CGT4255 / Cogent Biosci - LARVOL DELTA

Identification of CGT4255 an EGFR sparing, pan-mutant HER2 clinical development candidate with potential best-in-class brain penetration (AACR 2025) - "CGT4255 demonstrates robust efficacy in intracranial tumor growth inhibition studies and shows an additive effect on intracranial tumor shrinkage when combined with a HER2 ADC. Pre-clinical studies with the CGT4255 and T-DXd combination demonstrate enhancement of ADC internalization, thus highlighting a biological rationale for combination therapy."

Clinical • Lung Cancer • Oncology • Solid Tumor • EGFR • HER-2

Identification of CGT4255 an EGFR-sparing, pan-mutant HER2 clinical development candidate with potential best-in-class brain penetration (GlobeNewswire) - "New data presented on this compound describes CGT4255’s exceptional stability in human whole blood and liver cytosol fractions and high oral bioavailability and low clearance across preclinical species. In addition, CGT4255 is expected to have equivalent brain to plasma exposure suggesting potential best-in class properties."

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

Identification of CGT4255 an EGFR sparing, ErbB2 clinical development candidate with activity across activating mutations in systemic and CNS tumors (SABCS 2024) - "Current approved ErbB2 tyrosine kinase inhibitors have inferior potency against these mutations and lack sufficient brain penetration to be an impactful treatment option for patients. Herein, we describe advanced preclinical profiling of our EGFR-sparing, ErbB2 inhibitor clinical development candidate CGT4255 with best-in-class brain penetrance and activity against prevalent mutations."

Clinical • Breast Cancer • HER2 Breast Cancer • Oncology • EGFR • HER-2

Cogent Biosciences Presents Data Highlighting Potential Best-in-Class Potency and Selectivity of Novel, EGFR Sparing, CNS-Penetrant ErbB2 Inhibitor (GlobeNewswire) - "Cogent Biosciences...announced new preclinical data from the Company’s potent, selective, CNS-penetrant ErbB2 inhibitor program. The data are being presented in a poster session at the American Association for Cancer Research (AACR) 2024 Annual Meeting....The poster presented today describes CGT4255’s exceptional stability in human whole blood and liver cytosol fractions and high oral bioavailability and low clearance across preclinical species. In addition, CGT4255 demonstrated 80% brain penetrance in mice and was well-tolerated at 10x concentration, resulting in mouse tumor regression, suggesting potential best-in class properties."

Preclinical • CNS Tumor • Oncology

Cogent Biosciences Presents New Preclinical Data Highlighting Potential Best-in-Class Potency and Selectivity of ErbB2 and PI3Kα inhibitor programs at the San Antonio Breast Cancer Symposium (GlobeNewswire) - "Cogent Biosciences...presented updated preclinical data from its potent, selective and brain penetrant ErbB2 inhibitor program along with initial preclinical data from its newly disclosed H1047R mutant-selective PI3Kα inhibitor discovery program at the 2023 San Antonio Breast Cancer Symposium (SABCS)....The poster presented today shows that CGT4255 demonstrated low nM potency against ErbB2 wild-type and oncogenic ErbB2 mutations with 100-fold selectivity over wild-type-EGFR....CGT4824 demonstrated low nM potency in H1047R mutant PI3K cell lines, differentiated dose ascending PK in mice with high bioavailability and low clearance. CGT4824 also showed >95% inhibition of pAKT in a H1047R PD model, importantly without increases in insulin or C-peptide."

Preclinical • Breast Cancer