Prelude Announces Presentations at 2025 AACR Annual Meeting

Core Insights - Prelude Therapeutics has presented new preclinical data on its first-in-class SMARCA2 degrader PRT3789 and selective KAT6A degraders at the AACR Annual Meeting, highlighting their potential in treating cancers with specific mutations [1][2]. Group 1: SMARCA2 Degrader (PRT3789) - PRT3789 is a first-in-human SMARCA2 degrader that selectively induces deep and sustained degradation of SMARCA2, achieving high selectivity through a stable ternary complex formation with VHL [4]. - The resynthesis rate of SMARCA2 is 2-3 times slower than that of SMARCA4, enhancing the selectivity profile and contributing to a favorable safety profile observed in clinical studies [4]. - PRT3789 is currently under evaluation in Phase 1 and Phase 2 studies for patients with advanced solid tumors that have lost SMARCA4 [4]. Group 2: KAT6A Degraders - KAT6A is associated with cancer growth and is recurrently amplified in various cancers, making it a clinically validated target [5]. - Prelude has identified a series of first-in-class, sub-nanomolar, selective, and orally bioavailable KAT6A degraders that are advancing to candidate nomination [5]. - Preclinical data indicate that Prelude's selective KAT6A degraders drive significantly deeper anti-cancer responses compared to non-selective KAT6A/B inhibitors across multiple KAT6A-amplified tumors [5]. Group 3: Clinical Implications - The selective degradation of KAT6A is expected to improve hematological safety and provide robust single-agent activity compared to existing KAT6-targeted therapies [5]. - Prelude's KAT6A degraders exhibit sustained activity in various cancer models, including those resistant to endocrine therapy and CDK4/6 inhibitors, and show potential for combination benefits with standard of care therapies [8].