CStone Pharmaceuticals has announced the submission of a clinical trial application (CTA) in Australia for CS2009, an innovative trispecific antibody targeting PD-1, VEGFA, and CTLA-4. This first-in-human study, registered on Clinicaltrials.gov (NCT06741644), marks a significant step in CStone's Pipeline 2.0 strategy, aimed at developing novel therapies for solid tumors.
Innovative Design for Enhanced Efficacy and Reduced Toxicity
CS2009 features a unique molecular design that simultaneously targets PD-1, VEGFA, and CTLA-4. The antibody maintains a balanced affinity for PD-1 and CTLA-4, enabling preferential targeting of double-positive tumor-infiltrating T lymphocytes (TILs). This approach effectively blocks both PD-1 and CTLA-4 while sparing CTLA-4 on single-positive cells, potentially reducing systemic toxicity without compromising efficacy. Furthermore, CS2009 induces rapid internalization, leading to the down-regulation of PD-1 and CTLA-4 expression on TILs. The molecule retains full VEGF inhibitory function, and preclinical data suggest a synergistic effect between its anti-VEGF activity and immune checkpoint inhibitory functions.
Preclinical Data Highlights Superior Anti-Tumor Activity
At the 39th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) in 2024, CStone presented preclinical data demonstrating CS2009's superior anti-tumor activity compared to potential competitors. The data indicated that CS2009 could be effective against a wide range of tumor types, including non-small cell lung cancer, ovarian cancer, renal cell carcinoma, cervical cancer, hepatocellular carcinoma, and gastric cancer. These findings position CS2009 as a potential first-in-class or best-in-class next-generation immuno-oncology backbone.
Clinical Development Plans
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. According to Dr. Jason Yang, CEO, President of R&D, and Executive Director at CStone, this trial will explore the potential benefits of CS2009 for cancer patients, particularly those with low or negative PD-L1 expression who respond poorly to existing PD-(L)1 treatments.
About CS2009
CS2009 is designed to reinvigorate exhausted TILs while demonstrating VEGF neutralization comparable to existing anti-VEGF antibodies. Its trispecific design aims to improve upon existing therapies by combining three clinically validated targets into a single molecule.
