CGT4859 / Cogent Biosci - LARVOL DELTA

A first-in-human multi-center phase 1/2 study of a selective FGFR2/3 inhibitor, CGT4859, in patients with intrahepatic cholangiocarcinomas or other advanced solid tumors. (ASCO 2025) - P1/2 | "The preclinical data support the study of CGT4859 in this patient population with solid tumors harboring FGFR2 and/or FGFR3 genetic alterations. The phase I dose escalation study is currently enrolling at sites in the United States."

Clinical • Metastases • P1/2 data • Biliary Cancer • Cholangiocarcinoma • Genito-urinary Cancer • Metabolic Disorders • Nephrology • Oncology • Renal Disease • Solid Tumor • Urothelial Cancer • FGFR1 • FGFR2 • FGFR3

The reversible and selective FGFR2/3 inhibitor CGT4859 has superior target coverage of resistance mutations missed by leading FGFR inhibitors (AACR 2025) - "In vivo characterization of CGT4859 demonstrates robust efficacy in target-altered models at tolerated doses. Together, these data demonstrate CGT4859 as a potential best-in-class FGFR1-sparing pan-mutant FGFR2/3 inhibitor."

Biliary Cancer • Bladder Cancer • Cholangiocarcinoma • Genito-urinary Cancer • Oncology • Solid Tumor • FGFR2 • FGFR3

The Reversible and Selective FGFR2/3 inhibitor CGT4859 has superior target coverage of resistance mutations missed by leading FGFR inhibitors (GlobeNewswire) - "The poster presented today describes Cogent’s internally-developed FGFR2/3 inhibitor which maintains potency on FGFR2 mutations and is selective against the entire kinome and a broad panel of channels and receptors. Exploratory pharmacokinetics (PK) studies conducted across species showed CGT4859 to be a low-clearance compound with high oral bioavailability. Further, in an AN3 CA model, CGT4859 demonstrated dose-responsive tumor growth inhibition with complete regressions at >2.5 mg/kg QD or BID and was well-tolerated."

Preclinical • Oncology

Cogent Biosciences Announces Multiple Poster Presentations at 2025 American Association for Cancer Research (AACR) Annual Meeting (GlobeNewswire) - "Cogent Biosciences...announced four preclinical poster presentations at the upcoming 2025 AACR Annual Meeting being held in Chicago, IL April 25-30, 2025."

Preclinical • Solid Tumor

Projected Near-Term Milestones (GlobeNewswire) - "Enroll patients in the ongoing Phase 1 trial with CGT4859, a reversible, selective FGFR2 inhibitor in patients with documented FGFR mutations, including advanced cholangiocarcinoma. The trial is designed to explore the safety, tolerability and clinical activity of escalating doses of CGT4859 with a goal of selecting an active and well-tolerated dose for further clinical investigation....Submit an IND application in 2025 for CGT4255, a potent, selective ErbB2 inhibitor, highlighted by potential best-in-class brain-penetrant properties; Submit an IND application in 2025 for CGT6297, a potent allosteric inhibitor of PI3Kα, with 25-fold selectivity over PI3Kα WT."

Enrollment status • IND • Cholangiocarcinoma • Oncology • Solid Tumor

A Study of an FGFR2/3 Inhibitor (CGT4859) in Patients With Cholangiocarcinoma and Other Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=110 | Recruiting | Sponsor: Cogent Biosciences, Inc.

New P1/2 trial • Biliary Cancer • Cholangiocarcinoma • Oncology • Solid Tumor

Cogent Biosciences Reports Recent Business Highlights and Third Quarter 2024 Financial Results (GlobeNewswire) - "During the quarter, Cogent initiated a Phase 1 study of CGT4859, a reversible, selective FGFR2 inhibitor in patients with FGFR2 mutations, including advanced cholangiocarcinoma. The trial will explore the safety, tolerability and clinical activity of escalating doses of CGT4859 with a goal of selecting an active and well tolerated dose for further clinical investigation. Preliminary results from this trial are expected in 2025."

P1 data • Trial status • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor

Cogent Biosciences Reports Recent Business Highlights and Second Quarter 2024 Financial Results (GlobeNewswire) - "Anticipated Upcoming Milestones:...(i) Initiate a Phase 1 trial of the first Cogent-discovered pipeline program, designed as a potent, selective, reversible FGFR2 inhibitor with best-in-class potential in the second half of 2024; (ii) Select lead candidate and initiate IND-enabling studies from ongoing PI3Kα program, designed to potently and selectively target the H1047R driver mutation, which affects >30,000 cancer patients each year."

New P1 trial • Pipeline update • Preclinical • Oncology

Cogent Biosciences Announces Planned 2024 Milestones for Bezuclastinib and Emerging Portfolio of Selective and Potent Targeted Therapeutics (GlobeNewswire) - "Cogent Biosciences...highlighted the company’s key 2024 milestones ahead of its presentation at J.P. Morgan’s 42nd annual healthcare conference....Plan to initiate Phase 1 trial of CGT4859, a potential best-in-class, potent, selective and reversible FGFR2 inhibitor in 2H 2024."

New P1 trial • Oncology

Cogent Biosciences Presents Preclinical Data Highlighting Precision Oncology Pipeline at the 2023 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics (GlobeNewswire) - "Cogent Biosciences...announced updated preclinical data from the Company’s next-generation selective fibroblast growth factor receptor 2 (FGFR2) program being presented today in a poster presentation at the 2023 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics....In an AN3 CA model, CGT4859 demonstrated dose-responsive tumor growth inhibition with complete regressions at 5 mg/kg PO and was well-tolerated. Cogent plans to file an IND, and pending clearance from the FDA, initiate clinical trials in 2024."

IND • Preclinical • Oncology

In vivo characterization of a selective FGFR2 inhibitor with potency against gatekeeper and molecular brake mutations (AACR 2023) - "Most importantly, efficacy in a mouse tumor xenograft model at a dose that does not show elevated plasma phosphorus levels in the rat hyperphosphatemia model will be presented. Herein, the in vitro and in vivo characterization of a representative selective reversible FGFR2 inhibitor is described."

Preclinical • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • Uterine Cancer • FGFR2

Cogent Biosciences Reports Recent Business Highlights and Fourth Quarter and Full Year 2022 Financial Results (GlobeNewswire) - "Upcoming Milestones...Present initial clinical data from SUMMIT, a randomized, double-blind, placebo-controlled, global, multicenter, Phase 2 clinical trial of bezuclastinib in patients with NonAdvSM in the second half of 2023. Clinical data is expected to include safety/tolerability, pharmacokinetics and measures of clinical activity. Present updated preclinical data from Cogent’s selective FGFR2 and ErbB2 research programs at the American Association for Cancer Research annual meeting taking place April 14-19, 2023 in Orlando, Florida."

P2 data • Preclinical • Aggressive Systemic Mastocytosis • Oncology • Solid Tumor

In Vivo Pre-clinical characterization of a Novel Series of FGFR2 Selective Inhibitors with Potency Against Clinically Relevant Mutations (AACR-NCI-EORTC 2022) - "In vivo characterization to be presented includes dose escalating rodent pharmacokinetics, pharmacodynamics in tumor bearing mice, and efficacy in a mouse AN3 CA tumor xenograft model. Herein, the in vitro and in vivo characterization of a representative selective reversible FGFR2 inhibitor is described."

Preclinical • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • Uterine Cancer • FGFR2

Cogent Biosciences to Showcase Precision Therapy Pipeline at the EORTC-NCI-AACR Annual Meeting (GlobeNewswire) - "The first poster discussion will provide an update on Cogent’s next-generation fibroblast growth factor receptor 2 (FGFR2) program, which retains potency across all primary, gatekeeper and molecular brake resistance mutations. The poster includes an overview of ongoing optimization of the Cogent lead series, pharmacokinetic and pharmacodynamic assessment of an FGFR1-sparing novel molecule, as well as robust efficacy in model of FGFR2 clinical resistance (N549K)....The second poster will provide initial preclinical results from Cogent’s novel ErbB2 mutant selective program....Cogent’s exemplar molecule demonstrates robust cellular inhibition of all key resistance and primary driver mutations, while sparing wild type EGFR target engagement. In addition, the advanced compound demonstrates dose ascendable pharmacokinetics, robust tumor phospho-ErbB2 suppression (L755S), and superior tumor growth inhibition when compared to tucatinib."

PK/PD data • Preclinical • Oncology • Solid Tumor

Cogent Biosciences Reports Recent Business Highlights and Second Quarter 2022 Financial Results (GlobeNewswire) - "Present lead-in data from PEAK, a registrational randomized, open-label, global, Phase 3 clinical trial in patients with gastrointestinal stromal tumors (GIST), in the first half of 2023. File first internally developed Investigational New Drug application (IND) from Cogent’s potent, selective FGFR2 inhibitor program in the second half of 2023."

IND • P3 data • Gastrointestinal Cancer • Gastrointestinal Stromal Tumor • Oncology