bonretinib (OB756) / Biosun Pharma - LARVOL DELTA

Indirect treatment comparison of novel JAK2 Inhibitor OB756 versus ruxolitinib in polycythaemia vera with splenomegaly (ASH 2025) - "Overall, OB756 appears to show potential benefits in efficacy and safety in PV patients with splenomegaly compared to ruxolitinib in preliminary analyses of RESPONSE-1 study. These findings suggest that OB756 may offer advantages in reducing both hematological AEs such as anemia, thrombocytopenia, lymphopenia, neutropenia, and non-hematological AEs in JAK inhibitor-naïve PV patients with splenomegaly. However, these observations require confirmation through direct head-to-head studies."

Leukopenia • Neutropenia • Polycythemia Vera • Pulmonary Disease • Thrombocytopenia

Efficacy and safety of OB756 (a Novel Selective JAK2 Inhibitor) for essential thrombocythemia in patients intolerant or resistant to hydroxyurea or interferon: A phase II, open-label, multicenter study (ASH 2025) - "In summary, OB756 demonstrated favourable tolerability and marked clinical efficacy inpatients with ET who were resistant to or intolerant of hydroxyurea or interferon. The agent rapidlyinduced haematologic responses, reduced spleen volume, and lowered JAK2 V617F allelic burden.Sustained complete haematologic responses were maintained, and non-haematologic toxicities wereinfrequent, positioning OB756 as a highly promising new therapeutic option for ET patients who areresistant to or intolerant of hydroxyurea or interferon.Acknowledgement: This research was funded by the Zhejiang Provincial Health High-level InnovativeTalent Project (2022-2026). *Correspondence to: Prof Jian Huang, E-mail:househuang@zju.edu.cn"

Clinical • P2 data • Essential Thrombocythemia • Infectious Disease • Myeloproliferative Neoplasm • Neutropenia • Thrombocytosis

A Novel JAK2 Inhibitor OB756 Inhibits Megakaryopoiesis Differentiation and Proplatelet Biogenesis in Thrombocythemia and Polycythemia Vera (ASH 2024) - "2022ZYC-D09). *Correspondence to : Prof Jian Huang, E-mail : househuang@zju.edu.cn."

Hematological Disorders • Myeloproliferative Neoplasm • Oncology • Polycythemia Vera • Thrombocytopenia • Thrombocytosis • CD34 • ITGA2B • ITGB3

First in-Class JAK2 Inhibitor OB756 Therapy for Patients with Polycythemia Vera : A Phase 2, Open-Label, Multicenter Study (ASH 2024) - "OB756 also showed durable CHR and few non-hematological TEAEs, and may be a new treatment option for PV patients. Furthermore, a randomized double-blind phase 3 study is ongoing, aiming to assess the efficacy and safety of OB756 compared to hydroxyurea in patients with PV in China (CTR20240873)."

Clinical • P2 data • Anemia • Cardiovascular • Myeloproliferative Neoplasm • Polycythemia Vera • Thrombocytopenia • Thrombosis

A Novel JAK2 Inhibitor OB756 in Treatment of Janus Kinase Inhibitor-Naive Patients with Myelofibrosis: A Phase 1/2, Open-Label, Multicenter Study (ASH 2024) - "Conclusion : OB756 is well tolerated and showed meaningful clinical activity in patients with MF, especially for quick and durable spleen reduction. OB756 also showed few non-hematological TEAEs, and may be a new treatment option for MF patients."

Clinical • P1/2 data • Anemia • Myelofibrosis • Thrombocytopenia • CALR

Efficacy and safety of OB756 (a novel selective JAK2 inhibitor) for essential thrombocythemia in patients intolerant of or resistant to hydroxyurea or intolerant of interferon: A phase 2, open-label, multicenter study. (PubMed, Cancer) - "Overall, OB756 was well-tolerated and demonstrated acceptable efficacy, offering a promising therapeutic option for ET patients who are resistant to or intolerant of hydroxyurea or intolerant of interferon."

Clinical • Journal • P2 data • Essential Thrombocythemia • Hematological Disorders • Infectious Disease • Myeloproliferative Neoplasm • Neutropenia • Oncology • Thrombocytosis

Phase Ib/II Clinical Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of OB756 Tablets in Patients with Intermediate/High-Risk Myelofibrosis, Polycythemia Vera, and Essential Thrombocythemia (ChiCTR) - P1/2 | N=236 | Completed | Sponsor: The First Affiliated Hospital of Zhejiang University School of Medicine; Hangzhou Biosun Pharmaceutical Co., LTD

New P1/2 trial • Tumor mutational burden • Hematological Disorders • Myelofibrosis • Myeloproliferative Neoplasm • Polycythemia Vera • Thrombocytosis

A PHASE 2, OPEN-LABEL, MULTICENTER STUDY EVALUATING THE SAFETY AND EFFICACY OF OB756, A NOVEL JAK2 INHIBITOR, IN JAK INHIBITOR-NAÏVE PATIENTS WITH ESSENTIAL THROMBOCYTHEMIA (EHA 2025) - P1/2 | "Essential thrombocythemia (ET) has a relatively favorable prognosis among MPNs, but it still carries a heavy disease burden, and many patients are intolerant to hydroxyurea or interferon therapy. OB756 shows good tolerability and efficacy in ET patients, rapidly achieving hematologic remission, reducing spleen size, and lowering JAK2V617F allele burden, with durable responses and low non-hematologic toxicity, emerging as a promising new treatment option."

Clinical • P2 data • Anemia • Essential Thrombocythemia • Gene Therapies • Leukopenia • Myeloproliferative Neoplasm • Thrombocytopenia • Thrombocytosis

A NOVEL JAK2 INHIBITOR OB756 INHIBITS MEGAKARYOPOIESIS DIFFERENTIATION AND PROPLATELET BIOGENESIS VIA PI3K-AKT SIGNALING PATHWAY IN PATIENTS WITH PH-NEGATIVE MYELOPROLIFERATIVE NEOPLASMS (EHA 2025) - "The novel JAK2 inhibitor OB756 inhibits MKs differentiation, ploidy, and platelet biogenesis via PI3K-AKT signaling pathway in Ph- MPNs, highlighting its potential clinical benefits for MPN patients."

Clinical • Essential Thrombocythemia • Hematological Disorders • Myeloproliferative Neoplasm • Oncology • Polycythemia Vera • Thrombocytopenia • Thrombocytosis • CD34 • ITGA2B • ITGB3

OB756 Showcases Favorable Tolerability in JAK Inhibitor–Naive Myelofibrosis (OncLive) - P1b/2 | N=85 | CTR20201950 | "The investigative JAK2 inhibitor OB756 was found to be well tolerated and to elicit meaningful clinical activity in the form of rapid and durable spleen reduction in Chinese patients with myelofibrosis who did not have prior exposure to JAK inhibition, according to data from a phase 1/2 study (CTR20201950) presented during the 2024 ASH Annual Meeting. In the phase 1 portion of the research, no dose-limiting toxicities were reported when the agent was administered at twice daily doses ranging from 8 mg to 32 mg. Investigators ultimately identified 16 mg and 20 mg twice daily as the recommended phase 2 dose (RP2D) according to p-STAT3 inhibited percentage in an Imax model. Of 66 evaluable patients, 54.5% achieved a spleen volume reduction (SVR) of at least 35% (SVR35) at the end of cycle 6. Moreover, 59.1% of patients achieved SVR35 at the time of the last follow-up; at the end of cycle 12, 50.0% had achieved SVR35."

P1/2 data • Myelofibrosis

Phase Ib/II clinical study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and initial efficacy of OB756 tablets in moderate to high-risk patients with primary myelofibrosis, postcytoplasmic myelofibrosis, and postthrombocythemia primary myelofibrosis (ChiCTR) - P1/2 | N=120 | Completed | Sponsor: The First Affiliated Hospital of Zhejiang University School of Medicine; Hangzhou Biosun Pharmaceutical Co., LTD

New P1/2 trial • Hematological Disorders • Myelofibrosis • Polycythemia Vera • Thrombocytosis