Highly selective oral SMARCA2 degrader, PRT7732, shows robust anti-tumor activity in vivo as monotherapy and in combination with chemotherapy, at well-tolerated doses

Potentially best-in-class CDK9 inhibitor, PRT2527, in Phase 1 development, is highly effective in preclinical hematological models as monotherapy and provides improved depth and duration of response in combination with BTK/BCL2 inhibition

Next Generation CDK4/6 Inhibitor, PRT3645, is highly effective in combination with other targeted therapies in preclinical models of breast cancer, CRC and NSCLC

WILMINGTON, Del., April 09, 2024 (GLOBE NEWSWIRE) -- Prelude Therapeutics Incorporated (Nasdaq: PRLD), a clinical-stage precision oncology company, today announced the presentation of new preclinical data at the American Association for Cancer Research (AACR) Annual Meeting for its highly selective oral SMARCA2 degrader, its potentially best-in-class CDK9 inhibitor and its next-generation oral CDK4/6 inhibitor.

“These presentations demonstrate our core competencies in medicinal chemistry and cancer biology to optimize and deliver compounds to the clinic with the potential to succeed as differentiated first- and/or best-in-class new therapies,” said Andrew Combs, Ph.D., Chief Chemistry Officer at Prelude Therapeutics. 

Peggy Scherle, Ph.D., Chief Scientific Officer at Prelude, stated, “Advancement of our second highly selective SMARCA2 degrader strengthens Prelude’s leadership position in the emerging use of SMARCA2 protein degradation as a potential treatment option for underserved patients with cancer. With both a first-in-class IV SMARCA2 degrader, PRT3789, in Phase 1 clinical development and now our oral SMARCA2 degrader, PRT7732, expected to enter the clinic later this year, we believe these distinct modalities may offer new therapies for patients with SMARCA4 mutations.”

Details on the poster presentations are as follows:

Title: Preclinical Characterization of PRT7732: A Highly Potent, Selective, and Orally Bioavailable Targeted Protein Degrader of SMARCA2

Summary:

• Identified potent, selective, well-tolerated and orally bioavailable SMARCA2 degrader, PRT7732
• PRT7732 exhibits >3000-fold selectivity for SMARCA2 over SMARCA4, with low nanomolar potency in cell based assays
• Prelude completed IND-enabling studies for PRT7732 and is on track to enter Phase 1 clinical trials in the second half of 2024
  

Link: http://investors.preludetx.com/static-files/7b590cab-9f51-4e87-9b13-844599099dbf

Title: PRT2527, a Novel Highly Selective Cyclin-Dependent Kinase 9 (CDK9) Inhibitor, Has Potent Antitumor Activity in Combination with BTK and BCL2 Inhibition in Various Lymphoid Malignancies

Summary:

• PRT2527 is efficacious as monotherapy in preclinical models of DLBCL, CLL and MCL, and combines with both BTK and BCL2 inhibition to improve depth and duration of responses
• PRT2527 is currently being evaluated in a Phase I clinical trial in patients with relapsed/refractory hematologic malignancies as monotherapy and in combination with zanubrutinib (NCT05665530)

Link: http://investors.preludetx.com/static-files/ffa3bc31-4e5c-4151-bff7-ebd161f3df85

Title: The Brain Penetrant CDK4/6 Inhibitor, PRT3645, is Highly Effective in Combination with Other Targeted Therapies in Preclinical Models of Breast Cancer, CRC and NSCLC

Summary:

• Next generation CDK4/6 inhibitor, PRT3645, demonstrates preclinical synergy with SERDs, as well as MEK1/2 and CDK2 inhibition
• PRT3645 has the potential to improve patient outcomes when used in combination with other targeted therapies

Link: http://investors.preludetx.com/static-files/8dd469c6-6652-41bc-a191-2dc1ef054a7a

About Prelude Therapeutics

Prelude Therapeutics is a clinical-stage precision oncology company developing innovative drug candidates targeting critical cancer cell pathways. Prelude’s diverse pipeline is comprised of highly differentiated, potentially best-in-class proprietary small molecule compounds aimed at addressing clinically validated pathways for cancers with selectable underserved patients. Prelude’s pipeline includes: an IV administered, potent and highly selective SMARCA2 degrader, PRT3789, a preclinical oral SMARCA2 selective degrader, PRT7732, a potent and highly selective CDK9 inhibitor, PRT2527, and a next generation CDK4/6 inhibitor, PRT3645.

For more information, visit our website and follow us on LinkedIn.

Cautionary Note Regarding Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to, anticipated discovery, preclinical and clinical development activities for Prelude’s product candidates, the potential safety, efficacy, benefits, and the expected timeline for initiating clinical trials for Prelude’s product candidates. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. The words “believes,” “potential,” “anticipates,” “estimates,” “plans,” “expects,” “intends,” “may,” “could,” “should,” “likely,” “projects,” “continue,” “will,” “schedule,” and “would” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. These forward-looking statements are predictions based on the Company’s current expectations and projections about future events and various assumptions. Although Prelude believes that the expectations reflected in such forward-looking statements are reasonable, Prelude cannot guarantee future events, results, actions, levels of activity, performance or achievements, and the timing and results of biotechnology development and potential regulatory approval is inherently uncertain. Forward-looking statements are subject to risks and uncertainties that may cause Prelude's actual activities or results to differ significantly from those expressed in any forward-looking statement, including risks and uncertainties related to Prelude's ability to advance its product candidates, the receipt and timing of potential regulatory designations, approvals and commercialization of product candidates, clinical trial sites and our ability to enroll eligible patients, supply chain and manufacturing facilities, Prelude’s ability to maintain and recognize the benefits of certain designations received by product candidates, the timing and results of preclinical and clinical trials, Prelude's ability to fund development activities and achieve development goals, Prelude's ability to protect intellectual property, and other risks and uncertainties described under the heading "Risk Factors" in Prelude’s Annual Report on Form 10-K for the year ended December 31, 2023, its Quarterly Reports on Form 10-Q and other documents that Prelude files from time to time with the Securities and Exchange Commission. These forward-looking statements speak only as of the date of this press release, and Prelude undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date hereof, except as may be required by law. 

Investor Contact:
Lindsey Trickett
Vice President, Investor Relations
240.543.7970
ltrickett@preludetx.com

Media Contact:
Helen Shik
Shik Communications
617.510.4373
Helen@ShikCommunications.com