The compound is described as a first in class type II inhibitor targeting a signaling enzyme called JAK2, designed to bind the same enzyme in a different physical state than approved myelofibrosis drugs. Early Phase 1 data cover 23 people.
Lilly is testing the first human use of a drug designed to grip an enzyme in a shape its predecessors cannot reach, a different attack on the same target that approved drugs for a rare bone-marrow cancer eventually lose effect against. The drug, AJ1-11095, is a once-daily pill meant for patients with myelofibrosis whose disease has already been treated with the current standard class of JAK2 drugs, known as type I inhibitors, including ruxolitinib. In a 23-patient, single-arm Phase 1 reported on Friday, the company said most patients saw measurable reductions in spleen size and symptom burden. The result is a first signal from a first-in-class compound, not a confirmed efficacy readout, and the next test of the idea will be whether it holds up in a controlled trial.
Myelofibrosis is a rare blood cancer in which scar tissue replaces the normal bone marrow, often leaving the spleen enlarged, blood counts low, and patients dealing with fatigue, night sweats, and a heavy-feeling abdomen. Most patients carry one of three driver mutations in the JAK-STAT pathway, with JAK2 the most common, and for more than a decade the standard targeted therapy has been the type I JAK2 inhibitors ruxolitinib, then fedratinib, then pacritinib. Those drugs bind the enzyme in its active shape and can shrink the spleen and ease symptoms for years, but resistance and progression are routine, and the patients who have run out of options have had no clearly defined next step.
AJ1-11095 is meant to be that next step. It is designed to bind JAK2 in its inactive, or Type II, conformation, a different physical state of the same enzyme the approved drugs cannot reach. Lilly calls the approach first-in-class for myelofibrosis and is presenting the first clinical data on the compound at the European Hematology Association 2026 Annual Meeting in Stockholm, in oral Abstract S218. The drug arrived at Lilly through the company's April 2026 acquisition of Ajax Therapeutics, a New York-based biotech that Lilly had backed as a founding strategic investor. Ajax was co-founded by Memorial Sloan Kettering's Ross Levine, a long-time researcher of JAK2-driven blood cancers, and the company has framed AJ1-11095 as the product of that lineage.
The Phase 1, registered as NCT06343805, is a global, open-label, multicenter dose-escalation study in patients with primary, post-polycythemia-vera, or post-essential-thrombocythemia myelofibrosis, all of whom had previously been treated with a type I JAK2 inhibitor. Twenty-three patients enrolled across five once-daily dose levels (25, 50, 75, 100, and 125 mg), with a median of two prior therapies. Per the Lilly release, the spleen-volume reduction endpoint SVR35, defined as at least a 35% shrinkage in spleen volume by imaging, was reached as a best response in roughly 70% of patients, and the symptom score endpoint TSS50, at least a 50% improvement on the standard symptom scale, at week 12 was also reported in 70%. Driver-mutation variant allele frequency, a blood-marker proxy for disease burden, fell in 21 of 23 patients, including cases carrying JAK2, MPL, and CALR type 1 or type 2 mutations. In the 17 patients who had reached week 24 at the data cutoff, 59% had at least a 20% VAF reduction and 35% had at least a 50% VAF reduction.
The caveats here are structural. There is no comparator arm, the n is small, and the data come from a company press release rather than a peer-reviewed paper, with the EHA abstract not independently verified in this reporting. Lilly described the activity as being "in excess of what has been seen historically" in similar patients, which is a sponsor-asserted comparison, not a head-to-head benchmark, and the endpoints reported are best response rather than durable response at a fixed time point. On safety, Lilly said no dose-limiting toxicities were observed and 78% of dose-escalation patients remained on study at the time of the data cut, with the most common treatment-emergent adverse events being anemia, dysgeusia (taste distortion), decreased platelet count, and elevated alanine aminotransferase liver-enzyme readings.
The on-record voice in the release is the principal investigator, John Mascarenhas, a professor of medicine at the Icahn School of Medicine at Mount Sinai and a long-standing clinician in myeloproliferative neoplasms, who called the data "a clinically meaningful step for patients with prior JAK inhibitor exposure." The other quoted voice is Jacob Van Naarden, executive vice president and president of Lilly Oncology, who framed the asset as part of Lilly's broader effort to "advance outcomes for patients with myelofibrosis and related diseases." Both quotes are sponsor-distributed, and Mascarenhas has served on advisory boards that drug developers, including Lilly, have engaged in the past, a context that belongs in any read of the release.
The next set of decisions is where the mechanism either proves out or stalls. The expansion cohort in second-line myelofibrosis is ongoing, and Lilly said it plans to study AJ1-11095 in high-risk polycythemia vera and in JAK2-inhibitor-naive myelofibrosis, with registrational trials referenced but not yet on a public timeline. For patients whose disease has progressed after a type I JAK2 inhibitor, the open question is whether a conformation-selective inhibitor can deliver a real, durable response and not just an early signal in 23 people, and whether a randomized design can confirm that the type II binding, rather than a familiar pharmacology, is doing the work. The Stockholm presentation on Friday is the public moment the question gets asked in front of a hematology audience that has watched the type I class closely for fifteen years.