Prelude Therapeutics Incorporated · NASDAQ:PRLD
Prelude Therapeutics — Investor Presentation (August 2025)
30 slides from Prelude Therapeutics's investor presentation, Aug 14, 2025
Slide 1: Corporate Presentation August 2025
Corporate Presentation August 2025 Exhibit 99.2
Slide 2: Forward Looking Statements
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 Pre
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-in-class science focused on areas of highest patient unmet need Draw on decades of experience and proven leadership to dr
Slide 4: Experienced Leadership Team With Proven Track Records in Precision Oncology
Kris Vaddi, PhD Chief Executive Officer Jane Huang M.D. President and Chief Medical 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, and Corporate Secre
Slide 5: Prelude's Precision Medicine Pipeline & Discovery Engine
Prelude’s Precision Medicine Pipeline & Discovery Engine PROGRAM POTENTIAL INDICATIONS DISCOVERY/ PRECLINICAL PHASE 1 PHASE 2/3 Oral SMARCA2 Degrader SMARCA4-mutated NSCLC & other cancers Oral KAT6A Degrader UPCOMING MILESTONES Lead DC Advancing IND Filing 1H 2026 First Interim Phase 1 Data YE 2025
Slide 6: Prelude's First-in-Class SMARCA2 Degrader Program
Prelude’s First-in-Class SMARCA2 Degrader Program Oral SMARCA2 Degrader (PRT7732) Distinct new chemical entity with PK supporting once-daily dosing Daily dosing enables ‘around the clock’ target engagement Phase I underway – now enrolling at dose level 7 (125mg) IV SMARCA2 Degrader (PRT3789) Proof-o
Slide 7: Targeting SMARCA4-deficient Cancers By Selectively Degrading SMARCA2
Patients with SMARCA4 mutations are not typically eligible for other targeted therapies Currently treated with standard of care chemotherapy or chemo-immunotherapy Targeting SMARCA4-deficient Cancers By Selectively Degrading SMARCA2 Pancreatic: 3% NSCLC: 10% Esophageal: 8% Gastric: 8% Endometrial: 1
Slide 8: Outcomes for Patients with SMARCA4-mutated NSCLC are Poor with Current Standard of Care
Outcomes for Patients with SMARCA4-mutated NSCLC are Poor with Current Standard of Care Alessi JV, et al. Clinicopathologic and genomic factors impacting efficacy of first-line chemoimmunotherapy in advanced non-small cell lung cancer (NSCLC). J Thorac Oncol. 2023 Feb 10:S1556-0864(23)00121-1. PMID:
Slide 9: Initial Proof-of-Concept Observed With PRT3789 Monotherapy
Data cutoff: 30 November 2024 and patients enrolled by 31 August 2024. GI, gastrointestinal; NSCLC, non-small cell lung cancer; SLD, sum of longest diameter. * Confirmed partial response; [1], class 1 mutation; [2], class 2 mutation. Initial Proof-of-Concept Observed With PRT3789 Monotherapy: Change
Slide 10: PRT3789 Can Be Safely Combined with Docetaxel
Data cutoff: 30 November 2024 and patients enrolled by 24 September 2024. ALT, alanine aminotransferase. a Patient had both docetaxel dose hold and dose reduction. Phase 1 Study Also Demonstrated That a SMARCA2 Selective Degrader (PRT3789) Can Be Safely Combined with Docetaxel Adverse Events, n (%)
Slide 11: Oral SMARCA2 Degrader Offers Distinct Advantages Over Inhibitor Approaches
A Highly Selective Oral SMARCA2 Degrader Offers Distinct Advantages Over Inhibitor Approaches Inhibitors Degraders Potency High Selectivity Extended PD Disruption of the SWI/SNF Complex Oral Bioavailability X X Early attempts at achieving both potency and selectivity with inhibitor approaches had ch
Slide 12: PRT7732 is Potent and Orally Bioavailable With Near-Absolute Selectivity for SMARCA2
PRT7732 is Potent and Orally Bioavailable With Near-Absolute Selectivity for SMARCA2 Near-absolute cellular selectivity for SMARCA2 vs SMARCA4 (>3000 fold) in HiBit cell lines and >1000-fold in cell proliferation assays and selective across the proteome Sub-nanomolar SMARCA2 degradation potency * Ba
Slide 13: PRT7732-01: Phase I Trial is Underway and Enrollment has Progressed Rapidly
PRT7732-01: Phase I Trial is Underway and Enrollment has Progressed Rapidly Now enrolling patients in dose cohort 7 (125 mg QD) No DLTs observed to date No Gr3+ related AEs, all other Gr3+ unrelated AEs associated with progression occurring contemporaneously First interim data update on safety, PK,
Slide 14: Prelude's Discovery Engine Continues to Deliver Novel Candidates
Prelude’s Discovery Engine Continues to Deliver Novel Candidates Oral KAT6A Selective Degrader First-in-class program with potential to advance the standard of care in ER+ breast cancer and other solid tumors Prelude’s Precision ADC Platform Jointly advancing first novel degrader antibody conjugate
Slide 15: High unmet need for novel modalities to treat advanced breast cancer
15 There is a high unmet need for novel modalities to treat advanced breast cancer & other solid tumors Pfizer’s KAT6A/B inhibitor has demonstrated early clinical PoC in ER+ breast cancer in combination with fulvestrant, albeit with potential for dose limiting neutropenia1 Selectively degrading KAT6
Slide 16: Early KAT6A Degraders Demonstrated Picomolar Potency and Excellent Selectivity
Prelude’s Early KAT6A Degraders Demonstrated Picomolar Potency and Excellent Selectivity Globally and Against KAT Family Members, Including KAT6B & KAT7 J. Carter et. al., Discovery of first-in-class potent and selective oral degraders of KAT6A that demonstrate anti-cancer activity in pre-clinical m
Slide 17: KAT6A degraders demonstrate superior efficacy to a KAT6A/B dual inhibitor
KAT6A degraders demonstrate superior efficacy to a KAT6A/B dual inhibitor at clinically relevant doses Deep regressions and complete response observed with a 3 mg/kg oral dose of PRT05A that was well-tolerated Deep regressions also achieved with highly selective KAT6A degrader (PRT04A); dose respons
Slide 18: CFU-GM Assay Data Demonstrate Potential Benefit of KAT6A Selective Degradation
CFU-GM Assay Data Demonstrate Potential Benefit of KAT6A Selective Degradation in Reducing Bone Marrow Toxicity and Lowering Neutropenia Risk KAT6A selective degrader KAT6A/B dual degrader KAT6A/Bi Key Takeaways: KAT6A selective degraders show potential for: Lower bone marrow toxicity vs. KAT6A/B du
Slide 19: Improved Tolerability and Lower Neutropenia Risk Confer Potential for Improved Combinability
Improved Tolerability and Lower Neutropenia Risk Confer Potential for Improved Combinability with Other Commonly Used Agents in Breast Cancer Average ZIP = 13.9, % viability shown Average ZIP = 12.5, % viability shown KAT6A Degrader + PI3K Inhibitor KAT6A Degrader + CDK4/6 Inhibitor One of Prelude’s
Slide 20: Advancing a First-in-Class Oral KAT6A Selective Degrader Development Candidate
Now Advancing a First-in-Class Oral KAT6A Selective Degrader Development Candidate Highly potent (picomolar) and highly selective for KAT6A Excellent oral bioavailability across species Complete regressions observed with in vivo efficacy models as monotherapy at low doses No activity in CFU-GM assay
Slide 21: Precision ADCs (or DACs) Represent the Next Generation of ADCs
Precision ADCs (or “DACs”) Represent the Next Generation of ADCs 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 Limited Payload Diversity Broad Chemotherapy Liabilities Resistance Emerging
Slide 22: Strategic Partnership with AbCellera to Enable First Precision ADCs
Prelude Established a Strategic Partnership with AbCellera in 2023 to Enable First Precision ADCs High Unmet Need & Opportunity Potential for Optimized Payload Potential for Optimized Antibody Initial proof-of-concept demonstrated with a novel, highly potent SMARCA2/4 dual degrader as a “Precision P
Slide 23: 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 Precision ADC Properties Efficacy Tolerability Developability Exceptional Potency (pM) Allows low DAR; Low aggregation Permeable Enable localized
Slide 24: Extensive Optimization Provided a Broad Library of SMARCA2/4 Dual Degrader Payloads
Extensive Optimization Provided a Broad Library of Both VHL- and CRBN-based SMARCA2/4 Dual Degrader Payloads for Testing Prelude designed and optimized a series of SMARCA degrader payloads aided by extensive SAR from our IV and Oral SMARCA2 selective degrader programs Picomolar potencies in HiBit, W
Slide 25: Prostate and Myeloid Cancer Cell Lines Highly Sensitive to SMARCA Degraders
Prostate and Myeloid Cancer Cell Lines are Among The Cancer Types Most Highly Sensitive to Prelude’s SMARCA Degraders Carter J., et al., 2024 EORTC-NCI-AACR Symposium Poster (http://www.preludetx.com/science/publications) Prelude tested multiple highly potent and selective SMARCA2/4 dual degraders a
Slide 26: Early Anti-PSMA SMARCA DACs Demonstrated Tumor Regressions
Early Anti-PSMA SMARCA DACs Demonstrated Tumor Regressions and Significantly Better Efficacy Compared to Traditional Anti-PSMA Cytotoxic ADC Anti-PSMA SMARCA DACs using Prelude’s 1st gen payloads demonstrated robust efficacy in vivo and were well-tolerated Anti-PSMA SMARCA DACs enable maximal target
Slide 27: Mutated Calreticulin (mCALR) Represents a Promising ADC Target
Mutated Calreticulin (mCALR) Represents a Promising ADC Target and Pathway to Potential Molecular Remission in Both MF and ET 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 SMARCA deg
Slide 28: CALR x SMARCA pADCs Demonstrate Robust Anti-Tumor Activity In Vivo
CALR x SMARCA pADCs Demonstrate Robust Anti-Tumor Activity In Vivo and Are Well-Tolerated CALR x SMARCA pADCs drive robust tumor growth inhibition in a TF-1 CALRdel52 subcutaneous xenograft model highlighting their potent in vivo anti-tumor activity CALR x SMARCA pADCs efficiently degrade SMARCA2/4
Slide 29: Our Focus is Continued Execution Across Strategic Priorities
Our Focus is Continued Execution Across Strategic Priorities PRT2527 CDK9 PROGRAM Selective CDK Inhibitor PRT2527 PRT7732 SMARCA2 Degrader Program Discovery Engine KAT6A & Precision ADCs IND filing for lead KAT6A degrader development candidate(s) Advance first Precision ADC candidate in partnership
Slide 30: Thank You
Thank You Contact Us: Robert Doody SVP, Investor Relations rdoody@preludetx.com
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