ranosidenib (HMPL-306) / Hutchmed - LARVOL DELTA

A Study of HMPL-306 in Advanced Solid Tumors With IDH Mutations (clinicaltrials.gov) - P1 | N=42 | Terminated | Sponsor: Hutchmed | N=90 ➔ 42 | Trial completion date: Sep 2025 ➔ Feb 2025 | Active, not recruiting ➔ Terminated; The study was terminated based on strategic evaluation of the clinical development of HMPL-306 with no safety concerns

Enrollment change • Trial completion date • Trial termination • Solid Tumor

A Study to Evaluate HMPL-306 in Patients With IDH1or IDH2-mutated Acute Myeloid Leukemia (clinicaltrials.gov) - P3 | N=316 | Recruiting | Sponsor: Hutchmed | Trial completion date: Jun 2028 ➔ Sep 2029 | Trial primary completion date: Jun 2027 ➔ Dec 2028

Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Study on Mass Balance of [14C]HMPL-306（Isocitrate Dehydrogenase Inhibitor） in Healthy Chinese Adult Male Subjects (clinicaltrials.gov) - P1 | N=6 | Completed | Sponsor: Hutchmed | Active, not recruiting ➔ Completed

Trial completion

Phase I Study of HMPL-306 for the Treatment of Gliomas With IDH1 and/or IDH2 Mutations (clinicaltrials.gov) - P1 | N=52 | Recruiting | Sponsor: Hutchmed | Not yet recruiting ➔ Recruiting

Enrollment open • Brain Cancer • Glioma • Oncology • Solid Tumor

RAPHAEL: A RANDOMIZED, OPEN-LABEL, PHASE 3 STUDY TO EVALUATE HMPL-306 (RANOSIDENIB) IN PATIENTS (PTS) WITH IDH1- AND/OR IDH2-MUTATED RELAPSED/REFRACTORY (R/R) ACUTE MYELOID LEUKEMIA (AML) (EHA 2025) - P3 | "The independent cohorts will undergo separate randomization (1:1) to receive HMPL-306 (250 mg once daily [QD] at Cycle [C] 1 and 150 mg QD starting from C2) or investigator-selected salvage chemotherapy (28-day a cycle): MEC (etoposide + cytarabine + mitoxantrone), FLAG±Ida (granulocyte colony stimulating factor + fludarabine + cytarabine ± idarubicin), LoDAC (cytarabine), or azacitidine, based on disease status. RAPHAEL will investigate HMPL-306 efficacy and safety in R/R AML pts harboring mIDH1 and/or mIDH2."

Clinical • P3 data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • IDH1 • IDH2

Phase I Study of HMPL-306 for the Treatment of Gliomas With IDH1 and/or IDH2 Mutations (clinicaltrials.gov) - P1 | N=52 | Not yet recruiting | Sponsor: Hutchmed

New P1 trial • Brain Cancer • Glioma • Oncology • Solid Tumor

More than just another IDH inhibitor: Insights from the HMPL-306 phase 1 trial. (PubMed, Med) - "Hu et al. report the results of a phase 1 study of the dual IDH1/2 inhibitor HMPL-306 in relapsed/refractory IDH-mutant AML.1 The study highlights its manageable safety profile and robust preliminary efficacy, suggesting that it may be a valuable AML therapy."

Journal • P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • IDH1 • IDH2

A Multicenter, Randomized, Open-Label, Phase III Clinical Study to Evaluate the Efficacy and Safety of HMPL-306 vs. Salvage Chemotherapy Regimens in Patients with IDH1- and IDH2-mutated Relapsed/Refractory Acute Myeloid Leukemia (R/R AML) (ChiCTR) - P3 | N=790 | Recruiting | Sponsor: Peking University People's Hospital; Peking University People's Hospital

New P3 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • IDH1 • IDH2

Phase 1 study of HMPL-306, an inhibitor of mutant IDH1/IDH2 (mIDH1/2), in western patients (pts) with advanced mIDH solid tumor, including glioma. (ASCO 2025) - P1 | "'306 was well-tolerated in pts with mIDH1/2 solid tumors, showing target inhibition and durable responses in LGG."

Clinical • Metastases • P1 data • Anaplastic Astrocytoma • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Pain • Solid Tumor • IDH1 • IDH2

HUTCHMED Highlights Clinical Data to be Presented at the 2025 ASCO Annual Meeting (GlobeNewswire) - "HUTCHMED (China) Limited...announces that new data from several studies of compounds discovered by HUTCHMED including savolitinib, ranosidenib, fruquintinib and surufatinib, will be presented at the American Society of Clinical Oncology (“ASCO”) Annual Meeting taking place on May 30 – June 3, 2025 in Chicago, USA."

Clinical data • pMMR • Cholangiocarcinoma • Colorectal Cancer • Endometrial Cancer • Esophageal Squamous Cell Carcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Glioma • Hepatocellular Cancer • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Osteosarcoma • Ovarian Cancer • Pancreatic Ductal Adenocarcinoma

A Study of HMPL-306 in Advanced Hematological Malignancies With mIDH (clinicaltrials.gov) - P1 | N=46 | Terminated | Sponsor: Hutchmed | N=75 ➔ 46 | Trial completion date: Jun 2025 ➔ Jan 2025 | Recruiting ➔ Terminated | Trial primary completion date: Sep 2024 ➔ Jan 2025; The study was terminated based on strategic evaluation of the clinical development of HMPL-306 with no safety concerns

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Hematological Disorders • Hematological Malignancies • Oncology • IDH1 • IDH2

Study on Mass Balance of [14C]HMPL-306（Isocitrate Dehydrogenase Inhibitor） in Healthy Chinese Adult Male Subjects (clinicaltrials.gov) - P1 | N=6 | Active, not recruiting | Sponsor: Hutchmed | Recruiting ➔ Active, not recruiting

Enrollment closed

Discovery of HMPL-306 (Ranosidenib), a New Potent and Selective Dual Inhibitor of Mutant IDH1 and 2 in Clinical Development for Cancer Treatment. (PubMed, ACS Med Chem Lett) - "It demonstrated favorable preclinical pharmacokinetics and safety profiles, reduced 2-HG in vivo robustly and sustainably in the mutant IDH1 and 2 tumor xenograft models, and displayed high brain penetration in mice. In the clinical studies, the drug showed good safety and encouraging efficacy in patients with relapsed/refractory myeloid malignancies carrying IDH1 and/or IDH2 mutations."

Journal • Hematological Malignancies • Oncology • IDH1 • IDH2

HMPL-306 in relapsed or refractory IDH1- and/or IDH2-mutated acute myeloid leukemia: A phase 1 study. (PubMed, Med) - P1, P3 | "HMPL-306 showed an acceptable safety profile and promising preliminary efficacy. A phase 3, randomized study of HMPL-306 in R/R AML (this study was registered at ClinicalTrials.gov: NCT06387069) has been initiated."

Journal • P1 data • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • IDH1 • IDH2

Study on Mass Balance of [14C]HMPL-306（Isocitrate Dehydrogenase Inhibitor） in Healthy Chinese Adult Male Subjects (clinicaltrials.gov) - P1 | N=8 | Recruiting | Sponsor: Hutchmed | Not yet recruiting ➔ Recruiting

Enrollment open

Study on Mass Balance of [14C]HMPL-306（Isocitrate Dehydrogenase Inhibitor） in Healthy Chinese Adult Male Subjects (clinicaltrials.gov) - P1 | N=8 | Not yet recruiting | Sponsor: Hutchmed

New P1 trial

A Study of HMPL-306 in Advanced Solid Tumors With IDH Mutations (clinicaltrials.gov) - P1 | N=90 | Active, not recruiting | Sponsor: Hutchmed | Trial completion date: Sep 2024 ➔ Sep 2025 | Trial primary completion date: Mar 2024 ➔ Mar 2025

Metastases • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

Save the Date: HUTCHMED to Present R&D Updates on July 9, 2024 (GlobeNewswire) - "HUTCHMED (China) Limited...announces that it will host a R&D update in Shanghai, China, and via webcast on Tuesday, July 9, 2024....Additionally, the team will provide updates on certain programs within HUTCHMED’s extensive and innovative pipeline. This will include updates on...the surufatinib Phase II/III study for metastatic pancreatic ductal adenocarcinoma ('PDAC'); and the Phase III RAPHAEL study of our IDH1/2 inhibitor HMPL-306 in acute myeloid leukemia ('AML')."

P2/3 data • P3 data • Acute Myelogenous Leukemia • Gastrointestinal Cancer • Hematological Malignancies • Leukemia • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

PHASE 1 STUDY OF HMPL-306 IN PATIENTS WITH ADVANCED ACUTE MYELOID LEUKEMIA WITH ISOCITRATE DEHYDROGENASE (IDH) MUTATIONS: PRELIMINARY RESULTS OF THE DOSE ESCALATION COHORTS (EHA 2024) - P1 | "HMPL-306 exhibits favorable safety profiles at doses up to 400mg QD and a PK profile that supports once daily dosing in Western pts with relapsed/refractory AML harboring mIDH1 and/or mIDH2. MTD was not reached. HMPL-306 demonstrated promising anti-tumor activity which correlated with optimal 2-HG inhibition starting at 150mg QD dose, both in pts with mIDH1 and* mIDH2."

Clinical • Metastases • P1 data • Acute Myelogenous Leukemia • Anemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • Oncology • Pneumonia • Respiratory Diseases • IDH1 • IDH2

HMPL-306 IN PATIENTS WITH RELAPSED OR REFRACTORY MYELOID HEMATOLOGICAL MALIGNANCIES HARBORING IDH1 AND/OR IDH2 MUTATIONS: FINAL RESULT OF DOSE EXPANSION IN PHASE 1 STUDY (EHA 2024) - P1 | "These findings support that HMPL-306 is an effective, oral, targeted treatment for pts with mIDH1 and ormIDH2 AML, and two phase III randomized studies (IDH1 and IDH2) for registration will be launched soon."

Clinical • IO biomarker • P1 data • Acute Myelogenous Leukemia • Anemia • Hematological Disorders • Hematological Malignancies • Oncology • FLT3 • IDH1 • IDH2

A Study to Evaluate HMPL-306 in Patients With IDH1- and IDH2-mutated Acute Myeloid Leukemia (clinicaltrials.gov) - P3 | N=316 | Recruiting | Sponsor: Hutchmed | Not yet recruiting ➔ Recruiting

Enrollment open • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

HUTCHMED Highlights Sovleplenib Phase III ESLIM-01 Study and Hematological Malignancy Programs Data to be Presented at the upcoming EHA2024 Congress (GlobeNewswire) - "HUTCHMED (China) Limited...announces that...new and updated data related to novel investigational hematological malignancy therapies HMPL-306, HMPL-760 and tazemetostat, will be presented at the upcoming European Hematology Association ('EHA') Hybrid Congress."

Clinical data • Acute Myelogenous Leukemia • Lymphoma

HUTCHMED Initiates the RAPHAEL Registrational Phase III Trial of HMPL-306 for Patients with IDH1- and/or IDH2-Mutated Relapsed/Refractory Acute Myeloid Leukemia in China (GlobeNewswire) - "HUTCHMED (China) Limited...announces that it has initiated a registrational Phase III clinical trial of HMPL-306 in patients with mutated isocitrate dehydrogenase ('IDH') 1 or 2 relapsed / refractory acute myeloid leukemia ('AML') in China. The first patient received their first dose on May 11, 2024....RAPHAEL is a multicenter, randomized, open-label, registrational Phase III clinical trial designed to evaluate the safety and efficacy of HMPL-306 as a monotherapy in patients with relapsed or refractory AML harboring IDH1 and/or IDH2 mutations....The Company is looking to enroll approximately 320 patients for this registrational study..."

Trial status • Acute Myelogenous Leukemia

HUTCHMED Initiates the RAPHAEL Registrational Phase III Trial of HMPL-306 for Patients with IDH1- and/or IDH2-Mutated Relapsed/Refractory Acute Myeloid Leukemia in China (GlobeNewswire) - "The study follows positive data from a two-stage, open-label Phase I study evaluating the safety, pharmacokinetics, pharmacodynamics and efficacy of HMPL-306 in this indication (NCT04272957)....Results of the dose expansion stage of the study in over 50 patients demonstrated promising CR rates at the recommended Phase II dose are expected to be presented at the EHA Congress in June 2024."

P1 data • Acute Myelogenous Leukemia

A Study to Evaluate HMPL-306 in Patients With IDH1- and IDH2-mutated Acute Myeloid Leukemia (clinicaltrials.gov) - P3 | N=316 | Not yet recruiting | Sponsor: Hutchmed

New P3 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology