Prelude Therapeutics Incorporated · NASDAQ:PRLD
Prelude Therapeutics — Investor Presentation (January 2022)
30 slides from Prelude Therapeutics's investor presentation, Jan 10, 2022
Slide 1: Precision Oncology Redefined
Precision Oncology Redefined Corporate Presentation January 2022 Exhibit 99.1
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 oncology medicines to patients with underserved cancers
Slide 4: Prelude Therapeutics: Building for Success
Powered by experienced drug developers with a proven track record of multiple successful oncology medicines Internal Discovery Engine Prelude Therapeutics: Building for Success Effective integration between cancer biology and medicinal chemistry to rapidly iterate and discover optimized molecules in
Slide 5: Building a Deep Portfolio of Oncology Assets
Target MOA Molecule(s) Development Stage Target Cancers Building a Deep Portfolio of Oncology Assets MCL1 CDK9 SMARCA2 (BRM) mRNA Splicing & DNA Repair PRT543 & PRT811 Phase 1 Expansion Spliceosome Mutations Selected CNS HRD+ Apoptosis PRT1419 Phase 1 Escalation Venetoclax and TKI- Resistant Heme an
Slide 6: Diversified Precision Oncology Pipeline
Program Cancer Indications IND Enabling Phase 1 Escalation Phase 1 Expansion Phase 2/3 Upcoming Milestones PRT543 (PRMT5) ACC, HRD+, spliceosome mutations Data readouts 2H22 Selected myeloid malignancies (incl. MF and MDS) PRT811 (Brain Penetrant PRMT5) IDH+ high grade glioma, uveal melanoma Data re
Slide 7: 2021 Accomplishments and 2022 Goals
Complete expansion phases for both molecules Demonstrate PoC in one or more indications Advance PRMT5 program into Phase 2 Establish RP2D Demonstrate safety in combination with Venetoclax/Azacitidine Demonstrate PoC Complete dose escalation Establish safety, target engagement and RP2D File INDs Init
Slide 8: PRMT5 Program PRT543 & PRT811
PRMT5 Program PRT543 & PRT811
Slide 9: PRMT5 Pathway Drives Oncogenesis and Resistance
PRMT5 Pathway Drives Oncogenesis and Resistance Transcription Factors PRMT5 Spliceosome Proteins Histones Symmetric Dimethylation PRMT5 catalyzes symmetric arginine dimethylation (sDMA) of protein substrates including histones, transcription factors, and spliceosome proteins Dimethylated substrates
Slide 10: Potential Best-In-Class PRMT5 Inhibitors
PRT543 PRT811 Potential Best-In-Class PRMT5 Inhibitors Differentiated PRMT5 Inhibitors 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 pre
Slide 11: PRMT5: Phase Overview
PRMT5: Phase 1 Overview Dose Escalation Unselected Patients Expansion Cohorts Selected Patients Solid Tumors GBM Myeloid Malignancies Recommended Expansion Doses PRT543 PRT811 Completed Ongoing PRT543 45 mg 5x/wk (solids) 35 mg 5x/wk (heme) PRT811 600 mg QD 1 2 3 4 5 6 7 Adenoid Cystic Carcinoma (N~
Slide 12: PRT543 and PRT811 Demonstrate Desirable PK and PD Properties
PRT543 and PRT811 Demonstrate Desirable PK and PD Properties Dose-dependent Inhibition of Serum sDMA Dose-Dependent Increases in Cmax and AUC Data presented at 2021 AACR-NCI-EORTC Annual Meeting PRT543 PRT811
Slide 13: PRT543 and PRT811 Clinical Activity and Safety
Durable CR in a patient with HRD+ ovarian cancer (35 mg 5x/wk; still on Rx) Stable disease and tumor regressions (<30%) in 5 patients including ACC and uveal melanoma Sustained hemoglobin and anemia improvements in multiple patients with myeloid malignancies Unselected patient population with advanc
Slide 14: PRMT5 Phase 1: Key Takeaways and Next Steps
PRMT5 Phase 1: Key Takeaways and Next Steps Favorable Safety Profile Desirable PK & PD Profiles Preliminary Clinical Activity Next Steps PRT543 and PRT811 well tolerated Low incidence of dose-limiting toxicities at expansion doses Dose-dependent increase in exposure PRT811 demonstrated best-in-class
Slide 15: MCL1 Program
MCL1 Program Ca) <3 Prelude
Slide 16: MCL1: Targeting Cancer Cell Survival
MCL1: Targeting Cancer Cell Survival 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 malignacies MCL-1 is a bypass and resistance mechanism for venetoclax and multiple TKIs Ch
Slide 17: PRT1419 Differentiated Clinical-Stage MCL1 Inhibitor Candidate
PRT1419 Differentiated Clinical-Stage MCL1 Inhibitor Candidate MCL1 Inhibitor 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
Slide 18: PRT1419 Phase 1 Overview
Status Dose escalation (monotherapy) ongoing Oral – Myeloid malignancies IV – Solid tumors Next Steps Combination cohorts Venetoclax and/or HMA Identify RP2D and initiate expansion phase Report dose escalation data (2H2022) Dose Escalation (ongoing) AML and High Risk MDS (Oral) Solid Tumors (IV) Rec
Slide 19: CDK9 Program
CDK9 Program Prelude : PRT2527 THERAPEUTICS
Slide 20: CDK9: Targeting Cancer Through Transcriptional Regulation
CDK9: Targeting Cancer Through Transcriptional Regulation 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 mul
Slide 21: PRT2527 Potential Best-in-Class Selectivity and Potency CDK9 Inhibitor
PRT2527 Potential Best-in-Class Selectivity and Potency 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 En
Slide 22: PRT2527 Phase 1 Status and Next Steps
Status Next Steps Phase 1 Overview Phase 1 Baysian Design (ongoing) MYC-dependent Solid Tumors and Hematologic Malignancies MYC-dependent solid tumors Sarcoma Hematologic malignancies PoC Phase 2 (Target 1H 2023) Complete Phase 1 Select RP2D Initiate Phase 2 Dose Escalation Solid tumors Hematologica
Slide 23: SMARCA2 (BRM) Program
SMARCA2 (BRM) Program Prelude THERAPEUTICS ay
Slide 24: 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 dependency on SMARCA2 (BRM) Subsets of solid tumors exp
Slide 25: Achieving SMARCA2 Selectivity Through Degrader Approach
Achieving SMARCA2 Selectivity Through Degrader Approach SMARCA2 selectivity over highly homologous SMARCA4 isoform has been a challenging medicinal chemistry problem with traditional small molecule approaches Targeted Protein Degradation (TPD) of SMARCA2 selectively over SMARCA4 is possible through
Slide 26: PRT-SCA2: Potent and Selective SMARCA2 Degrader with in Vivo Activity
PRT-SCA2: Potent and Selective SMARCA2 Degrader with in Vivo Activity Prelude SMARCA2 Degraders Replicate Genetic Synthetic Lethality Highly Selective for SMARCA2 Degradation SMARCA2 Actin Veh 8h 24h SMARCA4 Hours after dosing In vitro In vivo HT1080 SM4 KO DMSO 0.1 1.0 10 100 1000 PRT007(nM): Calu-
Slide 27: SMARCA2 Degrader Program Overview
Status Next Steps Candidate molecule(s) identified IND enabling studies initiated File IND 2022 Initiate Phase 1 escalation study in SMARCA4 mutant cancers SMARCA4 Mutated NSCLC and other tumor types Phase 1 Dose Escalation Target 2H 2022 SMARCA2 Degrader Program Overview IND Filing IND Enabling Stu
Slide 28: Corporate Highlights
Corporate Highlights <3 Prelude
Slide 29: Our Investment Thesis
Our Investment Thesis Internal discovery engine Differentiated R&D approach Strong execution and commitment to discovery Focused clinical development in underserved cancers Strong financial position: ~$320M cash and marketable securities at 9/30/21 PMRT5 MCL1 CDK9 SMARCA2 (BRM) Data Rich 2022
Slide 30: Thank You
Thank You <3 Prelude cata
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