CStone Pharmaceuticals ("CStone", HKEX: 2616), an innovation-driven biopharmaceutical company focused on the research and development of anti-cancer therapies, announced the submission of clinical trial application in Australia for CS2009 (PD-1/VEGF/CTLA-4 trispecific antibody), a leading asset from the Company's Pipeline 2.0 to address various solid tumors. This first-in-human study has also been registered and published on Clinicaltrials.gov (NCT number: NCT06741644).

CS2009 features an innovative molecular design that targets PD-1, VEGFA, and CTLA-4 simultaneously, maintaining balanced affinity for PD-1 and CTLA-4. This design enables preferential targeting of double-positive tumor-infiltrating T lymphocytes (TILs), effectively blocking both PD-1 and CTLA-4 while sparing CTLA-4 on single-positive cells. This approach could potentially reduce systemic toxicity without compromising efficacy. Additionally, CS2009 induces high and rapid internalization, leading to the down-regulation of PD-1 and CTLA-4 expression on the TIL cell membrane. Notably, CS2009 retains full VEGF inhibitory function, and preclinical data indicate that its anti-VEGF activity exhibits significant synergistic effects with its immune checkpoint inhibitory functions—crosslinking with VEGFA markedly enhances both anti-PD-1 and anti-CTLA-4 activities.

At the 39th Annual Meeting of the Society for Immunotherapy of Cancer (SITC Annual Meeting) in 2024, CStone presented compelling preclinical data for CS2009, demonstrating superior anti-tumor activity compared to potential competitors. The data underscored the potential of CS2009 to address a wide range of tumor types, including non-small cell lung cancer, ovarian cancer, renal cell carcinoma, cervical cancer, hepatocellular carcinoma, and gastric cancer. CS2009 is positioned as a potential first-in-class or best-in-class next-generation immuno-oncology backbone.

Dr. Jason Yang, CEO, President of R&D, and Executive Director at CStone, stated: "We are excited to announce the timely submission of the Phase I clinical trial application for CS2009, marking another significant milestone in CStone's Pipeline 2.0 strategy. Designed and developed in-house since 2022, CS2009 has evolved into a tri-specific antibody with a novel molecular design and robust preclinical data, holding the potential to replace current anti-PD-(L)1 therapies. Thanks to close collaboration across departments, we have rapidly advanced CS2009 to the clinical stage. The first-in-human study will soon commence in Australia, and we look forward to exploring the potential benefits CS2009 could bring to cancer patients, particularly those with low or negative PD-L1 expression who respond poorly to existing PD-(L)1 treatments."

CStone plans to initiate a multi-regional, first-in-human clinical trial for CS2009 in Australia in early 2025, followed by expansion into China and the United States.