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. This decision comes after disappointing results in a phase 1 dose escalation trial, leaving the company with only one clinical program remaining in its pipeline.

PRT3789's Underwhelming Performance

The Delaware-based biotech revealed 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 only consider further development of PRT3789 with the assistance of a partner, shifting its internal resources to focus solely on PRT7732, another SMARCA2 degrader in its portfolio.

Refocusing on PRT7732

PRT7732, an orally administered SMARCA2 degrader, now stands as Prelude's primary clinical candidate. The company plans to explore its potential in SMARCA4 deleted cancers and determine the path forward for continued development by year-end.

Both PRT3789 and PRT7732 target the SMARCA2 protein, which is crucial for the survival of cancer cells with SMARCA4 mutations. These mutations are associated with more aggressive forms of cancer and are found in 10% of all non-small cell lung cancers and 5% of all cancers in general.

Pipeline Restructuring and Future Prospects

This latest development follows Prelude's previous decision to prioritize SMARCA2 degraders. In November 2023, the company discontinued two phase 1 assets—an MCL-1 inhibitor and a CDK4/6 inhibitor—to focus on PRT3789, which was then considered a "top priority."

Prelude expects to release first-in-human data for PRT7732 later this year. Additionally, the company is collaborating with AbCellera on preclinical antibody-drug conjugates targeting SMARCA2 and SMARCA4.

Despite the setback with PRT3789, Prelude's stock remained relatively stable, suggesting that investors may have already factored in the possibility of this outcome or are placing their hopes on the remaining clinical program and preclinical pipeline.