Increasingly confident in the potential of its SMARCA2 degrader and a CDK9 inhibitor to treat cancers, Prelude Therapeutics is scrapping the other half of its clinical pipeline.
The company’s “top priority” is now to generate initial proof-of-concept data for PRT3789, a first-in-class highly selective degrader of the SMARCA2 protein, Chief Medical Officer and President Jane Huang, M.D., said in a third-quarter earnings release. The biotech hopes the drug will one day benefit the about 70,000 patients in the U.S. and Europe who have cancers with the SMARCA4 mutation.
AbCellera appears to have bought into the idea. As part of its earnings announcement, Prelude also disclosed that the two biotechs have signed a multiyear collaboration to develop and commercialize cancer drugs for up to five programs. The first of these programs will comprise antibody-drug conjugates involving a SMARCA degrader.
Alongside this work, Prelude will be pushing its own SMARCA2 degrader through a phase 1 trial in patients with biomarker-selected SMARCA4-mutated cancer with a readout expected next year. “Provided these results are as we expect, we anticipate advancing the compound into a registrational phase 2/3 trial thereafter,” Huang said.
The Wilmington, Delaware-based biotech also plans to file an IND with the FDA next year to get an oral SMARCA2 degrader into the clinic.
The company’s remaining bandwidth will be on its CDK9 inhibitor, dubbed PRT2527. Prelude had been “encouraged by the emerging data in both solid and hematological cancers” from a recently completed phase 1 trial, Huang said.
“These data demonstrate that our highly targeted compound has been generally safe and well-tolerated with a strong inhibition of the pathway required for efficacy in preclinical models and is well-differentiated from other CDK9 inhibitors,” the CMO added.
Prelude’s ambition is for PRT2527 to become the most advanced CDK9 inhibitor for patients with B-cell malignancies and acute myeloid leukemia, with clinical proof-of-concept data on the candidate as a monotherapy and in combinations expected next year.
The focus on CDK9 means Prelude now considers its MCL-1 inhibitor, called PRT1419, to be surplus to requirements, despite having recently completed a phase 1 dose-escalation study in hematological malignancies. “Based on the potential to address the intended patient populations with the CDK9 inhibitor, which potently inhibits MCL-1, Prelude has made a decision to prioritize its CDK9 inhibitor over PRT1419,” the company explained.
The CDK4/6 inhibitor PRT3645 is in a similar position. Despite phase 1 dose-escalation data showing levels of drug in the plasma are reaching the amount needed for efficacy, the company is ending work on the program and will instead seek out potential partners.
“We made significant progress in the third quarter with our four clinical-stage molecules and, as planned, conducted a rigorous assessment of each program,” CEO Kris Vaddi, Ph.D., said in the earnings release.
“Based on this assessment, we are prioritizing our resources on our first-in-class SMARCA2 degrader molecules, IV and oral, and our potential best-in-class CDK9 inhibitor program,” Vaddi added. “We are confident that these two programs represent compelling opportunities for demonstrating clinical proof-of-concept in 2024, for advancing into potential phase 2/3 registration studies, and for becoming important new medicines.”
Prelude appears to have the financial fuel to see its near-stage ambitions bear fruit. The biotech ended September with $230.5 million in cash and equivalents, which it expects to fund operations into 2026.