Prelude Therapeutics Incorporated · NASDAQ:PRLD
Prelude Therapeutics — Investor Presentation (March 2025)
36 slides from Prelude Therapeutics's investor presentation, Mar 10, 2025
Slide 1: Corporate Presentation March 2025 Update
Corporate Presentation March 2025 Update 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 Lead SMARCA2 Degrader (IV) SMARCA4-mutated NSCLC & other cancers Oral SMARCA2 Degrader SMARCA4-mutated NSCLC & other cancers Precision ADCs SMARCA2/4 Degrader Payload Monot
Slide 6: Developing a First-in-Class Portfolio of SMARCA-Targeted Precision Medicines
Developing a First-in-Class Portfolio of SMARCA-Targeted Precision Medicines SMARCA - DACs + Lead SMARCA2 Degrader (PRT3789) Oral SMARCA2 Degrader (PRT7732) Precision ADCs with SMARCA2/4 Degrader Payload
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: SMARCA4 Mutations are Mostly Non-Overlapping with Other Driver Oncogenes
SMARCA4 Mutations are Mostly Non-Overlapping with Other Driver Oncogenes Schoenfeld et al. Clin Cancer Res. (2020); 26(21):5701-5708. Most Frequent Co-Occurring Mutations Distribution of SMARCA4 Mutation by Commonly Altered Gene Subgroup
Slide 9: 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 10: Prelude is Advancing Parallel SMARCA2 Degrader Programs in the Clinic
Prelude is Advancing Parallel SMARCA2 Degrader Programs in the Clinic Selectivity Achieved With Both VHL- and CRBN-based Degraders IV Candidate - VHL-TPD provided an expedited path to potential clinical development with QW dosing Oral Candidate - CRBN-TPD provided oral candidates, but required exten
Slide 11: PRT3789: A Highly Potent SMARCA2 Degrader with >1000-fold Selectivity Over SMARCA4
PRT3789: A Highly Potent SMARCA2 Degrader with >1000-fold Selectivity Over SMARCA4 Hulse et al. Cancer Res. (2022); 82 (12_Suppl) :3263. AACR 2022 Poster (http://www.preludetx.com/science/publications) Highly selective for SMARCA2 vs SMARCA4 (>1000 fold) and selective across the proteome Preclinical
Slide 12: PRT3789-01 (Monotherapy): Study Schema and Enrollment
Data cutoff: 30 November 2024 and patients enrolled by 31 August 2024. LOF, loss of function; NSCLC, non-small cell lung cancer. PRT3789-01 (Monotherapy): Study Schema and Enrollment Most recent data presented at 2025 JSMO Annual Meeting (Data cutoff: 30 November 2024) Monotherapy Dose-Escalation Co
Slide 13: PRT3789-01 (Monotherapy): Demographics and Disease Characteristics
Data cutoff: 30 November 2024 and patients enrolled by 31 August 2024. IHC, immunohistochemistry; VUS, variant of uncertain significance. PRT3789-01 (Monotherapy): Demographics and Disease Characteristics Characteristics Patients (N=69) Age, years Median 62 Sex, n (%) Male 37 (53.6) Female 32 (46.4)
Slide 14: PRT3789-01 (Monotherapy): Summary of Adverse Events
Data cutoff: 30 November 2024 and patients enrolled by 31 August 2024. ALT, alanine aminotransferase; AST, aspartate aminotransferase; CTCAE, common terminology criteria for adverse events; TEAE, treatment emergent adverse events. PRT3789-01 (Monotherapy): Summary of Adverse Events Adverse Events, n
Slide 15: PRT3789-01 (Monotherapy): Pharmacokinetics and Pharmacodynamics
Data cutoff: 30 November 2024 and patients enrolled by 31 August 2024. AUC, area under the curve over 1 week; C, cycle; D, day; DC50, half-maximal degradation concentration; PBMC, peripheral blood mononuclear cells. PRT3789-01 (Monotherapy): Pharmacokinetics and Pharmacodynamics Target Engagement Co
Slide 16: Change in Tumor Burden in Patients With NSCLC or Upper GI Cancer
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. PRT3789-01 (Monotherapy): Change in Tumor Burden in Patients With
Slide 17: Duration of Treatment in Patients With Class 1 Mutation
Data cutoff: 30 November 2024 and patients enrolled by 31 August 2024. GI, gastrointestinal; NSCLC, non-small cell lung cancer; PD, progressive disease; PR, partial response; SD, stable disease. # Patients with Upper Gi cancer (esophageal cancer or gastric cancer). PRT3789-01 (Monotherapy): Duration
Slide 18: Updated Activity in Lung & Upper GI Patients with Class 1 Mutations
Data cutoff as of 30 Nov 2024; patients dosed as of August 31, 2024 PRT3789-01 (Monotherapy): Updated Activity in Lung & Upper GI Patients with Class 1 Mutations Best Overall Response PRT3789 doses <283 mg (N=19) PRT3789 doses ≥283 mg (N=13) Partial Response (PR) 10.5% (2) 23.1% (3) Stable Disease (
Slide 19: PRT3789-01 (Combination): Study Schema and Enrollment
Data cutoff: 30 November 2024 and patients enrolled by 24 September 2024. LOF, loss of function; NSCLC, non-small cell lung cancer. PRT3789-01 (Combination): Study Schema and Enrollment Docetaxel + PRT3789 Dose-Escalation Cohorts Backfill Cohorts Eligibility criteria Any solid tumor Any SMARCA4 muta
Slide 20: PRT3789-01 (Combination): Demographics and Disease Characteristics
Data cutoff: 30 November 2024 and patients enrolled by 24 September 2024. VUS, variant of uncertain significance. PRT3789-01 (Combination): Demographics and Disease Characteristics Docetaxel + PRT3789 Characteristics Patients (N=11) Age, years Median 65 Sex, n (%) Male 8 (72.7) Female 3 (27.3) Prior
Slide 21: PRT3789-01 (Combination): Adverse Events
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. PRT3789-01 (Combination): Adverse Events Docetaxel + PRT3789 Adverse Events, n (%) PRT3789 + Docetaxel (N=11) Any adverse event 11 (100.
Slide 22: Prelude's First-in-Class Oral SMARCA2 Degrader Has Several Advantages
Prelude’s First-in-Class Oral SMARCA2 Degrader Has Several Advantages + Lead SMARCA2 Degrader (PRT3789) Oral SMARCA2 Degrader (PRT7732) Distinct new chemical entity with PK supporting once-daily dosing Potential to expand patient access and provide optionality Phase I underway and enrollment proceed
Slide 23: 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 24: 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 25: PRT7732-01: Phase I Trial is Underway and Enrollment is Progressing Rapidly
PRT7732-01: Phase I Trial is Underway and Enrollment is Progressing Rapidly As of March 2025, multiple sites are activated and enrollment is progressing ahead of plan No dose limiting adverse events or safety signals observed with initial patient cohorts to date Interim data update anticipated in th
Slide 26: What's Next for Both PRT3789 and PRT7732?
LOF = “Loss-of-function” What’s Next for Both PRT3789 and PRT7732? ‘3789 Monotherapy ‘7732 Dose Escalation SMARCA2 Program Priorities: Advance both ‘3789 and ‘7732 towards potential registrational trials, in parallel Further assess activity in Class 1 (LOF) vs. Class 2 patients across different tumo
Slide 27: PRT3789 and PRT7732 Address Distinct Patient Populations With High Unmet Need
PRT3789 and PRT7732 Address Distinct Patient Populations With High Unmet Need ~195,000 pts/year Up to 19,500 SMARCA4-mutated STAGE IV, First Line ~130,000 pts/year Up to 13,000 SMARCA4-mutated STAGE IV, 2L+ (R/R, Previously Treated) + US & EU5 only (2030 proj.): 1 GlobalData (SEER), Earlier Stage (I
Slide 28: Precision ADCs Further Expand Our Portfolio of SMARCA-Targeted Medicines
Precision ADCs Further Expand Our Portfolio of SMARCA-Targeted Medicines Precision ADCs with SMARCA2/4 Degrader Payload “DACs” represent the next generation of ADCs Potential for improved efficacy and safety over traditional ADCs Activity independent of SMARCA4 mutation status (broad reach) SMARCA -
Slide 29: 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 30: 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 We disclosed first data at ENA 2024 describing preclinical proof-of-concept using a novel, highly potent SM
Slide 31: Prostate and Myeloid Cancer Cell Lines are Highly Sensitive to SMARCA2/4 Dual Degraders
Prostate and Myeloid Cancer Cell Lines are Highly Sensitive to Prelude’s SMARCA2/4 Dual Degraders Carter J., et al., 2024 EORTC-NCI-AACR Symposium Poster (http://www.preludetx.com/science/publications) Prelude has optimized multiple highly potent and selective SMARCA2/4 dual degraders for use as nov
Slide 32: Anti-PSMA SMARCA2/4 DACs Demonstrated Tumor Regressions and Better Efficacy
Anti-PSMA SMARCA2/4 DACs Demonstrated Tumor Regressions and Significantly Better Efficacy Compared to PSMA-Targeted Cytotoxic ADCs Anti-PSMA SMARCA2/4 DACs using Prelude’s 1st gen payloads demonstrated robust target engagement and antigen-dependent efficacy in xenograft models while being well-toler
Slide 33: Extensive Optimization Provided a Library of SMARCA2/4 Degrader Payloads
Extensive Optimization Provided a Library of VHL- and CRBN-based SMARCA2/4 Degrader Payloads Prelude has since optimized our series of SMARCA2/4 payloads aided by extensive SAR from our SMARCA discovery programs Picomolar potencies in HiBit, Western and Proliferation assays are essential for deliver
Slide 34: Prelude's Value Proposition in the Emerging ADC / DAC Field
Prelude’s Value Proposition in the Emerging ADC / DAC Field Precision ADC Technology Platform Already Built Library of novel degraders as potential payloads and in-house conjugation expertise Full suite of assays and processes established for payload discovery, target selection, and ADC / DAC optimi
Slide 35: In 2025 Our Focus is Continued Execution Across Strategic Priorities
In 2025 Our Focus is Continued Execution Across Strategic Priorities PRT2527 CDK9 PROGRAM Report Phase 1 monotherapy clinical results Report Phase 1 docetaxel combination interim data PRT3789 Lead IV SMARCA2 Degrader Selective CDK Inhibitor PRT2527 Report first Phase 1 interim data (Safety, PK/PD, C
Slide 36: Thank You
Thank You Contact Us: Robert Doody SVP, Investor Relations rdoody@preludetx.com
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