Prelude Therapeutics Incorporated · NASDAQ:PRLD

Prelude Therapeutics — Technical Presentation (January 2022)

13 slides from Prelude Therapeutics's technical presentation, January 2022

  1. Slide 1: Phase 1 dose-escalation study of PRMT5 inhibitor PRT543 in advanced solid tumors and lymphoma

    A phase 1 dose-escalation study of protein arginine methyltransferase 5 (PRMT5) inhibitor PRT543 in patients with advanced solid tumors and lymphoma Meredith McKean, MD, MPH1; Manish R Patel, MD2; Robert Wesolowski, MD3; Renata Ferrarotto, MD4; Eytan M. Stein, MD5; Alexander N Shoushtari, MD5; David

  2. Slide 2: PRT543 is a Potent, Selective, Oral PRMT5 Inhibitor

    PRT543 is a Potent, Selective, Oral PRMT5 Inhibitor • PRMT5 catalyzes symmetric arginine dimethylation of protein substrates with important roles in the cell cycle, including histone modification, transcription, and spliceosome assembly • PRMT5 is overexpressed in a variety of cancers • PRT543 inhib

  3. Slide 3: PRT543 Demonstrates Robust Preclinical Antitumor Activity

    PRT543 Demonstrates Robust Preclinical Antitumor Activity PRT543 Demonstrates Anti-tumor Activity in Solid Tumor PDX Models of ACC and HRD+ Breast Cancer ACC (PDX)1 HRD+ Breast Cancer (PDX)2 ACC, adenoid cystic carcinoma; BID, twice a day; HRD+, homologous recombination deficiency-positive; PARP, po

  4. Slide 4: Study Design

    Phase 1 Dose-escalation Study of PRMT5 Inhibitor PRT543 Study Design Key Eligibility Criteria Key Objectives • Adults with advanced or metastatic • Safety/tolerability and RP2D solid tumors, including lymphoma • Pharmacokinetic/pharmacodynamic profile • Relapsed refractory disease • Preliminary sign

  5. Slide 5: Baseline Characteristics

    Phase 1 Dose-escalation Study of PRMT5 Inhibitor PRT543 Baseline Characteristics Total Patients Primary Cancer Diagnosis, Total Patients Demographics (N=49) n (%) (N=49) Age, years, median (range) 63.0 (31-82) Colon cancer 9 (18) Female, n (%) 31 (63) ACC 7 (14) Uveal melanoma 6 (12) ECOG PS, n (%)

  6. Slide 6: Pharmacokinetics

    Phase 1 Dose-escalation Study of PRMT5 Inhibitor PRT543 Pharmacokinetics Expansion Dose Parameter Values (CV%) (45 mg 5x/week) Cmax, nM 2,142 (32) AUC0-t, hr.nM 26,293 (33) T1/2, hrs 15 (7) • PRT543 demonstrated dose-dependent increases in Cmax and AUC • Drug accumulation was seen at the highest dos

  7. Slide 7: Pharmacodynamics

    Phase 1 Dose-escalation Study of PRMT5 Inhibitor PRT543 Pharmacodynamics PRT543 Exhibited Dose-Dependent Intron Retention, a Marker of PRMT5- Inhibition of Serum sDMA: Mediated mRNA Splicing Fidelity, was 69% Decrease Observed at the Observed with PRT543 Treatment at Expansion Dose (45 mg/5x Week)a

  8. Slide 8: Most Common Treatment-Related Adverse Events of Any Grade Occurring in ≥5% of Patients

    Phase 1 Dose-escalation Study of PRMT5 Inhibitor PRT543 Most Common Treatment-Related Adverse Events (TRAEs) of Any Grade Occurring in ≥5% of Patients Expansion Dose All Patients (N=49)a 45 mg 5x/week (N=6) AE, n (%) Any Grade Grade ≥3 Any Grade Grade ≥3 Patients with events 36 (73) 20 (41) 4 (67) 3

  9. Slide 9: Dose-limiting Toxicities (DLTs)

    Phase 1 Dose-escalation Study of PRMT5 Inhibitor PRT543 Dose-limiting Toxicities (DLTs) 5-45 mga 35 mg 50 mg 35 mg 25 mg 45 mg BIW 5x/week QD QD QD 5x/week N=17 N=5 N=4 N=11 N=6 N=6 G4 thrombocytopenia (n=2) G4 thrombocytopenia (n=2) G3 fatigue (n=1) G2 and G3 thrombocytopenia (n=1)b G4 thrombocytop

  10. Slide 10: Overall Response and Response Duration by Dose/Schedule and Diagnosis

    Phase 1 Dose-escalation Study of PRMT5 Inhibitor PRT543 Overall Response and Response Duration by Dose/Schedule and Diagnosisa b Starting Dose aAnalysis for patients treated with weekly dose higher than 175 mg. bPatient with pancreatic cancer enrolled but did not take study drug. ACC, adenoid cystic

  11. Slide 11: Best Target Lesion Response (RECIST v1.1)

    Phase 1 Dose-escalation Study of PRMT5 Inhibitor PRT543 Best Target Lesion Response (RECIST v1.1) Patients This analysis includes patients with target lesions at baseline and at least 1 post-baseline percentage change (from baseline to PD). RECIST v1.1 assessment by investigator. 4 patients had insu

  12. Slide 12: Response in Patient With HRD+ High-grade Serous Ovarian Cancer

    Phase 1 Dose-escalation Study of PRMT5 Inhibitor PRT543 Response in Patient With HRD+ High-grade Serous Ovarian Cancer Patient History • 2014 diagnosis (tumor origin in fallopian tube) • Multiple lines of prior therapy, including PARPi • HRD+ • DNA damage response (DDR) mutations: ATR, RAD51D, BRCA1

  13. Slide 13: Conclusions

    Phase 1 Dose-escalation Study of PRMT5 Inhibitor PRT543 Conclusions • PRT543 exhibited target engagement and inhibited PRMT5 activity • PRT543 was well tolerated • Most common treatment-related adverse events (TRAEs) of any grade in at least 10% of patients were fatigue, thrombocytopenia, anemia, na

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