Prelude Therapeutics (PRLD) investor relations material

Strategic pipeline overview

• Advancing multiple precision oncology programs targeting clinically validated mechanisms, with a focus on differentiated molecules for cancer treatment.

• Lead asset is a JAK2 V617F selective inhibitor for myeloproliferative neoplasms, aiming for disease modification beyond symptom control.

• KAT6A selective degrader for HR-positive breast cancer is entering clinical trials, designed to improve safety and efficacy over dual KAT6A/B inhibitors.

• Mutant CALR degrader antibody conjugate in discovery phase targets broader mutation classes in MPNs, aiming to eliminate disease-initiating cells.

• Multiple data catalysts and value inflection points anticipated through 2026 and 2027.

Key partnership and financial milestones

• Entered exclusive option agreement with Incyte for JAK2 V617F inhibitor, including $60M upfront ($25M cash, $35M equity) and a 15-month option expiring February 2027, extendable by three months.

• Option exercise triggers a $100M milestone payment, with up to $775M in additional clinical and regulatory milestones and low single-digit royalties.

• Milestones are tied to clinical and regulatory achievements, not sales-based metrics.

• Incyte’s discontinuation of a separate JAK2 program does not impact the current agreement or molecule development.

Clinical development and differentiation

• Phase I trial for JAK2 V617F inhibitor enrolls PV and MF patients in parallel, focusing on safety, hematological response, symptom improvement, and allele burden reduction.

• Key benchmarks include absence of hematological toxicity and demonstration of clinical activity in both PV and MF.

• Compound structurally designed for mutant selectivity by binding the deep pocket of JAK2 V617F, differentiating from competitors.

• KAT6A degrader offers selectivity and degradation advantages, aiming for improved therapeutic window and reduced bone marrow toxicity compared to dual inhibitors.

• Early clinical data for KAT6A program expected in the second half of 2027, with focus on differentiated safety and efficacy.