Prelude Therapeutics Incorporated · NASDAQ:PRLD
Prelude Therapeutics — Investor Presentation (September 2026)
34 slides from Prelude Therapeutics's investor presentation, Sep 10, 2026
Slide 1: Corporate Presentation September 2026
Corporate Presentation September 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: Patients Living with Cancer Deserve Better Therapies
Target first, modality flexible approach to cancer drug discovery focused on validated biologic pathways Fully resourced to deliver key data catalysts across multiple programs over the next 12-24 months 3 Patients Living with Cancer Deserve Better Therapies Our mission is to deliver practice-changin
Slide 4: 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 5: Advancing Multiple Differentiated Programs for Clinically Validated Targets
POTENTIAL INDICATIONS DISCOVERY IND-ENABLING PHASE 1 PROGRAM INTEREST ANTICIPATED MILESTONES KAT6A Selective Degraders HR+ breast cancer, other malignancies Phase 1 start 4Q 2026 JAK2V617F Mutant Selective JH2 Inhibitors VF+ Myeloproliferative Neoplasms (MPNs) (MF, PV, ET) Phase 1 Early Data 2027 mC
Slide 6: Three Key Programs With Data Catalysts Over the Next 12-24 Months
Three Key Programs With Data Catalysts Over the Next 12-24 Months JAK2V617F (PRT12396) Mutant Selective Inhibitor Potentially transformative JAK2V617F allosteric JH2 inhibitor designed to reduce mutant allele burden and modify the course of disease progression in patients with myeloproliferative neo
Slide 7: Patients With HR+/HER2- Breast Cancer Need Better Therapies
Patients With HR+/HER2- Breast Cancer Need Better Therapies 1. SEER Cancer Stats: Breast Cancer Subtypes, Global Data (EU5 only); NCCN Guidelines V5.2025 (accessed March 2026); Risk stratification varies based on guidelines and staging tools used; 2. Khatpe AS, et al., Cancers 2021. 3. Reinert T, et
Slide 8: Pfizer Validated KAT6 as a Target, but Showed the Limits of Dual A/B Inhibition
Pfizer Validated KAT6 as a Target, but Showed the Limits of Dual A/B Inhibition Limited clinical activity as monotherapy (5mg): 11.4% ORR; 3.3 mo mPFS Initial ORR/PFS in combo with fulvestrant (5mg, 500mg FUL): 37.2% ORR; 10.3 mo mPFS … with notable limitations 1,2: Neutropenia (Gr 3/4) 46% Dysgeusi
Slide 9: KAT6A Degradation May Be a Better Approach than KAT6A/B Dual Inhibition
Prelude AACR 2026 poster presentation (access here); Pfizer reference - Sharma S, et al., Discovery of a highly potent, selective, orally bioavailable inhibitor of KAT6A/B histone acetyltransferases with efficacy against KAT6A-high ER+ breast cancer. Cell Chemical Biology. 2023; 30(10):1191-1210.e20
Slide 10: PRT13722: Our First-in-Class KAT6A Selective Degrader Candidate
Prelude AACR 2026 poster presentation (access here); 1. Once-daily dosing projected based on preclinical PK and modeling; combinability based on preclinical data; 2. Mice harboring ZR-75-1 xenografts were treated with PRT13722; effects on tumor growth are shown; 3. Mice harboring T47-D xenografts we
Slide 11: PRT13722 Monotherapy Demonstrates Better Efficacy Head-to-Head Versus Prifetrastat
PRT13722 Monotherapy Demonstrates Better Efficacy Head-to-Head Versus Prifetrastat in Preclinical Studies Prelude AACR 2026 poster presentation (access here); mice harboring T47-D xenografts were treated with PRT13722 or a racemic mixture of PRT13722*; effects on tumor growth shown. # TGI, Tumor Gro
Slide 12: PRT13722 Completely Eradicates Tumors in Treatment Refractory PDX Models
PRT13722 Completely Eradicates Tumors in Treatment Refractory PDX Models: 100% Complete Response Rate as Monotherapy Prelude AACR 2026 poster presentation (access here); Prelude Data On File; Off-tx indicates treatment cessation HR+/HER2- CDK4/6 + ET Refractory In Vivo PDX (ST3164B) 100% of test ani
Slide 13: PRT13722 Lowers Bone-Marrow Toxicity Potential by Sparing KAT6B
Prelude Data on File; CFU-GM, Colony-Forming Unit-Granulocyte/Macrophage, myeloid progenitor cells found in bone marrow; LD, low dose; HD, high dose; CD, clinical dose *Study conducted with PRT13722 or a racemic mixture of PRT13722; Prelude AACR 2026 poster presentation (access here) PRT13722 Lowers
Slide 14: PRT13722 Shows Synergistic Potential in Combo with Current SoC Agents
Prelude AACR 2026 poster presentation (access here) PRT13722 Shows Synergistic Potential in Combo with Current SoC Agents ENDOCRINE THERAPY fulvestrant & oral SERDs ✓ Synergistic CDK4/6 INHIBITORS ribociclib, abemaciclib ✓ Synergistic PI3Kα INHIBITORS alpelisib, inavolisib ✓ Synergistic prifetrastat
Slide 15: Robust Phase 1 Designed to Show PRT13722 is in a Class of Its Own
Robust Phase 1 Designed to Show PRT13722 is in a Class of Its Own 1 2 3 2026 2027 2028 Phase 1 Dose Escalation - Monotherapy and Combinations IND cleared Ph 1 start 4Q 2026 HR+/HER2- BC (Monotherapy) Phase 1 Dose Escalation Mono & Combo Expansion Cohorts DL(n) (N=3-6) DL1 (N=3-6) DL2 (N=3-6) Mono, f
Slide 16: A New Backbone Therapy for HR+ BC Could Address a $40B+ Total Market
A New Backbone Therapy for HR+ BC Could Address a $40B+ Total Market Early-Stage Advanced / Metastatic Low Risk (60-70%) High Risk (30-40%) 1L 2L 3L+ $5-10B+ Potential peak sales (US/EU5) 1L–3L+ advanced BC only $40B+ Total addressable market (US/EU5) incl. neo/adjuvant use in early-stage disease Dr
Slide 17: Prelude's First-in-Class KAT6A Selective Degrader Program Summary
Prelude is advancing a highly selective oral KAT6A degrader (PRT13722) with potential to become a new backbone therapy in the treatment of HR+ breast cancer PRT13722 has potential to achieve more robust efficacy relative to KAT6A/B inhibitors as monotherapy or in combination with commonly used agent
Slide 18: Three Key Programs With Data Catalysts Over the Next 12-24 Months
Three Key Programs With Data Catalysts Over the Next 12-24 Months JAK2V617F (PRT12396) Mutant Selective Inhibitor Potentially transformative JAK2V617F allosteric JH2 inhibitor designed to reduce mutant allele burden and modify the course of disease progression in patients with myeloproliferative neo
Slide 19: Biomarker-Directed Therapy is the New Frontier in the Treatment of MPNs
DL Paz et al. Genetic basis and molecular profiling in myeloproliferative neoplasms. Blood (2023) 141 (16): 1909–1921. F. Passamonte et.al., Clinical Significance of JAK2 V617F mutant allele burden; Haematologica 2009 Jan;94(1):7–10; MPNs, myeloproliferative neoplasms; MF, myelofibrosis; PV, polycyt
Slide 20: Current JAK Inhibitors Do Not Selectively Target JAK2V617F+ Mutant Clones
Current JAK Inhibitors Do Not Selectively Target JAK2V617F+ Mutant Clones 1-4. Package Inserts; 5. Guglielmelli et al. Blood (2022) 140: 1788–1789. 6. Harrison et al. J.Clin Oncol. 2023; 41(19);3544 Molecular response is associated with improved patient outcomes and event-free survival (EFS).6 JAK2V
Slide 21: A JAK2V617F Mutant Selective Inhibitor Has Broad Potential in MPNs
Source: NCI SEER Database (accessed June 2026), Blood Cancer United (LLS) Facts & Figures. * Prevalence of V617F mutation in Primary Myelofibrosis (PMF); prevalence in post-PV/ET MF is 85-95%+. A JAK2V617F Mutant Selective Inhibitor Has Broad Potential in the Treatment of Myeloproliferative Neoplasm
Slide 22: Prelude Scientists Discovered the First Known JAK2 JH2 Deep Pocket Inhibitors
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 Prelude Data on
Slide 23: PRT12396: Our Lead JAK2V617F Mutant Selective JH2 Inhibitor
PRT12396: Our Lead JAK2V617F Mutant Selective JH2 Inhibitor *** p<0.001 by Mann-Whitney U test BaF3 model Prelude ASH Annual Meeting 2025 oral presentation (access here) Equivalent or better efficacy to ruxolitinib in preclinical in vivo models at well-tolerated doses PRT12396 has potential for impr
Slide 24: PRT12396: Designed to Overcome the Limitations of Current JAK Inhibitors
PRT12396: Designed to Overcome the Limitations of Current JAK Inhibitors * Dotted lines represent proliferation IC50 values from SET2 (VF) and UT-7 (WT) 7-day proliferation assay Prelude ASH Annual Meeting 2025 oral presentation (access here) SELECTIVITY Plasma exposures at efficacious doses remain
Slide 25: PRT12396: Phase 1 Study Now Enrolling MF and PV Cohorts in Parallel
PRT12396: Phase 1 Study Now Enrolling MF and PV Cohorts in Parallel MF 2026 2027 2028 Phase 1 Expansion Cohorts Phase 1 (enrolling MF & PV cohorts in parallel) Phase 1 Dose Escalation Expansion Cohorts DL(n) (N=3-6) DL1 (N=3-6) DL2 (N=3-6) Expansion in MF & PV at Dose OBJECTIVE CHR rate, durability
Slide 26: Option Agreement With Incyte Provides Significant Capital to Advance Pipeline
Exclusive option agreement with Incyte (announced November 2025) Option Agreement With Incyte Provides Significant Capital to Advance Pipeline
Slide 27: Three Key Programs With Data Catalysts Over the Next 12-24 Months
Three Key Programs With Data Catalysts Over the Next 12-24 Months JAK2V617F (PRT12396) Mutant Selective Inhibitor Potentially transformative JAK2V617F allosteric JH2 inhibitor designed to reduce mutant allele burden and modify the course of disease progression in patients with myeloproliferative neo
Slide 28: Mutated Calreticulin Represents a Promising Target for a Next Generation DAC
Sources: NCI SEER Database (accessed June 2026), Blood Cancer United (LLS) Facts & Figures; J.How et. al., Mutant calreticulin in myeloproliferative neoplasms, Blood (2019) 134 (25): 2242–2248; Tefferi A, et al. Type 1 versus Type 2 calreticulin mutations in essential thrombocythemia: a collaborativ
Slide 29: INCA989 Validated mCALR as a Target, Albeit with Notable Limitations
INCA989 Validated mCALR as a Target, Albeit with Notable Limitations 83% of patients achieved complete hematological response (CHR) at doses ≥ 400mg IV, with 47% durable CHR ≥12 weeks 52% and 31% of patients achieved >25% and >50% best mCALR variant allele frequency (VAF) reduction, respectively Gen
Slide 30: Degrader Antibody Conjugates Represent the Next Generation of ADCs
Degrader Antibody Conjugates (DACs) Represent the Next Generation of ADCs For a review of next generation ADC payloads, see Fu, Z., Li, S., Han, S. et al. Sig Transduct Target Ther 7, 93 (2022). Property Traditional ADC Precision DAC Potency Antibody Selectivity Payload Selectivity PD Marker - Paylo
Slide 31: mCALR-Targeted DACs Offer a Differentiated Approach to Eradicating CALR Mutant Clones
mCALR-Targeted DACs Offer a Differentiated Approach to Eradicating CALR Mutant Clones SMARCA2/4 Degrader Naked antibodies bind to the target impacting signaling and proliferation, but do not have the selective mutant cell killing potential of a DAC SMARCA2/4 degraders are highly active in mCALR MPN
Slide 32: Prelude is Advancing mCALR DACs Equipotent for Type 1 & 2 Mutations
Prelude is Advancing mCALR DACs Equipotent for Type 1 & 2 Mutations On Track to Nominate Development Candidate by YE 2026 >68x Selective Cytotoxicity in vitro Robust Tumor Growth Inhibition in vivo Fultang N., et al., EHA2025 Oral Abstract, 12 June 25; Discovery Of First-in-class Precision ADCs Targ
Slide 33: Executive Summary
Executive Summary First-in-class KAT6A selective degrader (PRT13722) on track to enter the clinic in the fourth quarter with potential to demonstrate differentiated efficacy and safety over KAT6A/B inhibitors JAK2V617F mutant selective inhibitor (PRT12396) IND cleared and Phase 1 study enrollment un
Slide 34: Thank You
Thank You Contact Us: Robert Doody SVP, Investor Relations rdoody@preludetx.com
Prelude Therapeutics — Investor Presentation (September 2026) on 6ix