Prelude Therapeutics Incorporated · NASDAQ:PRLD
Prelude Therapeutics — Investor Presentation (March 2026)
26 slides from Prelude Therapeutics's investor presentation, Mar 10, 2026
Slide 1: Corporate Presentation March 2026
Corporate Presentation March 2026 Exhibit 99.2
Slide 2: Forward-looking statements
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 and clinical development activities for Prelude’s product candidates a
Slide 3: Mission to extend precision medicine to every cancer patient in need
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
Kris Vaddi, PhD Chief Executive Officer Andrew Combs, PhD Chief Chemistry Officer Sean Brusky, MBA Chief Business & Strategy Officer Peggy Scherle, PhD Chief Scientific Officer Bryant Lim, J.D. Chief Financial Officer, Chief Legal Officer, Secretary Dr. Victor Sandor, former CMO at Array BioPharma a
Slide 5: Prelude's Pipeline & Discovery Engine
PROGRAM POTENTIAL INDICATIONS DISCOVERY/ LEAD OPT. IND-ENABLING PHASE 1 PROGRAM INTEREST MILESTONES JAK2V617F Mutant Selective JH2 Inhibitors VF+ myeloproliferative neoplasms (MPNs) (MF, PV, ET) Phase 1 initiation anticipated in 2Q 2026 KAT6A Selective Degraders ER+ breast cancer, other malignancies
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 KAT6A Highly Selective Oral Degraders JAK2V617F Mutant Selective Inhibitors First-in-class KAT6A degraders, with absolute selectivity over KAT6B – a differenti
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 blood cel
Slide 8: JAK2V617F Mutant Selective Inhibitor: Expansive Opportunity in MPN
A JAK2V617F Mutant Selective Inhibitor Could Become a Disease Modifying Option for the Majority of MPN Patients and Represents an Expansive Opportunity Essential Thrombocythemia (ET) Polycythemia Vera (PV) JAK2 V617F Mutated ~95% JAK2 V617F Mutated ~60% CALR Mutated MPL mutation Nonmutated Nonmutate
Slide 9: First Known JAK2 Inhibitors Binding the 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 Prelude JAK2 JH2 Inhibitors Bind into the “Deep Pocket” Adjacent to V617F Mutation Allosteric JH2 Regulatory Domain vs Catalytic Domain
Slide 10: Mutant Selective Inhibitors Differentiated From 1st Generation JAK Inhibitors
Global sales of ruxolitinib (Jakafi® /Jakavi®) alone grew to over $4.5B in 20241,2 Continuing strong sales growth for ruxolitinib in PV First generation JAK inhibitors have delivered transformative efficacy for MF patients Highly effective at reducing symptoms and spleen size However, toxicities fro
Slide 11: JAK2V617F Program: Phase 1 Study Design (Illustrative)
JAK2V617F Program1: Phase 1 Study Design (Illustrative) MF 2026 2027 2028 2029 Phase 1 Expansion Cohorts Phase 1 (MF & hrPV) First Look at Spleen/Symptoms/CHR Mutant Allele Burden Phase 1a Dose Escalation Expansion Cohorts DL(n) (N=3-6) DL1 (N=3-6) DL2 (N=3-6) Expansion in hrPV & MF at Dose OBJECTIV
Slide 12: Option Agreement With Incyte Provides Significant Capital
Exclusive option agreement with Incyte (announced November 2025) Option Agreement With Incyte Provides Significant Capital to Further Advance Our JAK2V617F and KAT6A Programs
Slide 13: 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 KAT6A Highly Selective Oral Degraders JAK2V617F Mutant Selective Inhibitors First-in-class KAT6A degraders, with absolute selectivity over KAT6B – a differenti
Slide 14: KAT6 is an emerging, clinically-validated target in ER+ breast cancer
KAT6 is an emerging, clinically-validated target in ER+ breast cancer A KAT6A/B dual inhibitor (PF-07248144, prifetrestat) has initiated a pivotal phase 2/3 trial in combination with fulvestrant, after progression on a CDK4/6 inhibitor1 Limited monotherapy activity, but compelling efficacy in combo
Slide 15: KAT6 Landscape is Evolving, Most Pursuing Inhibitor Approaches
KAT6 Landscape is Evolving, But Most Others Are Pursuing Inhibitor Approaches Pfizer Clinical Candidate PF-07248144 (prifetrastat) Clinical PoC in combination with fulvestrant for ER+ BC Advancing to Ph2/3 registrational trial Olema, Menarini and BeOne Starting Ph1 with chemotypes very similar to Pf
Slide 16: Selective KAT6A Degradation Represents a Differentiated Approach
Early-stage ER+ BC (adjuvant, neo-adjuvant) Selective KAT6A Degradation Represents a Differentiated Approach Versus KAT6A/B/(7) Inhibition With Significantly Broader Commercial Potential KAT6A/B/(7) Inhibitors Pfizer, BeOne, Olema, Ideaya, Menarini, Others 1L ER+/HER2- mBC 2L/3L+ r/r ER+/HER2- mBC C
Slide 17: PRT13722: Our Lead KAT6A Selective Degrader Development Candidate
PRT13722: Our Lead KAT6A Selective Degrader Development Candidate Prelude Data on File PRT13722: Highly Potent KAT6A Degrader in Preclinical Models Absolute kinetic selectivity for KAT6A over KAT6B (>1000-fold) Global proteomics demonstrates highly selective KAT6A degradation Excellent oral PK acros
Slide 18: PRT13722 demonstrates dose-dependent efficacy in preclinical models
PRT13722 demonstrates dose-dependent efficacy, driving tumor regressions at low oral doses in preclinical models Well-tolerated with no observed body weight loss in preclinical models PRT13722 Monotherapy Drives Tumor Regressions in the Challenging T47-D Breast Cancer Model with Improved Efficacy Ov
Slide 19: 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 Neutrophils Day 5 Dose Response of CFU-GM Low Dose High Dose High Dose Low Dose KAT6A degrader KAT6A degrader Ex vivo and in vivo studies with early KAT6A selective degra
Slide 20: KAT6A Selective Degrader Program Summary
Prelude is advancing a first-in-class, highly selective KAT6A degrader (PRT13722) with broad potential to become a new backbone therapy in the treatment of ER+ breast cancer PRT13722 has potential to achieve best-in-class efficacy relative to dual KAT6A/B inhibitors PRT13722 has completed dosing in
Slide 21: Degrader Antibody Conjugates Represent the Next Generation of ADCs
Degrader Antibody Conjugates (DACs) Represent the Next Generation of ADCs For a review of ADCs, see Fu, Z., Li, S., Han, S. et al. Sig Transduct Target Ther 7, 93 (2022). Precision DACs enable improved selectivity in two ways Antibodies target tumor-specific cell surface antigens sparing healthy cel
Slide 22: 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 Payload Rationale DAC Properties Prelude Degrader Payload-Linkers Efficacy Tolerability Developability Exceptional Potency (pM) Allows low DAR; Catalytic effect SMA
Slide 23: Mutated Calreticulin Represents a Promising Target for Next Generation DACs
Mutated Calreticulin (mCALR) Represents a Promising Target for Next Generation DACs Mutant CALR is a neoantigen presented on the cell surface of malignant cells but not normal cells and is found in 25-35% of patients with Myelofibrosis (MF) and ET SMARCA2/4 and CDK9 degraders are both highly active
Slide 24: CALR x SMARCA2/4 DACs Demonstrate Robust Tumor Growth Inhibition
CALR x SMARCA2/4 DACs Demonstrate Robust and Selective Tumor Growth Inhibition and Improved Potency vs. Antibody Alone in CALR Mutant Cells >68x Selective Cytotoxicity in vitro SMARCA2/4 Degrader Robust Tumor Growth Inhibition in vivo Fultang N., et al., EHA2025 Oral Abstract, 12 June 25; Discovery
Slide 25: Executive Summary
Executive Summary Lead JAK2V617F mutant selective inhibitor (PRT12396) IND accepted and on track for Phase 1 study initiation in 2Q 20261 First-in-class KAT6A selective degrader (PRT13722) on track to enter the clinic in 2026 with clear path to differentiation in ER+ breast cancer market Novel appro
Slide 26: Thank You
Thank You Contact Us: Robert Doody SVP, Investor Relations rdoody@preludetx.com
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