Slide 1: KOL Webinar for Phase 1/2 PYNNACLE study of PC14586
KOL Webinar for Phase 1/2 PYNNACLE study of PC14586 from the 2023 AACR-NCI-EORTC International Conference October 12, 2023 Exhibit 99.2
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, including the timing of disclos
Slide 3: Agenda
Agenda David Mack, PhD President and Chief Executive Officer Aparna Parikh, MD Director Global Cancer Care Program, Mass General Hospital Deepika Jalota, PharmD Chief Development Officer Leila Alland, MD Chief Medical Officer Panel 01 02 03 04 Introduction AACR-NCI-EORTC 2023 Update and Clinical Exp
Slide 4: PMV Pharma is Harnessing the Power of p53 to Treat Cancer
PMV Pharma is Harnessing the Power of p53 to Treat Cancer PMV’s lead candidate is PC14586, a first-in-class p53 Y220C reactivator The p53 Y220C mutation, a previously undruggable target, is found in 1% of solid tumors PC14586 has achieved clinical proof of concept with favorable safety and prelimina
Slide 5: TP53 Y220C Hotspot Mutation is Detected across Solid Tumor Types
TP53 Y220C Hotspot Mutation is Detected across Solid Tumor Types TP53 mutations are the most common genomic events across all human cancers1 Most TP53 mutations occur in the central DNA-binding domain and ten of them are referred to as ‘hot-spot’ mutations, accounting for ~30% of the TP53 mutations
Slide 6: 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 pocket contained in the p53 Y220C mutant protein1 Stabilizes the p53 Y220C mutant protein in the wild-type p53 conformation, thereby restoring transcription and tumor-s
Slide 7: Updated results from the PYNNACLE Phase 1/2 study of PC14586
Updated Phase 1 results from the PYNNACLE Phase 1/2 study of PC14586, a selective p53 reactivator, in patients with advanced solid tumors harboring a TP53 Y220C mutation Aparna Parikh, M.D., M.S. Director of the Global Cancer Care Program at Mass General Hospital Cancer Center
Slide 8: PYNNACLE Phase 1/2 Trial – Phase 1 Study Design
Primary objective Determine MTD, select RP2D, and evaluate safety and tolerability Secondary objectives PK Preliminary efficacy Exploratory objectives Biomarkers/PD PYNNACLE Phase 1/2 Trial – Phase 1 Study Design Patients With Advanced Solid Tumors Harboring TP53 Y220C Mutation BID, twice daily; MTD
Slide 9: Patient Demographics and Disease Characteristics
Patient Demographics and Disease Characteristics Efficacious dose range (1150 mg QD to 1500 mg BID) Cancer Type, n (%) n=67 Age, years Median (min–max) 63 (32–84) Sex, n (%) Female Male 41 (61) 26 (39) Race, n (%) White Asian Black or African American Other Not Reported/Unknown 51 (76) 5 (7) 6 (9) 1
Slide 10: PMV-586-101 Phase 1: Efficacy Evaluable Population
PMV-586-101 Phase 1: Efficacy Evaluable Population Efficacious Dose Range (1150 mg QD to 1500 mg BID) Full Analysis Set N=67 All treated patients within the Efficacious Dose Range (1150 mg QD to 1500 mg BID) Efficacy Evaluable with TP53 Y220C / KRAS WT N=38 All treated patients with measurable disea
Slide 11: Target Lesion Reduction Across Tumor Types
Best change in tumor target lesion (%) Target Lesion Reduction Across Tumor Types Efficacious dose range TP53 Y220C / KRAS WT (1150 mg QD to 1500 mg BID) Includes patients with measurable disease at baseline and 1 post-baseline assessment. One SCLC patient without tumor measurement at 1st scan is no
Slide 12: Confirmed Responses at RP2D And Across Efficacious Dose Range
Confirmed Responses at RP2D And Across Efficacious Dose Range In Multiple Tumor Types TP53 Y220C / KRAS WT Patients RP2D 2000 mg QD N=16 Efficacious Dose Range 1150 mg QD – 1500 mg BID N=38 ORR n (%) ORR n (%) Overall Partial Response (PR) Stable Disease (SD) Progressive Disease (PD) 6 (38%) 6 8 2 1
Slide 13: Time to Response & Duration of Treatment
Time to Response & Duration of Treatment Efficacious Dose Range – TP53 Y220C/KRAS WT Includes all patients with measurable disease at baseline, KRAS WT and ≥ 1 post-baseline assessment (n=38) Data cut-off Sep 5, 2023 Treatment post-progression First response Treatment ongoing Ovary Endometrial SCLC
Slide 14: PC14586 Displays Linear and Dose Proportional PK
PC14586 Displays Linear and Dose Proportional PK Median PC14586 T1/2 of 19 hours at steady state across all patients allowing for QD dosing
Slide 15: PC14586 Demonstrated a Favorable Safety Profile
PC14586 Demonstrated a Favorable Safety Profile Efficacious dose range (1150 mg QD to 1500 mg BID) *Includes 5 additional grade 3 treatment-related adverse events: neutrophil count decreased, acute kidney injury, pancreatitis, pneumonitis, and rash erythematous ** Includes 1 patient with grade 4 imm
Slide 16: Patient with Triple Negative Breast Cancer with Rapid Onset of Response
Patient with Triple Negative Breast Cancer with Rapid Onset of Response carbo, carboplatin; pac, paclitaxel; pembro, pembrolizumide; cp, cyclophosphamide; dox, doxorubicin; NGS, next-generation sequencing; PR, partial response; QD, once daily; TNBC, triple negative breast cancer. Baseline Post cycle
Slide 17: Conclusion
Conclusion PC14586 demonstrated single agent clinical efficacy in heavily pre-treated patients across multiple TP53 Y220C and KRAS WT tumor types. A favorable safety profile was observed, with improvement in gastrointestinal adverse events when PC14586 is taken with food. Based on the overall data,
Slide 18: Looking Ahead & Phase 2
Looking Ahead & Phase 2 | . reg PMVPharma
Slide 19: Defined Registration Paths in Ovarian and Tumor Agnostic Patient Populations
Defined Registration Paths in Ovarian and Tumor Agnostic Patient Populations FDA alignment on RP2D, patient population and pivotal single arm Phase 2 study design obtained at EOP1 Meeting Cohort 2:Lung cancer n ~18 Cohort 1: Ovarian cancern = 42 Cohorts Cohort 3:Breast cancern ~18 Cohort 4:Endometri
Slide 20: Most TP53 Y220C Patients are KRAS WT
Most TP53 Y220C Patients are KRAS WT Overall, approximately 90% TP53 Y220C patients are KRAS WT % KRAS WT in TP53 Y220C Y220C and KRAS WT KRAS Mutant 99% 98% 97% 90% 87% 54% 6% 91% Source: The prevalence of TP53 Y220C and KRAS across different diseases was analyzed by using the FoundationInsights® w
Slide 21: TP53 Y220C Frequency and US Patients by Tumor Type
Tumor Type TP53 Y220C Frequency (%)1 Patients (US) TP53 Y220C / KRAS WT 1,2 SOC ORR (%) all-comer, 2L+ 3-8 All Solid Tumors ~1 14,000+ <15 Ovarian 2.9 1,200 12 (platinum-resistant) Breast 1 2,800 12 (3L+, all subtypes) Lung 1 1,800 <15 (NSCLC 3L) 7 (SCLC 2L) Endometrial 1.1 700 <15 (3L) PC14586 May
Slide 22: PC14586 – Advancing to a Phase 2 Single Arm Pivotal Study
PC14586 – Advancing to a Phase 2 Single Arm Pivotal Study Single-agent clinical activity observed across multiple tumor types supporting continued tumor agnostic development Acceptable safety profile with Grade 1 / 2 adverse events most frequently observed Successful FDA EOP1 meeting completed in Q3
Slide 23: PC14586: On a Path to NDA Submission in 2026
2023 2024 2025 2026 Monotherapy (PC14586) Combination (PC14586 + pembro) PC14586: On a Path to NDA Submission in 2026 Phase 1b Phase 1 Phase 2 registrational NDA
Slide 24: Key Upcoming Milestones
Key Upcoming Milestones Program Update Timing PC14586 Monotherapy Initiate Phase 2 trial 2024 Initial Phase 2 data 2025 Planned NDA submission 2026 PC14586 + PD1 Combination Study Initial Phase 1b data 2024 Cash Balance As of June 30, 2023 $219mm
Slide 25: Q&A Session
Q&A Session | “A - reg PMVPharma