Slides
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Welcome to R&D Day June 11, 2025
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Disclaimer 2 Forward Looking Statements Certain statements included in this presentation (together with oral statements made in connection herewith, this “Presentation”) that are not historical facts are forward-looking statements for purposes of the safe harbor provisions under the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements generally are accompanied by words such as “believe,” “may,” “will,” “estimate,” “continue,” “anticipate,” “intend,” “expect,” “should,” “would,” “plan,” “predict,” “potential,” “seem,” “seek,” “future,” “outlook,” "aim" and similar expressions that predict or indicate future events or trends or that are not statements of historical matters. These forward-looking statements include, but are not limited to, statements by NewAmsterdam Pharma Company N.V. (“NewAmsterdam” or the “Company”) 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 activiti es, 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 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. These statements are based on various assumptions, whether or not identified in this Presentation, and on the current expectations of the Company’s management and are not predictions of actual performance. These forward-looking statements are provided for illustrative purposes only and are not intended to serve as and must not be relied on as a guarantee, an assurance, a prediction, or a definitive statement of fact or probability. Actual events and circumstances are difficult or impossible to predict and may differ from assumptions. Many actual events and circumstances are beyond the control of the Company. These forward-looking statements are subject to a number of risks and uncertainties, including changes in domestic and foreign business, market, financial, political, and legal conditions; risks related to the approval of NewAmsterdam’s product candidate and the timing of expected regulatory and business milestones; whether topline, initial or preliminary results from a particular clinical trial will be predictive of the final results of that trial and whether results of early clinical trials will be indicative of the results of later clinical trials; the potential for varying interpretations of the Alzheimer's disease sub-study results and the results of other trials; the potential for varying interpretations relating to the potential drivers of observed MACE reduction; ability to negotiate definitive contractual arrangements with potential customers; the impact of competitive product candidates; ability to obtain sufficient supply of materials; global economic and political conditions, including the Russia-Ukraine conflict, and the war in Israel; the effects of competition on NewAmsterdam’s future business; and those factors discussed in documents filed by the Company with the SEC. Additional risks related to NewAmsterdam’s business include, but are not limited to: uncertainty regarding outcomes of the company’s ongoing clinical trials, particularly as they relate to regulatory review and potential approval for its product candidate; risks associated with the Company’s efforts to commercialize a product candidate; the Company’s ability to negotiate and enter into definitive agreements on favorable terms, if at all; the impact of competing product candidates on the Company’s business; intellectual property-related claims; the Company’s ability to attract and retain qualified personnel; and the Company’s ability to continue to source the raw materials for its product candidate, together with the risks described in the Company’s filings made with the U.S. Securities and Exchange Commission from time to time. If any of these risks materialize or NewAmsterdam’s assumptions prove incorrect, actual results could differ materially from the results implied by these forward-looking statements. There may be additional risks that are presently unknown by the Company or that NewAmsterdam currently believes are immaterial that could also cause actual results to differ from those contained in the forward-looking statements. In addition, forward-looking statements reflect NewAmsterdam’s expectations, plans, or forecasts of future events and views as of the date of this Presentation and are qualified in their entirety by reference to the cautionary statements herein. NewAmsterdam anticipates that subsequent events and developments will cause the Company’s assessments to change. These forward-looking statements should not be relied upon as representing NewAmsterdam’s assessments as of any date subsequent to the date of this Presentation. Accordingly, undue reliance should not be placed upon the forward-looking statements. Neither NewAmsterdam nor any of its affiliates undertakes any obligation to update these forward-looking statements, except as 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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Today’s Agenda Corporate Update: Michael Davidson, MD, CEO, NewAmsterdam • Alzheimer’s Update • PREVAIL Update • Why is PREVAIL Derisked Science Update: John Kastelein, MD, PhD, FESC, CSO, NewAmsterdam • What we saw in BROADWAY (Subgroup Analysis) • Pooled/Updated MACE data • Particles Driving MACE • Lp(a) Driving MACE • Diabetes Commercial Update: BJ Jones, CCO, NewAmsterdam • Market Opportunity • Differentiated Product • HCP Preference • Commercial Launch Closing: Michael Davidson, MD, CEO, NewAmsterdam Q&A Date: June 11, 2025
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Secured funding to support US Commercial launch, if approved, with cash at 1Q25 of ~$810M Previous 18 Months Were a Time of Groundwork, Goals and Growth Published BROADWAY in NEJM Published TANDEM in The Lancet Announced Alzheimer’s topline Full AD data to be presented at AAIC 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 1H 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 4 2H 2025 EMA submission Completion of VINCENT Phase 2 trial
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Obicetrapib Observed to Impact Multiple Factors Associated with Cardiometabolic Disease 5 Note: NODM = New onset diabetes mellitus Lp(a) ↓ LDL-P ↓ Small LDL-P ↓ NODM ↓ HDL-C ↑ ApoA1 ↑ LDL-C ↓ Non-HDL-C ↓ ApoB ↓ sdLDL-C ↓ Obicetrapib
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lzheimer’s Update 6
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CETPi Bears Therapeutic Potential for Both Multi-infarct Dementia and lzheimer’s isease 7 Alzheimer's diseaseHealthy brain Alzheimer’s disease results in the generalized degeneration of the brain, with over 50M people affected WW and an economic burden of >$1 trillion (2) There is emerging evidence of a vascular component in multi-infarct dementia, implying that LDL-lowering would help reduce atherosclerosis in the brain (1) Multi-infarct dementia (ischemic stroke) Cortical shrinking Enlarged ventricles Shrinking of hippocampus Post-stroke necrosis Source: 1. M Kivipelto et al, Stroke, 2022: 53(2) 2. Alzheimer’s Disease International.
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+ Elevated Cholesterol Levels in the Brain Precede Formation of Amyloid- Beta ( β) 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 APOE, apolipoprotein E; CNS, central nervous system. Mahley RW. Arterioscler Thromb Vasc Biol. 2016;36(7):1305-1315.8 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
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Amyloid Beta (Aβ) and Tau Proteins Play Significant Roles in the Development and Progression of Alzheimer's Disease Amyloid (Aβ) plaques in cerebral spinal fluid Neurofibrillary tangles inside neurons Diseased neuron Disintegrating microtubules Tau particles (pTau; e.g., pTau 217, pTau 181) These significant issues in AD are caused by cholesterol dysregulation Oxidative stress Bioenergetic issues Myelination issues Inflammation issues Aβ plaques formation Neurofibrillary tangle formation BBB integrity Amyloid precursor is cleaved, releasing Aβ peptide Aβ peptide leaves membrane and aggregates Aβ plaque is formed Aβ peptide Cholesterol Cell membrane Cholesterol in membranes facilitates aggregation of Aβ peptides into amyloid plaques; improved clearance of cholesterol, therefore, may preempt progression of AD Aβ, amyloid β; AD, Alzheimer’s disease; BBB, blood brain barrier. 9 Aβ plaque formation inside AD brain cells AD is characterized by:
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poE4 is a isk Factor for Both CV and lzheimer’s isease1-5 % 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 Aβ, amyloid β; 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 2017. 4. Jeong W et al. Mol Cells. 2019;42(11):739-746. 5. Williams et al. BMC 2020.c 66% 10 APOE4 carriers exhibit 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 APOE4 carriers exhibit APOE4 Risk for CVD by 22-45% LDL-C HDL-C ApoC Lp(a)
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ApoE4 is the Strongest Genetic Risk Factor for Sporadic AD,1 With a Close Link to Increased pTau 217 Levels 0% 25% 50% 75% 100% 60 70 80 90 100 110 Percent free from lzheimer’s dementia Age P<0.0001 APOE 2/2 2/3 3/3 2/4 3/4 4/4 Age (years) 0.25 0.50 1.00Plasma pTau217, pg/mL0.75 8055 60 65 70 75 85 Noncarrier Carrier APOE4 status AAD, Alzheimer’s disease; APOE, apolipoprotein E. 1. Reiman EM et al. Nat Commun. 2020;11(1):667. 2. Reiman EM et al. Nat Commun. 2020;11(supplementary information):667. 2. Longitudinal trajectory of plasma pTau217 in cognitively unimpaired subjects according to APOE4 status. Interaction plot derived from linear mixed models of plasma pTau217 in healthy controls. Estimates come from the interaction effects of the best model for plasma pTau217. Predicted plasma pTau217 values are shown on the y -axis. The x- axis represents age in years. Colored lines are regression lines of APOE 𝜀4 carriers (blue) and noncarriers (teal), and the shaded area represents 95% CI. Age-related longitudinal trajectory was higher in APOE 𝜀4 carriers.11 Each copy of ApoE4 is associated with increased risk for AD. Therapies are needed that can slow down or prevent disease progression, particularly in ApoE4 carriers1 Plasma pTau217 levels by age according ApoE4 statusIncreased risk of lzheimer’s dementia for poE4 carriers and earlier in life1 65 Mean age in BROADWAY -1 SD +1 SD 65 Mean age in BROADWAY -1 SD +1 SD
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Plasma pTau217 is a Strong Predictor of AD Pathology 12 Specificity, % 0 20 100Sensitivity, % 80 20100 80 60 40 0 60 40 Plasma pTau217 (AUC=0.96) Plasma pTau181 (AUC=0.96) AD signature cortical thickness (AUC=0.78) Hippocampal volumes (AUC=0.74) Plasma NfL (AUC=0.50) pTau217 as a biomarker to assess AD progression Tangle density score 0 1 2 3 4 0 5 10 15 25Plasma pTau217, pg/mL 20 155 6 7 8 9 10 11 12 13 14 AD Non-AD pTau217 correlates with PET tangle density Source: Palmqvistet al. JAMA.2020;324(8):772–781.
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Recent News Further Validates pTau217 Levels Predict Presence of Amyloid Plaques in the Brain 13
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Obicetrapib is a Potent CETP Inhibitor Currently Being Studied for its Potential to Delay or Prevent AD in ApoE4 Carriers HDL LDL X Obicetrapib R AT I O N A L E Obicetrapib offers a mechanistically distinct approach that targets upstream lipid dysregulation vs downstream pathology AD, Alzheimer’s disease; APOE, apolipoprotein E; CETP, cholesteryl ester transfer protein; CSF, cerebrospinal fluid; HDL, hig h-density lipoprotein; LDL, low-density lipoprotein; MCI, mild cognitive impairment. Davidson MH et al. 2025. Manuscript in preparation.14 Unlike anti-amyloid therapies, obicetrapib addresses upstream lipid dysregulation, oxidation, and inflammation that may drive AD pathogenesis Phase 3 studies have shown the lipid-modifying ability of obicetrapib in >3000 patients with a favorable safety profile Key observations from a proof-of-concept study in 13 ApoE4 carriers with MCI and biomarker-proven AD: • Significant reductions in plasma and CSF levels of 24S- and 27-hydroxycholeterol • Increased levels of lipophilic antioxidants and carotenoids, in both plasma and CSF • Stabilization of key AD biomarkers, suggesting potential disease-modifying effects
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CETP Loss-of-Function (LoF) Genotype May be Associated with Slower Memory Decline and Lower AD Risk 15 Source :JAMA, January 13, 2010—Vol 303, No. 2 2 LoF CETP genes 1 LoF CETP gene Normal CETP CETP’s potential involvement in CNS cholesterol homeostasis is supported by genomic data CETP LoF may be associated with lower CETP activity & a corresponding increase in HDL levels
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Control diet 1% cholesterol diet WTCETP CETP transgenic mice have lower plasma HDL-C levels and increased brain cholesterol levels1 0 0.4 0.8 1.2 1.6 WT CETP WT CETP Cholesterol intensity 1% cholesterol dietControl diet P<0.05 P<0.05 0 0.5 1 1.5 2 2.5 0 20 40 60 80 100 Plasma LDL (mmol/L) NOR score (%) 0 1 2 3 0 20 40 60 80 100 Plasma HDL (mmol/L) NOR score (%) r2=0.5837 P=0.015 r2=-0.4042 P=0.0365 + HDL correlation - LDL correlation A separate study demonstrated that CETP inhibitors can enter the brain4 Novel object discrimination ratio (%) 100 60 40 80 10 0 WT P=0.0376 50% Cognitive impairment CETPAPP APP/CETP P=0.0435 Vehicle CETP inhibitor (Evacetrapib) Increased CETP demonstrates 22% increased brain cholesterol levels on high cholesterol diet CETP Knock-in Mice Have Increased Brain Cholesterol Levels and CETPi Observed to Rescue Cognition in Preclinical Models of CETP-induced AD1-3 16 CETP inhibition with evacetrapib led to cognitive improvement 2,3 Plasma Lipoproteins Were Correlated With NOR Score Positive correlation observed between NOR score and HDL quantification in CETP and APP/CETP-expressing female mice Negative correlation observed between NOR score and LDL quantification in CETP and APP/CETP-expressing female mice AD, Alzheimer’s disease; APP, amyloid precursor protein; CETP, cholesterol ester transfer protein; CETPi, CETP inhibitor; HDL, high-density lipoprotein; HDL-C, high-density lipoprotein cholesterol; LDL, low-density lipoprotein; NOR, novel object recognition; WT, wild-type. 1. Oestereich F et al. J Lipid Res. 2022;63(9):100260. 2. Phénix J et al. Alzheimer’s Dement. 2021;17(suppl3):e051134. 3. Phénix J et al. Poster presented at: Alzheimer’s Association International Conference; July 26-30, 2021; Denver, USA. 4. Phénix J et al. Front Pharmacol. 2023;14:1171937.
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Safety FU Safety FU Obicetrapib on Top of Max Tolerated Lipid-Modifying Therapy: lzheimer’s Biomarker Sub-study Placebo (n=800) Objective: To evaluate the effect of obicetrapib on biomarkers related to Alzheimer’s Disease compared to placebo over 12-months Visit: Days: 1 -28 to -1 6 270 2 1 4 84 3 30 Labs, PK Safety Labs, Safety Labs, PK Safety Eligibility: Labs, Safety 7 365 Labs, PK Safety Study design: Randomized, double-blind, placebo-controlled Main Inclusion Criteria: • CV disease < 3 months • HoFH • Uncontrolled hypertension Main Exclusion Criteria: Biomarker Endpoints: • p-tau217 (primary outcome measure) • Ratio of Aβ42 to Aβ40 (Aβ42/Aβ40) • GFAP • NFL • p-tau181 . Obicetrapib 10mg (n=1600) • Patients (n=2400) • HeFH and or ASCVD • ≥ 18 years • Baseline LDL-C: 98 mg/dL 5 180 Labs, PK Safety Baseline 8 +35 Vitals, conmeds, AEs assessed Endpoint Have a fasting serum LDL-C at Screening (Visit 1) as follows: • Have a fasting serum LDL-C ≥ 55 mg/dL (≥ 1.4 mmol/L) to <100 mg/dL (<2.6 mmol/L) OR non-HDL- C ≥ 85 mg/dL (≥ 2.2 mmol/L) to <130 mg/dL (<3.4 mmol/L) with at least 1 risk enhancer OR • Have a fasting serum LDL-C ≥ 100 mg/dL (≥ 2.6 mmol/L) OR non-HDL-C ≥ 130 mg/dL (≥ 3.4 mmol/L). 17
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What’s Next for Obicetrapib and lzheimer’s isease? Full data to be presented as an oral presentation in a Developing Topics session At the 2025 Alzheimer’s Association International Conference 18 “Today’s report from NewAmsterdam is incredibly promising and points to a future of powerful combination therapies that address the key aspects of the disease from a variety of angles, and the distinct possibility of effective prevention strategies.” “Reducing the progression of Alzheimer’s biomarkers suggests the potential to significantly alter the course of the disease, certainly in the studied population.” - lzheimer’s ssociation
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Obicetrapib Observed to Impact Multiple Factors Associated with Cardiometabolic Disease 19 Note: NODM = New onset diabetes mellitus Lp(a) ↓ LDL-P ↓ Small LDL-P ↓ NODM ↓ HDL-C ↑ ApoA1 ↑ LDL-C ↓ Non-HDL-C ↓ ApoB ↓ sdLDL-C ↓ Obicetrapib
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The Future of Hyperlipidemia Treatment Goes Beyond LDL-C 20 Note: NODM = New onset diabetes mellitus ApoE4 LDL-P ↓ Small LDL-P ↓ NODM ↓ HDL-C ↑ ApoA1 ↑ LDL-C ↓ Non-HDL-C ↓ ApoB ↓ sdLDL-C ↓ Lp(a) ↓ Obicetrapib
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PREVAIL Update 21
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BROADWAY and TANDEM Publications Outline Obicetrapib’s Potential Impact on LDL-C and Beyond 22 “We already have other effective LDL-C and ApoB lowering non-statins, so I am particularly impressed with the impact on small LDL-P, Lp(a) and NODM which is unique to obicetrapib.” – Cardiologist, Massachusetts “Obicetrapib could be the future of LDL-C lowering and could potentially replace PCSK9i mAb given the beneficial effects demonstrated on other lipoproteins beyond just LDL-C and ApoB reduction.” – Cardiologist, Ohio “The magnitude of Lp(a) reduction in BROOKLYN, BROADWAY and TANDEM could get patients with very high Lp(a) levels into the ‘normal’ range.” This is a huge advantage for obicetrapib that other existing LD-C lowering agents cannot achieve.” – Cardiologist, Pennsylvania “If the MACE benefit in PREVAIL follows the early MACE benefit shown in BROADWAY, there is no doubt obicetrapib could be positioned ahead of all other non-statins given the exceptional tolerability and oral route.” – Internal Medicine, Ohio
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PREVAIL Designed to Apply Lessons Learned from Previous CVOTs to educe isk and emonstrate Obicetrapib’s Full Benefit 23 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
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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 24 • 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: 70% • Ezetimibe: 23% • PCSK9i: 2% • SGLT2i: 14% • GLP-1: 6%
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Similar Patient Demographics Between BROADWAY and PREVAIL 25 Placebo N=844 Obicetrapib 10 mg N=1686 All N=9541 Mean Age (years) 65.3 65.4 65.0 <65 years 360 (42.7) 706 (41.9) 4266 (44.7) 65 to 74 years 352 (41.7) 683 (40.5) 3732 (39.1) 75+ years 132 (15.6) 297 (17.6) 1543 (16.2) Sex (F) n (%) 280 (33.2) 573 (34.0) 2952 (30.9) Region n (%) North America 313 (37.1) 591 (35.1) 3573 (37.4) Eastern Europe 282 (33.4) 580 (34.4) 2232 (23.4) Western Europe 104 (12.3) 213 (12.6) 2108 (22.1) Asia 145 (17.2) 302 (17.9) 1315 (13.8) Other1 -- -- 313 (3.3) Race n (%) White 647 (76.7) 1241 (73.6) 7986 (83.7) Asian 150 (17.8) 312 (18.5) 1044 (10.9) African American 39 (4.6) 112 (6.6) 397 (4.2) Other 8 (1.0) 21 (1.3) 114 (1.1) Source: Data on file | 1. South Africa and Australia
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Similar Patient emographics Between B O W and P EV IL (Cont’d) 26 Placebo N=844 Obicetrapib 10 mg N=1686 All N=9541 Height (cm) 170.1 169.9 169.9 Weight (kg) 86.3 85.2 86.3 BMI (mean) 29.7 29.4 29.8 < 25 kg/m² 162 (19.2) 352 (20.9) 1573 (16.5) 25 - 30 kg/m² 334 (39.6) 657 (39.0) 3906 (40.9) > 30 kg/m² 346 (41.0) 676 (40.1) 4042 (42.4) Missing 20 (0.2) Diabetes n (%) 336 (39.8) 624 (37.0) 3607 (37.8) HeFH 143 (16.9) 284 (16.8) N/A Statin n (%) 782 (93.0) 1533 (91.0) High Intensity 581 (68.8) 1152 (68.3) 70% Low or Moderate Intensity 201 (23.8) 381 (22.6) 22% None 62 (7.3) 153 (9.1) 8% Ezetimibe n (%) 220 (26.1) 453 (26.9) 2150 (22.5) PCSK9i n (%) 33 (3.9) 62 (3.7) 187 (2.0) GLP1 n (%) 48 (5.7) 111 (6.6) 540 (5.7) SGLT2 n (%) 92 (10.9) 188 (11.2) 1360 (14.2) Source: Data on file
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PREVAIL Selection of 4-Point MACE 27 General concepts for using a composite endpoint for regulatory filing: • Composite endpoints are used to aggregate events with a similar etiology in a way to increase the power of the study to be able to detect a statistically significant difference for the treatment under investigation. However, the composite endpoint must meet certain criteria: • The individual components of the composite endpoint should host clinically meaningful endpoints for the disease under investigation (in this case, atherosclerotic disease) • Individual components are expected to react similarly to the therapy under investigation, which means the expected relative risk reduction for each component is expected to be the same. – The individual components of the 4-point MACE endpoint – CHD death, non-fatal MI, fatal and non-fatal ischemic stroke, coronary revascularization – have proven to consistently show similar relative risk reduction for each component in previously conducted LDL-C lowering trials irrespective of the MOA for the treatment under investigation 3-Point MACE (CHD death, non-fatal MI, coronary revascularization) • Uncommon composite endpoint compared to previously conducted LDL-C lowering trials • Regulatory agencies, including the FDA, will conduct an independent assessment for various composite CV endpoints which will include the composite of fatal and non-fatal stroke 4-Point MACE (CHD death, non-fatal MI, fatal and non-fatal ischemic stroke, coronary revascularization) • Commonly accepted composite • Provides greater power to detect a robust statistically significant difference for the number of patients included in PREVAIL as in comparison to 3-point MACE this composite will generate more CV events
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Obicetrapib and Cardiovascular Events 28
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Exploratory Endpoint: Major Adverse Cardiovascular Events (MACE) 29 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) Coronary heart death – no. (%) 5 (0.6) 8 (0.5) 0.80 (0.26-2.44) First 4-point MACE – no. (%) 44 (5.2) 70 (4.2) 0.79 (0.54-1.15) 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 may be limitations on the interpretation of MACE data der ived from both BROOKLYN and BROADWAY studies given they were not designed to assess MACE as the primary and secondary endpoints. Placebo N = 962 Obicetrapib N= 1920 Hazard Ratio 95% CI All-cause mortality – no. (%) 14 (1.5) 20 (1.0) 0.78 (0.39-1.58) Coronary heart death – no. (%) 7 (0.7) 9 (0.5) 0.63 (0.24-1.70) First 4-point MACE – no. (%) 49 (5.1) 75 (3.9) 0.75 (0.53-1.08) BROADWAY + BROOKLYN Pooled MACE Data (1) BROADWAY MACE Data(1)
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Consistent Trend in MACE Across Multiple Components 30 BROADWAY BROOKLYN Pooled Cardiovascular events – no. (%) Obicetrapib Placebo Obicetrapib Placebo Obicetrapib Placebo Death from CHD, nonfatal MI, stroke, or coronary revascularization 70 (4.2) 44 (5.2) 5 (2.1) 5 (4.2) 75 (3.9) 49 (5.1) Death from CHD 5 (0.3) 4 (0.5) 1 (0.4) 2 (1.7) 6 (0.4) 6 (0.6) Nonfatal MI 20 (1.2) 11 (1.3) 1 (0.4) 0 (0.0) 21 (1.1) 11 (1.1) Stroke 14 (0.8) 5 (0.6) 1 (0.4) 0 (0.0) 15 (0.7) 5 (0.5) Coronary revascularization 31 (1.8) 24 (2.8) 2 (0.9) 3 (2.5) 33 (1.7) 27 (2.8) Pooled MACE Components
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Kaplan-Meier Curve Separates at Day 200 Driven by Attenuation of Events in the Obicetrapib Arm 31 4-point MACE: CHD death, Non-fatal myocardial infarction, non-fatal stroke, coronary revascularization Note: While not powered to detect a MACE benefit, we observed positive MACE data as part of our review of the exploratory end point. 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. Kaplan Meier Curve Landmark Analysis: Censored at 6 months
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Explaining B O W ’s Observed 21% M CE Reduction Based on the CTT line, the expectation for a 33% reduction in LDL-C from placebo would be a 9% MACE reduction, after 12 months The observed reduction was 21% after 12 months What is driving this greater than expected observed reduction? 32 LDL-C Alone Additional Reduction 9% 12% Obicetrapib’s Observed M CE Reduction 21% Potential Drivers Observed MACE Source: Cholesterol Treatment Trialists Collaboration. Lancet. 2010 376:1670 -81 Circulation. 2021;144:e564–e593 17065: Obicetrapib Lowers LDL-C in Patients Taking High Intensity Statins 1. PI Zetia table 7. refers to; Gagne, C et al. Am J Cardiol 2002. LDL-C measured only using Friedewald 2. PI Nexletol; study
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Residual LDL Particle Risk 33
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• Small dense LDL particles are more likely to be trapped in arterial wall than larger-sized LDL particles • High LDL-P levels typically signify that a patient has a higher proportion of small dense LDL particles vs. larger-sized LDL particles High LDL-P, Low LDL-C (n = 282) High LDL-P, High LDL-C (n = 1,251) Years of follow-up Event-free survival Low LDL-P confers a lower risk — even in patients with high LDL-C LDL-P Believed to be One of the Most Robust Predictors of Cardiovascular Risk LDL-P is observed to be a significantly better predictor of CV risk than LDL-C Even though all LDL particles contain only one ApoB protein, small dense LDL particles have less ApoB mass Low LDL-P, Low LDL-C (n = 1,249) Low LDL-P, High LDL-C (n = 284) Source: Cromwell WC, et al. Clin Lipidol. 2007 December 1; 1(6): 583–59234 = Larger-sized LDL = Small dense LDL High LDL-P confers a higher risk — even in patients with low LDL-C LDL-P LDL-C
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LDL Particles are a Strong Predictor of Risk 35 Cole, TG et al. Association of Apolipoprotein B and Nuclear Magnetic Resonance Spectroscopy –Derived LDL Particle Number with Outcomes in 25 Clinical Studies: Assessment by the AACC Lipoprotein and Vascular Diseases Division Working Group on Best Practices; Clinical Chemistry 59:5 000– 000 (2013)
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Obicetrapib Preferentially Reduces Small LDL Particles 36 Note: BROADWAY at Day 365, BROOKLYN at day 180, TANDEM at day 84. All percent reductions placebo adjusted Parameter Pooled (n=2538) BROADWAY (n=2041) BROOKLYN (n=239) TANDEM (n=182) Baseline LDL-P (nmol/L) 988.9 923.8 1224.9 1195.4 Baseline small LDL-P 662.2 647.4 680.8 792.2 Percent reduction LDL-P 40.1% 36.3% 52.5% 60.1% Percent reduction small LDL-P 100.6% 103.2% 102.4% 93.7%
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Changes in LDL-P Associated with Increased Risk 37 Study name Cromwell et al 2007 Otvos et al 2011 Otvos et al 2006 Lawler et al 2017 Fixed-Effects Model HR (95% CI) 0.75 1.50 2.00 A one standard deviation increase in LDL-P is associated with a 28% increase in cardiovascular events 1.00 1.75 Hsia et al 2008 n 3066 6814 1061 11984 404 events 431 319 364 296 202 Hsia et al 2008 304 152 1.25 Source: Quseda et al, Atherosclerosis 35 (2023) 165-177 weight 37.38% 25.18% 16.92% 12.70% 4.48% Risk [95% CI] 1.28 [1.17, 1.40] 1.35 [1.21, 1.51] 1.20 [1.05, 1.37] 1.19 [1.02, 1.39] 1.40 [1.08, 1.81] 3.34% 1.31 [0.97, 1.77] 100.00% 1.28 [1.21, 1.35]
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As Particle Numbers Rise, Risk Increases 38 *CDC Death + NFMI + Stroke + Coronary Revasc*CDC Death + NFMI + Stroke + Coronary Revasc Obicetrapib has greater benefit on smaller particles Cumulative incidence of MACE* in the placebo group by baseline total LDL-P, ITT population spline P=0.14 Cumulative incidence of MACE* in the placebo group by baseline Total LDL-P, ITT population spline P=0.14
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LDL-P Contributors to MACE 39 Source: Folse et al. Athero 2014, Quseda et al, Atherosclerosis 35 (2023) 165-177, Data on file Treatment of particles has been associated with a 6-8% additional MACE reduction in high-risk individuals above LDL-C alone Based on the observed LDL-P reduction in BROADWAY , we would estimate a 15% decrease in MACE events vs 9% for LDL-C alone We observed a HR of 0.84 based on LDL-P, again 7% greater than the 0.91 based on LDL-C alone The average of these three methods is an additional 6% reduction from LDL-P LDL-C Alone LDL Particles 9% 6% Obicetrapib’s Observed MACE Reduction 21% 6% Potential Drivers Observed MACE Additional Reduction Methods of Estimating MACE Reduction 1 2 3
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Residual Lp(a) Risk 40
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Lp(a) Concentrations Have Been Associated with Risk of ASCVD Lp(a) distribution in general population extrapolated from the graph Prevalence 20% 10% 5% 1% <0.1% Lp(a) levels 60 mg/dL 90 mg/dL 116 mg/dL 180 mg/dL 245 mg/dL Number (US) 64,000,000 32,000,000 16,000,000 3,200,000 320,000 Number (EU) 150,000,000 75,000,000 37,500,000 7,500,000 750,000 Globally 1,400,000,000 700,000,000 350,000,000 70,000,000 7,000,000 Estimated prevalence assumes 320 million in US, 750 million in EU and 7 billion globally Even with high prevalence, there are currently no pharmacologic therapies approved for reducing Lp(a) Source: Berman et al JACC VOL. 83, NO. 9, 2024 Lp(a) and Baseline ASCVD Status FIGURE 5 The Association of Lp(a) With the Primary Composite Outcome Based on ASCVD Status ASCVD MARCH 5, 2024:873–886 Patel AP, et al. Arteriosclerosis, Thrombosis, Vascular Biology.2021;41:465 Note: Lp(a) is not yet considered a validated surrogate endpoint by the FDA.41 0 1000 2000 3000 4000 Lp(a), nmol/L 0 200 400 Gray shaded area (> 200 nmol/L) Inclusion criteria for Amgen (olpasiran; siRNA) 50-150 nmol/L Red shaded area (> 150 nmol/L) Inclusion criteria for HORIZON Study (pelacarsen; Novartis; ASO) Green shaded area (> 175 nmol/L) Inclusion criteria for Lilly (lepodisiran; siRNA) Target obicetrapib patients (Lp(a) 50-150 nmol/L) Blue shaded area (<65 nmol/L): US Recommendation represents negligible risk for CVD and CAVS 600 Lp(a) percentile groups Lp(a) levels 1st-50th 0-41 nmol/L 51st-70th 42-111 nmol/L 71st-90th 112-215 nmol/L 91st-100th ≥216 nmol/L
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Increased Risk Begins at Lp(a) Levels as Low as 40 nmol/L 42 Source: Berman, A, Biery, D, Besser, S. et al. Lipoprotein(a) and Major Adverse Cardiovascular Events in Patients With or Wit hout Baseline Atherosclerotic Cardiovascular Disease. JACC. 2024 Mar, 83 (9) 873–886. Association of Lp(a) percentile group with the primary composite outcome, ASCVD patients A Composite endpoint of major adverse cardiovascular event for individuals with and without baseline ASCVD
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Significant Risk for ASCVD Patients Between 50 nmol/L and 150 nmol/L 43 Restricted cubic spine modeling the association of continuous lipoprotein(a) levels on the primary composite outcome (myocardial infarction, ischemic stroke, coronary revascularization, cardiovascular mortality) among individuals with a history of ASCVD (A) and among those without a history of ASCVD (B). Knots were set at 41nmol/L (50th percentile – reference), 111 nmol/L (70th percentile), and 215 nmol/L (90th percentile), and the splines are truncated at the 99th percentile (310 nmol/L). Abbreviations as in Figure 2. Source: Berman, A, Biery, D, Besser, S. et al. Lipoprotein(a) and Major Adverse Cardiovascular Events in Patients With or Without Baseline Atherosclerotic Cardiovascular Disease. JACC. 2024 Mar, 83 (9) 873–886.
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Lp(a) Reduction of 45% in Key Patient Population 44 Parameter Pooled (n=2538) BROADWAY (n=2041) BROOKLYN (n=315) TANDEM (n=182) Baseline Lp(a) 42.7 (12.3, 171.4) 42.6 (12.2, 170.1) 45.0 (14.1, 178.5) 38.9 (11.2, 187.2) Percent change Lp(a) Baseline Lp(a) ≥50 nmol/L -22.5 (-25.7, -19.3) -21.4 (-24.9, -18.0) -29.2 (-39.8, -18.5) -24.8 (-38.0, -11.6) Baseline Lp(a) 50-<150 nmol/L -44.8 (-50.7, -38.9) -42.8 (-49.5, -36.1) -52.2 (-70.6, -33.7) -52.4 (-73.5, -31.3) Baseline Lp(a) ≥150 nmol/L -12.8 (-15.7, -9.9) -12.6 (-15.9, -9.3) -13.3 (-21.2, -5.3) -12.6 (-25.9, 0.6) Absolute change Lp(a) (nmol/L) Baseline Lp(a) ≥50 nmol/L -35.0 (-39.6, -30.3) -33.6 (-38.7, -28.4) -39.8 (-53.8, -25.8) -40.0 (-61.2, -18.7) Baseline Lp(a) 50-<150 nmol/L -37.4 (-42.0, -32.7) -35.8 (-40.9, -30.7) -43.5 (-60.4, -26.6) -43.4 (-63.4, -23.4) Baseline Lp(a) ≥150 nmol/L -33.1 (-41.0, -25.2) -31.7 (-40.7, -22.7) -37.3 (-21.2, -5.3) -35.2 (-76.0, 5.7) Source: Data on file
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Pooled BROADWAY, BROOKLYN, and TANDEM effects on Lp(a) 45 -22.5 -44.8%-50 -35 -20 -5 ≥50 nmol/L 50 to <150 nmol/L Baseline Lp(a) Level -35.0 -37.4-40 -25 -10 Median percent change Median change, nmol/L ≥50 nmol/L 50 to <150 nmol/L Baseline Lp(a) Level Percentage Lp(a) reduction Absolute Lp(a) Reduction
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Mediation Analysis Predicts 26% of MACE Reduction from Lp(a) in BROADWAY Multivariate Mediation of OBI MACE Reduction A mediation analysis was performed to identify the proportion of the observed 21% reduction in cardiovascular events potentially attributable to Lp(a) Based on the analysis, we predict approximately 26% of the overall change in MACE could be explained by reduction in Lp(a) 26.1% 0% 20% 40% Lp(a) Mediation of MACE, % Source: Data on file
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Lp(a) Contributors to MACE 47 LDL-C Alone Lp(a) 9% 5%21% 7% Based on observational studies a 100 nmol/L reduction in the Lp(a) should equate to a 22% MACE reduction • In BROADWAY we see an ~35 nmol/L reduction, predicting 8% reduction in risk of MACE at two years or a 4% reduction at one year Mediation analysis predicts 5% contribution from Lp(a) Based on these two methods we estimate approximately 4-5% of absolute incremental benefit is attributable to Lp(a) Potential Drivers Observed MACE Additional Reduction Methods of Estimating MACE Reduction Obicetrapib’s Observed MACE Reduction 1 2 Source: Berman, A, Biery, D, Besser, S. et al. Lipoprotein(a) and Major Adverse Cardiovascular Events in Patients With or Wit hout Baseline Atherosclerotic Cardiovascular Disease. JACC. 2024 Mar, 83 (9) 873–886; Data on file.
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Cumulative Effect 48
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The Future of Hyperlipidemia Treatment Goes Beyond LDL-C 49 Note: NODM = New onset diabetes mellitus ApoE4 LDL-P ↓ Small LDL-P ↓ NODM ↓ HDL-C ↑ ApoA1 ↑ LDL-C ↓ Non-HDL-C ↓ ApoB ↓ sdLDL-C ↓ Lp(a) ↓ Obicetrapib
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Explaining B O W ’s Observed 21% M CE Reduction 50 Based on the CTT line, the expectation for a 33% reduction in LDL-C from placebo would be a 9% MACE reduction, after 12 months LDL-P potentially provides 6-7% additional MACE reduction, mainly driven by small LDL-P Lp(a) potentially provides an additional 5% MACE reduction These elements may not be additive as they are correlated to some extent. In this scenario, there is room for additional reduction to be driving incremental gains LDL-C Alone LDL-P 9% 21% 1% Lp(a)5% 6% Potential Drivers Observed MACE Additional Reduction Obicetrapib’s Observed M CE eduction Methods of Estimating MACE Reduction Note: Actual results may differ from hypothetical calculation. Source: Cholesterol Treatment Trialists Collaboration; Folse et al. Athero 2014, Quseda et al, Atherosclerosis 35 (2023) 165-177; Berman, A, Biery, D, Besser, S. et al. Lipoprotein(a) and Major Adverse Cardiovascular Events in Patients With or Without Baseline Atherosclerotic Cardiovascular Disease. JACC. 2024 Mar, 83 (9) 873–886; Data on file ** MACE includes CHD death, myocardial infarction, ischemic stroke and coronary revascularization in adults.
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LDL-C Reduction Alone Supports 20% Estimated MACE Benefit in PREVAIL 51 Note: Actual results may differ from hypothetical calculation. Assumes PREVAIL basline of 103 mg/dL LDL-C Source: Cholesterol Treatment Trialists Collaboration. Lancet. 2010 376:1670 -81 Circulation. 2021;144:e564–e593 17065: Obicetrapib Lowers LDL-C in Patients Taking High Intensity Statins 1. PI Zetia table 7. refers to; Gagne, C et al. Am J Cardiol 2002. LDL-C measured only using Friedewald 2. PI Nexletol; study 2. refers to; Goldberg, A et al. JAMA 2019;322(18):1780-1788. LDL-C measured using Friedewald and direct assay for LDL-C <50 mg/dL. 3. multiple studies: Blom, D et al. N Engl J Med 2014; Kereiakes, D et al. Am Heart J 2015.; Ray, K. N Engl J Med 2020. (1) Represents estimated average baseline LDL to be enrolled, not entry criteria. ** MACE includes CHD death, myocardial infarction, ischemic stroke and coronary revascularization in adults. CVOT MACE Benefit PCSK9s (1) 15% Bempedoic Acid (2) 13% Ezetimibe (3) 7% LDL-C reduction placebo adjusted Estimated MACE Benefit 25.0% 15.3% 27.5% 16.9% 30.0% 18.4% 32.5% 19.9% 35.0% 21.5% 37.5% 23.0% 40.0% 24.5% 42.5% 26.1% 45.0% 27.6% 47.5% 29.2% 50.0% 30.7% 0% 5% 10% 15% 20% 25% 30% 35% MACE Reduction 0 10 20 30 40 50 60 70 LDL-C Mean absolute LDL-C reduction between groups (mg/dL)
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Residual Diabetes Risk 52
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CETP Inhibition Demonstrates Potential to Improve β Cell Function 53 Blocking CETP increases HDL levels2 High HDL levels protect β cells by1: • Combating cellular lipid accumulation • Reducing ER stress • Preventing apoptosis High HDL levels also promote1,3: • Insulin secretion from β cells • Glucose uptake in peripheral tissues CETP inhibitor Adipose tissue Plasma glucose Skeletal muscle glucose uptake by myocytes Pancreas β cell ABCA1 ABCG1 ER stress Insulin production β cell apoptosis Insulin secretion High HDL/ApoA1 levels associated with less adipose tissue4 ABCA1, ATP-binding cassette transporter; ABCG1, ATP-binding cassette subfamily G member 1;ApoA1, apolipoprotein A1; CETP, cholesteryl ester transfer protein; ER, endoplasmic reticulum; HDL, high-density lipoprotein. 1. Siebel AL et al. Front Pharmacol. 2015;6:258. 2. Mabuchi H et al. Mol Cells. 2014;37(11):777-784. 3. Fryirs MA et al. Arterioscler Thromb Vasc Biol. 2010;30(8):1642-1648. 4. Therapeutic areas. NewAmsterdam Pharma. Accessed February 16, 2024. https://www.newamsterdampharma.com/therapeutic-areas
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Increases in HDL-C Reduce the 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 54 HDL-C, high-density lipoprotein cholesterol; T2DM, type 2 diabetes mellitus. Cao X et al. Lipids Health Dis. 2021;20(1):71. Association between HDL-C levels and T2DM risk for baseline levels of HDL-C (mmol/L) Reduced risk of diabetes incidence with increased HDL-C levels
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Statins Caused a Dose-dependent Increase in New Diagnosis of Type-2 Diabetes Irrespective of Age, Sex, BMI and Blood Sugar Levels 55 Events (% per annum) Observed-expected Statin (n=9935) Placebo (n=9895) o-e Var (o-e) Rate ratio (CI) Favors statin Favors placebo High-intensity statin Diabetes-related adverse events 246 (0.9) 174 (0.7) 37.0 105.0 1.42 (99% CI 1.11-1.83) Diabetes determined from co- medication 198 (0.8) 159 (0.6) 20.1 89.2 1.25 (99% CI 0.95-1.64) Subtotal: diabetes-related adverse events and co-medications 297 (1.1) 229 (0.9) 35.1 131.5 1.31 (95% CI 1.10-1.55) Biochemically determined diabetes 1078 (4.1) 788 (3.0) 149.3 465.7 1.38 (99% CI 1.22-1.55) Any new-onset diabetes 1221 (4.8) 905 (3.5) 163.9 530.8 1.36 (95% CI 1.25-1.48) 1.0 1.250.80.6 1.50 2.00 Source: Cholesterol Treatment Trialists’ (CTT) Collaboration. Lancet Diabetes Endocrinol 2024 High-intensity statin regimen resulted in a 36% increased risk of new -onset diabetes
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Obicetrapib 10 mg Reduced HbA1c Among Patients Without Diabetes and Demonstrated a Consistent Trend Toward Lower Risk of NoD in Patients with both Normoglycemia and Prediabetes at Baseline 56 ~70% of patients were on high intensity statins Source: National Lipid Association Conference 2025 (data on file)
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CETP Inhibition Has the Potential to Reverse Diabetes Risk, Potentially Ameliorating Key Concerns About High Dose Statins 57 Study name ILLUMINATE Dal-OUTCOMES ACCELERATE REVEAL Random-Effects Model HR (95% CI) 0.55 0.82 1.2 This is consistent with the effects seen 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) Source: National Lipid Association Conference 2025 (data on file)
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Safety FU Safety FU T2D/Metabolic Syndrome Study - RUBENS 58 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:
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Commercial Update 59
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Setting the Stage for Obicetrapib's Transformational Launch 60 1. Market Opportunity 2. Differentiated Product 3. HCP Preference 4. Commercial Launch
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Setting the Stage for Obicetrapib's Transformational Launch 61 2. Differentiated Product 3. HCP Preference 4. Commercial Launch 1. Market Opportunity
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Tailwinds are Making Lipid Lowering Space More Conducive to Commercial Success 62 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 Observations 3 Guidelines* have shifted to recommend more intense 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. Grundy SM, et al. J Am Coll Cardiol. 2019;73(24):3168-3209. 2. Lloyd-Jones DM, et al. J Am Coll Cardiol. 2022;80(14):1366-1418 3. 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 Repatha® growth continues to accelerate 10 years post launch with +47% Rx growth in the last 12 months 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
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Resulting in Continued Growth and Acceleration of Brand Use 63 Source: Based on third party prescription data on file 1. All Lipid Lowering therapies: Statins, Ezetimibe and combinations; PCSK9 and BPA; 2. Non-Statins : Ezetimibe and combinations; PCSK9 and BPA; 3. Branded: PCSK9 and BPA; 4. Merative Marketscan Claims Linked with Lab Data, 2019 - 2022, 12 months continuous data for each patient (6 months LB and 6 months LF from 1st observed statin treatment) Growth of 3.7% in 2024, which is the equivalent of 9 million additional TRx’s over 2023 5 years of consecutive growth Non-statins growing at high double digits Branded agents growing even faster 241MM 247MM 256MM 210MM 220MM 230MM 240MM 250MM 260MM 2022 2023 2024 14.7MM 17.2MM 20.6MM 0.0MM 5.0MM 10.0MM 15.0MM 20.0MM 2022 2023 2024 17.2% Growth 20.2% Growth 2.4% Growth 3.7% Growth 3.0M 3.7M 4.9M 0M 1M 2M 3M 4M 5M 6M 2022 2023 2024 26.0% Growth 31.9% Growth72 million1 Adults in US diagnosed with hypercholesterolemia ~10 million Diagnosed patients not treated with statin or LLT ~30 million Not at goal Over 40 million patients undertreated/ not treated Non-statin2 TRx Branded3 TRxLipid lowering Therapy TRx1Lipid lowering Therapy TRx4 2 3 41
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Guidelines are Being Updated for More Aggressive Intervention 64 2019 2020 2021 2022 LDL-C threshold of 55 mg/dL for the addition of nonstatin therapy among patients receiving maximally tolerated statin therapy2 2018 LDL-C threshold of 70 mg/dL for the addition of nonstatin therapy among patients receiving maximally tolerated statin therapy1 2023 2024 LDL-C threshold of 55 mg/dL for the addition of nonstatin therapy among hospitalized patients with ACS receiving maximally tolerated statin therapy * 2025 1Grundy/2019/pe296/ Fig 1 2Llloyd-Jones/2022/p1385/ Fig 2A2 3Sunil V. Rao, MD, FACC, FSCAI et al AHA/ACC=American Heart Association/American College of Cardiology; ASCVD= atherosclerotic cardiovascular disease; LDL -C=low density lipoprotein-cholesterol 1. Grundy SM, et al. J Am Coll Cardiol. 2019;73(24):3168-3209. 2. Lloyd-Jones DM, et al. J Am Coll Cardiol. 2022;80(14):1366-1418 3. 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 Guidance for very high-risk ASCVD patients:
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U.S. Regulators are Recognizing Unmet Need in LDL-C Lowering and Acting to Address It 65 Language in LLT labels has evolved in recent years, reducing access restrictions and setting the stage for expanded use for treatments beyond statins Indication / usage updates1,2,3 Previous: Updated: “Adjunct to diet and maximally tolerated statin therapy for the treatment of adults with HeFH or clinical ASCVD, who require additional lowering of LDL-C. ” “Adjunct to diet and statin therapy for the treatment of adults with primary hyperlipidemia, including HeFH, to reduce LDL-C” July 2023 “Adjunct to diet and maximally tolerated statin therapy for the treatment of adults with HeFH or established ASCVD who require additional lowering of LDL-C” “As an adjunct to diet, in combination with other LDL-C lowering therapies, or alone when concomitant (LDL-C) lowering therapy is not possible to reduce LDL-C in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (HeFH)” March 2024 1. Integrated reviews, Nexletol and Nexlizet 2. Leqvio (inclisiran). Prescribing information. Novartis; 2024 and 2023.; Nexletol (bempedoic acid). Prescribing information. Esperion Therapeutics Inc; 2024 and 2023. 3. HeFH, ASCVD, LDL-C are fully spelled out in label
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• 2015-2018 Repatha® approval rate: 54.1%1 • 2022 Repatha® approval rate: 87.5%1 • Repatha® PCP writer base grew 31% adding almost 24,000 new PCP writers in the last 12 months Critical Factors Improving Branded Market Dynamics 66 ACCESS Changes in payer reimbursement has seen significant increases in approval rates and decreases in rejection rates1,2 PROMOTION Increased product promotion and omnichannel brand marketing has enabled impactful awareness building and driven uptake PRESCRIBERS Widening prescriber target beyond specialists is expanding base to reach more HCPs treating patients in need of new LLT interventions • Repatha® reinitiated DTC (branded/unbranded) in May 2024 with a run rate of ~$60M per annum* • ~300 customer facing roles in 2022 increased to 600+ by 1Q 2025* 1.Circ Cardiovasc Qual Outcomes. 2024;17:e009988 2.. Based on third party prescription data on file * Competitive intelligence – data on file
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… and Leading to ccelerated Growth 67 2024 worldwide revenue of $2.2 Billion US revenues of $1.1 Billion WW PCSK9 class is approaching $4 Billion 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 2015 2016 2017 2018 2019 2020 2021 2022 2023 2024 TRx Volume (Millions) Approx. 5 Years to 1MM x’s / ear Approx. 2 Years to 2MM x’s / ear Approx. 2 Years to 4MM x’s / ear 1 2 3 2X GROWTH Repatha® volume continues 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
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Industry Agrees that the Outlook is Bullish 68 “We believe that AZD0780 has the potential to be a $5 billion-plus asset and an important option for patients who urgently need novel approaches to improve their outcomes.” Sharon Barr, EVP Astra Zeneca - BioPharmaceuticals R&D Astra Zeneca2Merck1 Turning to MK-0616[…] So you provide the same efficacy, similar efficacy to the injectables in a way that is simple… So again, significant patient population[…] But both innovations, both compounds*, we believe, have multibillion dollars. Chirfi Guindo - Merck & Co., Inc. - Senior VP & CMO for Merck Human Health 1. Merck & Co., Inc. Investor Event at ACC.23/WCC - Merck.com 2. Astrazeneca Q1 2025 Earnings Presentation Astrazeneca.com * Sotatercept & MK0616
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Setting the Stage for Obicetrapib's Transformational Launch 69 1. Market Opportunity 3. HCP Preference 4. Commercial Launch 2. Differentiated Product
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Obicetrapib Obicetrapib + Ezetimibe Evidence Supporting the Potential of Obicetrapib’s Portfolio is Grounded in Comprehensive, Outcomes-Driven Clinical Program 70 BROADWAY TANDEMBROOKLYN PREVAIL*ROSE ROSE2 JAPAN P H A S E 2 P H A S E 3 TULIP REMBRANDT* VINCENT* 1 2 *In Progress & RUBENS*
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Currently, Treatment of Hyperlipidemia is One-Dimensional 71 ApoA, apolipoprotein A; ApoB, apolipoprotein B; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; LDL-P, low-density lipoprotein particle concentration; Lp(a), lipoprotein (a); NODM, new-onset diabetes mellitus; sdLDL-C, small dense low-density lipoprotein cholesterol. LDL-C ↓ Obicetrapib
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Obicetrapib was observed to impact multiple factors associated with MACE, providing more comprehensive risk management across additional patient subpopulations The Future of Hyperlipidemia Treatment Goes Beyond LDL-C 72 ApoE4 LDL-P ↓ Small LDL-P ↓ NODM ↓ HDL-C ↑ ApoA1 ↑ LDL-C ↓ Non-HDL-C ↓ ApoB ↓ sdLDL-C ↓ Lp(a) ↓ Obicetrapib Note: NODM = New onset diabetes mellitus
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Small LDL-P Particle Concentration 73 ApoE4 LDL-P ↓ Small LDL-P ↓ NODM ↓ HDL-C ↑ ApoA1 ↑ LDL-C ↓ Non-HDL-C ↓ ApoB ↓ sdLDL-C ↓ Lp(a) ↓ Obicetrapib * Source: Toth, Peter P. et al. Atherosclerosis. Volume 235, Issue 2, 585 - 591. ^Hoogeveen RC, Gaubatz JW, Sun W, Dodge RC, Crosby JR, Jiang J, Couper D, Virani SS, Kathiresan S, Boerwinkle E, Ballantyne C M. Small dense low-density lipoprotein-cholesterol concentrations predict risk for coronary heart disease: the Atherosclerosis Risk In Communities (ARIC) study. Arterioscler Thromb Vasc Biol. 2014 May;34(5):1069-77. doi: 10.1161/ATVBAHA.114.303284. Epub 2014 Feb 20. PMID: 24558110; PMCID: PMC3999643. • Approximately 43 million patients with hyperlipidemia exhibit elevated levels of LDL-P of > 1300 nmol/L* • Prevalence is even higher in individuals with type 2 diabetes^ • Presence of LDL-P is a significant independent risk factor for coronary heart disease (CHD), even when traditional lipid measures like LDL-C and triglycerides are within normal ranges^
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Elevated Lp(a) Levels 74 Note: NODM = New onset diabetes mellitus ApoE4 LDL-P ↓ Small LDL-P ↓ NODM ↓ HDL-C ↑ ApoA1 ↑ LDL-C ↓ Non-HDL-C ↓ ApoB ↓ sdLDL-C ↓ Lp(a) ↓ Obicetrapib ** Tsimikas et al. J Am Coll Cardiol. 2022; 80: 934-946 ^^ Shapiro, M et al. Journal of Clinical Lipidology, Volume 19, Issue 1, 28 - 38 • In the US, close to 75 million patients have an elevated Lp(a) score of > 100-125 nmol/L** ^^ • An estimated 14.3 million of these patients also have hypercholesterolemia
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New-onset Diabetes Mellitus 75 Note: NODM = New onset diabetes mellitus ApoE4 LDL-P ↓ Small LDL-P ↓ NODM ↓ HDL-C ↑ ApoA1 ↑ LDL-C ↓ Non-HDL-C ↓ ApoB ↓ sdLDL-C ↓ Lp(a) ↓ Obicetrapib * Ray K, et al. European Journal of Preventive Cardiology (2021) 28, 1279 –1289. ^ Footnote: Prediabetes was defined as fasting plasma glucose values of 100 to 125 mg/dL or A1C values of 5.7% to 6.4%. Reference: National Diabetes Statistics Report | Diabetes | CDC • 27.9 million hyperlipidemia patients are estimated to have concomitant diabetes* • In addition, there are an estimated 27.2 million^ individuals with hyperlipidemia that are pre-diabetic
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ApoE4 Carriers 76 ApoE4 LDL-P ↓ Small LDL-P ↓ NODM ↓ HDL-C ↑ ApoA1 ↑ LDL-C ↓ Non-HDL-C ↓ ApoB ↓ sdLDL-C ↓ Lp(a) ↓ Obicetrapib Aβ, amyloid β; 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 2017. 4. Jeong W et al. Mol Cells. 2019;42(11):739-746. 5. Williams et al. BMC 2020.c • ApoE4 is the strongest genetic risk factor for late-onset AD1-5 • Approximately 20 million patients with hyperlipidemia are at increased risk for AD • Prevalence of ApoE4 in AD is up to 66%1-5
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No Other Asset Provides the Comprehensive Observed Benefits of Obicetrapib and Obi-Eze to Address Cardiometabolic Risk 77 • The bempedoic acid component of NEXLIZET is indicated: To reduce the risk of myocardial infarction and coronary revascularization in adults who are unable to take recommended statin therapy (including those not taking a statin) with: • established cardiovascular disease (CVD), or • a high risk for a CVD ev ent but without established CVD. • Competitive data on file CARD AND PCP TREATMENT PRIORITIES EZETIMIBE BEMPEDOIC ACID PCSK9i (injectable) ORAL PCSK9 OBICETRAPIB OBI-EZE* MACE at Launch • • • • • ≥ 30% LDL-C Reduction • • • • ApoA1 (≥ 30% increase) • • HDL-C (≥ 30% increase) • • Lp(a) • • • • ApoB • • • • • • Non-HDL • • • • • • LDL-P • • • • • • Small LDL-P >80% • • NODM • • Easy Dosing (Including Food Effect) • • • • • Oral Administration • • • • • Safe and Well-Tolerated • • • • • • & Product Profile Clinical Profile LDL-C+ Clinical Profile Simple, oral, once daily, low-dose Safety/Tolerability Profile Comparable to Placebo Obicetrapib & Obi-Eze
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Setting the Stage for Obicetrapib's Transformational Launch 78 1. Market Opportunity 2. Differentiated Product 4. Commercial Launch 3. HCP Preference
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How likely are you to Rx obicetrapib and obi-eze in the first 6 months after they become available? What Are Customers Saying About Obicetrapib, Obi-Eze and MK-0616? 79 5% 4% 17% 27% 29% 17% 4% 5% 16% 26% 26% 21% Magnolia March 2025 HCP Demand Study, N=252 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) tak en 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). 3 out of 4 HCP’s indicate a propensity to prescribe Obi & Obi-Eze within the first 6 months of availability Definitely would prescribe (7) OBICETRAPIB OBI-EZE Potentially would prescribe (4) Definitely would not prescribe (1) (2) (3) (5) (6)
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80 LDL-C reduction Affordable Cardiovascular (CV) death risk reduction Has a dosing schedule patients will accept Ease of dosing (e.g., dosing frequency, limited pill burden, effect of food, etc.) Lack of muscle related side effects Lack of long-term safety concerns based on clinical data Side effect profile similar to placebo Able to translate LDL and ApoB data to clinical outcomes Appropriate for all patients Product X (Obi) Product Y (Obi/EZE) Product Z (MK-0616) Importance Product Attribute Performance (Average 1-7 Performance Rating) Obicetrapib and Obi-Eze Perform Statistically Better then MK-0616 on Several Key Attributes Magnolia March 2025 HCP Demand Study, N=252 HCP Quantitative Respondents. MK-0616 target product profile described as an oral PCSK-9 inhibitor taken after 8 hours of fasting prior to and 30 minutes after taking. MK-0616 product profiles based on safety and efficacy profile reflecting publicly available Phase 2 data as of January 2025 (including LDL -C, ApoB, Non-HDL-C, HDL-C, Lp(a), 4-point MACE). Please indicate how well [Product X, Y, Z] performs on each of the following product attributes listed below. 1 indicates tha t the product “Performs very poorly”, 4 indicates that the product “Performs moderately well” and 7 indicates that the product “Performs extremely well”. Lower case letters note significant difference between products at 90 CI; upper case letters denote significant difference at 95 CI. *Ordered by descending product attribute importance. Obi & Obi-Eze have an advantage in terms of dosing and schedule Obi-Eze is seen as more affordable to MK-0616 – highlighting negative halo of early PCSK9 access challenges Obi & Obi-Eze are seen as appropriate for all patients over MK-0616 3 2 4 Obi-Eze portfolio is seen as on par with MK-0616 in terms of LDL-C 1 5.3 4.4 5.2 5.6Z 5.7Z 5.5 4.8 5.3 4.9 5.3z 5.6X 4.5z 5.3 5.7Z 5.7Z 5.4 5.0x 5.4 5.1x 5.3z 5.7X 4.2 5.3 5.2 5.0 5.4 4.9 5.3 5.1X 5.1 4 5 6 7 Average 1-7 Performance Rating
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ttributes that May Not ank Highly in Today’s Market Will be Considered Key Components of ifferentiation in Tomorrow’s Market 81 Magnolia March 2025 HCP Demand Study, N=252 HCP Quantitative Respondents. Target product profiles summarized on previous slid es. Please indicate how well [Product X, Y, Z] performs on each of the following product attributes listed below. 1 indicates tha t the product “Performs very poorly", 4 indicates that the product “Performs moderately well” and 7 indicates that the product “ Performs extremely well” Lower case letters note significant difference between products at 90 CI; upper case letters denote significant difference at 95 CI. *Ordered by descending product attribute importance 5.8Z 4.7Z 5.0 5.2z 5.3 5.1 5.1 5.3 5.6Z 5.8Z 4.5 5.0 5.3Z 5.3 5.2 5.3 5.3 5.5Z 5.5 4.4 4.9 5.0 5.2 5.1 5.2 5.5XY 4.44 5 6 7 Route of administration Reduced progression to Type 2 Diabetes Safety data on patient blood pressure levels Reduction of Lp(a) MACE reduction ApoB reduction Non-HDL reduction Mechanism of Action (MOA) HDL-C increase While the “H L-C” attribute is not considered as important as others, Obi & Obi-Eze score significantly higher than the competition MOA is the only attribute in which MK-0616 scores higher than Obi & Obi-Eze with statistical significance, due to familiarity with PCSK9i’s Product Attribute Performance (Average 1-7 Performance Rating) 1 2 Product X (Obi) Product Y (Obi/EZE) Product Z (MK-0616) Importance Average 1-7 Performance Rating
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With a Differentiated LDL-C+ Profile, Obicetrapib is Positioned to Become the First Choice Add-on Therapy to Statins 82 Statins 1 Why? Ezetimibe Or Nexletol/ Nexlizet Or PCSK9 3 Standard of care Oral Generic – payer requirement The Patient Journey Not at LDL-C goal Not at LDL-C goal Obicetrapib and Obi-Eze 2 ALL IN ONE: ✓ LDL-C+ efficacy ✓ Safe and well- tolerated in Phase 3 trials ✓ Oral Balancing: Incremental efficacy, safety and route of administration
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Setting the Stage for Obicetrapib's Transformational Launch 83 1. Market Opportunity 2. Differentiated Product 3. HCP Preference 4. Commercial Launch
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Demand Studies Support Obicetrapib and Obi-Eze as a Preferred Add-on LLT Over MK-0616 and AZD0780 70% 84 1x Demand MK-0616 1.3x AZD0780 1.7x Obicetrapib Franchise Magnolia March 2025 HCP Demand Study, US: N=252 HCP Quantitative Respondents. AZD0780 target product profile described as an oral PCSK-9 inhibitor taken with or without food and based on safety and efficacy profile reflecting publicly available Phase 2 data as of January 2025 (including LDL -C, ApoB, Non-HDL-C, HDL-C, Lp(a), 4-point MACE). See previous slides for target product profiles for Obicetrapib, Obi-Eze and MK-0616. more demand for the Obicetrapib franchise
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Preferential Demand for Obicetrapib Franchise Across Global Markets 85 Preference transcends diverse cultures, treatment preferences and healthcare systems Demand 1x MK-0616 1.3x AZD0780 1.7x Obicetrapib Franchise Source: Magnolia March 2025 HCP Demand Study, US: N=252 HCP Quantitative Respondents; Japan & China: N=120 HCP Quantitative R espondents In Each Market (240 Total). See previous slides for target product profiles. 1x MK-0616 1.8x AZD0780 2.8x Obicetrapib Franchise 1x MK-0616 1.8x AZD0780 2.6x Obicetrapib Franchise
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Obicetrapib’s Blockbuster Potential 86 2 3 1 Market Opportunity Large market with significant unmet need, recognized to be a multi-billion-dollar opportunity by potential new entrants HCP Preference Surveyed HCP’s strongly prefer Obicetrapib and Obi-Eze over competitive product profiles(1) Differentiated Product Unique clinical profile with potential to redefine efficacy as LDL-C+ (added benefit of LDL-P, Lp(a), NOD, ApoE4) Source: (1) Magnolia March 2025 HCP Demand Study, US: N=252 HCP Quantitative Respondents
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Obicetrapib’s Blockbuster Potential 87 $8 Billion+ potential worldwide market opportunity2 3 1 Market Opportunity Large market with significant unmet need, recognized to be a multi- billion-dollar opportunity by potential new entrants HCP Preference Surveyed HCP’s strongly prefer Obicetrapib and Obi- Eze over competitive product profiles (1) Differentiated Product Unique clinical profile with potential to redefine efficacy as LDL+ (added benefit of LDL-P, Lp(a), NOD, ApoE4) (1) Magnolia March 2025 HCP Demand Study, US: N=252 HCP Quantitative Respondents
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Access Not Expected to be a Barrier to Success 88 • 3 US Payer Advisory Boards • >40 Direct Payer Engagement Discussions • 2023 Payer & Office Manager Research • Secondary Analytics including payer coverage policies Primary & Secondary Payer Research “Control” of branded LLT space has led to broad coverage of PCSK9s and BA (Commercial/ PartD) Evidence suggests plans have also reduced PA restrictions on branded LLTs Obicetrapib is anticipated to establish a new class of LLT medications (CETPi) * 3 US Payor Advisory Boards held April14, 2023, September 22, 2023, April 12, 2024 Solstice Health Communications - Primary Research - 20 Plan MD and Pharm D; Initiated October 25, 2023 Solstice Health Communications - Primary Research - 16 Office (PCP & Cardiology) managers; Initiated December 13, 2023 Incremental value lies in differentiated data beyond LDL-C (LDL-P, Lp(a), new onset diabetes, ApoE4) 1 2 3 4 Payor feedback consistently reinforces broad access (Commercial and Medicare Part D) based on Product TPP5
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The Stage is Set for Obicetrapib’s Transformational Launch 89 Market opportunity continues to expand in a receptive environment Differentiated product provides meaningful benefit beyond LDL-C HCP preference strongly favors obicetrapib franchise in surveyed HCPs (1) Commercial launch aims to revolutionize LLT with LDL-C+ profile The Obicetrapib and Obi/Eze launch aims to surpass current branded LLT growth trends with enhanced demand in a receptive and dynamic market Current Branded growth trend A Rx Volume Time Graphic and launch curves are for illustrative purposes only Source: (1) Magnolia March 2025 HCP Demand Study, US: N=252 HCP Quantitative Respondents
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The Stage is Set for Obicetrapib’s Transformational Launch 90 Market opportunity continues to expand in a receptive environment Differentiated product provides meaningful benefit beyond LDL-C HCP preference strongly favors obicetrapib franchise in surveyed HCPs (1) Commercial launch aims to revolutionize LLT with LDL-C+ profile The Obicetrapib and Obi/Eze launch aims to surpass current branded LLT growth trends with enhanced demand in a receptive and dynamic market Rx Volume Current Branded growth trend A Anticipated obicetrapib accelerated launch curve vs. prior branded products B Time Graphic and launch curves are for illustrative purposes only Source: (1) Magnolia March 2025 HCP Demand Study, US: N=252 HCP Quantitative Respondents
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91 PATIENT AGE: 59 SEX: Female MEDICAL HISTORY: High LDL-C, High Lp(a), Elevated CAC score, Adopted, unknown family history MEDICATIONS: statin LIFESTYLE: Working professional, moderately active OCCUPATION: CFO OUR END GAME Lives Changed by Obicetrapib “Having heart disease weighs on me every day. I feel like I am a walking time bomb, waiting for it to be my turn to have a heart attack or stroke. I’ve worked so hard to take care of myself, but I still have markers that put me at high risk. I’m so grateful to have a cardiologist helping me take control, but I’m always thinking – is it enough?” Kari B. Doing Everything Right, Still Living in Fear
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Closing 92
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The Future of Hyperlipidemia Treatment Goes Beyond LDL-C 93 Note: NODM = New onset diabetes mellitus ApoE4 LDL-P ↓ Small LDL-P ↓ NODM ↓ HDL-C ↑ ApoA1 ↑ LDL-C ↓ Non-HDL-C ↓ ApoB ↓ sdLDL-C ↓ Lp(a) ↓ Obicetrapib
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The NewAmsterdam Value Proposition 94 Clinical Expertise: Data driven clinical development increases probability of success Unmet Need: Significant need for a potent, convenient, well-tolerated low- dose oral therapy Strong Balance Sheet: Cash sufficient to fund ongoing trials and support US commercial launch Experienced Leadership and Team: Expanding team comprised of cardiometabolic and biotechnology 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 Commercial Excellence: Track record of blockbuster launch success and innovative go-to-market model Differentiated Target Product Profile: Phase 2 data demonstrates obicetrapib’s potential impact on multiple CVD risk factors CMC Expertise and Manufacturing Capacity: Preparing to meet anticipated demand for obicetrapib and FDC, creating redundancy, expanding capacity and building inventory
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Our Mission is Clear and Simple 95 At NewAmsterdam Pharma, we are advancing a new era of life-saving treatment for cardiovascular disease and other lipid-related conditions. By prioritizing patients with high unmet needs and those who are underserved by current therapies, we are working toward a reality where cardiovascular disease is no longer the #1 killer of people worldwide.
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Q&A 96
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Thank You