Ojjaara (momelotinib) / GSK - LARVOL DELTA

Pacritinib is a potent ACVR1 inhibitor with significant anemia benefit in patients with myelofibrosis. (PubMed, Blood Adv) - "Pacritinib inhibited ACVR1 with greater potency (IC50 = 16.7 nM; Cmax:IC50 = 12.7) than momelotinib (IC50 = 52.5 nM; Cmax:IC50 = 3.2), fedratinib (IC50 = 273 nM; Cmax:IC50 = 1.0), or ruxolitinib (IC50 >1000; Cmax:IC50 <0.01). Among patients on PERSIST-2 who were not TI at baseline based on Gale criteria, a significantly greater proportion became TI on pacritinib compared to best available therapy (37% vs. 7%, P=0.001), and significantly more had a ≥50% reduction in transfusion burden (49% vs. 9%, P<0.0001). These data indicate that the anemia benefit of the JAK2/IRAK1 inhibitor pacritinib may be a function of potent ACVR1 inhibition."

Journal • Anemia • Hematological Disorders • Myelofibrosis • ACVR1 • IRAK1

Preliminary data from the Phase I/II study of nuvisertib, an oral investigational selective PIM1 inhibitor, in combination with momelotinib showed clinical responses in patients with relapsed/refractory myelofibrosis (ASH 2025) - P1/2 | "Nuvisertib (NUVI, TP-3654), an oralinvestigational highly selective PIM1 kinase inhibitor, alone and in combination with ruxolitinib (RUX)showed spleen size reduction and bone marrow (BM) fibrosis improvement in JAK2V617F and MPLW515LMF mouse models. NUVI + MMB combo appeared to be well tolerated. Preliminary data showed early clinicalactivity including 60% TSS50 response and absolute symptom improvement, 40% SVR25 response,cytokine modulation and anemia improvement in R/R MF pts with anemia. Preliminary data supportsfurther development of NUVI + MMB combo for pts with MF."

Clinical • Combination therapy • P1/2 data • Fibrosis • Hematological Disorders • Immunology • Myelofibrosis • Thrombocytopenia • ACVR1 • PIM1

Modulators of the Hepcidin Pathway in Polycythemia Vera and Myelofibrosis. (PubMed, Blood) - "Since hepcidin levels are relatively low in PV patients, hepcidin agonists (rusfertide, divesiran, sapablursen) are undergoing clinical development to control PV associated erythrocytosis, thereby reducing the need for therapeutic phlebotomies and myelosuppressive therapeutic options. A number of strategies to lower hepcidin levels (the JAK2 inhibitors pacritinib and momelotinib, anti-hemojuvelin monoclonal antibody DISC-0974C) are currently undergoing clinical development to make systemic iron available for erythropoiesis and alleviate the degree of MF associated anemia. These new therapeutic options that modulate iron trafficking in PV and MF patients represent the application of greater knowledge of iron trafficking to create novel therapeutic options to treat patients with hematological malignancies."

Journal • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Myelofibrosis • Oncology • Polycythemia Vera

Mechanistic insights into reactive oxygen species (ROS) homeostasis in ovarian cancer chemoresistance (AACR 2026) - "Pharmacologic inhibition was performed using GSI-MK0752 (NOTCH1/HES1) and CYT387 (JAK2/STAT5). A ROS-responsive NOTCH1/HES1 and IL11/STAT5 signaling axis plays a central role in maintaining CSC populations and promoting platinum resistance in ovarian cancer. Dual targeting of these signaling pathways disrupts the redox-regulated circuit and enhances cisplatin efficacy, supporting further investigation of this combinatorial strategy as a potential therapeutic approach for platinum-resistant ovarian cancer."

Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor • CD44 • HES1 • JAK2 • NOTCH1 • SOD2 • STAT5

Momelotinib: Unique polypharmacology and novel combination strategies for myelofibrosis and beyond (AACR 2026) - "Notably, the XPO1 inhibitor selinexor emerged as a combination partner that both inhibited malignant cell growth and deepened hepcidin suppression. These discoveries highlight momelotinib's unique activity, both as a monotherapy for expanded indications and as an ideal combination partner to more effectively control anemia and halt disease progression in MF patients."

IO biomarker • Hematological Malignancies • Myelodysplastic Syndrome • Myelofibrosis • Oncology • ACVR1 • BMP6 • IRAK1 • JAK1 • XPO1

Biochemical and cellular evaluation of HUNK inhibition by an FDA approved drug as potential therapeutic strategy for HER2+ breast cancer (AACR 2026) - "Kinase inhibitors have been on spotlight for cancer drug discovery ever since the approval of Imatinib and recently the 100th small molecule kinase inhibitor was approved by the FDA showing the potential of kinase inhibitors for cancer therapeutics and beyond. Furthermore, CellTiter-Glo assays demonstrated Momelotinib inhibits proliferation of HER2+ JIMT1 cells and triple-negative 4T1 breast cancer cells, while caspase-3/7 activation assays indicated Momelotinib induces apoptotic cell death in both lines. These findings highlight Momelotinib as a potential therapeutic candidate for overcoming HER2 inhibitor resistance in breast cancer."

Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Myelofibrosis • Oncology • Solid Tumor • Triple Negative Breast Cancer • ACVR1 • CASP3 • CASP7 • HER-2 • JAK1 • JAK2

A Study of JNJ-88549968 for the Treatment of Calreticulin (CALR)-Mutated Myeloproliferative Neoplasms (clinicaltrials.gov) - P1 | N=220 | Recruiting | Sponsor: Janssen Research & Development, LLC | Trial completion date: Dec 2027 ➔ Apr 2028

CALR • First-in-human • Trial completion date • Essential Thrombocythemia • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • CALR

A phase 2 study of canakinumab in patient with myelofibrosis: Results from part 1 (ASH 2025) - "Introduction Myelofibrosis (MF) is a myeloproliferative neoplasm (MPN) for which the only approved therapies are JAKinhibitors which improve splenomegaly and disease-related symptoms. Given the encouraging impact onMF symptoms, blood counts and reassuring safety profile, the study was amended to enroll pts on astable dose of a JAK inhibitor (ruxolitinib, fedratinib, momelotinib, or pacritinib) who have the potential tobenefit from additional therapy. Part 2 is currently enrolling at multiple sites and updated clinical andcorrelative data will be presented at the meeting."

Clinical • P2 data • Cardiovascular • Fibrosis • Immunology • Myelofibrosis • Myeloproliferative Neoplasm • Thrombocytopenia • CRP • IL1B

AN EVOLVING LANDSCAPE – HOW CHANGING CONDITIONING REGIMES CAN IMPROVE MYELOFIBROSIS TRANSPLANT OUTCOMES (EBMT 2026) - "The average age at transplant was 55 years, with a male predominance.Seven patients received Fludarabine/Busulphan/Antithymocyte globulin (Flu/Bu/ATG) conditioning (Fludarabine 30mg/m2 for 5 days, Busulphan 3.2mg/kg for 2 days and rabbit ATG 2.5mg/kg for 2 days), seven received Fludarabine/Cyclophosphamide (Flu/Cy) (Fludarabine 25mg/m2 for 5 days and Cyclophosphamide 1g/m2 for 2 days), and two received Fludarabine/Melphalan (Flu/Mel) (Fludarabine 25mg/m2 for 5 days and Melphalan 100mg/m2 on one day)...Therapies included Ruxolitnib, Momelotinib, splenic irradiation and Hydroxycarbamide amongst others.Cytogenetics were abnormal in four patients (two in each regimen group), normal in nine, and unknown in three... Although limited by a small sample size, these findings indicate that the Flu/Bu/ATG conditioning regimen may be associated with improved outcomes. This supports its adoption as the preferred approach, in line with BSH guidelines."

Acute Graft versus Host Disease • Chronic Graft versus Host Disease • Graft versus Host Disease • Immunology • Infectious Disease • Myelofibrosis • Pneumonia • Respiratory Diseases • Transplantation • CALR • JAK2

ALLOGENEIC STEM CELL TRANSPLANTATION IN MYELOFIBROSIS: SINGLE CENTRE EXPERIENCE (EBMT 2026) - "All transplants used peripheral blood as stem cells source and received antifungal and antiviral prophylaxis (letermovir for CMV-seropositive since available), as well as graft-versus-host disease (GVHD) prophylaxis with different regimens...Four received radiotherapy and 2 splenectomy.Seven patients received pre-transplant ruxolitinib; two responded to treatment: one had initial response that later lost, and the other one switched to momelotinib because of secondary anemia.Regarding donor type: 40% (6/15) were from matched related donors, 40% (6/15) mismatch unrelated, 13.3% (2/15) matched unrelated and 6.6% (1/15) haploidentical.Most commonly conditioning regimen was fludarabine-busulfan. Four patients received TBF (thiotepa, busulfan and fludarabine) and the rest other regimens (BuCy, FluMel).For GVHD prophylaxis, cyclosporine A was mainly used in combination with other immunosuppressants (methotrexate, mycophenolate mofetil)... Our cohort supports that AHSCT in..."

Clinical • Chronic Graft versus Host Disease • Essential Thrombocythemia • Graft versus Host Disease • Hematological Disorders • Hepatology • Immunology • Myelofibrosis • Polycythemia Vera • Transplantation • ASXL1 • CALR • JAK2 • TP53

MARKET SHARE AND ECONOMIC TRENDS OF JANUS KINASE INHIBITORS IN U.S. MEDICAID, 2011- 2023 (ISPOR 2026) - "This study describes utilization, spending, pricing, and market share of Medicaid-reimbursed JAK inhibitors (tofacitinib, upadacitinib, baricitinib, ruxolitinib, fedratinib, abrocitinib, ritlecitinib, momelotinib, and deucravacitinib) in the U.S. from 2011-2023. A retrospective descriptive analysis was conducted using the CMS Medicaid outpatient State Drug Utilization Data (2011-2023) for all FDA-approved JAK inhibitors reimbursed by Medicaid. Medicaid JAK utilization and spending increased over time, while market share shifted from Tofacitinib toward newer agents. Price growth among several high-cost agents, alongside market diversification, highlights continuing affordability concerns."

Medicaid • Reimbursement • US reimbursement • Immunology • Inflammation

Spleen Volume Reduction and Transfusion Independence With Momelotinib Versus Ruxolitinib and Associated Overall Survival With Momelotinib in JAK Inhibitor-Naive Patients With Myelofibrosis and Anemia: Subgroup Analyses of SIMPLIFY-1. (PubMed, Clin Lymphoma Myeloma Leuk) - P3 | "These results highlight that both spleen- and anemia-related benefits of momelotinib correlate with improved OS, supporting prioritization of TI in anemic patients for optimal long-term outcomes, and suggest that momelotinib may be the preferred JAK inhibitor in anemic patients with platelets < 200 × 109/L."

Journal • Anemia • Hematological Disorders • Myelofibrosis

Triple Targeting in Myelofibrosis with Momelotinib: Integrated Therapeutic Approach via JAK1/2 and ACVR1 Inhibition (ICKSH 2026) - "Practical guidance on initiating momelotinib therapy is provided, including dosing considerations, laboratory monitoring, and management of key safety watchpoints. Collectively, this integrated therapeutic approach highlights the role of momelotinib as a differentiated treatment option, particularly for patients with anemia , and underscores the need for phenotype -driven decision -making in the evolving MF treatment landscape."

Hematological Disorders • Myelofibrosis • Myeloproliferative Neoplasm • ACVR1 • JAK1 • JAK2

SENTRY-2: A Study of Selinexor Monotherapy in Subjects With JAK Inhibitor-naïve Myelofibrosis and Moderate Thrombocytopenia (clinicaltrials.gov) - P2 | N=58 | Recruiting | Sponsor: Karyopharm Therapeutics Inc | N=118 ➔ 58 | Trial primary completion date: Apr 2026 ➔ Jun 2027

Enrollment change • Monotherapy • Trial primary completion date • Hematological Disorders • Myelofibrosis • Thrombocytopenia

Overall survival with momelotinib vs. best available therapy in patients with ruxolitinib-experienced myelofibrosis: a matching-adjusted indirect comparison. (PubMed, Ann Hematol) - No abstract available

Journal • Hematological Disorders • Myelofibrosis

GFM-VEXAS-MMB: Momelotinib in VEXAS syndrome (clinicaltrialsregister.eu) - P1/2 | N=57 | Recruiting | Sponsor: Groupe Francophone Des Myelodysplasies

New P1/2 trial • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

Extended Access of Momelotinib in Adults With Myelofibrosis (clinicaltrials.gov) - P2 | N=200 | Not yet recruiting | Sponsor: Gilead Sciences

New P2 trial • Hematological Disorders • Hematological Malignancies • Myelofibrosis • Myeloproliferative Neoplasm • Thrombocytosis

Extended Access of Momelotinib in Adults With Myelofibrosis (clinicaltrials.gov) - P2 | N=237 | Active, not recruiting | Sponsor: GlaxoSmithKline | N=400 ➔ 237

Enrollment change • Hematological Disorders • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • Thrombocytosis

Extended Access of Momelotinib in Adults With Myelofibrosis (clinicaltrials.gov) - P2 | N=400 | Active, not recruiting | Sponsor: Sierra Oncology, Inc. | Enrolling by invitation ➔ Active, not recruiting

Enrollment closed • Hematological Disorders • Myelofibrosis • Myeloproliferative Neoplasm • Thrombocytosis

Extended Access of Momelotinib in Adults With Myelofibrosis (clinicaltrials.gov) - P2 | N=400 | Enrolling by invitation | Sponsor: Sierra Oncology, Inc. | Trial completion date: Dec 2024 ➔ Dec 2026 | Trial primary completion date: Dec 2024 ➔ Dec 2026

Trial completion date • Trial primary completion date • Hematological Disorders • Myelofibrosis • Myeloproliferative Neoplasm • Thrombocytosis

Extended Access of Momelotinib in Adults With Myelofibrosis (clinicaltrials.gov) - P2 | N=400 | Enrolling by invitation | Sponsor: Sierra Oncology, Inc. | Trial completion date: Jun 2020 ➔ Dec 2024 | Trial primary completion date: Jun 2020 ➔ Dec 2024

Trial completion date • Trial primary completion date • Hematological Disorders • Myelofibrosis • Thrombocytosis

Extended Access of Momelotinib in Adults With Myelofibrosis (clinicaltrials.gov) - P2 | N=400 | Enrolling by invitation | Sponsor: Sierra Oncology, Inc. | N=200 ➔ 400

Enrollment change • Hematological Disorders • Myelofibrosis • Myeloproliferative Neoplasm • Thrombocytosis

Bomedemstat (IMG-7289) in Combination With Momelotinib in Patients With Myelofibrosis (clinicaltrials.gov) - P2 | N=40 | Not yet recruiting | Sponsor: United Lincolnshire Hospitals NHS Trust

New P2 trial • Myelofibrosis

Spleen volume reduction and transfusion independence with momelotinib vs ruxolitinib and associated overall survival with momelotinib in JAK inhibitor–naive patients with myelofibrosis and anemia: subgroup analyses of SIMPLIFY-1 (Clin Lymphoma Myeloma Leuk) - "SVR35 rates were similar overall with momelotinib vs ruxolitinib (27/86 [31%] vs 31/94 [33%]), but higher with momelotinib in the baseline platelets <200×109/L subgroup (19/49 [39%] vs 8/47 [17%]) and with ruxolitinib in the baseline platelets ≥200×109/L subgroup (8/37 [22%] vs 23/47 [49%]). Week 24 SVR35+TI was also more common with momelotinib (23/86 [27%]) than with ruxolitinib (7/94 [7%]). Subsequent OS analysis focused on the momelotinib arm only, as the crossover trial design precluded analysis of long-term OS with ruxolitinib."

P3 data • Myelofibrosis

Momelotinib During and After HCT in Myelofibrosis (clinicaltrials.gov) - P1 | N=28 | Recruiting | Sponsor: Massachusetts General Hospital | Not yet recruiting ➔ Recruiting

Enrollment open • Hematological Malignancies • Myelofibrosis • Transplantation • ASXL1 • HLA-B • IDH1 • IDH2 • SRSF2 • U2AF1