-  Encouraging signs of anti-tumor activity including objective responses observed in patients with SMARCA4-mutated non-small cell lung cancer (NSCLC) and esophageal cancer in early PRT3789 monotherapy dose escalation

-  At doses studied to date, PRT3789 was generally well-tolerated with no dose-limiting toxicities or study drug-related serious adverse events

Prelude Therapeutics Incorporated (Nasdaq: PRLD), a clinical-stage precision oncology company, announced the first interim clinical data from its ongoing Phase 1 open-label, dose-escalation trial of PRT3789, a first-in-class SMARCA2 degrader, highly selective for SMARCA2 and designed to treat cancer patients with a SMARCA4 mutation. The data were presented at the European Society for Medical Oncology (ESMO) Congress 2024 in Barcelona, Spain.

The study investigators reported that, as of the August 5, 2024 data cutoff date (the Cutoff Date), 65 patients were safety evaluable, enrolled and treated. This included 46 efficacy evaluable patients (with a post-baseline scan) with any tumor type harboring any SMARCA4 mutation.

As reported today by the study investigators, PRT3789 was generally well-tolerated through 8 dosing cohorts. Dose escalation continues, now in the 9^th dosing cohort. The majority of adverse events reported by investigators have been mild to moderate. A maximum tolerated dose has not yet been identified.

Overall, of the 26 advanced, heavily pre-treated NSCLC or esophageal patients evaluable for efficacy, 7 had tumor shrinkage. RECIST confirmed partial responses (PRs) were observed in 3 patients. Additional patients demonstrated clinical benefit as measured by prolonged stable disease (SD) including one patient on treatment for more than 1 year.

“For cancer patients harboring a SMARCA4 mutation, the disease is particularly aggressive and prognosis with current standard of care is quite poor,” stated Robin Guo, M.D., Memorial Sloan Kettering Cancer Center. “The observation of durable stable disease and tumor regressions in Phase I monotherapy dose escalation, coupled with a tolerable emerging safety profile, is encouraging. This is what we hope to see with a first-in-class new therapy for a novel target in patients with a high unmet need.”

“We are encouraged by the early clinical activity and emerging safety profile observed to date with PRT3789,” stated Jane Huang, M.D., President and Chief Medical Officer of Prelude. “These data represent initial proof of concept that selective SMARCA2 degradation can yield antitumor activity in certain SMARCA4 mutated cancers.”

Continued Dr. Huang, “Monotherapy dose escalation continues, now at cohort 9 (500mg once weekly) with backfill cohorts continuing to enroll enriched for NSCLC and esophageal cancer patients with Class 1 mutations. We intend to confirm the biologically active dose for PRT3789 as monotherapy by year-end and continue to advance monotherapy and docetaxel combination studies in parallel to best position PRT3789 as a new treatment option for patients suffering from this aggressive type of cancer.”