On December 2024 CStone Pharmaceuticals (stock code: 2616.HK), an innovation-driven biopharmaceutical company focused on developing oncology drugs, reported that it has submitted a clinical trial application (CTA) in Australia for CS2009 (a trispecific antibody targeting PD-1, VEGF, and CTLA-4), its second-generation blockbuster product, for the treatment of various solid tumors (Press release, CStone Pharmaceauticals, DEC 23, 2024, View Source [SID1234656223]). The study has also been registered and publicly disclosed on Clinicaltrials.gov (registration number: NCT06741644).

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CS2009 is a trispecific antibody with an innovative structural design that simultaneously targets PD-1, VEGFA, and CTLA-4. CS2009 possesses balanced anti-PD-1 and anti-CTLA-4 affinities , preferentially targeting and blocking PD-1 and CTLA-4 on double-positive tumor-infiltrating lymphocytes (TILs) while sparing CTLA-4 on single-positive cells. This approach minimizes potential systemic toxicity while maintaining efficacy. CS2009 also induces efficient internalization, reducing the expression of the immunosuppressive molecules PD-1 and CTLA-4 on the surface of double-positive TILs. Furthermore, CS2009 retains full anti-VEGF activity, and preclinical data demonstrates a significant synergistic effect between its anti-VEGF activity and immune checkpoint inhibitory activity —cross-linking with VEGFA significantly enhances anti-PD-1 and anti-CTLA4 activity.

CStone Pharmaceuticals presented preclinical data for CS2009 at the 39th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper). These data demonstrate that CS2009 exhibits significantly superior anti-tumor activity compared to potential competitors, potentially targeting a broad range of tumor types, including non-small cell lung cancer, ovarian cancer, renal cell carcinoma, cervical cancer, liver cancer, and gastric cancer, making it a first-in-class/best-in-class, next-generation immunotherapy backbone product.

Dr. Jianxin Yang, CEO, President of R&D, and Executive Director of CStone Pharmaceuticals, said: "We are pleased to see the on-scheduled submission of the Phase I clinical trial application for CS2009. This marks another major milestone in CStone’s Pipeline 2.0. CS2009 is a novel trispecific antibody that we independently developed from molecular design, a project initiated in 2022. With extensive preclinical data supporting its potential as an alternative to existing PD-(L)1 therapies, CS2009 has smoothly entered clinical development. We will soon initiate its first-in-human study in Australia. We look forward to seeing CS2009’s potential benefit to cancer patients, particularly those with low PD-L1 expression or negative PD-L1 who have not responded well to PD-(L)1 therapies."

CStone Pharmaceuticals plans to initiate a global, multi-center, first-in-human study of CS2009 in Australia in early 2025, and will gradually expand to China and the United States in the future.

About CS2009 (PD-1/VEGF/CTLA-4 trispecific antibody)

CS2009 is a trispecific molecule targeting PD-1, VEGFA, and CTLA-4. As a trispecific antibody targeting major tumor types, it holds first-in-class/best-in-class potential. CS2009 boasts a differentiated molecular design, combining three clinically validated targets. It can reactivate near-exhausted tumor-infiltrating T cells and exhibits VEGF neutralization activity comparable to that of existing anti-VEGF antibodies. It covers a wide range of disease indications, including non-small cell lung cancer, ovarian cancer, renal cell carcinoma, cervical cancer, hepatocellular carcinoma, and gastric cancer.

In November 2024, CStone Pharmaceuticals presented preclinical data for CS2009 at the 39th Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting. These data demonstrated that CS2009 exhibited significantly superior anti-tumor activity compared to potential competing products, including dual PD-1/CTLA-4 antibodies, dual PD-1/VEGF antibodies, and anti-PD-1/anti-CTLA-4 combination therapies.