Prelude Therapeutics’ lead asset won’t be making it to the second act. The precision oncology outfit is pausing development of SMARCA2 degrader PRT3789, leaving just one clinical program left humming in its pipeline.
The decision comes after PRT3789 underwhelmed in a phase 1 dose escalation trial, Prelude said in an Aug. 14 release. The Delaware-based biotech will only take the asset forward with the help of a partner. The company’s internal resources will now focus solely on its other SMARCA2 degrader, PRT7732.
“While PRT3789 demonstrated initial proof of concept for the mechanism, a number of considerations—including the potential need for higher target coverage throughout the dosing interval, and capital needs to continue to advance both agents—contributed to this decision,” CEO Kris Vaddi, Ph.D., said in the filing.
PRT3789 and PRT7732 are designed to target the SMARCA2 protein, which cancer cells with a SMARCA4 mutation need to survive. The SMARCA4 mutation is linked to more aggressive forms of cancer, Prelude said in the release, and is found in 10% of all non-small cell lung cancers and 5% of all cancers in general.
While PRT3789 is given intravenously, PRT7732 is given orally. Given “the clinical profile observed to date with PRT7732,” Vaddi said, Prelude will “explore the potential for this mechanism in SMARCA4 deleted cancers and determine the path forward for continued development by year-end.”
Prelude’s ditching of PRT3789 comes after the company had previously decided to go all-in on SMARCA2 degraders. The company cut two phase 1 assets, an MCL-1 inhibitor and a CDK4/6 inhibitor, in November 2023 in order to make room for “top priority” PRT3789.
First-in-human data from the now-solo PRT7732 is expected later this year, Prelude said in the release, and the company is also working on preclinical antibody-drug conjugates for SMARCA2 and SMARCA4 in tandem with AbCellera.
Prelude’s stock seemed largely unaffected by the announcement of PRT3789’s curtain call, dipping slightly but then bouncing back to $0.96 per share by 10:35 a.m. ET, up from $0.91 at the prior day’s close.