Muzastotug

-掩蔽型抗CTLA-4安全抗体SAFEbody® ADG126（muzastotug）联合抗PD-1针对转移性微卫星稳定型（MSS）结直肠癌（CRC）治疗，在更高剂量、更高频率的多次重复给药方案中验证其临床获益，数据凸显了潜在同类最佳- -将正在进行的针对MSS CRC 2期与 PD-1的联合剂量扩展队列扩大到超过50名患者，其中包括启动新的20 mg/kg的起始负荷剂量组，预计在2024年公布数据- -安全抗体SAFEbody掩蔽技术通过与Exelixis和赛诺菲的合作进一步获得验证，表明天演技术平台在抗体偶联药物、双特异性与单克隆抗体等领域具有广泛的适用性- -现金结余约1.1亿美元，可支持公司至2026年的运营- 中国苏州和美国圣地亚哥 2024年4月1日 /美通社/ -- 天演药业（以下简称"公司"或"天演"）（纳斯达克股票代码：ADAG）是一家平台驱动的临床阶段生物制药公司，致力于发现并开发以原创抗体为基石的新型疗法。公司今日公布了2023年全年的财务业绩及最新业务进展。 天演首席执行官、董事长兼研发总裁罗培志博士表示： "安全抗体SAFEbody精准掩蔽平台技术一直是公司的价值核心，它能够拓宽包括双特异性T细胞衔接器以及抗体偶联药物在内基于抗体的多款疗法的治疗指数，以实现针对实体瘤更好的疗效。" 他指出： "关于临床产品管线，我们始终坚信，通过实现更高剂量更高频率的安全多次重复给药，CTLA-4疗法可以联合抗PD-1及其他疗法成为广谱抗癌疗法的基石。借助安全抗体SAFEbody平台增强肿瘤微环境下CTLA-4介导的调节性T细胞（Treg）清除效力，与纳武利尤单抗(Nivolumab)+伊匹木单抗(Ipilimumab)联用相比，ADG126与PD-1联用的治疗指数显著提升高达30倍，从而充分释放抗CTLA-4免疫疗法的潜能。" "值得一提的是，我们新启动的负荷剂量给药方案能让掩蔽型抗CTLA-4在肿瘤内快速达到激活抗体的稳态浓度，迅速启动CTLA-4通路与PD-1通路的肿瘤免疫协同效应，抑制肿瘤生长。基于10 mg/kg的重复给药剂量下仅出现有限的3级治疗相关不良事件和极低的迟发型毒性，从而实现在快速启动早期肿瘤抑制以及长期生存的临床获益。今年将陆续公布ADG126联用疗法针对MSS CRC的剂量扩展队列更多临床成果。" 产品管线亮点 Ib/2期数据表明，掩蔽型安全抗体SAFEbody ADG126结合独特的CTLA-4表位，基于CTLA-4的生物学基础，靶向肿瘤组织内调节性T细胞（Tregs）与默沙东抗PD-1药物帕博利珠单抗（KEYTRUDA®）联合疗法在针对MSS CRC、经PD-1治疗失败后出现进展以及PD-L1低表达肿瘤中显示出同类最佳潜力。 在2024年美国临床肿瘤学会胃肠道癌症（ASCO-GI）研讨会上公布的ADG126联合帕博利珠单抗（200 mg，每三周一次）的剂量递增与剂量扩展队列试验结果表明，ADG126在6 mg/kg至10 mg/kg的剂量范围内对经过大量多线治疗的晚期/转移性患者（N=46）具有差异化的安全性： 观察到有限的剂量依赖性毒性。 46名患者中，5名（10.8%）出现3级治疗相关不良事件（TRAE），未出现4级与5级治疗相关不良事件，中断率为6.5%（3/46）。 在针对不同肿瘤类型的剂量递增试验中，从3名接受剂量水平为10 mg/kg且每3周给药的ADG126治疗的患者身上观察到两例确认的部分缓解（PR），其中一名为经PD-1治疗耐药的宫颈癌患者，另一名子宫内膜癌患者。由此启动该给药方案的扩展队列。两例已确认的部分肿瘤缓解已持续超过一年，同时治疗方案显示了优异的安全性。 在针对MSS CRC的剂量扩展试验中，12名无肝转移的可评估患者接受剂量水平为10 mg/kg且每3周给药的强效治疗； 从其中9名无腹膜和肝转移的患者身上观察到两例确认的部分缓解，该组患者的总缓解率为22%。 这9名患者中有7名出现病情稳定（SD），总疾病控制率100%（2例部分缓解，7例病情稳定）。 根据Simon的两阶段设计，基于临床结果将该剂量水平的试验计划推进至第二阶段。 在对这些无肝和腹膜转移的MSS CRC患者的无进展生存期（PFS）初步分析中，接受10 mg/kg两个给药频率（每3周给药（n=9）和每6周给药一次（n=6））的ADG126治疗的患者的PFS中位数为7个月。随着一个更大型的患者队列在10 mg/kg、每3周给药试验中接受评估，ADG126联合帕博利珠单抗的持久临床疗效将得到进一步检验。 美国临床肿瘤学会胃肠道癌症研讨会后，天演公布了ADG126临床试验项目的进展和拓展，正在进行的2期剂量扩展队列将扩大到超过50名MSS CRC患者。项目的临床开发更新包含以下内容 ： 公司宣布正在进行的评估ADG126 10 mg/kg 每3周一次联合帕博利珠单抗治疗MSS CRC的2期剂量扩展队列已在2023年第四季度完成处于Simon两阶段设计的第二阶段的额外新增的12名患者入组。以上第二阶段的结果有望进一步验证近期在2024年美国ASCO-GI研讨会上公布的该队列第一阶段研究数据。 鉴于ADG126的安全性，天演还启动了针对20 mg/kg负荷剂量下ADG126联合帕博利珠单抗治疗晚期/转移性癌症患者的评估。公司目前正对这一给药方案进行安全性评估，并计划在随后开展的美国和亚太地区MSS CRC患者的扩展队列中评估20 mg/kg负荷剂量后10 mg/kg每3周一次维持剂量下联合帕博利珠单抗治疗的有效性。 公司已获国家药品监督管理局药品审评中心（CDE）批准于中国启动ADG126联合帕博利珠单抗的临床评估。这将有利于天演在和默沙东临床合作项目上于更多MSS CRC患者群体及潜在其他肿瘤类型中评估该联合疗法的疗效。 此外，近期公司在中国已启动开展针对晚期/转移性癌症患者进行 ADG126 30 mg/kg 每3周一次单药治疗评估，以确定 ADG126 单药治疗的潜在最大耐受剂量。 Ib/2 期数据表明，靶向独特表位的抗 CTLA-4 非掩蔽型新表位抗体 NEObody™ ADG116 在单一疗法以及与抗 PD-1 的联合疗法中均显示出良好的安全性与临床缓解。 ADG116单一疗法在最高剂量达到15mg /kg（N=59）的试验中显示出良好的安全性，并且其总缓解率（ORR）达到13%（3/23可评估），包括在多个不同肿瘤类型的患者中观察到确认的持久肿瘤缓解。 与抗PD-1疗法（N=22）的联合治疗试验结果表明，在剂量水平为3 mg/kg且每6周给药一次的剂量递增试验中，ADG116展现出可控的安全性与令人鼓舞的有效性。正在进行的联合治疗队列中观察到临床缓解，其中，一位头颈部鳞状细胞癌（HNSCC）患者在剂量水平为3mg /kg（最初每3周给药一次，然后每6周给药一次）的ADG116与特瑞普利单抗联合治疗的重复给药试验中观察到持续近两年的持久完全缓解（CR）（ORR = 20%；1/5可评估）。此外，一位MSS CRC患者在ADG116（剂量水平为3mg /kg，每6周给药一次）与特瑞普利单抗联合治疗的重复给药试验中观察到初步部分缓解，进一步验证与靶向独特的CTLA-4表位有关的临床效益和调节性T细胞清除对疗效的关键意义。 ADG116已观察到临床疗效，并准备在合理配备资源后进入更深入的临床开发。 经过 Fc 端优化的抗 CD137 IgG1 掩蔽型POWERbody TM 强力抗体ADG206针对晚期/转移性肿瘤患者的临床I期正在进行中： 正在进行的 1 期临床试验已招募 10名患者，以评估新一代抗 CD137 候选药物的安全性、有效性和耐受性。目前正在开展剂量水平为3 mg/kg且每3周给药一次的剂量递增试验。尚未达到最大耐受剂量（MTD）。 临床前数据表明，ADG206在多种肿瘤模型的单药治疗中具有良好的耐受性与稳定的抗肿瘤活性，在最大耐受剂量为 0.1 mg/kg每三周一次给药时，激活抗体对CD137激动型活性和T细胞共刺激比基准抗体（urelumab类似物）强4倍。 新一代抗CD137候选抗体ADG206是首个进入临床开发阶段的经过Fc端优化的掩蔽POWERbody™强力抗体候选药物，结合公司精准掩蔽、Fc端优化与创新表位技术，以应对抗CD137疗法的安全性与有效性挑战。 商务合作 Exelixis ： 根据双方为开发原创掩蔽型抗体偶联药物而达成的技术授权协议，2023年6月，天演在第二个合作项目中成功筛选到目标安全抗体SAFEbody®候选药物，并获得一笔来自Exelixis的300万美元里程碑付款。 赛诺菲 ： 天演与赛诺菲合作开发双特异性和单克隆SAFEbody®候选抗体，利用天演的安全抗体SAFEbody精准掩蔽技术研发临床前候选抗体，由赛诺菲进行开发和商业化。此项合作于2022年3月公布，包括一笔1750万美元的首付款，用于首先启动两个项目，和一笔提名额外两个项目的附加费用，还包括最高可达25亿美元的潜在里程碑付款，以及分级特许权使用费。 罗氏： 罗氏赞助并开展一项跨国1b/2期临床试验，评估ADG126联合阿替利珠单抗和贝伐珠单抗之三联免疫疗法在晚期肝细胞癌（HCC）的一线治疗中的效用。天演保留对ADG126的全球开发与商业化权利。 董事会人员变更 除非另有说明，以下天演董事会变动将于20-F形式的2023年公司年度报告（"2023年报"）提交后正式生效： Grawunder博士将以独立董事的身份加入公司董事会，并成为审计委员会和战略委员会成员。Grawunder博士是瑞士/德国资深生命科学企业家,在治疗性抗体开发行业拥有超过20年的经验。 现独立董事朱力博士将成为董事会薪酬委员会成员。 张耀梁先生、Mervyn Turner博士与谭文健先生的董事任期将继续延长。 现独立董事，审计委员会、薪酬委员会与提名和公司治理委员会成员利民博士，以及生物信息科技高级副总裁，现董事会成员李艳女士因个人原因将辞去董事会和相关委员会成员职务。李艳女士将于2024年6月15日正式退出董事会，未来将继续担任董事会观察员。利民博士与李艳女士均确认与董事会不存在分歧，关于二人的退出没有其他需要公司股东关注的问题。 公司董事会想借此机会向利民博士与李艳女士表示真诚的谢意，感谢他们在任期内为董事会所做的宝贵贡献。2023年年报对新任命董事的背景及委任条款均有详细介绍。 2024 年里程碑与可持续至 2026 年的现金储备 坚持现有规划，严格管控现金，天演预计公司资金可支持公司到2026年的运营活动，并预期实现以下里程碑： 正在进行的ADG126联合帕博利珠单抗的1b/2期临床试验，包括MSS CRC剂量扩展队列数据预计将在2024年逐步公布： 第一部分10 mg/kg、每3周给药 （n=12）和10mg /kg、每6周给药（n=10）可评估患者的随访研究数据 第二部分10 mg/kg、每3周给药（n=12）的患者数据 应美国FDA Optimus计划的要求评估不同剂量包括20 mg/kg负荷剂量 重复给药的安全性数据 MSS CRC患者（n~10）的剂量扩展数据 中国地区的更多患者数据（n≥10） 达成更多技术授权合作和/或里程碑。 财务 亮点 现金和现金等价物 现金和现金等价物2022年12月31日约1.438亿美元，2023年12月31日约1.099亿美元。截至2023年12月31日，公司从中国境内各商业银行获得的人民币贷款由2022年12月31日的2,780万美元减少至2023年12月31日的2,190万美元。从贷款中所获得资金主要用来支付公司在中国境内产生的研发费用。 净收入 净收入相较于2022年同期的930万美元增加到2023年12月31日的1,810万美元。净收入同比增长约95%。该增长包含了因公司履行了与Exelixis和赛诺菲分别签订的技术合作和授权协议中的履约义务而确认的净收入。净收入也包含了于2023年6月从Exelixis收到的300万美元里程碑付款。 研发费用 研发费用相较于2022年同期的8,130万美元下降到2023年12月31日的3,660万美元。研发费用同比下降了约55%。该下降源于公司重点优先发展针对抗CTLA-4的安全抗体疗法的ADG126临床项目。 管理费用 管理费用相较于2022年同期的1,190万美元下降到2023年12月31日的870万美元。管理费用的下降主要是由于成本控制措施所带来的人工及办公成本的减少。 其他净营业收入 截至2023年12月31日的其他净营业收入约350万美元。其他净营业收入包含了从一家合同制造商处获得的，与一份临床前项目外包协议相关的一次性补偿款。 净亏损 净亏损相较于2022年同期的8,000万美元下降到2023年12月31日的1,890万美元。 流通在外普通股 截至2023年12月31日，公司流通在外的普通股为55,145,839股。每一股美国存托股票(ADS)可换算为1.25股普通股。 非美国通用会计准则（ Non-GAAP ）下的 亏损 非美国通用会计准则下的净亏损定义为该期间的美国通用会计准则下的净亏损剔除股权激励费用。该金额从2022年同期的净亏损6,950万美元，下降至2023年12月31日的1,170万美元。请参阅本新闻稿中题为"美国通用会计准则（GAAP）和非美国通用会计准则（Non-GAAP）下的业绩调节表"部分了解详情。 天演药业使用Non-GAAP净亏损和Non-GAAP的每股普通股净亏损，用于评估本公司的经营成果，以及财务和经营决策。本公司认为，Non-GAAP净亏损和Non-GAAP的每股普通股净亏损有助于识别本公司业务的基本趋势，而这些趋势可能因本公司计入本期间亏损的某些费用的影响而扭曲。本公司认为，Non-GAAP净亏损和Non-GAAP的每股普通股净亏损提供了有关其经营成果的有用信息，整体提升了对其过去业绩和未来前景的全面了解，并使管理层在财务和运营决策中使用的关键指标更具可见性。 对于本年度的Non-GAAP财务指标的衡量，天演药业使用的Non-GAAP净亏损和Non-GAAP的每股普通股净亏损不应单独被考虑，也不应被视为该年度营业利润、净亏损或任何其他业绩衡量指标的替代品，或作为其经营业绩的衡量指标。公司鼓励投资者审阅该年度的Non-GAAP净亏损和Non-GAAP的每股普通股净亏损，并审阅最直接可比的美国通用会计准则下财务指标的调整过程。此处所列期间的Non-GAAP净亏损和Non-GAAP的每股普通股净亏损可能无法与其他公司提供的类似名称的财务指标相比较。其他公司可能会以不同的方式计算类似的财务指标，从而限制了它们作为公司可比数据的有用性。天演药业鼓励投资者和其他人全面审阅本公司的财务信息，而不是仅仅关注于单一的财务指标。 本年度计算的净利润指标下Non-GAAP净亏损和Non-GAAP的每股普通股净亏损，不包括股权激励费用。股权激励费用是向员工授予股票激励所产生的非现金费用。我们认为美国通用会计准则和非美国通用会计准则的调整信息能对管理层和投资人在进行公司运营表现的同期比较以及同业比较时有所助益。其原因有：（i）在某特定期间内的股权激励费用与公司的运营表现未必直接相关；（ii）因公司授予新的股权激励计划的时间安排，股权激励费用在不同期间内可能会发生较大变化；以及，（iii）其他公司可能采取不同的股权激励形式或者使用不同的估值方法。 请参阅本公告结尾的 "美国通用会计准则（GAAP）和非美国通用会计准则（Non-GAAP）下的业绩调节表"，获取本年度/期间Non-GAAP净亏损和Non-GAAP的每股普通股净亏损的完整的调整过程。 关于天演药业 天演药业（纳斯达克股票代码：ADAG）是平台驱动并拥有自主平台产出的临床产品开发阶段的生物制药公司，公司致力于发现并开发以原创抗体为基石的新型癌症免疫疗法。借力于计算生物学与人工智能，凭借其全球首创的三体平台技术（新表位抗体NEObody™，安全抗体SAFEbody ® 及强力抗体POWERbody™），天演药业已建立起聚焦于新型肿瘤免疫疗法的独特原创的抗体产品线，以解决尚未满足的临床需求。天演已和多个全球知名合作伙伴达成了战略合作关系，并以其多种原创前沿科技为合作伙伴的新药研发赋能。 如需了解更多信息，请访问： https://investor.adagene.com 并关注天演药业 微信 、 领英 及 推特 官方帐号。 SAFEbody ® 为天演在美国、中国、澳大利亚、日本、新加坡和欧盟的注册商标。 安全港声明 本新闻稿包含前瞻性陈述，包括关于临床数据对患者的潜在影响的陈述，以及天演药业的推进和预期的临床前活动、临床开发、监管里程碑以及其候选产品的商业化。由于各种重要因素，包括但不限于天演药业证明其候选药物的安全性和有效性的能力，实际结果可能与前瞻性陈述中所示的结果存在重大差异；其候选药物的临床结果，可能不支持进一步开发或监管批准；相关监管机构就天演药业候选药物的监管批准做出决定的内容和时间；如果获得批准，天演药业为其候选药物取得商业成功的能力；天演药业为其技术和药物获得和维持知识产权保护的能力；天演药业依赖第三方进行药物开发、制造和其他服务；天演药业有限的经营历史以及天演药业获得额外运营资金以及完成其候选药物的开发和商业化的能力；天演药业在其现有战略伙伴关系或合作之外签订额外合作协议的能力，以及COVID-19 流行对天演药业临床开发、商业和其他运营的影响，以及在天演提交给美国证券交易委员会的20-F形式的2022年的年度报告中"风险因素"部分更充分讨论的那些风险。所有前瞻性陈述均基于天演药业当前可获得的信息，除非依照法律之可能要求，天演药业不承担因新信息、未来事件或其他原因而公开更新或修改任何前瞻性陈述的义务。 未经审计的合并资产负债表（美国通用会计准则） 截止至 2022 年 12 月 31 日 截止至 2023 年 12 月 31 日 US$ US$ 资产 流动资产： 现金及现金等价物 143,758,678 109,934,257 应收关联方款项 619,432 222,027 其他流动资产和预付账款 4,937,323 3,287,445 流动资产总额 149,315,433 113,443,729 固定资产 2,782,963 1,835,121 使用权资产 191,877 365,103 其他非流动资产 109,572 84,885 资产总额 152,399,845 115,728,838 负债和股东权益 流动负债： 应付账款 3,666,124 3,093,752 合同负债 15,107,276 — 应付关联方款项 19,323,337 16,714,326 预提及其他流动负债 3,212,809 3,001,508 应付所得税 — 52,884 短期借款 10,768,745 4,235,673 一年内到期的长期借款 2,850,128 4,161,549 一年内到期的租赁负债 151,983 195,955 流动负债总额 55,080,402 31,455,647 长期借款 14,146,541 13,540,034 租赁负债 53,834 173,660 其他非流动负债 28,718 — 负债总额 69,309,495 45,169,341 股东权益： 股本 5,497 5,547 库存股 (4) (4) 资本公积 342,739,268 350,105,518 其他综合亏损 (849,305) (1,800,088) 累计亏损 (258,805,106) (277,751,476) 股东权益总额 83,090,350 70,559,497 负债和股东权益总额 152,399,845 115,728,838 未经审计的合并利润表 （美国通用会计准则） 截至 12 月 31 日的全年 2022 年 2023 年 US$ US$ 收入 技术许可合作收入 9,292,724 18,111,491 经营 费用 与收入 研发费用 (81,339,540) (36,639,146) 非关联方 (46,212,077) (33,978,642) 关联方 (35,127,463) (2,660,504) 管理费用 (11,873,867) (8,672,843) 其他净营业收入 — 3,480,632 营业亏损 (83,920,683) (23,719,866) 利息收入 377,501 4,283,085 利息费用 (693,323) (1,107,820) 其他净收入 2,168,388 1,843,437 汇兑损益 2,555,325 1,446,202 税前亏损 (79,512,792) (17,254,962) 所得税费用 (459,055) (1,691,408) 净亏损 (79,971,847) (18,946,370) 其他综合亏损 外币报表折算差异 (755,324) (950,783) 综合亏损总额 (80,727,171) (19,897,153) 净亏损 (79,971,847) (18,946,370) 归属于普通股股东净亏损总额 (79,971,847) (18,946,370) 用于计算每股普通股净损失的加权平均普通股股数： — 基本 54,135,084 54,737,530 — 稀释后 54,135,084 54,737,530 每股普通股净亏损 — 基本 (1.48) (0.35) — 稀释后 (1.48) (0.35) 美国通用会计准则（ GAAP ）和非美国通用会计准则（ Non-GAAP ）下的业绩调节表 截至 12 月 31 日的全年 2022 年 2023 年 US$ US$ 美国通用会计准则下归属于普通股股东净亏损总额 (79,971,847) (18,946,370) 调整： 股权激励费用 10,520,282 7,271,700 非美国通用会计准则下的普通股股东净亏损总额 (69,451,565) (11,674,670) 用于计算每股普通股净损失的加权平均普通股股数： — 基本 54,135,084 54,737,530 — 稀释后 54,135,084 54,737,530 非美国通用会计准则下的每股普通股净亏损 — 基本 (1.28) (0.21) — 稀释后 (1.28) (0.21)

- Data for masked anti-CTLA-4 SAFEbody® ADG126 (muzastotug) highlight best-in-class therapeutic index and demonstrate clinical benefits in metastatic microsatellite-stable (MSS) colorectal cancer (CRC) with higher, more frequent and repeat dosing of anti-CTLA-4 therapy in combination with anti-PD-1 - - Ongoing combination phase 2 dose expansion in MSS CRC increased to over 50 patients, including initiation of a new, unprecedented 20 mg/kg loading dose regimen, with data anticipated during 2024 - - Validation of SAFEbody masking technology by Exelixis and Sanofi showcases versatility of platform across modalities including antibody-drug conjugates, bi-specific and monoclonal antibodies - - Cash balance of approximately US$110 million funds streamlined operations into 2026 - SAN DIEGO and SUZHOU, China, March 29, 2024 (GLOBE NEWSWIRE) -- Adagene Inc. (“Adagene”) (Nasdaq: ADAG), a platform-driven, clinical-stage biotechnology company transforming the discovery and development of novel antibody-based therapies, today reported financial results for the full year 2023 and provided corporate updates. “The SAFEbody precision masking technology platform remains at the core of our value proposition given its ability to enhance next generation antibody-based therapies that span modalities, including bispecific T-cell engagers and antibody-drug conjugates, both areas where a wider therapeutic index is needed to fully address solid tumors,” said Peter Luo, Ph.D., Chairman, CEO and President of R&D at Adagene. He continued, “Turning to our clinical pipeline, we remain steadfast in our belief that anti-CTLA-4 therapy can be reimagined as a cornerstone of cancer care by enabling higher, more frequent and repeated doses in combination with anti-PD-1 and other therapies. With our SAFEbody platform, we have a 30-fold improved therapeutic index for ADG126 and a mechanism enabling CTLA-4 mediated intratumoral Treg depletion. We are taking anti-CTLA-4 therapy to a new level unleashing this proven immunotherapy where safety has limited its therapeutic potential.” “In particular, our new loading dose regimen in late-stage MSS CRC patients enables our masked anti-CTLA-4 therapy to reach a high initial concentration, close to the steady state of activated species within the tumor tissue to immediately engage the CTLA-4 pathway and stop the tumor from aggressive growth. This loading dose strategy, together with repeated maintenance doses at 10 mg/kg showing limited treatment-related grade 3 and no higher toxicities with minimal late-onset toxicities for ADG126, is expected to engage the CTLA-4 target consistently, thereby maintaining and sustaining clinical benefit, via both the initial response rate and prolonged survival benefit. We look forward to reporting more clinical results for the ADG126 combination dose expansion in MSS CRC later this year.” PIPELINE HIGHLIGHTS Phase 1b/2 data for ADG126, a masked anti-CTLA-4 SAFEbody targeting a unique epitope of CTLA-4 on regulatory T cells (Tregs) in tumor tissue as driven by the fundamental biology of CTLA-4, showed a potential best-in-class profile in combination with Merck’s anti-PD-1 therapy, KEYTRUDA® (pembrolizumab)*, in MSS CRC, PD-1 experienced and PD-L1 low tumors: Results presented at the 2024 American Society of Clinical Oncology (ASCO) Gastrointestinal (GI) Symposium from dose escalation and dose expansion cohorts of ADG126 in combination with pembrolizumab (200 mg/Q3W) demonstrated a differentiated safety profile for ADG126 at doses from 6 mg/kg to 10 mg/kg in heavily pre-treated advanced/metastatic patients (N=46): Limited dose-dependent toxicities were observed.Grade 3 TRAEs occurred in 5/46 patients (10.8%), with no Grade 4 or 5 TRAEs and a discontinuation rate of 6.5% (3/46). In dose escalation across tumor types, two partial confirmed responses (PRs) were observed among the three patients treated with ADG126 10 mg/kg Q3W, which triggered expansion cohorts at this dosing regimen. One of the patients had PD-1 refractory cervical cancer and the other had endometrial cancer. Both confirmed PRs are sustained after more than one year with repeat dosing while maintaining robust safety profiles.In dose expansion of patients with MSS CRC, 12 evaluable patients without liver metastases were treated at the active, potent dose of 10 mg/kg Q3W: Two confirmed PRs were observed in nine of these patients without peritoneal and liver metastases, resulting in an overall response rate of 22% in this subset.An additional seven of these nine patients experienced stable disease (SD) for an overall disease control rate of 100% (2 PRs and 7 SD).Observation of these clinical activities triggered further expansion into the second stage of the Simon’s 2-stage design for this dose level. In a preliminary progression-free survival (PFS) analysis of those MSS CRC patients free of liver and peritoneal metastasis, a median PFS of seven months was observed in those treated with ADG126 10 mg/kg at two dosing frequencies pooled together [every three weeks (n=9) and every six weeks (n=6)]. The durable clinical activity of ADG126 in combination with pembrolizumab will continue to be evaluated as a larger cohort of subjects becomes evaluable at the 10 mg/kg Q3W dose level.Following the ASCO GI Symposium, Adagene announced progress and expansion of the ADG126 clinical program, which increases the ongoing phase 2 dose expansion in MSS CRC to over 50 patients. Updates included: Enrollment of 12 additional patients in the second stage of the Simon’s 2-stage design was completed in the fourth quarter of 2023 for the ongoing phase 2 dose expansion cohort evaluating ADG126 10 mg/kg Q3W in combination with pembrolizumab in MSS CRC. These Part 2 results will supplement data from Part 1 of the dose expansion in MSS CRC as recently presented at the 2024 ASCO GI Symposium.Given the ADG126 safety profile, evaluation of the 20 mg/kg loading dose regimen has been initiated in combination with pembrolizumab in patients with advanced/metastatic cancer. Pending outcome of the ongoing safety evaluation, the company plans to evaluate the efficacy profile of the loading dose regimen in expansion cohorts, followed by maintenance with ADG126 10 mg/kg Q3W in combination with pembrolizumab at sites in the US and Asia Pacific.Clearance received from China’s Center for Drug Evaluation to initiate clinical evaluation of ADG126 in combination with pembrolizumab. This enables the company to broaden its dose expansion cohorts for MSS CRC at selected dosing regimens, and potentially in other tumor types, in its clinical trial collaboration and supply agreement with Merck. Additionally, the company recently initiated dosing of a small number of patients with advanced/metastatic cancers at 30 mg/kg ADG126 monotherapy Q3W in China to define the potential maximum tolerated dose of ADG126 monotherapy. Phase 1b/2 data for ADG116, an unmasked anti-CTLA-4 NEObody™ targeting a unique epitope, showed a favorable safety profile and clinical responses, both in monotherapy and in combination with anti-PD-1: ADG116 monotherapy has demonstrated a favorable safety profile at doses up to 15 mg/kg (N=59) and an overall response rate (ORR) of 13% (3/23 evaluable), including confirmed and durable PRs in multiple tumor types.In combination with anti-PD-1 therapy, ADG116 (3 mg/kg Q6W) (N=22) showed a manageable safety profile and an encouraging efficacy profile in dose escalation. Clinical responses from the combination cohorts include a complete response (CR) sustained for nearly two years in a head and neck squamous cell carcinoma (HNSCC) patient dosed with repeat cycles of ADG116 3 mg/kg (initially every three weeks, then every six weeks) plus toripalimab (ORR = 20%; 1/5 evaluable). An initial PR was also observed in a patient with MSS CRC dosed with repeat cycles of ADG116 3 mg/kg every six weeks plus toripalimab, further demonstrating the potential clinical benefit associated with targeting a unique epitope of CTLA-4 and the essential effects of Treg depletion.ADG116 is clinically active and ready to advance into further clinical development as resources allow. Phase 1 evaluation is ongoing for ADG206, a masked, IgG1 FC-enhanced anti-CD137 POWERbody™ in patients with advanced/metastatic tumors: Adagene has enrolled 10 patients in an ongoing phase 1 trial of ADG206 to evaluate safety, efficacy and tolerability profiles for this next generation anti-CD137 candidate. Dose escalation continues with a cohort ongoing at 3 mg/kg Q3W. No maximum tolerated dose (MTD) has yet been reached.Preclinical data demonstrated that ADG206 was well tolerated and had robust anti-tumor activity as a single agent in multiple tumor models, with 4-fold stronger anti-CD137 agonistic activity of its activated form than a benchmark antibody (urelumab analog) that displayed dose-dependent liver toxicity with an MTD of 0.1 mg/kg Q3W.ADG206 is the company’s first SAFEbody with Fc enhancement, called a POWERbody, to advance into clinic. ADG206 combines SAFEbody precision masking, Fc enhancement and targeting of a unique epitope to solve the safety and efficacy challenges of anti-CD137 therapies, reflecting versatility of Adagene’s dynamic antibody discovery and masking platform. COLLABORATIONS Exelixis: In June 2023, Adagene received a US$3.0 million milestone payment from Exelixis for the successful nomination of lead SAFEbody candidates for the second collaboration program under a technology licensing agreement to develop novel masked antibody-drug conjugate candidates. Sanofi: Adagene and Sanofi are collaborating to develop both bispecific and monoclonal SAFEbody antibody candidates, preparing preclinical candidates using Adagene’s SAFEbody precision masking technology for future development and commercialization by Sanofi. The collaboration announced in March 2022 included an upfront payment of US$17.5 million for the initial two programs, an option fee for two additional programs, potential milestone payments of up to US$2.5 billion, and tiered royalties. Roche: Roche is sponsoring and conducting a phase 1b/2 multi-national trial to evaluate ADG126 in a triple combination with atezolizumab and bevacizumab in first-line hepatocellular carcinoma (HCC). Adagene retains global development and commercialization rights to ADG126. CHANGE OF BOARD OF DIRECTORS The following changes to Adagene’s Board of Directors will be effective upon the filing of its 2023 annual report on Form 20-F (“2023 Annual Report”), unless otherwise noted: Dr. Ulf Grawunder will join the Board of Directors (the “Board”) as an independent director and serves as a member of Audit Committee and Strategy Committee of the Board. Dr. Grawunder is an experienced Swiss/German life-science entrepreneur with over 20 years of experience in the therapeutic antibody development industry.Dr. Zhu Li, currently an independent director, will serve as a member of Compensation Committee of the Board.Term of Mr. Andy (Yiu Leung) Cheung, Dr. Mervyn Turner and Mr. Man Kin (Raymond) Tam will be extended.Dr. Min Li, currently an independent director and a member of Audit Committee, Compensation Committee and Nominating and Corporate Governance Committee, and Ms. Yan Li, Senior Vice President of Bioinformatics and Information Technology and currently a member of the Board, will resign as directors of the Board and membership of the various committees, as applicable, due to person reasons. Ms. Yan Li's resignation from the board will be effective on June 15, 2024, after which she will continue to serve as an observer to the Board. Each of Dr. Min Li and Ms. Yan Li confirmed that he or she has no disagreement with the Board, and there is no other matter relating to his or her resignation that needs to be brought to the attention of the shareholders of the company. The Board would like to take this opportunity to express their sincere gratitude to Dr. Min Li and Ms. Yan Li for their valuable contributions to the Board during their tenure. Background of the newly appointed directors and their terms are detailed in the 2023 Annual Report. 2024 MILESTONES & CASH RUNWAY INTO 2026 Consistent with ongoing initiatives to prudently manage its cash balance, Adagene expects its current cash balance to fund activities into 2026, with the following milestones: Data from the ongoing phase 1b/2 clinical trial of ADG126 in combination with pembrolizumab, including dose expansion cohorts in MSS CRC, are anticipated throughout 2024: Follow up of Part 1 evaluable patients at 10 mg/kg Q3W (n=12) and 10 mg/kg Q6W (n=10)Data from Part 2 patients at 10 mg/kg Q3W (n=12)Evaluation of 20 mg/kg loading doses for Project Optimus requirements: Safety data with repeat dosesDose expansion in MSS CRC (n~10) Additional patients in China (n≥10) Additional technology licensing agreement(s) and/or milestone(s). FINANCIAL HIGHLIGHTS Cash and Cash EquivalentsCash and cash equivalents were US$109.9 million as of December 31, 2023, compared to US$143.8 million as of December 31, 2022. Total borrowings from commercial banks in China (denominated in RMB) decreased to US$21.9 million as of December 31, 2023 from US$27.8 million as of December 31, 2022. The associated loan proceeds were primarily used to pay for the company’s R&D activities in China. Net Revenue:Net revenue was US$18.1 million for the year ended December 31, 2023, compared to US$9.3 million in 2022. The increase of approximately 95% reflects net revenue recognized upon fulfillment of certain performance obligations associated with the collaboration and technology licensing agreements with Exelixis and Sanofi, respectively. Net revenue also included a milestone payment of US$3.0 million from Exelixis received in June 2023. Research and Development (R&D) Expenses: R&D expenses were US$36.6 million for the year ended December 31, 2023, compared to US$81.3 million in 2022. The decrease of approximately 55% in R&D expenses reflects clinical focus on and prioritization of the company’s masked, anti-CTLA-4 SAFEbody ADG126. Administrative Expenses:Administrative expenses were US$8.7 million for the year ended December 31, 2023, compared to US$11.9 million in 2022. The decrease was due to both a reduction in personnel and in office-related expenses as a result of cost-control measures. Other Operating Income, Net:Other operating income, net was US$3.5 million for the year ended December 31, 2023. Other operating income, net included a one-time compensation payment from a contract manufacturer for a preclinical-related outsourcing arrangement. Net Loss:Net loss attributable to Adagene Inc.’s shareholders was US$18.9 million for the year ended December 31, 2023, compared to US$80.0 million in 2022. Ordinary Shares Outstanding:As of December 31, 2023, there were 55,145,839 ordinary shares issued and outstanding. Each American depository share, or ADS, represents one and one quarter (1.25) ordinary shares of the company. Non-GAAP Net Loss:Non-GAAP net loss, which is defined as net loss attributable to ordinary shareholders for the period after excluding share-based compensation expenses, was US$11.7 million for the year ended December 31, 2023, compared to US$69.5 million in 2022. Please refer to the section in this press release titled “Reconciliation of GAAP and Non-GAAP Results” for details. Non-GAAP Financial MeasuresThe company uses non-GAAP net loss and non-GAAP net loss per ordinary shares for the year, which are non-GAAP financial measures, in evaluating its operating results and for financial and operational decision-making purposes. The company believes that non-GAAP net loss and non-GAAP net loss per ordinary shares for the year help identify underlying trends in the company’s business that could otherwise be distorted by the effect of certain expenses that the company includes in its loss for the year. The company believes that non-GAAP net loss and non-GAAP net loss per ordinary shares for the year provide useful information about its results of operations, enhances the overall understanding of its past performance and future prospects and allows for greater visibility with respect to key metrics used by its management in its financial and operational decision-making. Non-GAAP net loss and non-GAAP net loss per ordinary shares for the year should not be considered in isolation or construed as an alternative to operating profit, loss for the year or any other measure of performance or as an indicator of its operating performance. Investors are encouraged to review non-GAAP net loss and non-GAAP net loss per ordinary shares for the year and the reconciliation to their most directly comparable GAAP measures. Non-GAAP net loss and non-GAAP net loss per ordinary shares for the year here may not be comparable to similarly titled measures presented by other companies. Other companies may calculate similarly titled measures differently, limiting their usefulness as comparative measures to the company’s data. The company encourages investors and others to review its financial information in its entirety and not rely on a single financial measure. Non-GAAP net loss and non-GAAP net loss per ordinary shares for the year represent net loss attributable to ordinary shareholders for the year excluding share-based compensation expenses. Share-based compensation expense is a non-cash expense arising from the grant of stock-based awards to employees. The company believes that the exclusion of share-based compensation expenses from the net loss in the Reconciliation of GAAP and Non-GAAP Results assists management and investors in making meaningful period-to-period comparisons in the company's operating performance or peer group comparisons because (i) the amount of share-based compensation expenses in any specific period may not directly correlate to the company’s underlying performance, (ii) such expenses can vary significantly between periods as a result of the timing of grants of new stock-based awards, and (iii) other companies may use different forms of employee compensation or different valuation methodologies for their share-based compensation. Please see the “Reconciliation of GAAP and Non-GAAP Results” included in this press release for a full reconciliation of non-GAAP net loss and non-GAAP net loss per ordinary shares for the year to net loss attributable to ordinary shareholders for the year/period. About AdageneAdagene Inc. (Nasdaq: ADAG) is a platform-driven, clinical-stage biotechnology company committed to transforming the discovery and development of novel antibody-based cancer immunotherapies. Adagene combines computational biology and artificial intelligence to design novel antibodies that address globally unmet patient needs. The company has forged strategic collaborations with reputable global partners that leverage its SAFEbody® precision masking technology in multiple approaches at the vanguard of science. Powered by its proprietary Dynamic Precision Library (DPL) platform, composed of NEObody™, SAFEbody, and POWERbody™ technologies, Adagene’s highly differentiated pipeline features novel immunotherapy programs. The company’s SAFEbody technology is designed to address safety and tolerability challenges associated with many antibody therapeutics by using precision masking technology to shield the binding domain of the biologic therapy. Through activation in the tumor microenvironment, this allows for tumor-specific targeting of antibodies in tumor microenvironment, while minimizing on-target off-tumor toxicity in healthy tissues. Adagene’s lead clinical program, ADG126 (muzastotug), is a masked, anti-CTLA-4 SAFEbody that targets a unique epitope of CTLA-4 in regulatory T cells (Tregs) in the tumor microenvironment. ADG126 is currently in phase 1b/2 clinical studies in combination with anti-PD-1 therapy, particularly focused on Metastatic Microsatellite-stable (MSS) Colorectal Cancer (CRC). Validated by ongoing clinical research, the SAFEbody platform can be applied to a wide variety of antibody-based therapeutic modalities, including Fc enhanced antibodies, antibody-drug conjugates, and bi/multispecific T-cell engagers. For more information, please visit: https://investor.adagene.com. Follow Adagene on WeChat, LinkedIn and Twitter. SAFEbody® is a registered trademark in the United States, China, Australia, Japan, Singapore, and the European Union. *KEYTRUDA® is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Safe Harbor Statement This press release contains forward-looking statements, including statements regarding the potential implications of clinical data for patients, and Adagene’s advancement of, and anticipated preclinical activities, clinical development, regulatory milestones, and commercialization of its product candidates. Actual results may differ materially from those indicated in the forward-looking statements as a result of various important factors, including but not limited to Adagene’s ability to demonstrate the safety and efficacy of its drug candidates; the clinical results for its drug candidates, which may not support further development or regulatory approval; the content and timing of decisions made by the relevant regulatory authorities regarding regulatory approval of Adagene’s drug candidates; Adagene’s ability to achieve commercial success for its drug candidates, if approved; Adagene’s ability to obtain and maintain protection of intellectual property for its technology and drugs; Adagene’s reliance on third parties to conduct drug development, manufacturing and other services; Adagene’s limited operating history and Adagene’s ability to obtain additional funding for operations and to complete the development and commercialization of its drug candidates; Adagene’s ability to enter into additional collaboration agreements beyond its existing strategic partnerships or collaborations, and the impact of the outbreak of a widespread health epidemic on Adagene’s clinical development, commercial and other operations, as well as those risks more fully discussed in the “Risk Factors” section in Adagene’s annual report for the year of 2023 on Form 20-F filed with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Adagene, and Adagene undertakes no obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as may be required by law. Investor & Media Contact:Ami Knoefler650-739-9952ir@adagene.com FINANCIAL TABLES FOLLOW Unaudited Consolidated Balance Sheets December 31,2022December 31, 2023 US$US$ASSETS Current assets: Cash and cash equivalents143,758,678 109,934,257 Amounts due from related parties619,432 222,027 Prepayments and other current assets4,937,323 3,287,445 Total current assets149,315,433 113,443,729 Property, equipment and software, net2,782,963 1,835,121 Operating lease right-of-use assets191,877 365,103 Other non-current assets109,572 84,885 TOTAL ASSETS152,399,845 115,728,838 LIABILITIES AND SHAREHOLDERS’ EQUITY Current liabilities: Accounts payable3,666,124 3,093,752 Contract liabilities15,107,276 — Amounts due to related parties19,323,337 16,714,326 Accruals and other current liabilities3,212,809 3,001,508 Income tax payable— 52,884 Short-term borrowings10,768,745 4,235,673 Current portion of long-term borrowings2,850,128 4,161,549 Current portion of operating lease liabilities151,983 195,955 Total current liabilities55,080,402 31,455,647 Long-term borrowings14,146,541 13,540,034 Operating lease liabilities53,834 173,660 Other non-current liabilities28,718 — TOTAL LIABILITIES69,309,495 45,169,341 Commitments and contingencies Shareholders’ equity: Ordinary shares (par value of US$0.0001 per share; 640,000,000 shares authorized, and 54,065,709 shares issued and outstanding as of December 31, 2022; and 640,000,000 shares authorized, and 55,145,839 shares issued and outstanding as of December 31, 2023)5,497 5,547 Treasury shares, at cost (1 share as of December 31, 2022 and December 31, 2023)(4)(4)Additional paid-in capital342,739,268 350,105,518 Accumulated other comprehensive loss(849,305)(1,800,088)Accumulated deficit(258,805,106)(277,751,476)Total shareholders’ equity83,090,350 70,559,497 TOTAL LIABILITIES AND SHAREHOLDERS’ EQUITY152,399,845 115,728,838 Unaudited Consolidated Statements of Comprehensive Loss For the Year Ended December 31, 2022For the Year Ended December 31, 2023 US$US$Revenues Licensing and collaboration revenue9,292,724 18,111,491 Operating expenses and income Research and development expenses(81,339,540)(36,639,146)Third parties(46,212,077)(33,978,642)Related parties(35,127,463)(2,660,504)Administrative expenses(11,873,867)(8,672,843)Other operating income, net— 3,480,632 Loss from operations(83,920,683)(23,719,866)Interest income377,501 4,283,085 Interest expense(693,323)(1,107,820)Other income, net2,168,388 1,843,437 Foreign exchange gain, net2,555,325 1,446,202 Loss before income tax(79,512,792)(17,254,962)Income tax expense(459,055)(1,691,408)Net loss attributable to Adagene Inc.’s shareholders(79,971,847)(18,946,370)Other comprehensive loss Foreign currency translation adjustments, net of nil tax(755,324)(950,783)Total comprehensive loss attributable to Adagene Inc.’s shareholders(80,727,171)(19,897,153)Net loss attributable to Adagene Inc.’s shareholders(79,971,847)(18,946,370)Net loss attributable to ordinary shareholders(79,971,847)(18,946,370)Weighted average number of ordinary shares used in per share calculation: —Basic54,135,084 54,737,530 —Diluted54,135,084 54,737,530 Net loss per ordinary share —Basic(1.48)(0.35)—Diluted(1.48)(0.35) Reconciliation of GAAP and Non-GAAP Results For the Year Ended December 31, 2022For the Year Ended December 31, 2023 US$US$GAAP net loss attributable to ordinary shareholders(79,971,847)(18,946,370)Add back: Share-based compensation expenses10,520,282 7,271,700 Non-GAAP net loss(69,451,565)(11,674,670)Weighted average number of ordinary shares used in per share calculation: —Basic54,135,084 54,737,530 —Diluted54,135,084 54,737,530 Non-GAAP net loss per ordinary share —Basic(1.28)(0.21)—Diluted(1.28)(0.21)