Lilly reports Phase 1 results for AJ1-11095, a first‑in‑class type II JAK2 inhibitor
- AJ1-11095 is a first‑in‑class type II JAK2 inhibitor added to Lilly’s pipeline after acquiring Ajax Therapeutics.
- Phase 1 AJX-101 enrolled 23 myelofibrosis patients across five dose levels (25–125 mg once daily); all had prior type I JAK2 inhibitor exposure.
- Efficacy: SVR35 best response in 70% of patients; TSS50 at week 12 in 70%; VAF reductions in 21/23 patients, with 59% ≥20% and 35% ≥50% among 17 patients at week 24.
- Safety: generally manageable, no dose‑limiting toxicities observed; 78% of dose‑escalation patients remain on study; common TEAEs included anemia, dysgeusia, thrombocytopenia and increased ALT.
Study and context
AJ1-11095 (evaluated in the Phase 1 AJX-101 study) is a first‑in‑class, oral type II selective JAK2 inhibitor designed to bind JAK2 in its inactive conformation. Lilly added the program after completing the acquisition of Ajax Therapeutics. Results will be presented orally at the 2026 EHA Annual Meeting in Stockholm (Abstract S218).
Patient population and dosing
The dose‑escalation phase enrolled 23 patients with primary or secondary myelofibrosis who had a median of two prior therapies and all had received a type I JAK2 inhibitor. Five once‑daily dose levels were studied: 25, 50, 75, 100 and 125 mg.
Efficacy findings
AJ1-11095 produced clinically relevant responses: a spleen volume reduction ≥35% (SVR35) was observed as best response in 70% of patients, and symptom burden improvement ≥50% (TSS50) was seen in 70% at week 12 (data cutoff May 28, 2026). Reductions in driver mutation variant allele frequency (VAF) were seen in 21 of 23 patients; among 17 patients at week 24 (data cutoff May 12, 2026), 59% had ≥20% VAF reduction and 35% had ≥50% reduction across JAK2, MPL and CALR mutations.
Safety and next steps
The overall safety profile was generally manageable with no dose‑limiting toxicities observed and 78% of dose‑escalation patients remaining on study. Common treatment‑emergent adverse events included anemia, dysgeusia, decreased platelet count and increased alanine aminotransferase. AJ1-11095 is being evaluated in an expansion cohort in second‑line myelofibrosis, with planned investigations in high‑risk polycythemia vera and treatment‑naïve myelofibrosis (NCT06343805).
Source: Lilly