Prelude Therapeutics Incorporated · NASDAQ:PRLD
Prelude Therapeutics — Investor Presentation (November 2024)
71 slides from Prelude Therapeutics's investor presentation, Nov 6, 2024
Slide 1: Corporate Presentation November 2024
Corporate Presentation November 2024 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, anticipated discovery, preclinical and clinical development activities for Pre
Slide 3: Mission to extend precision medicine to every cancer patient
We are on a mission to extend the promise of precision medicine to every cancer patient in need Select the best modality to precisely target oncogenic mechanisms Strive for first- or best-in-class and anchor to patient unmet need Draw on decades of experience and proven leadership to drive innovatio
Slide 4: Experienced Leadership Team With Proven Track Records in Precision Oncology
Kris Vaddi, PhD Chief Executive Officer Jane Huang M.D. President and Chief Medical Officer Andrew Combs, PhD Chief Chemistry Officer Sean Brusky, MBA Chief Business Officer Peggy Scherle, PhD Chief Scientific Officer Bryant Lim, J.D. Chief Legal Officer, Corporate Secretary and Interim CFO Experien
Slide 5: Prelude's Evolution and Strategic Priorities
Prelude’s Evolution Strategic Priorities Continue to build SMARCA leadership Generate proof-of-concept data Prepare for global registrational trials Advance SMARCA “Pipeline in a Program” Explore collaborations to accelerate trials and global capabilities ~1 new IND every 12-18 months Successfully a
Slide 6: Prelude's Precision Medicine Pipeline & Discovery Engine
Prelude’s Precision Medicine Pipeline & Discovery Engine PROGRAM POTENTIAL INDICATIONS DISCOVERY PHASE 1 PHASE 2/3 Lead SMARCA2 Degrader (IV) SMARCA4-mutated NSCLC & other cancers Oral SMARCA2 Degrader SMARCA4-mutated NSCLC & other cancers SMARCA2/4 Precision ADCs* Dose Confirmation by YE2024; Phase
Slide 7: Industry Leading Portfolio of SMARCA-Targeted Precision Medicines
Developing an Industry Leading Portfolio of SMARCA-Targeted Precision Medicines SMARCA - DACs + Lead SMARCA2 Degrader (PRT3789) Oral SMARCA2 Degrader (PRT7732) Precision ADCs with SMARCA2/4 Degrader Payload
Slide 8: Targeting SMARCA4-mutated Cancer By Selectively Degrading SMARCA2
Patients with SMARCA4 mutations are not typically eligible for other targeted therapies Currently treated with standard of care chemotherapy or chemo-immunotherapy Targeting SMARCA4-mutated Cancer By Selectively Degrading SMARCA2 Pancreatic: 3% NSCLC: 10% Esophageal: 8% Gastric: 8% Endometrial: 13%
Slide 9: Outcomes for SMARCA4-mutated NSCLC are Poor with Current Standard of Care
Outcomes for Patients with SMARCA4-mutated NSCLC are Poor with Current Standard of Care Alessi JV, et al. Clinicopathologic and genomic factors impacting efficacy of first-line chemoimmunotherapy in advanced non-small cell lung cancer (NSCLC). J Thorac Oncol. 2023 Feb 10:S1556-0864(23)00121-1. PMID:
Slide 10: PRT3789: Highly Potent SMARCA2 Degrader with >1000-fold Selectivity
PRT3789: A Highly Potent SMARCA2 Degrader with >1000-fold Selectivity Over SMARCA4 Hulse et al. Cancer Res. (2022); 82 (12_Suppl) :3263. AACR 2022 Poster (http://www.preludetx.com/science/publications) Highly selective for SMARCA2 vs SMARCA4 (>1000 fold) and selective across the proteome Preclinical
Slide 11: PRT7732: First-in-Class Oral SMARCA2 Degrader – Phase I Initiated
PRT7732: First-in-Class, Highly Selective Oral SMARCA2 Degrader – Phase I Trial Initiated Sub-nanomolar SMARCA2 degradation potency in cell lines Very high selectivity for SMARCA2 over SMARCA4 Good oral bioavailability observed across species supports projected once-daily human dose Assay PRT7732 SM
Slide 12: Interim Update from PRT3789-01 at 2024 ENA Symposium
Interim Update from PRT3789-01 Presented at Plenary Session of the 2024 ENA Symposium Additional clinical activity observed in NSCLC patients with Class I mutations treated with PRT3789 monotherapy at doses ≥ 283 mg First look at safety and PK data from PRT3789 + docetaxel in combination demonstrate
Slide 13: PRT3789-01: Study Schema and Enrollment
PRT3789-01: Study Schema and Enrollment Study is enrolling patients with evaluable disease, any solid tumors, and any type of SMARCA4 mutation Dose escalation is on-going, now at cohort 10 (665 mg) Data presented includes additional follow-up on 65 patients treated in escalating doses from 24 to 376
Slide 14: PRT3789-01: Demographics and Disease Characteristics
65 patients with additional follow-up included in the analysis were treated and safety evaluable at time of data cutoff The primary tumor type, as characterized by investigators, was NSCLC (n = 30) along with other solid tumors 34 patients had Class 1 (loss of function) mutations and an additional 7
Slide 15: PRT3789-01: Summary of Adverse Events
PRT3789-01: Summary of Adverse Events PRT3789 was generally well tolerated at doses studied with no treatment related SAEs or dose-limiting toxicities reported Of all Treatment Emergent Adverse Events (TEAEs) of any grade, nausea, fatigue, anemia and decreased appetite had the highest incidence 2024
Slide 16: PRT3789-01: Interim PK Findings
PRT3789-01: Phase 1 Interim PK Findings Preliminary PK data are available from 24 mg to 376 mg General trend of increases in exposure (Cmax, AUC) with higher doses was observed At the 376 mg dose level, mean concentrations were above SMARCA2 plasma DC50 (21 nM) for approximately 8 hours As expected
Slide 17: PRT3789-01: SMARCA2 Protein Levels in PBMCs
At dose levels up to 160 mg, degradation of SMARCA2 was observed in PBMCs at early time points, but recovered or was above baseline by the end of the dosing interval (7 days) At dose levels 212 – 376 mg, greater consistency, dose dependency, and sustained degradation of SMARCA2 were observed through
Slide 18: PD Correlates with Efficacy in Preclinical Models
In preclinical models, correlation was observed between PBMC and tumor SMARCA2 degradation levels at efficacious doses Increasing doses resulted in increased reduction in SMARCA2 PD AUC in tumors and were associated with higher efficacy PD Correlates with Efficacy in Preclinical Models In vivo Effic
Slide 19: PRT3789-01: Interim Clinical Activity
PRT3789-01: Phase 1 Interim Clinical Activity Of the 29 patients with NSCLC or esophageal cancer evaluable for efficacy at time of data cutoff, 8 experienced tumor shrinkage RECIST confirmed partial responses (PRs) were observed in 4 patients (2 esophageal, 2 NSCLC) The two NSCLC responders had Clas
Slide 20: PRT3789-01: Interim Clinical Activity
PRT3789-01: Phase 1 Interim Clinical Activity As reported by Alessi et al., the median PFS for first-line SMARCA4-mutated NSCLC treated with chemoimmunotherapy was 2.7 months 1 Several patients had prolonged stable disease (SD) including a NSCLC patient who remains on treatment for more than a year
Slide 21: PRT3789-01: Response Rate By Dose Level
PRT3789-01: Response Rate By Dose Level As reported by Alessi et al., the objective response rate (ORR) for first-line SMARCA4-mutated NSCLC treated with chemoimmunotherapy was 21.9% 1 At doses ≥ 283 mg, as monotherapy, an interim ORR of 22.2% was observed in NSCLC patients with Class I SMARCA4-muta
Slide 22: PRT3789-01: Docetaxel Combination Study Schema
PRT3789-01: Docetaxel Combination Study Schema At time of data cutoff, 11 patients treated at 120 mg (n=6) and 283 mg (n=5) were evaluable for preliminary safety and PK assessment Enrollment continues with no dose limiting toxicities observed to date and is now enrolling at 500 mg Backfill cohorts e
Slide 23: Preliminary Safety Summary in Combination with Docetaxel
PRT3789-01: Preliminary Safety and Adverse Event Summary in Combination with Docetaxel In combination with docetaxel, PRT3789 was generally well tolerated at doses studied with no treatment related SAEs or dose-limiting toxicities reported Most frequent treatment emergent AEs of any grade included f
Slide 24: Preliminary PK Assessment in Combination with Docetaxel
PRT3789-01: Preliminary PK Assessment in Combination with Docetaxel At time of data cutoff, preliminary PK data was available from 6 patients in the 120 mg combination cohort PRT3789 PK in combination with docetaxel appears to be consistent with monotherapy at 120 mg Early signs of anti-tumor activi
Slide 25: What's Next for PRT3789?
KEYTRUDA® is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. LOF = “Loss-of-function”; QW, once weekly; YE, year end; NSCLC, non-small cell lung cancer; 2L+, second-line and beyond. What’s Next for PRT3789? ‘3789 Monotherapy Dose Confirmation ‘3
Slide 26: SMARCA2 Degrader Portfolio Addresses a Significant Unmet Need
Prelude’s SMARCA2 Degrader Portfolio Addresses a Significant Unmet Need ~195,000 pts/year Up to 19,500 SMARCA4-mutated STAGE IV, First Line ~130,000 pts/year Up to 13,000 SMARCA4-mutated STAGE IV, 2L+ (R/R, Previously Treated) + US & EU5 only (2030 proj.): 1 GlobalData (SEER), Earlier Stage (I-III)
Slide 27: Expanding Our Portfolio of SMARCA-Targeted Precision Medicines
Expanding Our Portfolio of SMARCA-Targeted Precision Medicines Precision ADCs with SMARCA2/4 Degrader Payload Cancers highly sensitive to SMARCA dysregulation Independent of SMARCA4 mutation status Initial focus of Prelude/AbCellera collaboration SMARCA - DACs + Lead SMARCA2 Degrader (PRT3789) Oral
Slide 28: Prelude and AbCellera Creating Novel Precision ADCs
Together, Prelude and AbCellera Are Creating Novel, First-in-Class Precision ADCs High Unmet Need & Opportunity Potential for Optimized Payload Potential for Optimized Antibody Data presented describe the first preclinical proof-of-concept of a novel, highly potent SMARCA2/4 dual degrader as a “Prec
Slide 29: Identification of Selective SMARCA2/4 Dual Degraders
Identification of Selective SMARCA2/4 Dual Degraders with Potent Anti-Cancer Activity (A) SMARCA2/4 degradation potency of 3 payloads in a HeLa HiBiT cell-based assay. (B) Global proteomics analysis following treatment of LNCaP human prostate cancer cells with 25 nM PRP0004 for 1h. (C) GI50 of a pan
Slide 30: Conjugation of Antibodies to SMARCA2/4 Degrader Payloads
Conjugation of Clinically-Validated Antibodies to SMARCA2/4 Degrader Payloads Drives Antigen-Dependent Internalization and Target Engagement Conjugation of PRP0004 to clinically-validated antibodies including PSMA, CEACAM5, C-MET, TROP2, and CD33 These DACs demonstrated potent and antigen-selective
Slide 31: Anti-PSMA SMARCA2/4 DAC Demonstrated Tumor Regression
Anti-PSMA SMARCA2/4 DAC Demonstrated Tumor Regression and Significantly Better Efficacy Compared to a Traditional PSMA-Targeted Cytotoxic ADC Anti-PSMA SMARCA2/4 DACs demonstrated robust target engagement and antigen-dependent efficacy in xenograft models while being well-tolerated These data highli
Slide 32: Highly Selective CDK9 Inhibitor PRT2527
Highly Selective CDK9 Inhibitor PRT2527
Slide 33: Phase 1 Trial of PRT2527 in Hematologic Malignancies is Underway
Initial safety and tolerability data for monotherapy dose escalation cohorts in hematologic malignancies Initial assessment of clinical activity in B-cell malignancies as monotherapy Initial clinical data with zanubrutinib from combination cohort *R/R disease following: At least 1 prior systemic the
Slide 34: Continued Execution Across Strategic Priorities
Continued Execution Across Strategic Priorities PRT2527 CDK9 Initiate zanubrutinib combination study Initiate myeloid cohort in the existing phase 1 study Complete monotherapy dose escalation in B-cell malignancies Report interim phase 1 clinical results in 2024 PROGRAM Report interim Phase 1 clinic
Slide 35: Thank You
Thank You Contact Us: Robert Doody SVP, Investor Relations rdoody@preludetx.com
Slide 36: Appendix Contents
Highly Selective SMARCA2 Degrader Program Discovery Effort & Oral Degrader Program (PRT7732) Preclinical Rationale for Combinations (2024 EORTC-NCI-AACR Symposium Update) Current Treatment Paradigm & Testing Landscape Precision ADCs First Preclinical Proof-of-Concept Data Presented at 2024 EORTC-NCI
Slide 37: Degraders Offer Distinct Advantages for Targeting SMARCA2
When it Comes to Targeting SMARCA2, Degraders Offer Distinct Advantages Inhibitors Degraders Potency High Selectivity Extended PD Oral Bioavailability X X Early attempts at achieving both potency and selectivity with inhibitor approaches had challenges Inhibitors do not degrade the target and need t
Slide 38: Selectively Targeting SMARCA2 Has Been a Significant Challenge
Selectively Targeting SMARCA2 Has Been a Significant Challenge for Industry Selective SMARCA2 Inhibition is an Unmet Medicinal Chemistry Challenge Bromodomain Binders Non-selective and inactive in SMARCA4 mutated cancer cells1 ATPase Inhibitors Inhibitors show low selectivity for SMARCA2 in cell pro
Slide 39: Prelude Scientists Solved the SMARCA2 Selectivity Enigma
Prelude Scientists Solved the SMARCA2 Selectivity Enigma PRT3789 (IV or SC formulation) PRT7732 (Oral Candidate) Parallel VHL- and CRBN-based SMARCA2 Degrader Programs IV or SC Candidate - VHL-TPDs provided an expedited path to potential clinical development with QW dosing Oral Candidate - CRBN-TPDs
Slide 40: SMARCA2 Oral Degrader Program Progressed Rapidly and Systematically
Our SMARCA2 Oral Degrader Program Progressed Rapidly and Systematically Confidential Solving for potency, selectivity and oral bioavailability was a challenge PRT7732: Lead Oral Candidate with >3000-fold Selectivity A and B: Two additional structurally distinct oral back-up candidates 0.1 1.0 10 100
Slide 41: Tertiary Complex of SMARCA2/PRT7732/CRBN-DDB1 E3 Ligase
Tertiary Complex of SMARCA2/ PRT7732/CRBN-DDB1 E3 Ligase PRT7732 binds to the SMARCA2 bromodomain and CRBN/DDB1 E3 ligase complex PRT7732 has been shown to catalyze the polyubiquitination of unique lysine residues expressed only in SMARCA2 and not SMARCA4 Unique conformational bias promotes selectiv
Slide 42: PRT7732 Highly Potent and Orally Bioavailable
PRT7732 is Highly Potent and Orally Bioavailable With Near-Absolute Selectivity for SMARCA2 Near-absolute cellular selectivity for SMARCA2 vs SMARCA4 (>3000 fold) in HiBit cell lines and >1000-fold in cell proliferation assays Sub-nanomolar SMARCA2 degradation potency * Based on highest concentratio
Slide 43: PRT7732 Anti-Tumor Activity in Xenograft Models
PRT7732 Has Significant Anti-Tumor Activity in SMARCA4-Deficient Cancer Xenograft Models Daily oral administration of PRT7732 demonstrates anti-tumor activity in SMARCA4-deficient but not SMARCA4 wild type tumors PRT7732 rapidly decreases SMARCA2 protein levels in tumor xenograft models at low doses
Slide 44: PRT3789 Potential for Synergy with Chemotherapy
PRT3789 Demonstrates Potential for Synergy with Chemotherapy and Apoptosis-Inducing Agents AACR 2022, 2023 Posters (http://www.preludetx.com/science/publications) BUB1B, CCNA2/B2, CDC25C, CDK1/2, CHEK1/2 FEN1, LIG1, MCM, PCNA, POLA1/2, POLD1/2/3, POLE/2/3 Docetaxel Gemcitabine Several oncogenic gene
Slide 45: PRT3789 + Taxanes Induce Durable Regressions
PRT3789 + Taxanes Induce Durable Regressions in SMARCA4-mutated NSCLC CDX & PDX Models Hulse M., et al., 2024 EORTC-NCI-AACR Symposium Poster (http://www.preludetx.com/science/publications) PRT3789 enhances chemotherapy efficacy as shown in NSCLC models with SMARCA4 mutations, including both cell li
Slide 46: No Adverse Drug-Drug Interaction Between PRT3789 and Taxanes
Preclinical PK/PD Data Shows No Adverse Drug-Drug Interaction Between PRT3789 and Taxanes PRT3789 treatment results in complete degradation of SMARCA2 protein as both monotherapy and in combination with docetaxel Taxanes do not interfere with the SMARCA2 degradation induced by PRT3789 in vivo PK ana
Slide 47: PRT3789 and Docetaxel Regulate Distinct Pathways
PRT3789 and Docetaxel Regulate Distinct Pathways Involved in Tumor Cell Growth and Apoptosis 2024 Triple Meeting Update Hulse M., et al., 2024 EORTC-NCI-AACR Symposium Poster (http://www.preludetx.com/science/publications)
Slide 48: PRT3789 Counteracts Docetaxel-Induced Cell Cycle Activation
PRT3789 Counteracts Docetaxel-Induced Cell Cycle Activation, Resulting in Enhanced Efficacy of the Combination 2024 Triple Meeting Update Differential expression analysis was performed comparing the groups: (A) PRT3789 vs Vehicle, (B) docetaxel vs Vehicle, (C) PRT3789+ docetaxel vs Vehicle. Differen
Slide 49: PRT3789 and Docetaxel Induce Dual G1 and G2/M Arrest
PRT3789 and Docetaxel Combination Induces a Dual G1 and G2/M Arrest and Enhances Apoptosis in SMARCA4-deleted Cells Cell cycle analysis was performed using the Invitrogen™ Click-iT™ EdU Pacific Blue™ Flow Cytometry Assay Kit on the SMARCA4-del NSCLC cell line NCI-H838 (A) and the SMARCA4-WT NSCLC ce
Slide 50: PRT7732 Shows Potential for Synergy With Other Agents
PRT7732 Also Shows High Potential for Synergy With Other Common Anti-Cancer Agents Oral daily administration of PRT7732 in combination with nab-paclitaxel induces tumor regressions in murine tumor xenograft models Shvartsbart, K. Ito et al., AACR Poster, April 2024. (http://www.preludetx.com/science
Slide 51: SMARCA2 Degraders May Potentiate PD1/PDL1 Immunotherapy
SMARCA2 Degraders May Also Help to Potentiate PD1/PDL1 Immunotherapy Confidential Add figure Increased antigen processing “Turning Cold Tumors Hot?” In SMARCA4-deficient cancer cell lines, SMARCA2 degradation… + SMARCA2 Degrader Upregulates antigen processing and presentation machinery Increases cyt
Slide 52: Preclinical Data Support Anti-PD1 Combination Rationale
Preclinical Data for PRT3789 Support Rationale for Anti-PD1 Combination Fluorescently labeled tumor cells + PRT3789 + T-cells + T-cells + PRT3789 SMARCA2 Degrader + Anti-PD1 Demonstrates Tumor Regression In Vivo PRT3789 Increases IFN-g Levels in Combination with anti-PD1 In Vitro PRT3789 Upregulates
Slide 53: Phase 2 Combination Study of PRT3789 + Pembrolizumab
Prelude Has Initiated a Phase 2 Combination Study of PRT3789 + Pembrolizumab PRT3789 upregulates genes encoding antigen processing and presentation machinery Trial will explore safety and anti-tumor activity of the combination Preclinical evidence provides rationale for enhanced efficacy with PRT378
Slide 54: Majority of Advanced NSCLC Patients Treated with Chemoimmunotherapy
Majority of Advanced NSCLC Patients Are Treated with Chemoimmunotherapy Advanced NSCLC Diagnosis (Stage IIIB or IV) Actionable Mutation Identified No Actionable Mutation Identified KRAS, MET, ERBB2, BRAF, ROS, RET, Others EGFR ALK ICI +/- Chemo Chemoimmunotherapy PDL1 > 50% PDL1 < 50% Note: Simplifi
Slide 55: SMARCA2 Degraders Expand Precision Medicine Access for NSCLC
SMARCA2 Degraders Have Potential to Expand Precision Medicine Access for NSCLC Patients Percent of Total Advanced NSCLC Patients Treated (FUTURE STATE) MET, ERBB2, BRAF, ROS, RET, Others EGFR ALK KRAS SMARCA Chemo +/- Immunotherapy Precision Medicines ILLUSTRATIVE Potentially more patients than ALK,
Slide 56: Appendix Contents
Highly Selective SMARCA2 Degrader Program Discovery Effort & Oral Degrader Program (PRT7732) Preclinical Rationale for Combinations (2024 EORTC-NCI-AACR Symposium Update) Current Treatment Paradigm & Testing Landscape Precision ADCs First Preclinical Proof-of-Concept Data Presented at 2024 EORTC-NCI
Slide 57: Need for Payload Diversification in Next Generation ADCs
Approved ADCs possess payloads with similar mechanisms of action to conventional chemotherapy such as Monomethyl Auristatin E (MMAE) Novel payloads may allow targeting of previously intractable biological pathways (e.g., SMARCA2/4) Novel payloads may open the ADC modality to other cancers that do no
Slide 58: Precision ADCs Designed to Improve Therapeutic Index
Prelude’s Precision ADCs are Designed to Improve the Therapeutic Index Over Traditional ADCs ADC Precision ADC Potency Antibody Selectivity Payload Selectivity PD Marker for Payload Therapeutic Index X Payload Selectivity Highly potent and cell line selective targeted protein degrader Antibody Selec
Slide 59: Prelude and AbCellera Precision ADC Collaboration
Together, Prelude and AbCellera are Creating Novel, First-in-Class Precision ADCs Multi-year global collaboration to jointly discover, develop and commercialize novel Precision ADCs for up to five programs AbCellera will lead manufacturing activities Prelude will lead clinical development and global
Slide 60: Framework for Precision ADC Differentiation
Framework for Precision ADC Differentiation Antibody Differentiation Off-the-shelf / approved mABs Novel, differentiated, highly engineered mABs Payload-Linker Differentiation Non-selective cytotoxin (e.g., DM1, MMAE) Traditional ADCs Precision ADCs Traditional ADCs deliver highly potent and broadly
Slide 61: PRP0004 Induces Apoptosis in Prostate Cancer Cells
SMARCA2/4 Degrader Payload (PRP0004) Induces Apoptosis and Regulates the Expression of Key Oncoprotein Drivers in Prostate Cancer Cells Triple Meeting Update Prostate cancer was amongst the most sensitive cell lines to SMARCA2/4 degradation rationalizing the use of PSMA-targeting antibodies for furt
Slide 62: PRP0004 Alone Induces Regressions But Narrow Therapeutic Index
SMARCA2/4 Degrader Payload (PRP0004) Administered On Its Own Induces Tumor Regressions in Prostate Cancer Models, But With a Narrow Therapeutic Index Triple Meeting Update On its own, payload PRP0004 demonstrated dose-dependent tumor growth inhibition in human prostate cancer CDX models However, as
Slide 63: Anti-PSMA SMARCA2/4 DACs Show Tumor Growth Inhibition
Anti-PSMA SMARCA2/4 DACs Demonstrate Robust and Significant Antigen-Selective Tumor Growth Inhibition Anti-PSMA SMARCA2/4 DACs were well tolerated and demonstrated robust target engagement and antigen-dependent efficacy in xenograft models These data highlight the potential of utilizing a SMARCA2/4
Slide 64: Degrader Antibody Conjugates a New Frontier
Degrader Antibody Conjugates (DACs) represent a new frontier in advancing the scientific and clinical potential of antibody drug conjugates (ADCs) Prelude is developing DACs with potent SMARCA2/4 dual degraders as payloads on tumor specific antibodies to achieve maximal target degradation in tumors
Slide 65: Appendix Contents
Highly Selective SMARCA2 Degrader Program Discovery Effort & Oral Degrader Program (PRT7732) Preclinical Rationale for Combinations (2024 EORTC-NCI-AACR Symposium Update) Current Treatment Paradigm & Testing Landscape Precision ADCs First Preclinical Proof-of-Concept Data Presented at 2024 EORTC-NCI
Slide 66: Hematologic Malignancies Refractory to Current Treatments Have Poor Outcomes
Source: 1) Maiti A et al. Haematologica 2021. https://doi.org/10.3324/haematol.2020.252569 2) Lew TE et al. Blood Advances 2021. https://doi.org/10.1182/bloodadvances.2021005083 Patients with Hematologic Malignancies Refractory to Current Treatments Experience Poor Outcomes After SoC (venetoclax + H
Slide 67: CDK9 Inhibition Targets MYC and MCL-1
CDK9 Inhibition Targets Two Major Validated Pathways (MYC and MCL-1) CDK9 is the primary transcriptional regulator of a major oncogene MYC and an apoptosis inducer MCL-1 Dysregulated pathways involving MYC and MCL-1 drive pathogenesis and resistance in hematologic cancers including lymphoid and myel
Slide 68: PRT2527 Potent, Highly Selective CDK9 Inhibitor
PRT2527 is a Potent, Highly Selective CDK9 Inhibitor That Depletes MCL-1 and MYC Highly Isoform Selective CDK9 Inhibitor Compound PRT2527 Biochemical* IC50 (nM) CDK9 0.95 Proliferation* IC50 (nM) 18 Plasma* IC50 (nM) 196 Fold Selectivity CDK9 vs Other Isoforms CDK1 73x CDK2 340x CDK3 35x CDK4 250x C
Slide 69: PRT2527 Highly Efficacious In Vivo
PRT2527 is Highly Efficacious In Vivo in Models of Hematologic Malignancies Monotherapy Karpas-422 (Double Hit DLBCL) MV4-11 (AML) Combination TMD-8 (ABC DLBCL) OCI-AML3 (VenR AML) ASH 2022 Presentation (https://www.preludetx.com/science/publications); Data on file
Slide 70: Initial Phase 1 Study of PRT2527 in Solid Tumors
Favorable tolerability with manageable neutropenia and absence of significant gastrointestinal events or hepatotoxicity Dose-dependent downregulation of CDK9 transcriptional targets – MYC and MCL-1 mRNA expression in PBMCs isolated from treated patients 12 mg/m2 QW dosing and higher showed optimal t
Slide 71: Thank You
Thank You Contact Us: Robert Doody SVP, Investor Relations rdoody@preludetx.com
Prelude Therapeutics — Investor Presentation (November 2024) on 6ix