On December 22, 2024 CStone Pharmaceuticals ("CStone", HKEX: 2616), an innovation-driven biopharmaceutical company focused on the research and development of anti-cancer therapies, reported 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 (Press release, CStone Pharmaceauticals, DEC 22, 2024, View Source [SID1234649250]). This first-in-human study has also been registered and published on Clinicaltrials.gov (NCT number: NCT06741644).
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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) (Free SITC Whitepaper) (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.
About CS2009 (PD-1/VEGF/CTLA-4 Trispecific Antibody)
CS2009 is a trispecific antibody targeting PD-1, VEGFA, and CTLA-4, with the potential to be first- or best-in-class for major tumor types. Its differentiated molecular design combines three clinically validated targets, preferentially invigorating exhausted TILs while demonstrating VEGF neutralization comparable to existing anti-VEGF antibodies. CS2009 covers a wide range of cancers, including non-small cell lung cancer, ovarian cancer, renal cell carcinoma, cervical cancer, hepatocellular carcinoma, and gastric cancer.
In November 2024, CStone presented preclinical data for CS2009 at the 39th SITC (Free SITC Whitepaper) Annual Meeting. These results show that CS2009 exhibits superior anti-tumor activity compared to potential competitors, including PD-1/CTLA-4 bispecific antibodies, PD-1/VEGF bispecific antibodies, and PD-1/CTLA-4 combination therapies.