BH-30236 / BlossomHill Therap - LARVOL DELTA

Anticipated Upcoming Milestones (GlobeNewswire) - "BH-501284: Q1 2027: Investigational New Drug submission. BH-30236: 1H 2027: Updated Phase 1 data on safety and anti-leukemic effect."

IND • P1 data • Acute Myelogenous Leukemia • Myelodysplastic Syndrome

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

A FIRST-IN-HUMAN STUDY OF THE ORAL CLK INHIBITOR BH-30236 IN ADULTS WITH RELAPSED/REFRACTORY ACUTE MYELOID LEUKEMIA OR HIGHER-RISK MYELODYSPLASTIC SYNDROME: MONOTHERAPY AND VENETOCLAX COMBINATION (EHA 2026) - P1 | "Summary/Conclusion BH-30236 is the first CLK inhibitor to demonstrate tolerability with once daily dosing and in combination with VEN. Preliminary anti-leukemic activity includes a CR observed early in VEN combination dose escalation, which is ongoing in the US and aiming to further validate the preclinical synergy seen with VEN."

Clinical • First-in-human • Monotherapy • P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome

BlossomHill Therapeutics to Present Initial Clinical Dose Escalation Data from the Phase 1/1b Trial of BH-30236 in Patients with R/R AML or HR-MDS at EHA2026 (GlobeNewswire) - "Dose escalation showed predictable pharmacokinetics without drug accumulation or reduction, and no significant drug-drug interactions were observed with venetoclax Early signs of clinical activity were observed: In the monotherapy cohort, 29% (n=5) of evaluable patients achieved at least a 50% reduction in bone marrow blast counts, including one HR-MDS patient treated at 60 mg with ongoing blast count reduction with duration of treatment 7.6 months; In the combination cohort, 55% (n=5) of evaluable patients experienced at least a 50% blast reduction, including one patient refractory to all prior therapy including venetoclax, who achieved a minimal residual disease (MRD)-negative complete remission...'In March of this year, the U.S. Food and Drug Administration granted Orphan Drug Designation to BH-30236..'"

First-in-human • Orphan drug • P1 data • Acute Myelogenous Leukemia • Myelodysplastic Syndrome

CLK inhibitor BH-30236 synergizes with venetoclax in anti-leukemia activity via splicing modulation in preclinical AML and CLL models (AACR 2026) - P1 | "This finding is consistent with BH-30236 modulation of leukemia stem cells via regulation of alternative splicing. BH-30236 is currently under clinical investigation, either as a single agent or in combination with venetoclax, in adults with relapsed or refractory AML or higher risk MDS in a Phase 1/1b clinical trial (NCT06501196)."

IO biomarker • Preclinical • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • MCL1

Poster: 'CLK inhibitor BH-30236 synergizes with venetoclax in anti-leukemia activity via splicing modulation in preclinical AML and CLL models' (GlobeNewswire) - "BlossomHill Therapeutics presents...at AACR 2026....Consistent synergy with venetoclax across multiple blood cancer models. Induced tumor regression in resistant acute myeloid leukemia (AML) xenografts, including complete responses. Sustained tumor-free survival following treatment discontinuation, consistent with effects on leukemia stem cell populations."

Preclinical • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia

BH-30236, a novel macrocyclic CLK inhibitor modulating RNA splicing, demonstrates potent inhibition of cancer cell growth in a broad panel of cancer cell lines (AACR 2024) - "Furthermore, BH-30236 demonstrated synergy with KRAS inhibitors in KRAS mutant cell lines, with EGFR inhibitors in RBM10 mutant H1975 cells, and with BCL2 inhibitor Venetoclax in MOLM-13 cells. Meanwhile, BH-30236 downregulated RNA expression of SRSFs and modulated BCL2 family to increase apoptosis. These results strongly support the clinical applications of the novel multikinase CLK inhibitor BH-30236 in hematological malignancies and solid tumors as a single agent or in combination with other therapies."

IO biomarker • Preclinical • Breast Cancer • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Hematological Malignancies • Leukemia • Lung Cancer • Neuroblastoma • Oncology • Solid Tumor • BCL2L1 • BCLAF1 • CDK1 • EIF4EBP1 • FLT3 • KRAS • RBM10

Novel multikinase CLK inhibitor BH-30236 targets hematological malignancies through alternative splicing regulation (AACR 2025) - P1 | "These observations support further evaluation of BH-30236 in combination with venetoclax for hematologic malignancies. A Phase 1 study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti-leukemic activity of BH-30236 in adults with relapsed/refractory AML and higher-risk MDS is currently ongoing (NCT06501196)."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • BCL2A1 • CDK1 • FLT3 • MCL1 • TP53

Discovery of BH-30236: A novel macrocyclic CLK inhibitor targeting alternative splicing in cancers (AACR 2024) - "In addition, BH-30236 has demonstrated good human ADME and preclinical safety profiles. Collectively, the preclinical study results strongly support the clinical applications of the novel multikinase CLK inhibitor BH-30236 in hematological malignancies and solid tumors, as a single agent or in combination with other therapies."

IO biomarker • Hematological Malignancies • Leukemia • Oncology • Solid Tumor • BCL2 • BCL2L1 • CD123 • CD33 • CDK1 • CLK2 • EIF4EBP1 • FLT3 • IL3RA • MCL1

Title: CLK inhibitor BH-30236 synergizes with venetoclax in anti-leukemia activity via splicing modulation in preclinical AML and CLL models (#5872) (GlobeNewswire) - "BlossomHill Therapeutics...announced it will introduce its next-generation KRAS pipeline at the American Association for Cancer Research (AACR) Annual Meeting 2026....BH-30236, a novel oral CLK1/2/4 inhibitor, modulates alternative splicing to induce apoptosis and suppress leukemia stem cell–associated pathways, demonstrating robust anti-leukemia activity in acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL) models. In combination with venetoclax, BH-30236 produced synergistic tumor regression, including durable, complete responses in resistant xenograft models."

Preclinical • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia

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 (ASH 2025) - P1 | "BH-30236 was more potent than gilteritinib in inhibition of FLT3-ITD, downregulated totalFLT3 expression level via NMD and led to more durable responses compared to gilteritinib in pre-clinicalmodels of mFLT3 AML...Furthermore, BH-30236 demonstrated profoundin vitro and in vivo synergy with venetoclax and the combination of BH-30236 with venetoclaxdemonstrated substantially better efficacy than standard of care venetoclax + azacytidine in venetoclaxresistant CDX AML models.This first-in-human trial evaluates BH-30236 as monotherapy or in combination with venetoclax inpatients with relapsed or refractory AML or higher risk (HR) MDS.Study Design and Patients ≥18 years with previously treated (≤5 lines of systemic treatment)R/R AML or HR-MDS are eligible for this phase 1/1b, multi-center, open-label, dose escalation study(NCT06501196) to evaluate the safety, tolerability, PK, PD and preliminary anti-leukemic activity of BH-30236 alone or in combination with..."

Clinical • First-in-human • IO biomarker • P1 data • PK/PD data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • FLT3

BH-30236, a Novel Macrocyclic Clk Inhibitor Modulating Aberrant RNA Splicing, Demonstrates Potent Anti-Cancer Activity Against Myeloid Malignancies (ASH 2024) - P1 | "In MOLM-13 and other cell-derived xenograft mouse models, combinations of BH-30236 with venetoclax, azacitidine, or cytarabine resulted in marked tumor growth inhibition or deep tumor regression, showing better efficacy than either single agent treatment.Collectively, these preclinical study results, together with the good human ADME and preclinical safety profiles of BH-30236, strongly support its clinical development. A Phase 1 study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti-leukemic activity of BH-30236 in adults with relapsed/refractory acute myelogenous leukemia and higher-risk myelodysplastic syndrome is currently ongoing (NCT06501196)."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • CDK1 • CLK2 • EIF4EBP1 • FLT3 • RUNX1 • RUNX1T1

Novel Multikinase Clk Inhibitor BH-30236 Targets Hematological Malignancies through Alternative Splicing Regulation (ASH 2024) - P1 | "Consistent with this, the combination of BCL2 inhibitor venetoclax with BH-30236 synergistically induced tumor growth inhibition and/or regression in highly resistant AML cell-derived xenograft models (Kasumi-1, MOLM-13). These observations support further evaluation of BH-30236 as a multikinase splicing modulator for hematologic malignancies, either as a single agent or in combination with other therapies. A Phase 1 study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti-leukemic activity of BH-30236 in adults with relapsed/refractory AML and higher-risk MDS is currently ongoing (NCT06501196)."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • BCL2A1 • BCL2L1 • CDK1 • FLT3 • MCL1

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 to Present at the 67th American Society of Hematology (ASH) Annual Meeting on Design of Phase 1/1b Study of BH-30236, an Oral Macrocyclic CLK Inhibitor, in R/R AML or HR-MDS (GlobeNewswire) - "The multi-center, open-label, Phase 1/1b dose escalation study is designed to evaluate the safety, tolerability, pharmacokinetics and preliminary anti-leukemic activity of BH-30236 as a monotherapy or in combination with venetoclax in adult participants with R/R AML or HR-MDS."

Clinical protocol • Acute Myelogenous Leukemia • Myelodysplastic Syndrome

BH-30236-01: A Study of BH-30236 in Relapsed/ Refractory Acute Myelogenous Leukemia and Higher Risk Myelodysplastic Syndrome (clinicaltrials.gov) - P1 | N=170 | Recruiting | Sponsor: BlossomHill Therapeutics | N=74 ➔ 170

Enrollment change • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

A Study of BH-30236 in Relapsed/ Refractory Acute Myelogenous Leukemia and Higher Risk Myelodysplastic Syndrome (clinicaltrials.gov) - P1 | N=74 | Recruiting | Sponsor: BlossomHill Therapeutics

New P1 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology