Prelude Therapeutics Incorporated · NASDAQ:PRLD
Prelude Therapeutics — Investor Presentation (November 2021)
36 slides from Prelude Therapeutics's investor presentation, Nov 12, 2021
Slide 1: Corporate Presentation November 2021
Corporate Presentation November 2021 Exhibit 99.2
Slide 2: Disclaimer
2 Disclaimer 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 expectations about timi
Slide 3: Prelude Therapeutics Vision
Powered by scientists with a track record of delivering precision oncology medicines Discovery Engine 3 Prelude Therapeutics Vision Efficient development path with potential for rapid regulatory approvals Regulatory Strategy Rapidly advancing potentially high value therapy candidates with a commitme
Slide 4: Prelude Discovery and Development Approach
Focused Clinical Development Optimized for early clinical POC and rapid execution of pivotal trials CHEMICAL LEADS NOVEL INTERVENTION POINTS Medicinal Chemistry Capabilities Rapidly building synthetically complex molecules Cancer Biology & Translational Expertise Deep understanding of oncogenic path
Slide 5: Prelude Therapeutics Pipeline
5 Prelude Therapeutics Pipeline
Slide 6: Prelude Roadmap for Value Creation
6 Prelude Roadmap for Value Creation Anticipated 2021/2022 Milestones Future Strategy PRMT5 Report P1 dose expansion data Generate POC in selected patients Leverage initial POC clinical data to inform design of P2 registration studies MCL1 Complete dose escalation and initiate expansion/combination
Slide 7: PRMT5 Programs
eee Rsy. 56 PRMT5 Programs Prelude
Slide 8: PRMT5 Pathway Drives Oncogenesis and Resistance
8 PRMT5 Pathway Drives Oncogenesis and Resistance PRMT5 Transcription Factors PRMT5 Spliceosome Histones Transcriptional Control of Oncogenesis and Resistance DNA Repair Genes HRD+ Cancers (e.g., Ovarian, Breast) Oncogenic Drivers (e.g., Myc / Myb) ACC, Lymphomas, Richter’s Splicing Dysregulation /
Slide 9: Prelude PRMT5 Program
9 Prelude PRMT5 Program Optimized for a well-balanced and differentiated profile Differentiating Mechanism of Action Prelude compounds are co-factor (SAM) competitive inhibitors Substrate competitive Inhibitors PRMT5
Slide 10: PRT543 / PRT811 Differentiated Clinical Stage Oral PRMT5 Inhibitors
10 PRT543 / PRT811 Differentiated Clinical Stage Oral PRMT5 Inhibitors PRT543 PRT811 Strong scientific rationale for pathway Highly selective and potent oral candidate Optimized PK profile Good oral bioavailability and long half-life (12+ hours) Applicability in both solid tumors and heme malignanci
Slide 11: PRT543/PRT811 Phase 1 Dose Escalation Data
PRT543 /PRT811 Phase 1 Dose Escalation Data
Slide 12: Study Demographics & Safety
12 Study Demographics & Safety 49 patients Unselected patient population with 18 different diagnoses 9 colon; 7 ACC; 6 uveal melanoma (2 patients SF3B1+); 5 ovarian cancer (2 patients HRD+) Median of 3 prior lines of systemic therapy PRT543 was well-tolerated Most common TRAEs of any grade in ≥ 5% o
Slide 13: PRT543: Exhibited Target Engagement and Inhibited PRMT5 Activity
13 PRT543: Exhibited Target Engagement and Inhibited PRMT5 Activity in Phase 1 Dose Escalation Study Dose-Dependent Increases in Cmax and AUC Dose-Dependent Inhibition of Serum sDMA Intron Retention Observed at Higher Dose Levels 45 mg/5x week selected as recommended Phase 2 dose Data presented at 2
Slide 14: PRT543 – Timeline and Clinical Plan
14 PRT543 – Timeline and Clinical Plan Myeloid Malignancies with Spliceosome Mutations (N~20) Myelofibrosis PRT543 + Ruxolitinib (N~20) Myelofibrosis/MDS Monotherapy (N~40) Dose escalation completed Expansion dose and schedule confirmed Dose expansion cohorts enrolling Dose expansion data readouts a
Slide 15: PRT811: Well-Tolerated with Evidence of Preliminary Clinical Activity
15 PRT811: Well-Tolerated with Evidence of Preliminary Clinical Activity in Phase 1 Dose Escalation Study *Data as of August 13, 2021 **Data as of September 20, 2021 Data presented at 2021 AACR-NCI-EORTC Annual Meeting 45 patients 27 across 16 unselected advanced solid tumors 18 patients with high-g
Slide 16: PRT811: Exhibited Target Engagement and Inhibited PRMT5 Activity
16 PRT811: Exhibited Target Engagement and Inhibited PRMT5 Activity in Phase 1 Dose Escalation Study Dose-Dependent Increases in Cmax and AUC Dose-dependent Inhibition of Serum sDMA Intron Retention Observed at Higher Dose Levels Data presented at 2021 AACR-NCI-EORTC Annual Meeting
Slide 17: PRT543 and PRT811: Overall Response and Response Duration
17 PRT543 and PRT811: Overall Response and Response Duration in Select Patient Cohorts From Dose Escalation Phase †Target lesions assessed using RECIST, except for patient 811-F with glioma assessed by RANO. ‡Data cutoff for PRT543 was 8.6.21, for PRT811 was 8.13.21, and for patient 811-E was 10.8.2
Slide 18: PRT543 and PRT811: Overall Response of Target Lesions
18 PRT543 and PRT811: Overall Response of Target Lesions (RECIST or RANO) in Select Patient Cohorts From Dose Escalation Phase *Data cutoff for PRT543 was 8.6.21, for PRT811 was 8.13.21, and for patient 811-E was 10.8.21. †Target lesions assessed using RECIST, except for patient 811-F with glioma as
Slide 19: PRT811 – Timeline and Clinical Plan
19 PRT811 – Timeline and Clinical Plan Dose escalation completed Dose expansion cohorts to begin enrolling Dose expansion data readouts anticipated in 2022 Demonstrate initial clinical proof of concept Design Phase 2/3 studies based on POC data from expansion cohorts Commence Phase 2/3 registration
Slide 20: MCL1 Program
MCL1 Program Prelude
Slide 21: Prelude MCL1 Program
21 Prelude MCL1 Program Dysregulated MCL1 expression occurs frequently in cancer MCL1 is a member of BCL2 family of proteins involved in blocking cell death proteins MCL1 is a validated bypass and resistance mechanism for venetoclax (BCL2 inhibitor) and TKIs Currently active competitor compounds are
Slide 22: PRT1419 Differentiated Clinical-Stage MCL1 Inhibitor Candidate
PRT1419 Differentiated Clinical-Stage MCL1 Inhibitor Candidate 22 MCL1 22
Slide 23: PRT1419: Potential Leading MCL1 Inhibitor
23 PRT1419: Potential Leading MCL1 Inhibitor Prelude compounds are competitive inhibitors of BIM binding Highly Potent Binding to MCL1 MCL1
Slide 24: PRT1419 Demonstrated Preclinical Activity as Monotherapy and in Combination
24 PRT1419 Demonstrated Preclinical Activity as Monotherapy and in Combination Monotherapy Combination MCL1
Slide 25: Oral PRT1419 Phase 1 Clinical Trial
Dose Escalation Expansion Cohorts 25 Oral PRT1419 Phase 1 Clinical Trial CURRENT MCL1 Group A Group B 100mg 1x/wk 200mg 1x/wk 100mg 1x/wk AML (N~20) AML or MDS PRT1419 + Venetoclax or Aza (N~20) NHL (B or T cell Lymphoma) (N~20) Multiple Myeloma (N~20) High Risk MDS (N~20) Recommended Expansion Dose
Slide 26: CDK9 Program
CDK9 Program PRT2527 Prelude
Slide 27: Prelude CDK9 Program
27 Prelude CDK9 Program CDK9 phosphorylates RNA Pol II and regulates transcription Regulates expression of several immediate early genes driving oncogenesis and resistance (i.e. MYC, MYB, MCL1) Non-selective CDK9 inhibitors have demonstrated clinical activity in multiple tumor types but poor tolerab
Slide 28: PRT2527: Potent and Highly Selective CDK9 Inhibitor Candidate
28 PRT2527: Potent and Highly Selective CDK9 Inhibitor Candidate Highly Selective CDK9 Inhibitor Candidate CDK9 Prelude compounds are ATP competitive inhibitors *Internal data; biochemical assay at 1 mM ATP, H929 CTG proliferation assay; **VIP151 was formerly BAY151and licensed to Vincera by Bayer
Slide 29: CDK9 Inhibitor Candidate: PRT2527
29 CDK9 Inhibitor Candidate: PRT2527 Improved Selectivity Sustained Regressions at Well-Tolerated Doses in Vivo Potent in Vitro Activity CDK9
Slide 30: SMARCA2 Program
SMARCA2 Program Prelude
Slide 31: SMARCA2 Targeted Degrader Program
31 SMARCA2 Targeted Degrader Program SMARCA4 and SMARCA2 Regulate Chromatin Accessibility and Gene Expression Loss of SMARCA4 Leads to SMARCA2 Dependency SMARCA2 SMARCA4 MUTANT TUMORS SMARCA2 Degradation Dysfunctional SMARCA4 Synthetic Lethality Tumor Cell Death SMARCA4
Slide 32: PRT-SCA2: Potent Selective SMARCA2 Degraders with In Vivo Activity
32 PRT-SCA2: Potent Selective SMARCA2 Degraders with In Vivo Activity SMARCA2 Prelude SMARCA2 Degraders Replicate Genetic Synthetic Lethality Sub-Nanomolar Potency for SMARCA2 Degradation Highly Selective for SMARCA2 Degradation %inhibition %Conc(nM) In vitro In vivo
Slide 33: Corporate Highlights
Corporate Highlights Prelude
Slide 34: Financial Summary
Financial Summary Shares Outstanding 47.0 million shares voting and non-voting common stock as of Nov 8, 2021 61.0 million shares fully diluted 34 Cash, Cash Equivalents and Marketable securities $320.9 million as of Sept 30, 2021 The Company believes that its current cash, cash equivalents and mark
Slide 35: Prelude Roadmap for Value Creation
35 Prelude Roadmap for Value Creation Anticipated 2021/2022 Milestones Future Strategy PRMT5 Report P1 dose expansion data Generate POC in selected patients Leverage initial POC clinical data to inform design of P2 registration studies MCL1 Complete dose escalation and initiate expansion/combination
Slide 36: Thank You
Thank You
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