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Welcome to Investor Day August 5 , 2026 M NewAmsterdam Pharma NewAmsterdam Pharma INVESTOR DAY
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Disclaimer 2 Forward Looking Statements This presentation and the accompanying oral statements made in connection herewith (collectively, this “Presentation”) contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995 and are subject to the “safe harbor” provisions created thereunder. All statements that are not historical facts are hereby identified as forwarding-looking statements for this purposes and include, among others, statements by NewAmsterdam Pharma Company N.V. (“NewAmsterdam”, the “Company”, “we” or “our”) regarding: estimates and forecasts of financial and performance metrics and projections of market opportunity; the Company's business and strategic plans; expectations and timing related to the success, cost and timing of product development activities, including timing of initiation, completion and data readouts for clinical trials and the potential approval of the Company’s product candidate; the timing for enrolling patients; the Company’s intention to conduct the PREVAIL interim analysis and expectations regarding the timing of the interim analysis, when the result of the interim analysis may be announced and the potential of PREVAIL to be stopped early for efficacy as a result of the interim analysis; the design and predictive ability of clinical trials; potential predictors of MACE benefit; potential drivers of the blinded event rates observed in PREVAIL; the timing and forums for announcing data; the size and growth potential of the markets for the Company’s product candidate; the Company's ability to achieve the broad degree of physician adoption and use and market acceptance necessary for commercial success; the therapeutic and curative potential of the Company’s product candidate; financing and other business milestones; the Company’s expected cash runway; and the Company’s plans for commercialization. The Company may not actually achieve the plans, intentions or expectations disclosed in these forward-looking statements, and you should not place undue reliance on these forward-looking statements. These forward-looking statements are based upon management’s current expectations and assumptions. Actual results or events could differ materially and adversely from the plans, intentions and expectations disclosed in these forward-looking statements as a result of various risks, uncertainties and other factors, including, among others: uncertainties and delays inherent in clinical development of drug products; uncertainties and delays regarding the initiation, enrollment and completion of the Company’s clinical trials; uncertainties regarding the outcome of the Company’s clinical trials and the result of the PREVAIL interim analysis, and whether such outcomes will be adequate to support regulatory review and approval of its product candidates; whether topline, initial or preliminary results, trends or analyses from a particular clinical trial will be predictive of the final results of that trial and whether results of early clinical trials and analyses will be indicative of the results of later clinical trials and analyses, or whether projections regarding clinical outcomes will reflect actual results in future clinical trials or clinical use of the Company’s product candidates; the potential for unknown or unadjudicated events to impact the trends observed in the preliminary blinded data in PREVAIL; risk that the trends observed in the blinded data in PREVAIL are not being driven by a treatment effect of obicetrapib; the potential for varying interpretation of the results of clinical trials and analyses, including with respect to the Alzheimer's disease sub-study results; the potential for varying interpretations relating to potential drivers of observed MACE reductions; risks related to the Company’s ability to achieve its business plans, objectives and milestones, including approval of the Company’s product candidates and potential commercialization; the risk that market and peak sales opportunities for the Company’s product candidates may be smaller than expected; the potential for unanticipated costs and expenses to negatively impact the Company’s cash runway; the Company’s ability to continue to source the raw materials for its product candidates and ensure adequate supply of product for clinical trials and, if approved, commercialization; the Company's ability to negotiate definitive contractual arrangements with potential customers; the Company’s ability to attract and retain qualified personnel; the impact of competing product candidates on the Company’s business; risks and uncertainties relating to intellectual property and regulatory exclusivities; changes in domestic and foreign business, market, financial, political, and legal conditions; and other important factors, any of which could cause the Company’s actual results to differ from those contained in the forward-looking statements, that are described in greater detail in the sections entitled “Risk Factors” in the Company’s Annual Report on Form 10-K filed with the Securities and Exchange Commission (“SEC”) on February 18, 2026 and its Quarterly Report on Form 10-Q filed with the SEC on August 5, 2026, as well as in other filings the Company may make with the SEC in the future, which are available at www.sec.gov. Any forward-looking statements contained in this Presentation speak only as of the date of this Presentation, and the Company expressly disclaims any obligation to update any forward-looking statements contained herein, whether because of new information, future events, changed circumstances or otherwise, except as otherwise required by law. Market Data Certain information contained in this Presentation relates to or is based on third-party studies, publications, data, surveys and NewAmsterdam’s own internal estimates and research. In addition, all of the market data included in this Presentation involves a number of assumptions and limitations, and there can be no guarantee as to the accuracy or reliability of such assumptions. Finally, while NewAmsterdam believes its internal research is reliable, such research has not been verified by any independent source and NewAmsterdam cannot guarantee and makes no representation or warranty, express or implied, as to its accuracy and completeness. Trademarks This Presentation contains trademarks, service marks, trade names, and copyrights of NewAmsterdam and other companies, which are the property of their respective owners. The use or display of third parties’ trademarks, service marks, trade name or products in this Presentation is not intended to, and does not imply, a relationship with NewAmsterdam or an endorsement or sponsorship by or of NewAmsterdam. Solely for convenience, the trademarks, service marks and trade names referred to in this Presentation may appear with the TM or SM symbols, but such references are not intended to indicate, in any way, that NewAmsterdam will not assert, to the fullest extent permitted under applicable law, their rights or the right of the applicable licensor to these trademarks, service marks and trade names.
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Agenda Corporate Update: Michael Davidson, MD, CEO, NewAmsterdam • Introduction • General Corporate Update Science Update: John Kastelein, MD, PhD, FESC, CSO, NewAmsterdam • Biomarker predictors of MACE and REVEAL • Potential Benefits of HDL • REMBRANDT • RUBENS • CETP and Alzheimer’s Disease PREVAIL Update: Michael Davidson, MD, CEO, NewAmsterdam • PREVAIL: Improving Probability of Success • Alzheimer’s Update Commercial Update: BJ Jones, CCO, NewAmsterdam • Market Momentum • Product Differentiation • US Launch Readiness • Prelaunch Activities • European Launch overview Closing: Michael Davidson, MD, CEO, NewAmsterdam Q&A Date: August 5, 2026 3
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Corporate Update 4
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Our Mission is Clear and Simple Our mission is to build a new standard of care for people living with cardiometabolic disease by challenging convention with courage, translating deep biological insight into meaningful patient impact, and delivering with rigor, precision and purpose. This is how NewAmsterdam is built to go beyond. 5
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The NewAmsterdam Value Proposition Clinical Expertise: Data driven clinical development increases probability of success Differentiated Target Product Profile: Phase 3 data demonstrates obicetrapib’s potential impact on multiple CVD risk factors Unmet Need: Significant need for a potent, convenient, well-tolerated low-dose oral therapy Experienced Leadership and Team: Expanding team comprised of accomplished industry executives KOL Support: Physician community aware of unmet need and eager to leverage obicetrapib's differentiated profile to achieve desired clinical benefit, if approved CMC Expertise and Manufacturing Capacity: Preparing to meet anticipated demand for obicetrapib and the fixed dose combination, creating redundancy, expanding capacity and building inventory Commercial Excellence: Growing team with track record of blockbuster launch success and innovative go -to-market model Strong Balance Sheet: Cash runway expected to be sufficient to support U.S. commercial launch 7
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Secured funding to support US commercial launch, if approved, with cash at end of 2Q 2026 of ~$678M* Previous Years Were a Time of Groundwork, Goals and Growth CHMP Positive Opinion Announced Alzheimer’s topline Full AD data was presented at AAIC on July 30 Building world-class commercial and MSL functions Doubled in size (>100) with new hires and offices in Amsterdam, NL, Miami, FL, and Philadelphia metro area Completed and announced results for BROOKLYN, BROADWAY , and TANDEM Phase 3 studies 20252024 Announced topline results for BROOKLYN Phase 3 trial Announced topline results for TANDEM Phase 3 trial Composition of matter IP granted Announced topline results for BROADWAY Phase 3 trial 2026 EMA submission * Includes cash and cash equivalents and marketable securities European Approvals 8
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Lipid Lowering Market Primed for Commercial Success 1 Very large opportunity – even small amounts of penetration can result in significant financial success We have seen LLT market growth each year for the last 5 years 2 Non-statin growth continues in the high double digits Shift towards more aggressive treatment using alternatives / adding to statins Observations1-4 3 Guidelines have shifted to recommend more intense and earlier intervention not only with statins, but with ezetimibe, PCSK9’s and bempedoic acid Governing bodies and KOL’s are prioritizing the importance of treating to goal 1. Based on third party prescription data on file 2. Grundy SM, et al. J Am Coll Cardiol. 2019;73(24):3168-3209. 3. Lloyd-Jones DM, et al. J Am Coll Cardiol. 2022;80(14):1366-1418 4. 2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines | Circulation Key Takeaways PCSK9 growth continues to accelerate 10 years post launch with 45%+ growth in net sales in each of the last 2 years Commercial success is being demonstrated and is accelerating 5 4 Access to PCSK9’s has been increasing, and utilization controls have been decreasing Payers are willing to cover medications in LLT space if priced appropriately FDA labeling changes continue to support broad access and earlier treatment Labels are less restrictive and support broad usage 6 9
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Positive CHMP Opinion Supports Potential Approval in Europe Positive CHMP opinion received in July 2026 based on robust data from the Phase 3 BROADWAY , BROOKLYN and TANDEM trials European Commission decision expected in 2H26 • Committee for Medicinal Products for Human Use ("CHMP") of the European Medicines Agency (“EMA”) adopted positive opinion recommending marketing authorization for Ubeslo ® (obicetrapib 10 mg monotherapy) and Evlarco® (10 mg obicetrapib plus 10 mg ezetimibe FDC) for patients with primary hypercholesterolemia, both HeFH and non- familial or mixed dyslipidemia • Final decision by European Commission (“EC”) has authority to grant centralized marketing authorization applicable across all 27 EU member states, and Iceland, Liechtenstein and Norway Partnership with Menarini provides commercial and regulatory infrastructure in EU under licensing agreement Menarini holds rights for obicetrapib in Europe NewAmsterdam entitled to tiered double-digit % royalties on net sales and up to an additional €833 million with achievement of various milestones 10
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Science Update 11
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Observed Effects of Obicetrapib on MACE Biomarkers 12
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Small LDL-P ↓ Total LDL-P ↓ ApoB ↓ LDL-C ↓ Non–HDL-C ↓ sdLDL-C ↓ oxLDL ↓ ApoE ↑ in E4 Carriers HDL-C ↑ ApoA1 ↑ CLM Through CETP InhibitionLp(a) ↓ ApoA1, apolipoprotein A1; ApoE, apolipoprotein E; ASCVD, atherosclerotic cardiovascular disease; CETP, cholesterol ester transfer protein; CVD, cardiovascular disease; LDL-P, low-density lipoprotein particle; MACE, major adverse cardiovascular events; oxLDL, oxidized low-density lipoprotein; sdLDL-C, small dense low-density lipoprotein cholesterol. 13 Obicetrapib Delivers Comprehensive Lipid Modulation Through CETP Inhibition
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What do Prior CETP Inhibitor Trials Tell Us About Lipoprotein Changes and MACE Reduction? 14
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Limitations of Prior CETP Inhibitor CVOTs EVACETRAPIB3 Overall mortality benefit (P =.04) – but CVOT was too short to demonstrate MACE benefit INSUFFICIENT TRIAL DURATION (only 2 years) Modest LDL-lowering (~17-36%) ANACETRAPIB4 Meaningful MACE benefit observed - but drug accumulated in fat tissue SAFETY LDL-LOWERING POTENCY CVOT DESIGN (DURATION & BASELINE LDL) Sufficient duration (4.1 years, with 6.3 year follow up) Baseline LDL too low (60 mg/dL) OFF-TARGET TOXICITY, INCREASED BLOOD PRESSURE, ALDOSTERONE (seen early in Phase 2) TORCETRAPIB1 Suffered from drug-specific toxicity issue COMMERCIALLY UNVIABLE High lipophilicity and fat tissue accumulation led to 4+ year half-life DALCETRAPIB2 Drug showed no LDL-lowering efficacy Safe & well-tolerated NO LDL-LOWERING OBICETRAPIB5 Tolerability profile observed in >4000 patients through Phase 3 No concerns seen in biomarker safety data, including blood pressure- associated biomarkers Favorable PK/PD profile No accumulation in fat tissue observed Modest LDL-lowering (17%) Safe & well-tolerated Safe & well-tolerated 35-40% LDL lowering observed in phase 3 ~50% LDL-lowering observed in fdc phase 3 Longer trial duration (4 yrs) + High baseline LDL (100 mg/dL)(1) Strong safety profile across ~59k patients COMMERCIAL VIABILITY (Pfizer) (Roche) (Lilly) (Merck) ~40% CETP inhibition at CVOT dose ~80% CETP inhibition at CVOT dose ~80% CETP inhibition at CVOT dose ~97% target coverage We believe that all prior CETPi were developed with a misguided focus on HDL increase (rather than LDL decrease) as the primary MoA for CVD risk reduction, leading to inappropriate compound selection or inappropriate CVOT design. Note: The above trials and data do not represent head-to-head comparisons. Obicetrapib has not been approved for marketing by any regulatory authority. Represents estimated average baseline LDL to be enrolled, not entry criteria. Evacetrapib measured using direct LDL-C assay. Sources: 1. Barter PJ, et al. N Engl J Med 2007;357:2109-2122; 2. Schwartz GG, et al. N Engl J Med 2012;367:2089-2099; 3. Lincoff AM, et al. N Engl J Med 2017;376:1933-1942; 4. The HPS3/TIMI55– REVEAL Collaborative Group. N Engl J Med 2017;377:1217-1227; 5. Data on file15
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REVEAL: The Largest CETP Inhibitor Outcomes Trial 30,449 patients with ASCVD Largest CVOT ever conducted1 (1 tertile is ~PREVAIL-sized) 17% LDL-C reduction With anacetrapib 100 mg/day on top of intensive statin therapy led to 9% MACE reduction1 75-80% CETP inhibition with 100 mg dose2 (Obicetrapib demonstrates 98% inhibition) ASCVD, atherosclerotic cardiovascular disease; CETP, cholesteryl ester transfer protein; CVOT, cardiovascular outcomes trial; LDL-C, low-density lipoprotein cholesterol; MACE, major adverse coronary events. 1. HPS3/TIMI55–REVEAL Collaborative Group. N Engl J Med. 2017;377(13):1217-1227. 2. Krishna R, et al. Br J Clin Pharmacol. 2009;68(4):535-545. 16 1 1 Although anacetrapib is a much weaker CETP inhibitor with only modest LDL-C lowering, REVEAL still achieved a statistically significant reduction in MACE validating CETP inhibition on top of statins as a potential route to cardiovascular risk reduction1
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What Did We Observe In REVEAL? Baseline characteristic Mean Lipid Difference (mg/dL) Anacetrapib (N=15,225) Placebo (N=15,224) Rate ratio (95%CI) Nominal P Value Trend P Value HDL-C Non-HDL- C Number of participants with events (%) LDL-C (mg/dL) <54 43 -11 527 (10.5) 558 (11.0) 0.96 (0.85-1.08) 0.504 ≥54<66 44 -17 492 (10.6) 553 (11.8) 0.90 (0.80-1.01) 0.076 ≥66 44 -24 621 (11.2) 692 (12.7) 0.87 (0.78-0.97) 0.012 0.230 Non-HDL-C (mg/dL) <85 42 -11 561 (9.9) 592 (10.4) 0.96 (0.85-1.07) 0.487 ≥85<101 44 -18 534 (10.9) 564 (11.6) 0.94 (0.83-1.06) 0.321 ≥101 45 -23 545 (11.6) 647 (13.9) 0.83 (0.74-0.93) 0.001 0.080 ApoB (mg/dL) <60 44 -12 693 (9.7) 752 (10.4) 0.93 (0.84-1.03) 0.163 ≥60<70 43 -19 505 (11.3) 548 (12.3) 0.92 (0.81-1.03) 0.174 ≥70 43 -26 442 (12.3) 503 (14.1) 0.86 (0.76-0.98) 0.020 0.390 .7 .8 .9 1 1.1 1.2 Anacetrapib better Placebo better ApoB, apolipoprotein B; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol. *Major coronary event was defined as a composite of coronary death, myocardial infarction, or coronary revascularization. HPS3/TIMI55–REVEAL Collaborative Group. N Engl J Med. 2017;377(13):1217-1227. 17 Patients with the highest baseline non-HDL-C showed a ~17% reduction in rate of MACE
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In REVEAL, Modest CETP and LDL-C Reduction in 10,000 Patients with Baseline non-HDL in the Range of PREVAIL Delivered a 17% reduction in MACE 18
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What Have We Observed with Obicetrapib and the FDC Compared to Anacetrapib? 19
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Most Recent Analysis of Obicetrapib Phase 3 Data 20
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PK-Confirmed, Placebo Controlled, On-Treatment Effectiveness of Obicetrapib in Pooled Analysis of BROOKLYN, BROADWAY, and TANDEM -43.5% -41.1% -50 -40 -30 -20 -10 0 Week 4 Week 12 Difference in mean change, % LDL-C De Kleer et al. ESC 2026. Abstract 89477. 140.7% 148.4% 0 20 40 60 80 100 120 140 160 Week 4 Week 12 Difference in mean change, % HDL-C 21
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PK-Confirmed, Placebo Controlled, On-Treatment Effectiveness of the Obicetrapib-Ezetimibe Fixed-Dose Combination in Analysis of TANDEM -63.5% -60.7% -70 -60 -50 -40 -30 -20 -10 0 Week 4 Week 12 Difference in mean change, % LDL-C 131.8% 135.8% 0 20 40 60 80 100 120 140 160 Week 4 Week 12 Difference in mean change, % HDL-C De Kleer et al. ESC 2026. Abstract 89477. 2222
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Obicetrapib Observed to Lower LDL-C More Than Twice as much as Anacetrapib 23 Note: This comparison is based on an indirect treatment comparison; no head-to-head clinical trials were conducted. Results should be interpreted with caution due to inherent limitations in cross-trial comparisons.
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Besides the REVEAL Study, What Is the Additional Evidence for CETP as a Target for Reduction of ASCVD Risk? 24
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CETP protein-truncating variant carriers had a lower probability of cumulative CV events compared with controls* 83,570Any atherosclerotic event or all-cause death 0.72 (0.56-0.93) 61,091Any atherosclerotic event 0.65 (0.48-0.90) 36,669All-cause death 0.80 (0.55-1.16) 3,671Peripheral atherosclerosis 1.18 (0.44-3.15) 29,505MACE 0.75 (0.49-1.14) 4,169CV death 0.52 (0.13-2.06) 20,617Myocardial infarction 0.87 (0.54-1.40) 10,497Ischemic stroke 0.61 (0.27-1.36) 52,701CHD 0.69 (0.49-0.96) CETP protein-truncating variants were associated with lower risk of any atherosclerotic event† In Press: Individuals with 50% Lower CETP Activity Show Lower Risk of CV Events Hazard ratio (95% Cl) 0.1 1.0 Avg 10 Hazard ratio (95% Cl)Cases Event probability (%) Age in years Hazard ratio, 0.65 (95% CI, 0.48- 0.90) Controls CETP protein- truncating variant carriers 0 5 10 15 20 25 30 40 50 60 70 80 *In a study of individuals from the UK Biobank, the effects of CETP protein-truncating variants on ASCVD risk were determined by analyzing ASCVD events in individuals with CETP protein-truncating variant carriers (n=385) and noncarriers (n=409,253). Shaded areas around each curve represent 95% confidence intervals. †In this analysis, the primary endpoint was any atherosclerotic disease event. All other endpoints were considered secondary endpoints. ASCVD, atherosclerotic cardiovascular disease; CETP, cholesteryl ester transfer protein; CHD, coronary heart disease; CI, confidence interval; CV, cardiovascular; MACE, major adverse cardiovascular events. Landfors F et al. medRxiv. 2024. 12.02.24318306 25
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Why Is the Hazard Ratio for Events So Large in Patients with Only a 50% Reduction in CETP? Does HDL, Besides Lp(a) and Small LDL Particles, Help Reduce MACE Independently of These Atherogenic Lipoproteins? 26
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Let's Look at Genetic Background First: Are Genetics Supportive of Clinical Data? 27
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When Did We Discover That Humans with Low CETP Activity Do Better Than The Rest of Us? 28
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CETP Loss of Function and the Ashkenazi Jewish Longevity Project CETP, cholesteryl ester transfer protein. 29
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The Low CETP Activity Gene Variant Is Associated with Exceptional Longevity and the Healthy Aging Phenotype CETP I405V genotype and lipoprotein characteristic and plasma CETP levels in families with exceptional longevity vs control Variable CETP I405V Genotype VV CETP I405V Genotype II P value (VV vs II Genotypes) HDL Concentration, mg/dL 57 55 0.53 Large particle size, % of total 56 60 0.10 Particle size, nm 9.28 9.07 0.02 LDL Concentration, mg/dL 114 123 0.16 Large particle size, % of total 67 56 0.02 Particle size, nm 21.29 20.88 0.002 CETP concentration, mg/mL 1.65 1.99 <0.001 CETP, cholesteryl ester transfer protein; HDL, high-density lipoprotein; LDL, low-density lipoprotein. Barzilai N et al. JAMA. 2003;290(15):2030-2040. 30 Individuals with exceptional longevity had significantly higher frequency of low CETP activity mutations
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Where Do We Find Individuals with No CETP Activity at All and Do They Live Longer Too? 31
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Egg embryonation of Schistosoma japonicum in the liver requires plasma HDL, and this process is impaired with CETP deficiency CETP deficiency,* resulting in high HDL-C levels, is common in populations from regions with endemic schistosomiasis Japanese 5.4%-8.1% (28.0%-33.0% in high HDLs) Yakutes 16.2% Koreans 9.2%-12.0%Chinese 3.3%-10.8% Vietnamese 6.9% Thai 26.0% in high HDLs North Indians 0% French 0% Scottish 0% Chinese in Taiwan 4.5%-7.7% CETP Deficiency Resulting in High HDL-C Levels Is Common in Regions With Endemic Schistosomiasis and May Confer Protection CETP inhibition is hypothesized to be a viable treatment strategy in schistosomiasis CETP, cholesteryl ester transfer protein; HDL, high-density lipoprotein; HDL-C, high-density lipoprotein cholesterol. *D442G mutation prevalence listed as percentage in each ethnic general population. Yokoyama S et al. J Biomed Res. 2015;29(3):176-188. 32
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What Do These Individuals Look Like Besides Having Protection Against Parasites? 33
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Characteristics of Individuals With CETP Deficiency AD, Alzheimer's disease; AMD, age-related macular degeneration; ApoB, apolipoprotein B; ASCVD, atherosclerotic cardiovascular disease; CETP, cholesteryl ester transfer protein; CV, cardiovascular; HDL, high-density lipoprotein; LoF, loss of function; Lp(a), lipoprotein (a). 1. Tall AR et al. Arterioscler Thromb Vasc Biol. 2007;27(2):257-260. 2. Barzilai N et al. JAMA. 2003;290(15):2030-2040. 3. Landfors F et al. medRxiv. 2024. 12.02.24318306. 4. Sanders AE et al. JAMA. 2010;303(2):150-158. 5. Yu C et al. J Am Heart Assoc. 2023;12(21):e031459. 6. Mehta N et al. Pharmacol Res. 2023;197:106972. 7. Li Q et al. World J Emerg Med. 2025;16(3):256-261. Lipid Profiles1 • >100% increase in HDL • 40% decreases in LDL- C and ApoB • 40% decrease in Lp(a) • No small LDL particles Lower ASCVD Risk3 CETP protein-truncating variant carriers have a lower probability of cumulative CV events Exceptional Longevity2 in individuals homozygous for the I405V allele (associated with lower CETP protein levels) Lower AD Risk4 Individuals with 1 or 2 LoF CETP genes have decreased risk of dementia and AD Lower Risk of AMD5,6 • No AMD in patients with CETP deficiency Lower Risk of Sepsis Mortality7 Genetically proxied CETP inhibition was associated with lower risk of sepsis- related critical care admission and death 34
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What is the consequence of such elevated HDL-C levels? 35
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Extremely High Levels of HDL-C* Are Very Uncommon in the General Population *Reference groups were participants with HDL-C levels between the 25th and 75th percentiles: median (IQR) HDL-C was 47.9 (41-56) mg/dL for men, and 60.2 (51-70) mg/dL for women. IQR, interquartile range; UK, United Kingdom. Ference BA et al. ESC 2026. Abstract 86367. Distribution of HDL-C (mg/dL) Percentage 0 1 2 3 0 50 100 150 HDL (mg/dL) 0 50 100 150 Men Women Median: 47.9 mg/dL (IQR: 41-56 mg/dL) HDL-C > 100 mg/dL HDL-C > 100 mg/dL Median: 60.2 mg/dL (IQR: 51-70 mg/dL) Among 207,741 men in the UK Biobank, 428 (0.5%) had HDL-C levels >100 mg/dL Among 239,129 women, 3,295 (2%) had HDL-C levels >100 mg/dL 36
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Participants With Extremely High HDL-C Had Progressively Higher Alcohol Use *Reference groups were participants with HDL-C levels between the 25th and 75th percentiles: median (IQR) HDL-C was 47.9 (41-56) mg/dL for men, and 60.2 (51-70) mg/dL for women. Individual participant data from a study of 429,892 participants enrolled in UK Biobank who had HDL-C measured at baseline. ApoB, apolipoprotein B; BMI, body mass index; ETOH, alcohol; freq, frequency; GGT, gamma-glutamyl transferase; ref, reference group; SBP, systolic blood pressure. Ference BA et al. ESC 2026. Abstract 86367. 4.79 9.45 10.49 11.97 15.25 3.20 5.30 5.60 5.90 6.50 7.50 9.10 10.90 11.90 Ref HDL 90-100 HDL 100-110 HDL 110-140 HDL > 140 3.10 HDL (10^-1) ETOH freq. ETOH amt. 4.79 9.45 10.49 11.97 15.25 3.20 5.30 5.60 5.90 6.50 7.50 9.10 10.90 11.90 Ref HDL 90-100 HDL 100-110 HDL 110-140 HDL > 140 3.10 HDL (10^-1) ETOH freq. ETOH amt. Men Women There Is a Stepwise Increase in Alcohol Consumption and Alcohol-Related Comorbidities Among Participants Who Have HDL-C Levels Above 90 mg/dL Participants with high HDL-C had higher alcohol use, alcohol frequency, GGT, SBP, and heart rate; and lower BMI, weight, and ApoB. Characteristics of severe alcohol-induced multisystem morbidity. 37
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The Mortality Associated with High HDL-C in Observational Studies May Be Explained by Alcohol-Induced Multisystem Disease 38
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In Fact: HDL-C Levels May be Associated With Decreased Cumulative Lifetime Risk for MACE and All Cause Mortality UK Biobank Participants: N=447,651; 29,876 Major Cardiovascular Events; includes both events (and age at event) occurring before and after enrolment to estimate lifetime risk of major coronary events by HDL-c level 35 30 25 20 15 1 0 5 0 30 35 40 45 50 55 60 65 80 Cumulaive Lifetime Risk of Major Cardiovascular Event (%) by HDL-C Level HDL-C 30-35 mg/dL HDL-C 40-45 mg/dL HDL-C 50-55 mg/dL HDL-C 70-75 mg/dL HDL-C 95-100 mg/dL 70 75 Age (years) 40 35 30 25 20 15 10 5 0 40 45 50 55 60 65 70 75 80 Cumulative Lifetime Risk of All Cause Mortality (%) by HDL-C Levels Age (years) HDL-C 30-35 mg/dL HDL-C 40-45 mg/dL HDL-C 50-55 mg/dL HDL-C 70-75 mg/dL HDL-C 95-100 mg/dL UK Biobank Participants: N=447,651; 31,215 Deaths (any fatal event); Median follow-Up 12.5 years 39 HDL-C, high-density lipoprotein cholesterol;
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What is the Safety of a 100% Increase in HDL-C ? 40
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Safety of HDL Increases With CETP Inhibition Were Observed With Anacetrapib in the REVEAL Trial In REVEAL, anacetrapib increased HDL-C by 104% relative to placebo This led to no increase in any fatal or non-fatal event in over 30,000 patients 0.60 0.80 1.00 1.50 Type of Event HR with 95% CI Fatal Events Cancer Death 1.00 [0.86, 1.16] Infection Death 1.03 [0.78, 1.37] Any Non-Cardiovascular Death 1.02 [0.91, 1.14] Heterogeneity: I2 = 0.00%, H2 = 1.00 1.01 [0.93, 1.10] Fatal or Non-Fatal Events GI Cancer 1.07 [0.89, 1.28] Respiratory Cancer 0.94 [0.79, 1.13] Breast Cancer 0.89 [0.51, 1.54] Melanoma 1.16 [0.75, 1.80] Genitourinary Cancer 1.08 [0.93, 1.27] Hematologic Cancer 0.85 [0.63, 1.13] Any Cancer 1.02 [0.93, 1.11] Eye Disorders 0.88 [0.73, 1.06] Endocrine Disorder 1.02 [0.69, 1.51] GI Disorders 1.03 [0.94, 1.13] Hepatobiliary Disorders 0.91 [0.76, 1.09] Infections 1.01 [0.95, 1.08] Metabolism Disorders 0.93 [0.84, 1.04] Musculoskeletal Disorders 1.01 [0.89, 1.16] Nervous System Disorders 0.96 [0.90, 1.03] Psychiatric Disorders 0.93 [0.72, 1.22] Renal Disorders 1.04 [0.91, 1.19] Respiratory Disorders 1.00 [0.90, 1.12] Vascular Disorders 0.98 [0.85, 1.14] Macular Degeneration 1.11 [0.94, 1.30] Heterogeneity: I2 = 0.00%, H2 = 1.00 1.00 [0.97, 1.03] Overall Events Any Fatal or Non-Fatal Event 1.00 [0.98, 1.02] HPS3/TIMI55–REVEAL Collaborative Group. N Engl J Med. 2017;377:1217–1227. 41
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Obicetrapib Clinical Trials Update: Going with the Evidence 42
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Obicetrapib Clinical Pipeline Update Obicetrapib is being studied in three clinical trials that are designed to demonstrate benefits beyond LDL-C lowering Phase 3 CCTA study to evaluate the effect of obicetrapib + ezetimibe FDC on coronary plaque burden in patients with ASCVD Phase 3 study to evaluate the effect of obicetrapib + ezetimibe FDC on LDL-C lowering in patients with metabolic syndrome and/or T2D Phase 2b study to evaluate the effect of obicetrapib on Alzheimer's disease biomarkers in high-risk APOE4 carriers with preclinical AD 43 AD, Alzheimer’s disease; APOE, apolipoprotein E; ASCVD, atherosclerotic cardiovascular disease; CCTA, coronary computed tomography angiography; FDC, fixed-dose combination; LDL-C, low- density lipoprotein cholesterol; T2D, type 2 diabetes.
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REMBRANDT: Impact of Obicetrapib + Ezetimibe FDC on Coronary Plaque Burden 44
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Obicetrapib + Ezetimibe FDC Delivers PCSK9i – Like* LDL-C Lowering Without Compromising Safety Any AE Serious AE FDC: Obi + Eze 51% 3% Obicetrapib (mono) 54% 6% Ezetimibe (mono) 53% 7% Placebo 37% 4% Obicetrapib + Ezetimibe FDC Demonstrates Robust Reductions in LDL-C Obicetrapib + Ezetimibe FDC Is Well Tolerated FDC, fixed-dose combination; LDL-C low-density lipoprotein cholesterol; PCSK9, proprotein convertase subtilisin/kexin type 9. *-PCSK9 label efficacy of 50-60% Sarraju A, et al. Lancet. 2025;405(10491):1757-1768. 45 -52.2%-60 -50 -40 -30 -20 -10 0 Obicetrapib + Ezetimibe FDC Placebo Adjusted Mean change in LDL-C (%)
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The decisive efficacy & safety read-out OBICETRAPIB MONOTHERAPY How do atherosclerotic plaques behave following treatment with obicetrapib + ezetimibe FDC? OBICETRAPIB + EZETIMIBE FDC PREVAIL Will Settle Efficacy and Safety — But What About the Plaque? ? PREVAIL delivers the decisive read-out — but atherosclerotic plaque behavior under the fixed-dose combination remains to be shown. The Plaque Question 46 FDC, fixed-dose combination.
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How Does Obicetrapib + Ezetimibe Perform in a Humanized Mouse Model? 47
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Obicetrapib plus Ezetimibe Robustly Decreases Non-HDL Cholesterol in Humanized Mouse Model *(blue) P<0.05 Obicetrapib vs control. *(red) P<0.05 ezetimibe vs control. *(yellow) P<0.05 ezetimibe vs control. *P<0.05. **P<0.01. ***P<0.001. #P<0.05 obicetrapib vs obicetrapib + ezetimibe. §P<0.05 ezetimibe vs obicetrapib + ezetimibe. Apo, apolipoprotein; CETP, cholesteryl ester transfer protein; HDL, high-density lipoprotein; HDL-C, high-density lipoprotein cholesterol; LDL, low-density lipoprotein; VLDL, very-low-density lipoprotein. Inia JA et al. J Clin Lipidol. 2025;19(3S):e111. 48 Total non-HDL-C exposureNon-HDL-C levels 0 4 8 12 16 20 0 4 8 12 16 20 24 28 Non-HDL cholesterol (nM) Time (weeks) ** # * § Control Obicetrapib Ezetimibe Obicetrapib + Ezetimibe Non-HDL cholesterol exposure (mmol/L *weeks) *** -56% -24% -79% * ** * *** 0 100 200 300 400
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How Did Atherosclerotic Plaques Respond to These Changes in Lipids? 49
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Atherosclerotic Lesions Remain Main Contributor to Risk for Heart Attack and Stroke Type V – Severe plaque • Media is severely damaged with broken internal elastic lamina • Cholesterol clefts and/or crystals, calcium mineralization and necrosis are often visible Type I – Early fatty streak Up to 10 foam cells in the intima Type II – Regular fatty streak Over 10 foam cells present in the intima Type III – Mild plaque Extension of foam cells into the media with presence of a fibrotic cap Type IV – Moderate plaque A more progressive lesion with affected media, without loss of architecture and fibrosis of the media Source: Data on File. NewAmsterdam Pharma. Atherosclerotic Lesion Typing According to AHA Classification 50
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Lesion Severity Obicetrapib plus Ezetimibe Decreased Surface Area of Severe Lesions in the Aortic Root by 98% *P<0.05. **P<0.01. ***P<0.001. Inia JA et al. J Clin Lipidol. 2025;19(3S):e111. 51 0 50 100 150 200 Atherosclerotic lesion area per cross-section (*1000 µm2) *** *** *** * -90% -98% -50% Control Obicetrapib Ezetimibe Obicetrapib + Ezetimibe Lesion Area
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Now Back to Humans …. 52
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Over 70% of Patients on Obicetrapib + Ezetimbe Achieved LDL-C <55 mg/dL % of patients achieving LDL-C thresholds at Day 84 53 Source: Data on file. LDL-C, low-density lipoprotein cholesterol.
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PK-Confirmed On-Treatment LDL-C Goal Attainment Was High For Obicetrapib Monotherapy and Obicetrapib + Ezetimibe FDC Obicetrapib + Ezetimibe FDC vs Placebo 84.8% 82.6% 20.4% 7.1% 0 10 20 30 40 50 60 70 80 90 100 LDL-C Goal <70 mg/dL LDL-C Goal <55 mg/dL Percent achieving LDL-C goal at week 12, % Obicetrapib + ezetimibe FDC Placebo Source: De Kleer et al. ESC 2026. Abstract 89477. 54
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REMBRANDT 55
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Effect of FDC Obicetrapib/Ezetimibe on Top of Maximally Tolerated Lipid-Modifying Therapy on Coronary Plaque Characteristics in Participants with or at High Risk for ASCVD Rationale: Despite reducing the progression of coronary atherosclerosis, statin therapy does not fully address residual CV risk. Adding the FDC obicetrapib/ezetimibe to statin therapy will further reduce the progression of coronary atherosclerosis in ASCVD patients with high residually risk Objective: To evaluate the effect of FDC obicetrapib/ezetimibe 10 mg FDC daily on total non-calcified coronary atherosclerotic plaque volume at 18 months Study design: Randomized, double-blind, placebo-controlled • Patients (n=~300) • Patients with sufficient non-calcified plaque Screening Phase Visit: Months: 1 Up to -2 2 0 5 12 3 3 Labs, PK Safety Labs, PK Safety Labs, PK CCTA Safety FU SAE FU Safety FU Safety FUPlacebo (n=150) FDC Obicetrapib/ezetimibe (n=150) Eligibility: Double-blind 4 6 Labs, PK Safety 6 18 Labs, PK Safety, Final CCTA Main inclusion criteria • Age > 45 years • ASCVD - Imaging evidence (CTA / Angio) of vascular disease. - Having established ASCVD (MI, Stroke, revasc, PAD) • Non calcified total plaque volume >75mm3 • Screening LDL-C level ≥ 70 mg/dL • On maximally tolerated lipid-modifying therapy Main exclusion criteria • Poorly controlled diabetes (HbA1c >10%) • Hypertension • Congestive heart failure • PCI/stroke/MI within 3 months • eGFR < 45mL/min • Ezetimibe use within 30 days Primary endpoint • % Change total NCPV in ALL major coronary arteries Secondary endpoint • Absolute change NCPV in ALL major coronary arteries • % change in LDL-C • % change NCPVMD • Absolute change NCPVMD • Change in FAI ASCVD, atherosclerotic cardiovascular disease; CCTA, coronary computed tomography angiography; CV, cardiovascular disease; FDC, fixed-dose combination; FU, follow-up; LDL-C, LDL-C, low- density lipoprotein cholesterol; MI, myocardial infarction; PK, pharmacokinetics; SAE, serious adverse events. 56
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REMBRANDT: CT Angiography Study Designed to Demonstrate Obicetrapib + Ezetimibe FDC’s Anti-Atherosclerotic May support labeling and promotion Positive traction with practicing cardiologists Increased utilization of CTA for diagnosis of cardiovascular disease Designed to demonstrate clinical benefit of FDC 1 Show LDL-C reduction yields benefit on underlying atherosclerosis 2 Demonstrate FDC regresses coronary plaque volume 3 Link FDC benefit directly to plaque improvement 4 Confirm efficacy and safety in high-risk patients FDC, fixed-dose combination; FU, follow-up; LDL-C, LDL-C, low-density lipoprotein cholesterol. 57
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Recent FDA Approval of New CCTA Imaging Technology “CaRi-Heart has received U.S. FDA De Novo authorization, becoming the first and only technology authorized in the U.S. to detect and quantify coronary inflammation from routine coronary CT angiography (CCTA).” 58
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REMBRANDT Is Fully Enrolled and Tracking to a Readout1,2 ENROLLMENT COMPLETE 323 patients enrolled (vs. ~300 target) 50 sites across 7 countries 18 mo double-blind treatment period per patient 2027 estimated trial completion Fully enrolled, on schedule, and on track to deliver the next major proof point for the FDC franchise 1. NewAmsterdam Pharma corporate updates (Jan & May 2026); 2.ClinicalTrials.gov NCT06305559. May 2024 First Patient Randomized March 2026 Last Patient Randomized YE2027 Est. Trial Completion 59
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From Plaque to Small LDL Particles and Diabetes 60
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CETP Inhibition Has the Potential to Reverse Diabetes Risk, Potentially Addressing Patient Concerns About High Dose Statins Study name ILLUMINATE Dal-OUTCOMES ACCELERATE REVEAL Random-Effects Model HR (95% CI) 0.55 0.82 1.2 This is consistent with the benefits observed in other CETP trials that have shown 17% reduction in new onset diabetes (HR=0.83, CI 0.77-0.90) 0.67 1 BROOKLYN + BROADWAY In the pooled BROADWAY and BROOKLYN studies, we observed a 23% reduction in new onset diabetes (HR=0.77, CI 0.57-1.04) CETP, cholesteryl ester transfer protein; CI, confidence interval; HR, hazard ratio. Data from CVOT trials not designed to demonstrate diabetes benefits National Lipid Association Conference 2025 (data on file). 61
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RUBENS: LDL-C and Small Dense Particle Lowering in Patients With Metabolic Syndrome/T2D 62
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LDL-C Lowering in Patients with Obesity, Metabolic Syndrome, and Type 2 Diabetes: The Sweet Spot for Obicetrapib 1. Laakso M, Silva LF. Front Endocrinol (Lausanne). 2023;14:1239335. 2. Dugani SB et al. JAMA Cardiol. 2016;1(2):136-145. 3. Toth PP et al. Am J Cardiol. 2018;121(3):308-314. 4. Ray KK et al. J Clin Lipidol. 2025;19(3S):e116-e117. 5. Data on File. NewAmsterdam Pharma. 6. Ballantyne CM et al. J Clin Lipidol. 2023;17(4):491-503. 7. Kastelein JJP et al. Curr Atheroscler Rep. 2024;26(2):35-44. 8. Nicholls SJ et al. Safety and efficacy of obicetrapib in patients with heterozygous familial hypercholesterolemia: the BROOKLYN trial [manuscript in preparation]. 9. Sarraju A et al. Fixed-dose combination of obicetrapib and ezetimibe for LDL cholesterol reduction [manuscript in preparation]. Shared patient population: patients with obesity, metabolic syndrome, and T2D are frequently prescribed statins Statins cut both ways: statins increase diabetes risk and preferentially reduce large LDL particles, leaving relatively more small LDL-Ps Obicetrapib fills the gap: obicetrapib lowers the NoD risk and dramatically reduces small LDL-Ps, potentially being the ideal complement to statin therapy 63
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How Might Obicetrapib Reduce Diabetes Risk? 64
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Increase in HDL-C Observed to Reduce Risk of Developing Type 2 Diabetes • Dose-response relationship observed between HDL-C and the risk of new-onset diabetes • Multivariate predictive models show robust negative correlation between HDL-C and risk of future T2DM incidence • 25-year follow-up data also show that increased HDL-C correlates with diminished T2DM risk, suggesting that HDL-C levels may influence glucose metabolism Association Between HDL-C Levels and T2DM Risk for Baseline Levels of HDL-C* (mmol/L) Increasing HDL-C levels across these four quartiles was associated with considerable differences in survival probabilities HDL-C, Cox model <1.15 1.00 (1.00-1.00) 1.15 – 1.39 0.96 (0.60-1.52) HR (95% CI) P=0.003 1.40 – 1.69 0.48 (0.27-0.86) >1.69 0.45 (0.25-0.81) Reduced Risk of Diabetes Incidence With Increased HDL-C Levels 0.7 0.8 0.8 0.9 0.9 1.0 1.0 0 5 10 15 20 25 Survival probability Time to event (years) HDL-C <1.15 (mmol/L) HDL-C 1.15-1.39 (mmol/L) HDL-C 1.40-1.69 (mmol/L) HDL-C ≥1.70 (mmol/L) *1 mmol/L HDL=38.67 mg/dL. CI, confidence interval; HDL-C, high-density lipoprotein cholesterol; HR, hazard ratio; T2DM, type 2 diabetes mellitus. Cao X et al. Lipids Health Dis. 2021;20(1):71. 65
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What Is the Science Behind Obicetrapib’s Impact on Small LDL Particles? 66
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Insulin Resistance-Induced Dyslipidemia is Characterized by Increased sdLDL, Which are More Atherogenic Due to Multiple Mechanisms 3. Enhanced arterial wall penetration ROS IbLDL sdLDL Atheromatous Plaques Foam cells Oxidized LDL Oxidized LDL Macrophage 1. Reduced LDL receptor clearance → longer plasma circulation time 122. Stronger proteoglycan binding → increased arterial retention 4. Increased oxidative susceptibility 4 3 Diabetic patients have ↑ CETP activity, ↓ mean LDL-P size and ↑ sdLDL-P2,3 lbLDL, large buoyant LDL; LDL-P, LDL particle; ROS, reactive oxygen species. 1. Hirano T. J Diabetes Investig. 2025;16(3):370-383. 2. He Q et al. Sci Rep. 2025;15(1):19500. 3. Siewert S et al. J Diabetes Investig. 2015;6(1):67-77. 67
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Statins Decrease Large LDL-P Concentration to a Greater Extent Than Small LDL-P 2.7 -4.2 -2.6 -5.3 -49† -39.6† -22† -57.5† -70 -60 -50 -40 -30 -20 -10 0 10 LDL-C Total LDL-P Small LDL-P Large LDL-P Percentage change from baseline to 12 months Lipoprotein Measurements After 12 Months of Treatment* Placebo Rosuvastatin Rosuvastatin treatment altered the LDL lipoprotein subclass distribution, resulting in smaller mean sizes (-1.5%; 95% CI, -3.7% to 0.5%) *Includes 9180 individuals with baseline and 12-month measurements. †Differences in change between groups were P<0.001 for all (calculated using the Wilcoxon rank sum test). CI, confidence interval; LDL, low-density lipoprotein; LDL-P, low-density lipoprotein particle concentration. Dugani SB et al. JAMA Cardiol. 2016;1(2):136-145. 68
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Consistent ~90% Reduction in Small LDL Particles Observed with Obicetrapib in a Pooled Analysis LS mean change from baseline, % -90.3 -86.5 -95.5-100 -80 -60 -40 -20 0 Overall No Diabetes Diabetes P<0.0001 P<0.0001 P<0.0001 69 LDL, low-density lipoprotein; LS, least squares. Davidson MH et al. Circulation. 2025;152(Suppl 3):Abstract 4368890.
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RUBENS Designed to Test the LDL-C Lowering Effects of Obicetrapib and Obicetrapib + Ezetimibe FDC in Diabetic Patient Population 70
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Safety FU Safety FU T2D/Metabolic Syndrome Study Placebo (n=100) Labs, PK Safety Labs, PK Safety Labs, PK Safety Obi 10 mg / EZE 10mg (n=100) • Patients (n=300) • T2D / Met Syn • Guideline recommended LLT Safety FU Safety FUObi 10mg (n=100) Main Inclusion Criteria: • Clinical ASCVD • HoFH • Uncontrolled hypertension Main Exclusion Criteria: Primary efficacy endpoint • % LS mean change from BL to Day 84 in LDL-C for obicetrapib & FDC using Martin-Hopkins • ≥ 18 years • T2D / Metabolic Syndrome • LDL ≥ 100 mg/dL • TG ≥ 150 < 400 mg/dL • Guideline recommended LLT Key secondary efficacy endpoint • LDL-C Goal attainment • Lp(a), LDL-P, sdLDL Objective: To evaluate the effect of obicetrapib and the FDC on LDL-C in patients with T2D / Met Syn Study design: Randomized, double-blind, placebo-controlled Visit: Days: 1 -28 to -1 2 1 4 84 3 30 8 +35 Eligibility: ASCVD, atherosclerotic cardiovascular disease; BL, baseline; eze, ezetimibe; FDC, fixed-dose combination; FU, follow-up; LDL, low-density lipoprotein; LDL-C, low-density lipoprotein cholesterol; LDL-P, low-density lipoprotein particles; LS, least squares; PK, pharmacokinetics; T2D, type 2 diabetes; TG, triglycerides. 71
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RUBENS Is Designed to Provide Insight into LDL-C and Small Particle Lowering in the Diabetic Population without ASCVD May support LDL-C lowering in a T2D/metabolic syndrome population in the label Positive traction with endocrinologists and diabetes specialists Large, underserved population: T2D/metabolic syndrome patients not at LDL-C goal despite statin therapy Designed to evaluate changes in LDL-C, sdLDL & Lp(a) 1 Show obicetrapib and FDC robustly lower LDL-C in T2D/metabolic syndrome patients 2 Demonstrate reduction of atherogenic sdLDL particles and Lp(a) 3 Establish CETP inhibition preserves glycemic control in patients on statin therapy 4 Confirm efficacy and safety in high-risk patients without ASCVD ASCVD, atherosclerotic cardiovascular disease; CETP, cholesteryl ester transfer protein; FDC, fixed-dose combination; LDL-C, low-density lipoprotein cholesterol. 72
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Moving from the Heart to the Brain… 73
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What is the Link Between Cholesterol, CETP, and AD? 74
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+ Elevated Cholesterol Levels in the Brain Precede Formation of Amyloid- Beta (Aβ) Plaques During early development, oligodendrocytes synthesize large quantities of cholesterol for myelination In adults, when myelination is complete, glial cells and, to a lesser extent, neurons account for the steady-state production of cholesterol The brain uses a unique mechanism for cholesterol recycling and redistribution • Involves an ApoE-mediated lipoprotein pathway unique to the CNS whereby cholesterol is turned over • Excess oxysterols are ultimately delivered to the liver for secretion into the bile Cholesterol itself does not exit the brain but instead is converted to a metabolite, 24S-hydroxycholesterol • 24S-hydroxycholesterol is a proxy for excess cholesterol that will be measured in our phase 2a clinical trial 20% cholesterol Amyloid precursor is cleaved, releasing Aβ peptide Aβ peptide leaves membrane and aggregates Aβ plaque is formed Aβ peptide Cholesterol Cell membrane Aβ plaque formation inside AD brain cells The brain is the most cholesterol-rich organ; it contains only 2% body mass but has 20% of the body’s cholesterol APOE, apolipoprotein E; CNS, central nervous system. Mahley RW. Arterioscler Thromb Vasc Biol. 2016;36(7):1305-1315. 75
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ApoE4 is a Risk Factor for Both CVD and Alzheimer’s Disease1-5 % of population with this genotype APOE2/E3 11% APOE3/E3 61% APOE2/E2 0.5% APOE4/E2 = 2% APOE4/E3 = 24% APOE4/E4 = 2% Cholesterol transport and clearance Lipid accumulation in brain Aβ aggregation Total cholesterol HDL-C receptor + binding N-term C-term Lipid binding (VLDL) R158 R61 R112 C255 • Disruption of neuronal synaptic function • Altered astrocytic glucose metabolism • Promotion of microglial inflammatory responses • Impaired oligodendrocyte remyelination 66% AD Risk Factors Prevalence of APOE4 in AD ApoE4-induced cholesterol dysregulation has cell-specific effects in the brain that all contribute to AD pathogenesis >25% of population at increased risk Elevated risk is mediated by the profound effect of APOE4 on lipid metabolism CVD CVD Risk Factors APOE4 Risk for CVD by 22-45% LDL-C HDL-C ApoC Lp(a) A AD, Alzheimer’s disease; Apo, apolipoprotein; CVD, cardiovascular disese; HDL-C, high density lipoprotein cholesterol; LDL-C, low density lipoprotein cholesterol; Lp(a), lipoprotein(a). 1. Abondio P et al. Genes (Basel). 2019;10(3):222. 2. Feringa FM et al. Front Aging Neurosci. 2021;13:690372. 3. Hottman DA et al. Neurobiol Dis. 2014;72(A):22-36. 4. Jeong W et al. Mol Cells. 2019;42(11):739-746. 5. Williams HC et al. Neurobiol Dis. 2020;136:104742. 6. Li Y et al. BMC Cardiovasc Disord. 2024;24(1):353. 7. Fernandez CG et al. Front Aging Neurosci. 2019;11:14. 8. Moriarty PM et al. Arterioscler Thromb Vasc Biol. 2017;37(3):580-588. 9. Xu M et al. Biomed Res Int. 2016;2016:3912175. 10. β, amyloid β; Mattsson N et al. Alzheimers Dement. 2018;14(7):913-924. 76
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CETP Loss-of-Function (LoF) Genotype May be Associated with Slower Memory Decline and Lower AD Risk 2 LoF CETP genes 1 LoF CETP gene Normal CETP CETP’s potential involvement in CNS cholesterol homeostasis is supported by genomic data1 CETP LoF may be associated with lower CETP activity & a corresponding increase in HDL levels2 Incidence of Dementia and Alzheimer’s Disease by CETP Genotype Group2 AD, Alzheimer’s disease; CETP, cholesteryl ester transfer protein; CNS, central nervous system; HDL, high-density lipoprotein. 1. Schmidt AF et al. Alzheimers Res Ther. 2024;16(1):228. 2. Sanders AE et al. JAMA. 2010;303(2):150-158. 77
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What Plasma Biomarkers Best Detect Early AD Pathology? 78
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Evidence Supports Plasma p-tau217 as a Predictive Biomarker of Amyloid PET, Which Is Predictive of Cognitive Decline Plasma p-tau217 Amyloid and Tau PET Cognitive Decline predicts • Higher Aβ PET burden is associated with greater cognitive decline1 • Lifetime risk of MCI and dementia increases with higher amyloid burden, with amyloid PET being the best predictor of future cognitive decline 4 Higher plasma p-tau217 is associated with faster Aβ and tau accumulation on PET1 predicts Plasma p-tau217 can predict underlying pathology in cognitively normal individuals and identify presymptomatic patients2,3 MCI, mild cognitive impairment; PET, positron emission tomography. 1. Yang HS et al. Nat Commun. 2026;17(1):3188. 3. Schindler SE et al. Alzheimers Dement. 2024;20(11):8074-8096. 4. Jack CR et al. Lancet Neurol. 2025;24(12). 2. Jonaitis EM et al. Brain Commun. 2023;5(2):fcad057. 79
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What Did we Discover in the BROADWAY Data? 80
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Patients With ASCVD Carry Undiagnosed AD Pathology, as Measured by p-tau217 Levels1-3 81 In the BROADWAY AD Biomarker Substudy of 1535 adults with ASCVD, nearly half (45.9%, n=730) had abnormally high p-tau217 levels (>0.42 pg/mL), indicating preclinical AD pathology3 AD, Alzheimer's disease; APOE, apolipoprotein E; ASCVD, atherosclerotic cardiovascular disease. 1. van Nieuwkerk AC et al. Stroke. 2023;54(8):2181-2191. 2. French SR et al. Alzheimers Dement. 2025;21(8):e70565. 3. Kastelein JJP et al. Poster presented at the Alzheimer’s Association International Conference 2026. July 12-15, 2026. London, UK. 33% 68% 43% 58% 42% 27% 33% 18% 38% 22% 27% 33% 33% 15% 19% 20% 31% 40% 0 10 20 30 40 50 60 70 80 90 100 E2/E2 E2/E3 E2/E4 E3/E3 E3/E4 E4/E4 Participants, % ≤0.42 pg/mL >0.42 to ≤0.62 pg/mL >0.62 pg/mLp-tau217: APOE Status: Baseline p-tau217 by APOE Status3 n=6 n=102 n=21 n=1081 n=349 n=30 73.3% of E4/E4 homozygotes had abnormally high p-tau217 (>0.42 pg/mL)
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Does Obicetrapib Impact AD Biomarkers in Asymptomatic APOE4 Carriers? 82
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Significant Reduction in p-tau217 Progression Over 12 Months Observed with Greater Reductions as ApoE4 Risk Factors Increase 2.09% 4.94% -10 -5 0 5 10 15 Obicetrapib Placebo Percent change from baseline, % Full Analysis Set* (n=1535) 2.84% benefit between obicetrapib and placebo (P=0.025) 1.45% 7.19% -10 -5 0 5 10 15 Obicetrapib Placebo Percent change from baseline, % ApoE4 Carriers* (n=367) 5.74% treatment benefit in ApoE4 carriers (P=0.022) -7.81% 12.67 % -10 -5 0 5 10 15 Placebo Percent change from baseline, % Obicetrapib ApoE4 Homozygotes* (n=29) 20.5% treatment benefit in ApoE4 homozygotes (P=0.010) *Results reflect adjustment for mean-centered baseline p-tau217 and mean-centered age. Participants with known ApoE status (based on phenotypic analysis), baseline p-tau217 above the lower limit of quantification (LLQ), and available end-of-study p-tau217 were included in the current analyses. ApoE, apolipoprotein E; p-tau, phosphorylated tau. ApoE4 carriers defined as ApoE3/E4 or ApoE4/E4, based on phenotypic analysis Davidson MH et al. 2025. Journal of Prevention of Alzheimer's Disease 83
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PREVAIL: Improving Probability for Success 84
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Setting Up PREVAIL for Success TODAY • Public Company • Guideline Updates • CHMP Recommendation • $683M in cash PREVAIL Initiated 2021 • Private Company • Limited Funding How has our knowledge MATURED? 2021 2022 2023 2024 20262025 BROADWAY • 21% Observed Reduction in MACE 85
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PREVAIL Designed to Apply Lessons Learned from Previous CVOTs to Demonstrate Obicetrapib’s Full Benefit Greater LDL-C lowering activity anticipated Targeting higher baseline LDL-C patients Higher absolute LDL-C reduction expected to lead to greater MACE benefit Longer duration of follow up Targeting higher-risk patient population Maximizes opportunity for MACE reduction Differentiated secondary endpoints Potentially enhanced commercial profile vs. other LDL-C lowering agents Primary endpoint selection Coronary heart disease (CHD) death, non-fatal MI, fatal and non-fatal ischemic stroke, coronary revascularization 86
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Changes in MACE-3/MACE-4 in-line with CTT Definition and Focused on LDL-C Modifiable Endpoints MACE-4 Urgent Revascularization MACE-3 Cardiovascular Death Non-Fatal MI Stroke MACE-4 Total Revascularization MACE-3 Coronary Heart Death Non-Fatal MI Fatal & Non-Fatal Ischemic Stroke MACE-4: Urgent/non-elective coronary revascularization updated to total coronary revascularization, given minimal difference in MACE reduction between the two definitions; but by utilizing total coronary revascularization the event number and overall study power increases Removal of: • Heart failure death • Hemorrhagic stroke Addition of: • Total revascularization 87
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PREVAIL Probability of Success and Study Power Increased Estimated Study Completion Primary Event Number Minimum Follow Up Expected Time to Majority of MACE benefit (1) Median Follow Up PREVAIL at Initiation YE 2026/1Q 2027 ~950 ~3.5 years ~2.5 years 2.0-2.5 years At Interim Analysis YE 2026/1Q 2027 >950 ~3.5 years ~2.5 years 2.0-2.5 years At end of 2027 YE 2027 >>950 ~4.5 years ~3.5 years 2.0-2.5 years PREVAIL study extension to the end of 2027 driven by slowing event rates plus desire to power the primary MACE-4 endpoint down to 15% through the addition of an additional one year of event accrual Interim analysis allows the opportunity to enter the market a year earlier, without jeopardizing efficacy or needed alpha for primary endpoint 88 1. Based on internal analysis
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Kaplan-Meier Curve Separates at Day 200 Driven by Attenuation of MACE- 4 Events in the Obicetrapib Arm 4-point MACE: CHD death, Non-fatal myocardial infarction, non-fatal stroke, coronary revascularization While not powered to detect a MACE-4 benefit, we observed positive MACE-4 data as part of our review of the exploratory endpoint. BROADWAY was not powered to measure MACE-4 benefit and the MACE-4 data presented below may not be predictive of the MACE data we observe in PREVAIL, which has been designed to measure MACE benefit. Kaplan Meier Curve Landmark Analysis: Censored at 6 months 89
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MACE Benefit Observed Across Multiple Components After 1 Year of Treatment Placebo N = 844 Obicetrapib N = 1686 Hazard Ratio 95% CI All-cause mortality – no. (%) 12 (1.4) 19 (1.1) 0.83 (0.40-1.71) First 4-point MACE – no. (%) 44 (5.2) 70 (4.2) 0.79 (0.54-1.15) Coronary heart death – no. (%) 5 (0.6) 8 (0.5) 0.80 (0.26-2.44) Nonfatal MI – no. (%) 11 (1.3) 20 (1.2) 0.91 (0.44-1.90) Stroke – no. (%) 5 (0.6) 14 (0.8) 1.39 (0.50-3.86) Coronary revascularization – no. (%) 34 (4.0) 49 (2.9) 0.72 (0.46-1.11) 4-point MACE: CHD death, Non-fatal myocardial infarction, non-fatal stroke, coronary revascularization (1) MACE was evaluated in BROADWAY as an exploratory endpoint. There are limitations on the interpretation of MACE data derived from both BROOKLYN and BROADWAY studies given they were not designed or powered to assess MACE. MACE data presented above may not be predictive of the MACE data we observe in PREVAIL, which has been designed to measure MACE benefit. BROADWAY MACE Data(1) 90
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Stroke Benefit Typically Delayed; Contributing in Later Years Source: Cholesterol Treatment Trialists Collaboration. Lancet. 2010 Meta-analysis of 21 CVOTs demonstrate delayed stroke benefit through LDL-C reductions 91 Year/Outcome Events (% p.a.) Statin / more Control / less RR (CI) per 1 mmol/L reduction in LDL–C YEAR 0–1 Major coronary event 1441 (1.7) 1727 (2.1) 0.84 (0.76 – 0.92) Coronary revascularization 1886 (2.3) 2150 (2.6) 0.88 (0.80 – 0.97) Stroke 557 (0.7) 588 (0.7) 0.96 (0.82 – 1.12) Major vascular event 3497 (4.3) 3952 (4.8) 0.88 (0.84 – 0.93) p<0.0001 YEAR 1–2 Major coronary event 1009 (1.3) 1256 (1.6) 0.78 (0.70 – 0.86) Coronary revascularization 997 (1.3) 1282 (1.7) 0.75 (0.67 – 0.84) Stroke 445 (0.6) 573 (0.7) 0.77 (0.66 – 0.91) Major vascular event 2112 (2.8) 2645 (3.6) 0.77 (0.73 – 0.82) p<0.0001
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LDL-C Studies: Generally Shown to be Predictive of CVOT Outcomes Concordance results for lipid lowering drugs evaluated Drug Sample Size MACE EVENTS (1st occurrence) CVOT¹ MACE HR (95% CI) Non-CVOT MACE RR (95% CI) Concordance N-active drug N-comparator Events-Drug Events-Comparator % Event Rate-Drug % Event Rate-Comparator Bempedoic Acid-CVOT 6992 6978 819 927 11.71 13.28 0.87 (0.79–0.96) Concordant Non-CVOT 2424 1197 117 75 4.83 6.27 0.77 (0.58–1.02) Evolocumab-CVOT 13,784 13,780 1344 1563 9.75 11.34 0.85 (0.79–0.92) Concordant Non-CVOT 2976 1489 28 30 0.94 2.01 0.47 (0.28–0.78) Alirocumab-CVOT 9462 9462 903 1052 9.54 11.12 0.85 (0.78–0.93) Concordant Non-CVOT 3182 1792 52 33 1.63 1.84 0.89 (0.57–1.37) Bococizumab-CVOT 13,720 13,718 352 397 3.16 3.59 0.88 (0.76–1.02) Concordant Non-CVOT 2377 2058 57 55 2.5 2.7 0.90 (0.62–1.29) 100% of Non-CVOT studies results were concordant with the CVOT outcome* 92 Source: Shear et al, American Heart Journal Plus: Cardiology Research and Practice 63 (2026) 100728. * Excludes CETP studies that were based on HDL-C raising, where only one was not concordant
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BROADWAY Designed to be a Predictor of PREVAIL Key Inclusion Criteria 13-months Placebo Obicetrapib 10 mg (2:1 randomization) N = 2532 13-months 1º endpoint – week 12 98 125 92 50 142 0 50 100 150 LDL-C Non-HDL-C ApoB HDL-C TG mg/dL Baseline Lipids Baseline Lipid Modifying Therapy • Any statin: 91% • High intensity statin: 65% • Ezetimibe: 26% • PCSK9i: 4% • SGLT2i: 11% • GLP-1: 6% Placebo Obicetrapib 10 mg (1:1 randomization) N = 9541 54-months LDL-C endpoint 103 133 97 48 155 0 50 100 150 200 LDL-C Non-HDL-C ApoB HDL-C TG mg/dL Source: Data on file 39 0 13 25 38 50 Lp(a) nmol/L Blinded mean Median Blinded mean 38 0 13 25 38 50 Lp(a) nmol/L Median • LDL-C≥ 100 mg/dL • Maximally tolerated lipid lowering therapy • ASCVD or HeFH • LDL-C ≥55 mg/dL w/risk factors, or Key Inclusion Criteria • LDL-C≥ 100 mg/dL • Maximally tolerated lipid lowering therapy • ASCVD • LDL-C ≥55 mg/dL w/risk factors, or Baseline Lipids Baseline Lipid Modifying Therapy • Any statin: >90% • High intensity statin: 74% • Ezetimibe: 26% • PCSK9i: 2% • SGLT2i: 14% • GLP-1: 6% 93
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BROADWAY and PREVAIL Year 1 Event Rates - Showing Similar MACE Rates in the Study Populations 4-point MACE: CHD death, Non-fatal myocardial infarction, non-fatal stroke, coronary revascularization (1) While not powered to detect a MACE benefit, we observed positive MACE-4 data as part of our review of the exploratory endpoint. BROADWAY was not powered to measure MACE benefit and the MACE data presented below may not be predictive of the MACE data we observe in PREVAIL, which has been designed to measure MACE benefit. PREVAIL data is preliminary and subject to change as MACE events continue to be identified and adjudicated (including with respect to periods presented above). Additionally, Year 1 and Year 2 MACE event trends may not be indicative of future trends. Blinded/Blended Year 1 Event Rates 94
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Trial Year Median Follow Up (Yr) 2 Age LDL (mg/dL)3 Diabetes Prior MI Calc. MACE-4 Event Rates1 Calc. MACE-3 Event Rates1 CLEAR SP Cohort 2023 3.4 65 139 46% 30% 4.60% 3.20% SOUL 2025 4.1 66 72 100% 100% 3.90% 3.35% SELECT 2023 3.33 62 78 0% 68% 3.68% 2.41% FOURIER 2017 2.2 63 92 37% 81% 5.14% 3.36% ODYSSEY 2018 2.8 59 87 29% 19% 5.57% 3.74% Average 3.2 63 88 42% 60% 4.58% 3.21% 2026 2.78 65 103 49% 50% 2023 1 66 97 38% 57% 5.20% 2.50% PREVAIL has a higher or comparable baseline risk vs comparator trials but blinded event rates are trending lower Source: Internal analysis | 1. Sayed et al. International Journal of Cardiology 406 (2024) 132074 2.McGuire et al. N Engl J Med 2025;392:2001-12. 3.Lincoff et al. N Engl J Med 2023;389:2221-32. 4. Sabatine et al. N Engl J Med 2017;376:1713-22. 5. Schwartz et al. N Engl J Med 2018;379:2097-107. Note: 1. Internal analysis based on annualized placebo rates for comparator trials calculated based on available data; MACE-4 was 4 pt CTT (3pt MACE + total coronary revasc; if not available: then 3 pt + ischemic driven revasc (IDR) or 3 pt + coronary/cerebral revasc (CCR) . 2. Approximate 3. Median values except for PREVAIL, BROADWAY, CLEAR Results should be interpreted with caution due to inherent limitations in cross-trial comparisons. PREVAIL Blinded Rates vs Contemporary Secondary Prevention CVOT Placebo Rates (2017–2025) 95
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Analysis Suggests Event Rates in CVOT Trials Have Remained Stable When Adjusting for Baseline LDL-C; Impact of Drop-In’s Minimal What effect could drops-in have?Has standard of care been reducing event rates? Although novel drug usage is increasing (GLP1, SGLT2, PCSK9, etc.) lower event rates in LDL-C based CVOTs are explainable by lower baseline LDL-C A 1% drop-in rate of a therapy that provides a 20% MACE benefit would only impact event rates by 0.009%, from 4.500% to 4.491% 10,000 patients 1% drop-in rate = 100 patients 4.5% event rate = 13.5 events over 3 years 3.6% 2.5% 2.6% CTT statin-control trials through 2009 CTT rate standardized to contemporary baseline LDL-C Recent CVOTs, endpoint-aligned -31% 96 Source: Internal analysis; 1. Sayed et al. International Journal of Cardiology 406 (2024) 132074; 2.McGuire et al. N Engl J Med 2025;392:2001-12; 3.Lincoff et al. N Engl J Med 2023;389:2221-32; 4. Sabatine et al. N Engl J Med 2017;376:1713-22; 5. Schwartz et al. N Engl J Med 2018;379:2097-107; 6. Cholesterol Treatment Trialists Collaboration. Lancet. 2010.
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Treatment Effect Believed to be Likely Explanation for Lower Event Rates Oversight of a Trial Execution Factor Missing events or Drop in/dropouts Drop in/dropouts in the low single digit percentages, similar to or better than most contemporary studies Patient Population & Background of Care Improving standard of care PREVAIL observed event accumulation is consistent with secular decline in CVOT placebo rates and even below contemporary average Treatment Efficacy Obicetrapib could be working better than expected, causing a substantial decrease of events in treatment arm and lowering blended rates 97
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PREVAIL Design Changes Increase Probability of Success Increased number of events at interim and end of study Encouraging blinded event trends believed to be driven by treatment effect, and not explained by standard of care or drop-ins CVOT precedents and blinded data suggest a potential benefit consistent with BROADWAY , providing margin to the powering assumptions and commercial hurdle Success is more important than the ultimate MACE value, driven by guideline updates, prescribing behavior, and differentiated product profile Optimistic around a successful study outcome, interim provides option to enter market earlier 98 The Study Should Not Fail the Drug
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A Future Worth Getting Ahead Of AGE 55 • FEMALE • APOE4 HOMOZYGOTE • FHx ALZHEIMER'S MEDICATIONS: STATIN • TRIATHLETE & MOUNTAINEER • PhD, BIOTECH EXECUTIVE ADVOCATE “ Wendy N. Living Fully, Still Waiting for Prevention I watched Alzheimer’s take so much from both my mother and now my father. Living with two copies of APOE4, I can’t help but fear that my daughters or I will face the same future. I’m healthy today, but waiting for symptoms is not enough. We need treatment options that enable earlier intervention. 100100
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Recombinant human serum albumin Plasma exchange LY4006895 CpG1018 AV-1980R Mivelsiran DUVAX AK152 AAV2-BDNF ALN-5288 BCG vaccine ION269 AV-1959D BIIB080 ADEL-Y01 LX1001 AV-1959R CM383 LY3954068 NIO752 PMN310 Probiotics RO7812653 THN391 AADvac1 + AAmAb ACI-24.060 ARO-MAPT Etalanetug + Lecanemab JNJ-64042056 Sargramostim SHR-1707 Trontinemab Semaglutide MK-2214 Semaglutide + Candesartan + Vitamin D + Calcium VHB937 VY7523 XPro1595 Posdinemab Sabirnetug Foralumab BMS-986446 AADvac1 AldesleukinAL101 BIIB080 Exercised plasma Donanemab Etalanetug + Lecanemab Gantenerumab Lecanemab RG6289 + Donanemab Semaglutide Solanezumab Tertomotide Trontinemab Gonadorelin Remternetug BnH-015B HHT201 NPT 2042 Astragalus Brivaracetam Cannabidiol CORT108297 DAOIB + AO Emestedastat IVL3003 KarXT + KarX-EC + Lecanemab Mevidalen MK-1167 NSC001 + Trospium NSC001 ONO-2020 Polypill Tadalafil Tisolagiline Trazodone Caffeine Donepezil Guanfacine Huperzine A KarXT + KarX-EC Latrepirdine Piromelatine Rotigotine + Rivastigmine Tricaprilin ACP-204 Escitalopram KarXT + KarX-EC KarXT Masupirdine Nabilone BMS-986368 Cannabidiol IGC-AD1 Dexmedetomidine ITI-1284 Methylphenidate + iTBS ML-007C-MA ONO-2020 Cannabidiol LY03017 Psilocybin Xenon REM0045392 Phenserine OLX-07010 Nicotinamide riboside MIB-626 Leucettinib-21 KS101 J4 Emtricitabine + Tenofovir alafenamide Emtricitabine DDN-A-0101 Choline Centella asiatica AS-S603 AR1001 Buntanetap Masitinib Metformin MLC901 Nilotinib RG6289 T3D-959 Valiltramiprosate Wujia Yizhi 2-HOBA Aluminum hydroxide Baricitinib Benfotiamine BEY2153 Brexanolone Bumetanide Ciprofloxacin + Celecoxib Contraloid acetate Daridorexant Dasatinib + Quercetin Dimethyl fumarate Edavarone Enrupatinib EX039 Fasudil Lemborexant Lenalidomide Leuprolide Levetiracetam LHP588 Losartan + Amlodipine Memantine MIB-626 Nicotinic Acid NTRX-07 Ozanimod Rifaximin RQC Siponimod Sodium pentaborate pentahydrate SPG302 Suvorexant Zervimesine Sirolimus Senicapoc RO7269162 Parthenolide + Ipriflavone Obicetrapib Targeted Pathophysiological Process Amyloid Tau APOE, Lipids and Lipoprotein Receptors Neurotransmitter Receptors Neurogenesis Inflammation Oxidative Stress Cell Death Proteostasis/Proteinopathies Metabolism and Bioenergetics Vasculature Growth Factors and Hormones Synaptic Plasticity/Neuroprotection Gut-Brain Axis Circadian Rhythm Epigenetic Regulators Multi-Target Undisclosed Lipid Metabolism (with downstream effects on inflammation and oxidative stress) Trial Population Healthy Volunteers Preclinical AD MCI (Prodromal) and MCI-Mild AD Dementia Mild-Moderate AD Dementia Severe AD Dementia 101 Obicetrapib Is the Only Therapy Targeting Upstream Lipid Metabolism for AD Prevention Source: Cummings et al. Alzheimer’s Dement. 2026;12:e70251
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Alzheimer’s Disease is Being Redefined as a Biological Process That Begins 20 Years Before Cognitive Decline AD continuum Relative change from baseline ~20 years before symptom onset NO DISEASE PRESYMPTOMATIC AD TYPES OF BIOMARKER Imaging CSF CSF and plasma CLOSEST PATHOLOGIC CORRELATION Amyloid plaques Neuroinflammation Neurofibrillary tangles Neurodegeneration STAGE OF DEVELOPMENT CLINICALLY APPROVED Investigational Biomarkers measured as endpoints in obicetrapib AD studies SYMPTOMATIC AD Amyloid PET Tau PET (cortical) MTBR-tau243 FDG PET tau368/t-TauAβ42 and Aβ42/40 GFAP pTau-217 and pTau231 pTau-181 t-Tau Brain-derived Tau pTau-205 NfL MRI volumetrics sTREM2 102
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Higher Plasma p-tau217 Levels Are Associated With Greater Risk of Progression to Cognitive Impairment in Unimpaired Adults* 103 *Study included 2684 cognitively unimpaired older adults with baseline plasma p-tau217 and Aβ PET imaging and longitudinal clinical follow-up from multiple well-characterized observational and clinical trial cohorts. Cognitive impairment was defined as a within-cohort diagnosis of mild cognitive impairment, dementia, or 2 consecutive global Clinical Dementia Rating scores of 0.5 or greater. Aβ, amyloid beta; CI, confidence interval; HR, hazard ratio; PET, positron emission tomography; SD, standard deviation; y, years. Buckley RF et al. JAMA. 2026:e2612556. Epub ahead of print. doi:10.1001/jama.2026.12556 Survival Free of Cognitive Impairment Over Time, by Baseline Plasma p-tau217 Group An increase of 1 SD in p-tau217 was associated with an HR for progression to cognitive impairment of 1.38 (95% CI, 1.30-1.46; P<0.001) 0 0.2 0.4 0.6 0.8 1.0 0 2 4 6 8 10 Time, y Survival without clinical progression to cognitive impairment 516 1087 598 483 Low Intermediate High Very high 451 983 520 425 296 625 358 285 197 404 195 143 53 139 49 27 19 65 16 11 No. of participants at risk Low Intermediate High Very high p-tau217 group LowBaseline p-tau217 group Intermediate High Very high p-tau217 (z-score) High and Very High Levels of p-tau217 Are Associated With the Greatest Risk of Progression Relative to the Low p- tau217 Group 0 20 40 60 80 100 Risk of cognitive impairment, % 2 5 10 Time horizon, y -2 -0.5 0 1.1 2 2.5 4 6
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SPINOZA 104
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Commercial Update 105
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Agenda • US Launch Preparations • European Launch Update 106
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US Launch Preparations Market Product Company 107
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Preparing The Market Market Product Company 108
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"It seems like no matter what I do, it goes up every year, a couple of points. It is an uphill battle with a boulder I can't seem to push." - Patient 34% 23% 10% 7% 6% What is the main reason you were not fully satisfied with your treatments for high cholesterol (hypercholesterolemia)? Patient Satisfaction With Current Therapies Is Low Source(s): 1) Magnolia March 2024 Patient Quant Research, N=276 Patient Quantitative Respondents 2) Klick Patient Ethnography Research, Jan 2026 3) Always Future Patient Physician Disconnect Study, April 2026 2 out of 3 Patients are not fully satisfied with their hypercholesterolemia treatment I am concerned about the safety of my current Rx Top 5 Reasons I experience side effects from my current Rx I believe my current Rx is not effective Safety/Tolerability Lack of Efficacy ”Every statin I've ever tried makes muscles in your body just ache." - Patient I just started my current Rx recently I experience muscle related side effects from my current Rx Market "When I started taking statins... I noticed a lot of aches and pains. I felt weak... I just did not feel like myself." - Patient "Frustration. Because some of the best advice I would give someone to lower their cholesterol, I follow. And my cholesterol, is still very high." - Patient 109
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Unmet Need Is Driving Increased Innovation Multiple companies are advancing LDL-C, Lp(a), and combination programs, reinforcing broad recognition that the LLT market continues to need new patient solutions VISIBLE INDUSTRY COMMITMENT 7 companies with listed LLT programs in the competitor timeline Merck AstraZeneca Novartis Amgen Lilly Esperion LIB Ther. LDL-C / PCSK9 • Enlicitide • Laroprovstat • Lerodalcibep Lp(a) • Pelacarsen • Olpasiran • Lepodisiran • Muvalaplin Combination / FDC • BPA + EZE + Statin Lipid management pipeline momentum, 2026–2030 Visible timelines include launch, filing, approval, data release, and outcomes readout activity across multiple mechanisms Industry investment across LDL-C, Lp(a), and combination approaches reinforces broad conviction that lipid management remains a large, active, and underpenetrated cardiovascular market Source: Timeline estimated based on publicly available sources PCSK9 / LDL-C Lp(a) Combination / FDC 2026 2027 2028 2029 2030 Data release FDA Approval US Launch • Oral PCSK9i + Statin LIB Merck AstraZeneca Novartis Amgen Lilly Esperion 110
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3.0MM 3.7MM 4.9MM 6.4MM 0MM 2MM 4MM 6MM 8MM 2022 2023 2024 2025 14.7MM 17.2MM 20.8MM 24.8MM 0MM 10MM 20MM 30MM 2022 2023 2024 2025 Non-statins growing at high double digits Branded agents grew 31% matching last year’s growth 241MM 247MM 256MM 262MM 210MM 230MM 250MM 270MM 2022 2023 2024 2025 2.2% Growth Non-Statins3 TRx Branded4 TRxStatin TRx2 3 4 6 years of consecutive growth Lipid lowering Therapy TRx2 Market Dynamics: Growth of Non-Statin (+19%) and Branded (+31%) Volume Continue to Grow Rapidly Year Over Year Market Growth of 2.3% in 2025, adds 6 million additional TRx’s, of which 1.5 million are branded TRx’s 3.9 % Growth 2.3 % Growth 17 % Growth 21 % Growth 19 % Growth 26 % Growth 32 % Growth 31 % Growth 2.3 % Growth 2 Statin TRx2 Over 60 million patients undertreated/ not treated Patient Population11 84 million Adults in US diagnosed with hyperlipidemia ~21 million Diagnosed patients not treated with statin or LLT ~40 million Not at goal Source: Based on third party prescription data on file 1. Forian Healthcare Closed Claims and EHR Data (2022-2024) 2. All Lipid Lowering therapies: Statins, Ezetimibe and combinations; PCSK9 and BPA; 3. Non-Statins : Ezetimibe and combinations; PCSK9 and BPA; 4. Branded: PCSK9 and BPA; Market 111
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Recent Updates to Guidelines Advocate for More Aggressive Intervention Guidance for patients with very high-risk ASCVD receiving maximally tolerated statin therapy 1. Grundy SM et al. J Am Coll Cardiol. 2019;73(24):e285-e350. 2. Lloyd-Jones DM et al. J Am Coll Cardiol. 2022;80(14):1366-1418. 3. Rao SV et al. Circulation. 2025; 151(13):e771-e862. 4. Blumenthal RS et al. Circulation. 2026;153(17):e1154-e1276. LDL-C threshold of 70 mg/dL for the addition of nonstatin therapy1 LDL-C threshold of 55 mg/dL for the addition of nonstatin therapy 2 Formal LDL-C goal of <55 mg/dL to guide the addition and intensification of nonstatin therapy4 LDL-C threshold of 55 mg/dL for the addition of nonstatin therapy among hospitalized patients with ACS 3 2018 2022 2025 20262019 2020 2021 2023 2024 NEW! Market 112
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13.1MM 14.3MM 15.5MM 16.5MM 37.4% 39.2% 40.3% 41.2% 30.0% 32.0% 34.0% 36.0% 38.0% 40.0% 42.0% 44.0% 12MM 13MM 14MM 15MM 16MM 17MM 18MM 19MM Jul '21 to Jun '22 Jul '22 to Jun '23 Jul '23 to Jun '24 Jul '24 to Jun '25 Patients on multiple therapies or MTS Penetration (% of all patients) Resulting In More Patients Treated and Greater Focus On Goal Attainment Source: Forian data from Jul ‘21 to Jun ’25 1All Lipid Lowering therapies: Statins, Ezetimibe and combinations; PCSK9 and BPA 2Atorvastatin 40 & 80 mg, Simvastatin 80 mg, Rosuvastatin 20 & 40 mg More aggressive treatment over time Patients on high intensity2 or add-on therapies Jul '21 to Jun '22 Jul '22 to Jun '23 Jul '23 to Jun '24 Jul '24 to Jun '25 Jul '24 to Jun '25 32.0MM 33.0MM 34.0MM 35.0MM 36.0MM 37.0MM 38.0MM 39.0MM 40.0MM 41.0MM 42.0MM Greater than 5 MM treated patients added in the last 3 years Patients on Lipid lowering Therapy1 34.9 MM 40.2 MM +1.5 MM (4.4%) +2.1 MM (5.8%) +1.7 MM (4.3%) 1 2 Market 113
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0.0 1.0 2.0 3.0 4.0 5.0 6.0 2015 2016 2017 2018 2019 2020 2021 2022 2023 2024 2025 TRx Volume (Millions) … Leading to Accelerated Brand Growth 2025 worldwide revenue of $3 Billion US revenues of $1.7 Billion WW PCSK9 class is approaching $5 Billion Approx. 5 Years to 1MM Rx’s / Year Approx. 2 Years to 2MM Rx’s / Year Approx. 2 Years to 4MM Rx’s / Year 1 2 3 2X GROWTH Repatha® volume continues to be on track to double every 2 years Accelerating growth is evidence of the demand for additional options in the LLT space Source: Based on third party prescription data and competitive intelligence on file 2X GROWTH Approx. 5.5MM Rx’s / Year 4 35% GROWTH Market Oct 2018: 60% Price Reduction to $5,850 WAC 114
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Obicetrapib Obicetrapib + Ezetimibe Evidence Supporting the Potential of Obicetrapib’s Portfolio is Grounded in Comprehensive, Outcomes-Driven Clinical Program BROADWAY TANDEMBROOKLYN PREVAIL*ROSE ROSE2 JAPAN PHASE 2 PHASE 3 TULIP REMBRANDT* VINCENT* 1 2 *In Progress & RUBENS* Product 116
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Statins, Ezetimibe, PCSK9i/oral PCSK9i, Bempedoic acid Obi: Has the potential to impact LDL-C, Lp(a), and multiple biomarkers in one product to address broad cardiometabolic risk Obi/ Obi-Eze redefines what physicians expect by addressing a broader set of lipid risk markers beyond LDL-C alone CURRENT LLT PARADIGM Obi Changes the Frame Atherogenic particle burden LDL-C ApoB Non-HDL LDL-P Residual lipid risk Lp(a) Small LDL-P NODM Functional lipid biology ApoA1 HDL-C HDL function Product Lipid Risk Remains Obi Delivers What LDL-Only Therapies Were Never Designed to Offer Atherogenic particle burden LDL-C ApoB Non-HDL LDL-P FUTURE LLT PARADIGM Oral, safe & well tolerated, once daily, simple dosing 117
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Obi Redefines Post-Statin Therapy For >60 Million Patients Not At Goal, Supported by a Differentiated LDL-C+ Profile Conceptual visual; not intended to represent quantified patient counts. STATIN THERAPY Broad treated population (up to 80% not at goal) ~63M Treated Patients Large & Growing Patient Opportunity → Other Add-on LLT Agents BPA, PCSK9i STATIN THERAPY: Standard of care Oral Generic – payer requirement NEXT STEP: ALL IN ONE ✓ ~50% LDL-C reduction ✓ Broader Lipid Impact (Lp(a), HDL-C) ✓ Safe and well-tolerated in Phase 3 trials ✓ Oral – once a day – simple dosing OBI/ OBI-EZE First add-on (up to 80% get to goal) ~44M Statin Treated Not-at-Goal ~84M HLD/ASCVD Patients Obicetrapib and Obicetrapib-Ezetimibe: the ideal choice after a statin — powerful LDL-C efficacy with broader lipid impact get up to 80% of patients to LDL-C goal 118
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7% 8% 20% 24% 23% 17% 4% 6% 25% 24% 24% 16% How likely are you to Rx obi and obi-eze in the first 6 months after they become available? What Are Customers Saying About Obi and Obi-Eze? Magnolia June 2026 HCP Quant Research, N=250 HCP Quantitative Respondents. Obicetrapib and obi-eze target product profile described as a once daily tablet for a small molecule CETP inhibitor (or CETP + Ezetimibe for FDC) taken with or without food; with safety and efficacy profile reflecting BROADWAY, TANDEM and BROOKLYN Phase 3 results (including LDL-C, ApoB, Non-HDL-C, HDL-C, Lp(a), 4-point MACE). *Source: Patient Physician Disconnect Research, April 2026. 2 out of 3 HCP’s indicate a propensity to prescribe Obi & Obi-Eze within the first 6 months Definitely would prescribe (7) OBICETRAPIB OBI-EZE Potentially would prescribe (4) Definitely would not prescribe (1) (2) (3) (5) (6) Safety/Tolerability Broad Efficacy* Convenience / Oral RoA “None of them can do what this medication can do, which is target the apoprotein B, the non-HDL, and the lipoprotein(a), which… has eluded us all this time.” - Card “I would just say it’s a novel product, you know, once daily, oral, easy to use that targets those harder to fix types of cholesterol, like the Lp(a) and ApoB and boost the HDL, which leads to better cardiovascular outcomes.” - PCP “Now we have something that is even more effective at getting you to goal with minimal side effects, and it's safe to take with your current medications and, you know, just reducing your overall risk.” - PCP Product 119 24%
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Preparing The Company Market Product Company 120
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NewAmsterdam Pharma Launch Leadership Team Company 121 BJ Jones Chief Commercial Officer Steven Albers Executive Vice President, Market Access & Public Affairs Michael Austwick Executive Vice President, Global Commercial Chris Deluzio Executive Vice President, Sales & Enterprise Operations Serina Fischer Executive Vice President, Global Marketing Debra Horner Executive Director, Operational Excellence Andy Hsieh Vice President, Medical Affairs Sanjay Keshav Vice President, Insights & Analytics Launch Success Requires A Great Asset, But Talent Is the Key To Unlocking Market Opportunity
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Already Deployed: Medical Affairs Education Investment in Obicetrapib’s scientific platform, engagement with the clinical community, and building value evidence are underway Company VALUE EVIDENCE FIELD MEDICAL CONGRESSES PUBLICATIONS 1 2 3 4 122
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In Market | Publications Most Influential Journals in Cardiovascular Medicine, Reaching Hundreds of Millions of Readers Company 356 Total Citations ” 88.5 Top Publication Impact Factor JOURNAL ↓ >220M Total Annual Readership/ Download Reach 26 # of Peer Reviewed Publications BROOKLYN (Nature Med) >25 million downloads/year BROADWAY AD Biomarker Substudy (JPAD) 9 citations >600,000 downloads/year Pooled MACE (JACC) 26 citations >2.1 million downloads/year BROADWAY (NEJM) 80 citations; Readership of >600,000 TANDEM (Lancet) 47 citations >155 million downloads/year PUBLICATIONS 1 123
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In Market | Value Evidence Health economic value narrative grounded in clinical benefit and economic value Company Milestones completed Phase 3 (BROADWAY/TANDEM) and Phase 2 (ROSE) CEAs ISPOR 2024 and 2026 posters US value dossier RWE unmet need and resource use 2026 NLA posters and JME publication VALUE EVIDENCE 2 124
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1,700+ Institutions engaged Engaged with the academic medical centers and health systems that shape practice 6000+ Engagements Sustained scientific dialogue with leading cardiovascular and lipidology KOLs 95+ Active scientific presence at every major cardiovascular and lipid society meeting 12 payer organizations Pre-launch scientific engagement with the medical teams to inform and educate on unmet need AT THE INSTITUTION WITH SCIENTIFIC LEADERS AT CONGRESSES WITH PAYER MEDICAL Scientific presentations In Market | Field Medical Built to engage institutions, leaders, and decision-makers shaping cardiovascular practice Company Deployed MSL team has over 260 years of combined medical affairs experience! 1 FIELD MEDICAL 3 125
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In Market | Congress Presence Scientific dialogue spanning North America, Europe, and Asia Company CARDIOVASCULAR SOCIETIES LIPID AND ATHEROSCLEROSIS SOCIETIES ACC American College of Cardiology United States AHA American Heart Association United States ESC European Society of Cardiology Europe ASPC American Society for Preventive Cardiology United States NLA National Lipid Association United States EAS European Atherosclerosis Society Europe JAS Japan Atherosclerosis Society Japan 2024 17 presentations 2025 40 presentations 2026 39 presentations & counting 1 CONGRESSES 4 126
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Coming Soon | Branded Launch! Company NAMS is a customer- centric organization focused on bringing transformational therapy and a seamless experience to each of its key customer groups 127 Prescribers Patients Provider Systems (IDNs, GPOs & Hospitals) Payers Pharmacists
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Agenda • US Launch Preparations • European Launch Update 128
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3 MM 5 MM 8 MM 12 MM 0MM 2MM 4MM 6MM 8MM 10MM 12MM 14MM 2022 2023 2024 2025 94 MM 122 MM 159 MM 199 MM 0MM 50MM 100MM 150MM 200MM 2022 2023 2024 2025 Non-statins growing at high double digits Branded agents have been growing more than 50% YoY 0.81 B 0.88 B 0.96 B 1.03 B 0.75 B 0.80 B 0.85 B 0.90 B 0.95 B 1.00 B 1.05 B 2022 2023 2024 2025 8.6% Growth Non-Statins3 : 30-Day TRx1 Branded4 : 30-Day TRx1Statin TRx2 3 Consecutive Years of 7% to 8% Market growth Lipid lowering Therapy2: 30-Day TRx1 EU Lipid Lowering Therapy Market is Large and Growing Rapidly Market Growth of 7.3% in 2025, adds 70 million additional TRx’s, of which 40 million are Non-Statin TRx’s Source: IQVIA MIDAS 1. 30 Day TRx: Using Standard units, 30-day Rx has been estimated based on unit usage in 30 days 2. All Lipid Lowering therapies: Statins, Ezetimibe and combinations; PCSK9 and BPA; 3. Non-Statins : Ezetimibe and its combinations; PCSK9 and BPA; 4. Branded: PCSK9 and BPA; Market 8.3% Growth 7.3% Growth 1 2 30% Growth 30% Growth 25% Growth 70% Growth 70% Growth 50% Growth 130
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Likelihood to Rx Obi/ Obi-Eze to At Least One Patient in the First 6 months After They Become Available (7-point likelihood to Rx scale; % HCPs selecting 6 or 7) Early Demand for Obicetrapib Franchise Across EU5 Markets 41% 43% Obi Obi/EZE 36% 43% Obi Obi/EZE 35% 37% Obi Obi/EZE 53% 59% Obi Obi/EZE 26% 35% Obi Obi/EZE Source: Magnolia March 2025 HCP Demand Study, US: N=252 HCP Quantitative Respondents; EU5 Countries: N=100 HCP Quantitative Respondents In Each Market (500 Total). 131
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EU Regulatory and Launch Timeline 132 2Q26 3Q26 4Q26 CHMP Opinion Anticipated EMA Approval Anticipated Menarini Launch in UK and Germany
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. EU4 + UK GPs SoV 11.2% TOP CORPORATIONS SOV% AstraZeneca2 5.3% GSK3 4.3% Boehringer Ingelheim 4 3.4% Italfarmaco5 3.0% Viatris6 2.9% Pfizer7 2.6% Cardiologists SoV 10.6% TOP CORPORATIONS SOV% Novartis 7.5% Daiichi Sankyo 7.0% AstraZeneca 6.8% Boehringer Ingelheim 6.0% Bayer 5.1% BMS 4.5% Internists SoV 8.5% TOP CORPORATIONS SOV% GSK2 5.8% AstraZeneca3 4.9% Daiichi Sankyo4 4.0% Boehringer Ingelheim 5 3.3% Sanofi6 3.2% Viatris7 2.7% Source: IQVIA Data — Weighted calls face-to-face MAT Q1 2025; EU4 + UK. GPs: General Practitioners; SoV: Share of Voice; MAT: Moving Annual Total. EU5 1 1 1 2 4 6 3 5 7 Menarini: Well-positioned to Launch Obi Driven by a Strong CV Heritage, Leading Share of Voice, and Significant Local Presence 133
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Summary: If Approved, Obi/ Obi-Eze Can Redefine Post-Statin Treatment By Getting Patients to LDL-C Goal, While Mitigating Residual Lipid Risk 134 >60M addressable market for Obi franchise in US alone (~21M untreated/ ~40M not at goal) Potential to be first LLT to launch with 3 successful Phase 3 studies (BROOKLYN / BROADWAY / TANDEM) and available outcomes data (PREVAIL) Observed powerful LDL-C efficacy, with differentiated benefit on Lp(a), Small LDL-P, and rate of NODM Simple, oral, once daily, low dose option with a reported safety/tolerability profile comparable to placebo Medical Affairs education and engagement underway, with industry-leading launch team on board Significant unmet need is driving innovation in the cardiometabolic space.
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Concluding Remarks 135
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2022 2023 2024 2025 2026E 2027E Phase 3 BROADWAY Trial Lipid Mono Study (HeFH or ASCVD; LDL-C ≥ 55 mg/dL; n=2,530) Phase 3 BROOKLYN Trial Lipid Mono Study (HeFH; LDL-C ≥ 70 mg/dL; n=354) Phase 3 CVOT PREVAIL Trial (ASCVD; LDL-C ≥ 55 mg/dL; n=9,541) Phase 3 RUBENS Trial Type 2 Diabetes / Metabolic Syndrome Study (T2D/Met Syndrome; LDL ≥ 70 mg/dL; n=300) Phase 2 VINCENT Trial Lp(a) change in combo w/ Repatha (Lp(a) ≥125 nmol/L, n=39; Lp(a) ≥50 nmol/L and <125 nmol/L, n=30) Phase 3 TANDEM Trial (LDL-C ≥ 70 mg/dL; n=407) Phase 3 REMBRANDT Trial Coronary plaque volume study (LDL-C ≥ 70 mg/dL; non–calcified coronary plaque > 75mm 3; n=300) *MAAs were filed and accepted for review by EMA, UK and Switzerland regulatory authorities Note: Other than as noted, the pipeline represents trials that are currently ongoing. 2026 and beyond are projections and subjec t to inherent limitations. Actual results may differ from expectations. Obicetrapib + Ezetimibe Fixed-Dose Combination (obicetrapib 10mg + ezetimibe 10mg) Enrollment CompleteInitiation Ph3 (estimated) CVOT Interim Ph2 (estimated) LEGEND TANDEM Ph3 Obicetrapib Monotherapy (obicetrapib 10mg) BROADWAY Ph3 BROOKLYN Ph3 PREVAIL CVOT VINCENT Ph2 Multiple Data Readouts to Drive Future Momentum REMBRANDT Ph 3 RUBENS Ph3 European Regulatory Filings* 136
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The NewAmsterdam Value Proposition Clinical Expertise: Data driven clinical development increases probability of success Differentiated Target Product Profile: Phase 3 data demonstrates obicetrapib’s potential impact on multiple CVD risk factors Unmet Need: Significant need for a potent, convenient, well-tolerated low-dose oral therapy Experienced Leadership and Team: Expanding team comprised of accomplished industry executives KOL Support: Physician community aware of unmet need and eager to leverage obicetrapib's differentiated profile to achieve desired clinical benefit, if approved CMC Expertise and Manufacturing Capacity: Preparing to meet anticipated demand for obicetrapib and the fixed dose combination, creating redundancy, expanding capacity and building inventory Commercial Excellence: Growing team with track record of blockbuster launch success and innovative go -to-market model Strong Balance Sheet: Cash runway expected to be sufficient to support U.S. commercial launch 137
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What to Expect in Next 12-18 Months with Potential Milestones Hitting as Momentum Continues to Build Lp(a) gaining momentum as target, testing added to guidelines Accelerated adoption of treatments adjunct to statins Recent guideline and label expansions Increased treatment aimed at hitting LDL-C goals Tailwinds Driving the Market PREVAIL CVOT Interim Analysis RUBENS Phase 3 LDL-C, Lp(a), Safety, in Type 2 Diabetics REMBRANDT Phase 3 NCPV, LDL-C, Lp(a), Safety Enrollment Complete SPINOZA Phase 2b trial Alzheimer’s Disease 138
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Q&A 139
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Thank You 140
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Appendix: Prior CVOT Baseline Characteristics 141 Source: Internal analysis | 1. Sayed et al. International Journal of Cardiology 406 (2024) 132074 2.McGuire et al. N Engl J Med 2025;392:2001-12. 3.Lincoff et al. N Engl J Med 2023;389:2221-32. 4. Sabatine et al. N Engl J Med 2017;376:1713-22. 5. Schwartz et al. N Engl J Med 2018;379:2097-107.
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Appendix: Prior CVOT Baseline Characteristics 142 Source: Internal analysis | 1. Sayed et al. International Journal of Cardiology 406 (2024) 132074 2.McGuire et al. N Engl J Med 2025;392:2001-12. 3.Lincoff et al. N Engl J Med 2023;389:2221-32. 4. Sabatine et al. N Engl J Med 2017;376:1713-22. 5. Schwartz et al. N Engl J Med 2018;379:2097-107.
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Appendix: Prior CVOT Baseline Characteristics 143 Source: Internal analysis | 1. Sayed et al. International Journal of Cardiology 406 (2024) 132074 2.McGuire et al. N Engl J Med 2025;392:2001-12. 3.Lincoff et al. N Engl J Med 2023;389:2221-32. 4. Sabatine et al. N Engl J Med 2017;376:1713-22. 5. Schwartz et al. N Engl J Med 2018;379:2097-107.