Prelude Therapeutics Incorporated · NASDAQ:PRLD
Prelude Therapeutics — Investor Presentation (May 2026)
27 slides from Prelude Therapeutics's investor presentation, May 12, 2026
Slide 1: Corporate Presentation May 2026
Corporate Presentation May 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: Experienced Leadership Team With Proven Track Record
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 Experienced Leadership Team With Proven Track Reco
Slide 4: Prelude's Pipeline & Discovery Engine
PROGRAM POTENTIAL INDICATIONS DISCOVERY IND-ENABLING PHASE 1 PROGRAM INTEREST ANTICIPATED MILESTONES JAK2V617F Mutant Selective JH2 Inhibitors VF+ myeloproliferative neoplasms (MPNs) (MF, PV, ET) Phase 1 now enrolling KAT6A Selective Degraders ER+ breast cancer, other malignancies Prelude wholly own
Slide 5: Our Investment Thesis Centers on Advancing Highly Differentiated Approaches
Our Investment Thesis Centers on Advancing Highly Differentiated Approaches to Clinically Validated Targets JAK2V617F (PRT12396) Mutant Selective Inhibitors Potentially transformative JAK2V617F allosteric JH2 inhibitor with potential to reduce mutant allele burden and modify the course of disease pr
Slide 6: 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 7: Prelude Scientists Discovered 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 JH1 Catalytic Domain Confidential
Slide 8: PRT12396 is a JAK2V617F Mutant Selective JH2 Inhibitor
PRT12396 is a JAK2V617F Mutant Selective JH2 Inhibitor with Disease Modifying Potential in MPNs *** p<0.001 by Mann-Whitney U test >200X selectivity over JAK1 and TYK2 and clean profile in KinomeSCAN™ panel of >450 kinases Selective anti-proliferative effects in JAK2VF MPN cells with minimal impact
Slide 9: PRT12396 Demonstrates ~10X Therapeutic Window In Vivo
No evidence of WT JAK2 inhibition in 2-week rat toxicology study at low and mid doses that provide efficacious exposures Reduction in neutrophils and reticulocytes observed only at high dose, consistent with plasma exposure approaching WT JAK2 IC50 AUC exposures required for efficacy are 10X lower t
Slide 10: PRT12396 Phase 1 Study in MF and PV Now Enrolling
PRT12396 – Phase 1 Study in MF and PV Cohorts in Parallel – Now Enrolling IND Cleared in January 2026 MF 2026 2027 2028 2029 Phase 1 Expansion Cohorts Phase 1 (MF & PV) 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=
Slide 11: Option Agreement With Incyte
Exclusive option agreement with Incyte (announced November 2025) Option Agreement With Incyte Provides Significant Capital to Further Advance Our JAK2V617F and KAT6A Programs
Slide 12: Our Investment Thesis Centers on Advancing Highly Differentiated Approaches
Our Investment Thesis Centers on Advancing Highly Differentiated Approaches to Clinically Validated Targets JAK2V617F (PRT12396) Mutant Selective Inhibitors Potentially transformative JAK2V617F allosteric JH2 inhibitor with potential to reduce mutant allele burden and modify the course of disease pr
Slide 13: Selective KAT6A Degradation Could Represent a Differentiated Approach
Selective KAT6A Degradation Could Represent a Differentiated Approach Versus KAT6A/B/(7) Inhibition With Potential for Broader Application Early-stage ER+ BC (adjuvant, neo-adjuvant) KAT6A/B/(7) Inhibitors Pfizer, BeOne, Olema, Ideaya, Menarini, Others 1L ER+/HER2- mBC 2L/3L+ ER+/HER2- mBC Current S
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, prifetrastat 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 E
Slide 15: KAT6A: An Emerging Target in ER+/HER2- Breast Cancer
KAT6A: An Emerging Target in the Treatment of ER+/HER2- Breast Cancer 1 - White J, et al. Histone lysine acetyltransferase inhibitors: an emerging class of drugs for cancer therapy. Trends Pharmacol Sci 45 (3): 243-254 (2024). 2 - Sharma S, et al. Discovery of a highly potent, selective, orally bioa
Slide 16: PRT13722: Our KAT6A Selective Degrader Development Candidate
PRT13722: Our KAT6A Selective Degrader Development Candidate Absolute selectivity for KAT6A over KAT6B (>1000-fold) based on both degrader kinetics and proteomics Excellent oral PK across species enabling once-daily oral dosing Compelling in vivo efficacy as monotherapy in ER+ BC models, both KAT6A
Slide 17: PRT13722 Monotherapy Drives Durable Tumor Regressions
Well-tolerated over treatment duration of 80 days with no observed body weight loss in animals PRT13722 compared to prifetrastat with >50-fold lower AUC at efficacious doses PRT13722 Monotherapy Drives Durable Tumor Regressions in the More Challenging T47-D Model with Improved Efficacy Over prifetra
Slide 18: PRT13722 Monotherapy Eradicates Tumors in Post-Tamoxifen PDX
PRT13722 achieved 100% complete response as a monotherapy in ER+/HER2- xenografts derived from a patient with recurrent disease following treatment with chemotherapy and tamoxifen Responses persisted following cessation of treatment No significant body weight loss observed in animals at either dose
Slide 19: PRT13722 Demonstrates Potential for Lower Bone Marrow Toxicity
PRT13722 Demonstrates Potential for Lower Bone Marrow Toxicity in Preclinical Models Compared to KAT6A/B Dual Inhibitors Ex Vivo Dose Response of CFU-GM LD KAT6A degrader KAT6A selective degraders show limited effects on neutrophils in contrast to dual KAT6A/B inhibitors, supporting potential for im
Slide 20: PRT13722 Demonstrates Synergistic Potential in Combination With SoC Agents
PRT13722 Demonstrates Synergistic Potential in Combination with Current SoC Agents (ET, CDK4/6i, PI3Kαi) In Vivo Deeper monotherapy and combination efficacy H2H vs. prifetrastat at clinical doses Excellent in vivo efficacy in combination with fulvestrant (ET), alpelisib (PI3Kαi) and abemaciclib (CDK
Slide 21: KAT6A Selective Degrader Program Summary
Prelude is advancing a potenial first-in-class, highly selective oral KAT6A degrader (PRT13722) with potential to become a new backbone therapy in the treatment of ER+/HER2- breast cancer PRT13722 has potential to achieve more robust efficacy relative to KAT6A/B/(7) inhibitors PRT13722 was well-tole
Slide 22: Our Investment Thesis Centers on Advancing Highly Differentiated Approaches
Our Investment Thesis Centers on Advancing Highly Differentiated Approaches to Clinically Validated Targets JAK2V617F (PRT12396) Mutant Selective Inhibitors Potentially transformative JAK2V617F allosteric JH2 inhibitor with potential to reduce mutant allele burden and modify the course of disease pr
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 degraders are highly active in CALR mutate
Slide 24: Precision Degrader Antibody Conjugates Represent Next Generation ADCs
Precision Degrader Antibody Conjugates (pDACs) Represent Next Generation 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
Slide 25: Prelude Discovered mCALR x SMARCA2/4 DACs
Prelude Discovered mCALR x SMARCA2/4 DACs With Robust and Selective in vitro and in vivo Activity and ~100x Improved Potency 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; Disc
Slide 26: Executive Summary
Executive Summary Lead JAK2V617F mutant selective inhibitor (PRT12396) IND cleared and Phase 1 study enrollment underway1 Potentially first-in-class KAT6A selective degrader (PRT13722) on track to enter the clinic in 2026 with a path to differentiation in ER+/HER2- breast cancer market Novel approac
Slide 27: Thank You
Thank You Contact Us: Robert Doody SVP, Investor Relations rdoody@preludetx.com
Prelude Therapeutics — Investor Presentation (May 2026) on 6ix