Undisclosed SMARCA2 Degrader / Amphista Therap - LARVOL DELTA

Rational development of novel DCAF16-mediated SMARCA2 selective Targeted Glues™ for the treatment of SMARCA4 deficient tumors (AACR 2026) - "Structural studies, including generation of multiple high resolution (sub-3Å) cryo EM ternary complex structures have enabled informed structure-activity relationship optimisations of degradation potency, kinetics and selectivity. Consequently, optimised compounds can deliver fast, deep degradation of SMARCA2 as demonstrated in-vivo in a disease-relevant SMARCA4 mutant model.We have achieved compound profiles that uniquely position Amphista to deliver class-leading SMARCA2 degraders for the treatment of SMARCA4-mutant NSCLC."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRT80 • PLAU • SMARCA2 • SMARCA4

Title: Rational development of novel DCAF16-mediated SMARCA2 selective Targeted Glues for the treatment of SMARCA4 deficient tumors (GlobeNewswire) - "Amphista Therapeutics...announces three upcoming presentations at the American Association for Cancer Research (AACR) 2026 Annual meeting....Comprehensive mode of action studies, including E3-ligase knock-out and cysteine mutant rescue experiments demonstrate that our SMARCA2 Targeted Glues induce degradation via selective recruitment of DCAF16 and covalent interaction with a single DCAF16 cysteine residue....Consequently, optimised compounds can deliver fast, deep degradation of SMARCA2 as demonstrated in-vivo in a disease-relevant SMARCA4 mutant model."

Preclinical • Oncology

Amphista Therapeutics discloses first details of its SMARCA2 degrader program (GlobeNewswire) - "Amphista has identified a series of SMARCA2 degraders that have demonstrated CNS penetration in vivo. This offers the potential to develop medicines which can treat CNS metastasis, which frequently occur in lung cancer....Amphista plans to present data from its SMARCA2 Targeted Glue program at a key forthcoming scientific conference."

Preclinical • Non Small Cell Lung Cancer • Solid Tumor