Prelude Therapeutics (PRLD) investor relations material

Strategic portfolio shift and pipeline focus

• Shifted focus from SMARCA2 program to JAK2V617F and KAT6A programs, aiming for clinical entry in 2026.

• Advancing a novel degrader antibody conjugate program targeting mutant CALR in myeloproliferative neoplasms (MPNs).

• Announced IND clearance for JAK2V617F in January and targeting IND for KAT6A by mid-year.

• Entered a business development deal with Incyte for JAK2V617F, extending financial runway into Q2 2027.

• Current cash position is $106 million, not including a potential $100 million option payment from Incyte.

JAK2V617F program differentiation and clinical plan

• JAK2V617F inhibitor is mutant-selective, aiming to spare wild-type JAK2 and potentially modify disease course.

• Molecule binds a unique deep pocket in the JH2 domain, providing selectivity and therapeutic window.

• Phase 1 trial will enroll both myelofibrosis and polycythemia vera patients in parallel, including JAK inhibitor-naive patients.

• Global trial design allows for earlier-stage patient enrollment and meaningful early data.

• Collaboration with Incyte provides upfront funding and potential for further cash influx if milestones are met.

KAT6A degrader program and competitive positioning

• KAT6A degrader designed for selectivity over KAT6B, aiming for better safety and efficacy.

• Preclinical data show tumor regression and reduced neutropenia compared to dual inhibitors.

• Clinical plan focuses on ER-positive breast cancer, with potential for combination with CDK4/6 inhibitors.

• Lower plasma concentrations expected due to high potency of degrader.

• Expansion cohorts will explore combinations and direct head-to-head comparisons with competitors.