AJ1-11095 is being evaluated in a phase 1 trial (NCT06343805) for the treatment of patients with myelofibrosis who received a type I JAK2 inhibitor and have either not responded or have lost response. Preclinical data presented in a poster during the 2025 ASH Annual Meeting and Exposition demonstrated that AJ1-11095 had a superior efficacy profile compared with ruxolitinib (Jakafi) in well-validated models of myeloproliferative neoplasms (MPNs).2 Moreover, in ruxolitinib-persistent JAK2-mutated cells, AJ1-11095 restored the inhibition of JAK/STAT signaling, supporting the hypothesis that the agent could overcome type 1 JAK2 inhibitor–mediated persistence.
“Orphan drug designation is an important milestone in our clinical development of AJ1-11095 for the treatment of [patients with] myelofibrosis,” David Steensma, MD, FACP, the chief medical officer of Ajax Therapeutics, stated in a news release.1 “This designation reinforces the compelling need for effective new treatment options for patients suffering from myelofibrosis, and supports our continued efforts to advance AJ1-11095 to address the unmet need for patients who would benefit from improved treatment efficacy, or who have not responded to existing therapies.”
How is the phase 1 trial designed?
The first-in-human, non-randomized, multi-center, open-label clinical trial is evaluating AJ1-11095 in patients with primary or secondary myelofibrosis previously treated with at least 1 type I JAK2 inhibitor.3 To be eligible for the study, patients need to be at least 18 years old and have a diagnosis of primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocythemia myelofibrosis. Other key eligibility criteria include having intermediate-2 or high-risk myelofibrosis with 10% or fewer blasts, regardless of JAK2 mutation status, per the Dynamic International Prognostic Scoring System, an estimated spleen volume of at least 450 cm3, an ECOG performance status of 3 or less, and a Myelofibrosis Symptom Assessment Form (MFSAF) Version 4.0Total Symptom Score (TSS) of at least 10 or at least 2 of 7 MFSAF-assessed symptoms with scores of at least 3.
The study will employ a 3+3 sequential dose escalation design followed by an expansion phase.AJ1-11095 will be administered orally.
The primary end points are the incidence of treatment-emergent adverse effects, dose-limiting toxicities, and establishing the maximum tolerated dose and/or recommended phase 2 dose. Secondary outcomes include clinical response per TSS, spleen volume assessments, spleen length assessments, and spleen size improvement. Pharmacokinetic measures will also be assessed as secondary end points.
What were the additional notable preclinical data presented during ASH?
Additional preclinical data demonstrated that AJ1-11095 showed superior efficacy compared with ruxolitinib in a JAK2VF knock-in competitive transplant model, including improvements in hematologic parameters and spleen weights, and marked reductions in mutant allele burden across peripheral blood, spleen, and bone marrow.2 Notable mutant allele burden reductions were also reported in animals that initially received ruxolitinib and went on to receive AJ1-11095, suggesting that the agent can reduce mutant allele burden following exposure to a type I JAK2 inhibitor. AJ1-11095 also showed superior efficacy vs ruxolitinib in an hMPLW515L myelofibrosis model, including improvements in hematologic parameters and spleen weights and significant reductions in bone marrow fibrosis and pro-fibrotic cytokine levels.
“The preclinical data presented today on our lead type II JAK2 development candidate, AJ1-11095, were what drove us to move the program into the clinic as a potential differentiated treatment option for patients with myelofibrosis whose disease has been refractory to type I JAK2 inhibitors,” Steensma, said in another news release. “Our phase 1 clinical study, AJX-101, continues to enroll well and we expect to transition to the expansion phase of the study early next year.”
References
- Ajax Therapeutics receives orphan drug designation from the U.S. FDA for AJ1-11095 for the treatment of myelofibrosis. News release. Ajax Therapeutics. December 2, 2025. Accessed December 10, 2025. https://www.ajaxtherapeutics.com/press-release/ajax-therapeutics-receives-orphan-drug-designation-from-the-u-s-fda-for-aj1-11095-for-the-treatment-of-myelofibrosis/
- Ajax Therapeutics presents preclinical data on differentiated efficacy profile of AJ1-11095, a first in class type II JAK2 Inhibitor, at the American Society of Hematology Annual Meeting.News release. Ajax Therapeutics. December 4, 2025. Accessed December 10, 2025. https://www.ajaxtherapeutics.com/press-release/ajax-therapeutics-presents-preclinical-data-on-differentiated-efficacy-profile-of-aj1-11095-a-first-in-class-type-ii-jak2-inhibitor-at-the-american-society-of-hematology-annual-meeting/
- A phase 1 study of AJ1-11095 in patients with primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (PPV-MF), or post-essential thrombocythemia myelofibrosis (PET-MF) who have been failed by a type I JAK2 inhibitor (JAK2i). ClinicalTrials.gov. Updated November 4, 2025. Accessed December 10, 2025. https://clinicaltrials.gov/study/NCT06343805
