Akeso Biomedical, Inc.

Akeso, Biopharma (9926. HK) ("Akeso") announced the patient enrollment completion for the Phase III clinical trial of Ivonescimab (PD-1/VEGF bi-specific antibody, AK112) combined with chemotherapy for the treatment of EGFR-mutant locally advanced or metastatic non-squamous non-small cell lung cancer (nsq-NSCLC) who have failed to epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment. This trial is a randomized, double-blind, multi-center Phase III clinical trial, which started patient enrollment in end of January 2022, and it has enrolled 320 participants as of the date of this press release. The primary endpoint of the trial is progression-free survival (PFS) assessed by IRRC. This therapy was granted Breakthrough Therapy Designation by the Center for Drug Evaluation, National Medical Products Administration (CDE, NMPA) lately in October 2022. Lung cancer is a malignant tumor with high incidence and high mortality rates worldwide. The incidences of lung cancer around the world and in China have exceeded 2.2 million and 810 thousand respectively in 2020. Non-small cell lung cancer (NSCLC) patients account for 85% of total lung cancer patients, and about 70% of NSCLC patients are diagnosed at advanced stages. In China, nsq-NSCLC accounts for 70% of NSCLC, and about 40%-50% of nsq-NSCLC patients have EGFR mutation. Immunotherapy plus anti-angiogenesis therapy has proved its combination advantages in previous studies worldwide. Lung cancer is one of the mainstream exploration areas of this therapy. AK112 could simultaneously block PD-1 and VEGF targets and has demonstrated favourable safety profile and promising anti-tumor efficacy in ongoing studies conducted by Akeso. AK112 in combination with chemotherapy is expected to provide a novel and effective therapy for the treatment of EGFR-mutated locally advanced or metastatic nsqNSCLC patients who have failed to EGFR-TKI treatment. ABOUT IVONESCIMAB (PD-1/VEGF BI-SPECIFIC ANTIBODY, AK112) Ivonescimab is a first-in-class and the first to enter phase III clinical trial PD-1/VEGF bi-specific antibody independently developed by Akeso. Engineered with our unique Tetrabody technology, Ivonescimab blocks PD-1 binding to PD-L1 and PD-L2, and blocks VEGF binding to VEGF receptors. PD-1 antibody combined with VEGF blocking agents have shown robust efficacy in various tumor types (including renal cell carcinoma, non-small cell lung cancer and hepatocellular carcinoma). In view of the co-expression of VEGF and PD-1 in the tumor microenvironment, Ivonescimab, as a single agent to block these two targets, may block these two pathways more effectively and enhance the antitumor activity, as compared to combination therapy. Currently, Akeso is conducting a phase III clinical trial of AK112 monotherapy versus Pembrolizumab monotherapy as the first-line treatment for NSCLC patients with positive PD-L1 expression. In addition, a phase III clinical trial of AK112 plus chemotherapy versus chemotherapy in EGFR mutated advanced non-squamous NSCLC that failed in prior EGFR-TKI therapy is ongoing. AK112 has been investigated in multiple clinical trials for various stages treatment of indications including non-small cell lung cancer and small cell lung cancer.

医药智能化质量管理平台——阿克索的源起，与创始团队一次数字化转型的经历有关。创始合伙人兼总经理冉军告诉动脉网：“几年前，阿克索创始人之一所在的药企进行数字化转型，需采购整合GMP文档管理系统、培训管理系统、质量管理系统的一体化平台。没想到先后调研了国内外多家厂商，都没能找到心仪的产品。”市面上数字化质量管理平台的海外传统厂商，以本地化部署的Trackwise和Documentum为主。而新一代厂商Veeva采用先进的公有云saas模式部署，提供质量管理一体化平台，克服了老一代系统实施周期长、部署成本高、用户友好度低等问题，一经推出便受到了多家全球顶尖药企的青睐。但对国内药企而言，其产品价格过高，年订阅费动辄数百万，甚至上千万，且数据库设在海外，响应速度慢，存在一定数据安全风险。简单来说，受海外产品价格昂贵、响应速度慢、运维风险、数据安全等因素的限制，国内药企正在寻找技术先进、性价比更高的国产化解决方案。目前市面上看到的国内提供质量管理系统的企业多数由IT背景团队组成，对制药GMP质量管理业务场景缺乏深入理解，难以契合客户实际需求，也存在合规性风险。“这就像卖农机，如果工厂没有任何农业知识，不知道怎么种地，生产出来的机器大概率不好使。”冉经理解释道。基于市面上对合规性、高性价比、先进的新一代数字化质量管理平台的迫切需求，阿克索联合了一批顶尖的AI专家、GMP专家、CSV（计算机系统验证）专家，组成既懂业务又懂IT的团队，契合药企真实需求，共同研发了Akso eGMP。依靠团队在IT、AI领域的沉淀和对药企质量管理业务的深刻洞察，阿克索eGMP质量管理一体化系统上线仅一年，就已经和天士力圣特、新华制药、海默尼等多家国内知名药企达成合作。我国药品质量管理理念始终在进步迭代早期质量管理通过检查保证质量，属于事后把关、被动管理；第二阶段质量管理理念将质量管理提前到生产过程，在生产过程中的每个环节，严格按照生产工艺和作业指导书要求进行；第三阶段质量管理理念提倡“质量是设计出来的”，从设计上，提升产品工艺的稳健性和质量水平；第四阶段质量管理应用大数据、AI、云计算等新一代创新技术，进一步提升质量管理合规高效。在不同的质量理念倡导下，药企对于质量管理解决方案的需求也不同。冉军表示：“在新的理念体系下，药企对数字化质量管理系统的需求主要聚焦于合规性、先进性和可配置性。”首先是合规性。医药行业与人体健康息息相关，合规性要求极高，即使是看起来简单的电子签名，背后也有一系列国际国内药证法规的严格规定。故此，厂商需要熟悉全球制药行业法规，在产品设计和开发中保证合规性，能够对数据进行分析，自动预警，前瞻性识别质量管理风险。其次是产品先进性和可配置性。医药客户的需求具有差异化，根据GAMP5的定义，定制化开发属于5类软件，药政官方检查合规性风险大，传统软件厂商很难确保定制开发系统的合规性；而只有高度可配置化的4类软件产品，类似于搭积木的方式来满足客户的需求，不但降低客户的验证和维护成本，还能减少合规风险。实际上要做到可配置的4类软件，比定制开发的5类系统来说，需要具备更高的技术能力，要投入更多的研发成本，阿克索坚持长期深耕医药质量管理，在研发方面投入了很多资源才做到了产品的高可配置性。迅速合作多家药企，效率提升明显在合规性上，阿克索拥有ISO27001信息安全管理系统认证、ISO9001质量管理体系认证，可保证信息安全管理、质量管理双合规性，符合全球法规要求。阿克索开发的eGMP质量管理一体化系统基于新一代SaaS模式，可拓展性强，部署周期短，配置灵活，学习成本低，做到了开箱即用。同时，该平台整合了GMP文档管理系统、培训管理系统、质量管理系统，实现了一体化互联互通，打破信息孤岛，有效帮助药企优化质量流程，确保合规性，提升质量管理效率。目前，Akso eGMP QMS质量管理系统、Akso eGMP DMS文档管理系统和Akso eGMP TMS培训管理系统已经先后上线，正式形成Akso eGMP质量管理一体化系统套件。产品上线之后，短期内迅速吸引了天士力圣特、新华制药、海默尼等多家国内头部知名药企进行合作。这些药企基本都是在市场上花了1-2年时间考察了多家厂商，或是与海外厂商有过短暂合作，一直没有找到满意产品，在了解阿克索eGMP质量管理系统后，迅速推进了合作。数据显示，上线阿克索eGMP质量管理系统以来，天士力圣特质量事务提效显著，效率提升86%。2021年9月，天士力圣特与阿克索进一步合作，引入升级版质量管理系统，以及文档管理和培训管理系统，成功实现eGMP一体化平台联动，完成质量管理数字化转型。药企数字化转型浪潮势不可挡在中国，数字经济已经上升到国家战略地位，提出要将互联网、大数据、人工智能等数字化技术与实体产业深度融合，要发展数字经济，建设数字中国。具体到医药领域，数字化正在快速渗透到药物研发、生产、销售各环节中。在新基建、智慧工厂、工业4.0与中国制造2025背景下，医药数字化转型势在必行。目前，数字化药物研发、数字化质量管理、数字化营销、数字化供应链等均是热门细分赛道。虽然医药数字化关注度极高，药企正在加大投入，但中国医药数字化整体进程较慢，大量环节还依靠人工、纸质方式处理。特别是在质量管理环节，有调研显示，超过90%的国内药企还未上线质量管理系统。“可以肯定的是，从药政当局监管趋势和行业先进企业的实践来看，数字化质量管理趋势势不可挡。一个房间里堆满纸质文档的场景将很快消失，从线下到线上越早启动质量管理数字化升级的企业将占据先机。”冉军表示。众多大型药企已经将质量管理数字化转型纳入规划中，接下来，药企对于数字化质量管理系统的需求将迸发。阿克索将持续迭代，匠心打造品质，让中国药企用上国际一流的数字化质量管理系统。想要联系动脉网报道的企业，请点击文末左下方“阅读原文”填写表单，我们的工作人员将尽快为您服务。左右滑动查看更多近期推荐声明：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

Akeso, Inc. (9926.HK) ( "Akeso" ), a China-based biopharmaceutical company focusing on the development and commercialization of innovative therapeutic antibodies for Oncology & Immunology, announced the publication of preclinical results of its PD-1/CD73 bi-specific antibody (AK131) at the American Association for Cancer Research (AACR) Annual Meeting 2022. AK131 has demonstrated to have potent in-vitro and in-vivo anti-tumor activities. Abstract: AK131, an anti-PD1/CD73 bispecific antibody for cancer immune therapy AK131 is a bi-specific antibody derived from Penpulimab (Akeso's marketed PD-1 antibody ) and AK119 (Akeso's CD73 antibody in clinical stage). AK119 is a dual mechanism antibody (2021 SITC poster #750) that both blocks the generation of adenosine and stimulates antigen specific B cell activation. Adenosine is a key immune suppressive molecule contributing to the resistance of PD-1 antibody therapy. Both CD73 and PD-1 are with high expression in the tumor microenvironment. Moreover, a growing body of literature evidence supports an important role of B cells in anit-tumor immunity. Thus the company developed a bi-specific PD-1/CD73 antibody with the capacity to relieve immune checkpoint control of T cells, activate B cells, and eliminate immune suppression by adenosine, for immune therapy of cancer. The results and observations in AK131's preclinical study support the development of AK131 as an anti-tumor agent in the clinic： AK131 effectively bound to human PD-1 and CD73 with high affinity. The interaction between PD-1 and its ligand PD-L1 was blocked by AK131 in reporter gene assay. In cellular assays, AK131 effectively promoted the secretion of IFN-γ and IL-2 by T cells in co-culture of PBMCs and Raji-PDL1 cells. Moreover, AK131 inhibited CD73 enzymatic activity and induced endocytosis of CD73. AK131 enhanced the expression of CD69, CD83, HLA-DR and IgM which are markers of B cell activation in an adenosine-independent manner. In in-vivo assay, AK131 successfully inhibited tumor growth in C57BL/6-hPD1/hPDL1/hCD73 transgenic mice MC38-hPDL1-hCD73 tumor syngeneic model.