Newamsterdam Pharma Company N.v. · NASDAQ:NAMS
Newamsterdam Pharma — Investor Presentation (September 2023)
33 slides from Newamsterdam Pharma's investor presentation, Sep 25, 2023
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: Developing oral obicetrapib as CETPi for hypercholesterolemia and cardiometabolic diseases
NewAmsterdam is developing oral obicetrapib as CETPi to address major unmet need in hypercholesterolemia and other cardiometabolic diseases OBICETRAPIB • Significant unmet need for oral LDL-lowering therapy as adjunct to Company history: Achievements and statins: 35mm+ patients in US/EU5 are not ach
Slide 4: Despite statins, tremendous unmet need remains
Despite availability of statins, tremendous unmet need remains – with resurgance of the “lower-is better” paradigm 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 preva
Slide 5: Obicetrapib could solve substantial unmet need in dyslipidemia
Obicetrapib has potential to solve a substantial unmet medical need in dyslipidemia (1) (1) 231 million 231 million Adults in US/EU5 with hypercholesterolemia Adults in US/EU5 with hypercholesterolemia <1mm >35mm patients not sufficiently (2) post-statin 84 million addressed by available treatment o
Slide 6: Approved post-statin LDL-lowering products fall short of patient needs
Currently approved post-statin LDL-lowering products all fall short of the profile patients need Patients need a drug that Nexletol PCSK9i Oral PCSK9 fits the following profile: (1) (1) Strong Modest Strong Potentially strong, Efficacy but significant food effect Oral, Injectable, Oral, Oral, High D
Slide 7: ~50% LDL-C reduction comparable to PCSK9 injectables
~50% LDL-C reduction efficacy would be virtually identical to PCSK9 injectables and is substantially better than other oral therapies Cross trial comparison of LDL-C reduction across different approaches (in %) Anacetrapib Evacetrapib Dalcetrapib Ezetimibe Nexletol Repatha Praluent Leqvio 1 2 3 4 5
Slide 8: Lipid biomarker changes for obicetrapib 10mg monotherapy across Phase 1/2 studies
Changes in lipid biomarkers for obicetrapib 10mg monotherapy across phase 1/2 studies Phase 1 MAD TULIP TA-8995-06 ROSE ROSE2 Japan N=10 per arm N=35 per arm N=13 per arm N=40 per arm N=26 per arm N=26 per arm 0 -10 -20 -24.2 -26.3 -30 -29.6 -29.7 -29.8 -32.7 -35.8 -37.0 -37.5 -40 -41.7 -42.9 -43.5
Slide 9: Current cash expected to fund development through value-creating milestones
Current cash expected to fund obicetrapib development through several value-creating milestones 2023 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 3 BROOK
Slide 10: Obicetrapib for Cardiovascular Disease
Obicetrapib for Cardiovascular Disease 10
Slide 11: 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 12: 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 13: 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 14: 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 15: 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 16: 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 17: Stronger LDL-lowering with ezetimibe in obicetrapib combo, potentially synergistic
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 18: Favorable safety profile observed in all 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 19: Obicetrapib shows no 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 20: Target biology and class overview: Key lessons learned
Target biology and class overview: Key lessons learned 20
Slide 21: Program designed to overcome limitations of 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 22: Absolute LDL-C and ApoB reduction and duration key to reducing cardiovascular 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 23: ACCELERATE, REVEAL and IMPROVE-IT support CVOT duration belief
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 24: REVEAL supports translation from non-HDL-C reduction to MACE benefit
REVEAL supports translation from absolute non-HDL-C reduction to MACE benefit EXPERIENCE: REVEAL (anacetrapib) 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 absolu
Slide 25: Obicetrapib for Alzheimer's Disease
Obicetrapib for Alzheimer’s Disease 25
Slide 26: CETP knock-in mice show higher 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 27: 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 increases in HDL levels CETP
Slide 28: 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 reduce 24s- and 27-OH in plasma alone • Obicetrapib was observed to be we
Slide 29: Clinical events and exclusivity timelines
Clinical events and exclusivity timelines 29
Slide 30: 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 31: Achieved and anticipated upcoming milestones
Achieved and anticipated upcoming milestones (1) 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 data FDC Phase 3 trial 2023 (1)
Slide 32: 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 Louise Kooij Marc Ditmarsch, M.D. CEO CSO COO CCO CFO CDO SANDER JULIET JAMIE NICHOLAS LOU MICHAEL JOHN JOHN W. JANNEKE SEASONED SLOOTWEG AUDET TOPPER DOWNING LAN
Slide 33: NewAmsterdam Pharma
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