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PMV Pharmaceuticals February 2026
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2 PMV’s lead candidate is rezatapopt, a first-in-class, investigational p53 Y220C reactivator The p53 Y220C mutation, a previously undruggable target, is found in 2.9% of ovarian cancer and 1% of all solid tumors Phase 1 PYNNACLE study has achieved proof of concept data for rezatapopt Pivotal Phase 2 PYNNACLE study interim clinical data demonstrates favorable efficacy and safety across multiple tumor types Strong balance sheet with $129.3 M as of September 30, 2025, with cash runway through 1Q2027 2 NDA submission planned in 1Q2027 in platinum-resistant/refractory ovarian cancer patients PMV Pharma is Harnessing the Power of p53 to Treat Cancer
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3 Rezatapopt Targets TP53 Y220C Hotspot Mutation Detected Across Solid Tumors • TP53 mutations are the most common genomic alterations 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 observed in human cancer1–2 • p53 Y220C is a key hot-spot TP53 missense mutation that destabilizes p531,3 • p53 Y220C present in ~1% of solid tumors4 • Addressable 2L+ U.S. & EU4/UK patients ~12K4,5 Deoxyribonucleic acid. 1 Baugh EH, et al. Cell Death Differ. 2018;25,154–160. 2 Roszkowska KA, et al. Int J Mol Sci. 2020;21:1334. 3 Bouaoun L, et al. Hum Mutat. 2016;37:865–876. 4 Foundation Insights, Schram et al. AACR-NCI-EORTC Conference 2023. 5 DRG Epidemiology Estimates 2028. Frequency of TP53 Y220C Across Common Solid Tumors Foundation Medicine Tissue and Heme assay test results collected between 1/1/2012 and5/31/2024 The prevalence of TP53 Y220C across different diseases was analyzed by using the FoundationInsights® web-based software platform to query a pan-solid tumor cohort of ~367,651 US-based, consented-for-research patients in the FoundationCore® Database4 that received FMI’s Commercial Tissue or Heme assays between 1/1/2012 and 5/31/2024. Ovarian 2.9% Breast 1% Lung 1% Endometrial 1.2%
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4 Rezatapopt 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 protein 1 • Stabilizes the p53 Y220C mutant protein in the wild -type p53 conformation, thereby restoring transcription and tumor - suppressor function1 • Inhibits proliferation across all Y220C-expressing cell lines p53 Y220C PC14586 Tumor regression in vivo 0 Days Tumor volume (mm3) 5 10 15 20 25 0 500 1000 1500 2000 2500 Vehicle, QDx21 PC14586, 25 mg/kg, QDx21 PC14586, 50 mg/kg, QDx21 PC14586, 100 mg/kg, QDx21 PC14586 (μM) P21 or MDM2/GAPDH 0.01 0.1 1 10 0 20 40 60 NUGC-3 (Y220C) NUGC-3_KO (KO) SJSA-1 (WT) HCT 116 (WT) A-431 (R273H) C-33 A (R273C) TOV-112D (R175H) NCI-H2029 (Y220D) SU.86.86 (G245S) SF-295 (R248Q) EFE-184 (R282W) p21 MDM2 p53 transcriptional activity restored Stabilizes p53 Y220C mutant in the WT p53 conformation PC14586 = rezatapopt NUGC-3 model MDM2, mouse double minute 2 homolog; KO, knockout; WT, wild-type. 1Dumble M, et al. Cancer Res. 2021;81(13_Suppl):Abstract LB006. NUGC-3: gastric cancer cell line
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5 Compelling Rezatapopt Monotherapy Phase 2 Interim Data 1 Natural history study (PMV data on file); ORR, overall response rate; FDA, Food and Drug Administration Across All Cohorts: • Encouraging efficacy in heavily pre-treated patients with a TP53 Y220C mutation with poor prognoses 1 • Promising rate of tumor responses observed across multiple tumor types • ORR: 34% • Median duration of response: 7.6 months • Differentiated safety and tolerability profile compared to standard of care Ovarian Cancer: • Significant unmet medical need • Strong response rate and benefit • ORR: 46% • Median duration of response: 8.0 months • Initial registrational opportunity in platinum -resistant or refractory ovarian cancer (PROC) informed by FDA feedback • TP53 Y220C mutation leads to a worse prognosis1 • Emerging clinical data supports rezatapopt as an effective, well- tolerated, oral option • Opportunity to deliver a novel, biomarker-selected chemo- alternative
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Rezatapopt Registrational Phase 2 Trial Design
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7 Overview of PYNNACLE Phase 2 Interim Data Overall results across all cohorts Ovarian cohort results NDA submission strategy Looking ahead
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8 PYNNACLE Phase 2 Study Design Ongoing Phase 2 study actively enrolling patients across ~60 sites globally Cohort 2: Lung cancer Cohort 1: Ovarian cancer Cohorts Cohort 3: Breast cancer Cohort 4: Endometrial cancer Cohort 5: All other solid tumors Basket N = ~200 Rezatapopt at 2000mg QD • Aged ≥ 12 years • Locally advanced or metastatic solid tumors, excluding primary CNS tumors • Documented TP53 Y220C and KRAS WT only • Prior standard therapy or ineligible for appropriate standard of care therapy Patient Population Accelerating development in key tumor types via a streamlined single-arm pivotal study design Primary endpoint: ORR per BICR - Across all cohorts - Ovarian cancer cohort WT, wild type; ORR, overall response rate; BICR, blinded independent central review
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9 Demographics and Baseline Characteristics (All Cohorts) Heavily pre-treated patients across broad spectrum of tumor types Data Cutoff 04Sep2025 Total N=112 Age (years) Median 65 Sex Female 73%, Male 27% ECOG PS 0: 44%, 1: 56% Prior line of systemic therapy Median of 3 prior lines (range 1-10) 3 or more prior lines 64% TP53 Y220C mutation status 100% KRAS status Wild type 100% a Includes 2 gastric cancer, 2 sarcoma, 1 small intestine cancer, 1 HCC, 1 pancreatic cancer, 1 thymic carcinoma and 1 esophagus carcinoma; ECOG PS, Eastern Cooperative Oncology Group Performance Status Cancer Type Ovarian cancer 46%, n=51 Lung cancer 17%, n=19 Breast cancer 15%, n=17 Endometrial cancer 5%, n=6 Colorectal cancer 5%, n=6 Ampullary carcinoma 2%, n=2 Gallbladder cancer 1%, n=1 Head and neck cancer 1%, n=1 Other solid tumorsa 8%, n=9
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10 Demographics and Baseline Characteristics (Ovarian Cancer) Heavily pre-treated population with poor prognostic features n=51 Age (years) Median 67 ECOG Performance Status 0: 47%, 1: 51% Prior lines of systemic therapy Median 4 prior lines (range 1-10) 3 or more prior lines: 73% Prior therapies Platinum-based tx: 100% Bevacizumab: 78% PARPi: 59% Platinum status at study entry Platinum-resistant: 59% Platinum-refractory: 35%* Platinum-sensitive 6% Histology High grade serous: 96% Somatic BRCA1/2 mutation BRCA1: 8%, BRCA2: 4% Heavily pre-treated patients: • 94% platinum-resistant or refractory • 78% received prior bevacizumab • 73% with three or more prior lines of therapy Ovarian Cancer * Including 14% (n=7) primary platinum-refractory ECOG, Eastern Cooperative Oncology Group Data Cutoff 04Sep2025
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11 TP53 Y220C / KRAS WT Efficacy Population a (n=103) Responses Observed Across All Cohorts in Eight Tumor Types By Cohort ORR n (%) Ovarian 22/48 (46%) b Platinum Resistant/Refractory Platinum Sensitive 21/45 (47%) 1/3 (33%) Breast 2/12 (17%) Lung 4/19 (21%) b Endometrial 3/5 (60%) Other Solid Tumors 4/19 (21%) 11 Ovarian Cancer 46% ORR 8.0 months median Duration of Response c Overall 34% Overall ORR 7.6 months median Duration of Response c Data Cutoff 04Sep2025 Across All Cohorts ORR n (%) ORR per Investigator assessment 35 (34%) Confirmed Complete Response (CR) 1 Confirmed Partial Response (PR) 29 Unconfirmed Partial Response (uPR) 5 b a Patients with the opportunity to reach first post-baseline scan. Patients discontinuing before the first post-baseline scan are included in the efficacy population. b As of 04Sep2025, uPRs were observed in 1 lung cancer patient and 4 ovarian cancer patients which subsequently converted to a confirmed PR post data cutoff. c DoR accounts only for confirmed responses. Post-data cutoff: • All 5 patients with auPR converted to a confirmed PR ORR, overall response rate; WT, wild type
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12 Target Lesion Reduction Observed in the Majority of Patients Including patients (n=92) with a post-baseline tumor assessment. Best overall responses are noted in the figure (* = uPR). At the time of data extraction, an additional uPR was recorded without tumor measurements reported as of yet. CR, complete response; NE, non-evaluable; PD, progressive disease; PR, partial response; SD, stable disease; uPR, unconfirmed partial response. Data Cutoff 04Sep2025
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13 CR, complete response; DoR, duration of response; PR, partial response; TTR, time to response; uPR, unconfirmed partial response Rapid Time to Response and Long Duration of Treatment Months 40% of patients remain on treatment All cohorts • Median TTR: 1.3 months • Median DoR: 7.6 months Ovarian cancer cohort • Median TTR: 1.3 months • Median DoR: 8.0 months CR PR uPR Treatment ongoing Ovarian cancer All other solid tumors Data Cutoff 04Sep2025
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14 • TRAEs were mostly Grade 1/2 • Most frequent TRAEs: Nausea, fatigue, blood creatinine increased, ALT increased • Laboratory abnormalities were manageable / monitorable with most cases being transient and reversible • Four patients (4%) discontinued treatment due to TRAEs • Administration of rezatapopt with food decreased incidence of gastrointestinal TRAEs compared with Phase 1 1,2 All TRAEs (≥ 10% of Patients) Preferred Term, n (%) Overall N = 112 Grade 1 Grade 2 Grade 3 Grade 4 Nausea 38 (34) 24 (21) 13 (12) 1 (1) - Fatigue 26 (23) 11 (10) 13 (12) 2 (2) - Bloodcreatinineincreased 22 (20) 5 (4) 16 (14) 1 (1) - Alanine aminotransferase increased 20 (18) 8 (7) 5 (4) 6 (5) 1 (1) Aspartate aminotransferase increased 16 (14) 6 (5) 3 (3) 7 (6) - Anemia 16 (14) 5 (4) 6 (5) 5 (4) - Decreasedappetite 14 (13) 11 (10) 3 (3) - - Vomiting 13 (12) 7 (6) 6 (5) - - Favorable Safety and Tolerability ALT, alanine aminotransferase; AST, aspartate aminotransferase; CTCAE, Common Terminology Criteria for Adverse Events; TRAE, treatment-related adverse event. 1. Kuo H-CD, et al. Clinical Pharmacology (ACCP) 2024; Poster presentation 044; 2. Schram AM, et al. Annual Meeting on Women’s Cancer (SGO). 2024; Oral presentation (abstract LBA 26). Data Cutoff 04Sep2025
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15 On Target Activity Supported by Significant Decreases in ctDNA TP53 Y220C Mutation VAF BOR, best overall response; CR, complete response; ctDNA, circulating tumor DNA; NE, non-evaluable; PD, progressive disease; PR,partial response; SD, stable disease; VAF, variant allele frequency. • 78 patients, including 35 ovarian cancer patients, had ctDNA TP53 Y220C VAF data available at baseline and on treatment (3 –6 weeks) • All patients experiencing a response had a reduction in TP53 Y220C VAF • 91% had a reduction in TP53 Y220C VAF - 73% had a reduction of ≥50% Data Cutoff 04Sep2025
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16 Ovarian Cancer as Lead Indication Informed by FDA Feedback T argeting 1Q2027 NDA submission seeking accelerated approval 1Q2026 4Q2026 1Q2027 Potential U.S. Launch in 2027 Ovarian cohort enrollment completion Ovarian cohort primary analysis data Ovarian cohort planned NDA submission Enroll an additional 20 -25 PROC patients having received prior SoC FDA, Food and Drug Administration; NDA, New Drug Application; PROC, platinum-resistant/refractory ovarian cancer; SoC, standard of care
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17 Market Research Feedback I would think this is going to be the go-to agent [for ovarian cancer]. With this current data, this beats everything in the market—if the patient does carry the mutation.” Community Oncologist, TX It’s meaningful if a patient doesn’t have to come in for an infusion all the time. PO [oral] is attractive...” Community Gynecologic Oncologist, GA Commercial Opportunity: • De-risked opportunity in PROC as lead indication with projected 2027 launch • Potential to expand label beyond PROC • Clear value proposition for rezatapopt relative to existing and emerging treatments • TP53 Y220C mutation broadly identifiable Rezatapopt Offers Compelling Commercial Opportunity “PROC, platinum-resistant/refractory ovarian cancer
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18 • Non-platinum-based Chemotherapy +/ - bevacizumab • Mirvetuximab (FR-alpha) • Trastuzumab deruxtecan (T-DXd) (HER2+) Platinum-Resistant Patients Platinum-Sensitive Patients 1st Line 2nd Line 3rd Line Platinum-based Chemotherapy Limitation of approved options: • Inconvenient IV administration • AEs requiring invasive monitoring • Chemotherapy offers limited efficacy Rezatapopt offers: • Biomarker-directed approach • Competitive and differentiated profile vs. other emerging therapies • Convenient oral administration • Common AEs are manageable Rezatapopt Well-Positioned for Success in Ovarian Cancer and Beyond AEs, adverse events
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19 TP53 Y220C Mutation is Broadly Identifiable on Existing NGS Panels • Molecular testing is now recommended by NCCN and ESMO across many cancer types including ovarian cancer, breast cancer, NSCLC, endometrial and others • Reimbursement of NGS testing is widely covered by Medicare and private insurance for qualifying patients NGS, next-generation sequencing; NCCN, National Comprehensive Cancer Network; ESMO, European Society for Medical Oncology; NSCLC, non-small cell lung cancer
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20 Total 2L+ TP53 Y220C Ovarian Cancer 1 Addressable patients estimated based on DRG drug -treated patients 2028. 2 Assumes net monthly pricing with 15% net discount, price range of $45 - $55K per month based on analog pricing. 3 Assume 1.5X U.S. potential; NDA, New Drug Application ~1,700 Addressable 2L+ U.S. & EU4/UK Patients1 ~$350 - 420M U.S. Market Potential2 ~$520 - 630M Global Market Potential3 • Ovarian cancer patient population will be pursued as initial NDA submission • Label expansion potential in other tumors TP53 Y220C 2L+ Ovarian Cancer Offers Meaningful Market Potential
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21 Future Opportunities to Grow Rezatapopt Beyond Ovarian Cancer • Monotherapy data continues to be generated in Phase 2 PYNNACLE • 2L+ endometrial cancer has the potential to add ~350 patients in U.S. and EU4/UK Endometrial • Monotherapy data continues to be generated in Phase 2 PYNNACLE • 2L+ Breast cancer has the potential to add ~2,000 patients in U.S. and EU4/UK Breast Monotherapy Combination Solid TumorsHematologic • Bevacizumab (PSOC) • KRAS inhibitors (NSCLC, Pancreatic, CRC) • R/R AML/MDS in combination with azacitidine (ongoing IIT) • Newly diagnosed AML/MDS in combination with azacitidine and venetoclax NSCLC, non-small cell lung cancer; CRC, colorectal cancer; PSOC, platinum-sensitive ovarian cancer; AML, acute myeloid leukemia;MDS, myelodysplastic syndrome; IIT, investigator-initiated trial
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22 Compelling Efficacy and Defined Registrational Path for Rezatapopt In the Phase 2 PYNNACLE trial interim data, rezatapopt demonstrated an ORR of 46% in ovarian cancer with a median DoR of 8.0 months Strong balance sheet with $129.3 M as of September 30, 2025, with cash runway through 1Q2027 22 NDA submission planned in 1Q2027 in platinum-resistant/refractory ovarian cancer patients ORR, overall response rate; DoR, duration of response; NDA, New Drug Application