Prelude Therapeutics Incorporated · NASDAQ:PRLD
Prelude Therapeutics — Investor Presentation (January 2026)
25 slides from Prelude Therapeutics's investor presentation, Jan 9, 2026
Slide 1: Corporate Presentation January 2026
Corporate Presentation JANUARY 2026 Exhibit 99.1
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 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 and current
Slide 5: Prelude's Pipeline & Discovery Engine
PROGRAM POTENTIAL INDICATIONS DISCOVERY/ LEAD OPT. IND-ENABLING PHASE 1 PROGRAM INTEREST UPCOMING 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 mal
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 Represents an Expansive Opportunity
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: JAK2V617F 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 Study Design (Illustrative)
JAK2V617F Program1: Phase 1 Study Design (Illustrative) MPNs 2026 2027 2028 2029 Phase 1b/2 Expansion Phase 1 (MPNs) 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 ~50 hrPV, hrET & MF at Dose OBJECTIVE
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 a clinically validated mechanism in ER+ breast cancer
KAT6 is a clinically validated mechanism in ER+ breast cancer A KAT6A/B dual inhibitor is now in pivotal phase 3 trials in combination with fulvestrant, after progression on a CDK4/6 inhibitor1 Demonstrated compelling efficacy in post CDK4/6 inhibitor setting in a broad population of ER+ BC1 Clinica
Slide 15: 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 Dual Inhibition May Lead to More Bone Marrow Toxicity* KAT6A Amplification and Overexpression in Cancer Leads to Increased Activity 1 3
Slide 16: Our Lead KAT6A Selective Degrader Development Candidate
Our Lead KAT6A Selective Degrader Development Candidate Prelude Data on File Lead DC is a Potent KAT6A Degrader in Preclinical Models Absolute kinetic selectivity for 6A/6B (>1000-fold) Global proteomics demonstrates selective KAT6A degradation Excellent oral PK across species Compelling in vivo eff
Slide 17: Lead DC demonstrates dose-dependent efficacy and tumor regressions
Lead DC demonstrates dose-dependent efficacy, driving tumor regressions at low daily oral doses in preclinical models Well-tolerated with no observed body weight loss in preclinical models Human dose of 5-10 mg QD projected to provide required exposure for efficacy Our Lead DC Drives Tumor Regressio
Slide 18: 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 KAT6A selective degraders s
Slide 19: KAT6A Selective Degrader Program Summary
Prelude has discovered and developed 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 clinical development Lead
Slide 20: Applying Targeted Protein Degradation to Next Generation DACs
Prelude is Applying Our Expertise in Targeted Protein Degradation to Advance the Next Generation of Degrader Antibody Conjugates (DACs) Fu, Z., Li, S., Han, S. et al. Sig Transduct Target Ther 7, 93 (2022). Toxicity & Cross Resistance Efficacy Therapeutic Index Non-selective, Genotoxic Payloads Limi
Slide 21: Prelude's Degrader Payloads
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 22: Mutated Calreticulin Represents a Promising Target for 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 23: CALR x SMARCA2/4 DACs Demonstrate Selective Degradation and Cytotoxicity
CALR x SMARCA2/4 DACs Demonstrate Robust and Selective Target Degradation and Cytotoxicity in CALR Mutant Cells and Robust Tumor Growth Inhibition In Vivo >68x Ba/F3 CALRins5 Ba/F3 CALRWT 0 .05 0.5 1 10 SMARCA2 0 .05 0.5 1 10 GAPDH SMARCA4 CALR DAC µg/ml Degradation Assay, 48h Anti-proliferation Ass
Slide 24: Executive Summary
Executive Summary Newly disclosed JAK2V617F mutant selective inhibitor program advancing to Phase 1 study initiation in 1st half of 2026 1 First-in-class selective KAT6A selective degrader program on track to enter the clinic in 2026 with clear path to differentiation in ER+ breast cancer market Pre
Slide 25: Thank You
Thank You Contact Us: Robert Doody SVP, Investor Relations rdoody@preludetx.com
Prelude Therapeutics — Investor Presentation (January 2026) on 6ix