SHANGHAI,Dec. 23,2024 -- CStone Pharmaceuticals ("CStone",HKEX: 2616),an innovation-driven biopharmaceutical company focused on the research and development of anti-cancer therapies,announced today 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.

About CS2009 (PD-1/VEGF/CTLA-4 Trispecific Antibody)

CS2009 is a trispecific antibody targeting PD-1,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,and gastric cancer.

In November 2024,CStone presented preclinical data for CS2009 at the 39th SITC 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.

About CStone

CStone (HKEX: 2616),established in late 2015,is an innovation-driven biopharmaceutical company focused on the research and development of anti-cancer therapies. Dedicated to addressing patients' unmet medical needs in China and globally,the Company has made significant strides since its inception. To date,the Company has successfully launched 4 innovative drugs and secured approvals for 16 new drug applications (NDAs) covering 9 indications. The company's pipeline is balanced by 17 promising candidates,featuring potentially first-in-class or best-in-class antibody-drug conjugates (ADCs),multispecific antibodies,immunotherapies and precision medicines. CStone also prides itself on a management team with comprehensive experiences and capabilities that span the entire drug development spectrum,from preclinical and translational research to clinical development,drug manufacturing,business development,and commercialization.For more information about CStone,please visit www.cstonepharma.com.

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PR contact: pr@cstonepharma.com

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