8-K

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, D.C. 20549

FORM 8-K

CURRENT REPORT

Pursuant to Section 13 or 15(d)

of the Securities Exchange Act of 1934

Date of Report (Date of earliest event reported): June 7, 2022

PMV Pharmaceuticals, Inc.

(Exact name of Registrant as Specified in Its Charter)

Delaware	001-39539	46-3218129
(State or Other Jurisdiction of Incorporation)	(Commission File Number)	(IRS Employer Identification No.)

8 Clarke Drive, Suite 3, Cranbury, NJ	08512
(Address of Principal Executive Offices)	(Zip Code)

Registrant’s Telephone Number, Including Area Code: (609) 642-6670

Not Applicable

(Former Name or Former Address, if Changed Since Last Report)

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

☐ Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

☐ Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

☐ Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

☐ Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Securities registered pursuant to Section 12(b) of the Act:

Title of each class	Trading Symbol(s)	Name of each exchange on which registered
Common Stock, $0.00001 par value per share	PMVP	The Nasdaq Global Select Market

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§ 230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§ 240.12b-2 of this chapter).

Emerging growth company ☐

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐

Item 7.01 Regulation FD Disclosure.

On June 7, 2022, on behalf of PMV Pharmaceuticals, Inc. (the “Company”), Ecaterina Ileana Dumbrava, M.D., Assistant Professor of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center delivered a scientific presentation at the 2022 American Society of Clinical Oncology (“ASCO”) Annual Meeting announcing the initial results from the Company’s ongoing Phase 1/2 PYNNACLE study of PC14586 in patients with advanced solid tumors harboring a p53 Y220C mutation. The initial results demonstrated anti-tumor activity across multiple tumor types with an acceptable safety profile. On June 7, 2022, the Company also issued a press release and held an investors conference call via webcast regarding its initial results from the ongoing Phase 1/2 PYNNACLE study of PC14586.

A copy of the press release and the ASCO investors presentation (the “ASCO Investors Presentation”) are attached as Exhibits 99.1 and 99.2, respectively, to this Current Report on Form 8-K.

The information in this Item 7.01 of this Form 8-K, including the attached Exhibits 99.1 and 99.2 to this report, is intended to be furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such a filing, whether made before or after the date hereof, regardless of any general incorporation language in such a filing.

The press release attached as Exhibit 99.1 and the ASCO Investors Presentation attached as Exhibit 99.2 to this Current Report on Form 8-K includes “safe harbor” language pursuant to the Private Securities Litigation Reform Act of 1995, as amended, indicating that certain statements contained therein are “forward-looking” rather than historical.

Item 9.01 Financial Statements and Exhibits.

(d) Exhibits:

Exhibit Number	Description
99.1	Press Release issued by PMV Pharmaceuticals, Inc., dated June 7, 2022.
99.2	ASCO Investors Presentation.
104	Cover Page Interactive Data File (embedded within the Inline XBRL document).

1

SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned thereunto duly authorized.

	PMV Pharmaceuticals, Inc.
Date: June 8, 2022	By:	/s/ Winston Kung
		Winston Kung
		Chief Operating Officer, and Chief Financial Officer (Principal Financial Officer)

2

EX-99.1

Exhibit 99.1

PMV Pharmaceuticals Initial PC14586 Phase 1 Data Presented at ASCO Demonstrated Anti-Tumor Activity Across Multiple Solid Tumor Types With a p53 Y220C Mutation

• Overall response rate (ORR) of 32% (8/25) achieved in higher dose cohorts per RECIST v1.1

• Partial responses observed across six distinct tumor types

• Data featured as an oral presentation at ASCO; Company to host investor event via webcast today at 6:30 pm CDT to review data presented

CRANBURY, N.J., June 7, 2022 (GLOBE NEWSWIRE) — PMV Pharmaceuticals, Inc. (Nasdaq: PMVP; “PMV Pharma”), a precision oncology company pioneering the discovery and development of small molecule, tumor-agnostic therapies targeting p53, today announced that preliminary results from the ongoing Phase 1/2 PYNNACLE study of PC14586 in patients with advanced solid tumors harboring a p53 Y220C mutation demonstrated anti-tumor efficacy across multiple tumor types with an acceptable safety profile. PC14586 is a first-in-class precision oncology small molecule investigational therapy that selectively targets the p53 Y220C mutation in solid tumors.

The data were featured in an oral presentation at the 2022 American Society of Clinical Oncology (ASCO) annual meeting. The presentation entitled, “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,” was delivered by Ecaterina Ileana Dumbrava, M.D., Assistant Professor of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center.

Dr. Dumbrava commented, “p53 is a target that until now was widely believed to be undruggable. The favorable safety and tolerability of PC14586, along with the clinical activity across six distinct tumor types, supports the potential of PC14586 to become a new treatment modality that can address the unmet need of patients with advanced solid tumors harboring a TP53 Y220C mutation.”

Safety

• The most common treatment-emergent adverse events (>15%) included nausea, vomiting, AST increase, ALT increase, anemia, blood creatinine increase, and fatigue.

• The maximum tolerated dose (MTD) was reached at 1500 mg twice daily.

• Enrollment at doses below the MTD is ongoing to support the determination of a recommended Phase 2 dose.

Efficacy

• ORR assessed by investigators according to RECIST v1.1 was 32% (8/25) in patients receiving an initial total daily dose of 1150 mg and above. Of the 8 responding patients, 6 have confirmed partial responses and 2 have unconfirmed partial responses, pending confirmation.

• ORR was 24% (8/33) across all dose cohorts.

• Responses were observed across six distinct tumor types including breast, endometrial, prostate, pancreatic, ovarian, and small cell lung cancer.

• Best Response of stable disease or partial response was observed in 19/25 patients at doses ≥1150 mg (76%).

“These encouraging Phase 1 safety and preliminary efficacy data provide proof of concept for PC14586 as monotherapy to selectively reactivate p53 across multiple tumor types,” said Leila Alland, M.D., Chief Medical Officer of PMV Pharma. “We look forward to completing the Phase 1 portion of the PYNNACLE study in the second half of this year and initiating the potentially pivotal Phase 2 portion of the study early in 2023.”

Investor Event

Management will host an investor event via webcast on June 7, 2022, at 6:30 pm CDT to discuss the PC14586 Phase 1 data. The event will feature a presentation by Dr. Dumbrava who will review the data presented at ASCO.

To listen to the webcast and view the accompanying slide presentation, please refer to the Events and Presentations section of the PMV Pharma website.

About the PYNNACLE Study

PYNNACLE is an open-label, multicenter Phase 1/2 clinical study assessing safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of PC14586 in patients with advanced solid tumors harboring a p53 Y220C mutation. A total of 41 patients were enrolled as of May 10, 2022; 36 patients with measurable disease at baseline including 33 patients determined to be eligible for response evaluation. During the Phase 1 dose-escalation portion of the study, multiple dose levels of PC14586 were evaluated (150 mg QD, 300 mg QD, 600 mg QD, 1150 mg QD, 1500 mg QD, 2000 mg QD, 2500 mg QD, and 1500 mg BID). Preliminary efficacy was assessed by RECIST v1.1. A recommended Phase 2 dose will be selected at the end of Phase 1. For more information on the Phase 1/2 PYNNACLE study (PMV-586-101), refer to www.clinicaltrials.gov (NCT study identifier NCT04585750).

About PC14586

PC14586 is a first-in-class, small molecule p53 reactivator designed to selectively bind to the crevice present in the p53 Y220C mutant protein, hence, restoring the wild-type, or normal, p53 protein structure and tumor-suppressing function. PC14586 is being developed for the treatment of patients with locally advanced or metastatic solid tumors that have a p53 Y220C mutation. Fast Track designation has been granted by the Food and Drug Administration (FDA) for evaluating PC14586 for the treatment of patients with locally advanced or metastatic solid tumors that have a p53 Y220C mutation.

About PMV Pharma

PMV Pharma is a precision oncology company pioneering the discovery and development of small molecule, tumor-agnostic therapies targeting p53. p53 mutations are found in approximately half of all cancers. The field of p53 biology was established by our co-founder Dr. Arnold Levine when he discovered the p53 protein in 1979. Bringing together leaders in the field to utilize over four decades of p53 biology, PMV Pharma combines unique biological understanding with pharmaceutical development focus. PMV Pharma is headquartered in Cranbury, New Jersey. For more information, please visit www.pmvpharma.com.

Forward-Looking Statements

Statements contained in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Such statements include, but are not limited to, statements regarding the Company’s future plans or expectations for PC14586, including expectations regarding success of its current clinical trial for PC14586 and any future commercialization plans for the product candidate; and the future plans or expectations for the Company’s discovery platform for its other early-stage and clinical candidates. Any forward-looking statements in this statement are based on management’s current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. Risks that contribute to the uncertain nature of the forward-looking statements include: the success, cost, and timing of the Company’s product candidate development activities and planned clinical trials, the Company’s ability to execute on its strategy and operate as an early

clinical stage company, the potential for clinical trials of PC14586 or any future clinical trials of other product candidates to differ from preclinical, preliminary or expected results, the Company’s ability to fund operations, and the impact that the current COVID-19 pandemic may have on the Company’s clinical trials, supply chain, and operations, as well as those risks and uncertainties set forth in the section entitled “Risk Factors” in the Company’s Annual Report on Form 10-K filed with the Securities and Exchange Commission (the “SEC”) on March 1, 2022, the Company’s Quarterly Report on Form 10-Q filed with the SEC on May 10, 2022 and its other filings filed with the SEC. All forward-looking statements contained in this press release speak only as of the date on which they were made. The Company undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.

Contacts

Investor Contact:

Winston Kung

PMV Pharmaceuticals, Inc.

investors@pmvpharma.com

Media Contact:

Kathy Vincent

Greig Communications

kathy@greigcommunications.com

EX-99.2

Exhibit 99.2 ASCO PC14586 INVESTOR EVENT June 7, 2022

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 regarding regulatory filings, our expectations regarding the relative benefits of our product candidates versus competitive therapies, and our expectations regarding the therapeutic and commercial potential of our product candidates. The words “believe,” “may,” “should,” “will,” “estimate,” “promise,” “plan”, “continue,” “anticipate,” “intend,” “expect,” “potential” and similar expressions (including the negative thereof), are intended to identify forward-looking statements. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Risks that contribute to the uncertain nature of the forward-looking statements include: our preclinical studies and clinical trials may not be successful; the U.S. Food and Drug Administration (FDA) may not agree with our interpretation of the data from clinical trials of our product candidates; we may decide, or the FDA may require us, to conduct additional clinical trials or to modify our ongoing clinical trials; we may experience delays in the commencement, enrollment, completion or analysis of clinical testing for our product candidates, or significant issues regarding the adequacy of our clinical trial designs or the execution of our clinical trials may arise, which could result in increased costs and delays, or limit our ability to obtain regulatory approval; the commencement, enrollment and completion of clinical trials and the reporting of data; the COVID-19 pandemic may disrupt our business and that of the third parties on which we depend, including delaying or otherwise disrupting our clinical trials and preclinical studies, manufacturing and supply chain, or impairing employee productivity; our product candidates may not receive regulatory approval or be successfully commercialized; unexpected adverse side effects or inadequate therapeutic efficacy of our product candidates could delay or prevent regulatory approval or commercialization; and we may not be able to obtain additional financing. Additional risks and uncertainties may emerge from time to time, and it is not possible for PMV Pharma’s management to predict all risk factors and uncertainties. All forward-looking statements contained in this presentation speak only as of the date on which they were made. Other risks and uncertainties affecting us are described more fully in our filings with the Securities and Exchange Commission. We undertake no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made. 2

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 Ahead Leila Alland, MD, Chief Medical Officer Q&A Session 04 3

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 PYNNACLE clinical Shenk, Ph.D. of PC14586 data at ASCO PC14586 granted Fast Track Designation 4

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 molecule, tumor- PYNNACLE trial across all solid tumors agnostic therapies targeting p53 with the p53 Y220C mutation Continued progress on hotspot p53 programs Our unique expertise and drug Compelling preclinical synergy discovery capabilities enable the observed with PC14586 and anti PD-1 identification and development of highly inhibitors support the planned clinical selective small molecules that evaluation of the combination reactivate and restore p53 function 5

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-Khoueiry, Andrae L. Vandross, 8 9 10 11 12 12 12 12 Shivaani Kummar, Aparna R. Parikh, Pamela N. Munster, Erika Daly, Laura DeLeon, Megan Khaddar, Kimberley LeDuke, Kimberly Robell, Lisa 12 12 12 12 13 Sheehan, Meagen St Louis, Amy Wiebesiek, Leila Alland, Alison M. Schram 1 2 3 4 The University of Texas MD Anderson Cancer Center, Houston, TX; Sarah Cannon Research Institute, Nashville, TN; NEXT Oncology, San Antonio, TX; Dana 5 6 7 Farber Cancer Institute, Boston, MA; Seattle Cancer Care Alliance, Seattle, WA; USC Norris Cancer Center, Los Angeles, CA; NEXT Oncology, Austin, TX; 8 9 10 OHSU Knight Cancer Institute, Portland, OR; Massachusetts General Hospital, Boston, MA; University of California, San Francisco, San Francisco, CA; 11 12 13 Cytel, Inc., Waltham, MA; PMV Pharmaceuticals, Inc., Cranbury, NJ; Memorial Sloan Kettering Cancer Center, New York, NY. 6

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 stress and Ub DNA damage p53 target p53 p53 § Supports DNA repair before cellular replication genes § Induces apoptosis 4 • Protein levels are tightly controlled by MDM2 MDM2 • Apoptosis • Cell cycle arrest • TP53 mutation resulting in p53 inactivation is a key 3 • Senescence step in oncogenesis Degradation DNA, deoxyribonucleic acid; MDM2, mouse double minute 2 homolog. 1. Chillemi G, et al. Cold Spring Harb Perspect Med. 2017;7:a028308. 2. Kastenhuber ER, et al. Cell. 2017;170:1062–1078. 3. Levine AJ. Nat Rev Cancer. 2020;20:471–480. 4. Levine AJ. J Mol Cell Biol. 2019;11:524–530. 7

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% • Most TP53 mutations occur in the central DNA- Lung 1% binding domain and ten of them are referred to as ‘hot-spot’ mutations, accounting for ~30% of the Pancreatic 1.4% 1–2 TP53 mutations observed in human cancer Gastric/ 1.1% Esophageal • p53 Y220C is a key hot-spot TP53 missense 1,3 mutation that destabilizes p53 CRC 0.6% Ovarian 2.9% 4 • p53 Y220C is present in ~1% of all solid tumors Prostate 0.5% CRC, colorectal cancer; DNA, deoxyribonucleic acid. 1. Baugh EH, et al. Cell Death Differ. 2018;25,154–160. The prevalence of TP53 Y220C across different diseases was analyzed by using the 2. Roszkowska KA, et al. Int J Mol Sci. 2020;21:1334. ® FoundationInsights web-based software platform to query a pan-solid tumor cohort of ~367,651 3. Bouaoun L, et al. Hum Mutat. 2016;37:865–876. ® 4 US-based, consented-for-research patients in the FoundationCore Database that received FMI’s 4. Westphalen CB, et al. NPJ Precis Oncol. 2021;20;5(1):69. Commercial Tissue or Heme assays between 1/1/12 and 12/31/2020 8

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 tumor-suppressor function Stabilizes p53 Y220C mutant in the p53 transcriptional Tumor regression in vivo WT p53 conformation activity restored Vehicle, QDx21 NUGC-3 (Y220C) 2500 PC14586, 25 mg/kg, QDx21 NUGC-3_KO (KO) PC14586, 50 mg/kg, QDx21 60 SJSA-1 (WT) 2000 PC14586, 100 mg/kg, QDx21 p21 HCT 116 (WT) A-431 (R273H) p53 Y220C 1500 40 C-33 A (R273C) PC14586 TOV-112D (R175H) 1000 MDM2 NCI-H2029 (Y220D) 20 SU.86.86 (G245S) 500 SF-295 (R248Q) 0 EFE-184 (R282W) 0 0.01 0.1 1 10 0 5 10 15 20 25 PC14586 (μM) Days MDM2, mouse double minute 2 homolog; KO, knockout; WT, wild-type. 1. Dumble M, et al. Cancer Res. 2021;81(13_Suppl):Abstract LB006. 9 P21 or MDM2/GAPDH 3 Tumor volume (mm )

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 1150 mg QD n=5 RP2D harboring p53 Y220C mutation 600 mg QD n=4 300 mg QD n=3 mTPI design; intrapatient dose escalation and backfill enrollment permitted 150 mg QD n=3 Enrollment 41 patients as of May 10, 2022 100 patients (estimated) Primary objective • Determine MTD, select RP2D, and evaluate safety and tolerability • ORR based on BICR Secondary objectives • PK • ORR based on investigator • Preliminary efficacy assessment, TTR, DoR, DCR, PFS, OS, safety, quality of life Exploratory objectives • Biomarkers (ctDNA, CTC) • Biomarkers BICR, blinded independent central review; BID, twice daily; CTC, circulating tumor cells; ctDNA, circulating tumor DNA; DCR, disease control rate; DoR, duration of response; MTD, maximum tolerated dose; mTPI, modified toxicity probability interval design; ORR, objective response rate by RECIST (Response Evaluation Criteria in Solid Tumors) 1.1; OS, overall survival; PFS, progression-free survival; PK, pharmacokinetics; QD, once daily; RP2D, recommended Phase 2 dose; TTR, time-to-response. NCT study identifier: NCT04585750. BICR, blinded independent central review; BID, twice daily; CTC, circulating tumor cells; ctDNA, circulating tumor DNA; DCR, disease control rate; DoR, duration of response; MTD, maximum tolerated dose; mTPI, modified 10 toxicity probability interval design; ORR, objective response rate by RECIST (Response Evaluation Criteria in Solid Tumors) 1.1; OS, overall survival; PFS, progression-free survival; PK, pharmacokinetics; QD, once daily; RP2D, recommended Phase 2 dose; TTR, time-to-response.

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=11) Black or African American 3 (7) Other 1 (2) Not Reported/Unknown 3 (7) Colon 12.2% (n=5) ECOG status, n (%) 0 18 (44) 1 23 (56) Prior systemic therapies, n (%)* Prostate 1–2 17 (42.5) Pancreas 12.2% (n=5) ≥3 23 (57.5) 19.5% (n=8) Median (min–max) 3 (1–9) Germline TP53 Y220C, n (%) Breast Negative 38 (93) 14.6% (n=6) Positive 2 (5) Pending 1 (2) Data cut-off May 10, 2022 *One patient with unknown prior systemic therapies. 11 *One patient with unknown prior systemic therapies.

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 treatment-related AE, n (%) 33 (80.5) 12 (29.3) 11 (26.8) 9* (22.0) 1* (2.4) creatinine increase, and fatigue​ Nausea 18 (43.9) 11 (26.8) 7 (17.1) Vomiting 11 (26.8) 6 (14.6) 5 (12.2) • Dose-limiting toxicities reported in AST increased 9 (22.0) 7 (17.1) 1 (2.4) 1 (2.4) 2 patients at 1500 mg BID​ ALT increased 8 (19.5) 2 (4.9) 4 (9.8) 2 (4.9) Anemia 7 (17.1) 1 (2.4) 4 (9.8) 2 (4.9) § Grade 3 AST/ALT increase​ Blood creatinine increased 7 (17.1) 3 (7.3) 4 (9.8) § Grade 3 acute kidney injury Fatigue 7 (17.1) 6 (14.6) 1 (2.4) Diarrhea 5 (12.2) 5 (12.2) • Maximum tolerated dose reached at Decreased appetite 3 (7.3) 2 (4.9) 1 (2.4) 1500 mg BID Headache 3 (7.3) 3 (7.3) Neutrophil count decreased 3 (7.3) 2 (4.9) 1 (2.4) • RP2D not yet defined Platelet count decreased 3 (7.3) 1 (2.4) 1 (2.4) 1 (2.4) Data cut-off May 10, 2022 *Grade 3 and 4 treatment-related AEs not shown in the table (each in one patient) are Grade 3 acute kidney injury, hypokalemia, and pneumonitis, and Grade 4 immune thrombocytopenia. AE, adverse event; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BID, twice daily; CTCAE, Common Terminology Criteria for Adverse Events; RP2D, recommended Phase 2 dose. 12

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 (Cohort 7, n=5) 300 mg QD (Cohort 2, n=3) 1500 mg QD (Cohort 8, n=2) 150 mg QD (Cohort 1, n=3) 10 0 0 500 1000 1500 2000 2500 3000 0 5 10 15 20 25 Dose (mg) Time (h) on Day 15 (steady state) AUC was multiplied by 2 to calculate AUC 0–12 0–24 Concentrations from 12–24 h imputed for 1500 mg BID dose group for 1500 mg BID dose group (3000 mg daily dose) Median half-life at Day 15 is 19 h Data are preliminary with 29 out of 41 patients having Day 15 samples at time of data cut-off. Dose-proportional increases in C were also observed (not shown). max AUC, area under the curve; BID, twice daily; C , maximum serum concentration; QD, once daily; SD, standard deviation. max 13 PC14586 plasma concentration (ng/mL) Mean (SD) AUC at Day 15 (ng.h/mL) 0–24

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 uPR 0 2 2 § SD 4 11 15 PD 4 3 7 * Not evaluable 0 3 3 *Patients without a post-baseline assessment are either excluded from “eligible for response evaluation’’ if ongoing, or considered “not evaluable” if discontinued; ‡ § ORR = PR + uPR; Includes three initially unconfirmed PR that progressed on the next tumor assessment. BID, twice daily; ORR, objective response rate; PD, progressive disease; PR, partial response; QD, once daily; RECIST, Response Evaluation Criteria in Solid Tumors; SD, stable disease; uPR, unconfirmed PR pending confirmation. Data cut-off May 10, 2022 14

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 -40 −50 -50 −60 -60 −70 -70 −80 -80 0 20 40 60 80 100 120 140 160 180 200 220 240 0 20 40 60 80 100 120 140 160 180 200 220 240 Study day Study day Dose Cohorts 4 through 8 Dose Cohorts 1 through 3 (1150 mg QD to 1500 mg BID) (150 mg QD to 600 mg QD) Data cut-off May 10, 2022 15 Change from baseline (%) Change from baseline (%)

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 with measurable disease and one post-baseline assessment. All doses are in mg. BID, twice daily; PD, progressive disease; PR, partial response; Data cut-off May 10, 2022 QD, once daily; SD, stable disease; uPR, unconfirmed PR pending confirmation. 16 Best change in tumor target lesion (%) 1150 QD 600 QD 1500 BID 150 QD 600 QD 2500 QD 1500 BID 300 QD 600 QD 150 QD 1150 QD 600 QD 2000 QD 2000 QD 1500 BID 2000 QD 2500 QD 1150 QD 1500 QD 1500 QD 1500 QD 2000 QD 1500 BID 300 QD 2000 QD 2500 QD 1500 BID 2500 QD 2000 QD 1150 QD

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 2500 QD Ovary SD 1500 BID Colon SD 300 QD Head and Neck SD 1500 QD Prostate uPR 1500 QD Pancreas uPR 1500 QD Ovary SDà 13 patients on treatment at the cut-off date 1150 QD Ovary PD à Treatment ongoing for 6 out of 8 responders 150 QD Breast PD 1500 BID Pancreas Ne 600 QD Colon PD 150 QD Colon PD 1150 QD Breast PD 1500 BID Ovary SD Treatment post-progression 1500 QD Ovary NE 1500 BID Germ Cell PD First response 2500 QD Pancreas SD 1500 BID Breast Ne Treatment ongoing 1500 QD Breast Ne 2000 QD Ovary SD 1150 QD Pancreas NE 600 QD Pancreas PD 1500 BID Head and Neck NE 0 1 2 3 4 5 6 7 8 9 Overall treatment duration (months) Data cut-off May 10, 2022 Includes all patients with measurable disease at baseline (n=36). All doses are in mg. BID, twice daily; NE: not evaluable; Ne, not eligible for response assessment; PD, progressive disease; PR, partial response; QD, once daily; SD, stable disease; uPR, unconfirmed PR pending confirmation. 17

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 All enrolled patients with ≥ 2 CTCs detected in ≥ 1 sample at baseline and Week 2 in ≥ 1 sample at baseline and Week 3 Data cut-off May 10, 2022 CTC, circulating tumor cells; ctDNA, circulating DNA, VAF: Variant Allelic Frequency 18

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, carboplatin and Tumor Target Lesions -20 Dose Escalation atezolizumab (10 months) § Topotecan (4 months) -40 • Prior radiotherapy of brain metastasis -60 • TP53 Y220C detected by NGS -80 • PC14586 1150mg QD was started § PR after 6 weeks with relief of -100 respiratory symptoms -120 § Increased to 2000mg QD at week 30 • Well tolerated with transient treatment Correlation between radiographic tumor 60% reduction in target lesions at Week 6 and related Grade 3 neutropenia shrinkage and Y220C ctDNA decrease at 70% at Week 12 • Treatment ongoing for 9+ months AE, adverse event; ctDNA, circulating tumor DNA; ES, extensive stage; NGS, next-generation sequencing; PR, partial response; QD, once daily; SCLC, small cell lung carcinoma; VAF, variant allelic frequency. Images courtesy of Dr Melissa Johnson, Sarah Cannon Research Institute. 19 % change from baseline

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 and sacral bone metastases prostate • Abiraterone adenocarcinoma • Radiotherapy of the prostate (Gleason Score 9) • Cabazitaxel with bone • Presence of TP53 Y220C detected metastases at diagnosis • PC14586 initiated at 2000 mg QD • Rapid reduction in PSA, with >50% decrease by 8 weeks and ongoing (nonmeasurable per RECIST v1.1) • PC14586 reduced to 1000 mg QD at week 25 due to Grade 2 creatinine increase • Disease control ongoing for 33 weeks and treatment continues 20

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 dose(s) below the MTD to support RP2D determination is ongoing 21

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 Cancer Institute, Boston, MA OHSU Knight Cancer Institute, Portland, OR NEXT Oncology, Austin, TX NEXT Oncology, San Antonio, TX Massachusetts General Hospital, Boston, MA MD Anderson Cancer Center, Houston, TX Memorial Sloan Kettering Cancer Center, New York, NY Sarah Cannon Research Institute, Nashville, TN Seattle Cancer Care Alliance, Seattle, WA UC San Francisco, San Francisco, CA USC Norris Cancer Center, Los Angeles, CA Hoag Cancer Institute, Newport Beach, CA Clinical trial is sponsored by PMV Pharmaceuticals, Inc. Medical writing was supported by SCION 22

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 Prostate including most common tumor types 0.5% 24 1 2 Dumbrava et al: ASCO 2022; Cancer Facts & Figures 2022, American Cancer Society

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 with measurable disease and one post-baseline assessment. All doses are in mg. BID, twice daily; PD, progressive disease; PR, partial response; QD, once daily; SD, stable disease; uPR, unconfirmed PR 25 pending confirmation. Best change in tumor target lesion (%) 1150 QD 1500 BID 2500 QD 1500 BID 1150 QD 2000 QD 2000 QD 1500 BID 2000 QD 2500 QD 1150 QD 1500 QD 1500 QD 1500 QD 2000 QD 1500 BID 2000 QD 2500 QD 1500 BID 2500 QD 2000 QD 1150 QD

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) Colorectal 1 1 (100) Germ Cell 1 Head & Neck 1 All 25 11 (44) 8 (32) Best Response of SD or PR observed in 19/25 patients (76%) 1 2 Includes 3 patients eligible for response assessment and without a post baseline assessment, ORR per tumor type per RECIST 1.1 based on Investigator assessment, 6 patients have confirmed partial responses; 1 26 pancreatic and 1 prostate patient have response confirmation pending

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 general population and not a CRC 3L+ 0.4-1% specific p53 Y220C population. Pancreatic 2L 8.5-10.8% PHASE 1 PYNNACLE TRIAL PATIENTS have generally exhausted all available treatment Ovarian (platinum-resistant) 2L 12.7% options (median of 3 prior systemic regimens) For illustrative purposes only, no head to head trials exist SOC = standard of care 27 Cortes et al. 2020, Herbst et al. 2016, Shepherd et al. 2000, Garon et al. 2014, Garassino et al. 2013, O’Brien et al. 2006, Grothey et al. 2013, Mayer et al. 2015, de Jesus et al 2020, Chae et al 2020, Gaillard et al 2021

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 RP2D Pacific planned to start in Addressing payors’ needs 1H2023 proactively to support accessibility 28

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 track to initiate in H2 2022 29

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 reactivation and frequently observed types supporting functional restoration in continued pan-tumor patients with p53 Y220C development mutant tumors 30

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

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