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HM99462 (SOS1 inhibitor)

Oncology

Preclinical

Overview
A SOS1 inhibitor demonstrating antitumor activity
against KRAS-mutant cancers
RAS is the most mutated oncogene in various human cancers. Son of sevenless homolog 1 (SOS1) is a guanine nucleotide exchange factor (GEF) on RAS that promotes the exchange of bound GDP to GTP.
SOS1 protein is a promising therapeutic target in RAS-mutant and other RTK-altered cancers.
A novel SOS1 inhibitor, HM99462, potently inhibits interaction of KRAS-SOS1.
Description
Antitumor activities
  • Potent inhibition of p-ERK and good antitumor activity regardless of KRAS mutation types and tumor types
  • Very low potential of CYP enzyme inhibition, enabling to apply combination with various targeted agents
  • Non-inferior to superior potency on antitumor activity to competitors when combined with sotorasib
  • (KRAS G12C inhibitor) or trametinib (MEK inhibitor) in various KRAS-driven tumor models
Clinical Development
  • IND enabling GLP-toxicity studies were initiated in 3Q 2022.
Publications
Poster
HM99462, a Novel SOS1 Inhibitor, Induces Tumor Regression and Synergistic Effect with KRAS or EGFR Targeted Therapy in Solid Tumors
EORTC-NCI-AACR (ENA) Symposium, 2024
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Poster
A novel SOS1 inhibitor, HM99462 demonstrates antitumor activity against KRAS-mutant cancers
American Association for Cancer Research (AACR) 114th Annual meeting, 2023
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