Prelude Therapeutics Incorporated · NASDAQ:PRLD
Prelude Therapeutics — Investor Presentation (March 2023)
37 slides from Prelude Therapeutics's investor presentation, Mar 15, 2023
Slide 1: Corporate Presentation March 2023
Corporate Presentation March 2023 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: our plans to develop and commercialize small molecule therapies, our expectati
Slide 3: Delivering Precision Medicines to Patients with Cancer
Prelude Therapeutics: Delivering Precision Medicines to Patients with Cancer 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 PROGRAMS APPROACH CDK9 MCL1 SMARCA2 CDK4/6 Target Mechanisms that drive meaningful benefit in patients with cancer Discover Optimized molecules that overcome the limitations of current treatments Translate Scie
Slide 5: Differentiated Programs with Transformative Potential for Patients with Cancer
Differentiated Programs with Transformative Potential for Patients with Cancer 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 Pro
Slide 6: Prelude Precision Oncology Pipeline: Diversified and Differentiated
PROGRAM CANCER INDICATIONS DISCOVERY PHASE 1 PHASE 2/3 AREAS OF CLINICAL FOCUS CDK9 PRT2527 Selected solid and hematologic malignancies R/R MCL, CLL, Aggressive Lymphomas as Monotherapy or in Combination with BTKi MCL1 PRT1419 Selected hematologic malignancies and solid tumors CLL Post Ven/BTKi, AML
Slide 7: Driving The Programs to Key Milestones and Value Creation
Driving The Programs to Key Milestones and Value Creation PRT2527 PRT1419 PRT3645 SMARCA2 CDK9 MCL1 Next Generation CDK4/6 Present solid tumor data at AACR 2023 RP2D in solid tumors in early-2023 RP2D in hematological malignancies in 2H Present initial clinical data for hematological malignancies in
Slide 8: PRT2527 CDK9 Inhibitor
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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: 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: 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: PRT2527: Broad Potential Addressing areas of High Unmet Need
PRT2527: Broad Potential Addressing areas of High Unmet Need 1. SEER Cancer Stat Facts: https://seer.cancer.gov/statfacts/html/clyl.html; 2. Gena Kanas, et. al. Epidemiology of diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) in the United States and Western Europe 3. CancerMPact®
Slide 15: PRT1419 MCL1 Inhibitor
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Slide 16: 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 17: PRT1419 is Potent MCL1 Inhibitor with Preclinical Activity
PRT1419 is Potent MCL1 Inhibitor with Demonstrated 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 P
Slide 18: PRT1419 Does Not Cause Cardiac Injury in Preclinical Toxicology Studies
PRT1419 Does Not Cause Cardiac Injury in Preclinical Toxicology Studies Doses: 0.3, 1, 3 and 6 mg/m2; once weekly Linear increases in exposure No troponin elevations observed at any doses, even high dose which covered EC90 for 24h No histopathological evidence of cardiac injury Pharmacokinetics Phar
Slide 19: MCL1 inhibitor: PRT1419 Phase 1 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 20: MCL1 Inhibitor Differentiation and Market Opportunity
MCL1 Inhibitor Differentiation and Market Opportunity Optimized PK Profile to Achieve Desired Target Engagement MCL1 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 improved safety
Slide 21: PRT1419: MCL1 Inhibitor Offers Potential Benefit for Patients with Poor Outcomes
PRT1419: MCL1 Inhibitor Offers Potential Benefit for Patients with Poor Outcomes 1. SEER, https://seer.cancer.gov/statfacts/html/clyl.html; 2,3,4, CancerMPact® Treatment Architecture, * MDS number represents annual incident patients, treated patient number may be higher. Broad Opportunity: ~95K pati
Slide 22: PRT3645 Next Generation CDK4/6 Inhibitor
PRT3645 Next Generation CDK4/6 Inhibitor
Slide 23: Next Generation CDK4/6 Inhibition: Targeting Cancer Through Cell Cycle Regulation
Next Generation CDK4/6 Inhibition: Targeting Cancer Through Cell Cycle Regulation Mechanism Validated mechanism with approval of Next Generation CDK4/6 inhibitors in HR+ breast cancer Resistance mechanism to other targeted therapies including KRAS G12C inhibitors Current CDK4/6 inhibitors limited by
Slide 24: PRT3645 – Highly Selective Next Generation CDK4/6 Inhibitor
PRT3645 – Highly Selective Next Generation CDK4/6 Inhibitor Bias towards CDK4 over CDK6 Compound Palbociclib Abemaciclib PRT3645 Biochemical* IC50 (nM) CDK4 25 5 3 Proliferation* IC50 (nM) 52 70 47 Phospho-Rb* IC50 (nM) 28 30 16 Fold Selectivity CDK4 vs Other Isoforms CDK6 1x 6x 5x CDK1 >500x >500x
Slide 25: PRT3645 Improved Tissue Penetration and Robust Activity in Preclinical Models
Next Generation CDK4/6 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 canc
Slide 26: Novel Combinations to Extend CDK4/6 Inhibition Beyond ER+ Breast Cancer
Novel Combinations to Extend the Potential of CDK4/6 Inhibition Beyond ER+ Breast Cancer 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 27: PRT3645 Phase 1 Study in Solid Tumors
Next Generation CDK4/6 Inhibitor: PRT3645 Phase 1 Study in Solid Tumors A differentiated and highly brain penetrant Next Generation 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 Bi
Slide 28: Next Generation CDK4/6 Inhibitor Differentiation and Market Opportunity
Next Generation 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 Next Generation CDK4/6 inhibitor Optimized to demonstrate deep tissue penetration including brain penetrance Imp
Slide 29: PRT3789 SMARCA2 Degrader
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Slide 30: 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 31: 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 32: 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 Significant Degradation of SMARCA2 Protein but not SMARCA4 in Preclinical Models SMARCA4 mutant SMARCA4 WT PRT3789 PRT3789 Vehicle Low Dose Mid Dose High Dose S
Slide 33: 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 10-20% of all non-small cell lung cancers SMARCA2 degradation to be evaluated in Phase 1 Study population: advanced, recurrent, or
Slide 34: SMARCA2 Differentiation and Market Opportunity
SMARCA2 Differentiation and Market Opportunity Potential First-in-Class SMARCA2 (BRM) Targeted Protein Degrader PRT3789 is a first-in-class SMARCA2 Degrader Potent and selective over the related isoform, SMARCA4, through a targeted protein degrader approach Improved tolerability compared to non-sele
Slide 35: PRT3789: Large Pan-Tumor Unmet Need in Patients with SMARCA4 Mutation
PRT3789: Large Pan-Tumor Unmet Need in Patients with SMARCA4 Mutation Broad Opportunity: Improvement vs SoC: Most common 2L mNSCLC regimen offers minimal benefit and significant toxicity 4 SMARCA 4 Degrader offers: First in Class Treatment Option in patients with no approved drugs mPFS ~ 4.5 months
Slide 36: Prelude Therapeutics: Key Takeaways and Reasons to Invest
Prelude Therapeutics: Key Takeaways and Reasons to Invest 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 inflection po
Slide 37: Experienced Management Team: Proven Track Records
Experienced Management Team: Proven Track Records Andrew Combs, PhD Executive Vice President and Head of Chemistry Peggy Scherle, PhD Chief Scientific Officer Jane Huang M.D. President and Chief Medical Officer Kris Vaddi, PhD Founder & Chief Executive Officer Laurent Chardonnet, MBA Chief Financial
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