BlossomHill Therapeutics has announced that its novel EGFR inhibitor, BH-30643, will be featured in a poster presentation at the upcoming American Association for Cancer Research (AACR) Annual Meeting in Chicago on April 29, 2025. The presentation will detail the design and discovery of this macrocyclic, reversible, mutant-selective OMNI-EGFR™ inhibitor currently being evaluated for non-small cell lung cancer (NSCLC).
The company's innovative approach targets structural features shared across activating EGFR mutations, potentially offering a single agent precision medicine for a broad spectrum of EGFR-positive lung cancers. BH-30643 is currently being evaluated in the Phase 1/2 SOLARA clinical trial for patients with locally advanced or metastatic NSCLC bearing EGFR or HER2 mutations.
A Novel Approach to EGFR Inhibition
"At BlossomHill, we set out to reimagine what an EGFR inhibitor could achieve as a single agent precision medicine," said Dr. Jean Cui, President and Chief Executive Officer of BlossomHill Therapeutics. "Using an intentional design approach, we targeted structural features shared across activating EGFR mutations, creating an opportunity to potently and selectively target a broad spectrum of EGFR positive lung cancers."
The development of BH-30643 addresses a significant challenge in the current treatment landscape for EGFR-mutated NSCLC. As Dr. Geoff Oxnard, Chief Medical Officer of BlossomHill Therapeutics, explained, "The growing diversity of treatments for different subgroups of EGFR mutations has added complexity – it can be hard for a doctor or patient to know which is the right treatment. We envision that a super-potent EGFR kinase inhibitor could help achieve in this disease the kinds of durable responses we are seeing with next-generation ALK and ROS1 targeted therapies."
Preclinical Profile of BH-30643
In preclinical studies, BH-30643 has demonstrated potent antitumor activity across a wide range of EGFR mutations. These include classical mutations such as exon 19 deletions and L858R, atypical mutations including G719X, L861Q, and S768I, as well as exon 20 insertions. Importantly, the compound maintains its potency in the presence of known resistance mutations, a significant advantage over existing therapies.
The macrocyclic structure of BH-30643 appears to be a key factor in its ability to overcome resistance mechanisms that limit the effectiveness of current EGFR inhibitors. This novel chemical approach may provide a more durable response for patients with EGFR-mutated NSCLC, potentially reducing the need for sequential therapies as resistance develops.
The SOLARA Clinical Trial
BH-30643 is currently being evaluated in the Phase 1/2 global SOLARA study (NCT06706076). The trial includes a dose escalation phase followed by expansion cohorts designed to further evaluate the drug's efficacy across a range of EGFR and HER2 mutations.
NSCLC with EGFR mutations represents approximately 15% of lung adenocarcinomas in the United States and up to 40% in East Asian populations. Despite advances in targeted therapies, resistance development remains a significant challenge, with median progression-free survival typically ranging from 9-19 months with current agents.
AACR Presentation Details
The poster presentation at AACR will provide comprehensive information on the design and discovery of BH-30643. The session details are as follows:
- Poster title: "Design and discovery of BH-30643: A novel, reversible, mutant-selective macrocyclic EGFR inhibitor invulnerable to common resistance mutations"
- Abstract number: 5608
- Session: Kinase and Phosphatase Inhibitors 3, Experimental and Molecular Therapeutics
- Date/Time: Tuesday, April 29, 2025, 2:00 p.m. – 5:00 p.m. CT
- Presenting Author: Jean Cui, Ph.D., Scientific Founder, President and Chief Executive Officer, BlossomHill Therapeutics
BlossomHill has announced that a copy of the poster will be available on the company's website coinciding with the start of the AACR poster presentation.
About BlossomHill Therapeutics
BlossomHill Therapeutics is a privately-held, clinical-stage biotechnology company headquartered in San Diego, California. The company focuses on the design and development of small molecule medicines for treating cancer and autoimmune diseases.
The company's approach to drug design first considers the unmet medical need through deep knowledge of the disease biology, then seeks to design novel chemotypes to provide the best chance of clinical success. In addition to BH-30643, BlossomHill is developing BH-30236 for the treatment of relapsed or refractory acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (HR-MDS).
BlossomHill Therapeutics is supported by leading investors including Cormorant Asset Management, OrbiMed, Vivo Capital, and Colt Ventures, positioning the company to advance its innovative pipeline of targeted therapies through clinical development.
