Inrebic (fedratinib) / BMS - LARVOL DELTA

Prescribing patterns in MDS/MPN syndromes (ASH 2025) - "Additionally, the prescribing patterns of Hydroxyurea, Hypomethylating Agents (HMA)- Azacitidine/Decitabine and JAK inhibitors Ruxolitinib/Cedazuridine/Pacritinib/Momelotinib/Fedratinib were analyzed in these patients. In this real-world analysis, our data demonstrate that over 90% of patients diagnosed with MDS/MPN overlap syndromes do not receive any treatment in routine clinical practice. The most prescribed medication in this cohort of patients with MDS/MPN was hydroxyurea, followed by hypomethylating medications (decitabine and azacitidine). Being untreated was associated with a significant decrement in survival, with untreated patients having up to twice the risk of death than those treated."

Atypical Chronic Myeloid Leukemia • Bone Marrow Transplantation • Chronic Myeloid Leukemia • Chronic Myelomonocytic Leukemia • Hematological Disorders • Hematological Malignancies • Juvenile Myelomonocytic Leukemia • Leukemia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm

XPO1 inhibition by selinexor blocks nucleo-cytoplasmic trafficking of multiple members of the NF-kb family in MPN cell lines and primary myelofibrosis cells (ASH 2025) - P3 | "The patient was previously treated with ruxolitinib, fedratinib, and ilginatinib/NS018, with adverse events and lack of response. Selinexor induced G0/G1 cell cycle arrest at 16 hours in HEL cells. Preliminary data showed that exposure of HEL cells to selinexor led to pronounced nuclear sequestration of several NF-κB family members. Cells with nuclear localization of RELA increased from 39.4% in DMSO-treated controls to 93.2% following selinexor treatment."

IO biomarker • Preclinical • Acute Myelogenous Leukemia • Fibrosis • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Myelofibrosis • Polycythemia Vera • CD33 • CD34 • JAK2 • NFKBIA • NRAS • PTPRC • RELA • RUNX1 • SRSF2 • TET2

Beyond mutations: RNA editing deaminase activation as a dynamic marker to track stem cell fitness and MPN progression (ASH 2025) - "In total,44.2% (N=57) of patients in our cohort received Inrebic, with 56% reaching the maximum dose of 400mg.To date, we selected four patients who were treated with Inrebic, progressed to sAML, underwent stemcell transplantation, and had cryopreserved peripheral blood and bone marrow mononuclear cells storedin our biorepository...Additionally, wholetranscriptome sequencing of FACS-purified hematopoietic stem cells (HSCs) revealed higher ADAR1expression and increased A-to-I RNA editing in JAK2 V617F⁺ patients compared with JAK2 wild-typepatients.These findings suggest that ADAR1 expression may serve as a dynamic marker for both diseaseprogression and disease stratification. Further single-cell RNA sequencing studies will further delineatedifferences in HSCs and HPCs at sequential time points for five MPN patients that progressed to sAML."

Acute Myelogenous Leukemia • Ewing Sarcoma • Hematological Malignancies • Leukemia • Myelofibrosis • Myeloproliferative Neoplasm • ADAR • ASXL1 • CALR • CD34 • STAT3

Clinical features and outcomes of myelofibrosis patients with MPL mutations (ASH 2025) - "Treatment regimensincluded JAK inhibitors, most commonly Ruxolitinib (n=31), Momelotinib (n=4), Fedratinib (n=2), andPacritinib (n=1). Anemia-directed therapies included erythropoietin-stimulating agents (ESA) in 21patients, Danazol (n=9), and Luspatercept (n=2)...A significant subset of patients progressed to accelerated-phase disease or AML (n=11, 15%).Despite this, only one-fifth underwent hematopoietic stem cell transplantation. These results highlightedthe need for improved risk stratification and the development of targeted therapeutic strategies for thisrare and understudied population."

Clinical • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Myelofibrosis • Myeloproliferative Neoplasm • Polycythemia Vera • ASXL1 • CALR • JAK2 • SRSF2 • U2AF1

An independent, multi-center analysis of the post-approval utilization and efficacy of pacritinib and momelotinib in patients with myelofibrosis (ASH 2025) - "Early JAK inhibitors(ruxolitinib (RUX) and fedratinib) result in myelosuppression that often exacerbates disease-relatedanemia and thrombocytopenia. The magnitude ofthese differences warrants further investigation. Overall, this real-world study highlights clinical nuancesin JAK inhibitor selection and emphasizes the opportunity to personalize treatment approach."

Clinical • Myelofibrosis • Thrombocytopenia • CALR

A phase II Study of fedratinib and nivolumab combination in patients with myelofibrosis and resistance or suboptimal response to JAK-inhibitor treatment – fraction Study / IKF051 / gsg-MPN-006 (ASH 2025) - "Introduction: Early clinical trials for patients with myelofibrosis (MF) are aimed to improve treatmentusing combinatorial therapies for patients with suboptimal response to Ruxolitinib therapy. Fedratinib-Nivolumab combination demonstrates promising clinical efficacy in a cohort of MFpts enriched for int-2 or high-risk, especially in those with proliferative features indicated by leukocytosisand thrombocytosis and was well tolerated leading to prolonged treatment durations. The safety profileis consistent with prior experience. Fedratinib's unique kinase inhibition profile may provide amechanism for enhanced effectiveness in this pt population."

Clinical • IO biomarker • P2 data • Hematological Disorders • Myelofibrosis • Thrombocytopenia • Thrombocytosis • JAK2 • PD-L1

Real-world treatment duration of ruxolitinib and use of transfusion among 2268 patients with myelofibrosis: An analysis of the Medicare fee-for-service claims database (ASH 2025) - "Most pts were treatment naive (n=1564 [69%]); 659 ( hydroxyurea (HU) prior to RUX.During the baseline period, supportive medication for anemia was received by 277 (12%) pts overall(anemia Dx, n=197 [17%]; transfusion, n=102 [26%]), most commonly erythropoiesis-stimulating agents(n=251 [11%]) or danazol (n=43 [2%])...After RUXdiscontinuation, 25% received another MF treatment; the most common treatments were HU (n=256[11%]), fedratinib (n=186 [8%]), and pacritinib (n=115 [5%]). In this real-world study with long-term follow-up of approximately 4 years, median durationof RUX treatment was 3.1 years... In this real-world study with long-term follow-up of approximately 4 years, median durationof RUX treatment was 3.1 years. On average, pts started RUX early after MF diagnosis (median, 4.5 mo),and approximately one-third remained on RUX treatment at end of study period, regardless of age orbaseline anemia status. Most pts did not require transfusions at baseline."

Claims database • Clinical • HEOR • Medicare • Real-world • Real-world evidence • Reimbursement • US reimbursement • Acute Myelogenous Leukemia • Diabetes • Heart Failure • Hematological Disorders • Hematological Malignancies • Leukemia • Metabolic Disorders • Myelodysplastic Syndrome • Myelofibrosis • Nephrology • Peripheral Arterial Disease • Pulmonary Disease • Renal Disease • Respiratory Diseases

Targeting HMGA1-driven leukemic transformation in myeloproliferative neoplasms with pacritinib (ASH 2025) - "This transcriptional reprogramming promotesproliferation, blocks differentiation, and accelerates leukemic progression in vivo.We discovered that HMGA1 overexpression confers resistance to ruxolitinib and fedratinib by sustainingE2F/G2-M programs. We identified HMGA1 as a critical driver and potent predictor of MPN-sAML transformation.HMGA1 protein expression, readily detectable by immunohistochemistry (IHC), demonstrated a stepwiseincrease from chronic MPN phases to sAML (P40.78%) in non-blast phase MPN predicted impending leukemic transformation within 12months (47% conversion rate), offering a median lead time of 6 months before overt blast crisis."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myeloproliferative Neoplasm • CCNB1 • CD34 • CDK2 • E2F1 • FLT3 • HMGA1 • IRAK1 • JAK2 • KIT • TP53

Fedratinib in combination with CC-486, an oral hypomethylating agent, in patients with accelerated phase myelofibrosis: Results from the phase I/II famy trial (ASH 2025) - "Combining a parentral hypomethylating agent (HMA) with the JAK inhibitor (JAKi)ruxolitinib is reported to be active in MPN-AP. For the first time, the feasibility of combining 300mg FED with CC-486 in MPN-AP is shown. Consideringthe dismal prognosis and lack of optimal therapies for MPN-AP, the preliminary but encouraging resultsof this regimen warrant further evaluation in an international trial."

Clinical • Combination therapy • P1/2 data • CNS Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Leukopenia • Myelofibrosis • Neutropenia • Thrombocytopenia • ASXL1

Preliminary experience from the ODYSSEY trial: Efficacy and safety of momelotinib in combination with luspatercept in patients with transfusion-dependent myelofibrosis (ASH 2025) - P2 | "WhileJAK inhibitors are the current standard of care in transplant-ineligible patients with intermediate- or high-risk MF, some such as ruxolitinib cause or worsen anemia...In cohort 2, previous or currentruxolitinib or fedratinib is permitted (no washout required), while discontinuation of other MF-directedtherapy is required ≥28 days before enrollment in both cohorts... ODYSSEY builds on the established anemia-related benefits of momelotinib andluspatercept in patients with MF and may highlight momelotinib as a potentially optimal JAK inhibitorbackbone for combination with emerging agents in patients with MF and anemia."

Clinical • Combination therapy • Anemia • Beta-Thalassemia • Genetic Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Myelofibrosis • ACVR1 • JAK1 • TGFB1

The transition from myelodysplastic neoplasm to secondary acute myeloid leukemia is revealed by molecular analysis, while functional drug screening demonstrates novel sensitivity patterns with clinical implication (ASH 2025) - "There are only a limited number of agentsthat are FDA approved for treatment of MDS including BCL2 and IDH inhibitors, hypomethylating agents(HMAs), ESAs, luspatercept and imetelstat...For MDS patients, weidentified the most effective agents with the proportion of sensitive samples noted in parentheses:mitoxantrone (100%), olutasidenib (78%), venetoclax (67%), dinaciclib (67%), trametinib (67%), olaparib(56%), GSK3368715 (56%), pacritinib (44%), lenalidomide (44%), fludarabine (55%), tasquinimod (44%),veliparib (44%). For sAML patients, we identified lenalidomide, olutasidenib, GSK3368715 have high DSSsin all tested samples, while fludarabine, fedratinib, tasquinimod, trametinib, veliparib, mitoxantrone andolaparib have high DSSs in 75% of the AML samples...Cancer Research 2024), and our samples included SF3B1 and U2AF1 mutations.Summary This study of the transition of MDS to sAML highlights molecular changes and reveals new drugsensitivity with agents that could be..."

Biomarker • Clinical • IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • CD34 • FLT3 • JAK2 • NRAS • PTPN11 • SF3B1 • U2AF1

Clonal architecture inferred from routine NGS data predicts outcome and response to JAK-inhibitors in myelofibrosis (ASH 2025) - "216 ptsreceived ruxolitinib (86.4%), 15 fedratinib (6%), 19 momelotinib (7.6%). This study highlights the impact of clonal architecture profile on response to JAKi in MF pts,particularly the role of mutations in epigenetic regulators when acquired as first-hit event. These findingswere generated using an inferential method based on VAF calculation from routine bulk sequencing, thatcan be easily implemented in practice and used to guide therapeutic strategies."

Biomarker • Next-generation sequencing • Hematological Malignancies • Leukemia • Myelofibrosis • ASXL1 • DNMT3A • IDH2 • KRAS • NRAS • SF3B1 • SRSF2 • TET2 • U2AF1 • ZRSR2

CD132 expression promotes AML aggressiveness via the JAK-STAT signaling pathway (ASH 2025) - "Fedratinib, a JAK2 inhibitor, was predicted to suppress AML cellproliferation and induce apoptosis. This prediction was subsequently validated through in vitro assaysand in vivo mouse models, demonstrating that JAK2 inhibition effectively impairs the proliferation ofCD132-positive AML cells.Our study identifies CD132 as a novel biomarker, prognostic indicator, and effective therapeutic target inAML. These findings provide potential drug candidate and cellular therapeutic target for the treatment ofR/R AML, laying a critical foundation for future clinical translation."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Metabolic Disorders • FCGR2A • FCGR2B • IL2RG • STAT5

Real-world treatment patterns and outcomes in patients with myelofibrosis who presented with thrombocytopenia and anemia at initiation of pacritinib treatment (ASH 2025) - "Most pts received PAC ast the first JAKinhibitors (55.4%; 62/112) while 44.6% (50/112) received ruxolitinib (n=49) or fedratinib (n=1) prior to PAC.The median follow-up from index was 8.9 months (6.9, 12) and a majority were still on PAC at the end ofthe 180-day observation period (70.5%; 79/112). Pts with MF who have both thrombocytopenia and anemia, treated with PAC in the real-world, experienced reduction or stabilization in spleen size category, along with improvements in MF-related symtpom burder, PLT and Hb. A majority of PAC treated pts experiecned symptom relief withbenefits observed as early as 30 days following treatment initiation. PAC may have clinical utility inaddressing unmet needs of pts with MF who have bicytopenias."

Clinical • HEOR • Real-world • Real-world evidence • Anemia • Hematological Disorders • Myelofibrosis • Thrombocytopenia • ACVR1 • IRAK1 • JAK1

Fedora preliminary analysis of a Phase II study evaluating the tolerability, safety and activity of fedratinib combined with ropeginterferon alfa-2b in patients with myelofibrosis. (ASH 2025) - "The combination of the JAK2 inhibitor fedratinib and ropeg interferon alfa-2b appearstolerable and safe. Symptom score responses and spleen reductions were observed and encouragingreductions in JAK2 allele burden seen in a proportion."

Clinical • P2 data • Myelofibrosis • Myeloproliferative Neoplasm • Ocular Inflammation • Ophthalmology • Uveitis

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

Leveraging real-world workshop insights for improving education design: Patient-centered care of myelofibrosis with JAK inhibitors (ASH 2025) - "As a resultof this education, relative improvements were observed in selecting guideline- and expert-concordantanswers to pre/post quesitons on: 1) individualizing front-line therapy with ruxolitinib dosing (30%baseline vs 71% post education; P <.001); 2) optimal use of front-line pacritinib for patients with MF andlow platelet count (20% baseline vs 62% post education; P <.001); 3) sequencing JAKi for second-linetherapy (eg, pacritinib, momelotinib, fedratinib) based on patient characteristics (34% baseline vs 69%post education; P <.001) and, 4) recognizing and effectively managing treatment-related AEs in patientsreceiving JAKi therapies (37% baseline vs 69% post education; P <.001). HCP confidence, knowledge, and competence in personalizing JAKi therapy for patients withMF was improved following participation in this multimodal educational program. This educationalinitiative demonstrated that integrating quantitative and qualitative insights from..."

Clinical • Real-world • Real-world evidence • Hematological Disorders • Myelofibrosis • Thrombocytopenia

An open-label, Phase I/II clinical trial of romaciclib (RVU120) as monotherapy and in combination with ruxolitinib in patients with intermediate or high-risk, primary or secondary myelofibrosis (POTAMI-61) (ASH 2025) - P2 | "Reduction ofBM fibrosis was seen after 12 weeks of treatment in a patient who failed prior lines of RUX andfedratinib; reduction of TSS of >50% was not observed in these 6 patients after 12 weeks.The most common AEs were nausea and vomiting, reported in 52% and 43% of patients, respectively.Majority of AEs were G1-2. Initial signs of clinical activity were observed, as demonstrated by SVR, TSSimprovements, and BM fibrosis reduction in some patients while data continue to mature. Initialevidence from POTAMI-61 study supports further investigation of romaciclib in patients with MF."

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

RALLY MF: A phase 2 Study of DISC-0974, an anti-hemojuvelin antibody, in patients with myelofibrosis and anemia (ASH 2025) - P1/2 | "A stable dose ofconcomitant hydroxyurea and/or Janus kinase (JAK) inhibitor (ruxolitinib and fedratinib for primarycohorts; momelotinib and pacritinib for exploratory cohort) was allowed. Based on these initial data, the protocol was amended to allowconcomitant momelotinib or pacritinib in all cohorts. Preliminary results, including baselinecharacteristics, PD, and hematologic responses across all cohorts, will be presented."

Clinical • P2 data • Anemia • Hematological Disorders • Immunology • Myelofibrosis

Ruxolitinib duration of treatment and effect on phlebotomy use among 2369 patients with polycythemia vera: A real-world analysis of the Medicare fee-for-service claims database (ASH 2025) - "Background : Ruxolitinib (RUX) is approved for the treatment of adults with polycythemia vera (PV) haveinadequate response to or are intolerant of hydroxyurea (HU)...Among the 691 patients who received phlebotomy at baseline, 60%(n=415) did not receive any phlebotomy during the first 6 months post-index, and 73% (n=506) did notreceive any phlebotomy during months 7–12 post-index.After RUX discontinuation, the most common treatments among all 2369 patients were HU (17%; n=410)and phlebotomy (14%; n=323), followed by fedratinib (3%, n=66), anagrelide (3%; n=64), pacritinib (2%; n=41), and interferon (n<11). In this large retrospective real-world study with over 4 years of follow-up, older patients withPV continued RUX treatment for a median of 3.6 years, and more than one-third of patients remained onRUX treatment at the end of the study period... In this large retrospective real-world study with over 4 years of follow-up, older patients withPV continued RUX treatment..."

Claims database • Clinical • Medicare • Real-world • Real-world evidence • Reimbursement • US reimbursement • Acute Myelogenous Leukemia • CNS Disorders • Diabetes • Essential Thrombocythemia • Hematological Malignancies • Leukemia • Metabolic Disorders • Myelodysplastic Syndrome • Myelofibrosis • Myeloproliferative Neoplasm • Nephrology • Peripheral Arterial Disease • Polycythemia Vera • Pulmonary Disease • Renal Disease • Respiratory Diseases • Vascular Neurology

ZE74-0282 is a novel JH2 domain JAK2 inhibitor with promising pre-clinical activity in JAK2 V617F mutant diseases (ASH 2025) - "Current available JAK2 inhibitortherapies such as ruxolitinib and fedratinib target the JH1 domain and provide symptomatic relief but arelimited by non-selective JAK inhibition and disruption of WT JAK2 signaling. ZE74-282 is a first-in-class, JH2 domain specific JAK2 inhibitor with potent and selectiveactivity against mutant JAK2V617F while preserving normal JAK2-mediated function. Compared with JH1directed JAK2 inhibitors ZE74-2882 offers a superior therapeutic index in preclinical models,pharmacology suggesting twice daily dosing, and exceptional "drug properties" with ADME studiescompleted to date. These findings support its further development as a potentially disease-modifyingtherapy for JAK2 V617F mutated diseases."

Preclinical • Essential Thrombocythemia • Hematological Malignancies • Myelofibrosis • Myeloproliferative Neoplasm • Polycythemia Vera • Thrombocytosis • ASXL1

Ernest Beutler Lecture and Prize (ASH 2025) - "The ensuing years have also shown benefit of ruxolitinib on survival for MF. Subsequently, three additional JAK inhibitors — each with their own incremental benefits — have been approved (fedratinib in 2019, pacritinib in 2022, and momelotinib in 2023). A new generation of more mutant selective JAK2 inhibitors (INCB160058, AJ1-11095) is currently in early clinical trials...Radek C. Skoda will describe how the JAK2-V617F mutation drives hematopoiesis causing MPNs and recent advances in understanding of how this mutation activates the JAK2 kinase, opening new ways to find candidate drugs preferentially targeting the mutated JAK2 protein.Dr. Ruben Mesa will summarize how the single-agent JAK inhibitors significantly helped decrease the burden of MPNs and the role of current agents, the next generation of new inhibitors, and combination approaches, as well as the impact JAK inhibitors have had on non-neoplastic inflammatory disorders."

Atopic Dermatitis • Chronic Graft versus Host Disease • Dermatitis • Dermatology • Essential Thrombocythemia • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Myelofibrosis • Myeloproliferative Neoplasm • Polycythemia Vera • Thrombocytosis • Vitiligo • CALR • TET2

Understanding Cardiovascular Events With JAK Inhibitors: Similarities and Differences of the Vascular Effects Between Different JAK Inhibitors on Endothelial Cells Exposed to Inflammatory Cytokines. (PubMed, ACR Open Rheumatol) - "All JAKi reduced EC inflammation but most JAKi could not prevent the up-regulation of adhesion molecules or the increase in procoagulant and the decrease in anticoagulant factors triggered by proinflammatory cytokines. Peficitinib and fedratinib exhibited cytotoxic effects causing EC apoptosis."

Journal • Cardiovascular • Oncology • ANXA5 • CXCL8 • ICAM1 • IL17A • IL6 • TNFA • VCAM1

Janus Kinase Inhibitors During Pregnancy and Adverse Drug Reactions: A Pharmacovigilance Disproportionality Analysis in VigiBase. (PubMed, Clin Transl Sci) - "This study analyzed VigiBase, the World Health Organization global pharmacovigilance database of individual case safety reports (ICSRs), to assess signals of disproportionate reporting (SDRs) for pregnancy-related adverse drug reactions (ADRs) reported with systemic JAKIs, including abrocitinib, baricitinib, deucravacitinib, fedratinib, filgotinib, itacitinib, momelotinib, pacritinib, peficitinib, ritlecitinib, ruxolitinib, tofacitinib, and upadacitinib. Findings should be interpreted cautiously given the limitations of spontaneous reporting systems and the exploratory nature of the analysis. Further studies are needed to better characterize the JAKI safety in pregnancy."

Adverse drug reaction • Adverse events • Journal • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

JAK inhibitor selection in challenging scenarios of myelofibrosis: a review. (PubMed, Haematologica) - "A total of four JAK inhibitors-ruxolitinib, fedratinib, pacritinib, and momelotinib-are now available for the treatment of myelofibrosis, each with distinct profiles and safety considerations that may inform selection. To illustrate the diverse clinical factors and key considerations associated with JAK inhibitor selection in practice, we discuss these data in the context of four hypothetical patient cases representing possible real-world scenarios, offering treatment recommendations based on our collective expertise in the field. As the myelofibrosis therapeutic landscape continues to evolve, a thorough understanding of the strengths and limitations of each JAK inhibitor relative to a given patient's presentation will support individualized treatment decisions for optimal long-term outcomes."

Journal • Bone Marrow Transplantation • Hematological Disorders • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • Transplantation