Vonjo (pacritinib) / SOBI - LARVOL DELTA

Pacritinib mitigates doxorubicin resistance in osteosarcoma by inhibiting WNT/β-catenin, efflux proteins and receptor tyrosine kinase network (AACR 2026) - "Notably, RNA-seq data of pacritinib-treated MG63-DXR cells showed a "reversal" trend: transcripts that were elevated in DXR (including β-catenin and efflux genes) were reduced by pacritinib treatment, whereas WNT antagonists increased, supporting pathway-level inhibition. An in vivo experiment is currently underway to validate that pacritinib exhibits synergistic effect with doxorubicin in suppressing MG63-DXR tumors in mice.Taken together, our data indicates that pacritinib synergistically enhances the effects of doxorubicin in suppressing the growth of MG63-DXR osteosarcoma tumors through a well-defined mechanism."

Oncology • Osteosarcoma • Sarcoma • Solid Tumor • ABCB1 • AXL • CTNNB1 • WIF1

Pacritinib, a Kinase Inhibitor of CSF1R, IRAK1, JAK2, and FLT3, in Adults and Pediatric Participants 12 Years of Age or Older With Myelodysplastic Syndromes or Myelodysplastic/Myeloproliferative Neoplasms (clinicaltrials.gov) - P1/2 | N=160 | Recruiting | Sponsor: National Cancer Institute (NCI) | Not yet recruiting ➔ Recruiting

Enrollment open • Hematological Malignancies • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Neutropenia • Oncology • Pediatrics

Experimental JAK inhibitors: the current, present and future in graft-versus-host disease management? (PubMed, Expert Opin Investig Drugs) - "We evaluate the efficacy and safety of selective and nonselective agents, including ruxolitinib, baricitinib, itacitinib, pacritinib, and rovadicitinib. We anticipate a transition from the current 'steroid-first' paradigm to risk-stratified algorithms utilizing biomarker profiling and novel combination strategies. While ruxolitinib is the current cornerstone, the development of highly selective inhibitors and the resolution of financial access barriers will be crucial for establishing JAK inhibitors as the frontline standard of care over the next decade."

Journal • Review • Acute Graft versus Host Disease • Chronic Graft versus Host Disease • Graft versus Host Disease • Immunology • Transplantation

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

Pacritinib in transplant-eligible myelofibrosis: final analysis of the phase II HOVON-134 trial. (PubMed, Bone Marrow Transplant) - No abstract available

Journal • P2 data • Myelofibrosis • Transplantation

Prospera (ABNL-MARRO 002): A randomized phase 2 study of pacritinib vs. hydroxyurea in patients with advanced proliferative chronic myelomonocytic leukemia (CMML) (ASH 2025) - P2 | "In the phase 3 DACOTA trial (Itzykson et al., JCO 2022),decitabine modestly delayed leukemic transformation compared to HU but did not improve event-free oroverall survival and was associated with increased early mortality. The primary endpoint is CBR at Week 24, defined by modified IWG MDS/MPNcriteria incorporating hematologic improvement, spleen volume reduction, and symptom response.Secondary endpoints include CBR at any time, duration of response, event-free survival, leukemia-freesurvival, and overall survival.Correlative studies will assess treatment-related changes in clonal dynamics, cytokine signaling, andhematopoietic composition using longitudinal peripheral blood and bone marrow sampling. Single-celltranscriptomic and immunophenotypic profiling will be employed to characterize pacritinib's impact onboth the malignant clone and the surrounding immune microenvironment."

Clinical • Metastases • P2 data • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelofibrosis • Myeloproliferative Neoplasm • Thrombocytopenia • IRAK1

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

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

JAK Inhibitors in the Treatment of T-Cell Lymphomas: Current Evidence and Future Directions. (PubMed, Cancers (Basel)) - "These include abrocitinib, cerdulatinib, golidocitinib, ruxolitinib, tofacitinib, and upadacitinib. Other drugs are currently being tested in clinicals trials, including pacritinib and ivarmacitinib, but results are not yet available...JAK inhibitors are associated with multiple adverse effects, including cytopenias and infections, and long-term safety data are lacking for newer agents. Future studies will need to clarify long-term safety and efficacy through well-designed clinical trials involving larger groups of patients."

Journal • Review • Cutaneous T-cell Lymphoma • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma

A Study to Assess the Effectiveness and Safety of Pacritinib in Patients With VEXAS Syndrome (PAXIS) (clinicaltrials.gov) - P2 | N=78 | Recruiting | Sponsor: Swedish Orphan Biovitrum | Active, not recruiting ➔ Recruiting

Enrollment open

Pathway -targeted combination screening in 3D -spheroids reveals synergistic interactions with everolimus in pancreatic neuroendocrine tumors (ENETS 2026) - " The AKT inhibitor Tuvusertib showed the strongest mo - notherapy effect, although its synergy combined with everolimus was limited. Cytostatic synergy with everolimus was observed with JAK/STAT pathway inhibitors (Conteltinib, Pacritinib) in BON spheroids and with ERK1/2 and PI3K α inhibitors (ASTX029, Gil - melisib) in BON-R spheroids...Cytoto - xic synergy with everolimus was mainly associated with inhibition of the MAPK/ERK pathway, involving ERK inhibitors (Tizaterkib, Ulexertinib) in BON-R spheroids and MEK inhibitors (Binimetinib, Cobimetinib, Trametinib) in both models. High-content 3D spheroid screening integrating NOGR-based growth metrics identified multiple synergistic inter - actions between everolimus and inhibitors targeting interconnec - ted signaling cascades. These findings highlight the potential of rational pathway-targeted combinations to overcome resistance and enhance therapeutic efficacy in pNET, warranting further preclinical investigation to..."

Gastrointestinal Neuroendocrine Tumor • Neuroendocrine Tumor • Oncology • Solid Tumor • PIK3CA

Selinexor and Pacritinib in JAK Inhibitor-naïve MF Patients With Cytopenias (clinicaltrials.gov) - P2 | N=26 | Not yet recruiting | Sponsor: John Mascarenhas

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

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

GEMFIN-MF-PACRI 2401: Pacritinib for Patients With Myelofibrosis Who Have Thrombocytopenia (clinicaltrialsregister.eu) - P1/2 | N=30 | Not yet recruiting | Sponsor:

New P1/2 trial • Fibrosis • Hematological Disorders • Immunology • Myelofibrosis • Thrombocytopenia

PAXIS: A Randomized, Double-Blind, Placebo-Controlled, Dose-Finding Phase 2 Study (Part 1) Followed by an Open-Label Period (Part 2) to Assess the Efficacy and Safety of Pacritinib in Patients with VEXAS Syndrome. (PubMed, J Clin Med) - P2 | "The PAXIS trial is the first prospective, randomized pharmacotherapeutic study conducted in this rare and severe disease. Utilizing a novel study design and disease-specific endpoints, the trial will evaluate the efficacy and safety of two dose levels of pacritinib compared with placebo in patients with VEXAS syndrome (NCT06782373, EUCTR: 2024-516347-41-00)."

Clinical • Journal • P2 data • Hematological Disorders • Inflammation • Targeted Protein Degradation • ACVR1 • IRAK1

Pacritinib With Standard of Care Azacitidine or Decitabine as a Bridge to Allogeneic Hematopoietic Stem Cell Transplant for Patients With Accelerated and Blast Phase Myeloproliferative Neoplasms (clinicaltrials.gov) - P2 | N=27 | Recruiting | Sponsor: University of Washington | Not yet recruiting ➔ Recruiting

Enrollment open • Bone Marrow Transplantation • Essential Thrombocythemia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Oncology • Transplantation

PROSPERA: Pacritinib vs. Hydroxyurea in Advanced Proliferative Chronic Myelomonocytic Leukemia (clinicaltrials.gov) - P2 | N=66 | Recruiting | Sponsor: Theradex | Not yet recruiting ➔ Recruiting

Enrollment open • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

MDS: Pacritinib With Aza for Upfront Myelodysplastic Syndrome (clinicaltrials.gov) - P1/2 | N=25 | Not yet recruiting | Sponsor: Thomas Jefferson University

New P1/2 trial • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Oncology

Pacritinib Response Is Associated With Overall Survival in Myelofibrosis: PERSIST-2 Landmark Analysis of Survival. (PubMed, Eur J Haematol) - P3 | "In patients with myelofibrosis and platelets ≤ 100 × 109/L, achieving SVR on pacritinib, but not BAT (including ruxolitinib), was associated with significant OS benefit, suggesting that pacritinib may offer a unique survival advantage in patients with myelofibrosis and thrombocytopenia who achieve any SVR. Trial Registration: ClinicalTrials.gov number: NCT02055781."

Journal • Hematological Disorders • Myelofibrosis • Thrombocytopenia • ACVR1 • IRAK1 • JAK2

Preliminary Data from the Phase I/II Study of TP-3654, a Selective Oral PIM1 Kinase Inhibitor, in Patients with Myelofibrosis Previously Treated with or Ineligible for JAK Inhibitor Therapy (ASH 2022) - P1/2 | "TP-3654 showed less hematopoietic inhibition than Janus kinase (JAK) inhibitors (ruxolitinib, pacritinib and momelotinib) in in vitro human megakaryocyte and erythrocyte cell colony formation. The preliminary clinical data in dose escalation show: 1) encouraging signs of clinical activity in spleen volume reduction, symptom improvement, and cytokine reduction with TP-3654 monotherapy in patients previously treated with JAK inhibitors, 2) TP-3654 is well tolerated with limited myelosuppressive adverse events. The non-clinical findings and preliminary clinical safety/efficacy data support accelerated development and assessment of TP-3654 as the optimal partner for combination with JAK inhibitors."

Clinical • P1/2 data • Hematological Disorders • Immunology • Myelofibrosis • CALR • IL18 • MMP9 • PIM1 • TIMP1

Post-FDA Approval Experience With Momelotinib in JAK Inhibitor-Naïve Myelofibrosis: Focus on Anemia Response and Treatment-Emergent Nephropathy and Peripheral Neuropathy. (PubMed, Am J Hematol) - "Real-world experience using momelotinib as first-line JAK2 inhibitor therapy in myelofibrosis. Anemia response was moderate (23%) while treatment-emergent adverse events included nephropathy (29%) and peripheral neuropathy (20%)."

FDA event • Journal • Anemia • Hematological Disorders • Myelofibrosis • Pain • Renal Disease

PACRIMYEL: Pacritinib For Bone Marrow Fibrosis In Patients With Myelofibrosis Who Have Thrombocytopenia (clinicaltrials.gov) - P2 | N=30 | Not yet recruiting | Sponsor: Grupo Español de Enfermedades Mieloproliferativas Crónicas PH Negativas

New P2 trial • Fibrosis • Hematological Disorders • Immunology • Myelofibrosis • Thrombocytopenia

Pacritinib Is a Potent ACVR1 Inhibitor with Significant Anemia Benefit in Patients with Myelofibrosis (ASH 2022) - "The subgroup of BAT that received erythroid support (erythropoiesis stimulating agents, danazol, thalidomide or analogs, or corticosteroids) was also analyzed...The inhibitory activity of pacritinib, momelotinib, fedratinib, and ruxolitinib against ACVR1 was assessed using a HotSpot assay (Reaction Biology Corporation)... Baseline characteristics of patients who were not TI (SIMPLIFY criteria) were similar between pacritinib (n=42) and BAT (n=44), including median hemoglobin (8.7 vs. 8.6 g/dL), median platelet count (43 vs. 41 x109/L), and percentage who received prior JAK2 inhibitor therapy (55% vs."

Clinical • Anemia • Hematological Disorders • Myelofibrosis • Thrombocytopenia • ACVR1 • IRAK1

Risk-adjusted safety analysis of the oral JAK2/IRAK1 inhibitor pacritinib in patients with myelofibrosis. (PubMed, EJHaem) - "To account for longer treatment durations on the pacritinib arms compared to best available therapy (BAT), we present a risk-adjusted safety analysis of event rates accounting for different time on treatment. While the rate of overall events was higher on pacritinib compared to BAT, the rate of fatal events was lower, and there was no excess in bleeding, cardiac events, secondary malignancy, or thrombosis on pacritinib, including in patients with severe thrombocytopenia."

Journal • Cardiovascular • Hematological Disorders • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • Thrombocytopenia • Thrombosis • IRAK1 • JAK2

Consistency of pacritinib for spleen and symptom reduction in patients with myelofibrosis regardless of cytopenias. (ASCO 2023) - P3 | "Pacritinib demonstrates consistent efficacy for spleen and symptom response in patients with MF regardless of blood counts. This consistent effect may be related to pacritinib’s unique kinome profile and its ability to be delivered at full dose in patients regardless of cytopenias. Clinical trial information: NCT01773187, NCT02055781."

Clinical • Hematological Disorders • Immunology • Myelofibrosis • Thrombocytopenia • ACVR1 • IRAK1