Pmv Pharmaceuticals, Inc. · NASDAQ:PMVP
Pmv Pharmaceuticals — ASCO 2022 PC14586 Investor Event
32 slides from Pmv Pharmaceuticals's conference presentation, Jun 8, 2022
Slide 1: ASCO PC14586 Investor Event
Exhibit 99.2 ASCO PC14586 INVESTOR EVENT June 7, 2022
Slide 2: Disclaimer: Forward-Looking Statements
Disclaimer Forward-Looking Statements This presentation contains forward looking statements. Such statements include, but are not limited to, statements regarding our research, preclinical and clinical development activities, plans and projected timelines for PC14586 and our pipeline programs, plans
Slide 3: Agenda
Agenda Introduction David Mack, PhD, President & Chief Executive Officer 01 Ecaterina Dumbrava, MD ASCO 2022 & Assistant Professor, Department of Investigational Cancer Therapeutics, Division 02 Clinical Experience of Cancer Medicine, The University of Texas MD Anderson Cancer Center 03 Looking Ahea
Slide 4: PMV founded on the expertise in p53 biology
PMV founded on the expertise in p53 biology 2013 2020 2021 2022 PMV Pharma founded by IPO on Nasdaq PC14586 preclinical data at Initial anti PD-1 preclinical David Mack, Ph.D., Arnold AACR combination data at AACR First patient dosed in Levine, Ph.D. and Thomas PYNNACLE Phase 1/2 Study Initial PYNNA
Slide 5: Novel Approach in Precision Oncology Harnessing the Power of p53
Novel Approach in Precision Oncology Harnessing the Power of p53 Mission Clinical Stage Discovery Stage Programs Programs Lead program PC14586 under WIP1 program targeting wild-type p53 PMV is pioneering the discovery and evaluation in the Phase 1/2 tumors in lead optimization development of small m
Slide 6: 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 1 2 3 4 5 6 7 Ecaterina E. Dumbrava, Melissa L. Johnson, Anthony W. Tolcher, Geoffrey I. Shapiro, John A. Thompson, Anthony B. El-Khoueir
Slide 7: p53 Has a Pivotal Role in the Body's Defense Against Cancer
p53 Has a Pivotal Role in the Body’s Defense Against Cancer 1–2 • DNA damage • TP53 is a tumor suppressor gene • Hypoxia • Viral infection • The p53 protein binds to DNA and has key roles Ub 1–3 in cell cycle arrest, DNA repair, and apoptosis Ub Ubiquitination Ub § Activated following cellular stres
Slide 8: TP53 Y220C Hotspot Mutation is Detected across Solid Tumor Types
TP53 Y220C Hotspot Mutation is Detected across Solid Tumor Types Frequency of TP53 Y220C Across Common Solid Tumors • TP53 mutations are the most common genomic Foundation Medicine Tissue and Heme assay test results 1 collected between 1/1/12 and 12/31/2020 events across all human cancers Breast 1%
Slide 9: PC14586 is a p53 Y220C-Selective First-in-Class p53 Reactivator
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 1 protein • Stabilizes the p53 Y220C mutant protein in the wild-type p53 conformation, thereby restoring transcription and 1
Slide 10: A Seamless Phase 1/2 Clinical Trial (PYNNACLE trial)
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 2000 mg QD n=7 • Locally advanced or 1500 mg QD n=5 metastatic solid tumors 11
Slide 11: Patient Demographics and Disease Characteristics
Patient Demographics and Disease Characteristics n=41 Cancer Type, n (%) Age, years Small Cell Lung Median (min–max) 62 (32–84) Germ Cell 2.4% (n=1) 2.4% (n=1) Sex, n (%) Head and Neck Female 25 (61) 4.9% (n=2) Male 16 (39) Race, n (%) Endometrial White 31 (76) 4.9% (n=2) Ovary Asian 3 (7) 26.8% (n=
Slide 12: Treatment-Emergent Treatment-Related Adverse Events
Treatment-Emergent Treatment-Related Adverse Events All Patients (n=41) All Treatment-Emergent Treatment-Related AEs • Most frequent treatment-related AEs (Occurring in ≥3 Patients) Max CTCAE (>15%) included nausea, vomiting, Preferred Term Any Grade 1 2 3 4 AST/ALT increase, anemia, blood Any trea
Slide 13: Dose-Proportional Increases in AUC at Steady State
Dose-Proportional Increases in AUC at Steady State 100,000 Patient Plasma Exposures Mean AUC (SD) by Total Daily Dose 0–24 500,000 10,000 400,000 300,000 1000 200,000 100 2500 mg QD (Cohort 6, n=3) 1150 mg QD (Cohort 4, n=3) 100,000 2000 mg QD (Cohort 5, n=7) 600 mg QD (Cohort 3, n=3) 1500 mg BID (C
Slide 14: Objective Response Rate Per RECIST 1.1 Based on Investigator Assessment
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 15: Target Lesion Reduction in Low vs High Dose Cohorts
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 20 20 10 10 0 0 −10 -10 −20 -20 −30 -30 −40 -
Slide 16: Target Lesion Reduction Across Tumor Types
Target Lesion Reduction Across Tumor Types 60 50 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 Ovary Colon Pancreas Head and Neck Breast Prostate Endometrial Small Cell Lung Germ Cell Includes patients
Slide 17: Duration of PC14586 Therapy
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 SD
Slide 18: CTC & ctDNA Decreases May Be Early Biomarkers of Anti-Tumor Activity
CTC & ctDNA Decreases May Be Early Biomarkers 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 -40 -100 -60 -150 ≤ 600mg QD ≥ 1150mg QD ≤ 600mg QD ≥ 1150mg QD -80 -200 All enrolled patients with Y220C detected A
Slide 19: SCLC Patient With Rapid and Sustained Partial Response
SCLC Patient With Rapid and Sustained Partial Response • 71-year-old woman with ES-SCLC Weeks Baseline Week 12 • Progressed after 2 prior lines of therapy 0 3 6 9 12 15 18 21 24 27 30 33 20 with worsening dyspnea and complete occlusion of the left bronchus with atelectasis 0 Y220C VAF § Etoposide, c
Slide 20: Metastatic Castration-Resistant Prostate Cancer Patient with Sustained PSA Response
Metastatic Castration-Resistant Prostate Cancer Patient with Sustained PSA Response Disease control for 8+ months and ongoing • Prior treatments 57-year-old man • Hormonal therapy X 2 years then switched to enzalutamide X 7 months with high grade • Multiple courses of Radiotherapy to the thoracic an
Slide 21: Conclusions
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 at
Slide 22: Acknowledgments
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 Dana Farber Ca
Slide 23: Looking Ahead
LOOKING AHEAD @ pmveharma
Slide 24: Opportunity to target mutant p53 Y220C across multiple tumor types
Opportunity to target mutant p53 Y220C across multiple tumor types 2 Y220C Mutation Frequency 1,2 Overall Annual US incidence ~1% All Solid Tumors 17,000 patients Ovarian 2.9% Pancreatic 1.4% 1.1% Gastric/Esophageal Breast 1% Lung 1% 0.6% CRC TP53 Y220C mutations occur in multiple tumor types Prosta
Slide 25: Target Lesion Reductions Across Different Tumor Types at Doses ≥ 1150mg
Target Lesion Reductions Across Different Tumor Types at Doses ≥ 1150mg 60 Ovary Colon Pancreas Head and Neck Germ Cell 50 Endometrial Small Cell Lung Breast Prostate 40 30 20 10 PD SD SD SD SD SD SD SD uPR uPR SD PR PR SD PR PR PR PR 0 PD PD SD SD -10 -20 -30 -40 -50 -60 -70 -80 Includes patients w
Slide 26: Responses Across Tumor Types Supports a Pan Tumor Approach
Responses Across 6 Tumor Types Supports a Pan Tumor Approach 32% ORR at Doses ≥ 1150mg 1 2 Tumor Type Response evaluable , n SD, n (%) ORR , n (%) Ovarian 8 4 (50) 2 (25) Prostate 4 2 (50) 2 (50) Pancreatic 5 3 (60) 1 (20) Breast 3 1 (33) 1 (33) Endometrial 1 1 (100) Small cell lung 1 1 (100) Colore
Slide 27: PC14586 Preliminary Efficacy Appears Favorable Relative to SOC
PC14586 Preliminary Efficacy Appears Favorable Relative to SOC Relevant 2L+ SOC Outcomes in Key Tumor Types Tumor Type Line of Tx ORR (%) SOC RESPONSE RATES in late line patients in tumor types of interest Breast 3L 3.9-11.2% are generally <15% NSCLC / SCLC 2L 3.3-15.5% / 7% SOC DATA reflect a gener
Slide 28: PC14586: Next Steps
PC14586: Next Steps RP2D Building the value Phase 2 clinical footprint optimization proposition expansion In line with Project New US trial sites late Real World Evidence Optimus FDA initiative 2022 generation to contextualize PC14586 data Determine optimal dose in Sites in Europe, Asia- support of
Slide 29: PC14586: Continued Development Progress
PC14586: Continued Development Progress 2022 2023 2024 2025 NDA PC14586 Monotherapy Dose optimization to determine RP2D ongoing Phase 1 Phase 2 registrational Phase 2 initiation early 2023 Combination (PC14586 + anti PD-1) Phase 1b Dose Expansion: PD-1 naïve & PD-1 pretreated POC Phase 1 trial on tr
Slide 30: PC14586: A first-in-class molecule for an "undruggable" target
PC14586 A first-in-class molecule for what has long been considered an “undruggable” target Proof of concept Acceptable initial safety Meaningful single-agent achieved with first profile with Grade 1 / 2 clinical activity observed demonstration of p53 adverse events most across multiple tumor reacti
Slide 31: Key Upcoming Milestones
Key Upcoming Milestones Program Update Timing Updated Phase 1 data Q4 2022/Q1 2023 PC14586 Monotherapy Initiation of Phase 2 study Early 2023 PC14586 + PD1 Combination Study Initiation of Combination trial 2H 2022 31
Slide 32: Q&A Session
Q&A SESSION y @ pmveharma
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