Incyte’s JAK insurance policy heads for the clinic

Prelude Therapeutics’ next-generation JAK inhibitor PRT12396 is heading into phase 1 next month, a new listing on the clinicaltrials.gov registry has revealed. That’s important not only for Prelude, but also for Incyte, a company with a significant stake in this approach, and which last year took out an option over a licensing deal for PRT12396.

Prelude’s slimmed-down approach also includes a preclinical KAT6A degrader, PRT13722, and coincidentally this mechanism also features among the latest first-in-human study initiations. That’s courtesy of Shanghai Henlius, which has advanced its KAT6A/B inhibitor HLX97 into a solid tumour trial where it will be tested as monotherapy or in combination with Faslodex.

Henlius’s move makes HLX97 the eighth project inhibiting KAT6 to go into the clinic, according to OncologyPipeline. Out in the lead is Pfizer's prifetrastat, in the phase 3 Katsis-1 trial. That company is taking several shots at this mechanism; however, Prelude’s PRT13722 appears to be the only degrader in development, and an IND filing for it is expected in mid-2026.

Disappointments

Prelude’s focus on PRT13722 and on the JAK2 V617F inhibitor PRT12396 that starts phase 1 next month follows several disappointments at this biotech.

The company was once best known for its work in PRMT5 inhibition, but discontinuations of two projects with this mechanism, PRT811 and PRT543, came alongside the termination of the clinical-stage MCL1 inhibitor PRT1419, and the shelving of two degraders of SMARCA2A, PRT3789 and PRT7732, after disappointing clinical data.

The idea behind PRT12396 is that JAK2 V617F is the primary driver mutation leading to JAK2 activation in myeloproliferative neoplasms, and selectively targeting JAK2 V617F could be safer than simply hitting JAK2, by virtue of sparing the wild-type protein. 

Incyte is the key player here, with the V617F mutation-selective molecule INCB160058 set to deliver proof-of-concept data this year. But, perhaps in a signal that it’s not too convinced by INCB160058, Incyte last November paid Prelude $35m in cash a plus $25m in equity for an option over PRT12396.

Perhaps once INCB160058 finally delivers proof-of-concept data – the results have been delayed by about a year – and certainly once the trial of PRT12396 that’s just getting under way shows its first efficacy numbers, Incyte will decide whether to stick with what it’s got or pay Prelude for full rights.

Recently disclosed first-in-human studies*

Note: *these projects were first listed on the clinicaltrials.gov database between 13 and 19 Mar 2026.

Two other projects among the latest first-in-human trial entrants are also worthy of note.

The first is Generate:Biomedicines’ GB-4362, an adjunct designed to neutralise unbound MMAE payload; the idea is that this could reduce the toxicity of prematurely released payload from ADCs like Padcev. Generate is a private US biotech that’s raised some $700m from venture financiers, and last month filed to go public, though the IPO is mostly predicated on its lead anti-asthma project.

The second is Biocon’s Bmab1700. As this is yet another MAb that hits PD-1 it seems fairly unspectacular, but what’s interesting is that its phase 1 trial tests it head-to-head against Opdivo, and aims to compare the two molecules’ pharmacokinetics.