Prelude Therapeutics Incorporated · NASDAQ:PRLD
Prelude Therapeutics — Investor Presentation (January 2023)
33 slides from Prelude Therapeutics's investor presentation, Jan 9, 2023
Slide 1: Corporate Presentation January 2023
Corporate Presentation January 2023 Exhibit 99.1
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: our plans to develop and commercialize small molecule therapies, our expectati
Slide 3: Prelude Therapeutics: Delivering Precision Medicines to Patients
Prelude Therapeutics: Delivering Precision Medicines to Patients Large Commercial Opportunities Diversified Pipeline Exceptional Team Well Capitalized Powerful R&D Engine
Slide 4: Prelude Discovery and Development Engine: Positioned to Succeed
Prelude Discovery and Development Engine: Positioned to Succeed R&D ENGINE DIFFERENTIATED PIPELINE APPROACH CDK9 inhibitor MCL1 inhibitor SMARCA2 degrader CDK4/6 inhibitor Internal Discovery Engine Clinical Development Expertise Target Mechanisms that drive meaningful benefit in patients with cancer
Slide 5: Experienced Management Team: Proven Track Records
Former CMO Former CEO General Partner Experienced Management Team: Proven Track Records Board of Directors Victor Sandor, MD Paul Friedman, MD CEO David Bonita, MD Julian C. Baker Managing Member Baker Brothers Investments Kris Vaddi, PhD Founder & Chief Executive Officer Mardi Dier Former CFO, CBO
Slide 6: Prelude Precision Oncology Pipeline: Diversified and Differentiated
PROGRAM CANCER INDICATIONS DISCOVERY IND ENABLING PHASE 1 PHASE 2/3 Anticipated Milestones PRT2527 (CDK9 Inhibitor) Selected solid and hematologic malignancies Report Clinical Data in Solid Tumors and Hematological Malignancies – 2023 PRT1419 (MCL1 Inhibitor) Selected hematologic malignancies and so
Slide 7: Differentiated Pipeline with Transformative Potential
Differentiated Pipeline with Transformative Potential Potentially Best-in-Class Selectivity Potential to avoid off-target toxicity and higher clinical activity Potent and Selective Degrader Potential to address major unmet need in biomarker-selected patients Optimized PK Profile Potential for maxima
Slide 8: PRT2527 CDK9 Inhibitor
PRT2527 CDK9 Inhibitor
Slide 9: CDK9 Inhibition: Targeting Cancer by Regulating Oncogene Expression
CDK9 Inhibition: Targeting Cancer by Regulating Oncogene Expression CDK9 regulates expression of several oncogenes that drive cancer cell growth and resistance (i.e. MYC, MYB, MCL1) Non-selective CDK9 inhibitors have demonstrated clinical activity in multiple tumor types but poor tolerability Improv
Slide 10: PRT2527: Potent and Highly Selective CDK9 Inhibitor
PRT2527: Potent and Highly Selective CDK9 Inhibitor Compound AZD4573 KB0742 VIP152** PRT2527 Biochemical* IC50 (nM) CDK9 1.9 483 16 0.95 Proliferation* IC50 (nM) 11 915 84 18 Plasma* IC50 (nM) 192 1056 923 196 Fold Selectivity CDK9 vs Other Isoforms CDK1 23x >20x 371x 73x CDK2 35x >20x 147x 340x CDK
Slide 11: CDK9 inhibitor: PRT2527 Phase 1 Dose-Escalation Study in Advanced Solid Tumors
CDK9 inhibitor: PRT2527 Phase 1 Dose-Escalation Study in Advanced Solid Tumors Phase 1 dose escalation study of PRT2527 is ongoing and enrolling following tumor types Selected sarcomas displaying a gene fusion Castrate resistant prostate cancer HR+ HER2- breast cancer Non-small cell lung cancer Soli
Slide 12: CDK9 Inhibitor: PRT2527 Phase Studies in Solid Tumors and Hematologic Malignancies
CDK9 Inhibitor: PRT2527 Phase 1 Studies in Solid Tumors and Hematologic Malignancies PRT2527 Solid Tumors N=11 PRT2527 MYC Amplified or Overexpressed Solid Tumors, Prostate Cancer N=15 Solid Tumors Dose dependent increases in exposure and target engagement observed in Phase 1 Clinical MYC and MCL1 d
Slide 13: CDK9 Inhibitor Differentiation and Market Opportunity
CDK9 Inhibitor Differentiation and Market Opportunity Potential for Improved Safety Based on Best-in-Class Kinome Selectivity PRT2527 is a highly potent CDK9 inhibitor with best-in-class kinome selectivity compared to competitor compounds Optimized PK profile to maximize therapeutic window Well-tole
Slide 14: PRT1419 MCL1 Inhibitor
PRT1419 MCL1 Inhibitor
Slide 15: MCL1 inhibition: Targeting Cancer Cell Survival
MCL1 inhibition: Targeting Cancer Cell Survival MCL1 is a member of the BCL2 family of inhibitors of apoptosis Established resistance mechanism to the BCL2 inhibitor Venetoclax Prolonged depletion of MCL1 is undesirable and may be associated with cardiac toxicity Optimizing the PK profile of an MCL1
Slide 16: PRT1419: Potent MCL1 Inhibitor with Strong Preclinical Activity
PRT1419: Potent MCL1 Inhibitor with Strong Preclinical Activity as Monotherapy and in Combination Monotherapy Combination Robust monotherapy activity also seen in models of DLBCL & MM Proliferation IC50 (nM) Whole Blood IC50 (nM) AMG176 150 1800 AZD5991 31 320 MIK665 4.5 430 PRT1419 80 210 Prelude c
Slide 17: MCL1 inhibitor: PRT1419 Phase Study in Hematologic Malignancies
MCL1 inhibitor: PRT1419 Phase 1 Study in Hematologic Malignancies PRT1419 Monotherapy AML/MDS/CMML CLL/SLL FL/MZL/MCL N=24-30 PRT1419 Combination PRT1419+Aza: AML/MDS/CMML PRT1419+Ven: AML/MDS/CMML PRT1419+Ven: MCL N=24-30 In the solid tumor PRT1419 dose escalation Phase 1, 26 patients have been tre
Slide 18: MCL1 Inhibitor Differentiation and Market Opportunity
MCL1 Inhibitor Differentiation and Market Opportunity Optimized PK Profile to Achieve Desired Target Engagement MCL1 Inhibitor CDK9 SMARCA2 CDK4/6 PRT1419 is a highly potent and selective MCL1 inhibitor Designed to have a PK profile with high clearance to provide desired target engagement with impro
Slide 19: PRT3645 CDK4/6 Inhibitor
PRT3645 CDK4/6 Inhibitor
Slide 20: CDK4/6 Inhibition: Targeting Cancer Through Cell Cycle Regulation
CDK4/6 Inhibition: Targeting Cancer Through Cell Cycle Regulation Mechanism Validated mechanism with approval of CDK4/6 inhibitors in HR+ breast cancer Resistance mechanism to other targeted therapies including KRAS G12C inhibitors Current CDK4/6 inhibitors limited by poor tolerability and lack broa
Slide 21: CDK 4/6 inhibitor PRT3645 Improved Tissue Penetration and Robust Activity
CDK 4/6 inhibitor PRT3645 Improved Tissue Penetration and Robust Activity in Preclinical Models PRT3645 demonstrates higher brain penetration than approved CDK4/6 inhibitors PRT3645 shows robust activity in vivo as monotherapy and in combination U87 glioblastoma model MCF7 breast cancer model
Slide 22: Novel Combinations to Extend the Potential of CDK4/6 Inhibition
Novel Combinations to Extend the Potential of CDK4/6 Inhibition H2122 NSCLC Model *** DFBM-355 PDX model of ER+/HER2+ Breast Cancer PRT3645 significantly enhances the activity of KRAS G12C inhibitor in NSCLC models and with HER2 kinase inhibitor in ER+/HER2+ BC models
Slide 23: CDK4/6 Inhibitor: PRT3645 Phase 1 Study in Solid Tumors
CDK4/6 Inhibitor: PRT3645 Phase 1 Study in Solid Tumors A differentiated and highly brain penetrant CDK4/6 inhibitor Potential to extend the reach of CDK4/6 inhibition beyond HR+ breast cancers, for which the first generation CDK4/6 inhibitors were approved PRT3645 Biomarker enriched patients with s
Slide 24: CDK4/6 Inhibitor Differentiation and Market Opportunity
CDK4/6 Inhibitor Differentiation and Market Opportunity Deep Tissue Penetration with Potential for Activity in Areas of Unmet Need PRT3645 is a highly potent and selective CDK4/6 inhibitor Optimized to demonstrate deep tissue penetration including brain penetrance Improved metabolism profile to allo
Slide 25: PRT3789 SMARCA2 Degrader
PRT3789 SMARCA2 Degrader
Slide 26: Targeting SMARCA2 (BRM): Leveraging Synthetic Lethality
Targeting SMARCA2 (BRM): Leveraging Synthetic Lethality The chromatin remodeling (SWI/SNF) complex is frequently mutated in cancer making it a potential therapeutic target Activity of the SWI/SNF complex requires either SMARCA4 (BRG1) or SMARCA2 (BRM) Loss of SMARCA4 (BRG1) through mutation leads to
Slide 27: SMARCA4 Mutations in NSCLC: An Opportunity with No Approved Therapies
Indication Any SMARCA4 Mutation1 NSCLC 10.0% Esophageal 8.0% Gastric (stomach adeno) 8.3% Skin (invasive and in situ melanoma)* 21.0% Endometrial (uterine corpus) 13.3% Squamous cell lung 7.7% Urinary (bladder) 9.0% Colorectal 6.0% Pancreatic 2.9% Melanoma (invasive) 8.7% SMARCA4 Mutations in
Slide 28: PRT3789: Potent and Selective SMARCA2 Degrader with In Vivo Activity
PRT3789: Potent and Selective SMARCA2 Degrader with In Vivo Activity Robust Tumor Growth Inhibition of SMARCA4 mutated but not WT Xenograft SMARCA4 mutant SMARCA4 WT PRT3789 PRT3789 Vehicle Low Dose Mid Dose High Dose SMARCA2 SMARCA4 LAMIN B1 SMARCA2 SMARCA4 LAMIN B1 Male Female Significant Degradat
Slide 29: SMARCA2 Degrader: PRT3789 Phase 1 Study in Solid Tumors
SMARCA2 Degrader: PRT3789 Phase 1 Study in Solid Tumors SMARCA2 inhibition has the greatest potential in patients with SMARCA4 deficient cancers, including approximately 5-10% of all non-small cell lung cancers SMARCA2 degradation to be evaluated in Phase 1 Study population: advanced, recurrent, or
Slide 30: SMARCA2 Differentiation and Market Opportunity
SMARCA2 Differentiation and Market Opportunity Potential First-in-Class SMARCA2 (BRM) Targeted Protein Degrader PRT3789 is a potent and highly selective first-in-class SMARCA2 Degrader Designed to achieve the requisite high selectivity for SMARCA2 over the related isoform, SMARCA4, through a targete
Slide 31: Prelude Therapeutics: Key Takeaways and Reasons to Invest
Prelude Therapeutics: Key Takeaways and Reasons to Invest Confidential Current cash runway expected through Q4 2024 Potentially first-in-class SMARCA2 degrader program with a significant lead over competitors and offers transformational potential for the company Opportunity to drive programs to key
Slide 32: Back Up
BACK UP
Slide 33: We Continue to Advance our Pipeline of Highly Innovative Oncology Medicines
We Continue to Advance our Pipeline of Highly Innovative Oncology Medicines Confidential PRT2527 PRT1419 PRT3645 SMARCA2 CDK9 MCL1 CDK4/6 Phase 1 dose escalation completed; RP2D solid tumors anticipated in early 2023 Dose dependent target engagement and exposure observed No adverse events leading to
Prelude Therapeutics — Investor Presentation (January 2023) on 6ix