Prelude Therapeutics Incorporated · NASDAQ:PRLD
Prelude Therapeutics — Investor Presentation (January 2021)
47 slides from Prelude Therapeutics's investor presentation, Jan 4, 2021
Slide 1: Corporate Presentation January 2021
Exhibit 99.1 Corporate January 2021 PresentationExhibit 99.1 Corporate January 2021 Presentation
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: Prelude Therapeutics Vision
Prelude Therapeutics Vision Building a patient-focused precision oncology company Regulatory Strategy Efficient development path with potential for accelerated regulatory approvals Discovery Engine Powered by scientists with proven ability to deliver precision oncology medicines Commercial Approach
Slide 4: Senior Management & Board of Directors
Senior Management & Board of Directors Board of Directors Experienced. Proven. Focused. Paul Friedman, MD CEO Former CEO Mardi Dier Parsaclisib CFO Former CFO, CBO PhD Andrew Combs PhD MD, PhD Peggy Scherle David Mauro Victor Sandor, MD Chief Medical Officer EVP and Chief Scientific Officer Former H
Slide 5: Prelude Therapeutics Corporate Highlights
Prelude Therapeutics Corporate Highlights INDs approved in 3 years; 3 clinical stage molecules 3 Pipeline focused on differentiated and validated targets Highly productive target class • 1 IND filed each year in 2018, 2019, and 2020 • At least 1 additional IND anticipated in 2021 agnostic discovery
Slide 6: Prelude Discovery and Development Approach
Prelude Discovery and Development Approach Target Selection Discovery Engine Pipeline Methyltransferases Identify target mechanisms Kinases with compelling biological Novel rationale Intervention Points Degraders Leverage our advanced medicinal chemistry capabilities to create Chemical better produc
Slide 7: Prelude Therapeutics Pipeline
Prelude Therapeutics Pipeline Discovery/ IND Worldwide Program Indications Phase 1 Phase 2 Phase 3 Upcoming Milestones Preclinical Enabling Rights Selected Solid Tumors • Expansion cohorts (incl. ACC, HRD+) 4Q2020/1H2021 PRT543* Selected Myeloid • Data presentation (PRMT5) Malignancies 2H2021 (incl.
Slide 8: PRMT5 Programs
PRMT5 Programs 8PRMT5 Programs 8
Slide 9: PRMT5 Pathway Drives Oncogenesis and Resistance
PRMT5 Pathway Drives Oncogenesis and Resistance Regulates transcription of genes linked to cancer cell growth and proliferation Cell cycle genes Cancer metabolism Tumor suppressors Spliceosome Histones Oncogenes Proliferative signaling Transcription Factors PRMT5 inhibition can be leveraged to poten
Slide 10: PRMT5 Regulates Drivers of DNA Damage Repair
PRMT5 Regulates Drivers of DNA Damage Repair PRMT5 inhibition suppresses DNA repair gene expression & growth of HRD+ cell lines PRMT5 promotes DNA repair and cell survival 1000 POLD1 BRCA1 100 ATM CHEK2 RAD51 ATR 10 BRCA2 PRMT5 regulates multiple DNA repair genes 1 -4 -3 -2 -1 0 1 2 3 4 PRT543 - 0.2
Slide 11: PRMT5 Pathway Is Clinically Validated in Multiple Cancers by GSK'595
PRMT5 Pathway Is Clinically Validated in Multiple Cancers by GSK'595 21% OR and mPFS of 11.2 mos observed with GSK'595 in Adenoid cystic carcinoma (ACC) Highly underserved cancer in which typical OR is <10% and PFS is 4 – 6 mos Objective responses reported in other cancers; currently in dose expansi
Slide 12: Prelude PRMT5 Program
Prelude PRMT5 Program Optimized for a well-balanced and differentiated profile Differentiating Mechanism of Action Potency Selectivity Optimal Chemical Substrate Prelude compounds Space competitive are co-factor (SAM) Inhibitors (GSK) competitive inhibitors ADME Pharmaceutical properties Designed an
Slide 13: PRT543 – Opportunity for Accelerated Development Path
PRT543 – Opportunity for Accelerated Development Path Potential best-in-class PRMT5 inhibitor Potential Rapid Path to Market Targets Selected Optimized Solid Tumors and PK Profile Phase 1 ongoing Differentiated Heme Malignancies PRMT5 Inhibitor Enrollment began in select High solid tumor expansion S
Slide 14: PRT543 – A Potent, Selective and Oral PRMT5 Inhibitor Candidate
PRT543 – A Potent, Selective and Oral PRMT5 Inhibitor Candidate PRT543 is Highly-Selective Dose-Dependent PD Vs 36 methyltransferases in addition to a broad panel of Modulation of sDMA (symmetric dimethylation) is a receptors, transporters and channels direct measure of PRMT5 activity ~50% reduction
Slide 15: PRT543 Demonstrated Broad Preclinical Activity
PRT543 Demonstrated Broad Preclinical Activity JAK2V617F MPN Model Monotherapy Combination Oral administration of PRT543 as monotherapy and in combination with ruxolitinib led to significant decrease in spleen size in the JAK2VF bone marrow transplant model of MF. Data represent mean Ł SEM. Dotted l
Slide 16: PRT543 Phase 1 Clinical Trial
PRT543 Phase 1 Clinical Trial as of September 1, 2020 4Q2020 / Early 2021 Expansion cohorts Expansion Cohorts Dose Escalation in selected patients 35mg Adenoid Cystic Carcinoma (N~20) QD 50mg Recommended QD Homologous Recombination 35mg Expansion Dose Deficient (HRD+) Solid Tumors 5x/wk 8 45mg (N~20
Slide 17: PRT543 Phase 1 – Interim PK/PD Results
PRT543 Phase 1 – Interim PK/PD Results Demonstrated Predictable Profile as of September 1, 2020 Dose-Proportional Increase in Exposure Dose-Dependent Decrease in Serum sDMA (Day 1) * PD Samples -72h post dose * * * * Serum was obtained from patients at various times following administration of PRT54
Slide 18: PRT543 Favorable Phase 1 Safety Profile
PRT543 Favorable Phase 1 Safety Profile as of September 1, 2020 Interim Safety data available for 41 patients 30 in Group A (solid tumors and NHL); 11 in Group B (myeloid malignancies) AE profiles similar between patient groups Primarily GI and manageable with standard treatments Diarrhea, nausea an
Slide 19: PRT543 Preliminary Efficacy Data
PRT543 Preliminary Efficacy Data as of September 1, 2020 Group A (Solid Tumors) Thirteen patients have received doses ≥35 mg 5x/week and are response evaluable per RECIST 1.1: One patient demonstrated durable confirmed complete response (CR) in HRD+ high grade serous ovarian cancer Four patients dem
Slide 20: Durable Confirmed CR in HRD+ High Grade Serous Ovarian Cancer
Durable Confirmed CR in HRD+ High Grade Serous Ovarian Cancer Patient History 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 21: PRT543 Clinical Update as of December 16, 2020
PRT543 Clinical Update as of December 16, 2020 Phase 1 clinical trial of PRT543 has enrolled 61 patients (42 with advanced solid tumors, one with NHL, 11 with MF, and seven with MDS) Overall safety profile unchanged from the September 1, 2020 data cutoff and consistent between both Groups A and B Ma
Slide 22: PRT543 Offers Broad Opportunity Across Tumor Types
PRT543 Offers Broad Opportunity Across Tumor Types US Market Opportunity Tumor Types ACC: 10-15,000 patients Scientific Rationale Ovarian: 63% of ovarian tumors HRD+ TNBC: 55% of TNBC tumors HRD+ Adenoid Cystic Carcinoma Transcriptional Prostate: 25% of mCRPC tumors HRD+ HRD+ Tumors (Ovarian, TNBC,
Slide 23: PRT811 – Expanding PRMT5 Opportunity into CNS Cancers
PRT811 – Expanding PRMT5 Opportunity into CNS Cancers Only clinical stage brain-penetrant PRMT5 inhibitor Differentiated Targeting GBM and Potential Rapid Brain-Penetrant CNS Metastatic Optimized Path to Market PRMT5 Inhibitor Brain Cancers PK Profile Phase 1 ongoing High target High and sustained e
Slide 24: PRT811 – A Potent, Selective and Brain Penetrant PRMT5 Inhibitor Candidate
PRT811 – A Potent, Selective and Brain Penetrant PRMT5 Inhibitor Candidate PRT811 is a Potent Equivalent Potency and 100-fold SAM-Competitive PRMT5 Inhibitor Higher Brain Exposure vs GSK’595 Highly selective vs 36 methyl transferases in addition to a GSK’595 PRT811 broad panel of receptors, transpor
Slide 25: PRT811 – Strong Activity Demonstrated in GBM Models
PRT811 – Strong Activity Demonstrated in GBM Models GBM Orthotopic Model - sDMA PRT811 in GBM Model PRT811 Inhibited Tumor Growth PRT811 Decreased sDMA Levels in Orthotopic Brain Tumor in GBM Model Model Vehicle PRT811 We believe PRT811 is uniquely positioned to potentially 25 treat PRMT5 sensitive
Slide 26: PRT811 Phase 1 Clinical Trial
PRT811 Phase 1 Clinical Trial as of September 1, 2020 Anticipated 1H2021 Dose Escalation* Expansion Cohorts Recommended Expansion cohorts Expansion Dose 200mg In selected patients QD 120mg Glioblastoma QD (N~20) 60mg QD 5 Primary CNS Lymphoma 30mg 4 QD (N~20) 15mg Advanced Solid 3 QD Tumors 2 Glioma
Slide 27: PRT811 Phase 1 Interim Results Demonstrated Dose-Dependent PK
PRT811 Phase 1 Interim Results Demonstrated Dose-Dependent PK as of September 1, 2020 PRT811 Pharmacokinetic Profile Day 1 M 1ean 1 5 mg 5 mg (n=3) M 3ean 3 0 mg 0 mg (n=3) 60 mg Mean 60 mg (n=3) 1000.0 Dose-dependent exposure 120 mg Mean 120 mg (n=4) 200 mg Mean 200 mg (n=4) Dose-dependent sDMA Inh
Slide 28: Confirmed PR in Glioblastoma Multiforme
Confirmed PR in Glioblastoma Multiforme Patient History 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 progressive disease in June 2020 E
Slide 29: PRT811 Clinical Update as of December 16, 2020
PRT811 Clinical Update as of December 16, 2020 Phase 1 clinical trial of PRT811 has enrolled 24 patients (eight with GBM and 16 with advanced solid tumors) Overall safety profile unchanged from the September 1, 2020 data cutoff Four patients have each experienced one SAE, none of which attributed to
Slide 30: PRT811 Expands PRMT5 Opportunity into CNS Cancers
PRT811 Expands PRMT5 Opportunity into CNS Cancers US Market Opportunity Tumor Types Scientific Rationale 10,000 patients annually Glioblastoma Multiforme Transcriptional Regulation Splicing Primary CNS Lymphoma ~2,000 -~2,500 patients annually Dysregulation PRMT5i-sensitive subset of 200,000 CNS Syn
Slide 31: MCL1 Program
MCL1 Program 31MCL1 Program 31
Slide 32: 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 33: PRT1419: Oral Differentiated Clinical-Stage MCL1 Inhibitor Candidate
PRT1419: Oral Differentiated Clinical-Stage MCL1 Inhibitor Candidate Targeting Selected Optimized PK Potential Rapid Heme Cancers Profile Maximizes Path to Market MCL1 Inhibitor Therapeutic Robust activity in Potent Window Phase 1 dose preclinical models with escalation ongoing once weekly dosing Se
Slide 34: PRT1419: Potential Leading Oral MCL1 Inhibitor
PRT1419: Potential Leading Oral MCL1 Inhibitor Assay AMG176 AZD5991 MIK665 PRT1419 Highly Potent Binding to MCL1 Proliferation IC (nM) 150 31 4.5 80 50 Whole Blood IC (nM) 1800 320 430 210 50 Prelude compounds -6 Caco-2 (x10 cm/s) 6 <0.1 0.2 11 are competitive inhibitors of BIM binding Human Hepat.
Slide 35: PRT1419 Demonstrated Preclinical Activity as Monotherapy and in Combination
PRT1419 Demonstrated Preclinical Activity as Monotherapy and in Combination Monotherapy Combination Dose-dependent activity with tumor regression at once- 35 weekly, oral dosing in hematological tumor models MCL1PRT1419 Demonstrated Preclinical Activity as Monotherapy and in Combination Monotherapy
Slide 36: PRT1419: Clinical Trial Program
PRT1419: Clinical Trial Program Phase 1 Initiated in 2H2020 2021 Current Dose Escalation Expansion Cohorts Expansion cohorts in selected patients Recommended AML (N~20) Expansion Dose AML or MDS 4 PRT1419 + Venetoclax or Aza (N~20) Group A 3 High Risk MDS (N~20) AML and 2 High Risk MDS 1 Recommended
Slide 37: PRT1419 Clinical Update as of December 16, 2020
PRT1419 Clinical Update as of December 16, 2020 Phase 1 clinical trial of PRT1419 has enrolled four patients with various hematological malignancies No adverse events above Grades 1 or 2 and no serious adverse events have been observed Currently enrolling AML and high-risk MDS patients into the seco
Slide 38: Preclinical Programs CDK9, SMARCA2
Preclinical Programs CDK9, SMARCA2 38Preclinical Programs CDK9, SMARCA2 38
Slide 39: 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 40: PRT2527: Potent and Highly Selective CDK9 Inhibitor Candidate
PRT2527: Potent and Highly Selective CDK9 Inhibitor Candidate Compound Dinaciclib AZD4573 PRT2527 Highly Selective CDK9 Inhibitor Biochemical IC (nM) CDK9 4.4 1.9 0.95 50 Candidate 11 18 Proliferation IC (nM) 50 192 196 WB IC (nM) 50 CDK1 98x 23x 73x CDK2 7x 35x 340x Prelude compounds CDK3 0.5x 2x 3
Slide 41: CDK9 Inhibitor Candidate: PRT2527
CDK9 Inhibitor Candidate: PRT2527 Improved Selectivity Potent in Vitro Activity PRT2527 Sustained Regressions at Well-Tolerated Doses in Vivo PRT2527 (nM) pSer2RNAP2 MV4-11 (AML) MCL1 1500 Vehicle AZD PRT2527 AZD4573 Myc 1000 Caspase Actin 500 79% 96% 0 8 11 14 17 20 23 Days post inoculation 41 PRT2
Slide 42: SMARCA2 Targeted Degrader Program
SMARCA2 Targeted Degrader Program SMARCA4 and SMARCA2 Regulate Chromatin Loss of SMARCA4 Leads to Accessibility and Gene Expression SMARCA2 Dependency Breast cancer Missense Pancreatic cancer Non-missense Loss of SMARCA4 Ovarian cancer Deep deletion Small cell lung cancer Lung squamous cell carcinom
Slide 43: Prelude Discovered Selective sub-nM SMARCA2 Degraders
Prelude Discovered Selective sub-nM SMARCA2 Degraders Prelude SMARCA2 Degraders Sub-Nanomolar Potency for Highly Selective for SMARCA2 SMARCA2 Degradation Replicate Genetic Synthetic Degradation Lethality PRT1003361 Cont. vs PRT2835 120 7 SMARCA2 100 6 80 PBRM1 5 60 4 40 3 SMARCD1 FEM1B 20 Degradati
Slide 44: Prelude Therapeutics Projected Milestones
Prelude Therapeutics Projected Milestones H1 H2 H1 H2 2020 2021 Upcoming Milestones Expansion cohorts PRT543 (PRMT5) PRT543 4Q2020/1H2021 Phase 1 Expansion Phases (N=~160) Data presentation 2H2021 PRT811 (Brain-penetrant PRMT5) PRT811 Expansion cohorts 1H2021 Initial clinical data 2H2021 Phase 1 Exp
Slide 45: Financial Highlights
Financial Highlights Cash and Cash Equivalents $218.3 million as of December 31, 2020 (unaudited) Includes $166.6 million net proceeds raised in September 2020 IPO Shares Outstanding 43.7 million shares voting and non-voting common stock as of September 30, 2020 55.5 million shares fully diluted 45F
Slide 46: Prelude Therapeutics Corporate Highlights
Prelude Therapeutics Corporate Highlights INDs approved in 3 years; 3 clinical stage molecules 3 Pipeline focused on differentiated and validated targets Highly productive target class • 1 IND filed each year in 2018, 2019, and 2020 • At least 1 additional IND anticipated in 2021 agnostic discovery
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