BH-30236 / 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 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

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

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

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

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