BH-30643
A mutant-selective OMNI-EGFR™ Inhibitor
We are evaluating a potentially better way to treat EGFR-positive NSCLC. BH-30643 is a mutant-selective OMNI-EGFR™ inhibitor with an aim to provide greater benefit to patients by:
- Super-high potency against common, atypical and compound EGFR mutations, including those induced by treatment with other EGFR inhibitors.
- Low potency against wild-type EGFR to decrease the risk of toxicities associated with wild-type EGFR activity, including skin rash.
- More potent against HER2 mutations than wild type HER2.
- Concurrently targeting activating mutations in EGFR and HER2 to reduce the chances of resistance.
BH-30643 has demonstrated a promising PK and safety profile, including good preclinical cardio-safety. An Investigational New Drug application (IND) submission is planned for mid-2024, with the Phase 1 proof-of-concept clinical trial slated for late 2024.
The Need for a Mutant-selective OMNI-EGFR™ Inhibitor
The presence of activating EGFR or HER2 mutations in subjects with non-small cell lung cancer (NSCLC) confers sensitivity to treatment with EGFR or HER2 inhibitors, respectively. Approximately 67% of observed EGFR mutations fall into the category of classical mutations, while the remaining 33% consist of atypical mutations that may occur independently or in combination with classical mutations.
EGFR inhibitors serve as the standard of care for EGFR-positive NSCLC. However, treatment resistance can arise due to various factors, including activation of EGFR-dependent and EGFR-independent signaling pathways, which ultimately limit their long-term efficacy. Notably, HER2 activation is a common resistance mechanism observed in response to EGFR inhibitors. Approved EGFR inhibitors are associated with specific toxicities, including a skin rash attributed to the inhibition of wild-type EGFR.
HER2 activating mutations have been identified in approximately 4% of patients with NSCLC and are linked to unfavorable patient outcomes. Unfortunately, there is currently no approved HER2 inhibitor specifically for NSCLC. The toxicities of systemic therapy have been well characterized, and platinum chemotherapy-based treatment options with or without immunotherapy and antibody drug conjugates containing a cytotoxic chemotherapy payload continue to be part of first- and second-line recommendations.
Despite advancements, a significant unmet need remains in the EGFR- and HER2-mutated NSCLC treatment landscape. Therefore, BlossomHill Therapeutics’ efforts are ongoing to develop a novel inhibitor that improves clinical outcomes, duration of response and tolerability in patients with locally advanced or metastatic NSCLC harboring EGFR classical and atypical mutations, as well as EGFR resistance mutations following prior EGFR therapy or in patients with HER2 activating mutations.
