Prelude Therapeutics Publishes Abstract for ESMO Congress 2024 Presentation

Prelude Therapeutics Incorporated (Nasdaq: PRLD), a precision oncology firm, has unveiled an abstract detailing data on PRT3789 at the European Society of Medical Oncology (ESMO) Congress 2024, scheduled in Barcelona, Spain from September 13 to 17. PRT3789 is a pioneering, highly selective SMARCA2 degrader, currently in Phase 1 clinical trials targeting patients with advanced solid tumors exhibiting SMARCA4 mutations.

Jane Huang, M.D., President and Chief Medical Officer of Prelude, expressed enthusiasm about presenting the first clinical data for this novel SMARCA2 degrader. She highlighted that patients with SMARCA4 mutations often face limited treatment choices and aggressive disease progression. Despite being in the early stages of development, PRT3789 has shown a promising safety profile, effective target engagement, and notable clinical activity.

PRT3789 is undergoing Phase 1 clinical development, focusing on patients with biomarker-selected SMARCA4 mutations. The recruitment for the study is progressing well, with expectations to complete the monotherapy dose escalation by the end of 2024 and to determine an optimal Phase 2 dose. Additionally, the company continues to enroll patients into back-fill cohorts specifically for non-small cell lung cancer (NSCLC) and other SMARCA4 loss-of-function mutations.

The primary objectives of this Phase 1 study include establishing the safety and tolerability of PRT3789 as a monotherapy and in combination with docetaxel. The study also aims to evaluate the drug’s activity, pharmacokinetics, and pharmacodynamics to identify a suitable dose and potential indications for a registrational clinical trial.

As of March 7, 2024, 40 patients had been enrolled in the study, including 18 with NSCLC, 5 with pancreatic cancer, 3 with breast cancer, 2 with esophageal cancer, and 12 with other types of cancer. Among these patients, 55% had loss-of-function mutations. The dose escalation process has covered six levels, ranging from 24 to 212 mg, with two backfill cohorts opened. No dose-limiting toxicities or serious adverse events related to the study drug have been reported. The most common adverse events, regardless of grade or relation, include nausea (25%), constipation and dyspnea (each 17.5%), decreased appetite and fatigue (each 15%), and anemia (12.5%).

Dose-related increases in the area under the curve (AUC) were observed, along with dose-dependent decreases in SMARCA2 levels at all doses. A trend for deeper and longer-lasting reductions in SMARCA2 levels was noted with higher doses. Minimal effects on SMARCA4 levels were seen. Thus far, the clinical activity of PRT3789 therapy includes partial responses according to RECIST criteria, tumor shrinkage, and prolonged stable disease in patients with advanced, heavily pretreated esophageal cancer and NSCLC, surpassing the response duration to their most recent therapy.

Prelude Therapeutics is dedicated to developing innovative cancer treatments. Their pipeline includes several novel drug candidates such as first-in-class, highly selective SMARCA2 degraders and a promising CDK9 inhibitor. The company also focuses on discovering and commercializing next-generation degrader antibody conjugates ("Precision ADCs") through collaborations.

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