Lilly Presents Early Clinical Data on First-in-Class Type II JAK2 Inhibitor for Myelofibrosis

Lilly reported initial data from AJX-101, a global open-label Phase 1 trial of AJ1-11095, the first oral type II JAK2 inhibitor, in 23 patients with primary, post-polycythemia vera, or post-essential thrombocythemia myelofibrosis who had previously received a type I JAK2 inhibitor. Patients had a median of two prior therapies and were dosed at 25–125 mg daily.

Lilly to present initial clinical data for first-in-class type II JAK2 inhibitor in patients with previously treated myelofibrosis at the 2026 EHA Annual Meeting

Myelofibrosis, a myeloproliferative neoplasm marked by splenomegaly, symptoms, and driver mutations (JAK2, MPL, CALR), is treated with type I JAK2 inhibitors that bind the active conformation and relieve symptoms but seldom lower mutant allele burden. After failure, patients have few options, underscoring the need for new mechanisms.

Lilly to present initial clinical data for first-in-class type II JAK2 inhibitor in patients with previously treated myelofibrosis at the 2026 EHA Annual Meeting

At week 12, 70 % of patients achieved >=35 % spleen volume reduction (SVR35) and 70 % attained >=50 % symptom improvement (TSS50). Variant allele frequency (VAF) fell in 21 of 23 patients; among 17 patients reaching week 24, 59 % showed >=20 % VAF decline and 35 % >=50 % decline. No dose-limiting toxicities were observed, and the most common adverse events were anemia, dysgeusia, thrombocytopenia, and elevated liver enzymes.

Lilly to present initial clinical data for first-in-class type II JAK2 inhibitor in patients with previously treated myelofibrosis at the 2026 EHA Annual Meeting

Targeting the inactive type II JAK2 conformation may achieve deeper disease modification than type I agents, as reflected by spleen, symptom, and VAF responses. Preclinical models showed AJ1-11095 superior to ruxolitinib. Confirmation in later trials could broaden therapeutic options for myeloproliferative neoplasms.

Lilly to present initial clinical data for first-in-class type II JAK2 inhibitor in patients with previously treated myelofibrosis at the 2026 EHA Annual Meeting

Dr. Mascarenhas noted the limited options after type I JAK2 inhibitor failure and highlighted the differentiated approach and safety profile of the early data. Van Naarden called the results proof of concept for the type II inhibitor and reaffirmed Lilly’s commitment to rapid development.

Lilly to present initial clinical data for first-in-class type II JAK2 inhibitor in patients with previously treated myelofibrosis at the 2026 EHA Annual Meeting

• “Patients with myelofibrosis who have been previously treated with an existing type I JAK2 inhibitor face very limited treatment options, highlighting an urgent need for new therapies,” — John Mascarenhas, MD, Principal Investigator, AJX-101

Lilly to present initial clinical data for first-in-class type II JAK2 inhibitor in patients with previously treated myelofibrosis at the 2026 EHA Annual Meeting

• “These early clinical findings suggest that selective targeting of the type II conformation of JAK2 may provide a differentiated approach. With an encouraging safety profile, meaningful spleen size reduction, symptom improvement, and decrease in underlying mutant disease burden, these data, while early, point to the potential to meaningfully impact treatment options for people with certain myeloproliferative neoplasms.” — John Mascarenhas, MD

Lilly to present initial clinical data for first-in-class type II JAK2 inhibitor in patients with previously treated myelofibrosis at the 2026 EHA Annual Meeting

• “The depth of response seen across spleen, symptoms, and VAF from these early phase results is in excess of what has been seen historically in this disease setting,” — Jacob Van Naarden, EVP & President, Lilly Oncology

Lilly to present initial clinical data for first-in-class type II JAK2 inhibitor in patients with previously treated myelofibrosis at the 2026 EHA Annual Meeting

• “These data provide clear proof of concept for what this selective type II JAK2 inhibitor could mean for patients with myelofibrosis and shed light on the conviction we brought to the acquisition of Ajax.” — Jacob Van Naarden, EVP & President, Lilly Oncology

Lilly to present initial clinical data for first-in-class type II JAK2 inhibitor in patients with previously treated myelofibrosis at the 2026 EHA Annual Meeting

An expansion cohort is testing AJ1-11095 as second-line therapy, with planned studies in high-risk polycythemia vera and JAK2-inhibitor-naïve myelofibrosis (NCT06343805).

Lilly to present initial clinical data for first-in-class type II JAK2 inhibitor in patients with previously treated myelofibrosis at the 2026 EHA Annual Meeting