Newamsterdam Pharma Company N.v. · NASDAQ:NAMS
Newamsterdam Pharma — Investor Presentation (January 2024)
41 slides from Newamsterdam Pharma's investor presentation, Jan 22, 2024
Slide 1: NewAmsterdam Pharma
Exhibit 99.4 bonis NewAmsterdam Pharma
Slide 2: Disclaimer
Disclaimer This presentation (together with oral statements made in connection herewith, this “Presentation”) is for informational purposes only. This Presentation shall not constitute an offer to sell, or the solicitation of an offer to buy, any securities, nor shall there be any sale of securities
Slide 3: Obicetrapib in multiple Phase 3 trials – key data expected in 2024
Obicetrapib in multiple Phase 3 trials for hypercholesterolemia – Key value- driving data expected in 2024 Significant unmet need for oral LDL-lowering therapy as adjunct Multiple pivotal data readouts to statins: expected from 2024-2026 • 35mm+ patients in US/EU5 are not achieving LDL-lowering • 1Q
Slide 4: Obicetrapib designed to address ~30M US patients on drug but not at goal
Obicetrapib designed to address the ~30M patients in US on drug but not at goal ~18 million ~43 million Not at goal of LDL-C Treated primary <100mg/dl prevention patients Of the ~30M treated patients not at goal, ~8 million ~72 million ~19 million High Risk ASCVD not at ~18M were “far from Adults in
Slide 5: Majority of ASCVD/HeFH patients are not achieving LDL-C targets
Majority of ASCVD/HeFH patients are not achieving LDL-C targets Primary prevention HeFH Despite availability of ASCVD patients with an LDL-C Very high risk ASCVD patients patients with treatments continue to see target of LDL<70 or <55 mg/dL with an LDL-C target <55 an LDL-C target <100 mg/dL minima
Slide 6: Increased CV events following removal of LDL-C guidelines in 2013
Increased CV events following removal of LDL-C guidelines in 2013 15 Risk of CV ≥70 LDL-C death, MI, 55-≤70 LDL-C LDL-C stroke goals Male deaths 40-≤55 LDL-C removed 10 in ≤20 LDL-C 2013 5 Female deaths P-value = 0.0001 5 0 0 1 2 3 4 5 Trends in prevalence of high LDL-C in US adults, 2 Year Time pos
Slide 7: Resurgence of the "lower is better" paradigm driving US market growth
Resurgence of the “lower is better” paradigm leading to significant US market growth 18% 3yr CAGR LDL-C goals removed Mortality 7% peaks 3yr CAGR Driven by generic ezetimibe, 7% total market growth in 18% non-statin patient growth given lack of convenient and the US efficacious alternatives Recent g
Slide 8: Few approved post-statin LDL lowering products, limited by efficacy, convenience, access
Few approved post-statin LDL lowering products, which are limited by efficacy, convenience and/or payor access (5) (5) (4) (1) (2) (3) Obicetrapib Obi + Eze Oral PCSK9 Ezetimibe Nexletol PCSK9i LDL data 2026E LDL data 2024E Approved Approved Approved LDL data 2025E Approval (CVOT data 2029E) (CVOT d
Slide 9: 40-50% LDL-C reduction comparable to high efficacy PCSK9 injectables
40-50% LDL-C reduction comparable to high efficacy PCSK9 injectables Cross trial comparison of LDL-C reduction across different approaches (in %) Anacetrapib Evacetrapib Dalcetrapib Ezetimibe Nexletol Repatha Praluent Leqvio 1 2 3 4 5 6 7 8 100mg 130mg 600mg 10mg 180mg 420mg 150mg 284mg 0 Prior CETP
Slide 10: Obicetrapib designed to overcome limitations of prior CETP inhibitors
Obicetrapib program designed to overcome limitations of prior CETP inhibitors (3) (1) (2) (4) (5) Evacetrapib Torcetrapib Dalcetrapib Anacetrapib Obicetrapib Observed LDL-C reduction 20% 7% 21% 17% 43% CETP inhibition 80% 40% 65% 90% 98% Dosing 60mg 600mg 100mg 100mg 10mg Blood pressure increase Yes
Slide 11: Enhanced LDL-C reduction with obicetrapib's greater potency
Enhanced LDL-C reduction with Obicetrapib’s greater potency Note: The above trials and data do not represent head-to-head comparisons. Actual results may differ from expectations. 11 Sources: 1. Barter et al. NEJM.2007; 2. Schwartz et al. NEJM.2012; 3. Lincoff et al. NEJM.2017 4. Bowman et al. NEJM.
Slide 12: Obicetrapib Phase 1/2 studies: consistent benefits in lipid biomarkers
Obicetrapib Phase 1/2 studies: Consistent benefits observed in lipid biomarkers Phase 1 MAD ROSE ROSE2 Japan Pooled data TA-8995-06 TULIP N=10 per arm N=40 per arm N=26 per arm N=26 per arm N=132 N=13 per arm N=35 per arm Median LS Mean Source: Company data for obicetrapib 10mg monotherapy, Pooled d
Slide 13: Sufficient cash to fund multiple pivotal data readouts 2024-2026
Sufficient cash expected to fund the Company through multiple potential pivotal data readouts 2024-2026 2024 2022 2023 2024 2025 2026 1H 2H 1H 2H 1H 2H 1H 2H 1H 2H Phase 3 BROADWAY Trial Lipid Mono Study BROADWAY Ph3 (HeFH or ASCVD; LDL-C ≥ 55 mg/dL; LDL n=2,532) regulatory filing BROOKLYN Ph3 Phase
Slide 14: BROOKLYN study design
BROOKLYN study design Objective: To evaluate the effects of obicetrapib in patients with heterozygous familial hypercholesterolemia (HeFH) Inclusion criteria Study design: Randomized, double-blind, placebo-controlled • HeFH by genetic confirmation, and/or WHO Criteria/Dutch Clinical Network, Obicetr
Slide 15: BROADWAY study design
BROADWAY study design Objective: To evaluate the effect of obicetrapib on top of max tolerated lipid-modifying therapy in patients with HeFH and or ASCVD Inclusion criteria Have a fasting serum LDL-C at Screening (Visit 1) as follows: Study design: Randomized, double-blind, placebo-controlled • Have
Slide 16: PREVAIL trial design leverages lessons learned
PREVAIL trial design leverages lessons learned Applying lessons from prior CVOTs • Study design: Greater LDL-lowering activity o n = 9000 Higher absolute LDL-C anticipated o Inclusion: ASCVD patients on maximally reduction expected to 42.6% observed in Phase 2 tolerated statins with risk enhancers a
Slide 17: 2023 achievements pave the way for 2024 value inflection milestones
2023 achievements pave the way for potential 2024 value inflection milestones 2Q 2023 3Q 2023 2H 2023 Complete enrollment Present ROSE2 Complete enrollment for Topline Japan Initial Alzheimer’s Select formulation for for BROOKLYN Phase 3 full data at NLA BROADWAY Phase 3 Phase 2b results Phase 2a da
Slide 18: Obicetrapib for Cardiovascular Disease
Obicetrapib for Cardiovascular Disease 18
Slide 19: Exceptional LDL goal attainment with ezetimibe + obicetrapib combination
Exceptional LDL goal attainment observed with ezetimibe + obicetrapib combination, including >87% of patients observed to attain <55 mg/dl LDL-C levels % of patients observed with the following LDL-C levels: <100 mg/dl <70 mg/dl <55 mg/dl 100% 93.5% 88.5% 87.1% 73.1% 66.7% 87.1% 73% of combo recipie
Slide 20: Lp(a) percent reduction from baseline in ROSE and ROSE2
1 2 Lp(a) percent reduction from baseline in ROSE and ROSE2 • Lp(a) is emerging as a strong and independent marker of CVD risk and an exciting new CVD drug target ROSE2 ROSE Placebo Obicetrapib 5mg Obicetrapib 10mg Obicetrapib 10mg Obi 10mg / Eze 10mg 10 10 4 0 0 -10 -10 -20 -20 -30 -30 -34 -40 -40
Slide 21: Obicetrapib/ezetimibe lowers LDL-C by 63.4% on top of HIS in ROSE2
Obicetrapib/ezetimibe observed to lower LDL-C by 63.4% on top of HIS in ROSE2 LDL-C (mg/dL), on-treatment population Median (min, max) LDL-C levels (mg/dL) at baseline & EoT Placebo Obicetrapib 10 mg Obi 10 / Eze 10 10 Time Placebo Obi 10 mg Obi 10 / Eze 10 0 95.5 100.0 87.0 Baseline -10 (60, 211) (
Slide 22: ROSE2: Non-HDL-C and ApoB percent change from baseline
ROSE2: Non-HDL-C and ApoB percent change from baseline (Day 84) Non-HDL-C (mg/dL), on-treatment population ApoB (mg/dL), on-treatment population Placebo Obicetrapib 10 mg Obi 10 / Eze 10 Placebo Obicetrapib 10 mg Obi 10 / Eze 10 10 10 5 0 0 -10 -5.6 -5 -2.1 -20 -10 -30 -15 -20 -40 -37.5 -25 -24.2 -5
Slide 23: LDL-P believed to be a robust predictor of cardiovascular risk
LDL-P believed to be one of the most robust predictors of cardiovascular risk • 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 Low LDL-P confers a lower risk higher proportion of smal
Slide 24: ROSE2 showed significant reduction in total and small LDL particles
ROSE2 showed significant reduction in total and small LDL particles, bringing patients (1) who had baseline elevated LDL-P to optimal parameters Patients taking the Obi/Eze combo Total LDL-P Small LDL-P observed to achieve optimal LDL-P profiles Lipoprotein ROSE2 ROSE2 fractionation 1 placebo Obi /
Slide 25: Stronger LDL-lowering with ezetimibe in obicetrapib combo vs. with statins
Stronger LDL-lowering observed with ezetimibe in obicetrapib combo vs. ezetimibe with (1) statins, potentially due to a synergistic mechanism of action for obi/eze combo Obicetrapib is designed to promote more cholesterol excretion Eze on top Eze on top into the intestines (via TICE) while ezetimibe
Slide 26: Favorable safety profile observed in all Phase 2 & 3 clinical studies
Favorable safety profile observed in all LDL Phase 1 & 2 clinical studies (1) (2) Comparator Pooled Obicetrapib (5, 10mg) (N=231) (N=309) TEAEs (%) TEAEs, total 136 (58.9) 173 (55.9) TEAEs, related 45 (19.5) 49 (15.8) TEAEs, severe 5 (2.2) 7 (2.3) TESAEs *TESAEs, total 6 (2.6) 4 (1.3) TESAEs, relate
Slide 27: Obicetrapib does not show an effect on blood pressure
Obicetrapib does not show an effect on systolic and diastolic blood pressure • A dedicated meta-analysis of the obicetrapib ROSE2, ROSE, TULIP, OCEAN, and TA-8995-203 study did not reveal any signal in systolic and diastolic blood pressure • By contrast, in the cardiovascular outcome trial ILLUMINAT
Slide 28: Target biology and class overview: Key lessons learned
Target biology and class overview: Key lessons learned 28
Slide 29: Obicetrapib program designed to overcome limitations of all prior CETP inhibitors
Obicetrapib program designed to overcome limitations of all prior CETP inhibitors SAFETY 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, 1 OFF-TARGET TOXICITY, T O R C E T R A P I B leading to
Slide 30: Absolute reduction of LDL-C and ApoB and its duration key to reducing risk
Absolute reduction of LDL-C and ApoB, and duration of that reduction are believed to be key to reducing cardiovascular risk Key factor 1: Absolute reduction Key factor 2: Study duration CTT meta-regression line shows a linear and Meta-analysis of CVOT duration shows that ~3.5 year median predictable
Slide 31: ACCELERATE, REVEAL and IMPROVE-IT support long CVOT duration
ACCELERATE, REVEAL and IMPROVE-IT support our belief that CVOT study duration should be long enough to see optimal MACE benefit Kaplan-Meier curves for these trial, with very similar absolute ApoB reductions, show separation later than 2 years, which is the point in time that ACCELERATE stopped MACE
Slide 32: REVEAL data supports translation from absolute LDL reduction to MACE benefit
REVEAL data supports translation from absolute LDL reduction to MACE benefit EXPERIENCE: REVEAL (anacetrapib) Hypothetical: PREVAIL (obicetrapib) ~ ~ (1) 61 mg/dL 17% 11 mg/dL 105 mg/dL 43% 45 mg/dL Low Drug showed modest Results in SMALL absolute Enrich for higher Stronger expected Expected to resu
Slide 33: REVEAL high tercile non-HDL-C data supports larger MACE benefit
REVEAL data in high tercile in non-HDL-C supports larger MACE benefit EXPERIENCE: REVEAL (anacetrapib) Hypothetical: Obicetrapib (Phase 2 Studies) ~110 21% 23 mg/dL ~140 mg/dL 40% ~56 mg/dL mg/dL Non-HDL-C PREVAIL non-HDL-C high tercile Drug showed modest Results in SMALL absolute Non-HDL-C lowering
Slide 34: Obicetrapib and Alzheimer's Disease
Obicetrapib and Alzheimer’s Disease 34
Slide 35: CETP knock-in mice show increased brain cholesterol; CETPi rescues cognition
CETP knock-in mice observed to increase brain cholesterol levels and CETPi rescues cognition in preclinical models of CETP-induced AD Control diet 1 % cholesterol diet p<0.05 p<0.05 1.6 1.2 CETPi shows 0.8 increased brain cholesterol 0.4 levels 0.0 WT CEPT WT CEPT Control diet 1 % cholesterol diet p
Slide 36: CETP loss-of-function genotype may be associated with slower memory decline
CETP loss-of-function (LoF) genotype may be associated with slower memory decline and lower AD risk • CETP’s potential involvement in CNS cholesterol homeostasis is supported by genetic data • CETP LoF genotype may be associated with lower CETP activity & a corresponding increase in HDL levels CETP
Slide 37: Obicetrapib decreases 24s- and 27-hydroxycholesterol in plasma and CSF
Initial data for Obicetrapib 10mg observed to decrease 24s- & 27-hydroxycholesterol (“OH”) in both plasma and cerebrospinal fluid (“CSF”) • In separate trials with different protocols and endpoints, Simvastatin was observed to only reduce 24s- and 27-OH in plasma • Obicetrapib was observed to be wel
Slide 38: Clinical events and exclusivity timelines
Clinical events and exclusivity timelines 38
Slide 39: Projected exclusivity timelines in the EU and US
Projected exclusivity timelines in the EU and US Assumes EU approval 4Q 2025 and US approval 1Q 2027 2023 2024 2025 2026 2027 2028 2029 2030 2031 2032 2033 2034 2035 2036 2037 2038 2039 2040 2041 2042 SPC max EU approval 10/35 10/36 EU Data exclusivity + market exclusivity (8 + 2 years) 10/40 10/1/2
Slide 40: Expert cardiometabolic leadership supported by top investors
Expert cardiometabolic leadership supported by top investors Michael Davidson, M.D. John Kastelein, M.D. Douglas Kling William ‘BJ’ Jones Ian Somaiya Louise Kooij Marc Ditmarsch, M.D. CEO CSO COO CCO CFO CAO CDO WILLIAM SANDER JULIET JAMIE NICHOLAS LOU MICHAEL JOHN JOHN W. JANNEKE SEASONED LEWIS SLO
Slide 41: NewAmsterdam Pharma
I” NewAmsterdam Ab Pharma
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