Prelude Therapeutics Incorporated · NASDAQ:PRLD
Prelude Therapeutics — Investor Presentation (November 2022)
32 slides from Prelude Therapeutics's investor presentation, Nov 14, 2022
Slide 1: Corporate Presentation November 2022
PRELUDE Corporate Presentation NOVEMBER 2022 Exhibit 99.2
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 Discovery and Development Approach
Target Class Agnostic CHEMICAL LEADS NOVEL INTERVENTION POINTS Medicinal Chemistry Capabilities Cancer Biology & Translational Expertise KINASES TARGETED PROTEIN DEGRADERS METHYLTRANSFERASES LEVERAGE Our advanced medicinal chemistry capabilities to create optimal clinical candidates PURSUE Targets t
Slide 4: Prelude Therapeutics: Key Highlights
Prelude Therapeutics: Key Highlights Effective Research Seamless integration between biology and chemistry Strong Execution Rapidly advancing a diversified proprietary pipeline Focused Clinical Development Developing meaningful medicines for patients with cancer Well Capitalized $224M cash, cash equ
Slide 5: Experienced Management Team: Proven Track Records
Former CMO Former CEO General Partner Experienced Management Team: Proven Track Records Board of Directors Victor Sandor, MD Paul Friedman, MD CEO David Bonita, MD Julian C. Baker Managing Member Baker Brothers Investments Kris Vaddi, PhD Founder & Chief Executive Officer Mardi Dier Former CFO, CBO
Slide 6: Diversified Precision Oncology Pipeline
Diversified Precision Oncology Pipeline PROGRAM CANCER INDICATIONS DISCOVERY PHASE 1 PHASE 2/3 PRT2527 (CDK9) Selected solid and hematologic malignancies PRT1419 (MCL1) Selected hematologic malignancies and solid tumors PRT3645 (Brain Penetrant CDK4/6) Solid tumors PRT3789 (SMARCA2) Multiple genomic
Slide 7: PRT2527: CDK9 Inhibitor
PRT2527: CDkg9 Inhibitor
Slide 8: 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 mu
Slide 9: PRT2527: Potent and Highly Selective CDK9 Inhibitor Candidate
PRT2527: Potent and Highly Selective CDK9 Inhibitor Candidate Compound AZD4573 KB0742 VIP152** PRT2527 Biochemical* IC50 (nM) CDK9 1.9 483 16 0.95 Proliferation* IC50 (nM) 11 915 84 18 Plasma* IC50 (nM) 192 1056 923 196 Fold Selectivity CDK9 vs Other Isoforms CDK1 23x >20x 371x 73x CDK2 35x >20x 147
Slide 10: PRT2527: CDK9 Inhibitor Phase Studies
PRT2527: CDK9 Inhibitor Phase 1 Studies PRT2527 Solid Tumors N=11 PRT2527 MYC Amplified or Overexpressed Solid Tumors, Prostate Cancer N=15 Solid Tumors Dose dependent increases in exposure and target engagement were observed MYC and MCL1 depletion to levels consistent with tumor regression in precl
Slide 11: PRT1419: MCL-1 Inhibitor
PRT1419: MCL-1 Inhibitor
Slide 12: 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 malignancies MCL1 is a bypass and resistance mechanism for Venetoclax and multiple TKIs Ch
Slide 13: PRT1419: Phase Study in Hematologic Malignancies
PRT1419: Phase 1 Study in Hematologic Malignancies PRT1419 Monotherapy AML/MDS/CMML CLL/SLL FL/MZL/MCL N=24-30 PRT1419 Combination PRT1419+Aza: AML/MDS/CMML PRT1419+Ven: AML/MDS/CMML PRT1419+Ven: MCL N=24-30 26 patients received ≥1 dose of PRT1419 with 15 patients @ 80 mg/m2 in the solid tumor study
Slide 14: PRT3645: CDK4/6
PRT3645: CDK4/6
Slide 15: CDK4/6: Targeting Cancer Through Cell Cycle Regulation
CDK4/6: Targeting Cancer Through Cell Cycle Regulation 15 Mechanism Cell cycle entry controlled by cyclin dependent kinases, CDK4 and CDK6 Validated mechanism with multiple CDK4/6 inhibitors approved for HR+ breast cancer Current CDK4/6 inhibitors are ineffective in treating brain metastasis and oth
Slide 16: PRT3645 Has High Brain Exposure and Demonstrates Robust Activity in Preclinical Models
PRT3645 Has High Brain Exposure and Demonstrates Robust Activity in Preclinical Models at Well-Tolerated Doses 16 PRT3645 demonstrates >10x higher brain penetration than approved CDK4/6 inhibitors PRT3546 shows robust activity in vivo as monotherapy and in combination
Slide 17: PRT3645: CDK4/6 Phase Study in Solid Tumors
PRT3645: CDK4/6 Phase 1 Study in Solid Tumors Initial clinical results at a medical conference in 2H 2023 RP2D in solid tumors expected in 2H 2024 A differentiated and highly brain penetrant CDK4/6 inhibitor Potential to extend the reach of CDK4/6 inhibition beyond HR+ breast cancers, for which the
Slide 18: PRT3789: SMARCA2 Degrader
PRT3789: SMARCA2 Degrader
Slide 19: Targeting SMARCA2 (BRM): Leveraging Synthetic Lethality
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
Slide 20: Achieving SMARCA2 Selectivity Through Degrader Approach
SMALL MOLECULE DEGRADER E3 LIGASE TARGET PROTEIN PROTEASOME UBIQUITINATED TARGET PROTEIN Mullard A. Nat Rev Drug Discov. 2019 SMARCA2 selectively over highly homologous SMARCA4 isoform has been a challenging medical chemistry problem with traditional small molecule approaches Target Protein Degradat
Slide 21: PRT3789: Potent and Selective SMARCA2 Degrader with In Vivo Activity
PRT3789: Potent and Selective SMARCA2 Degrader with In Vivo Activity Robust Tumor Growth Inhibition of SMARCA4 mutated but not WT Xenograft SMARCA4 mutant SMARCA4 WT PRT3789 PRT3789
Slide 22: Targeting SMARCA2 induces synthetic lethality in SMARCA4 mutated cancers
Targeting SMARCA2 induces synthetic lethality in SMARCA4 mutated cancers Frequency of SMARCA4 mutation in cancer A model for synthetic lethality Source: Ito K et al. Abstract 1139: Vol. 81, Cancer Research. AACR; 2021. p. 1139–1139. Subsets of solid tumors express SMARCA4 damaging mutations or gene
Slide 23: Significant Degradation of SMARCA2 Protein but not SMARCA4 in Rat PBMCs
Significant Degradation of SMARCA2 Protein but not SMARCA4 in Rat PBMCs with PRT3789 –PD Marker in Clinic Vehicle Low Dose Mid Dose High Dose SMARCA2 SMARCA4 LAMIN B1 SMARCA2 SMARCA4 LAMIN B1 Male Female
Slide 24: Frequency of SMARCA4 Mutations
Indication Any SMARCA4 Mutation1 NSCLC 10.0% Esophageal 8.0% Gastric (stomach adeno) 8.3% Skin (invasive and in situ melanoma)* 21.0% Endometrial (uterine corpus) 13.3% Squamous cell lung 7.7% Urinary (bladder) 9.0% Colorectal 6.0% Pancreatic 2.9% Melanoma (invasive) 8.7% Fernando et al. Natur
Slide 25: PRT3789: SMARCA2 Phase Study in Solid Tumors
PRT3789: SMARCA2 Phase 1 Study in Solid Tumors SMARCA2 inhibition has the greatest potential in patients with SMARCA4 deficient cancers, including approximately 5-10% of all non-small cell lung cancers Selective SMARCA2 degradation can be demonstrated in Phase 1 Study population: advanced, recurrent
Slide 26: Summary
Summary Current cash runway expected through Q4 2024 pending data and program updates Potentially first-in-class SMARCA2 degrader program with a significant lead over competitors and offers transformational potential for the company Opportunity to drive the programs to key inflection points in the n
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Slide 28: Expected Data Catalysts by Mid-2024
Expected Data Catalysts by Mid-2024 PRT2527 (CDK9) Hematology program POA PRT1419 (MCL-1) monotherapy activity in CLL Program Update in 2H 2023 PRT3645 (CDK4/6) Monotherapy Recommended Phase 2 Dose Potential for strategic partnership PRT3789 Demonstration of selective degradation of SMARCA2 Dose esc
Slide 29: Potential Development Timelines
Potential Development Timelines 2022 2023 2024 2025 2H 1H 2H 1H 2H 1H 2H PRT1419 (MCL1) PRT2527 (CDK9) PRT3645 (CDK4/6) PRT3789 (SMARCA2 IV) New Programs Phase 1 heme monotherapy Phase 1 heme combination Phase 1 heme Phase 1 solid tumor Phase 1 solid tumor Ph1 solid tumor Phase 1 solid tumor Phase 1
Slide 30: Maximal Inhibition of MCL-1 in Sensitive Species did not cause cardiac injury
Maximal Inhibition of MCL-1 in Sensitive Species (dog) did not cause cardiac injury in GLP Tox studies Doses: 0.3, 1, 3 and 6 mg/m2; once weekly Linear increases in exposure No troponin elevations observed at any doses, even high dose which covered EC90 for 24h No histopathological evidence of cardi
Slide 31: PRT1419 Plans for Heme Malignancies
PRT1419 Plans for Heme Malignancies CLL and NHL patients can improve dose escalation and give faster clarity on activity Expected benchmarks to demonstrate activity R/R AML: CR/CRi rate for venetoclax monotherapy is 19% (Konopleva et al 2016) r/r AML CR/CRi rate for HMA monotherapy is 16-17% (Itzyks
Slide 32: PRMT5
PRMT5 Decision to discontinue internal development of PRMT5 program, despite demonstration of a best-in-class safety profile and evidence of clinical activity in biomarker-selected patients with glioma and splicing mutated uveal melanoma Prioritization reflects the high benchmark we set for clinical
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