As reported on MedCity News, Eli Lilly has reported encouraging early-stage clinical data for AJ1-11095, an investigational therapy for myelofibrosis acquired through its recent purchase of Ajax Therapeutics. Findings, presented at the European Hematology Association (EHA) annual meeting in Stockholm, highlight the drug’s potential to address an unmet need in patients who have already been treated with existing JAK inhibitors.
Myelofibrosis is a chronic blood cancer characterized by bone marrow scarring and disrupted blood cell production, often leading to symptoms such as fatigue, anemia, and splenomegaly (enlarged spleen). While several therapies targeting the JAK signaling pathway are already approved, including ruxolitinib, fedratinib, momelotinib, and pacritinib, most act on the enzyme in its active (type I) conformation. AJ1-11095 introduces a differentiated approach by targeting the inactive (type II) form of JAK2, potentially offering an alternative mechanism for patients whose disease no longer responds to current treatments.
The Phase 1 dose-escalation study enrolled 23 patients with relapsed or refractory myelofibrosis, all of whom had previously received standard JAK inhibitor therapy. Participants had undergone a median of two prior treatment lines, reflecting a heavily pretreated population. Among the 20 evaluable patients at 12 weeks, 13 achieved a reduction in spleen volume of at least 35%, a commonly used benchmark for clinical benefit in this disease. Additional patients demonstrated moderate reductions, and two individuals reached the threshold after receiving higher doses.
Symptom improvement was also notable. Most patients experienced meaningful reductions in overall disease burden, with 17 achieving at least a 50% decrease in symptom scores after one treatment cycle, and further responses observed in subsequent cycles. These findings suggest that inhibiting JAK2 in its alternate conformation may help alleviate both physical manifestations and patient-reported symptoms.
From a safety perspective, AJ1-11095 was generally well tolerated in this early study. No dose-limiting toxicities or treatment discontinuations were reported. However, anemia emerged as the most common adverse effect, affecting a substantial proportion of patients, including cases of higher severity. This side effect is consistent with other therapies targeting the JAK pathway and remains an important consideration for further development.
Experts involved in the trial noted that the results support continued exploration of type II JAK2 inhibition as a therapeutic strategy. The observed reductions in spleen size, symptom burden, and disease markers provide early validation of the drug’s mechanism and clinical potential, though larger and longer-term studies will be required to confirm efficacy and safety.
AJ1-11095’s progress also underscores Lilly’s growing investment in hematologic malignancies. The company’s acquisition of Ajax Therapeutics—valued at up to $2.3 billion—reflects confidence in the compound’s potential role within an expanding oncology pipeline. Additional recent deals in the blood cancer space further signal Lilly’s strategic focus on advancing innovative treatments for these conditions.
While still in early development, AJ1-11095 could represent an important next step in the evolution of JAK-targeted therapies, particularly for patients with limited options following prior treatment.
