed through our collaborations, through the entire research and development process. Any of our other programs may show promise, yet fail to yield product candidates for clinical development or commercialization for many reasons. For more information regarding these risks, see the above risk factor section entitled “Risks Related to Preclinical and Clinical Development.”

Even if we obtain regulatory approval of any product candidates, such candidates may not gain market acceptance among physicians, patients, hospitals, third party payors and others in the medical community.

The use of the CRISPR/Cas9 system to create genome editing-based therapies is a recent development and may not become broadly accepted by patients, healthcare providers, third party payors and other stakeholders. A variety of factors will influence whether our product candidates are accepted in the market, including, for example:

Even if our products achieve market acceptance, we may not be able to maintain that market acceptance over time if new products or technologies are introduced that are more favorably received than our products, are more cost effective or render our products obsolete. In addition, adverse publicity due to the ethical and social controversies surrounding the therapeutic in vivo use of CRISPR/Cas9, genome edited modified cells, or other therapeutics mediums, such as viral vectors that we may use in our clinical trials may limit market acceptance of our product candidates. If our product candidates are approved but fail to achieve market acceptance among physicians, patients, hospitals, third party payors or others in the medical community, we will not be able to generate significant revenue. Our efforts to educate the healthcare providers, patients and third party payors about our products may require significant resources and may never be successful.

Third party claims of intellectual property infringement against us, our licensors or our collaborators may prevent or delay our product discovery and development efforts.

Our commercial success depends in part on our avoiding infringement of the valid patents and proprietary rights of third parties.

Numerous U.S. and foreign issued patents and pending patent applications owned by third parties exist in the fields in which we are developing our product candidates and in areas potentially related to components and methods we use or may use in our research and development efforts. As industry, government, academia and other biotechnology and pharmaceutical research expands and more patents are issued, the risk increases that our product candidates may give rise to claims of infringement of the patent rights of others. Our development candidates are complex and may include multiple components such as Cas9 protein or messenger ribonucleic acid encoding Cas9 protein, guide ribonucleic acids (“gRNAs”), targeting molecules, or formulation components such as lipids. We cannot guarantee that any of these components of our technology, processes, future product candidates or the use of such product candidates do not infringe third party patents. It is also possible that we have failed to identify relevant third party patents or applications. Because patent rights are granted jurisdiction-by-jurisdiction, our freedom

to practice certain technologies, including our ability to research, develop and commercialize our product candidates, may differ by country.

Third parties may assert that we infringe their patents or that we are otherwise employing their proprietary technology without authorization, and may sue us. There may be third party patents with claims to compositions, formulations, methods of manufacture or methods of use or treatment that cover product candidates we discover and develop. 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 or the manufacture, use or sale of our product candidates or products that we develop infringes these patents. If a court of competent jurisdiction were to hold that we infringed such patents, the holders of any such patents may be able to block our ability to commercialize the applicable product candidate or products unless we obtain a license under the applicable patents, or until such patents expire or are finally determined to be held invalid or unenforceable. Such a license may not be available on commercially reasonable terms or at all. Even if we were able to obtain a license, it could be non-exclusive, thereby giving our competitors access to the same technologies licensed to us. We could be forced, including by court order, to cease commercializing, manufacturing or importing the infringing technology or product. 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. A finding of infringement could prevent us from commercializing one or more of our product candidates or products that we develop, force us to redesign our infringing products or force us to cease some or all of our business operations, any of which could materially harm our business and could prevent us from further developing and commercializing such products or future product candidates, thereby causing us significant harm. If we are unable to obtain a necessary license to a third party patent on commercially reasonable terms, our ability to commercialize our product candidates or products that we develop may be impaired or delayed, which could in turn significantly harm our business. In addition, we may be obligated to defend and/or indemnify our existing or potential collaborators, clinical investigators, contract manufacturing organizations (“CMOs”), CROs, consultants or vendors if a third party asserts similar infringement claims against them based on use of our technologies or the manufacture, use or sale of our product candidates or products that we develop, including product candidates or products developed with our collaborators. Claims that we have misappropriated the confidential information or trade secrets of third parties could have a similar negative impact on our business. Even if we are not found liable for infringing or misappropriating the intellectual property of a third party, such claims could be expensive and time-consuming to defend and could result in adverse publicity that could harm our business.

Third parties may seek to claim intellectual property rights that encompass or overlap with intellectual property that we own or license from them or others. Legal proceedings may be initiated to determine the scope and ownership of these rights, and could result in our loss of rights, including injunctions or other equitable relief that could effectively block our ability to further develop and commercialize our product candidates or products that we develop, including product candidates or products developed with our collaborators. For example, through a license agreement between Caribou Biosciences, Inc. and us (the “Caribou License”), we sublicense the rights of the Regents of the University of California and the University of Vienna (collectively, “UC/Vienna”) to a worldwide patent portfolio that covers methods of use and compositions relating to engineered CRISPR/Cas9 systems for, among other things, cleaving or editing DNA and altering gene product expression in various organisms, including eukaryotic cells. We sublicense the UC/Vienna rights to this portfolio for human therapeutic, prophylactic and palliative uses, including companion diagnostics, except for anti-fungal and anti-microbial uses. This patent portfolio to-date includes, for example, multiple granted, allowed, and/or allowable patent applications in the U.S., as well as granted patents from the European Patent Office, the United Kingdom’s Intellectual Property Office, the German Patent and Trade Mark Office, Australia’s Intellectual Property agency and China’s Intellectual Property Office, among others. Because UC/Vienna co-own this portfolio with Dr. Emmanuelle Charpentier (who has separately licensed her rights to other parties), we refer to this co-owned worldwide patent portfolio as the “UC/Vienna/Charpentier patent family.”

Third parties could assert that our licensors, such as UC/Vienna/Charpentier, do not have rights to the licensed technology (such as the CRISPR/Cas9 technology in the case of the Caribou License), including inventorship and ownership rights to currently issued or allowable patents, or that any rights owned by our licensors, such as UC/Vienna/Charpentier, are limited. If such third parties were found to have rights to the licensed technology (such as CRISPR/Cas9 technology), we could be required to obtain rights from such parties or cease our development and commercialization efforts. For example, under our Caribou License, we have rights to patent applications owned by UC/Vienna/Charpentier covering certain aspects of CRISPR/Cas9 systems to edit genes in eukaryotic cells, including human cells (collectively, the “UC/Vienna/Charpentier eukaryotic patent family”). The Broad Institute, Massachusetts Institute of Technology, the President and Fellows of Harvard College and the Rockefeller University (collectively, the “Broad Institute”) co-own patents and patent applications that also claim CRISPR/Cas9 systems to edit genes in eukaryotic cells (collectively, the “Broad Institute patent family”). Because the respective owners of various

UC/Vienna/Charpentier patent applications and the Broad Institute patent family both allege owning intellectual property claiming overlapping aspects of CRISPR/Cas9 systems and methods to edit genes in eukaryotic cells, including human cells, our ability to market and sell CRISPR/Cas9-based human therapeutics may be adversely impacted depending on the scope and actual ownership over the inventions claimed in the competing patent portfolios. On June 25, 2019, the Patent Trial and Appeal Board (“PTAB”) of the U.S. Patent and Trademark Office (“USPTO”) declared an interference between the UC/Vienna/Charpentier eukaryotic patent family and the Broad Institute patent family to determine which research group first invented the use of the CRISPR/Cas9 technology in eukaryotic cells and, therefore, is entitled to the U.S. patents covering that invention. The interference involved 14 allowable patent applications from the UC/Vienna/Charpentier eukaryotic patent family and 13 patents and one patent application from the Broad Institute patent family. On February 28, 2022, the PTAB issued a Decision of Priority and Judgment in the interference finding that the Broad Institute patent family has priority over the UC/Vienna/Charpentier patent family with respect to the subject matter of the interference. An appeal and cross-appeal from the interference are pending at the United States Court of Appeals for the Federal Circuit as Case Nos. 22-1594 and 22-1653, and the oral argument occurred on May 7, 2024.

On December 14, 2020, the PTAB declared an additional interference between the same 14 allowable patent applications in the UC/Vienna/Charpentier patent family, and one patent application owned by ToolGen, Inc. And, on June 21, 2021, the PTAB declared another interference between the same 14 allowable patent applications in the UC/Vienna/Charpentier patent family and one patent application owned by Sigma-Aldrich Co. LLC (a subsidiary of Merck KGaA). Because the patent applications involved in these interferences also purport to cover the use of CRISPR/Cas9 for gene editing in eukaryotic cells, the PTAB seeks to determine between the various groups which one invented first and is entitled to the resulting U.S. patents. A decision on motions issued in the ToolGen interference on September 28, 2022, and the priority phase of that interference was suspended until a mandate concludes the Federal Circuit appeal and cross-appeal in the UC/Vienna/Charpentier interference with the Broad Institute. The Sigma-Aldrich interference is in its motions phase, and an order scheduling oral argument issued on October 24, 2022. If either the Broad Institute, ToolGen or Sigma-Aldrich were to succeed in any of their respective interferences, the prevailing party or parties could seek to assert its issued patents against us based on our CRISPR/Cas9-based activities, including commercialization. In addition, the prevailing party may assert similar infringement claims against our existing or potential collaborators, clinical investigators, CMOs, CROs, consultants or vendors, and we may be obligated to defend and/or indemnify those parties against such infringement claims.

In addition, other third parties, such as Vilnius University and Harvard University, filed patent applications claiming CRISPR/Cas9-related inventions around or within a year after the first patent application filed in the UC/Vienna/Charpentier patent family and allege (or may allege) that they invented one or more of the inventions claimed by UC/Vienna/Charpentier before UC/Vienna/Charpentier. If the USPTO deems the scope of any of such third party’s claims sufficiently overlap with the allowable claims from the applicable patent applications in the UC/Vienna/Charpentier patent family, the USPTO could declare other interference proceedings to determine the actual inventor of such claims. If these third parties were to prevail in their inventorship claims or obtain patent claims that cover our product candidates or related activities through these various legal proceedings, then we could be prevented from utilizing the intellectual property we have licensed from Caribou, as well as from developing and commercializing all or some of our products candidates unless we can obtain rights to the third parties’ intellectual property or avoid or invalidate it.

Further, many third parties, including the third parties described above, have also filed patent applications and obtained patents covering aspects of the CRISPR/Cas9 technology in other key jurisdictions, including the EU members, the U.K., China and Japan. If these patents are deemed valid and cover our product candidates or related activities, we could be prevented from developing and commercializing all or some of our product candidates unless we license the relevant intellectual property or avoid it.

Defense of any potential infringement claims, regardless of their merit, would involve substantial litigation expense, would be a substantial diversion of management and other employee resources from our business and may impact our reputation. In the event of a successful claim of infringement against us, or a third party that we are obliged to defend and indemnify, we may have to pay substantial damages, including treble damages and attorneys’ fees for willful infringement, obtain one or more licenses from third parties, pay royalties or redesign our infringing products, which may be impossible or require substantial time and monetary expenditure. In that event, we could be unable to further develop and commercialize our product candidates, which could harm our business significantly. Refer to “Item 1. Legal Proceedings” above for an example.

We depend on intellectual property licensed from third parties and termination or modification of any of these licenses could result in the loss of significant rights, which would harm our business.

We are dependent on patents, know-how and proprietary technology, both our own and licensed from others, including Caribou. Any termination of these licenses, loss by our licensors of the rights they receive from others, diminution of our rights or those of our licensors, or a finding that such intellectual property lacks legal effect, could result in the loss of significant rights and could harm our ability to commercialize any product candidates. For example, UC/Vienna could challenge Caribou’s rights under their agreement, including Caribou’s right to sublicense its rights to others, such as Intellia, and on what terms such a sublicense would be granted, each of which could adversely impact our rights under our agreement with Caribou. Similarly, Caribou or other licensors, or other third parties from which we derive rights, could challenge the scope of our licensed rights or fields under our license agreement, which could adversely impact our exclusive rights to use CRISPR/Cas9 technology in our human therapeutics field. For example, in connection with the arbitration regarding the scope of the Caribou License, we executed a leaseback agreement with Caribou granting it a sublicense to develop and commercialize CB-010, which is a chimeric antigen receptor T (“CAR-T”) cell therapy directed at CD19. The leaseback agreement could adversely affect our business or that of our collaborators developing similar human therapeutics.

Disputes have and may arise between us and our licensors, our licensors and their licensors, or us and third parties that co-own intellectual property with our licensors or their licensors, regarding intellectual property subject to a license agreement, including those relating to:

If disputes over intellectual property that we have licensed prevent or impair our ability to maintain our current licensing arrangements on acceptable terms, or are insufficient to provide us the necessary rights to use the intellectual property, we may be unable to successfully develop and commercialize the affected product candidates. If we or any such licensors fail to adequately protect this intellectual property, our ability to commercialize our products could suffer.

We depend, in part, on our licensors to file, prosecute, maintain, defend and enforce patents and patent applications that are material to our business.

Patents relating to our product candidates are controlled by certain of our licensors or their respective licensors. Each of our licensors or their licensors generally has rights to file, prosecute, maintain and defend the patents we have licensed from such licensor. If these licensors or any future licensees and in some cases, co-owners from which we do not yet have licenses, having rights to file, prosecute, maintain, and defend our patent rights fail to adequately conduct these activities for patents or patent applications covering any of our product candidates, our ability to develop and commercialize those product candidates may be adversely affected and we may not be able to prevent competitors from making, using or selling competing products. We cannot be certain that such activities by our licensors or their respective licensors have been or will be conducted in compliance with

applicable laws and regulations or in our best interests, or will result in valid and enforceable patents or other intellectual property rights. Pursuant to the terms of the license agreements with our licensors, the licensors may have the right to control enforcement of our licensed patents or defense of any claims asserting the invalidity of these patents and, even if we are permitted to pursue such enforcement or defense, we cannot ensure the cooperation of our licensors or, in some cases, other necessary parties, such as the co-owners of the intellectual property from which we have not yet obtained a license. We cannot be certain that our licensors or their licensors, and in some cases, their respective co-owners, will allocate sufficient resources or prioritize their or our enforcement of such patents or defense of such claims to protect our interests in the licensed patents. For example, with respect to our sublicensed rights from Caribou to UC/Vienna/Charpentier intellectual property, UC retained the right to control the prosecution, enforcement and defense of this intellectual property in its license agreement with Caribou and, pursuant to an Invention Management Agreement, shares these responsibilities with CRISPR Therapeutics AG and, under certain circumstances, ERS Genomics, Ltd., as the designated managers of the intellectual property. For these reasons, UC may be unable or unwilling to prosecute certain patent claims that would be best for our product candidates, or enforce its patent rights against infringers of the UC/Vienna/Charpentier patent family.

Even if we are not a party to legal actions or other disputes involving our licensed intellectual property, an adverse outcome could harm our business because it might prevent us from continuing to license intellectual property that we may need to operate our business. In addition, even when we have the right to control patent prosecution of licensed patents and patent applications, enforcement of licensed patents, or defense of claims asserting the invalidity of those patents, we may still be adversely affected or prejudiced by actions or inactions of our licensors and their counsel that took place prior to or after our assuming control.

We may not be successful in obtaining or maintaining necessary rights to product components and processes or other technology for our product development pipeline.

The growth of our business will likely depend in part on our ability to acquire or in-license additional proprietary rights. For example, our programs may involve additional product candidates, delivery systems or technologies that may require the use of additional proprietary rights held by third parties, including competitors. Our ultimate product candidates may also require specific modifications or formulations to work effectively and efficiently. These modifications or formulations may be covered by intellectual property rights held by others, including competitors. We may be unable to acquire or in-license any relevant third party intellectual property rights that we identify as necessary or important to our business operations.

Additionally, we sometimes collaborate with academic institutions to accelerate our preclinical research or development under written agreements with these institutions. Typically, these institutions provide us with an option to negotiate a license to any of the institution’s rights in technology resulting from the collaboration. Regardless of such option, we may be unable to negotiate a license 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 other parties, potentially blocking our ability to pursue our program.

The licensing and acquisition of third party intellectual property rights is a competitive practice and companies that may be more established, or have greater resources than we do, may also be pursuing strategies to license or acquire third party intellectual property rights that we may consider necessary or attractive in order to commercialize our product candidates. More established companies may have a competitive advantage over us due to their larger size and cash resources or greater clinical development and commercialization capabilities. There can be no assurance that we will be able to successfully complete such negotiations and ultimately acquire the rights to the intellectual property surrounding the additional product candidates that we may seek to acquire.

If we are unable to successfully obtain rights to valid third party intellectual property or to maintain the existing intellectual property rights we have, we may have to abandon development of such program and our business and financial condition could suffer.

We may be required to pay certain milestones and royalties under our license agreements with third party licensors.

Under our current and future license agreements and other technology agreements, we may be required to pay milestones and royalties based on our revenues, including sales revenues of our products, utilizing the technologies acquired, licensed or sublicensed from third parties, including Caribou and Rewrite Therapeutics, Inc. (“Rewrite”), and these milestones and royalty payments could adversely affect our ability to research, develop and obtain approval of product candidates, as well as the overall profitability for us of any products that we may seek to commercialize. In order to maintain our intellectual property rights under these agreements, we will need to meet certain specified milestones, subject to certain cure provisions, in the development of our product candidates. Further, our counterparties, including our licensors (or their licensors) or licensees, may dispute the terms,

including amounts, that we are required to pay under the respective agreements. If these claims were to result in a material increase in the amounts that we are required to pay to our counterparties, including licensors or their licensors, or in a claim of breach of the applicable agreement, our ability to research, develop and obtain approval of product candidates, or to commercialize products, could be significantly impaired.

In addition, these agreements contain diligence milestones and we may not be successful in meeting all of the milestones in the future on a timely basis or at all. We will need to outsource and rely on third parties for many aspects of the clinical development, sales and marketing of our products covered under our license agreements and other technology agreements. Delay or failure by these third parties could adversely affect the continuation of these agreements with their counterparties, including our licensors or their licensors.

We could be unsuccessful in obtaining or maintaining adequate patent protection for one or more of our products or product candidates, or asserting and defending our intellectual property rights that protect our products and technologies.

We anticipate that we will file additional patent applications both in the U.S. and in other countries, as appropriate. However, we cannot predict:

Composition of matter patents for biological and pharmaceutical products are generally considered to be the strongest form of intellectual property protection for those types of products, as such patents provide protection without regard to any method of use. We cannot be certain, however, that any claims in our pending or future patent applications covering the composition of matter of our product candidates will be considered patentable by the USPTO or by patent offices in foreign countries, or that the claims in any of our ultimately issued patents will be considered valid and enforceable by courts in the U.S. or foreign countries. Method of use patents protect the use of a product for the specified method, for example a method of treating a certain indication using a product. This type of patent does not prevent a competitor from making and marketing a product that is identical to our product for an indication that is outside the scope of the patented method. Moreover, even if competitors do not actively promote their product for our targeted indications, physicians may prescribe these products “off-label” for those uses that are covered by our method of use patents. Although off-label prescriptions may infringe or contribute to the infringement of method of use patents, the practice is common and such infringement is difficult to prevent or prosecute.

The strength of patents in the biotechnology and pharmaceutical field can be uncertain, and evaluating the scope of such patents involves complex legal and scientific analyses. The patent applications that we own or in-license may fail to result in issued patents with claims that cover any product candidates or uses thereof in the U.S. or in other foreign countries.

Further, the patent prosecution process is expensive and time-consuming, and we may not be able to file and prosecute all necessary or desirable patent applications at a reasonable cost, in a timely manner, or in all jurisdictions. 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 the patents, covering technology that we license from third parties. We may also require the cooperation of our licensors or other necessary parties, such as the co-owners of the intellectual property from which we have not yet obtained a license, in order to enforce the licensed patent rights, and such cooperation may not be provided. Therefore, these patents and applications may not be prosecuted and enforced in a manner consistent with the best interests of our business.

The laws of foreign countries may not protect our rights to the same extent as the laws of the U.S. and we may fail to seek or obtain patent protection in all major markets. For example, European patent law restricts the patentability of methods of treatment

of the human body more than U.S. law does. Publications of discoveries in the scientific literature often lag behind the actual discoveries, and patent applications in the U.S. and other jurisdictions are typically not published until 18 months after filing, or in some cases not at all. Therefore, we will be unable to know with certainty whether we were the first to make any inventions claimed in any patents or patent applications, or that we were the first to file for patent protection of such inventions, nor can we know whether those from whom we license patents were the first to make the inventions claimed or were the first to file.

The issuance of a patent is not conclusive as to its inventorship, scope, validity or enforceability, and our owned and licensed patents may be challenged in the courts or patent offices in the U.S. and abroad. There is a substantial amount of litigation as well as administrative proceedings for challenging patents, including interference, derivation, reexamination, and other post-grant proceedings before the USPTO and oppositions and other comparable proceedings in foreign jurisdictions, involving patents and other intellectual property rights in the biotechnology and pharmaceutical industries, and we expect this to be true for the CRISPR/Cas9 space as well. Indeed, a number of third parties have filed oppositions challenging the validity, and seeking the revocation, of several CRISPR/Cas9 genome editing patents granted to UC/Vienna/Charpentier by the European Patent Office (“EPO”). To date, UC/Vienna/Charpentier have successfully defended before the EPO’s opposition division the validity of their first European patent, which covers compositions comprising Cas9 and single gRNA molecules, as well as methods of editing DNA in vitro or ex vivo using Cas9 and single gRNAs. The opponents to this patent have appealed the decision of the EPO’s opposition division. If UC/Vienna/Charpentier fail in defending the validity of its first European patent, we may lose valuable intellectual property rights, such as the right to exclude others from using such intellectual property. Such an outcome could have a material adverse effect on our business in Europe. Similarly, third parties are opposing the other patents issued by the EPO to UC/Vienna/Charpentier, including their second European patent that was recently revoked by the EPO’s opposition division, a decision that UC/Vienna/Charpentier have appealed. Although the claims of these other patents are more limited in scope compared to the first European patent, the inability to defend their respective validity could result in loss of valuable rights. In addition, since the passage of the America Invents Act in 2013, U.S. law also provides for other procedures to challenge patents, including inter partes reviews and post-grant reviews, that add uncertainty to the possibility of challenge to our developed or licensed patents and patent applications in the future. Furthermore, for U.S. applications in which all claims are entitled to a priority date before March 16, 2013, an interference proceeding can be provoked by a third party or instituted by the USPTO to determine who was the first to invent any of the subject matter covered by the patent claims of our applications. See the above risk factor entitled “Third party claims of intellectual property infringement against us, our licensors or our collaborators may prevent or delay our product discovery and development efforts.”

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 practice the invention or stop others from using or commercializing similar or identical technology and products, or limit the duration of the patent protection of our technology and products. 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.

Furthermore, even if they are unchallenged, our patents and patent applications may not adequately protect our intellectual property or prevent others from designing their products to avoid being covered by our claims. If the breadth or strength of protection provided by the patent applications we hold is threatened, this could dissuade companies from collaborating with us to develop, and could threaten our ability to commercialize, product candidates. Further, if we encounter delays in our clinical trials, the period of time during which we could market product candidates under patent protection would be reduced. Because patent applications in the U.S. and most other countries are confidential for a period of time after filing, we cannot be certain that we were the first to file any patent application related to our product candidates.

Our pending and future patent applications or the patent applications that we obtain rights to through in-licensing arrangements may not result in patents being issued which protect our technology or future 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 U.S. and other countries may diminish the value of our patents or narrow the scope of our patent protection.

Litigation or other administrative proceedings challenging our intellectual property, including interferences, derivation, reexamination, inter partes reviews and post-grant reviews, may result in a decision adverse to our interests and, even if we are successful, may result in substantial costs and distract our management and other employees. Furthermore, there could be public announcement of the results of hearings, motions or other interim proceedings or developments in any proceeding challenging

the issuance, scope, validity and enforceability of our developed or licensed intellectual property. 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.

Any of these potential negative developments could impact the scope, validity, enforceability or commercial value of our patent rights and, as a result, have material adverse effect on our business, financial condition, results of operations or prospects.

We may be subject to claims challenging the inventorship of our patents and other intellectual property.

We may in the future be subject to claims that former employees, collaborators or other third parties have an interest in our patents or other intellectual property as an inventor or co-inventor or other claims challenging the inventorship of our patents or ownership of our intellectual property (including patents and intellectual property that we in-license). For example, the UC/Vienna/Charpentier patent family that is covered by our license agreement with Caribou is co-owned by UC/Vienna and Dr. Charpentier, and our sublicense rights are derived from the first two co-owners and not from Dr. Charpentier. Therefore, our rights to these patents are not exclusive and third parties, including competitors, may have access to intellectual property that is important to our business. In addition, we may have inventorship disputes arise from conflicting obligations of collaborators, consultants or others who are involved in developing our technology and product candidates. Litigation or other legal proceedings may be necessary to defend against these and other claims challenging inventorship. If we fail in defending any such claims, in addition to paying monetary damages, we may lose valuable intellectual property rights, such as exclusive ownership of, or right to use, valuable intellectual property. Such an outcome could have a material adverse effect on our business. Even if we are successful in defending against such claims, litigation could result in substantial costs and be a distraction to management and other employees.

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

We have limited intellectual property rights outside the U.S. Filing, prosecuting, maintaining and defending patents on product candidates in all countries throughout the world would be prohibitively expensive, and our intellectual property rights in some countries outside the U.S. can have a different scope and strength than do those in the U.S. In addition, the laws of some foreign countries, such as China, Brazil, Russia, India and South Africa, do not protect intellectual property rights to the same extent as federal and state laws in the U.S. Consequently, we may not be able to prevent third parties from practicing our inventions in all countries outside the U.S., or from selling or importing products made using our inventions in and into the U.S. or other jurisdictions. Competitors may use our technologies in jurisdictions where we have not obtained patent protection to develop their own products and further, may export otherwise infringing products to territories where we have patent protection, but enforcement rights are not as strong as those in the U.S. These products may compete with our products and our patents or other intellectual property rights may not be effective or adequate to prevent them from competing. In addition, in jurisdictions outside the U.S., a license may not be enforceable unless all the owners of the intellectual property agree or consent to the license. Further, patients may choose to travel to countries in which we do not have intellectual property rights or which do not enforce these rights to obtain the products or treatment from competitors in such countries.

Many companies have encountered significant problems in protecting and defending intellectual property rights in foreign jurisdictions. The legal systems of certain countries, such as China, Brazil, Russia, India and South Africa, do not favor the enforcement of patents, trade secrets and other intellectual property, particularly those relating to biopharmaceutical products, which could make it difficult in those jurisdictions for us to stop the infringement or misappropriation of our patents or other intellectual property rights, or the marketing of competing products in violation of our proprietary rights. Proceedings to enforce our patent and other intellectual property rights in foreign jurisdictions could result in substantial costs and divert our efforts and attention from other aspects of our business. Furthermore, such proceedings could put our patents at risk of being invalidated, held unenforceable, or interpreted narrowly, could put our patent applications at risk of not issuing, and could provoke third parties to assert claims of infringement or misappropriation 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 rights around the world may be inadequate to obtain a significant commercial advantage from the intellectual property that we develop or license.

We may be involved in lawsuits to protect or enforce our patents, the patents of our licensors or our licenses, which could be expensive, time-consuming, and unsuccessful.

Competitors may infringe our patents or the patents of our licensors. To cease such infringement or unauthorized use, we may be required to file patent infringement claims, which can be expensive and time-consuming. In addition, in an infringement

proceeding or a declaratory judgment action against us, a court may decide that one or more of our patents is not valid or is unenforceable, or may refuse to stop the other party from using the technology at issue on the grounds that our patents do not cover the technology in question. An adverse result in any litigation or defense proceeding could put one or more of our patents at risk of being invalidated, held unenforceable or interpreted narrowly and could put our patent applications at risk of not issuing. Defense of these claims, regardless of their merit, would involve substantial litigation expense and would be a substantial diversion of employee resources from our business.

Interference or derivation proceedings provoked by third parties or brought by the USPTO may be necessary to determine the priority of inventions with respect to, or the correct inventorship of, our patents or patent applications or those of our licensors. An unfavorable outcome could result in a loss of our current patent rights and could require us to cease using the related technology or to attempt to license rights to it from the prevailing party. Our business could be harmed if the prevailing party does not offer us a license on commercially reasonable terms. Litigation, interference or derivation proceedings may result in a decision adverse to our interests and, even if we are successful, may result in substantial costs and distract our management and other employees.

Further, if a party to our licenses, either a licensee or licensor, were to breach or challenge our rights under the relevant license agreement (or if one of our licensor’s own licensors were to challenge our licensor’s rights), we may have to initiate or participate in a legal proceeding to enforce our rights. Any such legal proceeding could be expensive and time-consuming. In addition, if a court or other tribunal were to rule against us, we could lose key intellectual property and financial rights. Pursuing or defending against these legal claims, regardless of merits, would involve substantial legal expense and would be a substantial diversion of employee resources from our business. Furthermore, because of the substantial amount of discovery required in connection with intellectual property litigation or contractual litigation there is a risk that some of our confidential information could be compromised by disclosure during this type of litigation or proceeding. In addition, there could be public announcements of the results of hearings, motions or other interim proceedings or developments. 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.

Issued patents covering our product candidates could be found invalid or unenforceable if challenged in court or before the USPTO or comparable foreign authority.

If we or one of our licensing partners initiate 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 U.S., defendant counterclaims alleging invalidity or unenforceability are commonplace, and there are numerous grounds upon which a third party can assert invalidity or unenforceability of a patent. Third parties may also raise similar claims before administrative bodies in the U.S. or other jurisdictions, even outside the context of litigation. Such mechanisms include re-examination, inter partes review, post-grant review and equivalent proceedings in foreign jurisdictions, such as opposition or derivation proceedings. Such proceedings could result in revocation or amendment to our patents in such a way that they no longer cover and protect our product candidates. The outcome following legal assertions of invalidity and unenforceability is unpredictable. With respect to the validity of our patents, for example, we cannot be certain that there is no invalidating prior art of which we, our patent counsel, and the patent examiner were unaware during prosecution. If a defendant were to prevail on a legal assertion of invalidity, unpatentability and/or unenforceability, we would lose at least part, and perhaps all, of the patent protection on our product candidates. For example, as highlighted in the above risk factor entitled “We could be unsuccessful in obtaining or maintaining adequate patent protection for one or more of our products or product candidates, or asserting and defending our intellectual property rights that protect our products and technologies,” various third parties have filed challenges to the validity of UC/Vienna/Charpentier’s European patents, which cover compositions comprising Cas9 and gRNA molecules, as well as methods of editing DNA in vitro or ex vivo using Cas9 and gRNAs. If UC/Vienna/Charpentier fail in defending the validity of these patents, we may lose valuable intellectual property rights, such as the exclusive right to use such intellectual property. Such an outcome could have a material adverse effect on our business in Europe.

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

Periodic maintenance fees on any issued patent are due to be paid to the USPTO and foreign patent agencies in several stages over the lifetime of the patent. 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. Although 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. Noncompliance 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 any such event, our competitors might be able to enter the market, which would have a material adverse effect on our business.

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.

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. Our unregistered trademarks or trade names may be challenged, infringed, 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 future, potential 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 unregistered trademarks or trade names. Over the long term, if we are unable to successfully register our trademarks and trade names and 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.

Confidentiality agreements with employees and third parties may not prevent unauthorized disclosure of trade secrets and other proprietary information.

In addition to the protection afforded by patents, we seek to rely on trade secret protection and confidentiality agreements to protect our proprietary and confidential information. We also utilize proprietary processes for which it would be difficult to enforce patents. In addition, other elements of our product discovery and development processes involve proprietary know-how, information, or technology that is not covered by patents. Trade secrets, however, may be difficult to protect. We seek to protect our proprietary processes, in part, by entering into confidentiality agreements with our employees, consultants, outside scientific advisors, contractors, and collaborators, and we also rely on federal and state laws requiring our directors, employees, contractors and collaborators to protect our proprietary information. Although we use reasonable efforts to protect our trade secrets, our employees, consultants, outside scientific advisors, contractors, and collaborators might intentionally or inadvertently disclose our trade secret information to competitors. In addition, competitors may otherwise gain access to our trade secrets or independently develop substantially equivalent information and techniques. Furthermore, the laws of some foreign countries do not protect proprietary rights to the same extent or in the same manner as the laws of the U.S. As a result, we may encounter significant problems in protecting and defending our intellectual property both in the U.S. and abroad. If we are unable to prevent unauthorized material disclosure of our intellectual property to third parties, or misappropriation of our intellectual property by third parties, we may not be able to establish or maintain a competitive advantage in our market, which could materially adversely affect our business, operating results, and financial condition. Our trade secrets and other confidential information of ours may also be exposed through cybersecurity attacks, ransomware attacks, and other hacking attempts directed at our information technology systems and those of our employees, consultants, outside scientific advisors, contractors, vendors and collaborators. For more information, see the risk factor section entitled “Risks Related to Data and Privacy.”

We may be subject to claims that our employees, directors, consultants, or independent contractors have wrongfully used or disclosed confidential information of third parties.

We have received confidential and proprietary information from third parties. In addition, we employ individuals who were previously employed at other biotechnology or pharmaceutical companies as well as academic research institutions. We may be subject to claims that we or our employees, directors, consultants, or independent contractors have inadvertently or otherwise used or disclosed confidential information of these third parties or our employees’ former employers. Litigation may be necessary to defend against these claims, which could result in money damages or a judicial order prohibiting the use of certain intellectual property. Even if we are successful in defending against these claims, litigation could result in substantial cost and be a distraction to our management and employees.

We have never generated any revenue from product sales and our ability to generate revenue from product sales and become profitable depends significantly on our success in a number of areas.

We have no products approved for commercial sale, have not generated any revenue from product sales, and do not anticipate generating any revenue from product sales until we have received regulatory approval for the commercial sale of one of our product candidates. Our ability to generate revenue, and achieve and retain profitability, depends significantly on our success in many areas, including:

Even if one or more product candidates that we discover and develop are approved for commercial sale, we anticipate incurring significant costs associated with commercializing any approved product candidate and the timing of such costs may be out of our control. If we are not able to generate revenue from the sale of any approved products, we may never become profitable.

Our operating history may make difficult the evaluation of our business’s success to date and assessment of our future viability.

We are a clinical-stage company. We were founded and commenced operations in mid-2014. All of our product candidates are still in preclinical development or clinical trials. We have not yet demonstrated our ability to successfully complete any clinical trials, including large-scale, pivotal clinical trials, obtain marketing approvals, manufacture clinical and commercial scale therapeutics, or arrange for a third party to do so on our behalf, or conduct sales and marketing activities necessary for successful commercialization. Our ability to generate product revenue or profits, which we do not expect will occur for many years, if ever, will depend heavily on the successful development and eventual commercialization of our product candidates, which may never occur. We may never be able to develop or commercialize a marketable product.

Each of our programs may require additional discovery research and then preclinical and clinical development, regulatory approval in multiple jurisdictions, obtaining manufacturing supply, capacity and expertise, building of a commercial organization, substantial investment and significant marketing efforts before we generate any revenue from product sales. In

addition, our product candidates must be approved for marketing by the FDA, or certain other foreign regulatory agencies, before we may commercialize any product.

Our operating history, particularly in light of the rapidly evolving genome editing field, may make it difficult to evaluate our current business and predict our future performance. Our relatively short history as an operating company makes any assessment of our future success or viability subject to significant uncertainty. We will encounter risks and difficulties frequently experienced by clinical-stage companies in rapidly evolving fields. If we do not address these risks successfully, our business will suffer.

We have incurred net losses in each period since our inception, anticipate that we will continue to incur net losses in the future and may never achieve profitability.

We are not profitable and have incurred losses in each period since our inception. Our net loss was $390.1 million for the nine months ended September 30, 2024. As of September 30, 2024, we had an accumulated deficit of $2,048.5 million. We expect these losses to increase as we continue to incur significant research and development and other expenses related to our ongoing operations, seek regulatory approvals for our future product candidates, scale-up manufacturing capabilities, maintain, expand and protect our intellectual property portfolio and hire additional personnel to support the development of our product candidates and to enhance our operational, financial and information management systems. We expect to finance our operations through a combination of collaboration revenue, equity or debt financings or other sources, which may include collaborations with third parties.

A critical aspect of our strategy is to invest significantly in our technology to improve the efficacy and safety of potential product candidates that we discover. Even if we succeed in discovering, developing and ultimately commercializing one or more of these product candidates, we will continue to incur losses for the foreseeable future relating to our substantial research and development expenditures to develop our technologies. We may encounter unforeseen expenses, difficulties, complications, delays and other unknown factors that may adversely affect our business. The size of our future net losses will depend, in part, on the rate of future growth of our expenses and our ability to generate revenue. Our prior losses and expected future losses have had and will continue to have an adverse effect on our stockholders’ equity and working capital. Further, the net losses we incur may fluctuate significantly from quarter to quarter and year to year, such that a period-to-period comparison of our results of operations may not be a good indication of our future performance.

We may need to raise substantial additional funding to fund our operations. If we fail to obtain additional financing, we may be unable to complete the development and commercialization of any product candidates.

Our operations have required substantial amounts of cash since inception, and we expect to spend substantial amounts of our financial resources on our discovery programs going forward and future development efforts. Before obtaining marketing approval from regulatory authorities for the sale of any product candidate, we must complete preclinical development, manufacture (or have manufactured) product candidates and components, and then conduct extensive clinical trials to demonstrate the safety and efficacy of any of our future product candidates in humans. Because preclinical and clinical testing is expensive and can take many years to complete, we may require additional funding to complete these undertakings. Further, if we are able to identify product candidates that are eventually approved, we will require significant additional amounts in order to launch and commercialize our product candidates. For the foreseeable future, we expect to continue to rely on additional financing to achieve our business objectives. Our future capital requirements will depend on and could increase significantly as a result of many factors, including the scope, progress, results and costs of drug discovery, preclinical development, laboratory testing and clinical trials for our current or future product candidates, including additional expenses attributable to adjusting our development plans (including any supply related matters).

We will require additional capital for the further development and commercialization of any product candidates and may need to raise additional funds sooner if we choose to expand more rapidly than we presently anticipate or due to other unanticipated factors. Disruptions in the financial markets in general have made equity and debt financing more difficult to obtain, and may have a material adverse effect on our ability to meet our fundraising needs.

We cannot be certain that additional funding will be available on acceptable terms, or at all. We have no committed source of additional capital and if we are unable to raise additional capital in sufficient amounts or on terms acceptable to us, we may have to significantly delay, scale back or discontinue the development, manufacture or commercialization of our product candidates or other research and development initiatives. Our collaboration and license agreements may also be terminated if we are unable

to meet the payment or other obligations under the agreements. We could be required to seek collaborators for product candidates at an earlier stage than otherwise would be desirable or on terms that are less favorable than might otherwise be available or relinquish or license on unfavorable terms our rights to product candidates in markets where we otherwise would seek to pursue development or commercialization ourselves.

Any of the above events could significantly harm our business, prospects, financial condition and results of operations and cause the price of our common stock to decline.

Raising additional capital may cause dilution to our stockholders and restrict our operations.

We will need additional capital in the future to continue our planned operations. To the extent that we raise additional capital through the sale of equity or convertible debt securities, the ownership interest of our existing stockholders may be diluted, and the terms of these securities may include liquidation or other preferences that adversely affect the rights of our common stockholders. In addition, the valuation of public companies may require selling equity at lower prices to ensure appropriate capitalization. Debt financing and preferred equity financing, if available, may involve agreements that include covenants limiting or restricting our ability to take specific actions, such as incurring additional debt, making capital expenditures or declaring dividends.

Unfavorable national or global economic conditions or political developments could adversely affect our business, financial condition or results of operations.

Our results of operations could be adversely affected by general conditions in the national or global economy and financial markets. For example, governmental statements, actions or policies, political unrest and global financial crises can cause extreme volatility and disruptions in the capital and credit markets. A severe or prolonged economic downturn, political unrest or additional global financial crises, could result in a variety of risks to our business, including weakened demand for our products, if approved, or our ability to raise additional capital when needed on acceptable terms, if at all. A weak or declining economy could also strain our suppliers, possibly resulting in supply disruption. Any of the foregoing could harm our business and we cannot anticipate all of the ways in which the current economic climate, further political developments and financial market conditions could adversely impact our business.

Inadequate funding for, or change of priorities or disruptions at, the FDA and other government agencies in or outside the U.S. could hinder their ability to hire, retain, or deploy key leadership and other personnel, prevent new products and services from being developed or commercialized in a timely manner or otherwise prevent those agencies from performing normal business functions on which the operation of our business may rely, which could negatively impact our business.

The ability of the FDA and other similar regulatory agencies to review and approve new products can be affected by a variety of factors, including government budget and funding levels, ability to hire and retain key personnel and authorization to accept the payment of user fees, reallocation of resources to address unique or new healthcare issues (or other future public health concerns), and statutory, regulatory, and policy changes. In addition, government funding of other government agencies on which our operations may rely, including those that fund research and development activities, is subject to the political process, which is inherently fluid and unpredictable. For example, over the last several years, the U.S. government has shut down several times and certain regulatory agencies, such as the FDA and the SEC, have had to furlough critical FDA, SEC and other government employees and stop critical activities.

If a prolonged government shutdown occurs in the U.S. or other jurisdictions where we plan to conduct our clinical trials, manufacturing, or other operations, it could significantly impact the ability of the relevant agency, such as the FDA, to timely review and process our regulatory submissions, which could have a material adverse effect on our business.

In vivo genome editing products and ex vivo engineered cell therapies based on CRISPR/Cas9 genome editing technology are novel and may be complex and difficult to manufacture. We could experience manufacturing problems that result in delays in the development, approval or commercialization of our product candidates or otherwise harm our business.

The manufacturing process used to produce CRISPR/Cas9-based in vivo and engineered cell therapy product candidates may be complex, as they are novel and have not been validated for late phase clinical and commercial production and may require components that are difficult to obtain or manufacture at the necessary quantities and in accordance with regulatory requirements. Several factors could cause production interruptions, including equipment malfunctions; facility unavailability or contamination;

raw material cost, shortages or contamination; natural disasters, such as pandemics or other outbreaks or similar public health crises; disruption in utility services; human error; insufficient personnel; inability to meet legal or regulatory requirements; or disruptions in the operations of our suppliers.

Because our product candidates are regulated as biologics, their processing steps will be more complex than those of most small molecule drugs. Moreover, unlike small molecules, the physical and chemical properties of a complex product such as ours generally cannot be fully characterized. As a result, assays of the finished product or relevant components may not be sufficient to ensure that the product will perform in the intended manner. For this reason, we will employ multiple steps to control the manufacturing process to ensure that the process results in product candidates that meet their specifications, but complications at any one step could adversely impact our manufacturing of products. Further, we may encounter problems achieving adequate quantities and quality of clinical grade materials that meet the FDA or other relevant regulatory agency’s applicable standards or our specifications with consistent and acceptable production yields and costs. Manufacturing process irregularities, even minor deviations from the normal process, could result in product defects or manufacturing issues that cause lot failures, product recalls, product liability claims and litigation, insufficient inventory or production interruption. In addition, product manufacturing and supply could be delayed if the FDA and other regulatory authorities require us to submit lot samples, testing results and protocols, or if they require that we not distribute a lot until they authorize the product’s release.

Further, certain of our product candidates may require components that are unavailable or difficult to acquire or manufacture at the necessary scale and in compliance with regulatory requirements to support our clinical trials or, if approved, commercial efforts. We expect to continue to rely on third party CMOs to manufacture these components and the final product candidates for the foreseeable future. We may not have full control of these CMOs and they may prioritize other customers or be unable to provide us with enough manufacturing capacity to meet our objectives. Further, we may rely on CMOs outside the U.S. for certain components of our product candidates, and may be subject to importation regulations that may affect our ability to manufacture or increase the cost of our product candidates.

We also may encounter problems developing our own manufacturing capabilities, including hiring and retaining the experienced scientific, engineering, quality and manufacturing personnel needed to operate or supervise the necessary manufacturing processes. These issues could result in delays in production or difficulties in maintaining compliance with applicable regulatory requirements.

Any of these manufacturing and supply issues or delays could restrict our ability to meet clinical or market demand for our products, and be costly to us and otherwise harm our business, financial condition, results of operations and prospects. Further, any problems in manufacturing processes or facilities could make us a less attractive collaborator for potential partners, including larger pharmaceutical companies and academic research institutions, which could limit our access to additional attractive development programs.

While the regulatory framework for approval of gene therapy including genome editing products exists, the limited precedent for genome-edited products makes the regulatory approval process potentially more unpredictable and we may experience significant delays in the clinical development and regulatory approval, if any, of our product candidates.

The research, testing, manufacturing, labeling, approval, selling, import, export, marketing and distribution of drug products, including genome editing therapeutics and engineered cell therapies, are subject to extensive regulation by the FDA in the U.S. and other regulatory authorities in other jurisdictions. For example, we are not permitted to market any drug or biological product, including in vivo products or engineered cell therapies, until we receive regulatory approval from the relevant regulatory agency, such as the FDA in the U.S. or EMA in the EU. We expect the novel nature of our product candidates to create challenges or raise questions from regulatory agencies in obtaining regulatory approval. For example, in the U.S., the FDA has not approved any in vivo gene editing-based therapeutic and has only approved one ex vivo CRISPR/Cas9 genome editing therapy for human therapeutic use. The FDA may also require a panel of experts, referred to as an Advisory Committee, to deliberate on the adequacy of the safety and efficacy data to support approval. The Advisory Committee’s opinion, although not binding, may significantly impact our ability to obtain approval of our product candidates. Moreover, while we are not aware of any specific genetic or biomarker tests for which regulatory approval would be necessary to advance any of our product candidates to clinical trials or commercialization, regulatory agencies could require the development and approval of such tests. Accordingly, the regulatory

approval pathway for such product candidates may be uncertain, complex, expensive and lengthy, as well as different in each jurisdiction, and approval may not be obtained in any, some or all jurisdictions.

Other non-regulatory entities may impact the regulatory agencies’ and ethics committees’ evaluation and approval decision regarding our product candidates. For example, in December 2018, the World Health Organization (“WHO”) established the Expert Advisory Committee on Developing Global Standards for Governance and Oversight of Human Genome Editing. While the standards are expected to focus primarily on germline modifications, the guidelines could impact somatic cell editing research programs, such as ours. In March 2019, the WHO Expert Advisory Committee recommended initiating the first phase of a new global registry (the “Registry”) to track research on human genome editing. Accepting this recommendation, the WHO announced plans in August 2019 for an initial phase of the registry using the International Clinical Trials Registry Platform. This phase will include worldwide registries for both somatic cell editing and germline editing clinical trials. Although registration of these clinical trials in the WHO’s Registry currently is voluntary, failure to register could impact the evaluation by the regulators and ethics committees. In July 2021, the WHO Expert Advisory Committee issued recommendations and a governance framework for human genome editing research intended for the international, regional, national and institutional level. For example, the WHO recommended that clinical trials using somatic human genome editing technologies be reviewed and approved by the appropriate research ethics committee before inclusion in its Registry; basic and preclinical gene editing research also be included in a registry; somatic or germline human genome editing research should only take place in jurisdictions with domestic policy and oversight mechanisms; and relevant patent holders help ensure equitable access to human genome editing interventions. We cannot predict the impact of the WHO’s current and future recommendations, or any policies or actions that ethics committees or regulatory agencies may take in response to such recommendations, on our research, clinical and business plans and results.

Patient enrollment is a significant factor in the timing of clinical trials and is affected by many factors, including willingness of physicians to use an experimental therapy, the availability of existing treatments, the trial’s geographic locations and the number of patients in each geographic location. In addition, our ability to enroll and dose patients may be delayed by the relevant regulatory authority, as well as the IRB or another ethics committee (whether local or national). For example, as set forth in the National Institutes of Health (“NIH”) Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules (“NIH Guidelines”), gene therapy clinical trials are also subject to review and oversight by an institutional biosafety committee (“IBC”), a local institutional committee that reviews and oversees research utilizing recombinant or synthetic nucleic acid molecules at that institution. Before a clinical trial can begin at any institution, that institution’s IRB and its IBC assesses the safety of the research and identifies any potential risk to public health or the environment. While the NIH Guidelines are not mandatory unless the research in question is being conducted at or sponsored by institutions receiving NIH funding of recombinant or synthetic nucleic acid molecule research, many companies and other institutions not otherwise subject to the NIH Guidelines voluntarily follow them. Further, a clinical trial may be suspended or terminated by us, the relevant IRBs or ethics committees of the trial, or the FDA or other regulatory authorities, or upon a recommendation of the trial’s DMC, due to a number of factors, including failure to conduct the clinical trial in accordance with regulatory requirements or our clinical protocols, unforeseen safety issues or adverse side effects, failure to demonstrate a benefit from using a product candidate, changes in governmental regulations or administrative actions or lack of adequate funding to continue the clinical trial. If we experience termination of, or delays in the completion of, any clinical trial of product candidates, the commercial prospects for such product candidates will be harmed, and our ability to generate product revenue will be impaired. In addition, any delays in completing any clinical trials will increase our costs, slow down our product development and approval process and jeopardize our ability to commence product sales and generate revenue.

We are currently conducting and may in the future conduct other clinical trials for our product candidates outside the U.S., and the FDA and comparable foreign regulatory authorities may not accept data from such trials.

We are currently conducting our Phase 3 clinical trial of NTLA-2001, and may in the future conduct clinical trials for our other product candidates outside the U.S. The acceptance of data from clinical trials conducted outside the U.S. or another jurisdiction by the FDA or comparable foreign regulatory authority may be subject to certain conditions or may not be accepted at all. The FDA will generally not consider the data from a foreign clinical trial not conducted under an IND unless (i) the trial was well-designed and well-conducted in accordance with good clinical practice (“GCP”) requirements, including requirements for the design, conduct, performance, monitoring, auditing, recording, analysis, and reporting of clinical trials in a way that provides assurance that the data and reported results are credible and accurate and that the rights, safety, and well-being of trial subjects are protected, and (ii) the FDA is able to validate the data from the trial through an onsite inspection, if necessary. Additionally, the FDA’s clinical trial requirements, including sufficient size of patient populations and statistical powering, must be met. Many foreign regulatory authorities have similar approval requirements. In addition, such foreign trials would be subject to the

applicable local laws of the foreign jurisdictions where the trials are conducted. There can be no assurance that the FDA or any comparable foreign regulatory authority will accept data from trials conducted outside of the U.S. or the applicable jurisdiction. If the FDA or any comparable foreign regulatory authority does not accept such data, it would result in the need for additional trials, which could be costly and time-consuming, and which may result in product candidates that we may develop not receiving approval for commercialization in the applicable jurisdiction.

We have received orphan drug designation for NTLA-2001 and NTLA-2002 and may in the future seek orphan drug designation for some of our other product candidates, but we may be unable to obtain such designations or to maintain the benefits associated with orphan drug status, including market exclusivity, which may cause our revenue, if any, to be reduced.

Regulatory authorities in some jurisdictions, including the U.S. and Europe, may in response to a request from the sponsor designate products for relatively small patient populations as orphan drugs. Under the Orphan Drug Act, the FDA may grant orphan drug designation to a product intended to treat a rare disease or condition, defined as a disease or condition with a patient population of fewer than 200,000 in the U.S., or a patient population of 200,000 or more in the U.S. when there is no reasonable expectation that the cost of developing and making available the product in the U.S. will be recovered from sales in the U.S. for that product. Orphan drug designation must be requested before submitting a BLA. In the U.S., orphan drug designation entitles a party to financial incentives such as opportunities for grant funding towards clinical trial costs, tax advantages and user-fee waivers. After the FDA grants orphan drug designation, the generic identity of the product and its potential orphan use are disclosed publicly by the FDA. In the EU, a medicinal product may be designated as orphan if (1) it is intended for the diagnosis, prevention or treatment of a life-threatening or chronically debilitating condition; (2) either (a) such condition affects no more than five in 10,000 persons in the EU when the application is made, or (b) it is unlikely that the product, without the benefits derived from orphan status, would generate sufficient return in the EU to justify the necessary investment in its development; and (3) there exists no satisfactory method of diagnosis, prevention or treatment of such condition authorized for marketing in the EU, or if such a method exists, the product will be of significant benefit to those affected by the condition. Orphan designation does not convey any advantage in, or shorten the duration of, the regulatory review and approval process.

Generally, if a product with an orphan drug designation subsequently receives the first marketing approval for the indication for which it has such designation, the product is entitled to a period of marketing exclusivity, which precludes the approval of another marketing application for the same drug for the same indication for that time period. The applicable period is seven years in the U.S. and ten years in the EU (which can be extended to 12 years if the sponsor complies with an agreed-upon pediatric investigation plan). Orphan drug exclusivity may be lost if the FDA or the EMA determines that the request for designation was materially defective or if the manufacturer is unable to assure sufficient quantity of the drug to meet the needs of patients with the rare disease or condition. In addition, the FDA can subsequently approve a marketing application for the same drug, or a product with the same active moiety, for treatment of the same disease or condition if it concludes that the later drug is clinically superior in that it is shown to be safer, more effective or makes a major contribution to patient care. Similarly, the EMA may grant a marketing authorization to a similar medicinal product for the same indication as an authorized orphan product at any time if it is established that the second product, although similar, is safer, more effective or otherwise clinically superior to the authorized product. The FDA and EMA also can approve a different drug for the same orphan indication, or the same drug for a different indication, during the orphan exclusivity period.

We have received orphan drug designation from the FDA for NTLA-2001 for the treatment of ATTR amyloidosis and from the FDA and European Commission (“EC”) for NTLA-2002 for the treatment of HAE. We may seek orphan drug designation for some of our other product candidates in orphan indications in which there is a medically plausible basis for the use of these product candidates. Even where we obtain orphan drug designation, exclusive marketing rights in the U.S. may be limited if we seek approval for an indication broader than the orphan designated indication and may be lost if the FDA later determines that the request for designation was materially defective or if the manufacturer is unable to assure sufficient quantities of the product to meet the needs of patients with the rare disease or condition. In addition, although we intend to seek orphan drug designation for other product candidates, we may never receive such designations.

The FDA may reevaluate the Orphan Drug Act and its regulations and policies. We do not know if, when, or how the FDA may change the orphan drug regulations and policies in the future, and it is uncertain how any changes might affect our business. In addition, proposed amendments to EU regulations regarding orphan medicines are under consideration that, if implemented, could reduce the current 10-year marketing exclusivity period in the EU for certain orphan medicines. Depending on what changes the FDA and the EC may make to their orphan drug regulations and policies, our business could be adversely impacted.

We have received regenerative medicine advanced therapy (“RMAT”) designation by the FDA for NTLA-2002 for the treatment of HAE, and may in the future seek such designation for some of our other product candidates, but such designation may not actually lead to a faster development or regulatory review or approval process and we may be unable to obtain or maintain the benefits associated with such designation.

We have received the RMAT designation from the FDA for NTLA-2002 for the treatment of HAE. A product candidate is eligible for RMAT designation if: (1) it is a cell therapy, therapeutic tissue engineering product, human cell or tissue product, or a combination product using any such therapies or products; (2) it is intended to treat, modify, reverse, or cure a serious or life-threatening disease or condition; and (3) there is preliminary clinical evidence that indicates that the product candidate has the potential to address unmet medical needs for such disease or condition. This program is intended to facilitate efficient development and expedite review of RMATs. A BLA for a product candidate with RMAT designation may be eligible for priority review or accelerated approval through (1) surrogate or intermediate endpoints reasonably likely to predict long-term clinical benefit or (2) reliance upon data obtained from a meaningful number of sites. Benefits of such designation also include early interactions with the FDA to discuss any potential surrogate or intermediate endpoint to be used to support accelerated approval. A product candidate that has RMAT designation and is subsequently granted accelerated approval and is subject to post-approval requirements may fulfill such requirements through the submission of clinical evidence, clinical studies, patient registries, or other sources of real-world evidence, such as electronic health records, the collection of larger confirmatory data sets, or post-approval monitoring of all patients treated with such therapy prior to its approval. RMAT designation is within the discretion of the FDA. Accordingly, even if we believe one of our product candidates meets the criteria for RMAT designation, the FDA may disagree and instead determine not to grant such designation. In any event, the receipt of RMAT designation for a product candidate may not result in a faster development process, review or approval compared to product candidates considered for approval under conventional FDA procedures and does not assure ultimate approval by the FDA. In addition, even if one or more of our product candidates qualifies for RMAT designation, the FDA may later decide that the product candidate no longer meets the conditions for qualification.

Obtaining and maintaining regulatory approval of our product candidates in one jurisdiction does not mean that we will be successful in obtaining regulatory approval of product candidates in other jurisdictions.

Obtaining and maintaining regulatory approval of our product candidates in one jurisdiction does not guarantee that we will be able to obtain or maintain regulatory approval in any other jurisdiction, but a failure or delay in obtaining regulatory approval in one jurisdiction may have a negative effect on the regulatory approval process in others. For example, even if the FDA approves a product candidate, comparable regulatory authorities in foreign jurisdictions must also authorize the marketing and sale of the product candidate in those countries. Approval procedures vary among jurisdictions and can involve requirements and review periods different from those in the U.S., including additional preclinical studies or clinical trials, as clinical studies conducted in one jurisdiction may not be accepted by regulatory authorities in other jurisdictions. In many jurisdictions outside the U.S., a product candidate must be approved for reimbursement before it can be sold in that jurisdiction. In some cases, the price that we are allowed to charge for our products is also subject to approval or to other legal restrictions.

Obtaining foreign regulatory approvals and compliance with foreign regulatory requirements could result in significant delays, difficulties and costs for us and could delay or prevent the introduction of our products in certain countries. If we fail to comply with the relevant regulatory requirements or to receive applicable marketing approvals, our target markets will be reduced and our ability to realize the full market potential of our product candidates will be harmed.

Even if we receive regulatory approval of any product candidates or therapies, we will be subject to ongoing regulatory obligations and continued regulatory review, which may result in significant additional expense and we may be subject to penalties if we fail to comply with regulatory requirements or experience unanticipated problems with our product candidates.*

If any of our product candidates are approved, they may be subject to ongoing regulatory requirements for manufacturing, labeling, packaging, distribution, storage, advertising, promotion, sampling, record-keeping, and submission of safety and efficacy data, and other post-market information and potential obligations (such as post-marketing studies), including both federal and state requirements in the U.S. and requirements of comparable foreign regulatory authorities. In addition, we will be subject to continued compliance with current good manufacturing practice (“cGMP”) and GCP, and in certain cases, current good tissue practice (“cGTP”) requirements for any clinical trials that we conduct post-approval.

Manufacturers and manufacturers’ facilities are required to comply with extensive FDA and comparable foreign regulatory authority requirements, as applicable, including ensuring that quality control and manufacturing procedures conform to cGMP and, in certain cases, cGTP requirements, and applicable product tracking and tracing requirements. As such, we and our CMOs will be subject to continual review and inspections to assess compliance with cGMP and adherence to commitments made in any BLA, other marketing applications, and previous responses to inspection observations. Accordingly, we and others with whom we work must continue to expend time, money, and effort in all areas of regulatory compliance, including manufacturing, production and quality control.

Any regulatory approvals that we receive for our product candidates may be subject to limitations on the approved indicated uses for which the product may be marketed or to the conditions of approval, or contain requirements for potentially costly post-marketing testing, including Phase 4 clinical trials and surveillance to monitor the safety and efficacy of the product candidate. For example, the FDA or other regulatory agencies may also require a REMS or similar program as a condition of approval of our product candidates, which could entail requirements for long-term patient follow-up, a medication guide, physician communication plans or additional elements to ensure safe use, such as restricted distribution methods, patient registries and other risk minimization tools. In addition, if the FDA or a comparable foreign regulatory authority approves our product candidates, we will have to comply with their respective legal or regulatory requirements including submissions of safety and other post-marketing information and reports and registration.

The FDA or other regulatory agencies may seek to impose consent decrees, withdraw approval or prohibit the export or import of a product if compliance with regulatory requirements and standards is not maintained or if problems occur after the product reaches the market. Later discovery of previously unknown problems with our product candidates, including adverse events of unanticipated severity or frequency, or with our third party manufacturers or manufacturing processes, or failure to comply with regulatory requirements, may result in revisions to the approved labeling to add new safety information; imposition of post-market studies or clinical studies to assess new safety risks; or imposition of distribution restrictions or other restrictions under a REMS program. Other potential consequences include, among other things:

The FDA strictly regulates marketing, labeling, advertising, and promotion of products that are placed on the U.S. market, and the relevant foreign regulatory agencies do the same in their respective jurisdictions. The FDA and other agencies actively enforce the laws and regulations prohibiting the promotion of off-label uses and a company that is found to have improperly promoted off-label uses may be subject to significant liability.

The FDA’s policies may change and additional government regulations may be enacted that could prevent, limit or delay regulatory approval of our product candidates. In addition, the U.S. Supreme Court’s June 2024 decision to overturn established case law giving deference to regulatory agencies’ interpretations of ambiguous statutory language has introduced uncertainty regarding the extent to which the FDA’s regulations, policies and decisions may become subject to increasing legal challenges, delays, and/or changes. If we or our collaborators are slow or unable to adapt to changes in existing requirements or the adoption of new requirements or policies, or if we or our collaborators are not able to maintain regulatory compliance, we or our collaborators may lose any marketing approval that we or our collaborators may have obtained, which would adversely affect our business, prospects and ability to achieve or sustain profitability.

Our employees, independent contractors, clinical investigators, CMOs, CROs, consultants, collaborators, commercial partners and vendors may engage in misconduct or other improper activities, including noncompliance with regulatory standards and requirements, which could have a material adverse effect on our business.

We are exposed to the risk of non-compliance, fraud, misconduct or other illegal activity by our employees, independent contractors, clinical investigators, CMOs, CROs, consultants, collaborators, commercial partners and vendors. Misconduct by these parties could include intentional, reckless and/or negligent conduct that fails to: comply with federal and state laws and those of other applicable jurisdictions; provide true, complete and accurate information to the FDA and other regulatory bodies in the U.S. or outside the U.S.; comply with manufacturing standards; comply with federal and state data privacy, security, fraud and abuse and other healthcare laws and regulations in the U.S. and similar foreign privacy or fraudulent misconduct laws; or report financial information or data accurately; or disclose unauthorized activities to us. If we obtain FDA approval of any of our product candidates and begin commercializing those products in the U.S., our potential exposure under such laws will increase significantly, and our costs associated with compliance with such laws are also likely to increase. These laws may impact, among other things, our current activities with clinical investigators and research patients, as well as proposed and future sales, marketing and education programs. In particular, the promotion, sales and marketing of healthcare products and services, as well as certain business arrangements in the healthcare industry, are subject to extensive laws and regulations intended to prevent fraud, misconduct, kickbacks, self-dealing and other abusive practices. These laws and regulations may restrict or prohibit a wide range of pricing, discounting, marketing and promotion, including promotion and marketing of off-label uses of our products, structuring and commission(s), certain customer incentive programs and other business arrangements generally. Activities subject to these laws also involve the improper use of information obtained in the course of clinical trials or creating fraudulent data in our preclinical studies or clinical trials, which could result in regulatory sanctions and cause serious harm to our reputation. It is not always possible to identify and deter misconduct by employees and other third parties, and the precautions we take to detect and prevent this activity may not be effective in controlling unknown or unmanaged risks or losses or in protecting us from governmental investigations or other actions or lawsuits stemming from a failure to comply with these laws or regulations. Additionally, we are subject to the risk that a person or government could allege such fraud or other misconduct, even if none occurred. If any such actions are instituted against us, and we are not successful in defending ourselves or asserting our rights, those actions could have a significant impact on our business, including the imposition of significant fines or other sanctions.

The exit of the United Kingdom from the EU may result in an increased regulatory burden of conducting business in Europe.

The U.K.’s withdrawal from the EU (“Brexit”), became effective on January 31, 2020. On December 24, 2020, the U.K. and EU signed an EU-U.K. Trade and Cooperation Agreement (“TCA”), which became provisionally applicable on January 1, 2021 and has been formally applicable since May 1, 2021. The TCA includes specific provisions concerning pharmaceuticals, which include the mutual recognition of cGMP, inspections of manufacturing facilities for medicinal products and cGMP documents issued, but does not provide for wholesale mutual recognition of U.K. and EU pharmaceutical regulations. At present, Great Britain has implemented EU legislation on the marketing, promotion and sale of medicinal products through the Human Medicines Regulations 2012 (as amended) (under the Northern Ireland Protocol, the EU regulatory framework currently continues to apply in Northern Ireland). The regulatory regime in Great Britain therefore currently aligns for the most part with EU regulations; however, it is possible that these regimes will diverge more significantly in the future now that Great Britain’s regulatory system is independent from the EU and the TCA does not provide for mutual recognition of U.K. and EU pharmaceutical legislation.

For instance, the Clinical Trials Regulation which became effective in the EU on January 31, 2022 and provides for a streamlined clinical trial application and assessment procedure covering multiple EU Member States has not been implemented into U.K. law, and a separate application must be submitted for clinical trial authorization in the U.K. In addition, Great Britain is no longer covered by the centralized procedure for obtaining European Economic Area (“EEA”)-wide marketing authorizations from the EMA for medicinal products and a separate process for authorization of drug products is required in Great Britain. On January 1, 2024, a new international recognition framework was put in place in the U.K. (known as the International Recognition Procedure (“IRP”)), whereby the MHRA will have regard to decisions made by certain foreign regulators, including the EMA and the competent authorities of the EU Member States. Under this procedure, the MHRA will take into account the decision-making of such foreign regulators and will conduct a targeted assessment of the applications submitted through the IRP, but will retain the authority to reject applications if the evidence provided is considered insufficiently robust. Any delay in obtaining, or an inability to obtain, any regulatory approvals, as a result of Brexit or otherwise, would delay or prevent us from commercializing our current or future product candidates in the U.K. and could restrict our ability to generate revenue from that market.

Failure to comply with health and data protection laws and regulations could lead to government enforcement actions (which could include civil or criminal penalties), private litigation, and/or adverse publicity and could negatively affect our operating results and business.

We and many of our existing or potential collaborators, clinical investigators, CMOs, CROs, consultants or vendors are subject to federal, state, and foreign data protection laws and regulations (i.e., laws and regulations that address privacy and data security). In the U.S., numerous federal and state laws and regulations, including federal health information privacy laws, state data breach notification laws, state health information privacy laws, and federal and state consumer protection laws (e.g., Section 5 of the Federal Trade Commission Act), that govern the collection, use, disclosure and protection of health-related and other personal information could apply to our operations or the operations of our collaborators. In addition, we may obtain health information from third parties (including research institutions from which we obtain clinical trial data) that are subject to privacy and security requirements under the Health Insurance Portability and Accountability Act of 1996 (“HIPAA”), as amended by the Health Information Technology for Economic and Clinical Health Act of 2009 (“HITECH”), or by comparable laws in other jurisdictions. Depending on the facts and circumstances, we could be subject to civil, criminal, and administrative penalties if we knowingly obtain, use, or disclose individually identifiable health information maintained by a covered entity in a manner that is not authorized or permitted by laws or regulations.

Compliance with U.S., both state and federal, and international data protection laws and regulations could require us to take on more onerous obligations in our contracts, restrict our ability to collect, use and disclose data, or in some cases, impact our ability to operate in certain jurisdictions. Failure to comply with these laws and regulations could result in government enforcement actions (which could include civil, criminal and administrative penalties), private litigation, and/or adverse publicity and could negatively affect our operating results and business. Moreover, clinical trial subjects, employees and other individuals about whom we or our existing or potential collaborators obtain personal information, as well as the providers who share this information with us, may limit our ability to collect, use and disclose the information. Claims that we have violated individuals’ privacy rights, failed to comply with data protection laws, or breached our contractual obligations, even if we are not found liable, could be expensive and time-consuming to defend and could result in adverse publicity that could harm our business.

If we, or our collaborators, clinical investigators, CMOs, CROs, consultants or vendors, fail to comply with environmental, health and safety, and laboratory animal welfare laws and regulations, we could become subject to fines or penalties or incur costs that could harm our business.

We and many of our existing or potential collaborators, clinical investigators, CMOs, CROs, consultants or vendors are subject to numerous federal, state and local environmental, health and safety, and laboratory animal welfare laws and regulations. These legal requirements include those governing laboratory procedures and the handling, use, storage, treatment and disposal of hazardous materials and wastes, as well as those which regulate the care and use of animals in research. Our operations, and those of our collaborators, clinical investigators, CMOs, CROs, consultants or vendors, acting on our behalf, may involve research using research animals and the use of hazardous and flammable materials, including chemicals and biological materials. Our operations, and those of our collaborators, clinical investigators, CMOs, CROs, consultants or vendors, acting on our behalf, also may produce hazardous waste products. We generally anticipate contracting with third parties for the disposal of these materials and waste. We will not be able to eliminate the risk of contamination or injury from these materials. In the event of contamination or injury resulting from any use by us of hazardous materials, we could be held liable for any resulting damages, and any liability could exceed our resources. We also could incur significant costs associated with civil or criminal fines and penalties for failure to comply with such laws and regulations.

Although we maintain workers’ compensation insurance to cover us for costs and expenses we may incur due to injuries to our employees resulting from the use of hazardous materials, this insurance may not provide adequate coverage against potential liabilities. We maintain insurance for environmental liability or toxic tort claims that may be asserted against us in connection with our storage or disposal of biological, hazardous or radioactive materials.

In addition, we may incur substantial costs in order to comply with current or future environmental, health and safety, and laboratory animal welfare laws and regulations. These current or future laws and regulations may impair our research, development or production efforts. Our failure to comply with these laws and regulations also may result in substantial fines, penalties or other sanctions.

Failure to comply with labor and employment laws and regulations could subject us to legal liability and costs, including fines or penalties, as well as reputational damage that could harm our business.

We are subject to numerous federal, state and local laws and regulations relating to the recruiting, hiring, compensation and treatment of employees and contractors. These laws and regulations cover financial compensation (including wage and hour standards), benefits (including insurance and 401(k) plans), discrimination, workplace safety and health, and workers’ compensation.

The Commonwealth of Massachusetts, where most of our employees are based, also has laws that expand on federal laws or create additional rights for employees or obligations for employers. For example, on July 1, 2018, the Massachusetts Equal Pay Act went into effect, which added protections employers must comply with regarding pay equity for “comparable work.” In addition, on July 31, 2024, Massachusetts passed the Frances Perkins Workplace Equity Act, requiring disclosure of the pay range for a particular job under certain circumstances, including job postings, promotions, or when an employee requests. There is currently uncertainty regarding the exact scope of these new legal limits and such uncertainty may remain for the foreseeable future. We may face increased employment and legal costs to ensure we are complying with these laws.

On October 1, 2018, a new Massachusetts non-compete law went into effect, placing additional restrictions on employers seeking to enter into non-competition agreements with employees. Further, other jurisdictions in which our employees may work limit enforcement of non-competition agreements. For example, in California non-competition agreements with employees are generally unenforceable after termination of employment and Illinois contains strict laws affecting the enforcement of non-competition agreements. These non-compete laws may negatively impact our ability to prevent employees from working with direct or indirect competitors in the future and may affect our ability to retain key talent in a competitive market.

Our failure to comply with these and other related laws could expose us to civil and, in some cases, criminal liability, including fines and penalties. Further, government or employee claims that we have violated any of these laws, even if ultimately disproven, could result in increased expense and management distraction, as well as have an adverse reputational impact on us.

Our technological advancements and any potential for revenue may be derived in part from our collaborations, including, for example, with Regeneron, and if the collaboration or co-development agreements related to a material collaboration were to be terminated or materially altered in an adverse manner, our business, financial condition, results of operations and prospects would be harmed.

We rely on strategic collaborations to advance our technology and co-develop products that we plan to co-commercialize. If our collaboration partner in a material collaboration fails to develop, obtain regulatory approval for or ultimately commercialize any product candidate from the development programs governed by the respective collaboration agreements, including, e.g., a co-development or co-commercialization agreement, or breaches or terminates our collaboration with it, our business, financial condition, results of operations and prospects could be harmed. In addition, any material alteration, in an adverse manner, of any material collaboration agreement, or dispute or litigation proceedings we may have related to a material collaboration in the future could delay development programs, create uncertainty as to ownership of or access to intellectual property rights, distract management from other business activities and generate substantial expense.

As described within Note 7, “Collaborations and Other Arrangements” of this Quarterly Report on Form 10-Q, we have entered into co-development and co-promotion arrangements with Regeneron. Regeneron may change its strategic focus or pursue alternative technologies in a manner that results in reduced, delayed or no revenue to us under these arrangements. For example, Regeneron has a variety of marketed products and product candidates either by itself or with other companies, including some of our competitors. In addition, the corporate objectives of our collaborators, such as Regeneron, may not be consistent with our best interests. Regeneron may change its position regarding its participation and funding of our joint activities, which may impact our ability to successfully pursue those programs.

Our existing and future collaborations will be important to our business. If we are unable to maintain any of these collaborations, or if these collaborations are not successful, our business could be adversely affected.

We have limited capabilities for product development and do not yet have any capability for sales, marketing or distribution. Accordingly, we have entered, and plan to enter, into collaborations with other companies, including our therapeutic-focused

collaboration agreements with Regeneron, which we believe can provide such capabilities. For example, in October 2023, we announced an expanded research collaboration with Regeneron to develop therapies for the treatment of neurological and muscular diseases. These current and future therapeutic-focused collaborations could provide us with important technologies and/or funding for our programs and technology. Our existing and future therapeutic collaborations may have a number of risks, including that collaborators:

If our therapeutic collaborations do not result in the successful discovery, development and commercialization of products or if a collaborator terminates its agreement with us, we may not receive any future research funding or milestone or royalty payments under the collaboration. All of the risks relating to product discovery, development, regulatory approval and commercialization summarized and described in this report also apply to the activities of our therapeutic collaborators.

Additionally, if one of our collaborators terminates its agreement with us, we may find it more difficult to attract new collaborators and our perception in the business and financial communities could be adversely affected.

As part of our business strategy, we may pursue acquisitions or licenses of assets or acquisitions of businesses, or disposition of assets or technologies. For example, in February 2022, we announced the acquisition of Rewrite in order to add additional capabilities to our growing platform, which acquisition included an exclusive license from the Regents of the University of California under certain patents related to DNA writing technology. We also may pursue strategic alliances and joint ventures that leverage our core technology and industry experience. If we decide to collaborate with other companies to discover, develop and commercialize therapeutic products, we face significant competition in seeking appropriate collaborators because, for example, third parties have comparable rights to the CRISPR/Cas9 system or similar genome editing technologies. In addition, we have limited experience with acquiring, disposing of or licensing assets or forming strategic alliances and joint ventures. Our ability to reach a definitive agreement for a collaboration will depend, among other things, upon our assessment of the collaborator’s resources and expertise, the terms and conditions of the proposed collaboration and the proposed collaborator’s evaluation of a number of factors. If we are unable to reach agreements with suitable collaborators on a timely basis, on acceptable terms, or at all, we may have to curtail, delay or abandon discovery efforts or development programs, and the development, manufacture or commercialization of a product candidate, or increase our expenditures and undertake these activities at our own expense. If we elect to fund and undertake discovery, development, manufacturing or commercialization activities on our own, we may need to obtain additional expertise and additional capital, which may not be available to us on acceptable terms or at all. If we fail to enter into collaborations and do not have sufficient funds or expertise to undertake the necessary discovery, development, manufacturing and commercialization activities, we may not be able to further develop our product candidates, manufacture the product candidates, bring them to market or continue to develop our technology and our business may be materially and adversely affected. Furthermore, we may not identify or complete these transactions in a timely manner, on a cost-effective basis, or at all, and we may not realize the anticipated benefits of any acquisition, license, strategic alliance or joint venture.

We currently rely, and expect to continue to rely in part on, third parties to manufacture our clinical product supplies, and we intend to rely on third parties for at least a portion of the manufacturing process of our product candidates, if approved. Our business could be harmed if the third parties fail to provide us with sufficient quantities of product inputs or fail to do so at acceptable quality levels or prices or fail to meet legal and regulatory requirements.

We are in the early stages of establishing our own manufacturing facility to provide preclinical, clinical and commercial supply of our product candidates and must rely on outside vendors, such as CMOs, to manufacture supplies and process our product candidates. We are manufacturing and processing product candidate components on a clinical scale and may not be able to successfully continue to do so. We are optimizing and will continue to optimize the manufacturing process for late-stage clinical and commercial supply, and cannot be sure that even minor changes in the process will result in therapies that are safe, pure and potent. We are also unable to predict how changing global economic conditions or ongoing geopolitical conflicts and related global economic sanctions, or potential global health concerns will affect our third party suppliers and manufacturers. Any negative impact of such matters on our third party suppliers and manufacturers may also have an adverse impact on our results of operations or financial condition.

Any facility that we may have in the future and the facilities used by our CMOs to manufacture our product candidates must be inspected and approved by, as applicable, the FDA or other foreign regulatory agencies after we apply for approval or marketing authorization. For the foreseeable future, we will be dependent on our CMO partners to properly manufacture adequate supply of our product candidates and components in a timely manner and in accordance with our specification. We also will depend on these entities for compliance with relevant legal and regulatory requirements for manufacture of our product candidates, including cGMP, and in certain cases, cGTP requirements. If we or our CMOs cannot successfully manufacture material that conforms to our specifications and the strict relevant regulatory requirements, we and our CMOs will not be able to secure or maintain regulatory approval for our respective manufacturing facilities. In addition, we have no control over the ability of our CMOs to maintain adequate quality control, quality assurance and qualified personnel, particularly as we increase the scale of our manufactured material. If the FDA or relevant foreign regulatory authority does not approve these facilities for the manufacture of our product candidates or if it withdraws any such approval, we may need to find alternative manufacturing facilities, which would significantly impact our ability to develop, obtain regulatory approval for or market our product candidates.

If any CMO with whom we contract fails to perform its obligations, we may be forced to manufacture the materials ourselves, for which we may not have the capabilities or resources, or enter into an agreement with a different CMO, which we may not be able to do on reasonable terms, if at all. In such scenario, our clinical trials supply could be delayed significantly as we establish alternative supply sources. In some cases, the technical skills required to manufacture our product candidates may be unique to the original CMO and we may have difficulty transferring such skills to a back-up or alternate supplier, or we may be unable to

transfer such skills at all. In addition, if we are required to change CMOs for any reason, we will be required to verify that the new CMO maintains facilities and procedures that comply with quality standards and with all applicable regulations. We will also need to verify, such as through a comparability study, that any new manufacturing process will produce our product candidate according to the specifications previously submitted to the FDA or another regulatory authority. The delays associated with the verification of a new CMO could negatively affect our ability to develop product candidates or commercialize our products in a timely manner. In addition, changes in manufacturers often involve changes in manufacturing procedures and processes, which could require that we conduct bridging studies between our prior clinical supply used in our clinical trials and that of any new manufacturer. We may be unsuccessful in demonstrating the comparability of clinical supplies which could require the conduct of additional clinical trials.

We currently rely, and expect to continue to rely on, third parties to conduct our preclinical studies and clinical trials. If these third parties do not successfully carry out their contractual duties or meet expected deadlines or comply with legal and regulatory requirements, we may not be able to obtain regulatory approval of or commercialize any potential product candidates.

We currently depend, and expect to continue to depend, upon third parties, including independent investigators, to conduct our clinical trials under agreements with universities, medical institutions, CROs, strategic partners and others. We expect to have to negotiate budgets and contracts with CROs, trial sites and other service and goods providers, which may result in delays to our development timelines and increased costs. For example, in February 2023, the U.S. Department of Justice investigated the research practices of a significant CRO with respect to their non-human primate imports. Issues of that nature may affect our ability to conduct preclinical studies that are required to advance our product candidates.

We currently rely, and expect to continue to rely heavily, on third parties over the course of our preclinical studies and clinical trials, and, as a result, will have limited control over the clinical investigators and other service providers, and limited visibility into their day-to-day activities, including with respect to their compliance with the approved clinical protocol and other legal, regulatory and scientific standards. Nevertheless, we are responsible for ensuring that each of our studies is conducted in accordance with the applicable protocol and legal, regulatory and scientific standards, and our reliance on third parties does not relieve us of our legal responsibilities. We and these third parties are required to comply with GCP, which are regulations and guidelines enforced by the FDA, EMA and comparable foreign regulatory authorities for product candidates in clinical development. Regulatory authorities enforce these GCP requirements through periodic inspections of trial sponsors, clinical investigators and trial sites. If we or any of these third parties fail to comply with applicable GCP requirements, the clinical data generated in our clinical trials may be deemed unreliable and the relevant regulatory authorities may require us to suspend or terminate these trials or perform additional preclinical studies or clinical trials before approving our marketing applications. We cannot be certain that, upon inspection, such regulatory authorities will determine that any of our clinical trials comply with the GCP requirements. In addition, our clinical trials must be conducted with product produced under cGMP, and in certain cases, cGTP, requirements and may require a large number of test articles for studies involving a large number of test patients.

Our or these third parties’ failure to comply with these requirements or to recruit a sufficient number of patients may require us to delay, suspend, repeat or terminate clinical trials, which would delay the regulatory approval process. Moreover, our business may be implicated if any of these third parties violates applicable federal, state or local, as well as foreign, laws and regulations, such as the fraud and abuse or false claims laws and regulations or privacy and security laws. In jurisdictions such as the U.K. and EU, penalties for violations of privacy laws and other regulations can be financially significant. Further, if any of our CROs, clinical investigators or others involved in our clinical trials fail to comply with such laws and regulations, we could be held responsible for its actions or omissions and be negatively impacted. In the event of non-compliance with the EU General Data Protection Regulation (“EU GDPR”) and the EU GDPR in such form as incorporated into the laws of the U.K. (“U.K. GDPR,” collectively with EU GDPR referred to as “GDPR”), we could be subject to substantial fines and other penalties, including fines of up to 20.0 million Euros (17.5 million GBP for the U.K. GDPR) or up to 4% of our total worldwide annual turnover for the preceding financial year, whichever is higher. The GDPR also confers a private right of action on data subjects and consumer associations to lodge complaints with supervisory authorities, seek judicial remedies, and obtain compensation for damages resulting from violations.

Any third parties conducting our current or future clinical trials will not be our employees and, except for remedies that may be available to us under our agreements with such third parties, we cannot control whether they devote sufficient time and resources to our ongoing preclinical, clinical, and nonclinical programs. These third parties may also have relationships with other commercial entities, including our competitors, for whom they may also be conducting clinical trials or other product development activities, which could affect their performance on our behalf. If these third parties fail to meet their contractual

obligations, legal requirements or expected deadlines, need to be replaced, or generate inaccurate or substandard clinical data by failing to adhere to our clinical protocols or regulatory requirements or for other reasons, our clinical trials may be extended, delayed or terminated and we may not be able to complete development of, obtain regulatory approval of or successfully commercialize our product candidates. As a result, our financial results and the commercial prospects for our product candidates would be harmed, our costs could increase and our ability to generate revenue could be delayed.

A resurgence of the COVID-19 pandemic (or other future public health concern) and measures taken in response by U.S. or other governments may have a significant impact on our CROs, clinical sites and other service and goods providers, which may affect our ability to initiate and complete preclinical studies and clinical trials.

If any of our relationships with these third party CROs, clinical sites or other third parties terminate, we may not be able to enter into arrangements with alternative CROs, clinical sites or other third parties or to do so on commercially reasonable terms. Switching or adding additional CROs, clinical sites or other providers involves additional cost and requires management time and focus. In addition, the transition to a new CRO may result in delays, which can materially impact our ability to meet our desired clinical development timelines. Though we carefully manage our relationships with these parties, there can be no assurance that we will not encounter similar challenges or delays in the future or that these delays or challenges will not have a material adverse impact on our business, financial condition and prospects.

Our internal computer systems, or those of our collaborators or other contractors or consultants, may fail or suffer security breaches or compromises, which could result in a material disruption of our operations and development efforts.

We are increasingly dependent upon information technology systems, infrastructure, and data to operate our business. In the ordinary course of business, we collect, store, and transmit large amounts of confidential information (including but not limited to intellectual property, such as trade secrets, proprietary business information, and personal information). It is critical that we do so in a secure manner to maintain the confidentiality and integrity of such confidential information. We have also outsourced elements of our operations to third parties, and as a result we manage a number of third party vendors who may or could have access to our confidential information. Our third party collaborators, vendors and service providers (including our CMOs and CROs) also have access to large amounts of confidential information relating to our operations, including our research and development efforts. The size and complexity of our information technology systems, and those of third party vendors, service providers and collaborators, and the large amounts of confidential information stored on those systems, make such systems potentially vulnerable to service interruptions or systems failures, or to cybersecurity incidents, breaches or compromises from inadvertent or intentional actions by our employees, third party vendors, service providers, collaborators, and/or business partners, or from cyber-attacks by malicious third parties.

In addition to such risks, the adoption of new technologies may also increase our exposure to cybersecurity incidents, breaches, compromises and failures. Further, having a significant portion of our workforce working from home for extended periods of time puts us at greater risk of cybersecurity attacks. Cyber-attacks are increasing in their frequency, sophistication, and intensity, and have become increasingly difficult to detect. Cyber-attacks could include the deployment of harmful malware, denial-of-service attacks, attacks enhanced or facilitated by artificial intelligence (“AI”), social engineering, “phishing” scams, ransomware, network security breaches, and other means to affect service reliability and threaten the confidentiality, integrity, and availability of information. Certain of our service providers have been subject to such attacks in the past, and while no such attacks have resulted in a material impact to our business, our company or our service providers may be materially impacted by such attacks in the future. Significant disruptions to our information technology systems could adversely affect our business operations and/or result in the loss, misappropriation, and/or unauthorized access, use, or disclosure of, or the prevention of access to, confidential information (including but not limited to trade secrets or other intellectual property, proprietary business information, and personal information), and could result in financial, legal, business, and reputational harm to us and would adversely affect our operations, including our discovery and research and development programs. Any security incidents, compromises or breaches that lead to unauthorized access, use, or disclosure of personal information, including personal information regarding our employees or current or future clinical trial participants, could harm our reputation, require us to comply with onerous legal requirements under laws and regulations that protect the privacy and security of personal information, and subject us to significant liability including fines, litigation, and loss of current and future business.

Also, the loss of preclinical or clinical trial data from completed or future preclinical or clinical trials, respectively, could result in delays in our regulatory approval efforts and significantly increase our costs to recover or reproduce the data. To the extent that any disruption or security breach were to result in a loss of, or damage to, our data or applications, or inappropriate disclosure

of confidential or proprietary information, we could incur liability, our competitive position could be harmed and the further development and commercialization of our product candidates could be delayed. Cybersecurity incidents, breaches, compromises, insider threats and other inappropriate access can be difficult to detect, and any delay in identifying them may lead to increased harm of the types summarized and described above. While we have implemented security measures to protect our information technology systems and infrastructure, there is no assurance that such measures will prevent service interruptions or security breaches, incidents or compromises that could adversely affect our business.

Interruptions in the availability of server systems or communications with internet or cloud-based services, or failure to maintain the security, confidentiality, accessibility or integrity of data stored on such systems, could harm our business.

We rely upon a variety of internet service providers, third party web hosting facilities, cloud computing platform providers and software as a service (“SaaS”) vendors to support our business. Failure to maintain the security, confidentiality, accessibility or integrity of data stored on such systems could result in interruptions in our operations, damage our reputation in the market, increase our service costs, cause us to incur substantial costs, subject us to liability for damages and/or fines, and divert our resources from other tasks, any one of which could materially adversely affect our business, financial condition, results of operations and prospects. If our security measures or those of our third party data center hosting facilities, cloud computing platform providers, SaaS vendors or third party service partners, are breached, and unauthorized access is obtained to our data or our information technology systems, we may incur significant legal and financial exposure and liabilities.

We also do not have control over the operations of the facilities of our cloud service providers, SaaS vendors or our third party web hosting providers, and they also may be vulnerable to damage or interruption from natural disasters, hardware or software outages, cybersecurity attacks, terrorist attacks and similar events or acts of misconduct. In addition, any changes in these providers’ service levels may adversely affect our ability to meet our requirements and operate our business.

Social media platforms and artificial intelligence-based platforms present new risks and challenges to our business.

As social media continues to expand, it also presents us with new risks and challenges. Social media is increasingly being used to communicate information about us, our programs and the diseases our therapeutics are being developed to treat. Social media practices in the pharmaceutical and biotechnology industries are evolving, which creates uncertainty and risk of noncompliance with regulations applicable to our business. For example, patients may use social media platforms to comment on the effectiveness of, or adverse experiences with, a product or a product candidate, which could result in reporting obligations or other consequences. Further, the accidental or intentional disclosure of non-public information by our workforce or others through media channels could lead to information loss. In addition, there is a risk of inappropriate disclosure of sensitive information or negative or inaccurate posts or comments about us, our products, or our product candidates on any social media platform. The nature of social media prevents us from having real-time control over postings about us on social media. We may not be able to reverse damage to our reputation from negative publicity or adverse information posted on social media platforms or similar mediums. If any of these events were to occur or we otherwise fail to comply with applicable regulations, we could incur liability, face restrictive regulatory actions or incur other harm to our business including quick and irreversible damage to our reputation, brand image and goodwill. While we have undertaken measures to restrict the use of public AI platforms, their use by people, including our vendors, suppliers and contractors, with access to our proprietary and confidential information, including trade secrets, may continue to increase and may lead to the release of such information, which may impact our ability to realize the benefit of our intellectual property.

We face significant competition in an environment of rapid technological change. The possibility that our competitors may achieve regulatory approval before we do or develop therapies that are more advanced or effective than ours may harm our business and financial condition or our ability to successfully market or commercialize our product candidates.

The biotechnology and pharmaceutical industries are extremely competitive in the race to develop new products. While we believe we have significant competitive advantages with our industry-leading expertise in genome editing, clinical development expertise and dominant IP position, we currently face and will continue to face competition for our development programs from companies that use genome editing or gene therapy development platforms and from companies focused on more traditional therapeutic modalities such as small molecules and antibodies. The competition is likely to come from multiple sources, including large and specialty pharmaceutical and biotechnology companies, academic research institutions, government agencies and public and private research institutions. Many of these competitors may have access to greater capital and resources than us. For any products that we may ultimately commercialize, not only will we compete with any existing therapies and those therapies currently in development, but we will also have to compete with new therapies that may become available in the future.

Specific to our NTLA-2001 program, we are aware of other companies that are currently commercializing or developing products and therapies used to treat ATTR amyloidosis, including Alnylam Pharmaceuticals, Inc., AstraZeneca Pharmaceuticals LP, BridgeBio Pharma Inc., Ionis Pharmaceuticals, Inc., Metagenomi Technologies, LLC, Novo Nordisk A/S and Pfizer, Inc.

Specific to our NTLA-2002 program, we are aware of other companies that are currently commercializing or developing products used to treat HAE, including ADARx Therapeutics, Inc., Astria Therapeutics Inc., BioCryst Pharmaceuticals Inc., BioMarin Pharmaceuticals Inc., CSL Limited, Ionis Pharmaceuticals, Inc., KalVista Pharmaceuticals, Inc., Pharming Group N.V., Pharvaris N.V. and Takeda Pharmaceutical Company Limited.

Competitors in our efforts to provide other genetic therapies to patients can be grouped into at least three sets based on their product discovery platforms:

Our platform and product foci are on the development of therapies using CRISPR-based technologies. Genome editing companies focused on CRISPR-based technologies include: Beam Therapeutics Inc., Caribou Biosciences, Inc., CRISPR Therapeutics AG, Editas Medicine, Inc., Metagenomi Technologies, LLC, Prime Medicine, Inc., ToolGen, Inc. and Verve Therapeutics Inc.

There are also companies developing therapies using additional genome editing technologies, which include Allogene Therapeutics, Inc., bluebird bio, Inc., Cellectis S.A., Homology Medicines, Inc., Poseida Therapeutics, Inc., Precision Biosciences, Inc., Prime Medicine, Inc. and Sangamo Therapeutics, Inc.

We are also aware of companies developing therapies in various areas related to our specific research and development programs. For ex vivo, these companies include Allogene Therapeutics, Inc., Cellectis S.A., CRISPR Therapeutics AG and Precision BioSciences, Inc. For in vivo, these companies include CRISPR Therapeutics AG, Editas Medicine, Inc., Excision Biotherapeutics, Inc., Locus Biosciences, Inc., Metagenomi Technologies, LLC, Precision Biosciences, Inc. and Verve Therapeutics Inc.

Our competitors will also include companies that are or will be developing other genome editing methods as well as small molecules, biologics, in vivo gene therapies, engineered cell therapies and nucleic acid-based therapies for the same indications that we are targeting with our CRISPR/Cas9-based therapeutics.

Any advances in gene therapy, engineered cell therapies or genome editing technology made by a competitor may be used to develop therapies that could compete against any of our product candidates.

Many of these competitors have substantially greater research and development capabilities and financial, scientific, technical, intellectual property, manufacturing, marketing, distribution and other resources than we do, and we may not be able to successfully compete with them.

Even if we are successful in selecting and developing any product candidates, in order to compete successfully we may need to be first-to-market or demonstrate that our CRISPR/Cas9-based products are superior to therapies based on the same or different treatment methods. If we are not first-to-market or are unable to demonstrate such superiority, any products for which we are able to obtain approval may not be commercially successful. Furthermore, in certain jurisdictions, if a competitor has orphan drug status for a product and if our product candidate is determined to be contained within the scope of a competitor’s orphan drug exclusivity, then approval of our product for that indication or disease could potentially be blocked, for example, for up to seven years in the U.S. and 10 years in the EU.

We may never succeed in any or all of these activities and, even if we do, we may never generate revenues that are significant or large enough to achieve profitability. If we do achieve profitability, we may not be able to sustain or increase profitability on a quarterly or annual basis. Our failure to become and remain profitable would decrease our value and could impair our ability to raise capital, maintain our research and development efforts, expand our business or continue our operations.

If, in the future, we are unable to establish sales, marketing and distribution capabilities or enter into agreements with third parties to sell, market and distribute products based on our technologies, we may not be successful in commercializing our products if and when any product candidates or therapies are approved and we may not be able to generate any revenue.

We do not currently have a sales, marketing or distribution infrastructure and, as a company, have no experience in the sale, marketing or distribution of therapeutic products. To achieve commercial success for any approved product candidate for which we retain sales and marketing responsibilities, we must build our sales, marketing, managerial and other non-technical capabilities or make arrangements with third parties to perform these services. There are risks involved with both establishing our own sales and marketing capabilities and entering into arrangements with third parties to perform these services.

Factors that may inhibit our efforts to commercialize our product candidates include:

If we enter into arrangements with third parties to perform sales, marketing and distribution services, we would likely have lower product revenue or profitability than if we ourselves were to market and sell our product candidates. In addition, we may be unable to enter into sales and marketing arrangements with third parties, or into arrangements with terms that are favorable 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 product candidates effectively. If we do not establish sales, marketing and distribution capabilities successfully, either on our own or through third parties, we may not be successful in commercializing our product candidates, and our business, results of operations, financial condition and prospects will be materially adversely affected.

Our future success depends on our ability to retain key executives and to attract, retain and motivate qualified personnel.

We are highly dependent on the research and development, clinical, manufacturing, commercialization, legal, financial and business development expertise of John M. Leonard, M.D., our President and Chief Executive Officer, James Basta, our Executive Vice President, General Counsel and Corporate Secretary, Eliana Clark, our Executive Vice President and Chief Technical Officer, Edward J. Dulac III, our Executive Vice President, Chief Financial Officer and Treasurer, Derek Hicks, our Executive Vice President and Chief Business Officer, David Lebwohl, our Executive Vice President and Chief Medical Officer, and Laura Sepp-Lorenzino, our Executive Vice President and Chief Scientific Officer, and Michael P. Dube, our Chief Accounting Officer, as well as the other principal members of our management, scientific and clinical teams. Although we have entered into employment arrangements with our executive officers, each of them may terminate their employment with us at any time. We do not maintain “key person” insurance for any of our executives or other employees.

Execution of our business plans and strategies requires capable personnel with specialized skills and expertise in the research, development, manufacturing and commercialization of biopharmaceutical products, and, as a result, we may encounter difficulties in hiring or retaining capable personnel in key positions.

Recruiting and retaining qualified scientific, clinical, manufacturing and sales and marketing personnel will also be important for our success. The loss of the services of our executive officers or other key employees could impede the achievement of our research, development and commercialization objectives, and seriously harm our ability to successfully implement our business strategy. Furthermore, replacing executive officers and key employees may be difficult and may take an extended period of time because of the limited number of individuals in our industry with the breadth of skills and experience required to successfully develop, gain regulatory approval of and commercialize products using our technology. Competition to hire from this limited pool is intense, and we may be unable to hire, train, retain or motivate these key personnel on acceptable terms given the

competition among numerous pharmaceutical and biotechnology companies, universities and research institutions for similar personnel. The market for qualified personnel in the biotechnology space generally, and genome editing and gene therapy fields in particular, in and around the Cambridge, Massachusetts area is especially competitive. In addition, we rely on consultants and advisors, including scientific and clinical advisors, to assist us in formulating our research and development and commercialization strategies. Our consultants and advisors may be employed by employers other than us and may have commitments under consulting or advisory contracts with other entities that may limit their availability to us. Further, some of the qualified personnel that we hire and recruit are not U.S. citizens, and there is uncertainty with regard to their future employment status due to the current U.S. administration’s announced intention of modifying the legal framework for non-U.S. citizens to be employed in the U.S. If we are unable to continue to attract and retain high quality personnel, our ability to pursue our growth strategy will be limited.

Coverage and reimbursement may be limited or unavailable in certain market segments for our product candidates, if approved, which could make it difficult for us to sell any product candidates or therapies profitably.

The success of our product candidates, if approved, depends on the availability of adequate coverage and reimbursement from third party payors, including government agencies, private health insurers and health maintenance organizations. There is significant uncertainty related to the insurance coverage and reimbursement of any newly approved product, but in particular novel genome editing and engineered cell products. All the therapeutic indications approved by the relevant authorities may not be covered or reimbursed. In addition, we cannot be sure that coverage and reimbursement will be available for, or accurately estimate the potential revenue from, our product candidates because they are novel treatments for diseases using a new technology and delivery approaches. For more information on coverage and reimbursement see the section entitled “Business – Government Regulation and Product Approval – Coverage and Reimbursement” in our annual report on Form 10-K for the year ended December 31, 2023.

In the U.S. and some other jurisdictions, patients generally rely on third party payors to reimburse all or part of the costs associated with their treatment. Adequate coverage and reimbursement from governmental healthcare programs, such as Medicare and Medicaid in the U.S., and commercial payors are critical to new product acceptance.

Government authorities and other third party payors, such as private health insurers and health maintenance organizations, decide which drugs and treatments they will cover and the amount of reimbursement. In the U.S., the principal decisions about reimbursement for new medicines are typically made by the Centers for Medicare & Medicaid Services (“CMS”), an agency within the U.S. Department of Health and Human Services. CMS decides whether and to what extent a new medicine will be covered and reimbursed under Medicare, and private payors often follow CMS’s coverage decisions. Other jurisdictions have agencies, such as the National Institute for Health and Care Excellence in the U.K., that evaluate the use and cost-effectiveness of therapies, which impact the utilization and price of the medicine in such jurisdiction.

In the U.S., no uniform policy of coverage and reimbursement for products exists among third party payors. As a result, obtaining coverage and reimbursement approval of a product from a third party payor is a time-consuming and costly process that could require us to provide supporting scientific, clinical and cost-effectiveness data for the use of our products to each potential payor, with no assurance that coverage and adequate reimbursement will be obtained from all or any of them. Even if we obtain coverage for a given product, the resulting reimbursement payment rates might be insufficient or may require co-payments that patients find unacceptably high, which may prevent us from achieving or sustaining profitability. Additionally, third party payors may not cover, or provide adequate reimbursement for, long-term follow-up evaluations required following the use of our genome editing products.

In addition, each country in which we seek approval to market our product candidates has unique laws and market practices regulating coverage and reimbursement for human therapeutics. Market acceptance and sales of our products in each country will depend on our ability to meet each of these jurisdiction’s requirements for coverage and reimbursement. Further, changes to the country’s existing requirements may also affect our ability to commercialize our products in the future, or achieve profitability from their sale.

We may be subject, directly or indirectly, to federal and state healthcare fraud and abuse laws, false claims laws, physician payment transparency laws, health information privacy and security laws and anti-corruption laws. If we are unable to comply, or have not fully complied, with such laws or their relevant foreign counterparts, we could face substantial penalties.

The sale, distribution and marketing of human therapeutics and our relationship with healthcare providers are strictly regulated by laws in the U.S. and most other jurisdictions in which we intend to seek approval for our product candidates. In addition, the collection and use of personal information, including Protected Health Information, is regulated by federal, state and foreign privacy, data security and data protection laws. Failure to comply with these laws could impair our ability to properly sell our product candidates in particular jurisdictions and subject us to liability from private and governmental entities. Addressing these diverse and sometimes contradictory requirements in myriad jurisdictions may necessitate that we expend significant resources on compliance efforts. Any failure to comply with these requirements may leave us exposed to possible enforcement actions and potential liability. For more information on these laws and regulations see the section entitled “Business – Government Regulation and Product Approval – Other Healthcare and Privacy Laws” in our annual report on Form 10-K for the year ended December 31, 2023.

The scope and enforcement of each of these laws is not always certain and is subject to legislative, judicial or prosecutorial changes. Further, because of the breadth of these laws, it is possible that some of our business activities could be subject to challenge under one or more of such laws. Indeed, U.S. federal and state enforcement bodies have increasingly scrutinized healthcare companies and providers interactions, which has led to a number of investigations, prosecutions, convictions and settlements in the industry. Ensuring business arrangements comply with applicable laws, as well as responding to possible investigations by government authorities, can be time- and resource-consuming and can divert the attention of our staff and resources from performing the duties required for the general operation of our business.

The increasingly global nature of our business operations, including clinical development efforts, subjects us to domestic and foreign anti-bribery and anti-corruption laws and regulations, such as the Foreign Corrupt Practices Act (“FCPA”) and the U.K. Bribery Act. These activities create the risk of unauthorized payments or offers of payments that are prohibited under the FCPA, the U.K. Bribery Act or similar laws. It is our policy to implement safeguards to discourage these practices by our employees and agents. However, these safeguards may ultimately prove ineffective, and our employees, consultants, and agents may engage in conduct for which we might be held responsible. Violations of the FCPA may result in severe criminal or civil sanctions, and we may be subject to other liabilities, which could negatively affect our business, operating results and financial condition.

Further, the U.S. federal and state governments, as well as other jurisdictions, have myriad laws regulating the collection, storage, distribution, safeguarding and use of personal information of employees, patients, agents, and others. These different laws governing the privacy and security of health and other personal information often differ from each other in significant ways and may not have the same effective requirements, thus complicating efforts to comply with their respective provisions. For example:

The costs associated with ensuring compliance with these laws, including in particular GDPR, may be onerous and may adversely affect our business, financial condition, results of operations and prospects. We may also need to rely on multiple third parties, such as partners and service providers, to meet these legal requirements, which could result in additional liability for us if they do not comply.

Efforts to ensure that we comply with all applicable healthcare and data privacy laws and regulations, as well as other domestic and foreign legal requirements, will involve substantial costs. It is possible that governmental and enforcement authorities in the U.S. or outside the U.S. will conclude that our business practices do not comply with current or future legal requirements. If any noncompliance actions are instituted against us, those actions could have a significant impact on our business, including the imposition of significant civil, criminal and administrative penalties, damages, disgorgement, monetary fines, individual imprisonment, exclusion from participation in federal healthcare programs (such as Medicare and Medicaid), contractual damages, reputational harm, diminished profits and future earnings, and curtailment or restructuring of our operations, as well as additional reporting obligations and oversight if we become subject to a corporate integrity agreement or similar agreement to resolve allegations of non-compliance with these laws, any of which could adversely affect our ability to operate our business and affect the results of our operations. Any action alleging a violation of these laws, even if successfully defended, could result in significant legal expenses and divert management’s attention from the operation of the business. Prohibitions or restrictions on sales (including importation or exportation) or withdrawal of future marketed products could materially affect business in an adverse way.

Healthcare cost control initiatives, including healthcare legislative and regulatory reform measures, may have a material adverse effect on our business and results of operations.

The U.S. and many other jurisdictions have enacted or proposed legal changes affecting the healthcare system that could prevent or delay marketing approval of our product candidates, affect our ability to profitably sell our product candidates once approved, and restrict or regulate post-approval activities. Changes in the legal requirements, or their interpretation, could impact our

business by compelling, for example, modification to: our manufacturing arrangements; product labeling; pricing and reimbursement arrangements; private or governmental insurance coverage; the sale practices for, or availability of, our products; or record-keeping activities. If any such changes were to be imposed, they could adversely affect the operation of our business. For more information on these laws and regulations see the section entitled “Business – Government Regulation and Product Approval – Healthcare Reform” in our annual report on Form 10-K for the year ended December 31, 2023.

Third party payors, whether domestic or foreign, or governmental or commercial, are developing increasingly sophisticated methods of controlling healthcare costs. In the U.S. and certain other jurisdictions, there have been, and are expected to continue to be, a number of legislative and regulatory changes to the healthcare system that could impact our ability to sell our products profitably. In the U.S., however, significant uncertainty exists regarding the provision and financing of healthcare because the newly elected administration and federal legislators have publicly declared their intention to review and potentially significantly modify the current legal and regulatory framework for the healthcare system.

We cannot predict the initiatives that may be adopted in the future. The continuing efforts of the government, insurance companies, managed care organizations and other payors of healthcare services to contain or reduce costs of healthcare and/or impose price controls may adversely affect:

Any reduction in reimbursement from Medicare or other government programs may result in a similar reduction in payments from private payors, which may adversely affect our future profitability.

If an active market for our common stock does not continue, it may be difficult for our stockholders to sell their shares without depressing the market price for the shares or sell their shares at or above the prices at which they acquired their shares or sell their shares at the time they would like to sell. Any inactive trading market for our common stock may also impair our ability to raise capital to continue to fund our operations by selling shares and may impair our ability to acquire other companies or technologies by using our shares as consideration.

The price of our common stock historically has been volatile, which may affect the price at which you could sell any shares of our common stock.

The market price for our common stock historically has been highly volatile and could continue to be subject to wide fluctuations in response to various factors. This volatility may affect the price at which you could sell the shares of our common stock, and the sale of substantial amounts of our common stock could adversely affect the price of our common stock. Our stock price is likely to continue to be volatile and subject to significant price and volume fluctuations in response to market and other factors, including:

Companies trading in the stock market in general, and in The Nasdaq Global Market in particular, have also experienced extreme price and volume fluctuations that have often been unrelated or disproportionate to the operating performance of these companies. Broad market and industry factors may negatively affect the market price of our common stock, regardless of our actual operating performance. In the past, following periods of volatility in the market, securities class-action litigation has often been instituted against companies. Such litigation, if instituted against us, could result in substantial costs and diversion of management’s attention and resources, which could materially and adversely affect our business, financial condition, results of operations and growth prospects.

If securities or industry analysts do not publish research, or publish inaccurate or unfavorable research, about our business, our stock price and trading volume could decline.

The trading market for our common stock will depend, in part, on the research and reports that securities or industry analysts publish about us or our business. Securities and industry analysts may not publish an adequate amount of research on us, which may negatively impact the trading price for our stock. In addition, if one or more of the analysts who cover us downgrade our stock or publish inaccurate or unfavorable research about our business, our stock price would likely decline. Further, if our operating results fail to meet the forecasts of analysts, our stock price would likely decline. If one or more of these analysts cease coverage of us or fail to publish reports on us regularly, demand for our stock could decrease, which might cause our stock price and trading volume to decline.

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

We have never declared or paid cash dividends on our capital stock. We currently intend to retain all of our future earnings, if any, to finance the growth and development of our business. In addition, the terms of any future debt agreements may preclude us from paying dividends. As a result, capital appreciation, if any, of our common stock will be your sole source of gain for the foreseeable future.

Our principal stockholders and management own a significant percentage of our stock and, if they choose to act together, will be able to control or exercise significant influence over matters subject to stockholder approval.*

Our executive officers, directors, 5% or greater stockholders and their affiliates beneficially own a significant percentage of our outstanding voting stock. These stockholders may have the ability to influence us through their ownership positions. These stockholders may be able to determine all matters requiring stockholder approval. For example, these stockholders, acting together, may be able to control elections of directors or approval of any merger, sale of assets or other major corporate transaction. This may prevent or discourage unsolicited acquisition proposals or offers for our common stock that you may believe are in your best interest as one of our stockholders.

We have broad discretion over the use of our cash, cash equivalents and marketable securities, and may not use them effectively, including that we may be exposed to liquidity issues and other systemic financial risks at the financial institutions holding our cash and cash equivalents.

Our management has broad discretion to use our cash, cash equivalents and marketable securities to fund our operations and could spend these funds in ways that do not improve our results of operations or enhance the value of our common stock. The failure by our management to apply these funds effectively could result in financial losses that could have a material adverse effect on our business, cause the price of our common stock to decline and delay the development of our product candidates. Pending our use to fund operations, we may invest our cash, cash equivalents and marketable securities in a manner that does not produce income or that loses value.

A portion of our cash may be held by financial institutions that may have been, or could in the future become, exposed to liquidity issues, bank failures or other systemic financial risks. Our uninsured cash deposits with such financial institutions may be at risk in the event they experience liquidity problems or other financial losses. For example, in May 2023, the Federal Deposit Insurance Corporation (“FDIC”) took control of First Republic Bank and JP Morgan Chase & Co. has since acquired a substantial amount of assets and certain liabilities of First Republic. Although the U.S. Department of Treasury, FDIC and Federal Reserve Board have announced a program to provide up to $25.0 billion of loans to financial institutions secured by certain government securities held by financial institutions to mitigate the risk of potential losses on the sale of such instruments, there is no guarantee that such loans will fully mitigate the risk of potential losses or that the U.S. Department of Treasury, FDIC and Federal Reserve Board will provide access to uninsured funds in the future in the event of the closure of other banks or financial institutions, or that they would do so in a timely fashion. We assess our banking relationships as we believe necessary or appropriate, but uncertainty remains over liquidity concerns in the broader financial services industry, and our business, our business partners, or industry as a whole may be adversely impacted in ways that we cannot predict at this time, including our ability to access cash in amounts adequate to finance or capitalize our current and/or projected business operations could be significantly impaired by factors that affect the financial institutions with which we have banking relationships, and in turn, us. These factors could include, among others, events such as liquidity constraints or failures, the ability to perform obligations under various types of financial, credit or liquidity agreements or arrangements (including cash management arrangements), disruptions or instability in the financial services industry or financial markets, or concerns or negative expectations about the prospects for companies in the financial services industry. In addition, our vendors, such as our CMOs, CROs or business partners, may be susceptible to the foregoing liquidity or other financial risks and factors, which could, in turn, have a material adverse effect on our current and/or projected business operations and results of operations and financial condition.

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

As a public company, and particularly since we are no longer an “emerging growth company” under applicable SEC regulations, we incur significant legal, accounting and other expenses. The Sarbanes-Oxley Act of 2002, the Dodd-Frank Wall Street Reform and Consumer Protection Act, the listing requirements of the Nasdaq Global Market and other applicable securities rules and regulations impose various requirements on public companies, including establishment and maintenance of effective disclosure and financial controls and corporate governance practices. Our management and other personnel devote a substantial amount of time to these compliance initiatives.

Pursuant to Section 404 of the Sarbanes-Oxley Act of 2002 (“Section 404”), we are required to furnish a report by our management on our internal control over financial reporting, including an attestation report on internal control over financial reporting issued by our independent registered public accounting firm. We conduct a process each year to document and evaluate our internal control over financial reporting, which is both costly and challenging. In this regard, we dedicate internal resources, engage outside consultants and adopt a detailed work plan to assess and document the adequacy of internal control over financial reporting, continue steps to improve control processes as appropriate, validate through testing that controls are functioning as documented and implement a continuous reporting and improvement process for internal control over financial reporting. Despite our efforts, there is a risk that neither we nor our independent registered public accounting firm will be able to conclude that our internal control over financial reporting is effective as required by Section 404. This could result in an adverse reaction in the financial markets due to a loss of confidence in the reliability of our consolidated financial statements.

Future sales and issuances of our common stock or rights to purchase common stock, including pursuant to our equity incentive plans and “at-the-market” offerings, could result in additional dilution of the percentage ownership of stockholders and could cause our stock price to fall.

We will need additional capital in the future to continue our planned operations. To the extent we raise additional capital by issuing equity securities, our stockholders may experience substantial dilution. We may sell common stock, convertible securities or other equity securities in one or more transactions at prices and in a manner we determine from time to time. If we sell common stock, convertible securities or other equity securities in more than one transaction, investors may be materially diluted by subsequent sales. These sales may also result in material dilution to our existing stockholders, and new investors could gain rights superior to our existing stockholders.

Given the volatility in the capital markets, we may not be willing or able to continue to raise equity capital. We may, therefore, need to turn to other sources of funding that may have terms that are not favorable to us, or reduce our business operations given capital constraints. In addition, sales of a substantial number of shares of our outstanding common stock in the public market could occur at any time. These sales, or the perception in the market that the holders of a large number of shares of common stock intend to sell shares, could reduce the market price of our common stock. We cannot predict the effect that future sales of common stock or other equity-related securities would have on the market price of our common stock. Investors who purchase shares in this offering at different times will likely pay different prices, and so may experience different outcomes in their investment results. We will have discretion, subject to market demand, to vary the timing, prices and numbers of shares sold, and there is no minimum or maximum sales price. Investors may experience a decline in the value of their shares as a result of share sales made at prices lower than the prices they paid.

Anti-takeover provisions in our charter documents and under Delaware law could make an acquisition of us difficult, limit attempts by our stockholders to replace or remove our current management and adversely affect our stock price.

Provisions of our certificate of incorporation and by-laws may delay or discourage transactions involving an actual or potential change in our control or change in our management, including transactions in which stockholders might otherwise receive a premium for their shares, or transactions that our stockholders might otherwise deem to be in their best interests. Therefore, these provisions could adversely affect the price of our stock. Among other things, the certificate of incorporation and by-laws:

In addition, because we are incorporated in Delaware, we are governed by the provisions of Section 203 of the Delaware General Corporation Law, which generally prohibits a Delaware corporation from engaging in any of a broad range of business combinations with any “interested” stockholder for a period of three years following the date on which the stockholder became an “interested” stockholder.

Our certificate of incorporation and by-laws designate certain courts as the sole and exclusive forums for certain disputes between us and our stockholders, which could limit our stockholders’ ability to obtain a favorable judicial forum for disputes with us or our directors, officers or employees.

Our certificate of incorporation and by-laws provide that, unless we consent in writing to the selection of an alternative forum, the Court of Chancery of the State of Delaware is the sole and exclusive forum for any state law claims for any derivative action or proceeding brought on our behalf alleging state law claims, any action asserting a breach of fiduciary duty, any action asserting a claim against us arising pursuant to the Delaware General Corporation Law, our certificate of incorporation or our by-laws, any action to interpret, apply, enforce, or determine the validity of our certificate of incorporation or bylaws, or any action asserting a claim against us that is governed by the internal affairs doctrine (the “Delaware Forum Provision”). The Delaware Forum Provision does not apply to claims arising under the Exchange Act or the Securities Act. Our by-laws further provide that the U.S. District Court for the District of Massachusetts will be the sole and exclusive forum for resolving any complaint asserting a cause of action arising under the Securities Act (the “Federal Forum Provision”). We have chosen the U.S. District Court for the District of Massachusetts as the exclusive forum for such Securities Act causes of action because our principal executive offices are located in Cambridge, Massachusetts. Our by-laws provide that any person or entity purchasing or otherwise acquiring any interest in any shares of our common stock is deemed to have notice of and consented to the foregoing Delaware Forum Provision and the Federal Forum Provision.

The Delaware Forum Provision and the Federal Forum Provision may impose additional litigation costs on stockholders in pursuing the claims identified above, particularly if the stockholders do not reside in or near the State of Delaware or the Commonwealth of Massachusetts. Additionally, the Delaware Forum Provision and the Federal Forum Provision may limit a stockholder’s ability to bring a claim in a judicial forum that it finds favorable for disputes with us or our directors, officers or other employees, which may discourage such lawsuits against us and our directors, officers and other employees. Alternatively, if a court were to find the Delaware Forum Provision and the Federal Forum Provision to be inapplicable or unenforceable in an action, we may incur additional costs associated with resolving such action in other jurisdictions, which could adversely affect our business and financial condition. The Court of Chancery of the State of Delaware or the U.S. District Court for the District of Massachusetts may also reach different judgments or results than would other courts, including courts where a stockholder considering an action may be located or would otherwise choose to bring the action, and such judgments may be more or less favorable to us than our stockholders.

The laws and rules dealing with U.S. federal, state and local income taxation are routinely being reviewed and modified by governmental bodies, officials and regulatory agencies, including the Internal Revenue Service and the U.S. Treasury Department. Since we were founded in 2014, many such changes have been made and changes are likely to continue to occur in the future. We cannot predict whether, when, in what form, or with what effective dates, tax laws, regulations and rulings may be enacted, promulgated or issued, that could result in an increase in our or our stockholders’ tax liability.

Our ability to use our net operating loss (“NOL”) carryforwards and certain other tax attributes may be limited.

We have incurred substantial losses during our history and do not expect to become profitable in the near future, and we may never achieve profitability. To the extent that we continue to generate taxable losses, unused losses will carry forward to offset future taxable income, if any, until such unused losses expire. As of December 31, 2023, we had federal and state NOLs of $954.0 million and $922.8 million, respectively, some of which begin to expire in 2034. Federal and certain state NOLs generated in taxable years ending after December 31, 2017 are not subject to expiration. As of December 31, 2023, we had federal and state research and development and other credit carryforwards of approximately $100.7 million and $64.1 million, which begin to expire in 2034 and 2029, respectively. Under Sections 382 and 383 of the Code, if a corporation undergoes an “ownership

change,” generally defined as a greater than 50 percentage point change (by value) in its equity ownership by certain stockholders over a three-year period, the corporation’s ability to use its pre-change NOLs, and other pre-change tax attributes (such as research and development tax credits) to offset its post-change income or taxes may be limited. During 2022, we completed an assessment of the available net operating loss carryforwards and other tax attributes under Section 382 that covered the period from inception through December 31, 2022. This analysis did not result in a material limitation to our other tax attributes. We have not completed an analysis through December 31, 2023. To the extent there was a change in control during 2023, our tax attributes could be subject to limitation. We may experience ownership changes in the future. As a result, if we earn net taxable income, our ability to use our pre-change NOLs and research and development tax credits to offset such taxable income and income tax, respectively, could be subject to limitations. Similar provisions of state tax law may also apply. As a result, even if we attain profitability, we may be unable to use a material portion of our NOLs and other tax attributes.

The following exhibits are incorporated by reference or filed as part of this report.

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned, thereunto duly authorized.


特拉华州	36-4785571
（成立或组织的）州或其他辖区	(国税局雇主识别号码)
或组织成立的州或其他司法管辖区)	识别号码)

40 Erie Street, Suite 130, 剑桥, 麻萨诸塞州	02139
（总部地址）	（邮政编码）


每个类别的标题	交易标的	每个注册交易所的名称
普通股，每股面值为0.0001美元	NTLA	纳斯达克全球市场


第一部分 - 财务信息

第一项。基本报表（未经审计）

2024年9月30日的总余额表及2023年12月31日	3

截至2024年9月30日和2023年控制项综合损益简明综合损益表	4

2024年9月30日和2023年截至九个月的股东权益简明合并报表	5

截至2024年和2023年9月30日九个月的综合现金流量简明合并财务报表	6

基本报表注记	7

项目2. 管理层对财务状况和营运结果的讨论与分析。	19

项目3.有关市场风险的定量和质量披露	29

第四项。控制和程序.	30

第二部分 - 其他信息项目1. 法律诉讼	31

第1A项。风险因素	31

I项目2。未登记出售股权证券及款项使用情况	75

项目5。其他信息。	75

项目6. 附件	76

签名	77


	九月三十日 2024			十二月 31, 2023
资产
流动资产：
现金和现金等价物	$	120,495		$	226,748
有价证券		537,619			685,475
应收账款		8,854			36,456
预付费用和其他流动资产		43,934			49,651
流动资产总额		710,902			998,330
有价证券-非流动		286,567			99,864
财产和设备，净额		28,763			32,760
经营租赁使用权资产		100,331			115,375
权益法投资		-			11,765
投资和其他资产		46,788			42,883
总资产	$	1,173,351		$	1,300,977
负债和股东权益
流动负债：
应付账款	$	13,145		$	7,452
应计费用		51,206			67,017
经营租赁负债的当前部分		19,177			18,599
递延收入的本期部分		22,155			22,140
流动负债总额		105,683			115,208
递延收入，扣除当期部分		22,607			38,853
长期经营租赁负债		82,446			96,747
负债总额		210,736			250,808
承付款和或有开支（注6）
股东权益：
普通股，$0.0001面值； 240,000,0002024 年 9 月 30 日和 2023 年 12 月 31 日授权的股份； 101,796,365和 92,997,158分别于 2024 年 9 月 30 日和 2023 年 12 月 31 日已发行和流通的股份		10			9
额外的实收资本		3,007,810			2,710,797
累计其他综合收益（亏损）		3,297			(2,258	)
累计赤字		(2,048,502	)		(1,658,379	)
股东权益总额		962,615			1,050,169
负债和股东权益总额	$	1,173,351		$	1,300,977


	截至9月30日的三个月						截至9月30日的九个月
	2024			2023			2024			2023
合作营业收入	$	9,111		$	11,992		$	45,003		$	38,192
营业费用：
研发		123,380			113,696			349,434			326,088
一般行政		30,501			29,403			93,385			87,503
营业费用总计		153,881			143,099			442,819			413,591
营业亏损		(144,770	)		(131,107	)		(397,816	)		(375,399	)
其他收益（费用），净:
利息收入		12,122			12,740			37,176			37,373
投资公允价值变动净额		(3,064	)		-			(29,483	)		-
权益法投资亏损		-			(3,857	)		-			(10,905	)
应计可变对价公允价值变动		-			-			-			(100	)
其他收入净额		9,058			8,883			7,693			26,368
净损失	$	(135,712	)	$	(122,224	)	$	(390,123	)	$	(349,031	)
基本和稀释每股净亏损	$	(1.34	)	$	(1.38	)	$	(3.99	)	$	(3.96	)
基本和摊薄的加权平均股份 64,788		101,002			88,645			97,842			88,204
其他综合收益:
市场证券未实现收益		4,452			142			3,423			1,649
其他共同基金的其他全面收益投资		-			154			-			2,240
综合损失	$	(131,260	)	$	(121,928	)	$	(386,700	)	$	(345,142	)


☒	根据1934年证券交易法第13或15(d)条款的季度报告。


☐	根据1934年证券交易法第13或15(d)条款的过渡报告


大型加速归档人	☒	加速归档人	☐
非加速归档人	☐	小型报告公司	☐
新兴成长型企业	☐


					额外的		其他积累						总计
	普通股				实缴		综合			累积的			股东的
	股份		金额		资本		收益（损失）			$			股权
2023年12月31日结余为		92,997,158	$	9	$	2,710,797	$	(2,258	)	$	(1,658,379	)	$	1,050,169
通过市场发行普通股，扣除融资费用后的净额发行成本之期权为$210		2,209,938		1		55,958		-			-			55,959
行使股票期权		110,734		-		1,958		-			-			1,958
受限制股票单位解除限制		1,015,543		-		-		-			-			-
基于股票的报酬		-		-		34,176		-			-			34,176
其他全面收益（损失）- 未实现损失期权市场证券		-		-		-		(821	)		-			(821	)
其他全面收益（损失）再分类- 其他全面收益（损失）再分类-股权法投资		-		-		-		2,132			-			2,132
净损失		-		-		-		-			(107,436	)		(107,436	)
2024年3月31日结存余额		96,333,373		10		2,802,889		(947	)		(1,765,815	)		1,036,137
通过市场定价发行普通股，净额发行成本为$14		1,592,823		-		38,399		-			-			38,399
行使股票期权		79,512		-		1,179		-			-			1,179
受限制股票单位解除限制		195,691		-		-		-			-			-
员工期权下的发行股份股票购买计划		87,751		-		1,669		-			-			1,669
基于股票的报酬		-		-		40,861		-			-			40,861
其他全面收益（损失）-未实现损失可交易证券		-		-		-		(208	)		-			(208	)
净损失		-		-		-		-			(146,975	)		(146,975	)
2024年6月30日余额		98,289,150		10		2,884,997		(1,155	)		(1,912,790	)		971,062
通过市场发行发行普通股净额发行成本$的净额14		3,201,609		-		80,497		-			-			80,497
行使股票期权		181,490		-		2,697		-			-			2,697
受限制股票单位解除限制		124,116		-		-		-			-			-
基于股票的报酬		-		-		39,619		-			-			39,619
其他综合收益（损失）- 未实现收益交易性证券		-		-		-		4,452			-			4,452
净损失		-		-		-		-			(135,712	)		(135,712	)
2024年9月30日的余额		101,796,365	$	10	$	3,007,810	$	3,297		$	(2,048,502	)	$	962,615

					额外的		其他积累						总计
	普通股				实缴		综合			累积的			股东的
	股份		金额		资本		收益（损失）			赤字			股权
2022年12月31日结存余额		87,103,007	$	9	$	2,420,223	$	(7,461	)	$	(1,177,187	)	$	1,235,584
通过市场发行普通股净额发行成本的金额为$62		35,349		-		1,466		-			-			1,466
支付给Rewrite持有人的应计对价		567,045		-		24,126		-			-			24,126
行使股票期权		48,353		-		755		-			-			755
受限制股票单位解除限制		342,025		-		-		-			-			-
基于股票的报酬		-		-		27,255		-			-			27,255
其他综合收益（损失）-未实现损益有价证券市场的不变现损益		-		-		-		2,989			-			2,989
其他综合收益（损失）-权益未实现收益使用投资方法进行未实现的损益		-		-		-		1,794			-			1,794
净损失		-		-		-		-			(103,126	)		(103,126	)
2023年3月31日的余额		88,095,779		9		2,473,825		(2,678	)		(1,280,313	)		1,190,843
行使股票期权		30,371		-		465		-			-			465
受限制股票单位解除限制		151,853		-		-		-			-			-
员工期权计划下股份发行员工购股计划		69,631		-		2,051		-			-			2,051
基于股票的报酬		-		-		36,400		-			-			36,400
其他全面收益(损失) - 证券投资未实现损失其他全面收益(损失) - 证券投资未实现损失		-		-		-		(1,482	)		-			(1,482	)
其他综合收益（损失）- 股权未实现收益方法投资		-		-		-		292			-			292
净损失		-		-		-		-			(123,681	)		(123,681	)
2023年6月30日的余额		88,347,634		9		2,512,741		(3,868	)		(1,403,994	)		1,104,888
通过市场发行普通股，净额发行成本的81		405,332		-		14,718		-			-			14,718
行使股票期权		241,123		-		4,384		-			-			4,384
受限制股票单位解除限制		103,732		-		-		-			-			-
以股票为基础的补偿		-		-		35,352		-			-			35,352
其他全面收益（损失）- 未实现利润有价证券的市场价值		-		-		-		142			-			142
其他全面收益（损失）- 股权未实现收益道具投资		-		-		-		154			-			154
净损失		-		-		-		-			(122,224	)		(122,224	)
2023年9月30日结余		89,097,821	$	9	$	2,567,195	$	(3,572	)	$	(1,526,218	)	$	1,037,414


	九月三十日		十二月 31,
	2024		2023
	（以千计）
应计研究和开发	$	24,325	$	27,411
员工薪酬和福利		20,551		26,615
应计法律和专业费用		2,677		2,063
应计施工成本		1,349		6,891
应计其他		2,304		4,037
应计费用总额	$	51,206	$	67,017


	截至9月30日的三个月						期至
	2024			2023			周期变动
	（以千计）
协作收入	$	9,111		$	11,992		$	(2,881	)
运营费用：
研究和开发		123,380			113,696			9,684
一般和行政		30,501			29,403			1,098
运营费用总额		153,881			143,099			10,782
营业亏损		(144,770	)		(131,107	)		(13,663	)
其他收入（支出），净额：
利息收入		12,122			12,740			(618	)
投资公允价值的变化，净额		(3,064	)		-			(3,064	)
权益法投资的亏损		-			(3,857	)		3,857
其他收入总额，净额		9,058			8,883			175
净亏损	$	(135,712	)	$	(122,224	)	$	(13,488	)


	截至9月30日的三个月				期间			百分比
	2024		2023		时期变化			变化
	(以千为单位)
按项目分的外部开发费用：
NTLA-2001	$	22,842	$	16,404	$	6,438			39	%
NTLA-2002		11,656		4,798		6,858			143	%
NTLA-3001		1,766		8,563		(6,797	)		-79	%
未分配的研发费用：
员工相关费用		29,666		32,317		(2,651	)		-8	%
研究材料和外包服务		17,922		16,084		1,838			11	%
设施相关费用		14,206		13,168		1,038			8	%
股权激励		24,224		21,235		2,989			14	%
其他		1,098		1,127		(29	)		-3	%
研发总费用	$	123,380	$	113,696	$	9,684			9	%


	Nine Months Ended September 30,						Period-to-
	2024			2023			Period Change
	(In thousands)
Collaboration revenue	$	45,003		$	38,192		$	6,811
Operating expenses:
Research and development		349,434			326,088			23,346
General and administrative		93,385			87,503			5,882
Total operating expenses		442,819			413,591			29,228
Operating loss		(397,816	)		(375,399	)		(22,417	)
Other income (expense), net:
Interest income		37,176			37,373			(197	)
Change in fair value of investments, net		(29,483	)		-			(29,483	)
Loss from equity method investment		-			(10,905	)		10,905
Change in fair value of contingent consideration		-			(100	)		100
Total other income, net		7,693			26,368			(18,675	)
Net loss	$	(390,123	)	$	(349,031	)	$	(41,092	)


	Nine Months Ended September 30,				Period-to-			Percent
	2024		2023		Period Change			Change
	(In thousands)
External development expenses by program:
NTLA-2001	$	51,206	$	39,523	$	11,683			30	%
NTLA-2002		31,125		16,408		14,717			90	%
NTLA-3001		7,005		16,724		(9,719	)		-58	%
Unallocated research and development expenses:
Employee-related expenses		98,184		103,437		(5,253	)		-5	%
Research materials and contracted services		46,930		46,003		927			2	%
Rewrite research milestone		-		874		(874	)		-100	%
Facility-related expenses		42,175		38,891		3,284			8	%
Stock-based compensation		69,824		60,517		9,307			15	%
Other		2,985		3,711		(726	)		-20	%
Total research and development expenses	$	349,434	$	326,088	$	23,346			7	%


Name (Title)	Action Taken (Date of Action)	Type of Trading Arrangement	Nature of Trading Arrangement	Duration of Trading Arrangement	Aggregate Number of Securities
James E. Basta (EVP, General Counsel)	Adoption (July 11, 2024)	Rule 10b5-1 trading arrangement	Sale	Until the earlier of (a) November 11, 2024; (b) the first date on which all trades have been executed or all trading orders related to such trades have expired; and (c) the date on which the plan holder gives notice to terminate the plan.	Indeterminable (1)
Muna Bhanji (Director)	Adoption (September 27, 2024)	Rule 10b5-1 trading arrangement	Sale	Until the earlier of (a) June 20, 2025; (b) the first date on which all trades have been executed or all trading orders related to such trades have expired; and (c) the date on which the plan holder gives notice to terminate the plan.	3,624


	截至9月30日的九个月
	2024			2023
经营活动产生的现金流量：
净损失	$	(390,123	)	$	(349,031	)
调整为净损失到经营活动现金流量净使用：
折旧与摊销		7,719			6,510
（出售固定资产的）损益收入		(76	)		5
基于股票的报酬		114,656			99,007
投资折现和溢价溢价的增值		(14,215	)		(19,590	)
(识别) 推迟股权法下子公司销售利润		(20,967	)		6,624
投资公允价值变动净额		29,483			-
权益法投资亏损		-			10,905
应计可变对价公允价值变动		-			100
经营性资产和负债变动:
应收账款		27,602			(2,723	)
预付费用和其他流动资产		4,643			(11,806	)
经营租赁权使用资产		15,044			14,148
其他		1,476			(836	)
应付账款		5,364			(1,419	)
应计费用		(14,336	)		(3,008	)
递延收入		(16,231	)		(37,705	)
经营租赁负债		(13,724	)		(12,213	)
经营活动使用的净现金流量		(263,685	)		(301,032	)

投资活动产生的现金流量：
购买固定资产		(4,797	)		(12,465	)
购买有市场流通的证券		(766,471	)		(754,689	)
市场证券的销售和到期		745,270			689,868
投资活动产生的净现金流出		(25,998	)		(77,286	)

筹资活动产生的现金流量：
通过市场定价发行普通股筹集的净收益		176,929			16,184
来自行权期权的收益		4,832			5,604
3. Based on my knowledge, the financial statements, and other financial information included in this report, fairly present in all material respects the financial condition, results of operations and cash flows of the registrant as of, and for, the periods presented in this report;		1,669			2,051
筹资活动产生的现金净额		183,430			23,839
现金、现金等价物和受限制的现金等价物净减少		(106,253	)		(354,479	)
期初现金、现金等价物和受限制的等价物		240,353			535,463
现金、现金等价物和受限现金等价物，期末	$	134,100		$	180,984


3.1		Second Amended and Restated Certificate of Incorporation of the Registrant. (incorporated by reference to the Registrant's Annual Report on Form 10-K (File No. 001-37766) filed with the Securities and Exchange Commission on February 22, 2024).
3.2		Second Amendment to the Second Amended and Restated Certificate of Incorporation of the Registrant dated June 12, 2024 (incorporated by reference to the Registrant's Current Report on Form 8-K (File No. 001-37766) filed with the Securities and Exchange Commission on June 13, 2024).

3.3		Second Amended and Restated By-laws of the Registrant. (incorporated by reference to Exhibit 3.1 to the Registrant's Quarterly Report on Form 10-Q (File No. 001-37766), filed with the Securities and Exchange Commission on May 7, 2020).

31.1		Certification of the Chief Executive Officer pursuant to Rules 13a-14(a) or 15d-14(a) of the Securities Exchange Act of 1934, as adopted pursuant to Section 302 of the Sarbanes-Oxley Act of 2002. (1)

31.2		Certification of the Chief Financial Officer pursuant to Rules 13a-14(a) or 15d-14(a) of the Securities Exchange Act of 1934, as adopted pursuant to Section 302 of the Sarbanes-Oxley Act of 2002. (1)

32.1		Certifications pursuant to 18 U.S.C. Section 1350, as adopted pursuant to Section 906 of The Sarbanes-Oxley Act of 2002, by John M. Leonard, M.D., President and Chief Executive Officer of the Company, and Edward J. Dulac III, Executive Vice President, Chief Financial Officer of the Company. (2)

101.INS		Inline XBRL Instance Document (1)

101.SCH		Inline XBRL Taxonomy Extension Schema With Embedded Linkbase Documents. (1)

104		Cover Page Interactive Data File (formatted as inline XBRL with applicable taxonomy extension information contained in Exhibits 101) (1)


		INTELLIA THERAPEUTICS, INC.

		By:		/s/ John M. Leonard
				John M. Leonard, M.D.
				President and Chief Executive Officer
				(Principal Executive Officer)

		By:		/s/ Edward J. Dulac III
				Edward J. Dulac III
				Executive Vice President, Chief Financial Officer
				(Principal Financial Officer)

		By:		/s/ Michael P. Dube
				Michael P. Dube
				Vice President, Chief Accounting Officer
				(Principal Accounting Officer)