EVT-0003023 / Evariste - LARVOL DELTA

Discovery and preclinical profiling of a novel PKMYT1 inhibitor, EVT-0003023, with high efficacy in late-stage, post-treatment non-small cell lung cancer models (AACR 2025) - "Machine learning-driven optimization delivered a preclinical candidate compound, EVT-0003023, with best-in-class selectivity and a significantly improved pharmacokinetic profile in relevant animal models, and in vivo efficacy in CCNE1-high and FBXW7-mutated xenograft models.Compounds from this series were used to validate a differentiated biomarker for sensitivity to PKMYT1 inhibition in cellular and PDX-derived models, expanding the patient population treatable with PKMYT1 inhibitors into non-small cell lung cancer. Using clinical data, we demonstrated that this biomarker is significantly up-regulated in patients who have progressed on existing standard-of-care treatment, and demonstrated exceptional monotherapy activity for EVT-0003023 in PDX models reflecting this patient population, as well as tumor regression when combined with low doses of chemotherapy."

Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CCNE1 • CDK1 • FBXW7 • PKMYT1