HH100937 / HaiHe Biopharma - LARVOL DELTA

Discovery and Characterization of HH100937, a potent and selective SOS1 inhibitor demonstrates synergistic efficacy in combination with KRAS/MAPK therapies (AACR 2024) - "HH100937 exhibited lower IC50s than BI-3406 and MTRX0902 in blocking ERK phosphorylation and cancer cell proliferation, leading to better anti-tumor efficacies in xenografts than reference compounds at same doses. HH100937 also showed synergistic effect with AMG510 in cancer cells with KRAS G12C mutation but refractory to AMG510...Our SOS1 inhibitor also exhibited synergistic effect with HH2710, a clinical-stage ERK inhibitor, in a broad panel of cancer cells with KRAS mutations.The pharmacological potency of HH100937 was highly selective over SOS2, other kinases tested or other targets in a safety panel of 47 targets...HH100937 also showed favorable DMPK properties in mice, rats and dogs, and acceptable safety profiles in vitro.Taken together, HH100937 is a highly potent and selective SOS1 inhibitor with better anti-tumor activities than some SOS1 inhibitors at clinical stage. It can be developed as mono therapy or in combination with other KRAS/MAPK targeting therapies."

Clinical • Combination therapy • Late-breaking abstract • Oncology • KRAS