基石药业首席执行官、研发总裁及执行董事杨建新博士表示：“很高兴看到CS2009如期递交I期临床试验申请，这是基石药业管线2.0又一重大里程碑进展。CS2009是我们2022年自立项，从分子设计开始自主研发的一款新型三特异性抗体，拥有充分的临床前数据支撑，有望替代现有 PD-1(L1)疗法。通过各部门之间密切配合和努力，CS2009非常顺利地迈入了临床开发阶段，近期我们将在澳大利亚启动其首次人体研究，期待早日看到CS2009能让癌症患者获益、尤其是那些PD-(L)1疗法响应不佳的PD-L1低表达或PD-L1阴性的群体。” On December 23, Gelonghui reported that CSTONE PHARMA-B (02616.HK) announced that the company's pipeline 2.0 major product CS2009 (a PD-1/VEGF/CTLA-4 trispecific antibody) has submitted a clinical trial application in Australia.
CS2009 is a trispecific antibody with an innovative structural design that targets PD-1, VEGFA, and CTLA-4 simultaneously. CS2009 has a balanced affinity for anti-PD-1 and anti-CTLA-4, which can preferentially target and block PD-1 and CTLA-4 on double-positive tumor-infiltrating lymphocytes (TILs), while not blocking CTLA-4 on single-positive cells, thus reducing potential systemic toxicity while ensuring efficacy. CS2009 can also induce efficient internalization, thereby reducing the expression of immunosuppressive molecules PD-1 and CTLA-4 on the surface of double-positive TILs. Additionally, CS2009 retains full anti-VEGF functionality, and preclinical data shows that CS2009's anti-VEGF function has a significant synergistic effect with immune checkpoint inhibition—interacting with VEGFA can significantly enhance the activity of anti-PD-1 and anti-CTLA-4.
CSTONE PHARMA presented preclinical data for CS2009 at the 39th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) in 2024. Preclinical data shows that CS2009 demonstrates significantly superior anti-tumor activity compared to potential competitors, with the potential to cover a wide range of tumor types, including non-small cell lung cancer, ovarian cancer, renal cell carcinoma, cervical cancer, liver cancer, and gastric cancer, positioning it as a first-in-class/ best-in-class next-generation tumor immunotherapy backbone product.
Dr. Yang Jianxin, CEO, President of R&D, and Executive Director of CSTONE PHARMA, stated: "We are pleased to see CS2009 submit its Phase I clinical trial application on schedule, marking another significant milestone in CSTONE PHARMA's pipeline 2.0. CS2009 is a new trispecific antibody independently developed from molecular design, which was initiated in 2022 and has ample preclinical data support, and is expected to replace existing PD-1 (L1) therapies. Through close cooperation and efforts among various departments, CS2009 has smoothly entered the clinical development stage, with plans to initiate its first human study in Australia soon, hoping to see CS2009 benefit cancer patients, especially those with poor responses to PD-(L)1 therapies, such as those with low PD-L1 expression or PD-L1 negativity."
