CSTONE PHARMA-B(02616): PD-1/VEGF/CTLA-4 triple specific antibody CS2009 global multicenter Phase I clinical trial successfully completed first patient dosing.

CSTONE PHARMA-B (02616) announced that the global multicenter Phase I clinical trial of its independently developed PD-1/VEGF/CTLA-4 triple-specific antibody CS2009 has successfully completed the first patient dose, with no infusion reactions or other adverse events reported. The trial will further evaluate the clinical application value of CS2009 in a variety of advanced solid tumors, including non-small cell lung cancer, liver cancer, gastric cancer, endometrial cancer, ovarian cancer, renal cell carcinoma, and cervical cancer, aiming to promote the development of innovative cancer immunotherapy. CS2009 is a new triple-specific antibody independently developed by Cstone Pharma, targeting three clinically validated targets: PD-1, VEGFA, and CTLA-4, to achieve multi-dimensional anti-tumor effects through synergistic action. Specifically, blocking PD-1 can reverse T cell exhaustion, blocking CTLA-4 can promote T cell activation and proliferation, and blocking VEGFA can inhibit tumor angiogenesis, thereby improving the tumor microenvironment. In the tumor microenvironment, the dual blocking action of PD-1 and CTLA-4 is significantly enhanced by the interaction with VEGFA. Additionally, CS2009 can selectively bind to tumor-infiltrating T cells with dual positivity for PD-1 and CTLA-4, and maximally weaken interference with the CTLA-4 regulatory pathway in peripheral T cells. This innovative molecular design is expected to enhance efficacy while reducing systemic toxicity. Preclinical studies have shown that CS2009 has better anti-tumor activity than potential competitors. By combining CTLA-4 inhibition and blockade of PD-1 and VEGFA, CS2009 is expected to further improve efficacy in patients with low expression of PD-L1 or PD-L1-negative who have a poor response to PD-(L)1 therapy, making it a potential next-generation cancer immunotherapy product to replace existing PD-(L)1-based therapies. Dr. Frank Jiang, CEO, President of R&D, and Executive Director of Cstone Pharma, stated, "The successful initiation of the first human study of CS2009 marks the official entry of this innovative therapy into the clinical validation stage. Our existing preclinical data has demonstrated its potential in various solid tumor indications. In vitro experiments have shown that CS2009 has effective specific activation of tumor-infiltrating T cells and efficient synergy with VEGF antagonistic function; in fully immunocompetent mouse models, the tumor-killing effect of CS2009 is superior to PD1/CTLA-4 bispecifics and PD-1/VEGF bispecifics; toxicology studies have shown that the safe dosage level of CS2009 is significantly higher than that of PD1/CTLA-4 bispecifics and comparable to PD-1/VEGF bispecifics. Based on this, we are confident in the clinical potential of CS2009 and look forward to releasing more clinical data to further demonstrate its excellent safety and anti-tumor activity, paving the way for a new era of next-generation cancer immunotherapy." Dr. Jason Sha, Chief Medical Officer of Cstone Pharma, said, "We are pleased to see the milestone of the first patient dose being successfully achieved with CS2009. As an innovative triple-specific antibody, CS2009 not only balances efficacy and safety but also has the potential to overcome the treatment bottleneck in patients with low expression of PD-L1 or PD-L1 negativity. We look forward to rapid and positive progress in this study, providing better treatment options for global solid tumor patients as soon as possible. We are also very grateful for the clinical team of Cstone Pharma, who, despite crossing multiple holidays both domestically and internationally, completed the entire process from clinical trial application submission in Australia to the first patient dose in just over two months. This once again demonstrates the outstanding clinical development efficiency of Cstone Pharma and our firm commitment to serving patients." Currently, the Phase I clinical trial of CS2009 is being conducted in multiple centers in Australia and will be expanded to China and the United States in the future. CS2009 is a triple-specific molecule targeting PD-1, VEGFA, and CTLA-4, as a triple-specific antibody targeting major tumor types, with the potential to be a first-of-its-kind and best-in-class agent. CS2009 has a differentiated molecular design, combining three clinically validated targets, and can reactivate tumor-infiltrating T cells close to exhaustion, with VEGF neutralizing capability comparable to that of original anti-VEGF antibodies. It covers a wide range of diseases, including non-small cell lung cancer, liver cancer, gastric cancer, endometrial cancer, ovarian cancer, renal cell carcinoma, and cervical cancer. In November 2024, Cstone Pharma presented the preclinical data of CS2009 at the 39th Annual Meeting of the Society for Immunotherapy of Cancer (SITC). Preclinical data showed that CS2009 has significantly better anti-tumor activity than potential competitors (including PD-1/CTLA-4 bispecifics, PD-1/VEGF bispecifics, and anti-PD-1/anti-CTLA-4 combination therapy).