Slide 1: PRT3789 Phase 1 Interim Clinical Data Update from 2024 ESMO Congress
PRT3789 Phase 1 Interim Clinical Data Update from 2024 ESMO Congress 13 September 2024 Investor Presentation 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: Opening Remarks
Kris Vaddi, Ph.D., CEO Prelude Therapeutics Incorporated Opening Remarks
Slide 4: 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- or best-in-class and anchor to patient unmet need Draw on decades of experience and proven leadership to drive innovatio
Slide 5: Industry Leading Portfolio of SMARCA-Targeted Precision Medicines
Developing an Industry Leading Portfolio of SMARCA-Targeted Precision Medicines SMARCA - DACs + Lead SMARCA2 Degrader (PRT3789) Oral SMARCA2 Degrader (PRT7732) Precision ADCs with SMARCA2/4 Degrader Payload
Slide 6: PRT3789 Overview and Phase 1 Interim Data
Dr. Jane Huang, President & Chief Medical Officer Prelude Therapeutics Incorporated A Phase 1 Trial of PRT3789, a First-in-Class SMARCA2 Degrader in Patients with Advanced Solid Tumors With a SMARCA4 Mutation Guo, R. et. al., ESMO Congress, 13 Sept 2024 PRT3789 Overview and Phase 1 Interim Data
Slide 7: Expert Perspective on SMARCA4-mutated Cancer
Dr. Timothy Yap, University of Texas MD Anderson Cancer Center Investigator on PRT3789-01: A Phase 1 Trial of PRT3789, a First-in-Class SMARCA2 Degrader in Patients with Advanced Solid Tumors With a SMARCA4 Mutation Expert Perspective on SMARCA4-mutated Cancer
Slide 8: Targeting SMARCA4-mutated Cancer 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-mutated Cancer By Selectively Degrading SMARCA2 Pancreatic: 3% NSCLC: 10% Esophageal: 8% Gastric: 8% Endometrial: 13%
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. doi:
Slide 10: PRT3789: 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: https://preludetx.com/wp-content/uploads/2022/05/Prelude_AACR_Hulse-SMARCA2-FINAL-21Mar2022.pdf Highly selective for SMARCA2 vs SMARCA4 (>1000 fold) and
Slide 11: PRT3789-01: Study Schema and Enrollment
LOF, loss of function; NSCLC, non-small cell lung cancer PRT3789-01: Study Schema and Enrollment Dose Escalation Cohorts Any Solid Tumor Any SMARCA4 Mutation Evaluable Disease Backfill Cohorts Enriched NSCLC LOF SMARCA4 Mutation Measurable Disease n=2 n=5 n=6 n=8 24 mg n=4 48 mg n=7 80 mg n=5 120 mg
Slide 12: PRT3789-01: Demographics and Disease Characteristics
65 patients were safety evaluable Primary tumor type was NSCLC (n = 34) patients along with a range of other solid tumors 34 patients had Class 1 loss of function mutations and additional 7 patients had loss of SMARCA4 protein by IHC PRT3789-01: Demographics and Disease Characteristics Guo, R. et al
Slide 13: PRT3789-01: Patient Disposition
PRT3789-01: Patient Disposition As of the data cutoff, 21.5% patients remained on treatment Only one patient discontinued treatment due to an adverse event, considered unrelated to study drug Data cutoff: 05 August 2024 Guo, R. et al., ESMO Congress, 13 Sept 2024
Slide 14: PRT3789-01: Summary of Adverse Events
PRT3789-01: Summary of Adverse Events 65 patients were safety evaluable PRT3789 was generally well tolerated; no drug related SAEs or dose limiting toxicities to date Of all adverse events, nausea, decreased appetite and fatigue had the highest incidence Guo, R. et al., ESMO Congress, 13 Sept 2024 D
Slide 15: PRT3789-01: Phase 1 Interim PK/PD Findings
PRT3789-01: Phase 1 Interim PK/PD Findings As expected with a potent degrader, the observed pharmacodynamic effect was more prolonged than pharmacokinetic half-life Increasing doses showed deeper and more prolonged SMARCA2 degradation in the peripheral blood monocytes (PBMCs) of patients PRT3789 sho
Slide 16: PRT3789-01: Phase 1 Interim Clinical Activity
PRT3789-01: Phase 1 Interim Clinical Activity Positive correlation observed between tumor shrinkage and a higher level of sustained SMARCA2 degradation Enrollment is now into dose cohort 9 (500 mg QW) Of the 26 NSCLC or esophageal patients with at least one post baseline scan who were evaluable for
Slide 17: PRT3789-01: Phase 1 Interim Clinical Activity
PRT3789-01: Phase 1 Interim Clinical Activity Guo, R. et al., ESMO Congress, 13 Sept 2024 The median progression free survival for first-line SMARCA4-mutated NSCLC treated with chemo-immunotherapy is 2.7 months1 In this heavily pretreated patient population of SMARCA4-mutated patients, some have dem
Slide 18: PRT3789-01: Patient Case Study
PRT3789-01: Patient Case Study Guo, R. et al., ESMO Congress, 13 Sept 2024 The patient images depicted here are representative of a “classical” patient with SMARCA4 mutations: poorly differentiated, aggressive disease This patient experienced a confirmed PR, with tumor shrinkage in liver lesions and
Slide 19: PRT3789-01: Key Takeaways
PRT3789-01: Key Takeaways Guo, R. et al., ESMO Congress, 13 Sept 2024 These data represent initial proof of concept that selective SMARCA2 degradation can yield anti-tumor activity in certain SMARCA4-mutated cancers
Slide 20: What's Next for PRT3789?
KEYTRUDA® is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. LOF = “Loss-of-function”; QW = once weekly; DLT = dose limiting toxicity; NSCLC – non-small cell lung cancer; 2L = second-line What’s Next for PRT3789? ‘3789 Monotherapy Dose Confirmat
Slide 21: PRT7732: First-in-Class, Highly Selective Oral SMARCA2 Degrader
PRT7732: First-in-Class, Highly Selective Oral SMARCA2 Degrader – Phase I Trial Initiated Sub-nanomolar SMARCA2 degradation potency in cell lines Very high selectivity for SMARCA2 over SMARCA4 Good oral bioavailability observed across species supporting once-daily projected human dose Preclinical As
Slide 22: Closing Remarks
Kris Vaddi, Ph.D., CEO Prelude Therapeutics Incorporated Closing Remarks
Slide 23: Open for Questions
Open for Questions Kris Vaddi, PhD Chief Executive Officer Jane Huang M.D. President and Chief Medical Officer Sean Brusky, MBA Chief Business Officer Peggy Scherle, PhD Chief Scientific Officer Bryant Lim, J.D. Chief Legal Officer, Corporate Secretary and Interim CFO
Slide 24: PD Correlates with Efficacy in Preclinical Models
Correlation observed between peripheral blood monocyte (PBMC) and tumor SMARCA2 degradation levels at efficacious doses Increasing doses result in increased reduction in SMARCA2 PD AUC in tumors and were associated with higher efficacy PD Correlates with Efficacy in Preclinical Models In vivo Effica
Slide 25: Dose Dependent Degradation of SMARCA2, but not SMARCA4
Dose Dependent Degradation of SMARCA2, but not SMARCA4 Pharmacodynamic Effect (AUC) Over 1 Week AUC normalized SMARCA2 AUC normalized SMARCA4 Pharmacodynamic Effect (AUC) Over 1 Week SMARCA2 AUC, n 4 4 4 4 9 10 5 3 SMARCA4 AUC, n 3 8 10 5 3