Our Pipeline
Each of our programs represents the application of our approach to a distinct target biology, intentional drug design, and patient population(s) with significant unmet medical need.
Development Pipeline
BH-30643
Target
EGFR
Clinical Program
BH-30643 is an investigational, novel, orally bioavailable, non-covalent, macrocyclic, mutant-selective, OMNI-EGFR™ inhibitor designed to overcome the limitations of currently approved EGFR inhibitors. In preclinical studies it demonstrated potent inhibitory activity across diverse EGFR mutation categories while maintaining marked selectivity over wild-type EGFR. BH-30643 is currently being evaluated in the Phase 1/2 SOLARA clinical trial in adults with locally advanced or metastatic NSCLC harboring EGFR or HER2 mutations.
BH-30236 +/- Venetoclax
Target
CLK
Clinical Program
BH-30236 is an investigational orally bioavailable, macrocyclic inhibitor of the CDC-like kinase (CLK) family. It is designed to modulate aberrant alternative splicing in cancerous tissue, targeting the same aberrant splicing machinery that drives acute myeloid leukemia (AML) and higher-risk myelodysplastic syndrome (HR-MDS) disease biology that cancer cells exploit to develop resistance to venetoclax, FLT3 inhibitors and cytarabine. BH-30236 is being evaluated in a Phase 1/1b multicenter, open-label, first-in-human dose escalation and expansion trial in adults with relapsed or refractory AML (R/R AML) and HR-MDS.
BH-501284
Target
pan-KRAS
Clinical Program
BH-501284 is a potent, selective, orally available non-covalent pan-KRAS inhibitor that demonstrates picomolar binding affinity, broad activity across KRAS mutations, and durable tumor regression in non-small cell lung cancer (NSCLC), colorectal cancer (CRC) and pancreatic ductal adenocarcinoma (PDAC models). By preferentially targeting inactive KRAS and maintaining activity under growth factor-driven resistance conditions, BH-501284 may overcome key limitations of existing KRAS inhibitors.
Our Scientific Approach
Advances in the understanding of genomic alterations that drive tumor initiation, growth and therapeutic resistance, together with increased use of cancer genomic profiling, have transformed cancer drug development. Although many targeted therapies have validated important disease mechanisms and changed the treatment paradigm for patients, validation of a target does not by itself resolve all of the biological and therapeutic challenges associated with that target. Across targeted oncology, prior generations of therapies have often improved outcomes meaningfully while still leaving important treatment gaps unresolved.
With each of our programs, we combine a deep understanding of disease and protein dynamics with our structure-based rational drug design expertise to identify the specific structural liabilities that limit existing therapies or approaches, and then design novel chemical scaffolds to directly address these limitations.
The BlossomHill approach encompasses four design components:
Identification of unmet medical need in defined targets
We focus on targets which have clinical proof of concept or well-established disease biology, but where structural or mechanistic liabilities limit the benefit of approved or clinical-stage therapies to patients.
Structural analysis of existing approaches and their limitations
After identifying a target of choice, we conduct a comprehensive structural audit of existing medicines and/or clinical candidates in the target class: their binding modes, the scaffold families they represent and the precise molecular contacts that generate both their potency and their vulnerabilities. We then leverage a deep understanding of target biology and protein dynamics, including the preferred conformation under disease conditions, to create design principles for overcoming the existing issues.
Precision drug designs based on deep understanding of target biology and protein structure dynamics
Using the insights we gain from our deep understanding of the biology behind a disease, the chemistry of prior therapies and candidates and the unique protein characteristics of the target, we design molecules with novel chemical structures and develop these into orally available small molecule therapeutic candidates.
Iterate and optimize toward specified performance objectives
As we employ our first-principles, rational drug design approach, we rigorously iterate until a set of essential performance objectives are optimized which includes high potency and target coverage, broad inhibition of driver and resistance mechanisms, a wide therapeutic window through selective inhibition of the oncogenic target while minimizing potency against off-target proteins, deep and durable target engagement through tight binding, and chemistry scalability and commercial viability.
Posters & Presentations
Epidermal Growth Factor Receptor (EGFR) Inhibitor
BH-30643
6 Items
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ASCO 2026 Oral Presentation
First-in-Human Trial of BH-30643, a Novel Macrocyclic, Non-Covalent, Mutant Selective OMNI-EGFR Inhibitor, in EGFR-Mutant (EGFRm) NSCLC
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AACR 2026 Poster
BH-30643 Addresses the Resistance and Potency Limitations of Contemporary EGFR TKIs & Demonstrates Potent and Durable Inhibition Across Models with Diverse EGFR-Mutations, Including C797S and T790M
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AACR-NCI-EORTC 2025 Poster
Preliminary Findings from the First-in-Human SOLARA trial of BH-30643, a Novel Macrocyclic, non-Covalent, Mutant Selective, Brain Active, OMNI-EGFR Inhibitor, in EGFR-mutant NSCLC
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ASCO 2025 Poster
A Phase 1/2 Open-Label, Multicenter, First-in-Human Study of the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of BH-30643 in Adult Subjects with EGFR and/or HER2 Mutations (SOLARA)
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ASCO 2025 Poster
Anti-tumor Activity of BH-30643, a Novel Macrocyclic Kinase Inhibitor, in EGFR-mutant Lung Cancer Models
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AACR 2025 Poster
Design and Discovery of BH-30643: A Novel, Reversible, Mutant-selective Macrocyclic EGFR Inhibitor Invulnerable to Common Resistance Mutations
CDC-like Kinase (CLK) Inhibitor
BH-30236
6 Items
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EHA Poster Presentation
A First-in-Human Study of the Oral CLK Inhibitor, BH-30236, in Adults with R/R AML or HR-MDS: Monotherapy and Venetoclax Combination
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AACR 2026 Poster
CLK Inhibitor BH-30236 Demonstrates Broad Anti-Proliferative Activity Through Modulated RNA Splicing
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ASH 2025 Poster
A Phase 1/1b Open-Label, Dose Escalation, First-in-Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Anti-leukemic Activity of the Orally Available CLK Inhibitor, BH-30236, in Adults with R/R AML or HR-MDS
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AACR 2025 Poster
Novel Multikinase CLK Inhibitor BH-30236 Targets Hematological Malignancies Through Alternative Splicing Regulation
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AACR 2024 Poster
BH-30236, a Novel, Macrocyclic CLK Inhibitor Modulating RNA Splicing, Demonstrates Potent Anti-Proliferation Activity in a Broad Panel of Cancer Cell Lines
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AACR 2024 Poster
Discovery of BH-30236: A Novel Macrocyclic CLK Inhibitor Targeting Alternative Splicing in Cancers
pan-KRAS Inhibitor
BH-501284
1 Item
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AACR 2026 Oral Presentation
Discovery and Characterization of BH-501284: A Potent non-Covalent, Pseudo-irreversible, pan-KRAS Inhibitor for Treatment of Diverse KRAS-mutant Tumors