Prelude Therapeutics' SMARCA2 Degrader PRT3789 Demonstrated Promising Initial Clinical Activity and Safety Profile in Phase 1 Trial

Core Insights - Prelude Therapeutics announced encouraging interim clinical data for PRT3789, a first-in-class SMARCA2 degrader targeting patients with SMARCA4 mutations, showing objective responses in non-small cell lung cancer (NSCLC) and esophageal cancer [1][5][12] - The drug was well-tolerated with no dose-limiting toxicities reported, and the company is advancing to the 9th dosing cohort in its ongoing Phase 1 trial [3][7][13] Patient Data - As of August 5, 2024, 65 patients were safety evaluable, with 46 patients being efficacy evaluable, all having tumors with SMARCA4 mutations [2][6] - Among 26 advanced NSCLC or esophageal patients evaluable for efficacy, 7 experienced tumor shrinkage, with 3 confirmed partial responses [4][9] Safety Profile - Adverse events reported were mostly mild to moderate, including nausea (24.5%), decreased appetite (18.5%), and fatigue (18.5%), with no serious adverse events related to the study drug [7][3] - A maximum tolerated dose has not yet been identified, and dose escalation continues [3][6] Pharmacokinetics and Pharmacodynamics - Preliminary pharmacokinetic data indicated a dose-dependent increase in exposure, with mean concentrations above the SMARCA2 plasma DC50 for approximately 8 hours at the highest dose [8] - Pharmacodynamic effects showed a 70-75% inhibition of SMARCA2 at higher doses, demonstrating the selectivity of PRT3789 [8] Future Plans - The company aims to confirm the biologically active dose for PRT3789 by year-end and continue studies in combination with docetaxel [5][13] - An investor conference call is scheduled for September 13, 2024, to discuss the findings further [10] Upcoming Presentations - Interim Phase 1 data will be presented at the EORTC-NCI-AACR Symposium on October 24, 2024, highlighting the clinical results of PRT3789 [11] Company Overview - Prelude Therapeutics focuses on developing innovative precision oncology medicines, including first-in-class SMARCA2 degraders, to address high unmet medical needs in cancer treatment [15]