Slide 1: American Heart Association 2025 Investor Presentation
American Heart Association 2025 Investor Presentation November 9, 2025
Slide 2: Forward-looking statement of Merck & Co., Inc.
Forward-looking statement of Merck & Co., Inc., Rahway, N.J., USA This presentation of Merck & Co., Inc., Rahway, N.J., USA (the “company”) includes “forward-looking statements” within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These state
Slide 3: Agenda
Cardiometabolic and Respiratory Portfolio Dr. Dean Li President, Merck Research Laboratories AHA Data and Enlicitide Strategy Dr. Joerg Koglin SVP, Head of General & Specialty Medicine, Global Clinical Development Agenda Addressing the Silent CV Epidemic Jannie Oosthuizen President, U.S. Human Healt
Slide 4: Cardiometabolic and Respiratory Portfolio
Cardiometabolic and Respiratory Portfolio Dr. Dean Li President, Merck Research Laboratories
Slide 5: Delivering and developing therapies in cardiometabolic and respiratory
Delivering and developing therapies with the goal of redefining care in cardiometabolic and respiratory Enlicitide First and only activin signaling First-in-class selective dual Potential first-of-its-kind oral inhibitor inhibitor of PDE3 and PDE4 PCSK9 inhibitor designed to Targets underlying disea
Slide 6: WINREVAIR continues to generate clinical evidence in PAH
WINREVAIR continues to generate clinical evidence that reinforces potential to transform treatment of PAH HYPERION Phase 3 study expanding benefit of reduction in risk of clinical worsening to recently diagnosed patients ZENITH Phase 3 study demonstrating reduction in risk of major morbidity and mor
Slide 7: Data at AHA and ZENITH label update
Data at AHA and ZENITH label update highlight profound effect on risk of major morbidity and mortality events Pooled post-hoc analysis ZENITH Label Update PULSAR, STELLAR and ZENITH studies show effect of WINREVAIR on major morbidity and mortality outcomes in broad range of adult patients with PAH1
Slide 8: OHTUVAYRE first-in-class mechanism for COPD maintenance treatment
OHTUVAYRE is a first-in-class novel mechanism with broad label for maintenance treatment of COPD in adults First novel inhaled mechanism Broad label, positive risk-benefit for treatment of COPD in more profile than 20 years Combines bronchodilatory and Positive real-world experience non-steroidal an
Slide 9: Enlicitide is the first oral PCSK9i with antibody-like efficacy
Enlicitide is the first oral PCSK9i designed to have antibody-like efficacy Profound efficacy with placebo-like Achieved LDL-C reduction surpassing other oral lipid lowering therapies used as safety and tolerability now add-on to statins demonstrated in two Phase 3 trials Broad atherogenic particle
Slide 10: AHA 2025 Data Highlights: enlicitide decanoate
AHA 2025 Data Highlights: enlicitide decanoate Dr. Joerg Koglin SVP, Head of General & Specialty Medicine, Global Clinical Development
Slide 11: Building on the legacy that changed cardiovascular medicine
Building on the legacy that changed cardiovascular medicine Legacy of innovation in atherosclerosis 2025 American Chemical Society National Historic Chemical Landmark recipient for development and commercialization of statins 11
Slide 12: Global CV epidemic and residual cardiovascular risk
Global CV epidemic claims 19 million lives per year Atherosclerosis Residual cardiovascular risk Patients at LDL-C goal 4S WOSCOPS CARE LIPID MIRACL PROSPER ASCOT-LLA CARDS SPARCL KLIS MEGA 0 100 -16 -15 -15 -14 10 -24 -24 20 80 (relative risk reduction) -30 -31 -33 Endpoint reduction -36 ~85% 30 -3
Slide 13: Goal to deliver the most effective LDL-C lowering pill
Goal to deliver the most effective LDL-C lowering pill and make it accessible to a broad range of patients globally PCSK9 monoclonal antibodies Enlicitide Direct PCSK9 binding Novel macrocyclic peptide platform offers ‒ PCSK9i mAbs act extracellularly and mAb-like selectivity at bind the PCSK9 prote
Slide 14: Development program evaluating enlicitide across ASCVD patients
Development program evaluating enlicitide across broad range of patients with ASCVD Secondary prevention and Secondary prevention and Heterozygous familial Secondary and high-risk intermediate to high-risk intermediate to high-risk Population primary prevention patients hypercholesterolemia primary
Slide 15: CORALreef Lipids evidence for potential first oral PCSK9i
CORALreef Lipids provides evidence for potential first approval of an oral PCSK9i Inclusion Criteria: Treatment period: 52 Weeks 8 weeks Primary Endpoint • LDL-C mean percent change from baseline at Week 24 Enlicitide 20 mg oral daily* Follow-up • Proportion of participants with AE; proportion or of
Slide 16: Broad primary and secondary prevention study population
Broad primary and secondary prevention study population Enlicitide 20 mg Placebo Total Select study population characteristics n=1,940 n=969 n=2,909 Sex, n (%) Female 775 (40) 367 (38) 1,142 (39) Age, mean (SD) years 62.8 (11) 62.7 (11) 62.8 (11) BMI, mean (SD) kg/m2 29.2 (6) 29.3 (6) 29.2(6) Histor
Slide 17: Enlicitide well tolerated with safety similar to placebo
Enlicitide was well tolerated with safety profile similar to placebo and high patient adherence Enlicitide Placebo Over 52-week study N = 1,935 N = 969 - 97% adherence with study intervention n (%) n (%) across treatment groups ≥1 Adverse Events 1,244 (64.3) 602 (62.1) Serious AEs 191 (9.9) 116 (12.
Slide 18: No meaningful differences in AEs between groups
No meaningful differences in proportion of participants with AEs between groups AEs reported in ≥10% of patients Enlicitide Placebo N = 1,935 N = 969 n (%) n (%) Gastrointestinal disorder 296 (15.3) 154 (15.9) Infections and Infestations 467 (24.1) 246 (25.4) Injury, poisoning and procedural complic
Slide 19: Statistically significant and durable LDL-C reductions
Enlicitide is the first oral PCSK9i designed to have antibody-like efficacy: statistically significant, clinically profound and durable reductions in LDL-C Primary endpoint: Mean percent change in LDL-C 55.8% 20 0 LDL-C reduction from baseline at in LDL-C From Baseline Mean (±SE) % change Week 24 -2
Slide 20: Majority of participants achieved rigorous LDL-C goals
Majority of participants achieved rigorous LDL-C goals Most participants reached study defined LDL-C goals, an important factor in lowering cardiovascular disease risk Over two-thirds of participants achieved rigorous prespecified goal requiring both LDL-C <55 mg/dL and >50% reduction from baseline1
Slide 21: Robust effect size on other atherogenic biomarkers
Enlicitide is the first oral PCSK9 designed to have antibody-like efficacy: robust effect size on other important atherogenic lipoprotein biomarkers Secondary Endpoints ApoB reduction Non-HDL-C reduction Lp(a) reduction -50.3% -53.4% -28.2% 21
Slide 22: CORALreef HeFH study design
CORALreef HeFH evaluated efficacy of enlicitide in adults with heterozygous familial hypercholesterolemia Inclusion Criteria: Treatment period: 52 Weeks 8 weeks Primary Endpoint • LDL-C mean percent change from baseline at Enlicitide 20 mg oral daily Week 24 HeFH with history of major (on top of sta
Slide 23: LDL-C reductions in CORALreef HeFH
Statistically significant, clinically profound and durable reductions in LDL-C in CORALreef HeFH Mean percent change in LDL-C over time 20 59.4% in LDL-C From Baseline 0 Mean (SE) % change -20 LDL-C reduction from baseline at Week 24 -40 -60 LDL-C reduction seen early and durable over 52 weeks1 -80
Slide 24: Consistently robust LDL-C lowering across enlicitide program
Consistently robust LDL-C lowering across enlicitide development program Enlicitide Phase 2 Study % LDL-C reduction from -57.0 (18mg) Statistically significant -57.12, -59.63 -58.2 baseline (enlicitide) -59.7 (30mg) and clinically meaningful4 Placebo-adjusted % LDL-C -58.3 (18 mg) n/a reduction from
Slide 25: Efficacy for other atherogenic predictors
Enlicitide demonstrated consistently robust efficacy for other atherogenic predictors of cardiovascular disease Secondary Endpoints Enlicitide (placebo-adjusted) Phase 2 Study -47.8 (18mg) % reduction in ApoB -50.3 -49.1 -51.8 (30mg) % reduction in non- -53.2 (18mg) -53.4 -53.0 HDL -55.8 (30mg) -21.
Slide 26: Phase 3 results support ambition for first oral PCSK9i
Phase 3 results support ambition to bring first oral PCSK9i designed to For have antibody-like efficacy to broad population globally Profound LDL-C reduction exceeding other oral lipid lowering therapies used as Ease of use, with placebo-like safety and an add-on to statins tolerability as well as n
Slide 27: Phase 3 studies support filing in early 2026
Phase 3 CORALreef Lipids and HeFH studies support filing in early 2026 2025 2026 2027 2028 2029+ LDL-C regulatory filings expected in early 2026 PCD: Nov 2029 PCD: 2033 Phase 3 study in children and adolescents with HeFH Co-administration with rosuvastatin 27
Slide 28: Enlicitide to address CV epidemic and anchor novel combinations
Enlicitide is designed to help address the CV epidemic and anchor future novel combinations Now Near Next Establish Elevate Outcomes Further Transform Foundation Expectations Treatment Pending approval, aim to Goal of demonstrating robust Expand into other atherogenic establish enlicitide as the ris
Slide 29: Addressing the Silent CV Epidemic
Addressing the Silent CV Epidemic Jannie Oosthuizen President, U.S. Human Health
Slide 30: Improving LDL-C control can reduce cardiovascular events
Improving LDL-C control can materially reduce cardiovascular events and positively impact the global CV epidemic Urgent need to address CVD 2024 Global Treated Patients1 #1 cause of mortality globally 85% of CV disease-related deaths each year are due to ASCVD Substantial economic burden Vast majori
Slide 31: Initial launch focused on patients needing additional LDL-C lowering
Initial launch of enlicitide focused on patients on lipid lowering therapy who require additional LDL-C lowering to achieve their goal Current State Early Launch Focus Low patient awareness of >80M Estimated treated, not-at-goal ASCVD and at-risk “asymptomatic” disease patients in the U.S., Europe,
Slide 32: Enlicitide investigational oral PCSK9i to address silent CV epidemic
Enlicitide is an investigational oral PCSK9i designed to have antibody-like efficacy and help address the silent CV epidemic A new bar for oral add-on lipid-lowering Profound efficacy therapy Potential to achieve more rigorous Robust LDL-C goal attainment guideline goals Ease of use Expected to enab
Slide 33: Strong growth anticipated from cardiometabolic and respiratory programs
Strong growth anticipated from cardiometabolic and respiratory programs well into next decade + ~$15B New multibillion opportunity with Commercial opportunity by mid-2030s1 Enlicitide has multibillion-dollar Early-phase programs and deep potential discovery research efforts 33 1. Non-risk adjusted
Slide 34: Q&A
Q&A Dr. Dean Li President, Merck Research Laboratories Dr. Joerg Koglin SVP, Head of General & Specialty Medicine, Global Clinical Development Jannie Oosthuizen President, U.S. Human Health Kshama Roberts SVP, Global Pharmaceuticals Peter Dannenbaum SVP, Investor Relations
Slide 35: Appendix
Appendix Copyright © 2024 Merck & Co., Inc., Rahway, NJ, USA and its affiliates. All rights reserved.
Slide 36: Effect of WINREVAIR on mortality and morbidity: pooled analysis
Effect of WINREVAIR on mortality and major morbidity outcomes in patients with pulmonary arterial hypertension: pooled analysis of the PULSAR, STELLAR, and ZENITH trial Pooled Analysis of the PULSAR, STELLAR, and ZENITH WINREVAIR Placebo HR (95% CI); n=323 n=278 P-value Time to composite first major
Slide 37: Acronyms
Acronyms AE = Adverse Event HDL-C = High-density lipoprotein cholesterol ApoB = Apolipoprotein B LDL-C = Low-density lipoprotein cholesterol ASCVD = Atherosclerotic cardiovascular disease LLT = Lipid lowering therapy BMI = Body mass index Lp(a) = Lipoprotein a COPD = Chronic obstructive pulmonary di
Slide 38: Dean Li, M.D., Ph.D.
Dean Li, M.D., Ph.D. President, Merck Research Laboratories Dr. Dean Li serves as executive vice president and president of Merck Research Laboratories (MRL). He leads the company’s worldwide human vaccines and therapeutics research and development organization. Since joining Merck in 2017, Dean has
Slide 39: Joerg Koglin, M.D., Ph.D.
Joerg Koglin, M.D., Ph.D. Senior Vice President, Head of General & Specialty Medicine, Global Clinical Development Dr. Joerg Koglin serves as senior vice president of Merck Research Laboratories (MRL) and head of General and Specialty Medicine Global Clinical Development. Joerg earned his MD from th
Slide 40: Jannie Oosthuizen
Jannie Oosthuizen President, Human Health U.S. Jannie Oosthuizen leads Merck Human Health U.S., which is Merck’s largest business globally. He is responsible for P&L, strategy, customer engagement and commercialization in the U.S. for Merck’s broad portfolio of human health medicines and vaccines. J
Slide 41: Kshama Roberts
Kshama Roberts Senior Vice President, Human Health U.S. Kshama Roberts leads the global pharmaceuticals franchise, overseeing the Human Health commercial team responsible for the portfolio and late-stage pipeline across multiple therapeutic areas, including cardiometabolic, immunology, ophthalmology