PRT7732, once daily oral SMARCA2 degrader, currently enrolling at the seventh dosing cohort (125 mg); Company to provide an update with preliminary clinical data, including PK/PD, safety and initial clinical activity by year end 2025 PRT3789 is designed to treat patients with a SMARCA4 mutation. Patients with SMARCA4-mutated cancer, a particularly aggressive form of the disease, have a very poor clinical prognosis. Approximately 10% of all non- small cell lung cancers and 5% of all cancers broadly, harbor a ...

Core Insights - Prelude Therapeutics reported strong execution in Q1 2025, focusing on the development of SMARCA2 degraders and KAT6A degraders for aggressive cancers [2][3] - The company has completed enrollment for the PRT3789 monotherapy and combination studies, with updated results expected in the second half of 2025 [1][4] - Prelude's financial position includes $103.1 million in cash and equivalents, projected to fund operations into Q2 2026 [1][14] Clinical Program Updates - PRT3789 is a first-in-class intravenous SMARCA2 degrader targeting SMARCA4 mutations, which are found in approximately 10% of non-small cell lung cancers [3][4] - The company has completed dose escalation for PRT3789 and selected a recommended Phase 2 dose of 500 mg once weekly [4] - A Phase 2 trial is underway evaluating PRT3789 in combination with KEYTRUDA® for patients with SMARCA4-mutated cancers [5] Financial Performance - R&D expenses for Q1 2025 increased to $28.8 million from $27.4 million in the prior year, primarily due to SMARCA2 clinical trials [15] - General and administrative expenses decreased to $5.8 million from $6.9 million, attributed to lower stock-based compensation [16][17] - The net loss for Q1 2025 was $32.1 million, consistent with the previous year, with a net loss per share of $0.42 [18][22] Upcoming Milestones - Initial data for the PRT7732 oral SMARCA2 degrader is expected in the second half of 2025, with rapid enrollment in the ongoing Phase 1 trial [1][8] - Prelude is advancing its KAT6A degrader program, with candidate nomination anticipated in Q2 2025 and an IND filing planned for 2026 [9][10] - The company will participate in the Citizens 2025 Life Sciences Conference on May 7, 2025, featuring key executives [12]

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].