Prelude Therapeutics Incorporated · NASDAQ:PRLD
Prelude Therapeutics — Investor Presentation (May 2025)
42 slides from Prelude Therapeutics's investor presentation, May 6, 2025
Slide 1: Corporate Presentation May 2025 Update
Corporate Presentation May 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 Oral KAT6A Degrader Monotherapy Update – 2H 202
Slide 6: Prelude's First-in-Class SMARCA2 Degraders
Prelude’s First-in-Class SMARCA2 Degraders + Lead IV SMARCA2 Degrader (PRT3789) First-in-class, novel biology, leading investigators engaged Proof-of-concept established in Phase I dose escalation Confirmed responses in NSCLC and EC/GC as monotherapy Oral SMARCA2 Degrader (PRT7732)
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 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 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: 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 candidates requiring extensive lead
Slide 11: PRT3789: Highly Potent SMARCA2 Degrader with >1000-fold Selectivity
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
Data cutoff: 30 November 2024 and patients enrolled by 24 September 2024. VUS, variant of uncertain significance. PRT3789-01 (Combination): Demographics Docetaxel + PRT3789 Characteristics Patients (N=11) Age, years Median 65 Sex, n (%) Male 8 (72.7) Female 3 (27.3) Prior lines of systemic anticance
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: SMARCA2 Degraders Currently Advancing In Parallel
Prelude’s First-in-Class SMARCA2 Degraders Currently Advancing In Parallel + Lead IV 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
Slide 23: Highly Selective Oral SMARCA2 Degrader Offers Advantages Over Inhibitors
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
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 Underway and Enrollment Progressing Rapidly
PRT7732-01: Phase I Trial is Underway and Enrollment is Progressing Rapidly As of April 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 First interim data update anticipated
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 to decision on best path forward for one or both programs Further assess activity in Class 1 (LOF) vs. Class 2 patients across different
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: 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 SoC in ER+ breast cancer and other solid tumors Precision ADC Platform & First Development Candidate First novel degrader antibody conjugate (“DAC”) fro
Slide 29: Advancing the Industry's First Oral KAT6A Selective Degraders
Prelude is Advancing the Industry’s First* Oral KAT6A Selective Degraders 29 There is a high unmet need for novel modalities to treat advanced breast cancer & other solid tumors KAT6A is part of the 8p11 amplicon and histone acetyltransferase (HAT) complex which regulates the expression of ER & PR R
Slide 30: KAT6A Degraders Demonstrate Picomolar Potency and Excellent Selectivity
Prelude’s KAT6A Degraders Demonstrate 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 models,
Slide 31: 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 32: CFU-GM Assay Data Demonstrate Potential Reduction in Bone Marrow Toxicity
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 33: Improved Tolerability and Lower Neutropenia Risk Confer 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 34: KAT6A Selective Degrader Lead Candidate Profile and Next Steps
KAT6A Selective Degrader Lead Candidate Profile Highly potent (picomolar) and highly selective Excellent oral bioavailability across species Regressions observed in in vivo efficacy models No activity in CFU assay for BM toxicity Studies in progress In vivo PK/PD and efficacy studies In vivo bone ma
Slide 35: Precision ADCs (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 36: 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 37: Library of Ultra Potent SMARCA2/4 Degrader Payloads
Extensive Optimization Provided a Library Ultra Potent SMARCA2/4 Degrader Payloads Prelude optimized a range of SMARCA2/4 payloads aided by extensive SAR from our SMARCA discovery programs Picomolar potencies in HiBit, Western and Proliferation assays are essential for delivering highly efficacious
Slide 38: SMARCA2/4 Dual Degraders as Differentiated Payloads in Prostate Cancer
SMARCA2 and SMARCA4 are the core ATPase catalytic subunits of the SWI/SNF chromatin remodeling complex required for function The SWI/SNF complex is dysregulated in prostate cancer leading to abnormal activation of AR signaling pathways promoting uncontrolled cell growth SMARCA2/4 dual degraders decr
Slide 39: Early Anti-PSMA SMARCA2/4 DACs Demonstrated Tumor Regressions
Early Anti-PSMA SMARCA2/4 DACs Demonstrated Tumor Regressions and Significantly Better Efficacy Compared to Traditional Anti-PSMA Cytotoxic ADC Anti-PSMA SMARCA2/4 DACs using Prelude’s 1st gen payloads demonstrated robust efficacy in vivo and were well-tolerated SMARCA2/4 DACs enable maximal target
Slide 40: Value Proposition in the Emerging Degrader Antibody Conjugate Field
Prelude’s Value Proposition in the Emerging Degrader Antibody Conjugate 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, an
Slide 41: 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 42: Thank You
Thank You Contact Us: Robert Doody SVP, Investor Relations rdoody@preludetx.com
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