Prelude Therapeutics Incorporated · NASDAQ:PRLD
Prelude Therapeutics — Investor Presentation (August 2024)
30 slides from Prelude Therapeutics's investor presentation, Aug 12, 2024
Slide 1: Corporate Presentation August 2024
Corporate Presentation August 2024 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- or best-in-class and anchor to patient unmet need Draw on decades of experience and proven leadership to drive innovatio
Slide 4: Prelude's Evolution and Strategic Priorities
Prelude’s Evolution Strategic Priorities Continue to build SMARCA leadership Generate proof-of-concept data Prepare for global registrational trials Advance SMARCA “Pipeline in a Program” Explore collaborations to accelerate trials and global capabilities ~1 new IND every 12-18 months Successfully a
Slide 5: Experienced Leadership Team in Precision Oncology
Kris Vaddi, PhD Founder & 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 Legal Officer, Corporate Secretary and Interim CF
Slide 6: Prelude's Precision Medicine Pipeline & Discovery Engine
Prelude’s Precision Medicine Pipeline & Discovery Engine PROGRAM POTENTIAL INDICATIONS DISCOVERY PHASE 1 PHASE 2/3 Lead SMARCA2 Degrader (IV) SMARCA4-mutated NSCLC & other cancers Oral SMARCA2 Degrader SMARCA4-mutated NSCLC & other cancers SMARCA2/4 Precision ADCs* Interim Phase 1 Data at ESMO Congr
Slide 7: First-in-Class, Highly Selective SMARCA2 Degraders PRT3789 and PRT7732
Prelude’s First-in-Class, Highly Selective SMARCA2 Degraders PRT3789 (IV) and PRT7732 (Oral) Click Here to Access Prelude’s Educational Video Series on SMARCA2 Degraders
Slide 8: SMARCA4 mutations occur in ~10% of all NSCLC
Over half of SMARCA4 mutations are Class I loss of function / deleterious mutations (>5% of NSCLC) SMARCA4 mutations are associated with aggressive disease and poor prognosis across a range of cancers Patients with SMARCA4 mutations are not typically eligible for other targeted therapies Currently t
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. doi:
Slide 10: Selective Targeting of SMARCA2 to Treat SMARCA4 Mutated Cancers
Selective Targeting of SMARCA2 is an Attractive Approach to Treat SMARCA4 Mutated Cancers Mutations in the chromatin remodeling complex drive cancer growth and resistance Cancer cells with SMARCA4 mutations become highly dependent on SMARCA2 for survival Selectively degrading SMARCA2 induces "synthe
Slide 11: PRT3789 Solved the Selectivity Enigma With a >1000 fold Selective Degrader
PRT3789 Solved the Selectivity Enigma With a >1000 fold Selective Degrader 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 selecti
Slide 12: PRT3789: Phase 1 Study Underway, Enrolling Backfill and Combo Cohorts
Initial safety and tolerability data for monotherapy dose escalation cohorts (any solid tumor with any SMARCA4 mutation) Early look at pharmacokinetic profile and pharmacodynamic effects Initial review of monotherapy clinical activity across different tumor types at escalating doses * Includes any m
Slide 13: Combination Study of PRT3789 + Pembrolizumab in Q4 2024
Prelude to Initiate Phase 2 Combination Study of PRT3789 + Pembrolizumab in Q4 2024 PRT3789 upregulates genes encoding antigen processing and presentation machinery and may turn ‘cold’ tumors ‘hot’ Trial will explore safety and anti-tumor activity of the combination Preclinical rationale supportive
Slide 14: Next Steps for Development of PRT3789 and Future Directions
Next Steps for Development of PRT3789 and Future Directions Full Phase I Trial Results: 2025 Full safety and tolerability data for monotherapy dose escalation, backfill, and chemotherapy combination cohorts Assessment of PK profile and PD effects to support recommended expansion/Phase 2 dose Assessm
Slide 15: Expanding Our Portfolio of SMARCA-Targeted Precision Medicines
Expanding Our Portfolio of SMARCA-Targeted Precision Medicines SMARCA - DACs + Lead SMARCA2 Degrader (PRT3789) Oral SMARCA2 Degrader (PRT7732) Expands access for advanced NSCLC patients (first-line) Enables use in earlier stage disease (adjuvant / neo-adjuvant) Provides optionality across other SMAR
Slide 16: PRT7732: First-in-Class Oral SMARCA2 Degrader Advancing to Clinic
PRT7732: First-in-Class, Highly Selective Oral SMARCA2 Degrader Advancing to Clinic Sub-nanomolar SMARCA2 degradation potency Very high selectivity (>1000 fold*) for SMARCA2 over SMARCA4 Good oral bioavailability across species FDA investigational new drug (IND) authorization received in Q3 2024 On
Slide 17: PRT7732 Anti-Tumor Activity in SMARCA4-Deficient Xenograft Models
PRT7732 Has Significant Anti-Tumor Activity in SMARCA4-Deficient Cancer Xenograft Models Daily oral administration of PRT7732 demonstrates anti-tumor activity in SMARCA4-deficient but not SMARCA4 wild type tumors PRT7732 rapidly decreases SMARCA2 protein levels in tumor xenograft models at low doses
Slide 18: Expanding Our Portfolio: Precision ADCs with SMARCA Degrader Payload
Expanding Our Portfolio of SMARCA-Targeted Precision Medicines Precision ADCs with SMARCA Degrader Payload Cancers with dysregulated SMARCA pathway Independent of SMARCA4-mutation status Initial focus of AbCellera collaboration SMARCA - DACs + Lead SMARCA2 Degrader (PRT3789) Oral SMARCA2 Degrader (P
Slide 19: Prelude and AbCellera Creating First-in-Class Precision ADCs
Together, Prelude and AbCellera are Creating Novel, First-in-Class Precision ADCs Multi-year global collaboration to jointly discover, develop and commercialize novel Precision ADCs for up to five programs AbCellera will lead manufacturing activities Prelude will lead clinical development and global
Slide 20: Prioritizing Initial Precision ADC Programs
Prioritizing Initial Precision ADC Programs Based on Patient Unmet Need and Scientific Rationale High Unmet Need & Opportunity Potential for Optimized Payload Potential for Optimized Antibody Initial program will link an optimized Prelude SMARCA2/4 dual degrader as a “Precision Payload” to an optimi
Slide 21: SMARCA Portfolio Strategy Addresses a Significant Unmet Need
Prelude’s SMARCA Portfolio Strategy Addresses a Significant Unmet Need ~220,000 pts/year Up to 22,000 SMARCA4-mutated FIRST LINE ~150,000 pts/year Up to 15,000 SMARCA4-mutated SECOND LINE + 1 US & EU5 only: Journal of Thoracic Oncology (US, 2021): https://doi.org/10.1016/j.jtho.2021.01.485; Globocan
Slide 22: Highly Selective CDK9 Inhibitor PRT2527
Highly Selective CDK9 Inhibitor PRT2527
Slide 23: Hematologic Malignancies Refractory to Current Treatments Have Poor Outcomes
Source: 1) Maiti A et al. Haematologica 2021. https://doi.org/10.3324/haematol.2020.252569 2) Lew TE et al. Blood Advances 2021. https://doi.org/10.1182/bloodadvances.2021005083 Patients with Hematologic Malignancies Refractory to Current Treatments Experience Poor Outcomes After SoC (venetoclax + H
Slide 24: CDK9 Inhibition Targets MYC and MCL-1 Pathways
CDK9 Inhibition Targets Two Major Validated Pathways (MYC and MCL-1) CDK9 is the primary transcriptional regulator of a major oncogene MYC and an apoptosis inducer MCL-1 Dysregulated pathways involving MYC and MCL-1 drive pathogenesis and resistance in hematologic cancers including lymphoid and myel
Slide 25: PRT2527 is a Potent, Highly Selective CDK9 Inhibitor
PRT2527 is a Potent, Highly Selective CDK9 Inhibitor That Depletes MCL-1 and MYC Highly Isoform Selective CDK9 Inhibitor Compound PRT2527 Biochemical* IC50 (nM) CDK9 0.95 Proliferation* IC50 (nM) 18 Plasma* IC50 (nM) 196 Fold Selectivity CDK9 vs Other Isoforms CDK1 73x CDK2 340x CDK3 35x CDK4 250x C
Slide 26: PRT2527 is Highly Efficacious In Vivo in Hematologic Malignancy Models
PRT2527 is Highly Efficacious In Vivo in Models of Hematologic Malignancies Monotherapy Karpas-422 (Double Hit DLBCL) MV4-11 (AML) Combination TMD-8 (ABC DLBCL) OCI-AML3 (VenR AML) Presented at ASH 2022; https://preludetx.com/wp-content/uploads/2023/03/ASH-2022_PRT2527-Presentation.pdf; Data on file
Slide 27: Initial Phase 1 Study of PRT2527 in Solid Tumors
Favorable tolerability with manageable neutropenia and absence of significant gastrointestinal events or hepatotoxicity Dose-dependent downregulation of CDK9 transcriptional targets – MYC and MCL-1 mRNA expression in PBMCs isolated from treated patients 12 mg/m2 QW dosing and higher showed optimal t
Slide 28: Phase 1 Trial of PRT2527 in Hematologic Malignancies Underway
Initial safety and tolerability data for monotherapy dose escalation cohorts in hematologic malignancies Initial assessment of clinical activity in B-cell malignancies as monotherapy Initial clinical data with zanubrutinib from combination cohort *R/R disease following: At least 1 prior systemic the
Slide 29: Continued Execution Across Strategic Priorities
Continued Execution Across Strategic Priorities PRT2527 CDK9 Initiate zanubrutinib combination study Initiate myeloid cohort in the existing phase 1 study Complete monotherapy dose escalation in B-cell malignancies Report interim phase 1 clinical results in 2024 PROGRAM Initiate docetaxel combinatio
Slide 30: Thank You
Thank You Contact Us: Robert Doody SVP, Investor Relations rdoody@preludetx.com
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