Prelude Therapeutics Incorporated · NASDAQ:PRLD
Prelude Therapeutics — Investor Presentation (March 2021)
40 slides from Prelude Therapeutics's investor presentation, Mar 17, 2021
Slide 1: Corporate Presentation March 2021
Corporate Presentation March 2021 Exhibit 99.1
Slide 2: Disclaimer
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 timing
Slide 3: Building a patient-focused precision oncology company
Powered by scientists with proven ability to deliver precision oncology medicines Discovery Engine Rapidly advancing potentially high value therapy candidates with a commitment to future patient access, awareness, and support Commercial Approach Highly selected patient populations & cancers with sig
Slide 4: Senior Management & Board of Directors
Former CMO Former CEO General Partner Andrew Combs, PhD Executive Vice President and Head of Chemistry Parsaclisib Senior Management & Board of Directors Experienced. Proven. Focused. Peggy Scherle, PhD Chief Scientific Officer Board of Directors Victor Sandor, MD Paul Friedman, MD CEO David Bonita,
Slide 5: Prelude Therapeutics Corporate Highlights
Prelude Therapeutics Corporate Highlights 4 INDs cleared to date; 3 Clinical stage programs; 3 Preclinical assets Highly productive target class agnostic discovery engine Pipeline focused on differentiated and validated targets Multiple wholly owned programs with fast-to-market potential Lead progra
Slide 6: Focused Clinical Development
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 7: Prelude Therapeutics Pipeline
Prelude Therapeutics Pipeline Program Indications Discovery/ Preclinical IND Enabling Phase 1 Phase 2 Phase 3 Upcoming Milestones Worldwide Rights PRT543 (PRMT5) Selected Solid Tumors (incl. ACC, HRD+) Escalation complete; additional expansion cohorts early 2Q2021 Data presentation 2H2021 Selected M
Slide 8: PRMT5 Programs
PRMT5 Programs <3 Prelude
Slide 9: PRMT5 Pathway Drives Oncogenesis and Resistance
PRMT5 Pathway Drives Oncogenesis and Resistance PRMT5 inhibition can be leveraged to potentially treat a broad range of solid tumors and hematologic malignancies PRMT5 Transcription Factors PRMT5 Spliceosome Histones Transcriptional Control of Oncogenesis and Resistance DNA Repair Genes HRD+ Cancers
Slide 10: Designed and synthesized >600 compounds to select PRT543 and PRT811
Designed and synthesized >600 compounds to select PRT543 and PRT811 for advancement Prelude PRMT5 Program Optimized for a well-balanced and differentiated profile Potency Selectivity ADME Pharmaceutical properties OPTIMAL CHEMICAL SPACE Differentiating Mechanism of Action Prelude compounds are co-fa
Slide 11: PRT543 Opportunity for Accelerated Development Path
PRT543 Opportunity for Accelerated Development Path Potential best-in-class PRMT5 inhibitor PRMT5 Differentiated PRMT5 Inhibitor Highly selective and potent Targets Selected Solid Tumors and Heme Malignancies Strong scientific rationale Clinical PoC for target Optimized PK Profile High oral bioavail
Slide 12: PRT543 demonstrated optimized potency, dose-dependent PD, and selectivity
PRT543 demonstrated optimized potency, dose-dependent PD, and selectivity offering best-in-class potential PRT543 – A Potent, Selective and Oral PRMT5 Inhibitor Candidate Vs 36 methyltransferases in addition to a broad panel of receptors, transporters and channels Modulation of sDMA (symmetric dimet
Slide 13: PRT543 Phase 1 Clinical Trial
Dose Escalation Expansion Cohorts Potential for PoC in multiple cancers in 2H2021 PRT543 Phase 1 Clinical Trial 4Q2020 / EARLY 2021 1 2 3 4 5 MDS and Myelofibrosis 40 mg BIW 5mg BIW 10mg BIW 20mg BIW 40 mg TIW Group B 50mg QD 5mg BIW 10mg BIW 15mg BIW 22.5mg BIW 45mg BIW 35mg 5x/wk 35mg or 45mg 5x/w
Slide 14: PRT543 Phase 1 Interim PK/PD Results
100 PRT543 Phase 1 – Interim PK/PD Results Demonstrated Predictable Profile Dose-Proportional Increase in Exposure (Steady State) Dose-Dependent Decrease in Serum sDMA Trough Level target based on Preclinical models Serum was obtained from patients at various times following administration of PRT543
Slide 15: PRT543 Phase 1 Clinical Trial Safety Profile
PRT543 Phase 1 Clinical Trial Safety Profile Phase 1 clinical trial of PRT543 enrolled 61 patients 42 with advanced solid tumors (including two with HRD+ high grade serous ovarian cancer) 11 with MF Seven with MDS One with NHL Overall safety profile consistent between both Groups A and B Majority of
Slide 16: Durable Confirmed CR in HRD+ High Grade Serous Ovarian Cancer
WEEK 8 BASELINE Durable Confirmed CR in HRD+ High Grade Serous Ovarian Cancer Diagnosed in 2014 with tumor origin in fallopian tube Seven prior lines of therapy including PARPi Enrolled in 35mg, 5x/week; currently ongoing Based on genomic analysis of archival tumor tissue, HRD+ Mutations in genes in
Slide 17: PRT543 Offers Broad Opportunity Across Tumor Types
PRT543 Offers Broad Opportunity Across Tumor Types PRMT5 Scientific Rationale Tumor Types Transcriptional Regulation Synthetic Lethality Splicing Dysregulation Adenoid Cystic Carcinoma HRD+ Tumors (Ovarian, TNBC, Others) Myeloid Malignancies (Myelofibrosis and MDS) Uveal Melanoma ACC: 10-15,000 pati
Slide 18: PRT811 Expanding PRMT5 Opportunity into CNS Cancers
PRT811 Expanding PRMT5 Opportunity into CNS Cancers Only clinical stage brain-penetrant PRMT5 inhibitor PRMT5 Differentiated Brain-Penetrant PRMT5 Inhibitor Highly selective and potent Targeting GBM and CNS Metastatic Brain Cancers High target engagement in the brain and preclinical activity Optimiz
Slide 19: PRT811 high oral bioavailability, high brain exposure, no dose-limiting toxicities
PRT811 has high oral bioavailability, high brain exposure, and no dose-limiting toxicities to date PRT811 – A Potent, Selective and Brain Penetrant PRMT5 Inhibitor Candidate Highly selective vs 36 methyl transferases in addition to a broad panel of receptors, transporters and channels < 1% > 80% % C
Slide 20: PRT811 Phase 1 Clinical Trial
PRT811 Phase 1 Clinical Trial ANTICIPATED MID-2021 Dose Escalation Expansion Cohorts Glioblastoma (N~20) Primary CNS Lymphoma (N~20) * (2 weeks on/1 week off) 21-day cycles ** (Continuous 3 weeks on) 21-day cycles Potential PoC in CNS cancers in 2H2021 1* 2* 3* 4* 5* 200mg QD Advanced Solid Tumors G
Slide 21: PRT811 Phase 1 Interim Results Demonstrated Dose-Dependent PK/PD
IC50 PRT811 Phase 1 – Interim Results Demonstrated Dose-Dependent PK/PD PRT811 offers the potential to achieve desired levels of PRMT5 inhibition in tissues including brain PRT811 Pharmacokinetic Profile DAY 1 Data as of March 15, 2021 PRT811 Pharmacodynamic Profile Serum sDMA PRT811 Pharmacokinetic
Slide 22: PRT811 Phase 1 Clinical Trial Safety Profile
PRT811 Phase 1 Clinical Trial Safety Profile Phase 1 clinical trial of PRT811 enrolled 24 patients 16 with advanced solid tumors Eight with GBM Overall safety profile Four patients each experienced one SAE, none of which was attributed to study therapy No dose limiting toxicities observed One patien
Slide 23: Confirmed PR in Glioblastoma Multiforme
Confirmed PR in Glioblastoma Multiforme BASELINE WEEK 7 Patient History Study Follow-Up Diagnosed with recurrent GBM and originally treated with surgery and chemoradiation with Temodar in July 2019 Patient has not been treated with steroids or Avastin, and clinical status is stable Presented with pr
Slide 24: PRT811 Expands PRMT5 Opportunity into CNS Cancers
PRT811 Expands PRMT5 Opportunity into CNS Cancers PRMT5 Scientific Rationale Tumor Types Transcriptional Regulation Synthetic Lethality Splicing Dysregulation Glioblastoma Multiforme CNS Metastatic Disease Primary CNS Lymphoma 10,000 patients annually PRMT5i-sensitive subset of 200,000 CNS metastati
Slide 25: MCL1 Program
MCL1 Program a3 Prelude
Slide 26: Prelude MCL1 Program
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 IV
Slide 27: PRT1419 Differentiated Clinical-Stage MCL1 Inhibitor Candidate
PRT1419 Differentiated Clinical-Stage MCL1 Inhibitor Candidate MCL1 MCL1 Inhibitor Potent and selective Oral and IV formulations Targeting Selected Heme Cancers Robust activity in preclinical models with once weekly dosing Synergistic with venetoclax Optimized PK Profile Maximizes Therapeutic Window
Slide 28: PRT1419 is a potent MCL1 inhibitor candidate with no preclinical evidence of cardiac toxicity
PRT1419 is a potent MCL1 inhibitor candidate with no preclinical evidence of cardiac toxicity PRT1419: Potential Leading MCL1 Inhibitor Prelude compounds are competitive inhibitors of BIM binding Highly Potent Binding to MCL1 Assay AMG176 AZD5991 MIK665 PRT1419 Proliferation IC50 (nM) 150 31 4.5 80
Slide 29: PRT1419 Demonstrated Preclinical Activity as Monotherapy and in Combination
Dose-dependent activity with tumor regression at once-weekly, oral dosing in hematological tumor models PRT1419 Demonstrated Preclinical Activity as Monotherapy and in Combination Monotherapy Combination MCL1
Slide 30: PRT1419 Phase 1 Clinical Trial
Dose Escalation Expansion Cohorts Phase 1 dose escalation ongoing; only Grade 1-2 AEs observed AML (N~20) AML or MDS PRT1419 + Venetoclax or Aza (N~20) NHL (B or T cell Lymphoma) (N~20) Multiple Myeloma (N~20) Oral PRT1419 Phase 1 Clinical Trial Phase 1 Initiated in 2H2020 1 2 3 4 AML and High Risk
Slide 31: Preclinical Programs CDK9, SMARCA2
Preclinical Programs CDK9, SMARCA2
Slide 32: Prelude CDK9 Program
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 tolerabili
Slide 33: PRT2527: Potent and Highly Selective CDK9 Inhibitor Candidate
PRT2527: Potent and Highly Selective CDK9 Inhibitor Candidate Compound Dinaciclib AZD4573 PRT2527 Biochemical IC50 (nM) CDK9 4.4 1.9 0.95 Proliferation IC50 (nM) 11 18 WB IC50 (nM) 192 196 Fold Selectivity CDK9 vs Other Isoforms CDK1 98x 23x 73x CDK2 7x 35x 340x CDK3 0.5x 2x 35x CDK4 13x 53x 250x CD
Slide 34: CDK9 Inhibitor Candidate: PRT2527 Improved Selectivity
CDK9 Inhibitor Candidate: PRT2527 Improved Selectivity PRT2527 AZD4573 MV4-11 (AML) PRT2527 (nM) 4 DMSO 12 37 111 333 1000 1.37 0.46 Myc pSer2RNAP2 MCL1 Caspase Actin PRT2527 IND expected to be filed in 2021 Sustained Regressions at Well-Tolerated Doses in Vivo Potent in Vitro Activity CDK9
Slide 35: SMARCA2 Targeted Degrader Program
SMARCA2 Targeted Degrader Program SMARCA4 and SMARCA2 Regulate Chromatin Accessibility and Gene Expression Loss of SMARCA4 Leads to SMARCA2 Dependency Opportunity to target 10 – 12% NSCLC with SMARCA4 deletions SMARCA2 Loss of SMARCA4 SMARCA4 MUTANT TUMORS NORMAL CELL Paralog Dependency SMARCA4 Comp
Slide 36: Prelude Discovered Selective sub-nM SMARCA2 Degraders
Degradation IC50: 0.76nM Prelude Discovered Selective sub-nM SMARCA2 Degraders SMARCA2 Lead optimization in progress – IND-enabling anticipated in the first half of 2021 Prelude SMARCA2 Degraders Replicate Genetic Synthetic Lethality Sub-Nanomolar Potency for SMARCA2 Degradation Highly Selective for
Slide 37: Prelude Therapeutics Projected Milestones
Prelude Therapeutics Projected Milestones Expansion cohorts 4Q2020/1H2021 Data presentation 2H2021 Expansion cohorts mid-2021 Initial clinical data 2H2021 Addition of expansion cohorts expected 2H2021 (oral) IND 2021 UPCOMING MILESTONES PRT2527 (CDK9) IND TARGET SMARCA2 IND-ENABLING PRT811 (Brain-pe
Slide 38: Financial Highlights
Financial Highlights Shares Outstanding 43.7 million shares voting and non-voting common stock as of December 31, 2020 60.5 million shares fully diluted Excludes 2.9 million shares voting and non-voting common stock issued in January 2021 follow-on offering Cash and Cash Equivalents $218.3 million a
Slide 39: Prelude Therapeutics Corporate Highlights
Prelude Therapeutics Corporate Highlights 4 INDs cleared to date; 3 Clinical stage programs; 3 Preclinical assets Highly productive target class agnostic discovery engine Pipeline focused on differentiated and validated targets Multiple wholly owned programs with fast-to-market potential Lead progra
Slide 40: Thank You
Thank You
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