It’s all change at Prelude Therapeutics. The precision oncology biotech is waving goodbye to its chief medical officer, pausing work on SMARCA2 degraders and selling a licensing option to Incyte Therapeutics.
This morning’s multifaceted strategic shake-up includes offering an exclusive option for Prelude’s mutant selective JAK2V617F JH2 inhibitor program to Incyte for $35 million in upfront cash as well as a $25 million equity investment. Should Incyte take up the option to acquire the preclinical program outright, the JAK inhibitor experts would need to stump up another $100 million and would also be on the hook to pay out up to $775 million in potential milestones.
With only $52 million to hand, the $60 million from Incyte will already more than double Prelude’s funding pot, extending its financing runway into 2027. Should Incyte go all-in on the JAK2V617F JH2 inhibitors, Prelude expects to be financially stable into the third quarter of 2028.
Prelude has kept the existence of the JAK2V617F JH2 inhibitor program under wraps until this morning. Incyte has already achieved blockbuster success with its Novartis-partnered first-generation JAK2 JH1 inhibitor Jakafi. Prelude CEO Kris Vaddi, Ph.D., said the company’s program is designed to improve on the standard of care established by Jakafi and its JAK2 peers.
“Our research team made significant progress discovering the first known inhibitors that bind into the JAK2 JH2 ‘deep pocket’ where the V617F mutation resides,” Vaddi explained in an Nov. 4 release.
“These potent and orally bioavailable compounds demonstrate mutant-specific inhibition and the potential for disease modification in multiple preclinical models of MPNs,” the Prelude CEO added. “Today’s agreement with Incyte provides us with the capital needed to advance further our JAK2V617F program, while also allowing us to advance the development of our other pipeline programs.”
The biotech used a separate announcement this morning to explain how the Incyte deal fits into Prelude’s broader pipeline shake-up. This involves pausing work on the company’s SMARCA2 degrader program.
The SMARCA4 mutation is linked to more aggressive forms of cancer and is found in 10% of all non-small cell lung cancers and 5% of all cancers in general.
But Prelude had already called time on its SMARCA2 degrader PRT3789 back in August on the back of underwhelming phase 1 data, leaving just one clinical program left in its pipeline.
“Having actively pursued the clinical development of our SMARCA2 selective degraders, we determined that complex biology and aggressiveness of disease in patients with SMARCA4 deletions will likely require early intervention and combination strategies to make a meaningful impact for patients,” Vaddi explained in one of Prelude’s releases today.
“We are not resourced to explore the mechanism fully in the timeframe needed to deliver a concrete and viable path forward,” the Prelude CEO added. “In addition, we believe that optimally resourcing the JAK2V617F mutant selective inhibitor and KAT6A degrader programs are of paramount importance and as noted in this morning’s previous announcement, the agreement with Incyte brings in significant capital enabling us to advance both programs.”
The SMARCA2 program wasn’t the only loss at Prelude—the company also announced this morning that President and Chief Medical Officer Jane Huang, M.D., has left to “pursue other opportunities.”
For now, Prelude board member Victor Sandor, M.D.—former CMO of Array Biopharma—will provide “strategic and operational oversight of clinical development” at Prelude.
“The company will seek to augment the clinical development leadership in a timeframe that fits with the maturation of the programs,” Prelude added.
As well as the JAK2V617F JH2 inhibitors—which Prelude will continue to lead on unless Incyte takes up its option to acquire the program—Prelude’s other priority will be KAT6A degraders for ER+ breast cancer. The biotech is planning to take its first KAT6A degrader into the clinic next year.
Investors appeared unimpressed with the pivot, sending Prelude’s stock down 45% to $2.19 at 9:30 a.m. ET Tuesday from a Monday closing price of $3.98.