Prelude Therapeutics Reports Full Year 2024 Financial Results and Provides Program Outlook for 2025

PRT3789 has demonstrated clinical proof-of-concept that selectively degrading SMARCA2 is generally safe and has monotherapy anti-tumor activity in patients with SMARCA4-deficient, non-small cell lung (NSCLC), gastric and esophageal cancer

PRT3789 monotherapy dose escalation enrollment is nearing completion and dose escalation in combination with docetaxel continues with plans to present additional results from both cohorts in the second half of 2025

Enrollment into the Phase 1 study of Prelude's once daily, oral SMARCA2 degrader, PRT7732 is on track and an interim data update is anticipated in the second half of 2025

Current cash runway into second quarter of 2026 with $133.6 million in cash, cash equivalents and marketable securities as of December 31, 2024

WILMINGTON, Del., March 10, 2025 (GLOBE NEWSWIRE) -- Prelude Therapeutics Incorporated (Nasdaq: PRLD), a clinical-stage precision oncology company, today reported its financial results for the full year and fourth quarter ended December 31, 2024 and provided an update on its clinical development pipeline and other corporate developments.

"2024 was a productive year for Prelude highlighted by our efforts to advance the first ever highly selective SMARCA2 degraders to treat cancer patients who harbor SMARCA4 deleterious mutations," stated Kris Vaddi, Ph.D., Chief Executive Officer of Prelude. "These patients have a very poor clinical prognosis and are faced with limited treatment options. Through our development efforts to date with both monotherapy and combination approaches with PRT3789, we were the first to establish that selectively targeting SMARCA2 in patients with SMARCA4-deficient cancers could represent an important new class of therapy. Our SMARCA2 degraders appear generally safe and well-tolerated in clinical trials and have anti-tumor activity in several types of SMARCA4-deficient cancers."

Continued Vaddi, "We look forward to sharing data throughout the year both from our ongoing dose escalation and combination studies with PRT3789, and the first clinical data from our ongoing clinical trial of our once-daily oral SMARCA2 degrader, PRT7732. Lastly, our research and development organization was incredibly productive throughout 2024 continuing our mission to deliver new precision oncology medicines for patients with significant unmet need. We anticipate providing an update on our emerging discovery pipeline in the first half of 2025."

Clinical Program Updates and Upcoming Milestones

PRT3789 -- A first-in-class, highly selective, intravenous SMARCA2 Degrader

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. For example, fewer than 10% of patients with advanced stage, SMARCA4-mutated NSCLC are expected to respond to standard of care chemotherapy and are not eligible for other targeted therapies. We believe that this represents an area of high unmet medical need.

PRT3789 is in Phase 1 clinical development in patients with biomarker selected SMARCA4-mutated cancers. The Company is nearing conclusion of monotherapy dose escalation which is now at the 665 mg once weekly IV dose and identifying dose(s) for advancement to any potential future trials. In addition, enrollment of patients in dose escalation in the combination of PRT3789 with docetaxel is ongoing.

The Company also initiated a Phase 2 clinical trial evaluating PRT3789 in combination with KEYTRUDA$(R)$ (pembrolizumab) in patients with SMARCA4-mutated cancers, per the previously announced collaboration with Merck (known as MSD outside of the US and Canada).

KEYTRUDA(R) is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Interim Phase 1 data presented at the 2025 Japanese Society of Medical Oncology Annual Meeting

The Company presented an encore oral presentation titled: PRT3789, a First-in-Class Intravenous SMARCA2 Degrader, in Advanced Solid Tumors with a SMARCA4 Mutation: Phase 1 Trial at the 2025 Japanese Society of Medical Oncology Annual Meeting on March 8, 2025. The presentation can be found at Publications - Prelude Therapeutics.

As reported by investigators, PRT3789 was generally safe and well-tolerated at doses tested to date. Of the 32 advanced NSCLC or esophageal patients with Class 1 (loss of function) mutations who were treated with monotherapy (all doses) and evaluable for efficacy as of the November 30, 2024 data cutoff, RECIST confirmed partial responses (PRs) were observed in 5 patients (2 esophageal, 2 NSCLC, 1 gastric).

Of the 13 patients with Class 1 mutations treated at doses of 283 mg or higher, 3 had RECIST confirmed partial responses (2 NSCLC, 1 gastric). Tumor shrinkage was observed in patients with both Class 1 and Class 2 SMARCA4 mutations. Additional patients on-study demonstrated clinical benefit as measured by prolonged SD, including one advanced NSCLC patient on study for more than a year.

Initial observations of safety from evaluable patients in the PRT3789 plus docetaxel combination dose escalation arm of the trial through the first three cohorts (500 mg + docetaxel) were also presented. To date, PRT3789 in combination with docetaxel has demonstrated an acceptable safety profile.

PRT7732 -- A potent, highly selective and orally bioavailable SMARCA2 Degrader

PRT7732 is a highly selective and orally bioavailable SMARCA2 degrader. The Company initiated and enrolled our first patients in a phase 1 multi-dose escalation trial of PRT7732 (NCT06560645) in biomarker selected SMARCA4 mutated cancers. The Company expects to provide an interim data update in the second half of 2025.

Precision ADCs with SMARCA2/4 dual degrader payload

Prelude is developing potent SMARCA2/4 dual degraders that robustly inhibit cancer cell growth and induce cell death across multiple cancer types as payloads for precision ADCs. The Company presented the first preclinical data from its Precision ADC platform at the 36(th) EORTC-NCI-AACR Symposium in October. The data demonstrated potent activity of a SMARCA2/4 degrader payload when conjugated to a range of commercially available antibodies, including PSMA, TROP2, C-MET, CEACAM5, and CD33. The SMARCA2/4 degrader payload conjugated to an anti-PSMA antibody demonstrated tumor regressions and significantly better in vivo efficacy compared to a traditional PSMA-targeted cytotoxic (MMAF) ADC in xenograft models of prostate cancer at well tolerated doses. The presentation can be found at Publications - Prelude Therapeutics.

PRT2527 -- A potent and highly selective CDK9 inhibitor

PRT2527 is a potent and highly selective CDK9 inhibitor that has the potential to avoid off-target toxicities observed with other less selective CDK9 inhibitors. The Company presented interim phase 1 results of the dose-escalation study as part of a poster session at the 66(th) American Society of Hematology Annual Meeting $(ASH)$ in the fourth quarter of 2024. PRT2527 demonstrated activity across a range of relapsed/refractory lymphoid malignancies, including patients who received prior CAR-T therapy. The presentation can be found at Publications - Prelude Therapeutics.

The Company also announced that it intends to seek a partner for any future continued advancement of PRT2527, as a result of the Company's strategic focus on the SMARCA2 degrader development program.

Corporate Updates

In February 2025, the Company named Bryant D. Lim as the Company's permanent Chief Financial Officer. Mr. Lim has been serving as interim Chief Financial Officer since April of 2024 in addition to his role as Chief Legal Officer and Corporate Secretary.

Upcoming Investor Conference

The Company will participate in the Barclays 27(th) Annual Global Healthcare Conference taking place in Miami, FL. On Tuesday, March 11, 2025 at 12:30 PM ET, Kris Vaddi, Ph.D., Chief Executive Officer, and Jane Huang, M.D., President and Chief Medical Officer, and Bryant Lim, Chief Financial Officer will participate in a fireside chat.

A live webcast of the fireside chat can be accessed here and on the Company's website under Events and Presentations. The recording will be archived and available on the Company's website for 90 days.

Full Year 2024 Financial Results

Cash, Cash Equivalents, and Marketable securities:

Cash, cash equivalents and marketable securities as of December 31, 2024 were $133.6 million. The Company anticipates that its existing cash, cash equivalents and marketable securities will fund Prelude's operations into the second quarter of 2026.

Research and Development (R&D) Expenses:

For the year ended December 31, 2024, R&D expense increased to $118.0 million from $103.4 million for the prior year period. Included in the R&D expense for the year ended December 31, 2024 was $12.1 million of non-cash expense related to stock-based compensation expense, including employee stock options, compared to $12.6 million for year ended December 31, 2023. Research and development expenses increased due to a higher number of patients enrolled in clinical trials during 2024 driving an increase in related costs, such as chemistry, manufacturing and controls ("CMC") expenses, to support the trials. Research and development expenses may fluctuate from period to period depending upon the stage of certain projects and the level of preclinical and clinical trial-related activities.

General and Administrative (G&A) Expenses:

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