Newamsterdam Pharma Company N.v. · NASDAQ:NAMS
Newamsterdam Pharma — Technical Presentation (July 2025)
22 slides from Newamsterdam Pharma's technical presentation, Jul 30, 2025
Slide 1: Obicetrapib in Alzheimer's Disease (AD): First-in-Class Evidence from BROADWAY
Obicetrapib in Alzheimer’s Disease (AD): First-in-Class Evidence from BROADWAY July 30, 2025
Slide 2: Disclaimer
Disclaimer This presentation (together with oral statements made in connection herewith, this “Presentation”) is for informational purposes only. Forward Looking Statements Certain statements included in this presentation (together with oral statements made in connection herewith, this “Presentation
Slide 3: CETPi Bears Therapeutic Potential for Both Multi-infarct Dementia and Alzheimer’s Disease
CETPi Bears Therapeutic Potential for Both Multi-infarct Dementia and Alzheimer’s Disease Healthy brain Multi-infarct dementia Alzheimer's disease (ischemic stroke) Post-stroke Cortical shrinking necrosis Enlarged ventricles Shrinking of hippocampus There is emerging evidence of a vascular Alzheimer
Slide 4: Elevated Cholesterol Levels in the Brain Precede Formation of Amyloid-Beta Plaques
Elevated Cholesterol Levels in the Brain Precede Formation of Amyloid- Beta (Aβ) Plaques The brain is the most cholesterol-rich organ; it contains only 2% body mass but has 20% of the body’s cholesterol During early development, oligodendrocytes synthesize large quantities of cholesterol for myelina
Slide 5: ApoE4 is a Risk Factor for Both CVD and Alzheimer's Disease
ApoE4 is a Risk Factor for Both CVD and Alzheimer’s Disease1-5 CVD APOE4 carriers exhibit APOE4 APOE4 carriers exhibit Prevalence of APOE4 in AD Cholesterol transport Risk for CVD by 22-45% and clearance R158 Lipid LDL-C receptor + binding Lipid accumulation in brain 66% binding (VLDL) HDL-C R112 Aβ
Slide 6: BROADWAY AD Biomarker Analysis: Design and Baseline Characteristics
BROADWAY AD Biomarker Analysis: Design and Baseline Characteristics AD, Alzheimer’s disease. 6
Slide 7: BROADWAY Trial Design and Baseline Characteristics
BROADWAY Trial Design and Baseline Characteristics Obicetrapib on Top of Maximum-Tolerated Lipid-Modifying Therapies: A Placebo-Controlled, Double-Blind, Randomized Phase 3 Study to Evaluate the Effect of 10 mg Obicetrapib in Participants With Underlying HeFH and/or Atherosclerotic Cardiovascular Di
Slide 8: BROADWAY AD Biomarker Analysis
BROADWAY AD Biomarker Analysis Objective: To assess plasma AD biomarkers in patients enrolled in the BROADWAY trial* and evaluate the effects of longer duration of therapy (12 months) with a prespecified population of ApoE3/4 or 4/4 carriers Outcomes assessed change in AD biomarkers from baseline AD
Slide 9: Baseline Demographics
Baseline Demographics E3/E3 E2/E2, E2/E3 E3/E4 E4/E4 P value* Obicetrapib Placebo Obicetrapib Placebo Obicetrapib Placebo Obicetrapib Placebo (n=695) (n=350) (n=65) (n=38) (n=225) (n=113) (n=19) (n=10) Age, y 67 (61, 73) 68 (61, 73) 70 (60, 74) 67 (58, 72) 67 (60, 72) 66 (59, 72) 68 (55, 72) 69 (66,
Slide 10: BROADWAY AD Biomarker Study: Primary Results
BROADWAY AD Biomarker Study: Primary Results AD, Alzheimer’s disease. 10
Slide 11: Significant Reduction in p-tau217 Progression Over Months with Greater Reductions as ApoE4 Risk Factors Increase
Significant Reduction in p-tau217 Progression Over 12 Months with Greater Reductions as ApoE4 Risk Factors Increase 2.99% benefit between 5.74% treatment benefit 20.5% treatment benefit in obicetrapib and placebo (P=0.019) in ApoE4 carriers (P=0.022) ApoE4 homozygotes (P=0.010) Full Analysis Set* Ap
Slide 12: Changes in p-tau217 Progression by Subgroups With Increasing Risk of AD Pathology
Changes (%) in p-tau217 Progression by Subgroups With Increasing Risk of AD Pathology Full Analysis Set ApoE4 ApoE4, Age ≥60 ApoE4, Age ≥70 E4/E4 (n=1515) (n=367) (n=283) (n=139) (n=29) -8.39 P=0.039 20 -5.74 -20.48 P=0.022 -5.40 P=0.010 -2.99 P=0.06 14.78 p-tau 217 Mean Percent Change, % P=0.019 15
Slide 13: Obicetrapib Impact on Additional AD Biomarkers in the Full Analysis Set
Obicetrapib Impact on Additional AD Biomarkers in the Full Analysis Set NFL GFAP p-tau181 Aβ42:40 p-tau217/ p-tau217 Aβ42:40 10 -4.04 P=0.0042 -2.99 P=0.0188 6.55 Mean Percent Change, % 4.98 5 3.4 2.51 1.99 1.68 1.48 1.27 1.03 0 -0.44 -1.2 -2.03 -5 Obicetrapib Placebo Aβ, amyloid beta; AD, Alzheimer
Slide 14: Obicetrapib's Impact on Additional AD Biomarkers in E4/E4 Carriers
Obicetrapib’s Impact on Additional AD Biomarkers in E4/E4 Carriers NFL GFAP p-tau181 Aβ42:40 p-tau217/ p-tau217 Aβ42:40 -22.65 P=0.032 24 -20.48 20.98 20 P=0.010 -15.24 -17.31 P=0.006 16 P=0.020 12.67 Mean Percent Change, % -13.67 P=0.06 12 8.85 -7.96 8 6.82 P=0.013 4 3.16 0 -0.36 -4 -1.67 -8 -6.39
Slide 15: A Benefit in p-tau217 Was Observed Across Age Ranges
A Benefit in p-tau217 Was Observed Across Age Ranges* All Participants ApoE4 Carriers 0.10 0.10 Placebo Predicted Absolute Change 95% Cl Placebo Predicted Absolute Change 95% Cl Obicetrapib Predicted Absolute Change 95% Cl Obicetrapib Predicted Absolute Change 95% Cl p-tau217 Absolute Change, pg/mL
Slide 16: Greater Decreases in p-tau217 With Higher Baseline Concentrations Seen With Obicetrapib
Greater Decreases in p-tau217 With Higher Baseline Concentrations Seen With Obicetrapib All Participants ApoE4 Carriers 0.10 0.10 Placebo 95% Cl Placebo 95% Cl Obicetrapib 95% Cl Obicetrapib 95% Cl p-tau217 Absolute Change, pg/mL p-tau217 Absolute Change, pg/mL 0.05 0.05 0.00 0.00 -0.05 -0.05 -0.10
Slide 17: APOE4 and p-tau217
APOE4 and p-tau217 17
Slide 18: APOE4 is the Strongest Genetic Risk Factor for Sporadic AD
APOE4 is the Strongest Genetic Risk Factor for Sporadic AD,1 With a Close Link to Increased pTau 217 Levels 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 Increased risk of Alzheimer
Slide 19: Plasma pTau217 is a Strong Predictor of AD Pathology
Plasma pTau217 is a Strong Predictor of AD Pathology pTau217 as a biomarker to assess AD progression pTau217 correlates with PET tangle density 100 25 AD Non-AD 80 20 Plasma pTau217, pg/mL Sensitivity, % 60 15 Plasma pTau217 (AUC=0.96) 40 10 Plasma pTau181 (AUC=0.96) AD signature cortical thickness
Slide 20: Conclusions
Conclusions 20
Slide 21: Obicetrapib: The Future of Hyperlipidemia Treatment Goes Beyond LDL-C
The Future of Hyperlipidemia Treatment Goes Beyond LDL-C LDL-C ↓ LDL-P ↓ Non-HDL-C ↓ Small LDL-P ↓ ApoB ↓ sdLDL-C ↓ ApoE4 Lp(a) ↓ HDL-C ↑ ApoA1 ↑ NODM ↓ Obicetrapib 21 Note: NODM = New onset diabetes mellitus 21
Slide 22: The Future of Hyperlipidemia Treatment Goes Beyond LDL-C
The Future of Hyperlipidemia Treatment Goes Beyond LDL-C Obicetrapib was observed to impact multiple risk factors, potentially leading to more comprehensive risk management across additional ASCVD patient subpopulations LDL Particles Lp(a) Diabetes ApoE4 • Approximately 43 million • In the US, close
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