BH-30643 / BlossomHill Therap - LARVOL DELTA

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 CDC-like Kinase Inhibitor, BH-30236, in Adults with R/R AML or HR-MDS (ASH 2024) - P1 | "BH-30236 was more potent than gilteritinib in inhibition of FLT3-ITD. Furthermore, BH-30643 downregulated FLT3 expression level via inhibition of CLK leading to NMD...Exploratory analyses will include assessment of measurable residual disease, longitudinal profiling of genomic alteration markers and characterization of gene expression and alternative splicing modulation in the bone marrow and/or peripheral blood. Enrollment is ongoing in the US."

Clinical • First-in-human • P1 data • PK/PD data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Solid Tumor • FLT3

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 (AACR-NCI-EORTC 2025) - P1/2 | "While follow-up is limited at the time of data cut off (median 10.3 weeks), incidence of EGFR wildtype-associated toxicities (rash, diarrhea) is lower than reported with osimertinib at similar exposures, suggesting effective sparing of wildtype EGFR and HER2 inhibition through selective targeting of the active conformation of the kinases. These data support the potential for a novel, super-potent, non-covalent macrocyclic OMNI-EGFR inhibitor to effectively target mutant EGFR and overcome and/or prevent on-target resistance while avoiding wildtype toxicity. Global enrollment to dose escalation and expansion cohorts is ongoing to support the determination of RP2D."

First-in-human • Late-breaking abstract • P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

BlossomHill Therapeutics Presents Preliminary Findings from Phase 1/2 SOLARA Trial of BH-30643 in EGFR-mutant NSCLC at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics (GlobeNewswire) - "As of the cut-off date of August 28, 2025, 39 patients with previously treated EGFR-mutant NSCLC were enrolled into the Phase 1 dose escalation portion of the ongoing SOLARA trial across dose cohorts ranging from 20 mg to 160 mg total daily dose of BH-30643. High plasma exposures were observed, well exceeding target EC90 at candidate doses, and comparing favorably with the exposures seen with contemporary EGFR inhibitors....'We look forward to sharing more findings from the Phase 1/2 SOLARA trial in 2026'."

P1/2 data • Non Small Cell Lung Cancer

BlossomHill Therapeutics Announces Upcoming Poster Presentation on Phase 1/2 SOLARA Trial of BH-30643, a First-in-class, Macrocyclic OMNI-EGFR Inhibitor, at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics (GlobeNewswire) - "SOLARA is a global, open label, Phase 1/2 clinical trial designed to assess the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary anti-tumor activity of BH-30643 in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) bearing EGFR and/or HER2 mutations."

P1/2 data • Non Small Cell Lung Cancer

BlossomHill Therapeutics Announces First Patient Dosed in Expansion Cohorts of the Phase 1/2 SOLARA Trial, Evaluating BH-30643 in Advanced EGFR-mutant Non-Small Cell Lung Cancer (GlobeNewswire) - "The expansion cohorts of the SOLARA trial will assess single-agent objective response rate (ORR) of BH-30643 in NSCLC patients with diverse EGFR mutations, including patients who have not received prior EGFR targeted therapy."

Trial status • Non Small Cell Lung Cancer

Anti-tumor activity of BH-30643, a novel macrocyclic kinase inhibitor, in EGFR-mutant lung cancer models. (ASCO 2025) - P1/2 | "BH-30643 was administered twice daily via oral gavage; osimertinib when used as a comparator was dosed daily. These preclinical studies demonstrate broad activity of BH-30643 against classical and atypical EGFR activating mutations, EGFR ex20ins, as well as acquired resistance EGFR mutations. Such an "OMNI-EGFR" inhibitor may be able to overcome some of the limitations of earlier agents. Supported by favorable ADME and preclinical safety profiles, BH-30643 is now being assessed in a first-in-human study in locally advanced or metastatic NSCLC harboring EGFR and/or HER2 mutations (NCT06706076, SOLARA)."

Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • HER-2 • ROS1

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 locally advanced or metastatic NSCLC harboring EGFR and/or HER2 mutations (SOLARA). (ASCO 2025) - P1/2 | "Plasma is collected for circulating tumor DNA (ctDNA) analysis at baseline and on treatment. Enrollment is underway, with planned enrollment across ~35 sites in multiple continents."

Clinical • Metastases • P1/2 data • PK/PD data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • HER-2 • ROS1

Design and discovery of BH-30643: A novel, reversible, mutant-selective macrocyclic EGFR inhibitor invulnerable to common resistance mutations (AACR 2025) - "First-generation (1G) (e.g. gefitinib) and second-generation (2G) (e.g. afatinib) EGFR TKIs share an anilinoquinazoline scaffold which is vulnerable to T790M gatekeeper resistance. Third-generation (3G) (e.g. osimertinib) EGFR TKIs employ a less potent pyrimidine scaffold and obtain good potency including T790M through introduction of an irreversible binding at C797...The unique profile of BH-30643 offers a promising strategy to target a range of classical and non-classical EGFR activating mutations without vulnerability to common on-target resistance mutations. Such an "OMNI-EGFRTM" inhibitor may represent a new generation of EGFR TKIs with potential to overcome some of the limitations of earlier agents."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • HER-2 • ROS1

BlossomHill Therapeutics to Present the Design and Discovery of BH-30643, the Company’s OMNI-EGFR Inhibitor, at the 2025 AACR Annual Meeting (Businesswire) - "BlossomHill Therapeutics, Inc...announced that an abstract describing the design and discovery of the company’s novel, macrocyclic, reversible, mutant-selective OMNI-EGFR inhibitor, BH-30643, was accepted for a poster presentation at the upcoming American Association for Cancer Research (AACR) Annual Meeting in Chicago, IL on April 29, 2025."

Clinical • Non Small Cell Lung Cancer

BlossomHill Therapeutics Doses Patients in the First Cohort of the Phase 1/2 SOLARA Clinical Trial of BH-30643 for EGFR- and HER2-Mutated Non-Small Cell Lung Cancer (Businesswire) - "BlossomHill Therapeutics...announced the first cohort of patients has been dosed in the SOLARA study (NCT06706076). SOLARA is a global, open label, dose escalation and expansion Phase 1/2 clinical trial assessing the safety, efficacy and tolerability of BH-30643 for locally advanced or metastatic non-small cell lung cancer (NSCLC) bearing EGFR or HER2 mutations."

Trial status • Non Small Cell Lung Cancer