Eli Lilly’s up-to-$2.3 billion acquisition of Ajax Therapeutics is facing its first major public test, and the initial clinical data show why the pharma giant made the bet.
The Ajax acquisition was a familiar story of an early investor turned buyer. Behind the deal was a novel idea that targeting the Type II conformation of the JAK2 kinase might offer a better approach compared with existing Type I-bound JAK inhibitors, such as Incyte’s blockbuster Jakafi, for myeloproliferative neoplasms (MPNs), including myelofibrosis.
Lilly invested in the startup early on, with Ross Levine, M.D., chief scientific officer at Memorial Sloan Kettering Cancer Center, serving as the biotech’s scientific cofounder, whom Lilly’s business development and oncology head, Jake Van Naarden, said he has known “for a super long time.”
Over the years, Lilly kept investing in the business as it produced AJ1-11095, a candidate that looked promising preclinically. Then, with the right clinical trial showing “this medicine started working right out of the gate, with a good safety profile,” Lilly deepened its commitment to a buyout, Van Naarden told Fierce in an interview.
“To their credit, they designed the right study. It was an entirely JAK2 pre-treated myelofibrosis population, so you don't have to guess as to whether or not the signal is real,” Van Naarden said. “It is the right population.”
The public now gets to see the data that fueled Lilly’s multibillion-dollar conviction and why the candidate could threaten Incyte’s stranglehold on the myelofibrosis market.
‘Working right out of the gate’
Debuting at the European Hematology Association (EHA) 2026 annual meeting, AJ1-11095 showed strong early results from a phase 1 trial, which, according to Van Naarden, were better than what was historically recorded in similar patients with pretreated myelofibrosis.
An impressive 70% of patients (16 out of 23) achieved a best response of at least a 35% reduction in spleen volume, an endpoint known as SVR35. The readout came from a May 28, 2026, data cutoff of the phase 1 AJX-101 trial evaluating AJ1-11095 across five dose levels—from 25 mg to 125 mg once daily—in its dose-escalation phase. All patients had previously failed a Type I JAK inhibitor, and their median line of prior therapies was two.
Historically, post-JAK inhibitor SVR35 response rates ranged from 0% to 32%, according to an EHA presentation by John Mascarenhas, M.D., from the Icahn School of Medicine at Mount Sinai and principal investigator of the AJX-101 study.
At week 12, 70% of patients achieved a 50% or greater reduction in their total symptom score, an endpoint known as TSS50. The rate was 65% at week 24 or 96% at any point in the study.
Another unique promise of Type II JAK2 inhibitors is the potential to reduce mutant JAK2 allele burden that drives MPNs. In its initial data set, AJ1-1109 triggered a reduction in driver mutation variant allele frequency (VAF) in 21 out of 23 patients. Among the 17 patients who reached week 24 of treatment, 59% saw a reduction of 20% or greater on this measure and 35% saw a reduction of 50% or greater.
In terms of safety, the drug saw no dose-limiting toxicities, and 78% of patients enrolled in the dose escalation phase remained on therapy as of a May 12, 2026, data cutoff.
Among 23 patients, grade 3 or above anemia happened in 12 (52%) patients, and seven (30%) patients had a grade 3 or above platelet count decrease, although 19 patients entered the trial already with anemia.
Altogether, five treatment discontinuations have been reported so far, none due to drug-related toxicity. These include one transplant, one for logistics reasons, two non-response cases and one unrelated adverse event.
“These early clinical findings suggest that selective targeting of the type II conformation of JAK2 may provide a differentiated approach,” Mascarenhas said in a June 13 statement. “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.”
Putting Incyte on notice
Lilly’s latest data place a target on Incyte’s myelofibrosis franchise. The Jakafi maker is developing candidates for specific myelofibrosis mutation subtypes. One of them, INCA033989, is an antibody against myelofibrosis harboring CALR mutations, which account for around one-fourth to one-third of all myelofibrosis cases.
At the 2025 American Society of Hematology annual meeting in December, Mascarenhas presented early phase 1 data showing 31.3% (15/48) patients achieved SVR35 as best SVR while on INCA033989 monotherapy dosed intravenously every two weeks between 24 mg to 2,500 mg. A small number of patients had received no prior JAK therapy before entering the trial.
Among patients resistant or intolerant to an existing JAK inhibitor, at week 24, the SVR35 rate was 27.6%, and the TSS50 rate was 35.7% in this study. Sixty percent of patients achieved TSS50 as best response throughout the study.
At that time, Pablo Cagnoni, M.D., Incyte’s president and head of R&D, said the results—along with other data in another MPN called essential thrombocythemia—reinforced the company’s confidence in the mutCALR-targeted agent’s “transformative potential.” Based on those data, William Blair analysts estimated the drug’s peak sales could reach $1.9 billion.
Incyte provided an updated look at the INCA033989 program at EHA 2026. With additional patients from the dose expansion cohort evaluating the drug at 250 mg and 2000 mg doses, the results do not look materially different from its ASH numbers.
Counting 69 patients, best SVR35 rate was 39%. At Week 24, 27% (17/62) patients achieved SVR35, including 47% from those who were JAK-ineligible and 20% among JAK-experienced individuals.
As for symptom improvements, best TSS50 was met in 53% (37/70) of patients. At Week 24, 32% (18/56) of patients achieved the endpoint.
At least based on the ASH data, “the efficacy quotient there is meaningfully less than what we’re seeing here,” Lilly’s Van Naarden noted.
Besides, while the Incyte candidate targets CALR mutations, Lilly’s Type II JAK2 inhibitor is meant to be more inclusive. Its VAF reduction was observed in patients across JAK2, MPL and CALR mutations. At least for now, Lilly didn’t spot any specific subtype that AJ1-11095 doesn’t work in, although Van Naarden cautioned that data are very early with only 23 patients.
Incyte has also explored combining INCA033989 with Jakafi, although efficacy data there were immature and not materially different from monotherapy. In that cohort, three of 12 patients (25%) achieved SVR35 at week 24, and three of nine (33.3%) achieved TSS50 at that point.
For Lilly, Van Naarden said the focus will be on monotherapy development for now.
“The efficacy here is pretty striking, so I think the initial plan is to declare a dose and get into phase 3 in the second-line MF setting as quickly as we can,” Van Naarden said.
Lilly is now treating patients in the dose-expansion phase, first using the 75 mg dosage, and then the study will “probably have a couple more cohorts,” he said. The 125 mg dose is “probably off the table” as the company started to see some toxicity, he added. Liver enzyme elevations were observed primarily at that high dose, although they were described as transient and were resolved following treatment.
Besides second-line myelofibrosis, Lilly plans to investigate the drug in patients with high-risk polycythemia vera and JAK2 inhibitor-naïve myelofibrosis.
“Could this be a better version of Jakafi? I don’t know. We have to build to that level of conviction over time,” Van Naarden said. “And then along the way, if there are rational combinations to do, we could consider that for sure.”
A two-pronged BD strategy
Ajax is among about 10 acquisitions by Lilly that have been announced so far this year.
“We are not done,” Van Naarden said.
The Lilly exec is currently running two strategies in dealmaking.
One model draws a comparison to early venture capital investment. Over the past few years, the Indianapolis pharma has been making high-volume, early-stage deals that are “generally not that expensive,” according to the executive. Van Naarden noted that in 2025, the company signed roughly 40 deals but only spent $4 billion in total. Many of these transactions were so small that they were never publicly announced in a press release.
“The strategy there is, most of these things won’t work,” Van Naarden explained. “But we haven’t spent that much money in total, so if one or two work, it easily pays for the entire endeavor.”
But 2025 ushered in a new era for Lilly, triggered by the company’s skyrocketing commercial success with its obesity and diabetes business. Meanwhile, some macro risks—such as government pricing talks and manufacturing bottlenecks—have largely been resolved.
Lilly found itself flush with an unprecedented amount of capital to deploy. Coupled with the brutal reality of the pharmaceutical life cycle, where even the biggest blockbusters must eventually be replaced, Lilly’s leadership recognized the need to use this window of time to reinvent its pipeline. It is against this backdrop that Van Naarden took on the additional role of head of corporate business development toward the end of 2025.
Now, Lilly is ramping up a strategy that invests in candidates that “at the time of the deal, you know are real,” Van Naarden said. That’s different from early-stage assets, where the assumption is that most projects won’t pan out. These more validated assets are more expensive, but they give Lilly the luxury of proof-of-concept clinical data.
Recent buyouts like Ajax, orexin receptor 2 player Centessa Pharmaceuticals and in vivo CAR-T company Kelonia Therapeutics fit this paradigm, according to Van Naarden.
“On the balance of 2026 but also going forward, we’re not done with either of these two strategies,” he said.
Lilly is not setting price limits on deals, Van Naarden said. But hunting for de-risked assets also accentuates the importance of maintaining financial discipline.
“My general observation is that the more mature the company is, the more Wall Street knows how to value it, and the more difficult therefore it is for us to do a deal where the price actually makes sense for us,” Van Naarden said.
Without strict price discipline, Van Naarden warned that the second strategy would quickly become “a very time-consuming way of allocating capital badly.”
Editor's Note: This story was updated at 12:05 p.m. ET to include Incyte's updated EHA data.