VivaVision Biotech Inc.

作为一个具有高成长性、高壁垒的双高赛道，眼科行业一直以来被誉为资本市场的“黄金赛道”。 近年来，随着人口老龄化进程加快、生活方式变化、电子产品的普及等，眼部疾病的发病率及用药需求均在不断提升，带来的是眼科药物市场的快速增长。与此同时，眼科疾病高度细分、专业性较强，很多眼病的病理机制不够明确，也导致眼科用药技术壁垒高，新药研发难度较大。 眼科药物技术的迭代与发展对于全民眼健康的整体水平提升具有重要意义。新型眼科药物的研发致力于更长效的治疗效果，替代疗效欠佳的传统药物，并为缺乏药物治疗的眼疾带来创新治疗手段。 然而在我国，由于对许多眼科疾病发病机制的认知相对滞后，加上患者对眼科疾病的认知和重视程度有限，我国眼科药物市场起步较晚，目前以仿制药和license-in为主，自主研发的创新药不多。通过仿制和License-in能够迅速缩短药物的研发周期，快速将药物推向市场，并降低药物研发的风险。但这也是造成市场药物同质化问题的根源。 可以说，眼科创新药的自主研发是一条更难走的路。基于此，我们对眼科创新药物进行盘点。随着创新药适应症的不断拓展，未来眼科药物市场还将进一步放量，在确定的市场需求之下，谁将率先抢占市场先机？ 12款新药获批，融资超20亿，眼科创新药正在狂奔 当前，全球眼科市场整体呈现出稳定增长、集中度较高的特点。数据显示，2023年，全球眼科创新药市场规模在2023年估计达到了37.82亿美元，并预计从2024年到2030年将以8.34%的复合年增长率增长，到2030年将达到66.06亿美元。 2023年，FDA 发布了2项相关指南，用以指导产业在眼科药物开发过程中的药品质量/CMC和临床研究工作。指南的发布也带来了眼科药物的一系列突破性进展。 其中，2023年10月，FDA为了更好地指导眼科药物开发，发布了《局部眼科用药质量考量要点》的指南草案。指南重点讨论了用于眼内和眼周局部给药的眼科药品（即溶液、混悬液、乳剂、凝胶、软膏和乳膏）的质量注意事项；2023年2月，FDA 发布了《新生血管性老年黄斑变性：开发治疗药物》，旨在向申办方提供有关资格标准、试验设计的考虑因素和疗效终点的建议，以提高治疗nAMD的药物临床试验的数据质量和药物开发项目的效率。 2023年，FDA批准了12款新型眼科药物上市，药物类型包含抗VEGF药物、双抗药物、补体药物、小分子药物等，适应症涉及年龄相关性黄斑变性 （AMD）、由AMD引发的地图样萎缩（GA）、干眼症、老花眼、散瞳等。 2023年，FDA批准了12款新型眼科药物 在国内，眼科创新药也一直是资本重点关注的领域。我国目前有4亿患者饱受各类眼部疾病困扰，而随着社会老龄化程度的加深和现代人生活方式的改变，我国眼科疾病负担将会越发凸显，市场空间增长潜力大。  2023年1月至今，国内眼科创新药融资事件（不完全统计） 据不完全统计，从2023年至今（数据统计至2024年8月30日），我国眼科创新药领域共有21家企业发生了24起融资事件，总融资金额超过20亿人民币。 在巨大的市场需求下，尽管投融资大环境不算乐观，仍有不少眼科创新药企业顺利融到资金，为公司推动管线研发和未来发展注入新鲜血液。 抗VEGF、基因疗法、补体药物……眼科药物机制创新不断 当前，眼科创新药物市场正迎来快速增长，特别是在几个关键疾病领域。 其中，年龄相关性黄斑变性（AMD）由于其与老龄化人口的直接关联，已成为增长潜力最大的领域之一。糖尿病性黄斑水肿（DME）因糖尿病患者数量的增加亦成为重要的治疗领域。青光眼作为全球主要的不可逆性致盲眼病，其治疗市场随着患病率的上升而扩大。干眼症（DED）的发病率在数字化时代背景下不断上升，由于长时间使用电子屏幕导致的眼睛干涩问题日益普遍，对治疗药物的需求持续增长。近视控制药物的需求也在上升，尤其是在东亚地区，近视患者数量庞大。 此外，眼部炎症和感染的治疗市场同样受到人口老龄化和生活方式变化的推动，发病率的增加带来了对新治疗方法的需求。 基于眼科疾病细分种类多且复杂，眼科领域的创新药物研究致力于通过多种作用机制实现创新，以期为患者提供更有效和耐受性更好的治疗方案。 其中，抗血管内皮生长因子（VEGF）药物在治疗新生血管性眼病方面取得了显著进展，通过抑制异常血管的生长来改善视力；补体C5蛋白抑制剂如Lzervay通过降低补体系统的活性，为地图样萎缩（GA）等眼底疾病提供了新的治疗选择。双特异性抗体，如法瑞西单抗，通过同时作用于VEGF和Ang-2两条通路，为眼底血管性疾病患者带来了更为有效的治疗手段，等等。 在遗传性眼科疾病的治疗上，基因治疗技术正展现出巨大潜力，通过替换或修复缺陷基因来治疗如Leber遗传性视神经病变和色素性视网膜炎等疾病。 低浓度阿托品则被证实能有效延缓近视的进展，为控制近视提供了新的策略。同时，针对开角型青光眼的治疗，新药如VVN539通过双靶点机制降低眼压，为患者提供了新的治疗选择。 ● 抗VEGF药物：四款产品在国内上市，已上市产品收益颇丰 常见的新生血管性眼病主要有湿性年龄相关性黄斑变性（wet-AMD）、糖尿病视网膜病变（DR）、糖尿病黄斑水肿（DME）和视网膜静脉阻塞（RVO）。由于抗VEGF药物能有效抑制新生血管的形成并促进已有的新生血管消退，已成为治疗眼底血管疾病的主要手段。 抗VEGF药物在眼科治疗领域具有革命性的意义，它们通过多种机制发挥作用，以治疗各种眼底疾病。首先，这些药物能够抑制VEGF的活性，从而阻止病理性血管的生成，这是治疗湿性AMD和DME等眼病的关键。其次，通过降低血管的通透性，减少血浆蛋白和液体从血管中渗漏到视网膜，有效减轻黄斑水肿。此外，抗VEGF药物还能促进已有异常血管的消退，进一步改善视网膜的病理状态。 在提高视力方面，抗VEGF药物通过上述作用机制，有助于延缓疾病进展，甚至在某些情况下提高视力。随着研究的深入，新一代的双特异性抗体药物能够同时靶向VEGF-A和Ang-2，提供更全面的治疗效果。同时，口服抗VEGF药物的研发也在进行中，这将极大地提高患者的依从性和生活质量。 尽管抗VEGF药物在临床上已经取得了显著的疗效，但仍存在一些挑战，如注射频率高、潜在的全身副作用和药物不应答等问题。为了克服这些限制，科学家们正在不断探索新的药物形式和给药方式，旨在为眼科疾病患者提供更有效、更安全的治疗选择。 目前，全球已有雷珠单抗、阿柏西普、康柏西普和布西珠单抗、法瑞西单抗5款眼用抗VEGF药物获批上市。其中，雷珠单抗、康柏西普、阿柏西普和法瑞西单抗四款药物已经在中国获批上市。  国内获批的抗VEGF药物  罗氏与诺华联合开发的雷珠单抗最早获批，于2006年获FDA批准上市，是首个抗VEGF眼用生物药，其显著的疗效也使得抗VEGF药物在眼科治疗领域声名鹊起。2011年，该产品登陆中国市场。凭借先发优势，雷珠单抗销量一路攀升，2014年达到峰值，超过43亿美元。 阿柏西普是由再生元与拜耳共同研发的全球首个完全人源化的融合蛋白。虽然比雷珠单抗晚上市约5年，但阿柏西普卓越的疗法及亲民的价格，短时间内就奠定了其全球AMD领域的绝对优势地位。阿柏西普上市第一年销售额就达到了8.38亿美元；2022年，阿柏西普销售额为96.47亿美元，是全球销售额最高的抗VEGF眼科药物。 康柏西普是中国企业康弘药业自主研发的一款抗VEGF受体与人免疫球蛋白Fc段基因重组的融合蛋白，作为国内首款国产VEGF单抗，打破了高价进口药对中国眼科市场的垄断，成为当时中国创新药的标志性产品之一。 与雷珠单抗不同，康柏西普的活性蛋白是新一代抗VEGF融合蛋白，结构上为100%人源化，能有效地结合VEGF-A、VEGF-B、PIGF等多个病理性新生血管相关的靶点，具有更佳的治疗效果、更少的注射次数以及更好的药物依从性。自2013年在国内获批以来，康柏西普凭借先发和性价比优势迅速实现销售额上涨。2023年，康柏西普实现营收19.36亿元，同比增长41.73%，占总营收的比例高达48.93%。 布罗鲁珠单抗是诺华研发的一款人源化单链抗体片段（scFv），分子量为26kDa，具有体积小、组织渗透性强、对VEGF-A异构体有强大抑制作用及高度亲和力。该产品是首个可以间隔3个月给药的抗VEGF药物，于2019年10月获FDA批准上市。据EvaluatePharma预测，该产品到2024年全球销售额有望达到13.2亿美元。 罗氏的法瑞西单抗是首款针对眼科疾病获批的双抗，不仅靶向VEGF-A，还同时靶向Ang-2。这种双通路的作用机制使得法瑞西单抗在治疗眼底疾病时，除了抑制新生血管生成，还能增强血管稳定性，从而提升治疗效果。 在国内，巨大的市场空间也使得国内企业纷纷瞄准这一潜力领域。国内药企中，齐鲁是细分领域的重要布局者。2022年4月，齐鲁制药提交了阿柏西普生物类似药QL1207的上市申请；2023年1月，齐鲁制药提交的雷珠单抗生物类似药QL1205的上市申请获受理。 除此之外，在阿柏西普生物类似药中，博安生物的LY09004、迈威生物的9MW0813也进入临床3期。一旦批准上市，国内眼科抗VEGF生物药领域将进入创新药和仿制药混战的局面，市场竞争将逐步加剧。 在抗VEGF创新药赛道上，目前国内还是一片蓝海，药品研发速度以及创新性和差异化，必将成为未来脱颖而出的关键。 ● 基因疗法：眼科AVV基因疗法黄金赛道，国内超20家企业布局 基因疗法是眼科疾病的理想候选对象，在眼科治疗中展现出巨大优势。一方面，眼睛是免疫特权空间，血-眼屏障使得眼睛与免疫系统相对独立，基因疗法可以减少治疗引起的免疫反应风险。另一方面，由于许多眼部疾病是由于单个或多个基因的缺陷造成的，很多遗传性眼科疾病的突变已经被精准识别，为基因疗法开发提供了众多的靶点选择。基因疗法旨在通过一次性治疗实现长期效果，减轻患者长期用药的负担。 优势之外，基因疗法在眼科治疗中也面临挑战，包括基因递送效率、长期安全性、制造成本、监管和伦理问题等等。未来随着科学研究的深入和技术的不断进步，这些挑战有望被逐步克服，从而使得基因疗法在未来眼科治疗中发挥更大的作用。 目前全球共有137款基因治疗药物处于研发阶段，大多数处于临床开发阶段的基因疗法都集中在最常见的遗传性眼科疾病上，如色素性视网膜炎、脉络膜血症、Leber遗传性视神经病变、Leber先天性黑蒙（LCA）、色盲和X连锁视网膜色素变性（XLRS）等。 2017年12月，全球首个眼科基因疗法Luxturna在美国获批上市，掀起了眼科基因疗法的热潮。相对其他器官而言，眼睛体积较小，只需要低剂量的药物就可以达到治疗效果，而且具有免疫豁免、系统风险低等优势，成为各方药企率先布局的一大领域。 目前国内聚焦眼科AVV基因疗法，已有超20家企业在布局，其中不少在研新药已经进入临床试验阶段，将为遗传性眼病的治疗带来新希望。包括纽福斯生物、朗信生物、嘉因生物、天泽云泰、康弘药业、中因科技、辉大基因、安龙生物、金唯科、本导基因、九天生物、方拓生物、鼎新基因、凌意生物、极目生物、星眸生物、目镜生物、纽伦捷生物、领诺医药、埃微路新、南京贝思奥、瑞风生物、因诺惟康等众多创新药企积极布局，其中不少在研药物已经进入临床试验。 纽福斯生物是国内在眼科基因疗法领域走在前列的企业，其核心管线NFS-01旨在治疗ND4突变引起的Leber遗传性视神经病变（LHON）。2022年1月，NFS-01通过FDA IND申请，是首个获得FDA临床试验许可的国产眼科基因治疗药物。目前纽福斯生物已经建立了13条管线，涵盖遗传性视神经病变、视神经损伤疾病、遗传性视神经萎缩、血管性视网膜病变等四大领域。 ● 补体药物：干性AMD治疗的中坚力量，能否开启下一波热潮？ 近两年，补体药物临床开发不断取得积极进展，一些罕见病患者已经充分从中受益。在罕见病之外，补体药物在眼科等常见病的开发应用逐渐活跃起来。 在眼科创新药物研发中，补体药物的作用机制主要涉及调节补体系统的活性，以减轻补体介导的炎症反应和病理过程。补体系统是人体免疫系统的一部分，参与了多种疾病的发生和发展，包括眼科疾病如年龄相关性黄斑变性（AMD）。在AMD的发病机制中，补体系统的异常活化被认为是一个重要的因素，它可以通过形成膜攻击复合物（MAC）导致细胞损伤，以及通过促进炎症反应来加剧疾病的进展。 补体药物通过靶向补体系统的特定成分，如C3、C5或补体调节蛋白，来抑制补体系统的过度激活。例如，IBI302（Efdamrofusp Alfa）是一种抗VEGF-补体双靶点药物，它能够同时抑制VEGF介导的信号通路和减轻补体活化介导的炎症反应。IBI302的N端能够与VEGF家族结合，阻断VEGF介导的信号通路，从而抑制血管新生，改善血管渗透性，减少血管渗漏；C端能够通过特异性结合C3b和C4b，抑制补体经典途径和旁路途经的激活。这种双靶点作用机制旨在提供更全面的治疗效果，改善视力，减少视网膜水肿，并可能对黄斑萎缩及纤维化有潜在的改善作用。 此外，补体药物的研发还包括其他策略，如使用补体因子H的生物大分子药物GEM103，它通过恢复AMD患者眼内适当的替代途径调节来发挥作用。还有针对补体因子C5的生物大分子药物Avacincaptad pegol (ACP)，它是一种补体C5的强效特异性抑制剂，能够抑制C5的切割，进而减缓AMD的进展。       目前，眼科创新药物研发中，已有一些补体药物上市，包括依库珠单抗（Eculizumab）、可伐利单抗（Ravulizumab）、阿柏西普（Aflibercept）、Avacincaptad Pegol (ACP)、IBI302 （Efdamrofusp Alfa）等。这些药物的上市为眼科疾病治疗带来了新的选择，尤其是在补体系统介导的疾病中显示出了显著的疗效。 目前，抗VEGF药物仍是wAMD等在内眼底新生血管病治疗的主旋律，实现了大多数眼底新生血管病患的视力改善，使原来几乎不能治疗的眼底疾病得到了有效控制和治疗。 相比之下，占到AMD80%以上的干性AMD市场仍处于空白，目前尚无任何有效治疗和预防药物。补体药物作为当下集中干性AMD治疗中坚力量，在通过临床验证之后，等待的将是4、5倍于wAMD的巨大市场。那么补体药物会开启抗VEGF药物之后的下一个热潮吗？未来值得期待。 国内生物类似药进展较快，创新药研发仍存挑战 近年来，国内在眼科生物类似药方面的研发进展迅速，尤其是在抗VEGF药物领域，国内已有几款生物类似药获批上市，比如齐鲁制药的雷珠单抗生物类似药QL1205。此外，信达生物、科伦药业等也在积极布局眼科用药领域，有多款1类新药和首仿药在研。 尽管在生物类似药方面取得进展，但国内在眼科创新药研发方面与美国相比仍存在一定差距，眼科新药研发格局也截然不同。 据此前动脉网调研，美国眼科药物市场起步早，经过一系列并购整合，美国的眼科药物研发企业聚焦且头部化，不论是小分子、大分子还是基因药物，基本集中在诺华、罗氏、博士伦等大企业中。 中国则不同，近年来随着资本介入、优秀科学家回国创业，中国眼科新药企业如雨后春笋般纷纷涌出，各项专利技术分散在各个小公司手中，每个细分赛道上都有优质的企业，如小分子赛道的锐明新药、维眸生物，大分子赛道有信达、康弘药业等。换言之，中国还没有产生真正的头部眼科创新药企业。 同时，由于中国眼科创新药赛道仍处于起步阶段，也就不可避免地存在着一些挑战。首先在资本层面，国内眼科创新药研发费用主要来自投资机构，而国内投资机构相对更趋避风险。这导致目前在研的眼科创新药基本都是“正风险”，以外部引进为主，缺乏自主创新，很少开发真正意义的first in class药物。这一策略虽然能在短时间内取得一定成绩，但长期来看并没有解决基础技术问题，加大自主创新力度仍然迫在眉睫。 其次在监管审批层面，中国药监局对眼科创新药赛道法规还在逐渐完善中，审批沟通环节成了制约研发速度的重要因素。目前美国有成熟的眼科创新药法规体系，而中国药监局在湿性黄斑性病变、干眼症等眼科创新药审批上缺乏经验，审批速度较慢，这对企业的研发进度和市场准入构成了挑战。 此外，针对更为前沿的细胞基因治疗等领域，因国内缺乏相关的产品，导致目前市场上的监管、审批等法律法规尚不明晰，也会给走在前端的企业带来一定挑战。 最后，从企业角度来说，眼科药物赛道参与者渐多，如何找到准确的定位和擅长的方向，选择合适的疾病领域、商业运营、研发注册策略。此外，从公司策略来讲，外部引进只是辅助手段，最重要的还是自研能力。需要给予研发风险较高的first in class药物更多信心和耐心，助力自主研发创新，吸引更多优秀的科学家投入眼科创新药赛道。 未来，随着中国眼科创新人才越来越多，行业越来越规范，中国与美国的眼科创新药研发差距将越来越小，各种药物、机制、疗法将不断涌现，细分赛道呈现出百花齐放的新局面，最终形成一个健康的眼科创新药发展体系。我们拭目以待。 * 参考资料： “看得见”的力量：百亿眼科赛道品种分析——凯莱英 资本涌入，赛道火热，如何打造眼科新药研发健康体系？——动脉网 2023年，FDA批准了这12款新型眼科药物，涉及干眼症、老视、散瞳等——眼视光观察 *封面图片来源：壹图网 如果您想对接文章中提到的项目，或您的项目想被动脉网报道，或者发布融资新闻，请与我们联系；也可加入动脉网行业社群，结交更多志同道合的好友。 近 期 推 荐 声明：动脉网所刊载内容之知识产权为动脉网及相关权利人专属所有或持有。未经许可，禁止进行转载、摘编、复制及建立镜像等任何使用。 动脉网，未来医疗服务平台

作者 | 陈芋 来源 | 赛柏蓝 首个国产斑秃新药申报上市，一批国内药企布局千亿脱发市场。 01 “一哥”即将进入脱发市场 多家国内企业布局 近日，恒瑞医药发布公告，其硫酸艾玛昔替尼片（SHR0302片）药物上市许可申请获国家药监局受理，用于成人重度斑秃患者治疗，是首个在国内斑秃适应症上市申请获得受理的本土JAK抑制剂。 这也意味着，在礼来、辉瑞产品相继在中国获批后，恒瑞很可能成为首个打入国内斑秃市场的本土企业。 成人重度斑秃已是艾玛昔替尼申报的第四项适应症，其在去年还先后申报了成人和12岁及以上青少年中度至重度特应性皮炎，强直性脊柱炎，以及中重度活动性类风湿关节炎适应症。 参考辉瑞利特昔替尼胶囊2022年9月上市申请获国家药监局受理，11月被纳入优先审评审批程序，次年10月正式获批上市的进度，恒瑞的艾玛昔替尼斑秃适应症若也能被纳入优先审评审批程序，或可在明年下半年获批上市。 此前，艾玛昔替尼的II期数据显示：2mg、4mg、8mg艾玛昔替尼及安慰剂治疗斑秃，24周SALT较基线下降30.51%、56.11%、51.01%和19.8%。 可以发现，艾玛昔替尼在2mg和4mg组呈现剂量依赖性，但是在4mg、8mg组剂量上没有剂量依赖，即艾玛昔替尼在4mg能达到治疗效应。 今年6月，艾玛昔替尼片又在Ⅲ期临床试验主要研究终点达到方案预设的优效标准。 该研究由全国31家中心共同参与，共入组330例成人重度斑秃患者。结果显示，艾玛昔替尼片8mg和4mg两个剂量组在主要终点上均显著优于安慰剂组，且在成人重度斑秃患者中长期治疗的安全性、有效性良好，与其他JAK1抑制剂相比未发现新的安全性信号。 除了恒瑞，泽璟制药自主研发的JAK和ACVR1双抑制剂盐酸吉卡昔替尼（曾用名：盐酸杰克替尼），也在今年6月完成了重症斑秃Ⅲ期临床研究。 此外，科伦药业的JAK1/2抑制剂KL130008胶囊、启元生物的JAK1/TYK2抑制剂QY201的斑秃适应症也均进入了II期临床阶段。 02 千亿脱发市场 线上渠道或成主战场 国家卫健委数据显示，中国目前有超过2.5亿人受脱发问题困扰，据灼识咨询报告预测，这一群体到2026年将达到3.43亿人。 除斑秃外，雄激素性脱发、瘢痕性脱发也是较常见的脱发类型，其中雄脱患者占所有脱发类型的九成以上。《中国人雄激素性脱发诊疗指南》显示，在中国，男性雄脱患病率约为21.3%，女性患病率约为6%。 据悉，雄脱是进行性加重，从毛囊微小化、生长期变短，毛发变细变少，进而脱发的过程，从治疗层面看需要长期用药。 庞大的患者人群和长期用药属性叠加，使得雄脱治疗市场规模也相当可观。据弗若斯特沙利文数据，中国毛发医疗服务市场规模在2020年已达到184亿元，预计到2030年将达到1381亿元，年复合增长率高达22.3%。 具体药物方面，《中国人雄激素性脱发诊疗指南》对非那雄胺和米诺地尔均进行等级高推荐，其中，非那雄胺为口服药，主要适用于男性，米诺地尔为外用药，对性别没有明显使用限制。 米内网数据显示，近年来，米诺地尔在三大终端的合计销售规模逐年攀升，2023年突破25亿元。分品牌看，三生制药的米诺地尔酊（蔓迪）、振东制药的米诺地尔搽剂（达霏欣）和美商医药的米诺地尔酊（美商）分别排名前三，销售额均超过1亿元。 相较于具有免疫类疾病属性的斑秃，雄脱治疗药物市场在院外，尤其线上渠道拥有更广阔的空间。 以米诺地尔为例，2023年其在公立医疗机构终端销售额超2亿元；在城市实体药店终端，其连续三年保持两位数增速，销售额破3亿元；在网上药店终端，米诺地尔销售额超过19亿元，创下历史新高。 2023年中国三大终端六大市场米诺地尔品牌TOP6（单位：亿元） 注：销售额不足1亿元用*表示 传统药物销售规模保持高速增长的同时，脱发治疗市场还在不断迭代中。 一方面是老药创新，多家企业通过优化米诺地尔等传统产品剂型提高药物渗透速度。 另一方面是新药研发，今年5月，开拓药业自主研发的KX-826酊剂1.0%治疗雄脱的临床试验获NMPA批准；2月，特科罗生物的外用涂抹制剂TDM-105795用于治疗雄脱的首个Ⅱ期临床试验顺利完成；1月，和其瑞医药HMI-115治疗雄脱的Ib期临床研究已完成并取得积极结果。 兼具医疗、消费属性的脱发用药市场，未来将在产品细分、渠道多元的方向上更进一步。 END 内容沟通：郑瑶（13810174402） 医药代理商产品交流群 扫描下方二维码加入 银发经济市场机遇交流群 扫描下方二维码加入 左下角「关注账号」，右下角「在看」，防止失联

Results Highlights for Interim Results ended 30 June 2024 Revenue reached RMB981.8 million Gross profit amounted to RMB339.1 million Net profit grew by 956.0 YoY to RMB144.2 million Adjusted non-IFRS net profit reached RMB168.2 million, increased by 15.1% YoY HONG KONG, Aug. 29, 2024 /PRNewswire/ -- On August 29, 2024, Viva Biotech Holdings Group ("Viva Biotech", "the Group" or "the Company", stock code: 1873.HK) announced that the Group achieved a revenue RMB981.8 million; and the Group's gross profit of RMB339.1 million. The Group's net profit amounted to RMB144.2 million, a significant improvement from the net profit of RMB13.7 million for the corresponding period of last year, mainly benefiting from the elimination of relevant financial adjustments due to the full repayment of convertible bonds; Adjusted non-IFRS net profit improved from RMB146.1 million for the corresponding period of last year to an adjusted non-IFRS net profit of RMB168.2 million, representing a year-on-year increase of nearly 15.1%. This was mainly attributable to the investment income from the group successful exit of certain portfolio companies as well as the positive contribution from initiatives to reduce costs and increase efficiency. In addition, since the Group completed the introduction of strategic investors such as Temasek, HighLight Capital, True Light Capital and Investment Corporation of Dubai in 2023, the strategic investors have brought synergies in corporate governance, business operations, investment and financing plans and strategic development of the Group. CRO Growth to Gradually Recover in the Future Despite Fluctuations in the Short to Medium Term In the first half of 2024, the Company's revenue from CRO business amounted to RMB385.9 million and achieved a corresponding adjusted gross profit of RMB167.2 million. The revenue for the first half of 2024 decreased compared to last year, primarily due to the short-term impact from challenges in global biopharmaceutical investment and financing on the R&D of innovative drugs, as well as the strategic contraction of the Company's EFS business last year. Nevertheless, the Company effectively implemented measures such as cost reduction and efficiency enhancement to maintain a solid profitability for the CRO business. The gradual recovery of new CRO orders since the second quarter of 2024 will provide a strong support for the Company's business results in the second half of the year. As at June 30, 2024, the Company has cumulatively delivered more than 74,109 protein structures to our clients, approximately 9,074 of which were newly delivered in the first half of 2024. The Company's R&D has accumulated over 2,065 independent drug targets, 79 of which were newly delivered in the first half of 2024. Currently, the Company maintains a leading global position in the industry in the field of protein structure analysis. The cumulative number of CRO clients served had increased to 1,465, including the global top 10 pharmaceutical companies (by reported total revenue for the first half of 2024), and revenue from the top 10 customers accounted for 25.7% of our total revenue. Clients of CRO business are geographically diverse, overseas clients contributed approximately 88.8% of our total revenue, while those from the Chinese Mainland contributed approximately 11.2% of our total revenue. During the Reporting Period, our utilization of synchrotron radiation source reached 873 hours. The Company established long-term cooperation with 13 synchrotron radiation source centers around the world, which are distributed in ten countries/regions, i.e., Shanghai, China, the United States, Canada, Japan, Australia, the United Kingdom, France, Germany, Switzerland and Taiwan, China, thus guaranteeing uninterrupted data collection all year round. Continuing to Expand CDMO Capacity and Increase CMC Projects The Group is committed to building a one-stop service platform for global innovative drugs from research and development to production, and improved the production layout through acquisition of the entire equity interests in Langhua Pharmaceutical. In particular, we continued to expand CDMO capacity to prepare for commercial production of new molecules in the future. In addition, constant efforts were made to optimize and channel resources towards the CMC business during the Reporting Period. In the first half of 2024, Langhua Pharmaceutical's revenue amounted to RMB595.9 million, and its adjusted gross profit amounted to RMB179.0 million, primarily attributable to the impact from the delivery schedule of certain CDMO orders, most of which are expected to be delivered in the second half of 2024. As at June 30, 2024, Langhua Pharmaceutical had served a total of 885 clients, with the top ten clients accounting for 63.2% of its total revenue and a 100% retention rate of top ten clients. In addition, Langhua Pharmaceutical provided CMC and CDMO services to 12 incubator companies of the Group as well as companies channeled from CRO business. During the Reporting Period, in respect of production capacity, our current available total capacity reaches 860 cubic meters. Furthermore, Langhua Pharmaceutical plans to establish a new production capacity of 400 cubic meters between 2024 and 2025 to cater to commercial production of new molecules. The civil engineering project is largely completed while internal fire control facilities are under installation, and the next phase will involve procurement and installation of equipment. This endeavor will provide sufficient guarantee for the Company's revenue growth with the launch of new products and release of reserved capacity. The number of CMC projects continued to grow, but the new business is still in the profit ramp-up phase. Since its establishment, CMC has completed and is currently progressing with a total of 218 new drug projects. During the Reporting Period, CMC generated revenue of nearly RMB21.0 million. In the future, the Group plans to strengthen BD and channeling efforts for acquiring high-quality CMC projects. By fully utilizing internal project resources and implementing cost reduction and efficiency enhancement measures, the Group aims to achieve a balanced financial outcome for its CMC business. In addition, in terms of the number of customer orders, external BD accounted for nearly 75.0%, while channeled accounts from Viva represented approximately 25.0%. In terms of order amount, external BD contributed 49.0%, while channeled accounts from Viva contributed 51.0%. Successful Exits of Certain Incubation Portfolio Companies Continued to Realize Investment Returns, Accretive to the Group's Profits During the Reporting Period, the Company achieved partial investment exits from a number of portfolio companies (Focus-X, Saverna, Dogma and Riparian), realizing corresponding investment returns and generating total proceeds of nearly RMB144.1 million. In addition, the Company also achieved investment exit from one portfolio company (Nerio) subsequent to the Reporting Period in the end of July 2024, but the investment income therefrom will not be recognized in the interim report for the Reporting Period. As at June 30, 2024, the Group had invested in a total of 92 portfolio companies. The portfolio companies are mainly from the United States, Canada, Europe and China. 67.0% of the portfolio companies are from North America and 26.0% are from China. In the first half of 2024, five of our portfolio companies completed or were close to completing a new round of financing, raising approximately US$117.0 million in total. The R&D efforts of the portfolio companies were advancing smoothly, with the total number of pipeline projects reaching close to 222, of which 185 pipelines are in the preclinical stage and 37 pipelines in the clinical stage. So far, the Group has successfully realized 13 investment exits or partial exits. Furthermore, the Group may have several potential exits of our portfolio companies, and it also can be foreseen that a peak season of investment exits will arrive in the next three years. As at the end of the Reporting Period, Viva has strategically invested in a series of high-quality assets, including portfolio companies such as Dogma, Arthrosi, Basking, Triumvira, Deka, Mediar, Cybrexa, VivaVision, Haya and Nerio. In the future, as these portfolio companies continue to develop successfully, secure ongoing financing, and realize exits, the initial investments will gradually enter the harvesting phase, providing sustained cash returns and investment income for the Group. T echnological highlights and R&D Breakthrough s Riding on the rapid development of artificial intelligence (AI) technology recently, Viva has further introduced AI technology on the basis of structure-based drug discovery (SBDD) technology, focusing on new targets, novel mechanisms of action (MOA) and new modality to develop a unique AI-enabled SBDD one-stop R&D service platform for innovative novel drugs. Firstly, from the perspective of current research on new targets, new targets are the most important source of original innovation. During the Reporting Period, our R&D has accumulated over 2,065 independent drug targets, 79 of which were newly delivered in the first half of 2024. So far, the Company has delivered to clients a series of target protein structures that have not been reported in the Protein Structure Database (PDB), and clarified the structural principles of these proteins in functioning, laying a solid foundation for subsequent drug molecular design. For example, in the cancer therapeutic area, industry players are still searching for new targets as breakthroughs, in addition to traditional target proteins such as kinases, proto-oncogenes/tumor suppressor genes, immune checkpoints, etc. In the fields of new tumor target proteins related to cell division control and mRNA stability, we successfully analyzed many previously unreported protein structures and complex structures of proteins and drug candidate molecules, and explained structural details of the interaction between target proteins and compounds, which provide clear guidance for designing more effective compounds and lead to the emergence of a range of new drug candidate molecules. Besides, the Company contributed a number of new structures in the molecular glue protein complex structural field, which further provide effective clues for rational design and improvement of molecular glue drugs. Secondly, regarding novel MOA research progress, our CRO business has successfully established a one-stop platform for novel MOA-based drug discovery and research, and set up relevant technical platforms covering protein production, preparation and structure research, Cryo-EM technology, membrane protein research technology, drug screening technology, bioassay and so on. Moreover, based on the validation and tests of hit compounds, the Company can rely on its strong pharmaceutical chemistry team and computing team to help clients further optimize the structure of hit compounds until they reach the preclinical candidate (PCC) milestone. Meanwhile, the Company's pharmacology and pharmacokinetics platform can also provide clients with systematic compound druggability evaluation services for the development of novel MOA-based compounds. Thirdly, regarding current progress of new modality related technology platforms, during the Reporting Period, Viva Biotech drew upon a wealth of projects completed over the years to gradually integrate its macromolecular drug/antibody platform, peptide platform and micromolecule drug platform into a cross-field XDC platform. Deeply integrating computational chemistry and artificial intelligence technology with XDC technology, the Company explored in a wide range of innovative fields such as coupling site screening design, linker-drug payload design, overall hydrophobicity and stability modification of XDC drugs, and development of novel coupling reactions, expanding new directions for XDC drug R&D. On this basis, the Company further integrated the XDC platform with DNA encoded library (DEL) technology, leveraging strong screening capabilities of the Viva DEL platform to help screen special micromolecule linkers and drugs, and relying on its team's unique experience in nucleic acid conjugation to establish an antibody-oligonucleotide conjugate (AOC) platform. So far, based on full integration of our existing technology platforms across multiple fields, we have established a powerful, comprehensive and one-stop XDC technology service platform. Besides, regarding construction progress in the peptide technology platform, the Company has achieved the capability to synthesize a wide range of peptides, particularly the challenging and technologically advanced peptide chains. Extensive research and technical expertise have been accumulated in peptide coupling, peptide drug conjugates (PDC), radionuclide drug conjugates (RDC), monocyclic peptides, stapled peptides and other complex multi-cyclic peptides (involving peptide folding and selective cyclization), biotin-labeled peptides and fluorescent-labeled peptides. In terms of peptide coupling, our peptide platform works with antibody department to expand the peptide platform to the field of peptide antibody coupled APC, and has delivered relevant products. In the future, Viva's peptide technology platform envisions a collaborative approach with Viva's phage display platform and V-DEL platform, aiming to provide customers with one-stop comprehensive services encompassing the entire process from the discovery and validation of hit peptide chains to the identification and optimization of lead compounds, and ultimately the determination of candidate compounds. In addition, Viva also provides services relevant to PROTAC/molecular glue drug R&D, and revenue generated in this regard accounted for almost 10.87% of total revenue from the CRO business. Our services primarily include studies on protein preparation and structure, screening of PROTAC/molecular glue, kinetics, drug metabolism, pharmaceutical chemistry, Bioassay, computer-aided drug discovery (CADD)/ artificial intelligence in drug discovery (AIDD), etc. As at June 30, 2024, the Company has studied more than 50 E3 ligase complexes and delivered 140 PROTAC ternary complex structures. The PROTAC business also became a revenue contributor to the growth of our CRO business. Last but not least, regarding our AI-enabled SBDD one-stop R&D service platform for innovative novel drugs, our CADD and AIDD platforms employ physical chemistry models and artificial intelligence algorithms to advance drug R&D projects, based on deep understanding of structures and mechanisms of action to truly practice computation-driven drug R&D. Our computing platform has developed a series of project-specific advanced algorithms to solve practical problems in drug design such as covalent and non-covalent free energy perturbations (FEP), resulting in higher computational accuracy and larger adjustable parameter range. Addressing gaps in the traditional computational chemistry methodology, the computing platform introduced generative artificial intelligence algorithms, which break through the limitation of chemical space with ab initio generation, enabling drug design to achieve the breakthrough from zero to one with the aid of computation. Furthermore, ADME/PK prediction models were developed under the platform, enabling comprehensive coverage of various drug R&D stages and systematic integration of computing tools. The methods developed under the computational chemistry and artificial intelligence platform have been applied in the R&D of various drug modalities, such as small molecules, antibodies, peptides and RNA-targeting small molecules. In the process of algorithm development, our platforms maintain the integration of dry-lab and wet-lab and the computational results are verified through experimental validation, during which computational models are iteratively optimized to ultimately achieve breakthroughs. Generally, Viva's CADD and AIDD platforms have the capability to develop proprietary algorithms and enhance platforms and the experience in exploring various drug modalities, and fully leverage our advantages in SBDD, which can comprehensively empower various early drug R&D aspects with the computing power supported by the Shanghai supercomputing cluster. S taff and Facilities As at June 30, 2024, the Group had a total of 2,043 employees, of whom the number of CRO R&D personnel reached 1,117, and the headcount of Langhua Pharmaceutical was 704. The Company has well-established office and laboratory facilities in line with its workforce expansion plans, and is expanding production capacity to meet the fast-growing business needs, including: The Group's new headquarters in Zhoupu, Shanghai with a total area of approximately 40,000 square meters had been put into full operation. The incubation center located in Faladi Road, Shanghai has an actual usable area of approximately 7,576 square meters, including 5,552 square meters of laboratory area. The park in Chengdu has a GFA of approximately 64,564 square meters, of which 12,210 square meters of properties had been put into use as at June 30, 2024, including 10,800 square meters of laboratory area. A park in Suzhou with a total GFA of approximately 7,545 square meters, including nearly 5,305 square meters of laboratory area. A park in Jiaxing with a GFA of approximately 6,362 square meters, including nearly 5,335 square meters of laboratory area. Shanghai Supercomputing Center has been officially put into operation. At present, it can support CADD computation, AIDD related computation, and crystal structure and Cryo-EM (Micro-ED) computation. The factory of Langhua Pharmaceutical in Taizhou, Zhejiang has a GFA of approximately 35,168 square meters, including the Taizhou R&D center with an area of approximately 2,500 square meters. The R&D center of Ningbo Nuobai has an area of approximately 1,300 square meters and the office building of Ningbo Nuobai has an area of approximately 1,500 square meters. Dr. Cheney Mao, Chairman and Chief Executive Officer of Viva Biotech Holdings, stated, "With unique advantages in structure-based drug discovery (SBDD), the company will increase the cross-sell between biological and chemical businesses, continue to strengthen the construction of its one-stop innovative novel drug R&D platform and manufacturing service platform, deepen the synergy between CRO and CDMO business, improve the capacity building for front-end services and drive business to back-end services to further enhance the business funnel effect. Actively building an open collaboration platform and a win-win ecosystem for global biopharma innovators." About Viva Biotech Established in 2008, Viva Biotech (01873.HK) provides one-stop services ranging from early-stage Structure-Based Drug R&D to commercial drug delivery to global biopharmaceutical innovators. We offer leading early-stage to late-phase drug discovery expertise by integrating our dedicated team of experts, cutting-edge technology platforms, and state-of-the-art equipment in X-ray crystallization, Cryo-EM, DEL, ASMS, SPR, HDX-MS, AIDD/CADD, and much more. Our business covers all aspects of therapeutic strategies and drug modalities, including small molecules and biologics across the pharma and biotech spectrum. The experienced chemistry team, led by senior medicinal chemists and drug discovery biologists, provides services for drug design, medicinal chemistry (hit to lead and lead optimization), custom synthesis, chemical analysis and purification, kilogram scale-up, peptide synthesis and corresponding bioassays. With our subsidiary Langhua Pharmaceutical, we offer worldwide pharmaceutical and biotech partners a one-stop integrated CMC (Chemical, Manufacturing, and Control) service from preclinical to commercial manufacturing. Additionally, Viva Biotech embedded an equity for service (EFS) model to high potential startups to address unmet medical needs. As of June 30, 2024, Viva Biotech had cumulatively provided drug R&D and manufacturing services to 2,350 biotech and pharmaceutical clients around the world. We have invested and incubated 92 biotech start-ups in total. In the future, the company will continue to strengthen its technological barriers and improve R&D, production levels, and our service capacity to provide high-quality and diversified services for more drug discovery start-ups, as well as medium and large pharmaceutical enterprises around the world. SOURCE Viva Biotech Holdings