Prelude Therapeutics (PRLD) The Citizens JMP Hematology and Oncology Summit Conference summary

Company overview and strategy

• Focused on developing novel precision medicines for cancer, leveraging a highly experienced team with a track record in transformative therapies like Jakafi and Brukinsa.

• Pipeline centers on first-in-class SMARCA2 degraders, targeting cancers with SMARCA4 mutations, which are present in 5%-10% of many cancers and associated with poor outcomes.

• Two lead SMARCA2 programs: PRT3789 (IV) and PRT7732 (oral), both in clinical development, offering flexibility in treatment approaches.

• Additional progress with a selective CDK9 inhibitor (2527), with data to be presented at ASH.

• Multiple milestones and data catalysts expected in 2025, including clinical data from ongoing studies and new preclinical program disclosures.

Clinical data and development progress

• Achieved industry-first clinical proof of concept for SMARCA2 degraders, with preliminary data showing responses in patients with SMARCA4 loss-of-function mutations.

• Selectivity of SMARCA2 over SMARCA4 demonstrated a favorable safety profile, with higher doses yielding a 22% response rate in lung cancer patients.

• Dose selection for further development (RP2D) expected by year-end, with ongoing efforts to enrich patient populations for optimal efficacy.

• Combination studies with docetaxel and pembrolizumab are underway, aiming to improve response rates beyond current standards.

• Preliminary safety data for the docetaxel combination show high tolerability and brisk enrollment, with no treatment-related serious adverse events reported.

Forward-looking plans and milestones

• Key 2025 milestones include completion of dose escalation, presentation of clinical data, and reporting initial data from the oral SMARCA2 program.

• Go/no-go criteria for advancing programs are based on surpassing response rates of standard comparators like docetaxel, aiming to double or triple these benchmarks.

• Registrational study prioritization will depend on response rates and the potential of both IV and oral SMARCA2 molecules, with a focus on maximizing patient benefit and speed to market.

• Oral SMARCA2 offers potential advantages in convenience and pharmacokinetics, possibly enabling higher and more consistent target degradation.

• Capital allocation will be guided by data, with a focus on programs with the highest likelihood of success and impact.