Prelude Therapeutics Incorporated · NASDAQ:PRLD
Prelude Therapeutics — Investor Presentation (February 2022)
33 slides from Prelude Therapeutics's investor presentation, Feb 16, 2022
Slide 1: Precision Oncology Redefined
Exhibit 99.1 Precision Oncology Redefined February 2022
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: Vision
Prelude Therapeutics: Vision Build a fully integrated oncology company on the foundation of drug discovery excellence to deliver novel precision cancer medicines to underserved patients 3
Slide 4: Experienced Management Team: Proven Track Records
Experienced Management Team: Proven Track Records Board of Directors Paul Friedman, MD Founding member CEO Former CEO Mardi Dier CFO Laurent Chardonnet Former CFO, Kris Vaddi, PhD Deborah Morosini, MD, MSW Chief Financial Officer CBO Executive Vice President Founder & and Chief of Clinical Affairs C
Slide 5: Prelude Therapeutics: Key Reasons to Invest
Prelude Therapeutics: Key Reasons to Invest Internal Effective Focused Strong Well Discovery R&D Clinical Execution Capitalized Engine Approach Development Seamless ~$320M cash Driving to ‘go/no Scientists with Proprietary integration & marketable go’ decisions with proven track diversified between
Slide 6: Precision Oncology: Targeting Clinically Relevant Pathways
Precision Oncology: Targeting Clinically Relevant Pathways SMARCA2 TARGET PRMT5 MCL1 CDK9 (BRM) mRNA Splicing & Transcriptional Synthetic Apoptosis MOA DNA Repair Regulation Lethality Spliceosome Venetoclax SMARCA4 (BRG1) MYC Amplified SELECTABLE Mutations, Resistance Mutations PATIENTS HRD+ CANCERS
Slide 7: Current Pipeline: Diversified and Growing
Current Pipeline: Diversified and Growing PHASE 1 PHASE 1 PHASE 2/3 PROGRAM CANCER INDICATIONS IND ENABLING ESCALATION EXPANSION REGISTRATION PRT543 Solid Tumors, Myeloid Cancers (PRMT5) IDH+ High Grade Glioma, PRT811 Uveal Melanoma (Brain Penetrant PRMT5) PRT1419 AML, MDS, CLL (MCL1) PRT2527 Sarcom
Slide 8: 2022 Goals: Aggressive with Clear Deliverables
2022 Goals: Aggressive with Clear Deliverables PRMT5 MCL1 CDK9 SMARCA (BRM) PRT543/PRT811 PRT1419 PRT2527 PRT-SCA2 Complete dose Complete Establish RP2D escalation expansion phases File IND for both molecules Demonstrate Establish safety, safety in target Demonstrate PoC combination with engagement,
Slide 9: PRM
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Slide 10: PRMT5 Pathway Drives Oncogenesis and Resistance
PRMT5 Pathway Drives Oncogenesis and Resistance PRMT5 • PRMT5 catalyzes symmetric arginine dimethylation (sDMA) of protein substrates SYMMETRIC including histones, transcription factors, and DIMETHYLATION spliceosome proteins • Dimethylated substrates of PRMT5 control key TUMOR CELL oncogenic and re
Slide 11: Differentiated PRMT5 Inhibitors
Differentiated PRMT5 Inhibitors PRT543 PRT811 • Highly selective and potent oral candidates • PRT811 is highly differentiated in the class with high brain penetration potential Applicability in Both Solid Tumors and Heme • Strong scientific rationale and robust preclinical activity across broad rang
Slide 12: PRMT5: Phase Data Will Drive Phase 2/3 Indication Selection
PRMT5: Phase 1 Data Will Drive Phase 2/3 Indication Selection PRMT5 Part 1 Part 2 Dose Escalation Expansion Cohorts COMPLETED ONGOING RECOMMENDED EXPANSION DOSES Adenoid Cystic Carcinoma (N~40) PRT543 PRT543 45 mg 5x/wk Homologous Recombination Deficient (HRD+) (solid tumors) Solid Tumors (N~40) 35
Slide 13: PRT543 and PRT811 Demonstrate Desirable PK and PD Properties
PRT543 and PRT811 Demonstrate Desirable PK and PD Properties PRMT5 Dose-Dependent Increases in Cmax and AUC Dose-dependent Inhibition of Serum sDMA 500 400 300 200 PRT543 100 0 PRT811 13 Data presented at 2021 AACR-NCI-EORTC Annual Meeting. serum sDMA (ng/ml) ± Mean± SEM Baseline ≤ 22.5 mg BIW 45 mg
Slide 14: PRMT5 Phase 1: Key Takeaways and Next Steps
PRMT5 Phase 1: Key Takeaways and Next Steps PRMT5 FAVORABLE DESIRABLE PK & PRELIMINARY NEXT STEPS SAFETY PROFILE PD PROFILES CLINICAL ACTIVITY PRT543 and PRT811 well Dose-dependent increase Objective responses in Complete expansion tolerated in exposure solid tumors phases for both molecules IWG ane
Slide 15: Prelude
Prelude & THERAPEUTICS 4 % Rs <
Slide 16: MCL1: Targeting Cancer Cell Survival
MCL1: Targeting Cancer Cell Survival MCL1 • MCL1 is a member of family inhibitors of apoptosis (BCL2); often overexpressed in cancers • BCL2 family is clinically validated – Venetoclax approved for lymphoid and myeloid malignancies Mechanism • MCL1 is a bypass and resistance mechanism for Venetoclax
Slide 17: MCL1 Inhibitor PRT1419
MCL1 Inhibitor PRT1419 • Potent and selective • No cardiotoxicity signal in GLP-toxicology studies Targeting Selected Heme and Solid Cancers • Robust activity in preclinical models with once weekly dosing • Potential combination strategy with Venetoclax and/or HMAs in Hematological malignancies Diff
Slide 18: MCL1: Phase Overview
MCL1: Phase 1 Overview MCL1 Dose Expansion Phase 1 Dose Escalation Dose Escalation Combination Combination (Ven + Aza) Monotherapy (mg/m2) 1419 VEN+ AZA R/R AML/MDS ✓✓ ✓ 1419 + AZA R/R AML/MDS 1H 2022 2H 2022 1H 2023 18 18
Slide 19: Prelude
Prelude THERAPEUTICS 4 % Rs
Slide 20: CDK9: Targeting Cancer Through Transcriptional Regulation
CDK9: Targeting Cancer Through Transcriptional Regulation CDK9 • CDK9 phosphorylates RNA Pol II and regulates transcription SUPER ENHANCER uper nhancer • Regulates expression of several immediate early genes driving oncogenesis and resistance (i.e. MYC, MYB, MCL1) F F F MYC & MYB Mechanism • Non-sel
Slide 21: PRT2527 CDK9 Inhibitor
PRT2527 CDK9 Inhibitor • Most selective in the class vs CDK family and across the kinome • Low nanomolar potency in blocking tumor cell proliferation Targeting Selected Heme and Solid Cancers • Robust activity in preclinical models at well-tolerated doses • Enhanced sensitivity in tumors that are MY
Slide 22: Robust Activity in Preclinical Models at Well-Tolerated Doses
Robust Activity in Preclinical Models at Well-Tolerated Doses Sustained Regressions at CDK9 Well-Tolerated Doses in Vivo in both Heme Sustained Regression at Well-Tolerated Doses In Vivo in both and Solid Tumor Models Heme and Solid Tumor Models 7 NSCLC PDX MV4-11 (AML) (MYC Amplified) 6 800 1500 Ve
Slide 23: CDK9: Clinical Overview
CDK9: Clinical Overview Phase 1 Dose Escalation (Bayesian Design) ONGOING Phase 2 With Recommended Dose From Completed Phase 1 Trial (TARGET 1H 2023) MYC-Dependent Solid Tumors (NSCLC, Prostate) Sarcoma MYC-dependent solid tumors Hematologic Malignancies Hematologic Malignancies 23
Slide 24: SMARCA2 (BRM) Program PRT-SCA2
SMARCA2 (BRM) Program PRT-SCA2
Slide 25: Targeting SMARCA2 (BRM): Leveraging Synthetic Lethality
Targeting SMARCA2 (BRM): Leveraging Synthetic Lethality SMARCA2 • 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) Mechanism ‒ Loss of SMARCA4 (BRG1) t
Slide 26: Achieving SMARCA2 Selectivity Through Degrader Approach
Achieving SMARCA2 Selectivity Through Degrader Approach SMARCA2 • SMARCA2 selectively over highly homologous SMARCA4 isoform has been a challenging SMALL MOLECULE DEGRADER medical chemistry problem with traditional small molecule approaches E3 LIGASE PROTEASOME • Target Protein Degradation (TPD) of
Slide 27: PRT-SCA2: Potent and Selective SMARCA2 Degrader with In Vivo Activity
PRT-SCA2: Potent and Selective SMARCA2 Degrader with In Vivo Activity SMARCA2 Highly Selective for SMARCA2 Highly Selective for SMARCA2 Prelude SMARCA2 Degraders Replicate Degradation In Vitro Degradation In Vivo Genetic Synthetic Lethality PRT007(nM): DMSO 0.1 1.0 10 100 1000 Hours after dosing NCI
Slide 28: PRT-SCA2: Potent and Selective SMARCA2 Degrader with In Vivo Activity
PRT-SCA2: Potent and Selective SMARCA2 Degrader with In Vivo Activity SMARCA2 Robust Tumor Growth Inhibition of SMARCA4 mutated but not WT Xenograft Vehicle 1800 600 Vehicle PRT-SCA2 1600 PRT-SCA2 1400 1200 400 1000 SMARCA4 mutant SMARCA4 WT 800 600 200 400 200 0 0 0 2 4 6 8 10 12 14 0 4 8 12 16 20
Slide 29: SMARCA2: Degrader Program Overview
SMARCA2: Degrader Program Overview SMARCA2 Candidate molecule(s) identified Phase 1 Dose Escalation IND enabling studies initiated TARGET 1Q 2023 IND Enabling Studies IND Filing 2H 2022 SMARCA4-MUTATED NSCLC AND OTHER TUMOR TYPES 29
Slide 30: Summary
Summary 7% Prelude cia
Slide 31: 2022 Goals: Aggressive with Clear Deliverables
2022 Goals: Aggressive with Clear Deliverables PRMT5 MCL1 CDK9 SMARCA (BRM) PRT543/PRT811 PRT1419 PRT2527 PRT-SCA2 Complete dose Complete Establish RP2D escalation expansion phases File IND for both molecules Demonstrate Establish safety, safety in target Demonstrate PoC combination with engagement,
Slide 32: Prelude Therapeutics: Key Reasons to Invest
Prelude Therapeutics: Key Reasons to Invest Internal Effective Focused Strong Well Discovery R&D Clinical Execution Capitalized Engine Approach Development Seamless ~$320M cash Driving to ‘go/no Scientists with Proprietary integration & marketable go’ decisions with proven track diversified between
Slide 33: Thank You
Thank You 7% Prelude cia
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