Undisclosed SMARCA2 inhibitor / Coultreon Biopharma - LARVOL DELTA

Discovery of novel SMARCA2 small molecule inhibitors with best-in-class potency and selectivity for the treatment of SMARCA4-mutant cancers (AACR 2026) - "Lead compounds exhibited single digit to sub-nanomolar activity and over 30-fold selectivity for SMARCA2 versus SMARCA4, as demonstrated in a KRT80 qRT-PCR assay using SMARCA2/4 isogenic knockout cell lines.Notably, these lead compounds combined potent anti-proliferative effects in SMARCA4-deficient cells with favourable in vitro ADME characteristics, a supportive safety profile and pharmacokinetic properties suitable for in vivo evaluation. Following oral administration, the compounds achieved sustained target engagement and elicited pronounced anti-tumor activity in a SMARCA4-deficient RERF-LC-A1 CDX mouse model without evidence of SMARCA4-related body weight loss.These unique SMARCA2-selective lead compounds are currently further profiled as potential clinical candidate with the ultimate goal of delivering transformative efficacy and enhanced safety for patients with SMARCA4-deficient cancers."

IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS • KRT80 • SMARCA2 • SMARCA4