Prelude Therapeutics Incorporated · NASDAQ:PRLD
Prelude Therapeutics — Investor Presentation (November 2025)
24 slides from Prelude Therapeutics's investor presentation, Nov 4, 2025
Slide 1: Corporate Presentation November 2025
Prelude THERAPEUTICS Corporate Presentation November 2025
Slide 2: Forward Looking Statements & Disclaimers
Forward Looking Statements & Disclaimers This presentation 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 activities for Prelude’s produ
Slide 3: Mission to extend the promise of precision medicine to every cancer patient
We are on a mission to extend the promise of precision medicine to every cancer patient in need Select the best modality to precisely target oncogenic mechanisms Strive for first- or best-in-class and anchor to patient unmet need Draw on decades of experience and proven leadership to drive innovatio
Slide 4: Experienced Leadership Team With Proven Track Records
Experienced Leadership Team With Proven Track Records Kris Vaddi, PhD Chief Executive Officer Peggy Scherle, PhD Chief Scientific Officer Andrew Combs, PhD Chief Chemistry Officer Sean Brusky, MBA Chief Business Officer Bryant Lim, J.D. Chief Financial Officer,Chief Legal Officer, Secretary Dr. Vict
Slide 5: Prelude's Pipeline & Discovery Engine
Prelude’s Pipeline & Discovery Engine
Slide 6: Our Investment Thesis Centers on Advancing Two Programs
Our Investment Thesis Centers on Advancing Two Programs – Both Representing Highly Differentiated Approaches to Clinically Validated Targets JAK2V617F Mutant Selective Inhibitors Potentially transformative JAK2V617F allosteric JH2 inhibitors with potential to reduce mutant allele burden and modify t
Slide 7: JAK2V617F is the Primary Driver Mutation in MPNs
JAK2V617F is the Primary Driver Mutation Leading to Activated JAK-STAT Signaling, Uncontrolled Proliferation, and Disease Progression in MPNs • The JAK-STAT pathway mediates growth factor signaling, most notably: − Thrombopoietin receptor for platelet production − Erythropoietin receptor for red blo
Slide 8: JAK2V617F Mutant Selective Inhibitor Could Become Disease Modifying Option for Majority of MPN Patients
A JAK2V617F Mutant Selective Inhibitor Could Become a Disease Modifying Option for the Majority of MPN Patients and Represents an Expansive Opportunity Sources: NCI SEER Database (accessed Dec 2024), Leukemia & Lymphoma Society Facts & Figures; F. Passamonte et.al., “Clinical Significance of JAK2 V6
Slide 9: First Known JAK2 Inhibitors That Bind in the JAK2 JH2 Deep Pocket
Prelude Scientists Recently Discovered the First Known JAK2 Inhibitors That Bind in the JAK2 JH2 “Deep Pocket” Where the V617F Mutation Resides Allosteric JH2 Regulatory Domain vs Catalytic Domain Prelude JAK2 JH2 Inhibitors Bind into the “Deep Pocket” Adjacent to V617F Mutation
Slide 10: JAK2V617F Mutant Selective Inhibitors Highly Differentiated From 1st Generation JAK Inhibitors
JAK2V617F Mutant Selective Inhibitors Are Highly Differentiated From 1st Generation JAK Inhibitors in a Large and Growing Market • Global sales of ruxolitinib (Jakafi® /Jakavi®) in MPNs grew to over $4.5B in 20241,2 − Continuing strong sales growth for ruxolitinib in PV • First generation JAK inhibi
Slide 11: Option Agreement With Incyte Provides Significant Capital
Option Agreement With Incyte Provides Significant Capital to Further Advance the JAK2V617F and KAT6A Degrader Programs Exclusive option agreement with Incyte announced November 2025
Slide 12: Our Investment Thesis Centers on Advancing Two Programs
Our Investment Thesis Centers on Advancing Two Programs – Both Representing Highly Differentiated Approaches to Clinically Validated Targets JAK2V617F Mutant Selective Inhibitors Potentially transformative JAK2V617F allosteric JH2 inhibitors with potential to reduce mutant allele burden and modify t
Slide 13: Prelude's First-In-Class Oral KAT6A Selective Degraders
Prelude’s First-In-Class Oral KAT6A Selective Degraders • A KAT6A/B dual inhibitor is now in pivotal phase 3 trials in combination with fulvestrant, after progression on a CDK4/6 inhibitor − Demonstrated efficacy in post CDK4/6 inhibitor setting in a broad population of ER+ BC including PIK3CA-, ESR
Slide 14: Selectively Degrading KAT6A is a Novel Approach
Selectively Degrading KAT6A is a Novel Approach with Potential to Deliver Differentiated Safety and Efficacy Over Non-Selective KAT6A/B Inhibitors
Slide 15: Lead KAT6A Selective Degrader Development Candidate is a Potent Degrader
Our Lead KAT6A Selective Degrader Development Candidate Lead DC is a Potent KAT6A Degrader in Preclinical Models Absolute Degradation Selectivity (KAT6A vs KAT6B) In Vivo Efficacy • Absolute kinetic selectivity for 6A/6B (>1000-fold) • Global proteomics demonstrates selective KAT6A degradation • Exc
Slide 16: Lead DC Drives Tumor Regressions in T47-D Model
Our Lead DC Drives Tumor Regressions in T47-D Model with Significantly Greater Monotherapy Activity than KAT6A/B Inhibitor + Fulvestrant Combination Tumor Regressions Observed at Low Doses Significant TGI as Monotherapy vs. KAT6A/Bi + fulvestrant • Lead DC demonstrates dose-dependent efficacy, drivi
Slide 17: KAT6A Selective Degraders Show Potential for Lower Bone Marrow Toxicity
KAT6A Selective Degraders Show Potential for Lower Bone Marrow Toxicity in Preclinical Models Compared to KAT6A/B Dual Inhibitors Dose Response of CFU-GM Neutrophils Day 5 Ex vivo and in vivo studies with KAT6A selective degraders show limited effects on neutrophils in contrast to dual KAT6A/B inhib
Slide 18: KAT6A Selective Degrader Program Summary
KAT6A Selective Degrader Program Summary • Prelude invented multiple first-in-class, highly selective KAT6A degraders which demonstrate favorable preclinical results • KAT6A degraders show potential to achieve best-in-class efficacy and ability to differentiate on safety and combinability early in c
Slide 19: Applying Targeted Protein Degradation to Next Generation Degrader Antibody Conjugates
Prelude is Applying Our Expertise in Targeted Protein Degradation to Advance The Next Generation of Degrader Antibody Conjugates (DACs) Traditional ADCs • Non-selective Genotoxic Payloads • Limited Payload Diversity • Broad Chemotherapy Liabilities • Resistance Emerging to Common Cytotoxic Payloads
Slide 20: Prelude's Degrader Payloads: Engineered to Improve Efficacy and Tolerability
Prelude’s Degrader Payloads: Engineered to Improve Efficacy, Tolerability and Developability Compared to Traditional Cytotoxic Payloads Prelude’s Degrader Payloads Have the Potential to Deliver Novel DACs with Improved Efficacy and Therapeutic Index
Slide 21: Mutated Calreticulin Represents a Promising Target for Next Generation DACs
Mutated Calreticulin (mCALR) Represents a Promising Target for Next Generation DACs CALR mutations are important in MPNs, associated with poor clinical prognosis and disease progression Mutant CALR is a neoantigen presented on the cell surface of malignant cells but not normal cells and is found in
Slide 22: CALR x SMARCA2/4 DACs Demonstrate Degradation and Cytotoxicity in CALR Mutant Cells
CALR x SMARCA2/4 DACs Demonstrate Robust and Selective Target Degradation and Cytotoxicity in CALR Mutant Cells and Robust Tumor Growth Inhibition In Vivo
Slide 23: Executive Summary
Executive Summary • Newly disclosed JAK2V617F mutant selective inhibitor program subject of a strategic option agreement with Incyte, with first disclosure at ASH 2025 • First-in-class KAT6A selective degrader program poised to enter the clinic in 2026 with clear path to differentiation in ER+ breas
Slide 24: Thank You
Thank You Contact Us: Robert Doody SVP, Investor Relations rdoody@preludetx.com
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