Momelotinib Dihydrochloride

New investigational data from Phase 1/2 study of enzomenib (DSP-5336) in patients with relapsed/refractory acute myeloid leukemia (AML) show clinical activity in various leukemia subtypes driven by genomic alterations Promising preliminary data, particularly in patients without prior venetoclax or menin inhibitor exposure, seen in Phase 1 study of enzomenib in combination with venetoclax and azacitidine in patients with relapsed/refractory AML Preliminary data from Phase 1/2 study of nuvisertib (TP-3654) in combination with momelotinib in patients with relapsed/refractory myelofibrosis (MF) with anemia show treatment combination appears to be well tolerated with early clinical activity and improvements in spleen and symptom responses MARLBOROUGH, Mass., Dec. 8, 2025 /PRNewswire/ -- Sumitomo Pharma America, Inc. (SMPA) today presented new clinical data supporting further development of enzomenib, an investigational, oral selective menin inhibitor being researched for the treatment of relapsed or refractory acute leukemia, and nuvisertib, an oral investigational highly selective small molecule PIM1 kinase inhibitor, being researched for the treatment of relapsed or refractory myelofibrosis (MF), at the 67th American Society of Hematology (ASH) Annual Meeting and Exposition. Updated Data Shared with the Use of Enzomenib in Acute Myeloid Leukemia Updated preliminary data were presented from the ongoing Phase 1/2 study of enzomenib monotherapy, which as of October 4, 2025, included 116 total patients with acute leukemia, most of whom (93.1%, 108/116) had acute myeloid leukemia (AML) with a median of two prior regimens. Genomic abnormalities of leukemia subtypes including KMT2A rearrangement (KMT2Ar) were documented in 61 patients (52.6%), NPM1 mutation (NPM1m) in 34 patients (29.3%), and other HOXA9/MEIS1-driven abnormalities in 21 patients (17.7%). Enzomenib was escalated from 40 mg twice a day (BID) to 400 mg BID with no dose-limiting toxicities (DLTs). Treatment-related adverse events (TRAEs) observed in at least 10% of patients were nausea (16.4%), and vomiting (11.2%). Differentiation syndrome (DS) was reported in 12.9% of patients and did not result in patient deaths, study discontinuations, or dose reductions of enzomenib. No treatment-related deaths were observed in the study. Dose-dependent increases in exposure were observed, particularly at doses greater than 140 mg BID. Little to no drug accumulation was observed, and CYP3A4 inhibitor azoles did not have a significant impact on exposure. In patients with KMT2Ar, dose optimization of 200, 300, and 400 mg BID is complete, and the RP2D has been determined as 300 mg BID. At RP2D, in patients with KMT2Ar who had not received prior treatment with a menin inhibitor (n = 15), the objective response rate (ORR) was 73.3% and CR+CRh was 40%. Across the optimization dose levels, the duration of CR+CRh (n = 11) was 12.5 months and in all optimization patients (n = 39) median overall survival (mOS) was 11.8 months. For patients with NPM1m AML, dose optimization is ongoing at 200, 300, and 400 mg BID with a focus on 200 and 300 mg BID in patients who have not received a prior menin inhibitor. In the NPM1m dose optimization population (n=25, pts who received ≥ 200 mg BID), ORR is 52% and CR+CR is 44% with a duration of CR+CRh of 5.7 months. The mOS was 8.5 months. "Despite improved understanding of the genetic factors of certain high-risk subtypes in acute leukemias, poor prognosis for patients remains a significant unmet need," said Naval G. Daver, M.D., professor and director of the Leukemia Research Alliance Program in the Department of Leukemia at MD Anderson Cancer Center in Houston. "The data from this ongoing Phase 1/2 study continue to show that enzomenib exhibits promising clinical activity, with encouraging overall and complete response rates, duration of response, and no significant drug interactions with azoles in patients with relapsed or refractory KMT2Ar or NPM1m AML. As an intentionally designed oral therapy to inhibit menin and KMT2A protein interaction, these encouraging clinical results combined with a promising safety profile support the potential of enzomenib as a therapeutic option for relapsed or refractory acute leukemia patients with KMT2A-rearranged or NPM1-mutated subtypes of the disease." Also presented were preliminary results of a Phase 1 study of enzomenib at dose levels of 140 mg, 200 mg, and 300 mg BID in combination with azacitidine and venetoclax (VEN/AZA) in patients with relapsed or refractory AML with KMT2Ar or NPM1m. VEN was administered on days 1-14 of a 28-day study cycle, AZA on days 1-7, and enzomenib was administered on days 1-28 with and without azole antifungal agents. A total of 40 patients were enrolled, of which 18 had KMT2Ar (45%) and 22 (55%) had NPM1m. The median number of prior regimens was 2, with 15 patients having received prior venetoclax (37.5%) and 11 patients (27.5%) a prior menin inhibitor. There were no DLTs observed in the 40 patients enrolled. Hematologic TRAEs related to any regimen component observed in at least 15% of patients included thrombocytopenia (45%), leukopenia (35%), neutropenia (30%), anemia (22.2%), and lymphopenia (15%). Non-hematologic TRAEs were nausea (25%), diarrhea (20%), and AST increased and constipation (15% each). Any-cause QT interval prolongation was reported in 4 patients (10%) with no grade 3 or higher events; no cases were considered related to enzomenib. There were also 4 events of non-serious DS with 0 events grade 3 or higher. Pharmacokinetic data indicated that there were no significant drug-drug interactions between enzomenib and VEN. As of the clinical data cutoff on October 4, 2025, clinical activity data is available for 26 of the 40 total patients as 11 patients were still in Cycle 1 (n = 9) or Cycle 2 (n = 2), and 3 patients had cutaneous leukemia without measurable disease in the bone marrow (bone marrow blasts <5%). Promising preliminary clinical activity has been observed, particularly in patients without prior VEN or menin inhibitor exposure (N=13). The ORR is 85% (11/13) and the composite complete remission (CRc) rate is 62% (8/13). Local MRD assessments were available in 9 patients and 7/9 (78%) achieved MRD negativity as of the cut-off. These data support evaluating enzomenib with VEN/AZA in patients with newly diagnosed AML. Study arms are being added to investigate the combination regimen for patients with newly diagnosed disease. Enzomenib will be administered at 200 mg or 300 mg BID using VEN/AZA administered according to the FDA label. Enrollment of newly diagnosed patients with KMT2Ar or NPM1m AML will begin in early 2026. Nuvisertib in Patients with Relapsed or Refractory (R/R) MF For the first time, clinical data were presented from the ongoing global Phase 1/2 study evaluating the safety and efficacy of nuvisertib in combination with momelotinib (MMB) in 18 patients with R/R MF with anemia. All enrolled patients in the study had previously been treated with a JAK inhibitor, the current standard of care for patients with MF, and 61% of patients had high molecular risk mutation. Preliminary data showed that the treatment with nuvisertib and MMB combination appeared well tolerated, with early clinical activity observed, including ³50% total symptom score reduction (TSS50 response) in 58% of patients with an absolute reduction in all individual symptoms, a spleen volume reduction ³ 25% (SVR25 response) in 50% of patients, anemia improvement, and cytokine modulation in patients with relapsed or refractory MF with anemia. These preliminary data, collected as of October 15, 2025, support further development of nuvisertib in combination with MMB as a potential treatment option for patients with MF. Additionally, data presented from the ongoing global Phase 1/2 study of nuvisertib in patients with relapsed or refractory MF (N=77) showed that nuvisertib monotherapy continued to be well tolerated with no DLTs and limited myelosuppression. The results showed that treatment with nuvisertib monotherapy led to SVR25 response in 20% of patients, TSS50 response in 45% of patients with absolute reduction in all individual symptoms. Data also showed that treatment with nuvisertib resulted in significant cytokine modulation over time, correlating with spleen and symptom responses and one-year overall survival rate of 81%. "Patients living with myelofibrosis with anemia usually have a dismal prognosis, still continue to face limited treatment options," said John Mascarenhas, M.D., Director of the Center of Excellence for Blood Cancers and Myeloid Disorders, Icahn School of Medicine at Mount Sinai, New York. "The promising preliminary results from the combination of nuvisertib and momelotinib underscore the urgent need for new therapeutic approaches that may offer meaningful clinical benefits to a difficult to treat disease." "We are excited to present the first-ever myelofibrosis data with a momelotinib-based combination, specifically nuvisertib in combination with momelotinib. The development of innovative therapies—both alone and in combination with other treatments—are critical for physicians and patients with blood cancers such as AML or MF who are in urgent need of new effective therapies," said Jatin Shah, M.D., Chief Medical Officer, Oncology, SMPA. "Based on these updated preliminary data presented at ASH, which continue to show promising clinical activity and safety profiles for both enzomenib and nuvisertib, we remain committed to accelerate the clinical development in these programs with the ultimate goal of improving patient outcomes." About Leukemia Leukemia is a type of cancer that forms in blood-forming tissue, characterized by the uncontrolled growth of blood cells, usually white blood cells, in the bone marrow. Acute leukemia, a form of leukemia, requires immediate treatment as blood cells multiply rapidly leading to a sudden onset of symptoms.1 Approximately 30% of patients with AML have NPM1 mutations,2 and 5%-10% of patients with AML have KMT2A rearrangements.3 About Myelofibrosis (MF) MF is a rare type of blood cancer that is characterized by the buildup of fibrous tissue in the bone marrow, which can affect the production of blood cells. This buildup is caused by dysregulation in the JAK signaling pathway. MF is a serious and rare disease with 0.7 new cases per 100,000 people worldwide each year.4 About Enzomenib (DSP-5336) Enzomenib is an investigational, oral, small molecule inhibitor of the menin and Lysine (K)-specific methyltransferase 2A (KMT2A) protein interaction, a key interaction in acute leukemia and other tumor cell proliferation and growth. Menin is a scaffold nuclear protein, which plays key roles in gene expression and protein interactions involved in many biological pathways, including cell growth, cell cycle, genomic stability, and hematopoiesis.5,6 In preclinical studies, enzomenib has shown selective growth inhibition in human acute leukemia cell lines with KMT2A rearrangements or NPM1 mutations.5,7 Enzomenib reduced the expression of the leukemia-associated genes HOXA9 and MEIS1 and increased the expression of the differentiation gene CD11b in human acute leukemia cell lines with KMT2A rearrangements and NPM1 mutation.8,9 The safety and efficacy of enzomenib is currently being clinically evaluated in a Phase 1/2 dose-escalation/dose-expansion study in patients with relapsed or refractory acute leukemia (NCT04988555). Additionally, the registrational Phase 2 Horizen-1 R/R mono AML/ALL (KMT2Ar + NPM1m) study is now open for enrollment. The FDA granted Orphan Drug Designation for enzomenib for the indication of acute myeloid leukemia in June 2022. The FDA granted Fast Track Designation for enzomenib for the indication of relapsed or refractory acute myeloid leukemia with KMT2Ar or NPM1m in June 2024. Japan's Pharmaceuticals and Medical Devices Agency (PMDA) granted Orphan Drug Designation for enzomenib for the indication of relapsed or refractory acute myeloid leukemia with KMT2Ar or NPM1m in September 2024. About Nuvisertib (TP-3654) Nuvisertib is an oral investigational selective inhibitor of PIM1 kinase, which has shown potential antitumor and antifibrotic activity through multiple pathways, including induction of apoptosis in preclinical models.10,11 Nuvisertib was observed to inhibit proliferation and increase apoptosis in murine and human hematopoietic cells expressing the clinically relevant JAK2 V617F mutation.10 Nuvisertib alone and in combination with ruxolitinib showed white blood cell and neutrophil count normalization and reduced spleen size and bone marrow fibrosis in JAK2 V617F and MPLW515L murine models of myelofibrosis.11 The safety and efficacy of nuvisertib is currently being clinically evaluated in a Phase 1/2 study in patients with intermediate- and high-risk myelofibrosis (NCT04176198). The FDA granted Orphan Drug Designation to nuvisertib for the indication of myelofibrosis in May 2022. The Japan Ministry of Health, Labour and Welfare (MHLW) granted Orphan Drug Designation to nuvisertib for the treatment of myelofibrosis in November 2024. The FDA granted Fast Track Designation to nuvisertib for the indication of myelofibrosis in July 2025. About Sumitomo Pharma Sumitomo Pharma Co., Ltd. is a global pharmaceutical company based in Japan with key operations in the U.S. (Sumitomo Pharma America, Inc.) and Canada (Sumitomo Pharma Canada, Inc.) focused on addressing patient needs in oncology, urology, women's health, rare diseases, cell & gene therapies and CNS. With several marketed products in the U.S., Canada, and Europe, and a diverse pipeline of early- to late-stage investigational assets, we aim to accelerate discovery, research, and development to bring novel therapies to patients sooner. For more information on SMPA, visit our website or follow us on LinkedIn. The Sumitomo corporate symbol mark is a trademark of Sumitomo Pharma Co., Ltd., used under license. SUMITOMO PHARMA is a trademark of Sumitomo Pharma Co., Ltd., used under license. SUMITOMO is a registered trademark of Sumitomo Chemical Co., Ltd., used under license. Sumitomo Pharma America, Inc., is a U.S. subsidiary of Sumitomo Pharma Co., Ltd. ©2025 Sumitomo Pharma America, Inc. All rights reserved. References Chennamadhavuni A, Lyengar V, Mukkamalla SKR, et al. Leukemia. [Updated 2023 Jan 17]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: Brandi ML, Agarwal SK, Perrier ND, Lines KE, Valk GD, Thakker RV. Multiple Endocrine Neoplasia Type 1: Latest Insights. Endocr Rev. 2021;42(2):133-170. doi:10.1210/endrev/bnaa031 Borkin D, Klossowski S, Pollock J, et al. Complexity of Blocking Bivalent Protein-Protein Interactions: Development of a Highly Potent Inhibitor of the Menin-Mixed-Lineage Leukemia Interaction. J Med Chem. 2018;61(11):4832-4850. doi:10.1021/acs.jmedchem.8b00071 Hernández-Boluda JC, Czerw T. Transplantation algorithm for myelofibrosis in 2022 and beyond. Best Pract Res Clin Haematol. 2022;35(2):101369. doi:10.1016/j.beha.2022.101369 Cierpicki T, Grembecka J. Challenges and opportunities in targeting the menin-MLL interaction. Future Med Chem. 2014;6(4):447-462. doi:10.4155/fmc.13.214 Matkar S, Thiel A, Hua X. Menin: a scaffold protein that controls gene expression and cell signaling. Trends Biochem Sci. 2013;38(8):394-402. doi:10.1016/j.tibs.2013.05.005 Kühn MW, Song E, Feng Z, et al. Targeting Chromatin Regulators Inhibits Leukemogenic Gene Expression in NPM1 Mutant Leukemia. Cancer Discov. 2016;6(10):1166-1181. doi:10.1158/2159-8290.CD-16-0237 Eguchi K, Shimizu T, Kato D, et al. Preclinical Evaluation of a Novel Orally Bioavailable Menin-MLL Interaction Inhibitor, DSP-5336, for the Treatment of Acute Leukemia Patients with MLL-Rearrangement or NPM1 Mutation. Blood 2021; 138 (Supplement 1): 3339. Available at: Daver N, Zeidner JF, Yuda J, et al. Phase 1/2 First-in-Human Study of the Menin-MLL Inhibitor DSP-5336 in Patients with Relapsed or Refractory Acute Leukemia. Blood 2023; 142 (Supplement 1): 2911. Available at: Dutta A, Nath D, Yang Y, et al. Genetic ablation of Pim1 or pharmacologic inhibition with TP-3654 ameliorates myelofibrosis in murine models. Leukemia. 2022;36(3):746-759. doi:10.1038/s41375-021-01464-2 Foulks JM, Carpenter KJ, Luo B, et al. A small-molecule inhibitor of PIM kinases as a potential treatment for urothelial carcinomas. Neoplasia. 2014;16(5):403-412. doi:10.1016/j.neo.2014.05.004 SOURCE Sumitomo Pharma America 21% more press release views with Request a Demo

First patient dosed in Phase I/II HEMA-MED clinical trial (NCT06887803) evaluating the tolerability and efficacy profile of roginolisib (PI3Kδ inhibitor) plus ruxolitinib in myelofibrosis (MF) patients unresponsive to Janus kinase (JAK) inhibitors Dual-target approach: combining PI3Kδ and JAK inhibition addresses complementary disease mechanisms and may overcome unresponsiveness to JAK inhibitors in MF New supporting non-clinical data to be presented at the 67th American Society of Hematology (ASH) Annual Meeting in Orlando, Florida: Data from ex-vivo models of MF demonstrate roginolisib monotherapy activity and synergy with JAK inhibition GENEVA, AMSTERDAM and CAMBRIDGE, Mass., Dec. 4, 2025 /PRNewswire/ -- iOnctura, a clinical-stage biopharmaceutical company combating neglected and hard-to-treat cancers, today announces it has dosed the first patient in its Phase I/II clinical trial evaluating roginolisib in patients with MF who are no longer responding to JAK inhibition. Further details of the trial will be presented in a poster presentation at the 67th American Society of Hematology (ASH) Annual Meeting in Orlando, Florida on Sunday, December 7 at 6pm EST. This milestone marks an important step toward addressing the significant unmet medical needs of MF patients who face diminishing therapeutic options, as their disease progresses or becomes resistant to standard-of-care JAK inhibitor treatment. The Phase I/II trial is part of a comprehensive development program evaluating next-generation PI3Kδ inhibitor roginolisib's tolerability and anti-tumor response across a number of solid and hematologic malignancies. "Based on non-clinical data being presented at ASH, we anticipate that targeting both the PI3Kδ and JAK pathways could have a synergistic effect in MF — an approach that has previously eluded older generation PI3Kδ inhibitors because of their unfavorable tolerability profiles." said Dr Michael Lahn, Chief Medical Officer of iOnctura. Overactivation of the PI3K-Akt signaling pathway contributes to the occurrence and progression of cancer[1]. In MF, pathway activation is a well described mechanism of resistance in response to JAK inhibition[2]. Inhibition of this pathway using roginolisib may overcome the lack of response and lead to a beneficial therapeutic effect. Non-clinical evidence in support of this mechanism is being presented at ASH on Monday, December 8, 2025 at 6pm EST. These data demonstrate monotherapy activity of roginolisib against MF cell lines and in vitro models of primary MF cells. Further, roginolisib and JAK inhibition (ruxolitinib or momelotinib) exerts a synergistic anti-cancer effect. These data support the rationale behind the ongoing HEMA-MED clinical trial. Professor Alessandro Vannucchi, Professor of Hematology and Department Head of the Center for Research and Innovation in Myeloproliferative Neoplasms (CRIMM) at the University of Florence, Florence, Italy and Principal Investigator of the HEMA-MED study said: "Myelofibrosis patients often have suboptimal responses to ruxolitinib and/or acquire resistance over time. Roginolisib's intriguing mechanism of action and favorable toxicity profile position it as a compelling partner for ruxolitinib. By combining these agents, we could unlock more durable responses and redefine therapeutic expectations for this challenging rare disease." In addition to the two posters related to MF, trials in progress posters for the ongoing investigations of roginolisib in peripheral T-cell lymphoma and chronic lymphocytic leukemia (CLL) will also be presented at ASH. iOnctura poster presentations at the 67th ASH Annual Meeting in Orlando, Florida, USA: 1. A Vannucchi et al. Trial in progress: Sunday, December 7, 06:00 PM - 08:00 PM EST Abstract 25-4153: A study of roginolisib in combination with ruxolitinib in patients with myelofibrosis who are unresponsive to JAK inhibitors (HEMA-MED) 2. M Balliu et al.: Monday, December 8, 06:00 PM - 08:00 PM EST Abstract 25-7102: The selective PI3Kd inhibitor roginolisib synergizes with ruxolitinib against progenitor cells from naïve and JAK-inhibitor-refractory/resistant patients with myelofibrosis 3. D Sibon et al. Trial in progress: Sunday, December 7, 06:00 PM - 08:00 PM EST Abstract 25-11050: PlatΤform: A multicenter, multi-arm, academic platform trial evaluating novel agents and combinations in relapsed or refractory peripheral T-cell lymphomas 4. J Brown et al. Trial in progress: Sunday, December 7, 06:00 PM - 08:00 PM EST Abstract 25-7765: Roginolisib (IOA-244), an orally bioavailable, selective PI3Kδ inhibitor, in combination with venetoclax and rituximab in patients with relapsed chronic lymphocytic leukemia (CLL) About myelofibrosis (MF) MF is a rare myeloproliferative neoplasm marked by activation and growth of mutated cells in the bone marrow, with approximately 0.5 cases per 100,000 individuals diagnosed globally a year[3]. JAK inhibitors are a key treatment option for MF patients and improve symptoms and quality of life, but approximately half of patients discontinue therapy within three years[4]. Reasons for discontinuation include disease progression, tolerability and adverse events and death resulting from resistance to the JAK therapy[5],[6]. About the HEMA-MED clinical trial The HEMA-MED trial (NCT06887803) is a prospective, multi-center, open-label Phase I/II single arm trial consisting of two parts. Part 1 (Phase 1) will enroll 13 patients to assess the safety of the combination of the PI3Kδ inhibitor roginolisib in combination with the JAK inhibitor ruxolitinib, and Part 2 (Phase 2) will expand to enroll 13 additional patients to further allow the assessment of benefit/risk for all 26 patients. In addition to safety, the secondary endpoints of the HEMA-MED trial include blood biomarker and spleen reduction responses, and improvements of MF related symptoms. Exploratory measures will assess endpoints associated with the mechanism of action (MOA) of roginolisib. About iOnctura iOnctura is a clinical-stage precision oncology company combating neglected and hard-to-treat cancers with a pipeline of first-in-class small molecules. The bold new treatments extend lives and improve healthspans, changing the outlook for patients and their families. Lead asset, roginolisib, is a non-ATP competitive, allosteric modulator of PI3Kδ with a unique chemical structure and binding mode. Allosteric modulation is a new archetype for precise inhibition of PI3Kδ, promising clinical activity without the detrimental tolerability seen with previous generations of inhibitors. Roginolisib is being investigated in multiple randomized Phase II studies in solid and hematological malignancies. iOnctura is headquartered in Amsterdam, The Netherlands with subsidiaries located in Geneva, Switzerland and Cambridge, MA, USA. iOnctura is backed by specialist institutional investors including Syncona, M Ventures, Inkef Capital, EIC Fund, VI Partners, Schroders Capital and XGEN Venture. About roginolisib Roginolisib is a first-in-class, non-ATP competitive, allosteric modulator of PI3Kδ with a unique chemical structure and binding mode. Allosteric modulation is a new archetype for precise inhibition of PI3Kδ, promising clinical activity without the detrimental tolerability seen with previous generations of inhibitors. The PI3K signaling pathway is one of the most commonly dysregulated pathways across multiple cancer types. The potential of roginolisib has been validated by positive clinical signals in Phase I in solid tumor and hematological malignancies, including a doubling of overall survival compared to historical controls in rare eye cancer, uveal melanoma. The company has carefully designed its clinical program to allow full development in uveal melanoma, while in parallel validating the program in larger market indications. The Phase II OCULE-01 study in uveal melanoma started in March 2025, the PULMO-01 study in non-small cell lung cancer (NSCLC) started in May 2025 and the HEMA-MED Phase I/II study in myelofibrosis began in November 2025. For more information contact: Corporate Press Office: [email protected] [1] He et al., 2021 [2] Moyo et al., 2023 [3] Titmarsh et al., 2014 [4] Verstovsek et al., 2015 [5] Kuykendall et al., 2018 [6] Newberry et al., 2017 Logo - SOURCE iOnctura 21% more press release views with Request a Demo