BH-30643 / BlossomHill Therap - LARVOL DELTA

Anti-Tumor Activity of BH-30643, a Novel Macrocyclic EGFR TKI, in Patients With Secondary EGFR Resistance Mutations (IASLC-WCLC 2026) - P1/2 | "Responses were observed across different C797S co-mutations (e.g., exon 19 del, L858R, G719S, T790M) and following different targeted therapies (e.g., osimertinib, afatinib, amivantamab). Conclusions : BH-30643 can achieve clinical and molecular responses in heavily pretreated NSCLC patients with secondary EGFR resistance mutations across diverse molecular contexts, supporting its potential as monotherapy in the treatment of resistance to 3rd-generation EGFR TKIs. Expansion cohort enrollment is ongoing with a focus on C797S-positive resistance."

Clinical • First-in-human • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HER-2 • KRAS • MET

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

BlossomHill reports 45% ORR, 88% DCR for BH-30643 in C797S-positive NSCLC; Phase 2 planned (TradingView) - "Phase 1/2 SOLARA update shows 45% ORR (18/40) and 88% DCR (35/40) in C797S-positive patients; 63% (25/40) of patients remained on treatment at median 6.9 months follow-up, suggesting durability; Favorable safety: among 174 patients at expansion doses, treatment-related dose reductions 9% and discontinuations 3%; Activity observed in a heavily pretreated, heterogeneous cohort: 98% prior osimertinib; 35% had concurrent T790M...plans a global Phase 2 in C797S-positive NSCLC in Q1 2027."

New P2 trial • P1 data • Non Small Cell Lung Cancer

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

Anticipated Upcoming Milestones: BH-30643 (GlobeNewswire) - "Q4 2026: End of Phase 1 meeting regarding a recommended Phase 2 dose selection and a potential accelerated approval pathway in C797S resistance; Q1 2027: First patient dosed in anticipated pivotal Phase 2 trial; 1H 2027: Updated Phase 1 data, including C797S durability; 2H 2027: Updated Phase 1 data on TKI-naive durability and initial chemo combo cohort data."

FDA event • P1 data • Trial status • Non Small Cell Lung Cancer

First-in-human trial of BH-30643, a novel macrocyclic, non-covalent, mutant-selective OMNI-EGFR inhibitor, in EGFR-mutant (EGFRm) NSCLC. (ASCO 2026) - P1/2 | "Leveraging a novel macrocyclic scaffold, BH-30643 is the first TKI monotherapy to demonstrate clinical responses against C797S both with or without T790M. High plasma exposures combined with super-potency, CNS activity, and favorable safety offers potential for deep and durable EGFR inhibition. Enrollment into backfill and expansion cohorts is ongoing to better characterize activity in both TKI-naïve and resistant pts."

First-in-human • P1 data • Dental Disorders • Inflammation • Lung Cancer • Mucositis • Non Small Cell Lung Cancer • Pneumonia • Solid Tumor • Stomatitis • ALK • HER-2 • KRAS • ROS1 • UGT1A1

BlossomHill Therapeutics to Present Updated Data from Ongoing Phase 1/2 SOLARA Trial of its Macrocyclic OMNI-EGFR Inhibitor, BH-30643, in EGFR-mutant NSCLC at the 2026 World Conference on Lung Cancer (GlobeNewswire) - "Data to be presented in a mini-oral session will describe anti-tumor activity of BH-30643 in patients with secondary EGFR resistance mutations such as EGFR C797S."

P1/2 data • Non Small Cell Lung Cancer

BlossomHill Therapeutics Announces FDA Fast Track Designation for BH-30643, a Macrocyclic OMNI-EGFR Inhibitor for the Treatment of Advanced EGFR C797S-positive NSCLC (GlobeNewswire) - "BH-30643 is being evaluated in SOLARA, a global Phase 1/2, first-in-human clinical trial enrolling patients at more than 40 sites in 10 countries."

Fast track • Non Small Cell Lung Cancer

SOLARA: A Study of BH-30643 in Subjects With Locally Advanced or Metastatic NSCLC Harboring EGFR and/or HER2 Mutations (clinicaltrials.gov) - P1/2 | N=675 | Recruiting | Sponsor: BlossomHill Therapeutics | N=266 ➔ 675

Enrollment change • First-in-human • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • HER-2

BlossomHill eyes $112M IPO harvest to bankroll potential Tagrisso challenger (FierceBiotech) - "A total of $70 million of this IPO cash has been earmarked for the company’s lead asset, a macrocyclic EGFR-targeting molecule called BH-30643...the biotech intending to use some of this sum to launch a 'potentially registrational' phase 2 trial...Meanwhile, around $20 million of the IPO haul will be used to push ahead with a phase 1 study of BH-30236, which the company is pitching as the first drug to successfully target a CDC-like kinase. The study is enrolling patients with relapsed or refractory acute myeloid leukemia or higher-risk myelodysplastic syndrome...There’s also $5 million that will be set aside to take the pan-KRAS inhibitor BH-501284 from IND-enabling studies into the clinic."

Financing • Acute Myelogenous Leukemia • Myelodysplastic Syndrome • Non Small Cell Lung Cancer • Solid Tumor

Severe IL-6-dominant immune-mediated inflammatory response complicated by probable arginine vasopressin deficiency following ivonescimab-based therapy in advanced EGFR-mutant lung squamous cell carcinoma: a case report. (PubMed, Front Oncol) - "We report a 72-year-old man with stage IV squamous NSCLC harboring an EGFR mutation and PD-L1 tumor proportion score of 90% who developed persistent fever shortly after first exposure to ivonescimab combined with nab-paclitaxel and carboplatin. His prior treatments included concurrent chemoradiotherapy, osimertinib, the investigational EGFR inhibitor BH-30643, afatinib, and recent gamma knife for cerebellar metastases plus palliative radiotherapy for bone metastases...Symptoms improved with corticosteroids, tocilizumab, and desmopressin, consistent with probable arginine vasopressin deficiency (AVP-D), possibly secondary to hypophysitis-though pituitary metastasis cannot be ruled out without biopsy...Advanced age, EGFR-mutant/PD-L1-high tumor biology, recent radiotherapy, and Parkinsonism may have contributed to the inflammatory environment, though none can be proven causal in a single case and each deserves prospective study. Early recognition of persistent..."

IO biomarker • Journal • CNS Disorders • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Movement Disorders • Non Small Cell Lung Cancer • Oncology • Parkinson's Disease • Solid Tumor • Squamous Cell Carcinoma • EGFR • IL6 • PD-1 • PD-L1

BlossomHill Therapeutics to Present Preliminary Results From Phase 1 Dose Escalation/Backfill Cohorts in Phase 1/2 SOLARA Trial of OMNI-EGFR Inhibitor, BH-30643, in Advanced EGFR-mutant NSCLC at the 2026 ASCO Annual Meeting (GlobeNewswire) - "Preliminary results (March 2, 2026, data cut, with efficacy follow-up through April 29, 2026) from the Phase 1 dose escalation/backfill in Phase 1/2 SOLARA trial in patients with heavily pretreated and heterogeneous EGFR-mutant NSCLC. The Phase 1 dose escalation/backfill portion enrolled 82 patients (median of 3 prior lines of therapy, 66% with history of brain metastases, and 71% ECOG=1) across dose cohorts ranging from 20 mg to 160 mg total daily dose of BH-30643....32 patients with C797S mutations were response evaluable across escalation and expansion cohorts; favorable overall response rate (ORR, confirmed or unconfirmed and ongoing) were seen both without prior chemo (50%) and with prior chemo (39%)."

P1 data • Non Small Cell Lung Cancer

BH-30643, a novel macrocyclic non-covalent, mutant-selective EGFR inhibitor, addresses the resistance and potency limitations of contemporary EGFR TKIs (AACR 2026) - P1/2 | "In the presence of EGFR ligands, BH-30643 maintained cell potency in all cell lines, while potency of osimertinib steeply fell, particularly in cells with EGFR L858R mutation. The first-in-human trial of BH-30643 (SOLARA) is now enrolling globally, with a focus on advanced EGFR-mutant NSCLC either with TKI resistance or prior to targeted therapy exposure (NCT06706076)."

First-in-human • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Poster: 'BH-30643, a novel macrocyclic non-covalent, mutant-selective EGFR inhibitor, addresses the resistance and potency limitations of contemporary EGFR TKIs' (GlobeNewswire) - "BlossomHill Therapeutics presents...at AACR 2026....Potent and durable inhibition across diverse EGFR-mutant models, including C797S and T790M. Maintained low nanomolar potency in presence of EGFR ligands. Showed prolonged suppression of tumor cell growth compared to approved EGFR TKIs. Induced deep tumor regression across multiple in vivo models, including intracranial models."

Preclinical • Solid Tumor

Title: BH-30643, a novel macrocyclic non-covalent, mutant-selective EGFR inhibitor, addresses the resistance and potency limitations of contemporary EGFR TKIs (#5877) (GlobeNewswire) - "BlossomHill Therapeutics...announced it will introduce its next-generation KRAS pipeline at the American Association for Cancer Research (AACR) Annual Meeting 2026....In preclinical studies, BH-30643 demonstrated prolonged suppression of tumor cell proliferation compared to osimertinib, including under growth factor-mediated resistance conditions."

Preclinical

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

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

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

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