Prelude Therapeutics (PRLD) Goldman Sachs 45th Annual Global Healthcare Conference summary

Strategic vision and company evolution

• Focus on developing first-in-class and best-in-class precision oncology medicines targeting challenging oncogenic pathways.

• Evolved from a discovery-stage startup in 2016 to a mature R&D organization with a robust pipeline.

• Prioritized internal development of SMARCA2 and CDK9 programs, with some assets partnered externally.

• Assembled a management team with proven expertise in drug discovery, development, and commercialization.

• Not tied to a single technology, enabling tailored therapies for diverse patient needs.

Pipeline highlights and clinical progress

• Lead SMARCA2 IV degrader (PRT3789) in phase I dose escalation, aiming for proof of concept later this year.

• Oral SMARCA2 degrader (PRT7732) advancing to clinic in the second half of the year.

• Discovery-stage SMARCA4 dual degraders as ADC payloads, expanding potential patient reach.

• Next-generation CDK9 inhibitor (PRT2527) in phase I for hematological malignancies, with initial POC data expected this year.

• Productive discovery engine with additional first-in-class opportunities approaching IND stage.

Scientific rationale and unmet need

• SMARCA4 mutations prevalent in up to 10% of non-small cell lung cancer and other cancers, with poor outcomes on current therapies.

• Synthetic lethality approach: targeting SMARCA2 in SMARCA4-mutant tumors induces tumor cell death.

• Achieved unprecedented selectivity for SMARCA2 over SMARCA4 (>1,000-fold) with PRT3789.

• Phase I trial includes all SMARCA mutations and multiple tumor types, with enrichment for loss-of-function and NSCLC patients.

• Combination studies with docetaxel initiated based on preclinical synergy.