Sumitomo Pharma America Highlights New Clinical and Translational Research for Nuvisertib and Enzomenib at EHA 2026
Sumitomo Pharma America, Inc. (SMPA) has unveiled new clinical and translational research findings at the 2026 Congress of the European Hematology Association (EHA), showcasing progress across its hematology-oncology pipeline. The presentations, delivered during the meeting held from June 11–14 in Stockholm, Sweden, included the first public disclosure of preliminary clinical data evaluating the investigational PIM1 inhibitor nuvisertib in combination with momelotinib for patients with myelofibrosis (MF), as well as new translational insights into the biological mechanisms underlying treatment responses observed with the therapy.
In addition, researchers presented new findings related to acquired resistance patterns associated with the investigational menin inhibitor enzomenib in acute leukemia, offering important information that could help guide future treatment strategies and sequential therapeutic approaches.
The data presented at EHA 2026 underscore Sumitomo Pharma America’s continued efforts to address significant unmet needs in hematologic malignancies through innovative therapies that target multiple disease-driving pathways.
Advancing Therapeutic Innovation in Hematologic Cancers
Hematologic malignancies such as myelofibrosis and acute leukemia remain challenging diseases despite advances in targeted therapies. Many patients eventually experience disease progression, treatment resistance, or persistent symptoms that negatively affect quality of life.
According to Tsutomu Nakagawa, Ph.D., President and Chief Executive Officer of Sumitomo Pharma America, the latest findings reflect the company’s commitment to advancing novel treatment approaches that address the complex biological mechanisms underlying these diseases.
Nakagawa noted that the company is encouraged by the preliminary clinical results observed with the combination of nuvisertib and momelotinib, as well as by the growing understanding of how nuvisertib and enzomenib interact with disease biology. He emphasized that these programs are designed to tackle some of the most persistent challenges in hematologic cancer treatment and could ultimately contribute to improved patient outcomes.
Encouraging Early Results for Nuvisertib and Momelotinib in Myelofibrosis
One of the most closely watched presentations at the congress focused on the ongoing global Phase 1/2 clinical study evaluating nuvisertib in combination with momelotinib in patients with relapsed or refractory myelofibrosis and anemia.
The study, identified as NCT04176198, was presented by Dr. James McCloskey, Interim Chief of the Division of Leukemia at the John Theurer Cancer Center in Hackensack, New Jersey.
As of December 6, 2025, investigators had enrolled 26 patients across four escalating dose levels of nuvisertib. Participants received doses of 240 mg, 360 mg, 480 mg, or 720 mg twice daily under fed conditions, combined with the approved myelofibrosis dose of momelotinib at 200 mg once daily.
The enrolled patient population represented a particularly difficult-to-treat group. Every participant had previously received at least one approved Janus kinase (JAK) inhibitor, and approximately 41% carried high molecular risk mutations that are generally associated with poorer outcomes.
Despite these challenges, the combination therapy demonstrated a favorable safety profile during the early stages of the study.
Researchers reported no dose-limiting toxicities across the evaluated dose levels. The most frequently observed treatment-related adverse events occurring in at least 20% of patients included diarrhea, nausea, and thrombocytopenia. The most common Grade 3 treatment-related adverse event was thrombocytopenia without bleeding, which was reported in three patients.
Importantly, investigators observed that average hemoglobin levels and platelet counts remained generally stable throughout the first 24 weeks of treatment, an encouraging finding given the prevalence of anemia and cytopenias among patients with advanced myelofibrosis.
Evidence of Clinical Activity Across Multiple Disease Measures
Beyond safety, the combination demonstrated promising signals of efficacy among patients who completed at least 12 weeks of therapy.
Among the 15 efficacy-evaluable patients, meaningful improvements were observed across several key clinical endpoints commonly used to assess myelofibrosis treatment effectiveness.
One of the most important measures in myelofibrosis studies is spleen volume reduction, as enlargement of the spleen is a hallmark feature of the disease and often contributes significantly to patient symptoms.
At Week 12, 73% of evaluable patients achieved at least a 25% reduction in spleen volume. Among patients who remained on therapy through Week 24, all five evaluable individuals achieved this level of spleen volume reduction.
The therapy also produced encouraging symptom improvements. At Week 12, 53% of patients achieved at least a 50% reduction in total symptom score, a measure that captures disease-related symptoms such as fatigue, night sweats, abdominal discomfort, and bone pain. By Week 24, 60% of evaluable patients met this symptom improvement threshold.
Anemia improvement represented another notable finding. Using criteria established by the International Working Group and European LeukemiaNet (IWG-ELN 2024), investigators reported anemia responses in 50% of patients at some point during treatment.
Perhaps most significantly, 60% of patients who reached the Week 24 evaluation achieved what researchers described as a “triple response.” These patients simultaneously met criteria for meaningful symptom improvement, spleen volume reduction, and anemia response, suggesting broad therapeutic activity across multiple manifestations of the disease.
Scientific Rationale Behind the Combination Approach
The development of the nuvisertib and momelotinib combination is based on a growing understanding of the complex biological pathways that drive myelofibrosis progression.
Current standard therapies primarily target the JAK signaling pathway, which plays a central role in disease development. While JAK inhibitors have significantly improved patient care, many individuals eventually experience inadequate responses or disease progression.
Research has shown that additional signaling pathways can contribute to disease persistence even when JAK signaling is suppressed. One such pathway involves PIM1, a kinase frequently upregulated in myelofibrosis.
Scientists have found that PIM1 expression can be maintained through JAK-independent mechanisms, including pathways involving Nuclear Factor-kappa B (NF-kB) and Ets Related Gene (ERG). These alternative signaling routes may enable malignant cells to survive despite JAK inhibitor treatment.
Nuvisertib was designed to inhibit PIM1, while momelotinib targets both JAK signaling and Activin A Receptor Type 1 (ACVR1). By combining these therapies, researchers hope to simultaneously block multiple disease-driving pathways and potentially achieve deeper and more durable responses.
New Translational Research Sheds Light on Hemoglobin Improvements
Additional translational research presented at the congress offered new insights into why patients receiving nuvisertib may experience stabilization or improvement in hemoglobin levels.
The research was presented by Joseph M. Scandura, M.D., Ph.D., of the Weill Cornell Leukemia Program in New York.
Laboratory and biochemical studies revealed that nuvisertib may have broader biological activity than previously recognized. In addition to inhibiting PIM1, the compound appears capable of binding to and inhibiting ACVR1.
This finding is particularly important because ACVR1 influences the production of hepcidin, a hormone that serves as a key regulator of iron metabolism. Elevated hepcidin levels are commonly associated with anemia and impaired red blood cell production.
Investigators found that ACVR1 inhibition by nuvisertib reduced hepcidin messenger RNA expression in laboratory models. Preliminary clinical observations from an ongoing Phase 1/2 monotherapy study further demonstrated reductions in hepcidin levels among patients with relapsed or refractory myelofibrosis.
These findings may help explain the hemoglobin stability and anemia improvements observed in patients treated with nuvisertib and suggest that the therapy could offer benefits beyond direct suppression of malignant signaling pathways.
Dr. Raajit Rampal, Director of the Myeloproliferative Neoplasms Program at Memorial Sloan Kettering Cancer Center, commented that the emerging data support the hypothesis that combining nuvisertib with momelotinib may provide broader suppression of disease biology than current therapeutic approaches.
He noted that the combination’s encouraging effects on symptoms, spleen size, and anemia, together with evidence suggesting dual PIM1 and ACVR1 inhibition, indicate the potential for meaningful clinical benefit in patients with myelofibrosis.
New Insights Into Resistance Mechanisms in Acute Leukemia
Beyond myelofibrosis, Sumitomo Pharma America also presented important translational research related to enzomenib, its investigational menin inhibitor being studied in acute leukemia.
The findings were presented by Jevon Cutler, Ph.D., Assistant Professor of Cell, Developmental and Cancer Biology at Oregon Health & Science University School of Medicine.
The research focused on understanding how leukemia cells develop resistance following an initial response to menin inhibitor therapy.
Through serial molecular profiling of patients receiving enzomenib, investigators identified distinct mutations within the MEN1 gene that emerged during relapse. Among these, the E368K mutation appeared to be the dominant resistance signature.
The mutation was detected in 53% of patients who relapsed after initially responding to enzomenib treatment.
Importantly, preclinical modeling had previously predicted E368K as a likely resistance mechanism, and further laboratory analyses suggest that this mutation may not impair sensitivity to certain other menin inhibitors.
These findings raise the possibility that sequential treatment strategies using different menin inhibitors could potentially overcome resistance and prolong therapeutic benefit.
The research presented at EHA 2026 highlights the growing sophistication of Sumitomo Pharma America’s oncology development strategy, which combines clinical investigation with deep translational science to better understand disease biology and treatment response.
The preliminary results from the nuvisertib and momelotinib combination study suggest potential activity across multiple key manifestations of myelofibrosis, while mechanistic studies provide new insights into how the therapy may improve anemia and overall disease control.
At the same time, the identification of specific resistance signatures associated with enzomenib offers valuable guidance for future drug development efforts in acute leukemia.
As both programs continue to advance through clinical development, Sumitomo Pharma America hopes to generate additional evidence supporting new therapeutic options for patients facing difficult-to-treat hematologic malignancies, an area where significant unmet medical needs remain despite recent advances in targeted cancer therapies.
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.) focused on addressing patient needs in oncology, urology, women’s health, rare diseases, cell & gene therapies, and CNS. With products in the U.S., Canada, and Europe, and a diverse pipeline of early- to late-stage assets, we aim to accelerate discovery, research, and development to bring novel therapies to patients sooner. For more information on SMPA, visit our website https://www.us.sumitomo-pharma.com or follow us on LinkedIn.
The Sumitomo corporate symbol mark is a registered 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.
