Pmv Pharmaceuticals, Inc. · NASDAQ:PMVP
Pmv Pharmaceuticals — ASCO 2022
16 slides from Pmv Pharmaceuticals's conference presentation, June 2022
Slide 1: First-in-Human Study of PC14586, a Small Molecule Structural Corrector of Y220C Mutant p53
First-in-Human Study of PC14586, a Small Molecule Structural Corrector of Y220C Mutant p53, in Patients With Advanced Solid Tumors Harboring a TP53 Y220C Mutation Ecaterina E. Dumbrava,1 Melissa L. Johnson,2 Anthony W. Tolcher,3 Geoffrey I. Shapiro,4 John A. Thompson,5 Anthony B. El-Khoueiry,6 Andra
Slide 2: p53 Has a Pivotal Role in the Body's Defense Against Cancer
2 p53 Has a Pivotal Role in the Body’s Defense Against Cancer • DNA damage • Hypoxia • TP53 is a tumor suppressor gene1–2 • Viral infection Ub • The p53 protein binds to DNA and has key roles in cell Ub Ubiquitination cycle arrest, DNA repair, and apoptosis1–3 Ub ▪ Activated following cellular stres
Slide 3: TP53 Y220C Hotspot Mutation is Detected across Solid Tumor Types
3 TP53 Y220C Hotspot Mutation is Detected across Solid Tumor Types • TP53 mutations are the most common genomic Frequency of TP53 Y220C Across Common Solid Tumors Foundation Medicine Tissue and Heme assay test results events across all human cancers1 collected between 1/1/12 and 12/31/2020 Breast 1%
Slide 4: PC14586 is a p53 Y220C-Selective First-in-Class p53 Reactivator
4 PC14586 is a p53 Y220C-Selective First-in-Class p53 Reactivator • Orally available small molecule designed to selectively bind to the crevice contained in the p53 Y220C mutant protein1 • Stabilizes the p53 Y220C mutant protein in the wild-type p53 conformation, thereby restoring transcription and
Slide 5: A Seamless Phase 1/2 Clinical Trial (PYNNACLE trial)
5 A Seamless Phase 1/2 Clinical Trial (PYNNACLE trial) Patients With Advanced Solid Tumors Harboring p53 Y220C Mutation Phase 1 Phase 2 currently enrolling planned 1500 mg BID n=10 Patients 2500 mg QD n=4 • ≥12 years of age • Locally advanced or 2000 mg QD n=7 metastatic solid tumors 1500 mg QD n=5
Slide 6: Patient Demographics and Disease Characteristics
6 Patient Demographics and Disease Characteristics n=41 Cancer Type, n (%) Age, years Median (min–max) 62 (32–84) Small Cell Lung Germ Cell 2.4% (n=1) 2.4% (n=1) Sex, n (%) Female 25 (61) Head and Neck Male 16 (39) 4.9% (n=2) Race, n (%) White 31 (76) Endometrial Asian 3 (7) 4.9% (n=2) Ovary Black o
Slide 7: Treatment-Emergent Treatment-Related Adverse Events
7 Treatment-Emergent Treatment-Related Adverse Events All Patients (n=41) All Treatment-Emergent Treatment-Related AEs (Occurring in ≥3 Patients) Max CTCAE Preferred Term Any Grade 1 2 3 4 Any treatment-related AE, n (%) 33 (80.5) 12 (29.3) 11 (26.8) 9* (22.0) 1* (2.4) • Most frequent treatment-rela
Slide 8: Dose-Proportional Increases in AUC at Steady State
8 Dose-Proportional Increases in AUC at Steady State 100,000 Patient Plasma Exposures Mean AUC0–24 (SD) by Total Daily Dose 500,000 PC14586 plasma concentration (ng/mL) Mean (SD) AUC0–24 at Day 15 (ng.h/mL) 10,000 400,000 300,000 1000 200,000 100 2500 mg QD (Cohort 6, n=3) 1150 mg QD (Cohort 4, n=3
Slide 9: Objective Response Rate Per RECIST 1.1
9 Objective Response Rate Per RECIST 1.1 Based on Investigator Assessment Dose Cohorts All 150 mg QD–600 mg QD 1150 mg QD–1500 mg BID Enrolled, n 10 31 41 Patients with measurable disease at 8 28 36 baseline, n Eligible for response evaluation*, n 8 25 33 ORR‡, n (%) 0 (0) 8 (32.0) 8 (24.2) PR 0 6 6
Slide 10: Target Lesion Reduction in Low vs High Dose Cohorts
10 Target Lesion Reduction in Low vs High Dose Cohorts % Change From Baseline in Tumor Target Lesion % Change From Baseline in Tumor Target Lesion (150 mg QD–600 mg QD dose Level) (1150 mg QD–1500 mg BID dose level) 60 60 50 50 Treatment ongoing 40 40 30 30 Change from baseline (%) Change from basel
Slide 11: Target Lesion Reduction Across Tumor Types
11 Target Lesion Reduction Across Tumor Types 60 50 Best change in tumor target lesion (%) 40 30 20 10 Breast PD SD SD SD SD SD SD SD SD uPR uPR SD PR SD PR SD PR PR PR PR 0 PD PD PD PD PD SD SD SD SD PD -10 -20 -30 -40 -50 -60 -70 -80 1500 BID 1500 BID 600 QD 1500 BID 1500 BID 1500 BID 600 QD 150 Q
Slide 12: Duration of PC14586 Therapy
12 Duration of PC14586 Therapy 1150 QD Small Cell Lung PR 600 QD Pancreas SD 2000 QD Prostate SD 300 QD Colon SD 2500 QD Pancreas SD 2000 QD Pancreas SD 2500 QD Breast PR 2000 QD Endometrial PR 1500 BID Ovary PR 1500 BID Ovary PR 1150 QD Breast SD 600 QD Colon SD 2000 QD Prostate PR 2000 QD Prostate
Slide 13: CTC & ctDNA Decreases May Be Early Biomarkers of Anti-Tumor Activity
13 CTC & ctDNA Decreases May Be Early Biomarkers of Anti-Tumor Activity Change from Baseline 40 Change from Baseline to 2 Weeks in CTC Counts to 3 Weeks in ctDNA Y220C VAF 50 20 0 0 -50 -20 -100 -40 -150 -60 ≤ 600mg QD ≥ 1150mg QD ≤ 600mg QD ≥ 1150mg QD -80 -200 All enrolled patients with ≥ 2 CTCs d
Slide 14: SCLC Patient With Rapid and Sustained Partial Response
14 SCLC Patient With Rapid and Sustained Partial Response • 71-year-old woman with ES-SCLC Baseline Week 12 Weeks • Progressed after 2 prior lines of therapy 0 3 6 9 12 15 18 21 24 27 30 33 with worsening dyspnea and complete 20 occlusion of the left bronchus with atelectasis 0 % change from baselin
Slide 15: Conclusions
15 Conclusions • PC14586 has an acceptable safety profile, with MTD reached • PC14586 exposure is generally dose proportional over a wide dose range and supports once daily dosing • Preliminary efficacy in patients across solid tumor types harboring TP53 Y220C mutation was demonstrated • Enrollment
Slide 16: Acknowledgments
16 Acknowledgments We would like to thank: ▪ All the patients, their families and caregivers who have participated, and continue to participate in this clinical trial ▪ Investigators and research staff ▪ MedPace, Resolution Biosciences, Foundation Medicine, and Rarecyte US clinical trial sites - Dan