CS2009 / CStone Pharma - LARVOL DELTA

CStone Pharmaceuticals…announced that the Investigational New Drug (IND) application for the Phase Ⅱ clinical trials of CS2009 (PD-1/VEGF/CTLA-4 tri-specific antibody) combination therapies for advanced solid tumors has been approved by the China National Medical Products Administration (NMPA) (CStone Pharma Press Release) - "The Phase II study is currently actively enrolling patients in Australia. The approval of the IND in China will further accelerate the clinical development progress, allowing us to explore and validate the broad therapeutic potential of CS2009."

Trial status • Solid Tumor

CS2009, a novel PD-1/VEGF/CTLA-4 trispecific antibody, in patients with advanced solid tumors: An open-label, multicenter, phase I first-in-human study (ESMO 2025) - P1/2 | "Preclinical studies demonstrated robust immune-oncology functionality with full VEGF blockade comparable to bevacizumab. Full phase 1a data with about 40 pts will be presented at the conference. Conclusions CS2009 exhibits a favorable early safety profile and signals of antitumor activity, supporting further clinical development."

Clinical • First-in-human • Metastases • P1 data • Trispecific • Bladder Cancer • Cervical Cancer • Genito-urinary Cancer • Non Clear Cell Renal Cell Carcinoma • Oncology • Ovarian Cancer • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • CTLA4 • PD-1

ESMO 2025: CStone Discloses Phase I Data for CS2009 (PD-1/VEGF/CTLA-4 Trispecific Antibody) (PRNewswire) - "Among all 49 evaluable patients, overall response rate (ORR) was 12.2%; DCR was 71.4%....Higher ORR (25.0%) at tentative recommended Phase 2 dose (RP2D, 30 mg/kg) and higher dose....Non-Small Cell Lung Cancer (NSCLC): ORR: 11.8%...; Ovarian Cancer (OC): ORR: 16.7%, DCR: 66.7%; Triple-Negative Breast Cancer (TNBC): ORR: 25.0%, DCR: 75.0%; Non–Clear Cell Renal Cell Carcinoma (nccRCC): ORR: 33.3%, DCR: 100.0%; Soft Tissue Sarcoma (STS): ORR: 11.1%, DCR: 66.7%."

P1 data • Non Small Cell Lung Cancer • Ovarian Cancer • Renal Cell Carcinoma • Soft Tissue Sarcoma • Triple Negative Breast Cancer

ESMO 2025 Preview: CStone to Present Phase I Dose-Escalation Data for PD-1/VEGF/CTLA-4 Trispecific Antibody and Trial-in-Progress Update for ROR1 ADC (CStone Pharma Press Release) - "The CS2009 abstract only contains data from 9 patients as of May 8, 2025 (abstract submission deadline) at the trial’s initial stage, meeting ESMO’s abstract submission requirements. CStone will disclose updated preliminary data from the ongoing Phase I dose-escalation clinical study for CS2009 at the upcoming ESMO poster presentation, in approximately 70 advanced solid tumor patients....The Phase Ib study design abstract for...CS5001...will be presented as an electronic poster (ePoster) during the congress."

Clinical protocol • P1 data • Lymphoma • Solid Tumor

Phase I Dose-Escalation Study Demonstrates Promising Profile (CStone Pharma Press Release) - "In the Phase I dose-escalation study (6 cohorts, 1-45mg/kg, escalation and backfilling), CS2009 showed: (i) Favorable Safety: No dose-limiting toxicities (DLT) observed across all evaluated doses, and well-tolerated in dozens of patients....; (ii) Broad & Deepening Antitumor Activity: Notable anti-tumor activity was observed across all doses, and the activity continued to strengthen with prolonged follow-up....Phase I data will be presented at the European Society for Medical Oncology (ESMO) Congress in October 2025."

P1 data • Solid Tumor

CStone Announces First Patient Enrollement in Global Phase II Trial of CS2009 (PD-1/VEGF/CTLA-4 Trispecific Antibody) in Australia (CStone Pharma Press Release) - "The trial enrollment is currently ongoing in Australia and China, with subsequent expansion planned for the United States."

Enrollment status • Solid Tumor

A Phase I/II Study of CS2009 as Monotherapy and Combination Therapy in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=660 | Recruiting | Sponsor: CStone Pharmaceuticals | Phase classification: P1 ➔ P1/2 | N=230 ➔ 660

Enrollment change • Monotherapy • Phase classification • Oncology • Solid Tumor

ESMO 2025: CStone to Debut CS2009 Clinical Data and CS5001 Trial Design (CStone Pharma Press Release) - "CStone will showcase clinical advancements from its Pipeline 2.0 at one of the premier global oncology conferences, the European Society for Medical Oncology (ESMO) Congress 2025 in Berlin, Germany (October 17-21). Key presentations include the latest first-in-human Phase Ia data for the novel PD-1/VEGF/CTLA-4 trispecific antibody CS2009, and the global multicenter Phase Ib study design for its ROR1-targeting antibody-drug conjugate (ADC) CS5001....The ESMO presentation marks the first disclosure of clinical data for CS2009 and represents among the earliest clinical reports globally for a PD-1/VEGF/CTLA-4 trispecific antibody....CS5001 continues to advance through Phase Ib dose expansion. CStone’s ESMO update will detail the design of its ongoing multiregional study across the U.S., Australia, and China."

Clinical protocol • P1 data • Lymphoma • Solid Tumor

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 (AACR 2025) - "For instance, cadonlimab (targeting PD-1/CTLA-4) and ivonescimab (targeting VEGFA/PD-1) have been approved in China for the treatment of advanced cervical carcinoma, gastric or gastroesophageal junction adenocarcinoma, and EGFR-mutant non-small cell lung cancer, respectively. CS2009 is a promising trispecific antibody for the treatment of various advanced solid tumors, with potential to be a next-generation backbone therapy with combined checkpoint inhibition and anti-angiogenesis. Current preclinical data support further clinical investigation of CS2009."

Checkpoint inhibition • IO biomarker • Trispecific • Cervical Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD4 • CD8 • CD80 • EGFR • ICOS • KDR

CStone Presents the Latest Preclinical Findings of CS2009 (PD-1/VEGF/CTLA-4 trispecific antibody) at 2025 AACR (PRNewswire) - "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....CS2009 exhibited comparable pharmacokinetic (PK) profiles to those of monoclonal antibodies."

Preclinical • Solid Tumor

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 (PRNewswire) - "CStone to showcase...latest research achievements at AACR 2025....Abstract Number: 7299....Key Findings: In the proof of mechanism studies, CS2009 demonstrated strong synergy between the PD-1 and CTLA-4 arms, and the checkpoint inhibitory activity from the PD-1/CTLA4 arms was also greatly enhanced through crosslinking between its anti-VEGF arms with VEGFA dimers....CS2009 exhibited a PK profile comparable to those of monoclonal antibodies and demonstrated dose-dependent T-cell activation in cynomolgus monkeys."

Preclinical • Oncology

A Phase I Study of CS2009 in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=230 | Recruiting | Sponsor: CStone Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • Oncology • Solid Tumor

CStone Announces First Patient Dosed in Global Multicenter Phase I Clinical Trial of CS2009, a PD-1/VEGF/CTLA-4 Trispecific Antibody (GlobeNewswire) - "CStone Pharmaceuticals...today announced that the first patient has been successfully dosed in the global multicenter Phase I clinical trial of its novel PD-1/VEGF/CTLA-4 trispecific antibody, CS2009, with no infusion reactions or other adverse events observed....This trial aims to evaluate the clinical potential of CS2009 in a wide range of advanced solid tumors including, but not limited to, non-small cell lung cancer, hepatocellular carcinoma, gastric adenocarcinoma, endometrial cancer, ovarian cancer, renal cell carcinoma, and cervical cancer, in efforts to advance the development of innovative tumor immunotherapies....Currently, the multicenter Phase I clinical trial of CS2009 is being conducted in Australia, with plans to expand into China and the United States in the near future."

Trial status • Cervical Cancer • Endometrial Cancer • Gastric Adenocarcinoma • Gynecologic Cancers • Hepatocellular Cancer • Lung Cancer • Non Small Cell Lung Cancer • Ovarian Cancer • Renal Cell Carcinoma

CS2009, a novel first-in-class trispecific antibody targeting PD-1, CTLA-4, and VEGFa, demonstrates promising anti-tumor activity in preclinical evaluation (SITC 2024) - "One strategy to overcome this problem is to build bispecific molecules aiming to 1) attenuate anti-CTLA-4 arm to balance the immune-toxicity and immune-efficacy (e.g. cadonilimab and KN046); 2) preferentially bind to PD-1/CTLA-4 double positive tumor infiltrating T cells (TILs) (e.g. volrustomig and vudalimab). To improve the effect of ICB, VEGF inhibitors including bevacizumab, ramucirumab, lenvatinib, etc. were applied to interrupt tumor angiogenesis, hence promote vascular normalization in tumor immune microenvironment, and improve T lymphocyte infiltration...In the studies using immune competent humanized mice, J30 showed superior anti-tumor activities to its major competitors such as cadonilimab, AK112 and volrustomig...Conclusions J30 is a promising trispecific molecule for the treatment of various advanced solid tumors as a next-generation ICB. Current data supports further clinical research on CS2009."

IO biomarker • Preclinical • Trispecific • Oncology • Solid Tumor

CS2009, a novel first-in-class trispecific antibody targeting PD-1, CTLA-4, and VEGFa, demonstrates promising anti-tumor activity in preclinical evaluation (SITC 2024) - "One strategy to overcome this problem is to build bispecific molecules aiming to 1) attenuate anti-CTLA-4 arm to balance the immune-toxicity and immune-efficacy (e.g. cadonilimab and KN046); 2) preferentially bind to PD-1/CTLA-4 double positive tumor infiltrating T cells (TILs) (e.g. volrustomig and vudalimab). To improve the effect of ICB, VEGF inhibitors including bevacizumab, ramucirumab, lenvatinib, etc. were applied to interrupt tumor angiogenesis, hence promote vascular normalization in tumor immune microenvironment, and improve T lymphocyte infiltration...In the studies using immune competent humanized mice, J30 showed superior anti-tumor activities to its major competitors such as cadonilimab, AK112 and volrustomig...Conclusions J30 is a promising trispecific molecule for the treatment of various advanced solid tumors as a next-generation ICB. Current data supports further clinical research on CS2009."

IO biomarker • Preclinical • Trispecific • Oncology • Solid Tumor

CStone Announces Submission of Clinical Trial Application in Australia for CS2009, an Innovative PD-1/VEGF/CTLA-4 Trispecific Antibody (PRNewswire) - "CStone Pharmaceuticals...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)....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."

Trial status • Solid Tumor

A Phase I Study of CS2009 in Participants with Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=230 | Not yet recruiting | Sponsor: CStone Pharmaceuticals

Metastases • New P1 trial • Trispecific • Oncology • Solid Tumor

CStone Presents Preclinical Data on CS2009 at the 2024 SITC Annual Meeting (CStone Pharma Press Release) - "CS2009 preferentially blocks PD-1 and CTLA-4 on double-positive tumor-infiltrating T cells, without interfering CTLA-4 regulation on peripheral T cells, thereby enhancing safety without compromising efficacy. CS2009 also induces rapid internalization of PD-1 and CTLA-4 on double-positive T cells, reducing the levels of these two immune checkpoint molecules....In immunocompetent mouse models, CS2009 demonstrated superior anti-tumor activity compared to potential competitors, including PD-1/CTLA-4 bispecific antibody, PD-1/VEGFA bispecific antibody, and PD-1/CTLA-4 combination therapies."

Preclinical • Solid Tumor

CStone to Present Preclinical Data on CS2009 at the 2024 SITC Annual Meeting (CStone Pharma Press Release) - "CStone Pharmaceuticals...announced a presentation at the 39th Annual Meeting of the Society for Immunotherapy of Cancer (SITC), reporting preclinical data of CS2009....Preclinical data has demonstrated that CS2009 exhibits superior anti-tumor activity in immune-competent mouse models, compared to potential competitors, such as PD-(L)1/CTLA-4 and PD-(L)1/VEGFa bispecific antibodies. CS2009 is currently in Investigational New Drug (IND)-enabling stage, and we expect to submit IND application by the end of 2024 or in early 2025, followed by initiation of the first-in-human trial in early 2025."

IND • Preclinical • Oncology

CStone Reports 2024 Interim Results and Recent Corporate Updates (PRNewswire) - "Anticipated near-term catalysts include:...(i) CS2009: IND submissions expected in 2024/2025; (ii) CS5006: IND submission expected in 2025; (iii) CS5005: IND submission expected in 2025; (iv) CS2011/CS5007: IND submission expected in 2025."

IND • Solid Tumor

CStone Pharmaceuticals Reports 2023 Annual Results and Business Updates (CStone Pharma Press Release) - "(i) CS2009: submit clinical trial notification ('CTN') to Australian Human Research Ethics Committee ('HREC') by the end of 2024, and apply for China IND in the first quarter of 2025; (ii) CS5006: nominate PCC in the first half of 2024, and expect to file IND in 2025; (iii) CS5005: nominate PCC in 2024, and expect to file IND in 2025."

IND • New molecule • New trial • Solid Tumor