CStone Begins Global Phase I Trial of CS2009 Trispecific Antibody

SUZHOU, China, March 3, 2025 – CStone Pharmaceuticals, a company dedicated to innovative cancer treatments, has announced the successful dosing of the first patient in its international Phase I clinical trial for CS2009, a novel trispecific antibody. This milestone marks an important step in evaluating CS2009's potential against a wide array of advanced solid tumors. The trial will investigate its effectiveness on various cancers, such as non-small cell lung cancer, hepatocellular carcinoma, gastric adenocarcinoma, endometrial cancer, ovarian cancer, renal cell carcinoma, and cervical cancer.

CS2009 is an advanced trispecific antibody developed by CStone, targeting three validated cancer-related proteins: PD-1, VEGFA, and CTLA-4. Its mechanism is designed to provide a comprehensive anti-tumor response. The antibody works through multiple pathways – reversing T cell exhaustion via PD-1 blockade, promoting T cell activation and proliferation by inhibiting CTLA-4, and preventing tumor angiogenesis by blocking VEGFA. This innovative approach could lead to improved treatment outcomes with potentially reduced systemic toxicity. In the tumor microenvironment, the interaction between these targets is optimized to enhance the antibody's efficacy.

In preclinical evaluations, CS2009 demonstrated superior anti-tumor effects compared to similar therapies. By integrating the inhibition of CTLA-4 with PD-1 and VEGFA blockade, it may offer enhanced benefits for patients who exhibit low or negative PD-L1 expression, a group that typically has a poor response to existing PD-(L)1 therapies. CS2009 holds promise as a new foundational immunotherapy, with the potential to surpass existing PD-(L)1-based treatments.

Dr. Jason Yang, CEO and President of R&D at CStone, shared his enthusiasm about the commencement of the first-in-human study for CS2009. The strong preclinical results have shown its potential across various solid tumor types. In laboratory studies, CS2009 has effectively activated tumor-infiltrating T cells and exhibited a robust synergistic effect with anti-VEGF activity. In animal models, its anti-tumor effects surpassed those of PD-1/CTLA-4 and PD-1/VEGF bispecific antibodies. Toxicology studies indicated a favorable safety margin for CS2009, better than the PD-1/CTLA-4 bispecific antibody and comparable to the PD-1/VEGF bispecific one. These findings bolster confidence in its clinical application, with anticipation of further data to support its safety and efficacy.

Dr. Qingmei Shi, Chief Medical Officer at CStone, expressed satisfaction with reaching the first-patient-dosed milestone. CS2009 is designed to offer both efficacy and safety, addressing the unmet needs of patients with low or negative PD-L1 expression. The study is expected to progress swiftly, and the company is eager to introduce enhanced treatment options for solid tumor patients globally. Dr. Shi praised the dedication of the clinical team in achieving this milestone, noting their efficiency in navigating the process from trial application to dosing in a short span, even during major holidays in China and Australia.

Currently, the Phase I clinical trial of CS2009 is underway in Australia, with plans to expand into China and the United States soon. This study is part of CStone's broader effort to develop innovative therapies for cancer treatment.

CStone Pharmaceuticals, established in 2015, focuses on developing cutting-edge cancer therapies, aiming to meet unaddressed medical needs both in China and internationally. Since its inception, CStone has launched four innovative drugs and secured approvals for 16 new drug applications, covering nine indications. The company's pipeline features a balanced selection of 16 candidates, including potentially first-in-class or best-in-class therapies. CStone's management team boasts extensive experience across the drug development spectrum, from research and clinical development to manufacturing and commercialization.