ADG-106

- 抗 CTLA-4 候选抗体从设计上提升了治疗指数 30 倍以上，致力于 CTLA-4 介导调节性 T 细胞（ Treg ）清除以进一步提升患者疗效， 具备同类最佳潜力 - 安全抗体 SAFEbody ® ADG126 在 10 mg/kg 剂量下每 3 周给药一次与帕博利珠单抗联合，针对转移性微卫星稳定型（ MSS ）结直肠癌（ CRC ）的单臂 2 期试验中观察到强烈的疗效信号 - 根据 Simon 两阶段的 2 期单臂临床试验设计，基于 10 mg/kg 剂量每 3 周一次的给药频率，安全抗体 SAFEbody ® ADG126 与帕博利珠单抗联合疗法针对转移性微卫星稳定型结直肠癌拓展队列 正在入组第二阶段的 10 例 患者 - 罗氏启动了安全抗体 SAFEbody ® ADG126 原创三联强力疗法肝细胞癌一线治疗的随机 1b /2 期临床试验 -1.288 亿美元的现金可支持公司至 2025 年底的运营活动 中国苏州和美国圣地亚哥 2023年9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。公司今日公布了截至2023年6月30日止六个月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："目前我们自研的抗CTLA-4项目临床数据表明，通过合适的给药方案可提高抗CTLA-4疗法治疗指数并释放其临床潜能，为与PD-1及与其他药物的联合治疗奠定基础。得益于优异的安全性和多次重复给药方案，我们在最初入组的患者包括冷肿瘤（如转移性微卫星稳定型结直肠癌）患者和PD-L1低表达患者及PD-1耐药性热肿瘤患者的身上观察到了令人印象深刻的临床缓解，体现了 CTLA-4 介导的 Treg 清除对于疗效结果至关重要。" 罗博士继续补充道："这些安全性和有效性数据使我们能够首次在晚期/转移性微卫星稳定型结直肠癌患者这一特定肿瘤患者中评估 ADG126联用帕博利珠单抗的疗效，该单臂临床2期试验采用了Simon两阶段设计。我们非常高兴在第一阶段观察到强烈的疗效信号， 顺利进入第二阶段的患者入组工作，给药剂量为10 mg/kg，每3周一次。我们对突破抗CTLA-4 疗法的边界，致力于提高癌症治疗的能力充满信心。" 抗 CTLA-4 项目亮点 1b /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 15 mg/kg （N=59）的试验中显示出良好的安全性。 在针对经过大量预治疗的肿瘤患者的治疗中，ADG116单一疗法的总缓解率（ORR）达到13%（3/23可评估），其中， 肾细胞癌 （RCC）患者与高度微卫星不稳定（MSI-H）型子宫内膜癌患者观察到确认的部分缓解（PR） ， 卡波西氏肉瘤患者观察到初步缓解。 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3 mg/kg（最初每3周给药，然后每6周给药）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超过一年的持久完全缓解（CR）（ORR = 20%；1/5可评估）。 此外，一位转移性微卫星稳定型结直肠癌患者在ADG116（剂量水平为 3 mg/kg ，每6周给药）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。 ADG116已观察到临床疗效，并准备在合理配备资源后进入随机2期试验，其目前正在进行剂量扩展试验，以评估ADG116与抗PD-1药物联合治疗的疗效。 来自高剂量重复给药试验的 ADG126 1b /2 期临床数据表明，与 ADG116 靶向同一独特表位的精准掩蔽型抗 CTLA-4 安全抗体 SAFEbody® ADG126 在单一治疗与联合疗法中均展现出令人信服的安全性与良好的有效性： 2023年美国癌症协会（AACR）年会上公布的数据显示，在针对晚期/转移性实体瘤患者最高剂量为20 mg/kg且每三周重复给药的单一疗法剂量递增试验中，ADG126展现出良好的耐受性，未观察到剂量限制性毒性与3级或以上治疗相关不良事件（N=30）。 在与抗PD-1药物联合疗法（N=31）中，包括每3周或6周以10 mg/kg的剂量水平重复给药超过4个周期，ADG126也表现出与抗PD-1药物双联的同类最佳的安全性，未来有望与其他药物三联使用。 美国癌症协会年会上公布的数据显示，ADG126（剂量水平10 mg/kg）在与特瑞普利单抗联合治疗中展现出强大的有效性，包括在肛门鳞状细胞癌患者和阴茎鳞状细胞癌患者中观察到两例确认的部分缓解，以及在冷肿瘤（包括肝转移的转移性微卫星稳定型结直肠癌）患者中观察到明显肿瘤萎缩（靶病灶缩小≥20% ）和持续病情稳定。 美国癌症协会年会上公布的数据显示，另一例确认部分缓解来自一位高度微卫星不稳定型子宫内膜癌患者，该患者接受了剂量水平为10 mg/kg的ADG126与抗PD-1抑制剂帕博利珠单抗的联合治疗。 在美国癌症协会年会之后，接受ADG126（剂量水平10 mg/kg）与帕博利珠单抗联合治疗的剂量拓展队列，在转移性微卫星稳定型结直肠癌患者外，又观察到另两例确认的临床缓解。 一例确认部分缓解来自一位宫颈癌患者，该患者在既往两线治疗（包含9个周期的帕博利珠单抗单一治疗）后出现疾病进展，符合PD-1耐药标准。 一位头颈部鳞状细胞癌患者观察到确认部分缓解以及靶病灶完全萎缩。患者既往未接受过免疫治疗，CPS评分较低。 在剂量递增试验阶段接受剂量水平为10 mg/kg且每3周给药的ADG126与抗PD-1联合治疗的可评估患者中，观察到40%的总缓解率（4/10），以及10%的3级治疗相关不良事件概率，未观察到3级以上治疗相关不良事件，也未观察到剂量限制性毒性。在每6周10 mg/kg和每3周6 mg/kg的给药频率和剂量下同样也观察到了临床疗效。 针对无肝转移的微卫星稳定型晚期结直肠癌的剂量扩展队列采用了两组给药方案：分别是ADG126，10 mg/kg，每6周给药（10名患者）联合帕博利珠单抗治疗，及ADG126 10 mg/kg，每3周给药（13名患者）联合帕博利珠单抗治疗。基于10 mg/kg剂量水平每3周给药一次的给药频率下观察到更有力的疗效信号，根据Simon两阶段的二期单臂临床试验设计，公司需要在该给药方案下继续招募10例患者，其初步有效性数据评估及统计分析预计将于2023年底或2024年初公布。 其它最新动态 罗氏： 根据 2022年12月签订的临床试验合作协议 ，罗氏启动了一项跨国1b/2期临床试验，对照罗氏的阿替利珠单抗和贝伐珠单抗的标准治疗方案，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）的一线治疗中的有效性与安全性。该随机试验目前已启动患者入组工作，计划纳入多达60名患者，利用罗氏肿瘤免疫治疗开发平台MORPHEUS项目的全球临床试验网络。罗氏正赞助并开展该试验，天演将保留对ADG126的全球开发与商品化权利。 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 ： 天演与赛诺菲延续双方于2022年3月达成的合作，开发双特异性和单克隆SAFEbody®候选抗体，利用天演的技术制备的临床前候选抗体，由赛诺菲进行开发和商品化。 ADC Therapeutics （ ADCT ）： 截至本公告发布之日，ADCT与天演于2019年4月签订的生物材料转移与合作协议已经到期，ADCT选择不行使其对相关许可协议的选择权。未来，双方将保持开放态度，继续探索在创新抗体疗法的发现和开发方面的合作机会。 ADG153 （抗 CD47 IgG1 安全抗体 SAFEbody® ）： 天演在美国癌症协会年会上公布的数据显示，ADG153在临床前研究中展现出同类最佳潜力，ADG153是一种IgG1亚型候选抗体，采用安全抗体SAFEbody®精准掩蔽技术优化其安全性，正处于新药申请的临床前研究。该 海报展示 总结了相关数据，表明ADG153在实体瘤模型中展现出强大的体内抗肿瘤活性，且优先在肿瘤微环境中与CD47靶点结合，因而具备出众的安全性。ADG153具有很强的抗体依赖性细胞介导的细胞毒性作用（ADCC）和抗体依赖性细胞介导的吞噬作用（ADCP），旨在充分释放抗 CD47 治疗血液肿瘤和实体恶性肿瘤的潜力。 董事会最新动态： 今年8月，天演任命朱力博士为董事会成员。朱博士自2020年起担任金斯瑞及传奇生物科技有限公司（Legend Biotech）董事，目前是金斯瑞生物科技有限公司（Genscript Biotech Corporation）的首席战略官，其在企业战略、战略合作及联盟管理方面拥有着丰富的经验，尤其在传奇生物（金斯瑞的子公司）和跨国药企战略合作谈判的早期阶段发挥了关键作用。 此外，杜方勇博士， 2020年 起任天演首席技术官，因个人原因退出董事会。同时，公司任命天演创始团队成员，生物信息科技高级副总裁李艳担任董事一职。 今年早些时候，天演公布了董事会的最新动态：Mervyn Turner博士，默沙东研究实验室（Merck research Laboratories）前全球许可和外部研究部门负责人，被任命为董事；王雨濛接替孙乐非担任由泛大西洋投资集团新加坡办事处（General Atlantic Singapore AI Pte. Ltd）指定的董事；刘毓文因首次任期届满，辞去董事会及审计委员会成员职务。 科学顾问委员会： 今年3月， 医学博士Aurélien Marabelle教授 被任命为公司科学顾问委员会成员。Marabelle教授是法国Gustave Roussy癌症中心药物开发部（DITEP）的医学科学家，也是肿瘤学和免疫学领域的专家。他在肿瘤特异性调节性T细胞（Treg）清除方面拥有深刻见解，开创性地引入肿瘤内而非系统给药抗CTLA-4疗法，从而克服抗CTLA-4疗法剂量依赖性毒性问题。 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14,380万美元，2023年6月30日约12,880万美元。 截至2023年6月30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6月30日的2,490万美元。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，包括在临床及临床前研发项目中产生的CMC费用。 净收入 净收入同比增长了约341%。净收入相较于2022年同期的390万美元增加到2023年6月30日1,730万美元。该增长包含了因公司履行了与赛诺菲和Exelixis所分别签订的技术合作和授权协议中的履约义务而确认的收入。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 研发费用同比下降了约53%。研发费用相较于2022年同期的4,510万美元下降到2023年6月30日的2,130万美元。该下降源于临床前项目支出的减少和ADG106相关的临床项目的逐渐收尾，与针对抗CTLA-4疗法增加的投入所抵消。公司重点发展优质临床项目，并采取了包括减少人员成本在内的一系列成本控制措施。 管理费用 管理费用相较于2022年同期的680万美元减少到2023年6月30日的450万美元。管理费用的减少主要是由于成本控制带来的人工及办公成本的减少。 其他营业收入 其他营业收入2023年6月30日约340万美元。其他营业收入包含了从一家合同制造商处获得的，针对公司在一份临床前项目外包协议中产生的损失的一次性补偿款。 净亏损 净亏损相较于2022年同期的4,760万美元减少到2023年6月30日的410万美元。 流通在外普通股 截止至2023年6月30日，公司流通在外的普通股为54,793,339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4,190万美元，下降至2023年6月30日的10万美元。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。 对于本期间的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，也不应被视为该期间营业利润、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期间的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。 本期间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。 财务报表 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 6月30日 US$ US$ 资产 流动资产: 现金及现金等价物 143,758,678 128,759,962 应收关联方款项 619,432 393,969 其他流动资产和预付账款 4,937,323 3,524,688 流动资产总额 149,315,433 132,678,619 固定资产 2,782,963 2,222,200 使用权资产 191,877 292,523 其他非流动资产 109,572 108,922 资产总额 152,399,845 135,302,264 负债和股东权益 流动负债: 应付账款 3,666,124 4,483,776 合同负债 15,107,276 812,916 应付关联方款项 19,323,337 17,216,032 预提及其他流动负债 3,212,809 2,834,565 应付所得税 — 1,895,063 短期借款 10,768,745 8,995,544 一年内到期的长期借款 2,850,128 2,594,868 一年内到期的租赁负债 151,983 158,859 流动负债总额 55,080,402 38,991,623 长期借款 14,146,541 13,348,003 租赁负债 53,834 141,431 其他非流动负债 28,718 27,679 负债总额 69,309,495 52,508,736 股东权益: 股本 5,497 5,556 库存股 (4) (4) 资本公积 342,739,268 346,958,523 其他综合亏损 (849,305) (1,256,635) 累计亏损 (258,805,106) (262,913,912) 股东权益总额 83,090,350 82,793,528 负债和股东权益总额 152,399,845 135,302,264 未经审计的合并利润表 （美国通用会计准则） 截至 6 月30日 的 6个月 2022 2023 收入 技术许可合作 收入 3,923,174 17,295,745 费用 研发费用 (45,148,357) (21,289,434) 管理费用 (6,848,925) (4,470,520) 费用 总额 (51,997,282) (25,759,954) 其他营业收入 — 3,415,230 营业亏损 (48,074,108) (5,048,979) 利息收入 14,931 1,918,971 利息费用 (211,434) (573,507) 其他收入 430,671 3,702,660 汇兑损益 756,085 1,620,415 税前亏损 (47,083,855) (1,795,670) 所得税费用 (558,944) (2,313,136) 净亏损 (47,642,799) (4,108,806) 其他综合收益 外币报表折算差异 284,148 (407,330) 综合亏损总额 (47,358,651) (4,516,136) 净亏损 (47,642,799) (4,108,806) 归属于普通股股东净亏损总额 (47,642,799) (4,108,806) 用于计算每股普通股净损失的加权平均普通股股数 : —基本 54,533,161 54,604,787 —稀释后 54,533,161 54,604,787 每股普通股净亏损 —基本 (0.87) (0.08) —稀释后 (0.87) (0.08) 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 6 月30日 的 6个月 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 (47,642,799) (4,108,806) 调整: 股权激励费用 5,725,868 4,030,214 非美国通用会计准则下的普通股股东净亏损总额 (41,916,931) (78,592) 用于计算每股普通股净损失的加权平均普通股股数： —基本 54,533,161 54,604,787 —稀释后 54,533,161 54,604,787 非美国通用会计准则下的每股普通股净亏损 —基本 (0.77) (0.00) —稀释后 (0.77) (0.00)

- Best-in-class anti-CTLA-4 candidates designed for more than 30-fold increase in therapeutic index, addressing patient populations where CTLA-4-mediated Treg depletion is essential for efficacy – - Strong efficacy signal observed in MSS CRC phase 2 single arm study for SAFEbody® ADG126 in combination with pembrolizumab at the 10 mg/kg every three weeks dosing regimen - - Advancing MSS CRC cohort with ten more patients at the active every three weeks dosing regimen for SAFEbody ADG126 plus pembrolizumab following Simon’s two-stage statistical design – - Roche initiates randomized phase 1b/2 trial with SAFEbody ADG126 in novel triple combinationfor first-line hepatocellular carcinoma - - Cash balance of US$128.8 million supports operations to late 2025 – SAN DIEGO and SUZHOU, China, Aug. 31, 2023 (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 six months ended June 30, 2023 and provided corporate updates. “Our anti-CTLA-4 clinical programs demonstrate that an enhanced therapeutic index is capable of unleashing the clinical potential of CTLA-4 treatment, with the right dosing regimens, as a cornerstone in combination with PD-1 and beyond,” said Peter Luo, Ph.D., Chairman, CEO and President of R&D at Adagene. “We have observed impressive clinical responses in the initial basket trial for ADG126 plus PD-1 therapy in patients where CTLA-4-mediated Treg depletion is essential for efficacy, including cold tumors such as MSS CRC, PD-L1 low expressing and PD-1 resistant warm tumors, enabled by our safety profile for higher, more frequent and repeat dosing.” He continued, “This safety and efficacy profile allows us to evaluate ADG126 plus pembrolizumab in a homogenous patient group for the first time in advanced/metastatic MSS CRC patients, following Simon’s two-stage statistical design for a single arm phase 2 trial. We are very excited to observe a strong efficacy signal in the first stage and we are now enrolling patients in the second stage with the active dose of ADG126 10 mg/kg every three weeks. We are optimistic about our ability to push the boundaries of CTLA-4 therapy to improve cancer care.” ANTI-CTLA-4 HIGHLIGHTS 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).In heavily pre-treated patients across tumors, ADG116 monotherapy resulted in an overall response rate (ORR) of 13% (3/23 evaluable), including confirmed partial responses (PR) in renal cell carcinoma (RCC) and MSI-H endometrial cancer, as well as an initial PR in Kaposi’s sarcoma.ADG116 (3 mg/kg Q6W) in combination with anti-PD-1 therapy (N=22) showed a manageable safety profile and an encouraging efficacy profile in dose escalation. Clinical responses from the ongoing combination cohorts include a sustained complete response (CR) for greater than one year 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).Additionally, an initial PR was observed in a patient with MSS CRC dosed with repeat cycles of ADG116 3 mg/kg every six weeks plus toripalimab (ORR = 14%; 1/7 evaluable).ADG116 is clinically active and ready to advance into randomized phase 2 studies as resources allow, while combination dose expansion is evaluating ADG116 with anti-PD-1 therapy. Phase 1b/2 data for ADG126, a masked anti-CTLA-4 SAFEbody targeting a unique epitope, showed compelling safety and promising efficacy profiles at high dose levels with repeat dosing both in monotherapy and in combination with anti-PD-1: Data presented at the American Association for Cancer Research (AACR) annual meeting 2023 showed ADG126 monotherapy was well tolerated in dose escalation with no dose-limiting toxicities or Grade 3 or higher TRAEs observed (N=30) in patients with advanced/metastatic solid tumors. ADG126 was administered up to 20 mg/kg every three weeks with repeat dosing.The safety profile of ADG126 in combination with anti-PD-1 therapy (N=31) also showed best-in-class potential, including repeat dosing beyond four cycles at 10 mg/kg every three or six weeks, potentially enabling triple combination with other agents on top of ADG126 plus anti-PD-1 backbone therapy.Data presented at AACR showed a strong efficacy profile for ADG126 10 mg/kg in combination with the anti-PD-1 therapy toripalimab, including two confirmed PRs in patients with anal SCC and penile SCC, as well as significant tumor shrinkage (≥20% reduction in target lesion) and prolonged stable disease observed in patients with cold tumors, including MSS CRC with liver metastases.At the 2023 AACR annual meeting, an additional confirmed PR was reported in a patient with MSI-H endometrial cancer who received ADG126 10 mg/kg in combination with the anti-PD-1 inhibitor pembrolizumab.Following the AACR annual meeting, two additional confirmed responses were observed in patients treated with ADG126 10 mg/kg plus pembrolizumab outside of the MSS CRC dose expansion cohort: A confirmed PR in a cervical cancer patient who had progressed after two lines of prior therapy, including nine cycles of pembrolizumab monotherapy, meeting criteria for PD-1 resistance.A confirmed PR with complete reduction in target lesions in a patient with HNSCC. The patient was IO-naïve with a low CPS score. In dose escalation, among the evaluable patients dosed at 10 mg/kg every three weeks in combination with anti-PD-1 therapy, a 40% overall response rate (4/10) was observed, with 10% Grade 3 TRAEs reported, no TRAEs greater than Grade 3 reported, and no dose limiting toxicities. Activity has also been observed at 10 mg/kg every six weeks and at 6 mg/kg every three weeks.Adagene has dosed two different arms in its dose expansion cohort of patients with MSS CRC without liver metastases treated with ADG126 in combination with pembrolizumab: ADG126 10 mg/kg every six weeks plus pembrolizumab (10 patients) and ADG126 10 mg/kg every three weeks plus pembrolizumab (13 patients). Based on the strong efficacy signal observed in the ADG126 10 mg/kg three-week cohort, the company is enrolling an additional 10 patients treated with this active dosing regimen, following Simon’s two-stage statistical design for a single-arm phase 2 trial.Preliminary evaluation and analysis of efficacy data from this tumor type-specific cohort in MSS CRC is expected later this year or early 2024. ADDITIONAL UPDATES Roche: Under a clinical trial collaboration agreement entered in December 2022, Roche has initiated a phase 1b/2 multi-national trial to evaluate the efficacy and safety profiles of ADG126 in a triple combination with atezolizumab and bevacizumab, versus the approved combination of atezolizumab and bevacizumab alone in first-line hepatocellular carcinoma (HCC). The randomized trial in up to 60 patients has opened for enrollment, leveraging Roche’s global clinical trial network for the MORPHEUS program. Roche is sponsoring and conducting the trial while Adagene retains global development and commercialization rights to ADG126.Exelixis: Adagene has received a US$3.0 million milestone payment in June 2023 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 continue working together in their collaboration entered in March 2022 to develop both bispecific and monoclonal SAFEbody antibody candidates, preparing preclinical candidates using Adagene’s technology for future development and commercialization by Sanofi.ADC Therapeutics: As of this announcement, the material transfer and collaboration agreement dated April 2019 between ADCT and Adagene has expired, and ADCT elected not to exercise its option for the related license agreement. The parties remain open to explore opportunities for collaboration on the discovery and development of innovative antibody therapeutics in the future.ADG153 (a masked anti-CD47 IgG1 SAFEbody): At the AACR annual meeting, Adagene presented preclinical data that showed the best-in-class profile for ADG153, an IND-ready candidate in IgG1 format which applies SAFEbody precision masking technology to optimize safety. The poster presentation summarized data demonstrating strong in vivo anti-tumor activities in solid tumor models and a robust safety profile due to preferential CD47 target engagement in the tumor microenvironment. ADG153 is differentiated by its strong antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) activity designed to realize the full potential of anti-CD47 therapy for both hematologic and solid tumor indications.Board of Directors Updates: In August, Adagene appointed Li Zhu, Ph.D. to its board of directors. Dr. Zhu has served as director at GenScript and Legend Biotech since 2020 and is currently Chief Strategy Officer at GenScript Biotech Corporation. Dr. Zhu brings deep experience in corporate strategy, strategic collaborations and alliance management, especially his experience in negotiations and deal-making between Legend (a subsidiary of GenScript) and multinational pharmaceutical companies.Additionally, Fangyong (Felix) Du, Ph.D, Chief Technology Officer at Adagene since 2020, is stepping down from the board for personal reasons. The company also appointed Yan Li, one of the founding members and Senior Vice President of Bioinformatics and Information Technology at Adagene, as director.Earlier this year, Adagene also announced the following updates to its board: Mervyn Turner, Ph.D., former head of worldwide licensing and external research at Merck Research Laboratories appointed director; Yumeng Wang replaced Lefei Sun as a director designated by General Atlantic Singapore AI Pte. Ltd; and Yuwen Liu resigned from the Board and audit committee due to expiration of her initial appointment. Scientific and Strategic Advisory Board (SAB): In March, Professor Aurélien Marabelle, MD, PhD was appointed to the company’s SAB. Professor Marabelle is a physician-scientist with expertise in oncology and immunology working within the Drug Development Department (DITEP) of Gustave Roussy Cancer Center in France. Professor Marabelle brings deep insight in tumor-specific Treg depletion for anti-CTLA-4 therapies delivered intratumorally to overcome dose dependent toxicities through systemic delivery of anti-CTLA-4 therapies. FINANCIAL HIGHLIGHTS Cash and Cash Equivalents:Cash and cash equivalents were US$128.8 million as of June 30, 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$24.9 million as of June 30, 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, including CMC costs of clinical and preclinical programs. Net Revenue:Net revenue was US$17.3 million for the six months ended June 30, 2023, compared to US$3.9 million for the same period in 2022. The increase of approximately 341% reflects net revenue recognized upon fulfillment of certain performance obligations associated with the collaboration and technology licensing agreements with Sanofi and Exelixis, 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$21.3 million for the six months ended June 30, 2023, compared to US$45.1 million for the same period in 2022. The decrease of approximately 53% in R&D expenses reflects a reduction in preclinical spending and winding down of the ADG106 clinical program, offset by investment in the anti-CTLA-4 franchise. The Company prioritized its high value clinical projects and implemented a series of cost control measures, including a reduction in personnel. Administrative Expenses:Administrative expenses were US$4.5 million for the six months ended June 30, 2023, compared to US$6.8 million for the same period in 2022. The decrease was due to reduction in both personnel and office related expenses as a result of cost-control measures. Other Operating income, Net:Other operating income, net was US$3.4 million for the six months ended June 30, 2023. Other operating income, net included a one-time compensation payment from a contract manufacturer in relation to company losses for a preclinical-related outsourcing arrangement. Net Loss:Net loss attributable to Adagene Inc.’s shareholders was US$4.1 million for the six months ended June 30, 2023, compared to US$47.6 million for the same period in 2022. Ordinary Shares Outstanding:As of June 30, 2023, there were 54,793,339 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 LossNon-GAAP net loss, which is defined as net loss attributable to ordinary shareholders for the period after excluding share-based compensation expenses, was US$0.1 million for the six months ended June 30, 2023, compared to US$41.9 million for the same period 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 period, 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 period 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 period. The company believes that non-GAAP net loss and non-GAAP net loss per ordinary shares for the period 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 period should not be considered in isolation or construed as an alternative to operating profit, loss for the period 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 period and the reconciliation to their most directly comparable GAAP measures. Non-GAAP net loss and non-GAAP net loss per ordinary shares for the period 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 period represent net loss attributable to ordinary shareholders for the period 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 period to net loss attributable to ordinary shareholders for the 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 unmet patient needs. 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. Adagene has forged strategic collaborations with reputable global partners that leverage its technology in multiple approaches at the vanguard of science. 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. 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 COVID-19 pandemic 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 2022 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. FINANCIAL TABLES FOLLOW Unaudited Consolidated Balance Sheets December 31,2022 June 30,2023 US$ US$ASSETS Current assets: Cash and cash equivalents143,758,678 128,759,962 Amounts due from related parties619,432 393,969 Prepayments and other current assets4,937,323 3,524,688 Total current assets149,315,433 132,678,619 Property, equipment and software, net2,782,963 2,222,200 Operating lease right-of-use assets191,877 292,523 Other non-current assets109,572 108,922 TOTAL ASSETS152,399,845 135,302,264 LIABILITIES AND SHAREHOLDERS’ EQUITY Current liabilities: Accounts payable3,666,124 4,483,776 Contract liabilities15,107,276 812,916 Amounts due to related parties19,323,337 17,216,032 Accruals and other current liabilities3,212,809 2,834,565 Income tax payable— 1,895,063 Short-term borrowings10,768,745 8,995,544 Current portion of long-term borrowings2,850,128 2,594,868 Current portion of operating lease liabilities151,983 158,859 Total current liabilities55,080,402 38,991,623 Long-term borrowings14,146,541 13,348,003 Operating lease liabilities53,834 141,431 Other non-current liabilities28,718 27,679 TOTAL LIABILITIES69,309,495 52,508,736 Commitments and contingencies Shareholders’ equity: Ordinary shares (par value of US$0.0001 per share; 640,000,000 shares authorized, and 54,278,981 shares issued and outstanding as of December 31, 2022; and 640,000,000 shares authorized, and 54,793,339 shares issued and outstanding as of June 30, 2023)5,497 5,556 Treasury shares (1 share as of December 31, 2022 and June 30, 2023)(4) (4)Additional paid-in capital342,739,268 346,958,523 Accumulated other comprehensive income (loss)(849,305) (1,256,635)Accumulated deficit(258,805,106) (262,913,912)Total shareholders’ equity83,090,350 82,793,528 TOTAL LIABILITIES AND SHAREHOLDERS’ EQUITY152,399,845 135,302,264 Unaudited Consolidated Statements of Comprehensive Loss For the Six MonthsEnded June 30, 2022 For the Six MonthsEnded June 30, 2023 US$ US$Revenues Licensing and collaboration revenue3,923,174 17,295,745 Expenses Research and development expenses(45,148,357) (21,289,434)Administrative expenses(6,848,925) (4,470,520)Total expenses(51,997,282) (25,759,954)Other operating income, net— 3,415,230 Loss from operations(48,074,108) (5,048,979)Interest income14,931 1,918,971 Interest expense(211,434) (573,507)Other income, net430,671 287,430 Foreign exchange gain (loss), net756,085 1,620,415 Loss before income tax(47,083,855) (1,795,670)Income tax expense(558,944) (2,313,136)Net loss attributable to Adagene Inc.’s shareholders(47,642,799) (4,108,806)Other comprehensive income (loss) Foreign currency translation adjustments, net of nil tax284,148 (407,330)Total comprehensive loss attributable to Adagene Inc.’s shareholders(47,358,651) (4,516,136)Net loss attributable to Adagene Inc.’s shareholders(47,642,799) (4,108,806)Net loss attributable to ordinary shareholders(47,642,799) (4,108,806)Weighted average number of ordinary shares used in per share calculation: —Basic54,533,161 54,604,787 —Diluted54,533,161 54,604,787 Net loss per ordinary share —Basic(0.87) (0.08)—Diluted(0.87) (0.08) Reconciliation of GAAP and Non-GAAP Results For the Six Months Ended June 30, 2022 For the Six Months Ended June 30, 2023 US$US$GAAP net loss attributable to ordinary shareholders(47,642,799) (4,108,806)Add back: Share-based compensation expenses5,725,868 4,030,214 Non-GAAP net loss(41,916,931) (78,592)Weighted average number of ordinary shares used in per share calculation: —Basic54,533,161 54,604,787 —Diluted54,533,161 54,604,787 Non-GAAP net loss per ordinary share —Basic(0.77) (0.00)—Diluted(0.77) (0.00)