CStone Presents the Latest Preclinical Findings of CS2009 (PD-1/VEGF/CTLA-4 trispecific antibody) at 2025 AACR

06.05.25 02:00 Uhr

SUZHOU, China, May 5, 2025 /PRNewswire/ -- CStone Pharmaceuticals ("CStone", HKEX: 2616), an innovation-driven biopharmaceutical company focused on anti-cancer therapies, announced today that a poster presentation of preclinical data of CS2009 (PD-1/VEGF/CTLA-4 trispecific antibody), a key asset in CStone Pipeline 2.0, has been delivered at the 2025 American Association for Cancer Research (AACR) Annual Meeting. CS2009 global phase I trial is ongoing in Australia with first patient dosed in this March and will soon be expanded to China and the US.

PD-1, VEGFA, and CTLA-4 are clinically validated targets for immunotherapies, which can exert complementary, multi-dimensional anti-tumor effects through synergistic mechanisms. Blockade of PD-1 and CTLA-4 has demonstrated synergistic effects, extending overall survival  benefits as well as progress-free survival benefits in many tumor types including NSCLC, which could be further strengthened by the blockade of VEGFA signaling. By integrating these three mechanisms of actions in one molecule, CS2009 holds great potential to deliver superior clinical benefits over PD-(L)1 antibodies or PD-(L)1/VEGF and PD-(L)1/CTLA4 bispecific antibodies. 

CS2009 is a promising trispecific antibody targeting PD-1, VEGFA, and CTLA-4, which demonstrates broad clinical application prospects for solid tumors with the great potential to become the next-generation immune-oncology backbone to replace current anti-PD-(L)1-based therapies.

Key Highlights:

  • CS2009 exhibited enhanced affinity upon simultaneous PD-1/CTLA-4 engagement. CS2009 enhances anti-tumor efficacy by preferentially targeting PD-1/CTLA-4 double positive T cells in TME.
  • CS2009 exhibited an approximately 150-fold enhancement in checkpoint inhibitory activity on PD-1/CTLA-4 dual-reporter assay through crosslinking with VEGFA dimers. In PD-1 reporter assay, the CS2009/VEGFA combination demonstrated approximately 300-fold greater immune checkpoint activity compared to CS2009 alone. Mixed lymphocyte reaction (MLR) assays evaluating primary T cell activation revealed that crosslinking with VEGFA dimer significantly increases the activity of CS2009. These findings indicate enhanced activity of CS2009 in VEGFA-enriched TME and minimized peripheral overactivation-induced immune-related toxicity, thereby expanding its therapeutic window.
  • CS2009 demonstrated dose-dependent T-cell activation during GLP-toxicity study in cynomolgus monkeys.
  • CS2009 exhibited comparable pharmacokinetic (PK) profiles to those of monoclonal antibodies.
  • CS2009 demonstrates superb tolerability with the highest non-severely toxic dose (HNSTD)/ the no observed adverse effect level (NOAEL) identified as 100 mg/kg.
  • In summary, 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 tumor infiltrating lymphocytes (TILs) while demonstrating VEGF neutralization comparable to existing anti-VEGF antibodies. CS2009 covers a wide range of cancers, including but not limited to non-small cell lung cancer, hepatocellular carcinoma, gastric adenocarcinoma, endometrial cancer, ovarian cancer, renal cell carcinoma, and cervical cancer. Our results show that CS2009 exhibits superior anti-tumor activity compared to potential competitors, including PD-(L)1/CTLA-4 bispecific antibodies, PD-(L)1/VEGF bispecific antibodies, and PD-(L)1/CTLA-4 combination therapies.

    Poster Information:

    Title: CS2009: A first-in-class trispecific antibody targeting PD-1, CTLA-4, and VEGFA with potential to be a next-generation backbone therapy with combined checkpoint inhibition and anti-angiogenesis
    Session Title: Overcoming Checkpoint Inhibition and Tumor Suppression
    Abstract Number: 7299
    Date & Time: Wednesday, April 30, 2025, 9:00 AM - 12:00 PM ET
    Location: Poster Section 39, Board #14

    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 covering 9 indications. The company's pipeline is balanced by 16 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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    SOURCE CStone Pharmaceuticals