Prelude Therapeutics Halts Development of Lead SMARCA2 Degrader

Prelude Therapeutics, a precision oncology company, has announced the suspension of development for its lead asset, PRT3789, a SMARCA2 degrader. The decision comes after disappointing results in a phase 1 dose escalation trial, leaving the company with only one clinical program remaining in its pipeline.

Disappointing Phase 1 Results Lead to Program Pause

The Delaware-based biotech revealed on August 14 that PRT3789, while demonstrating initial proof of concept for its mechanism, failed to meet expectations in early clinical testing. CEO Kris Vaddi, Ph.D., cited several factors contributing to this decision, including "the potential need for higher target coverage throughout the dosing interval, and capital needs to continue to advance both agents."

Prelude will now shift its focus to PRT7732, another SMARCA2 degrader in its portfolio. Unlike the intravenously administered PRT3789, PRT7732 is an oral medication, which may offer advantages in terms of patient convenience and dosing strategies.

Strategic Shift and Pipeline Realignment

This development marks a significant change in Prelude's strategy, particularly given the company's previous commitment to SMARCA2 degraders. In November 2023, Prelude had made the decision to prioritize PRT3789, cutting two phase 1 assets – an MCL-1 inhibitor and a CDK4/6 inhibitor – to allocate resources to what was then considered their "top priority" program.

With the suspension of PRT3789, Prelude's clinical pipeline now consists solely of PRT7732. The company expects to release first-in-human data for this compound later this year, which will likely play a crucial role in determining the future direction of their SMARCA2 degrader program.

Market Response and Future Outlook

Despite the setback, the market reaction to Prelude's announcement was relatively muted. The company's stock saw only a slight dip before recovering, trading at $0.96 per share by 10:35 a.m. ET on the day of the announcement, up from $0.91 at the previous day's close.

Looking ahead, Prelude is not entirely abandoning PRT3789, stating that they will only pursue its development with the help of a partner. Additionally, the company is exploring the potential of PRT7732 in SMARCA4 deleted cancers, with plans to determine the path forward for continued development by the end of the year.

Prelude is also diversifying its approach, working on preclinical antibody-drug conjugates targeting SMARCA2 and SMARCA4 in collaboration with AbCellera. This multi-pronged strategy may help mitigate risks associated with setbacks in any single program.