Newamsterdam Pharma Company N.v. · NASDAQ:NAMS
Newamsterdam Pharma — Investor Presentation (March 2023)
49 slides from Newamsterdam Pharma's investor presentation, Mar 7, 2023
Slide 1: NewAmsterdam Pharma March 2023
Exhibit 99.1 bonis NewAmsterdam Pharma March 2023
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 O B I C E T RA P I B Company history: Achievements and milestones: • Significant unmet need for oral LDL-lowering therapy as adjunct to statins: 35mm+ patients
Slide 4: Expert cardiometabolic leadership supported by top investors
Expert cardiometabolic leadership supported by top investors Michael Davidson, M.D. John Kastelein, M.D. Douglas Kling Lina Gugucheva Louise Kooij Marc Ditmarsch, M.D. CEO CSO COO CBO CFO CDO SANDER SLOOTWEG JULIET JAMIE NICHOLAS LOU MICHAEL DAVIDSON JOHN JOHN W. SEASONED BOARD AUDET TOPPER DOWNING
Slide 5: Net proceeds expected to fund obicetrapib development through several milestones
Net proceeds 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 LDL (ASCVD; LDL-C ≥ 55 mg/dL; n=2,400) regulatory filing Phase 3 BROOKLYN Trial BROOKLYN Ph
Slide 6: Obicetrapib for Cardiovascular Disease
Obicetrapib for Cardiovascular Disease 6
Slide 7: Despite statins, CVD remains the leading cause of death worldwide
Despite availability of statins, CVD remains the leading cause of death worldwide (1) 231 million Adults in US/EU5 with hypercholesterolemia LDL-C goals (2) 84 million removed in Treated with prescription medication 2013 <1 million post-statin (4) (3) (3) 8 million 22 million patients treated with S
Slide 8: Cardiovascular field returning to "Lower is Better"
Cardiovascular field is returning to the mantra of “Lower is Better”, as supported by recently published FOURIER-OLE analysis In patients with atherosclerotic cardiovascular disease, long-term achievement of lower LDL-C levels, down to <20 mg/dL (<0.5 mmol/L), was associated with lowest of cardiovas
Slide 9: Approved post-statin LDL-lowering products fall short of the profile patients need
Currently approved post-statin LDL-lowering products all fall short of the profile patients need Patients need a drug that fits Ezetimibe Nexletol PCSK9 the following profile: (1) (1) Modest Modest Strong Strong Efficacy Oral, Oral, Injectable, Oral, Low Dose High Dose High Dose Administration/ 10mg
Slide 10: ~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 %) Obicetrapib Anacetrapib Evacetrapib Dalcetrapib Ezetimibe Nexletol Repatha Praluent Leqvi
Slide 11: Obicetrapib has potential to be ideal complement to statin therapy
Obicetrapib has potential to be ideal complement to statin therapy STATINS STATINS LDL-C + Lp(a) Diabetes STATINS ApoB risk effects Lowering + OBI OBI OBI = finally achieve 55 mg/dl LDL goal CETPi has been shown clinically to Obicetrapib’s robust Lp(a)-lowering Obicetrapib’s LDL and ApoB lowering re
Slide 12: Obicetrapib has potential to solve substantial unmet medical need in dyslipidemia
Obicetrapib has potential to solve a substantial unmet medical need in dyslipidemia (1) 231mm Patients with >35mm patients not sufficiently addressed by available treatment options hyperlipidemia OBICETRAPIB Fewer than 1mm patients treated with 10mg current branded options: ü ~50% LDL-lowering obser
Slide 13: US market research indicates strong prescriber and payor enthusiasm
US market research indicates strong prescriber and payor enthusiasm, wide window of pricing opportunity to enable broad market access strategy Strong enthusiasm from prescribers Broad market access opportunity: and payors: Market access hurdles plague existing brands: PRESCRIBER ENTHUSIAM: “There is
Slide 14: Developing monotherapy and FDC in parallel builds optionality
Developing monotherapy and FDC in parallel builds in optionality for patients and prescribers, optimizes chances of broad market access o Expected to be preferred: • Initially, by less aggressive prescribers and those seeking more experience with CETPi class Obicetrapib Monotherapy • By prescribers
Slide 15: Obicetrapib will launch 2-3 years ahead of any oral PCSK9
Obicetrapib will launch at least 2-3 years ahead of any oral PSCK9 with a better optimized product profile Obicetrapib Oral PCSK9 • True small molecule• Peptide (not small molecule) • Needs high-dose complex gut- • Simple 10mg low-dose penetrating formulation formulation • Formulation poses signific
Slide 16: Disease background and summary of clinical data
Disease background and summary of clinical data 16
Slide 17: ROSE Phase 2b: robust LDL-C lowering on high intensity statins
In ROSE Phase 2b clinical trial, obicetrapib demonstrated robust LDL-C lowering as adjunct 1 to high intensity statins Preparative ultra-centrifugation (PUC) is “gold-standard” for LDL-C quantification Median (min, max) LDL-C levels (mg/dL) at baseline and EoT Placebo Obicetrapib 5mg Obicetrapib 10m
Slide 18: Robust consistency of efficacy profile across multiple studies
Robust consistency of efficacy profile across multiple studies and within ROSE LDL-C lowering activity of obicetrapib 10mg across all efficacy ROSE waterfall: 10mg vs. placebo studies to-date • Almost all patients experienced meaningful LDL-C reductions • LDL-C reduction of >60% was observed in 40%
Slide 19: ApoB & Lp(a) percent reduction from baseline in ROSE
1 ApoB & Lp(a) percent reduction from baseline in ROSE • ApoB is currently considered the most important biomarker for CVD risk reduction (in addition to non-HDL and LDL-C) • Elevated Lp(a) is emerging as a strong and independent marker of cardiovascular risk and an exciting new CVD drug target ApoB
Slide 20: Obicetrapib safety profile in ROSE and across multiple studies
Obicetrapib safety profile in ROSE and across multiple studies: overview of AEs, SAEs and withdrawals Clean safety profile; Similar rates of drug discontinuation were observed for obicetrapib and placebo Obicetrapib Pooled ROSE Safety Pooled Safety (1) (2) Comparator 5mg + 10mg Placebo Obicetrapib,
Slide 21: Target biology and class overview: Key lessons learned
Target biology and class overview: Key lessons learned 21
Slide 22: CETP inhibition lowers LDL via a two-step mechanism of action
CETP inhibition works to lower LDL via a two-step mechanism of action STEP 1: CETPi stops transfer of cholesterol from LDL to HDL, increasing HDL- STEP 2: Increase in HDL particles leads to increased LDL-R expression in the C and lowering LDL-C liver, promoting further clearance of LDL Increased HDL
Slide 23: Absolute LDL-C and ApoB reduction and duration are key to reducing CV risk
Absolute reduction of LDL-C and ApoB, and duration of that reduction are key to reducing cardiovascular risk Key factor 1: Absolute reduction Key factor 2: Study duration CTT meta-regression line shows a linear and predictable Meta-analysis of CVOT duration shows that ~3.5 year median follow relatio
Slide 24: Obicetrapib 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, leading to 1 OFF-TARGET TOXICITY, INCREASED BLOOD T O R
Slide 25: ACCELERATE, REVEAL and IMPROVE-IT show CVOT duration matters
ACCELERATE, REVEAL and IMPROVE-IT demonstrate 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 benefi
Slide 26: REVEAL MACE benefits as expected, informing obicetrapib CVOT design
MACE benefits in CVOT of anacetrapib (REVEAL) observed to be exactly as expected, informing NewAmsterdam’s CVOT design for obicetrapib At 4.1 years, two important learnings: Learning 1: Predictable MACE benefit Learning 2: Baseline levels were too low M M ACE ACE be be ne nfe it fs its • 9% drop in
Slide 27: REVEAL supports translation from absolute LDL reduction to MACE benefit
REVEAL supports translation from absolute LDL reduction to MACE benefit EXPERIENCE: REVEAL (anacetrapib) PREDICTION: PREVAIL (obicetrapib) ~ 51% ~ (1) 61 mg/dL 17% 11 mg/dL 100 mg/dL 50 mg/dL anticipated Low Drug showed modest Results in SMALL absolute LDL Enrich for higher baseline Stronger expecte
Slide 28: PREVAIL trial design and power calculations leverage lessons learned
PREVAIL trial design & power calculations leverage lessons learned Differentiation over prior CVOTs • Study design: Superior LDL-lowering activity o n = 9000 Higher absolute LDL-c 51% observed in Phase 2b o Inclusion: ASCVD patients on maximally tolerated plus reduction leads to greater statins with
Slide 29: Therapeutic area expansion opportunities
Therapeutic area expansion opportunities 29
Slide 30: HDL and apoA1 effects offer expansion in Alzheimer's, AMD and diabetes
HDL and apoA1 effects potentially offer pipeline expansion opportunities in Alzheimer’s , AMD and diabetes • HDL is the “vacuum cleaner” of the body, POSITIVE TISSUE EFFECTS IN THE BRAIN HDL effluxing free cholesterol out of peripheral • Increasing HDL and apoA1 is expected to 2 tissues to promote h
Slide 31: Clinical development and exclusivity timelines
Clinical development and exclusivity timelines 31
Slide 32: Net proceeds expected to fund obicetrapib development through several milestones
Net proceeds 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 LDL (ASCVD; LDL-C ≥ 55 mg/dL; n=2,400) regulatory filing Phase 3 BROOKLYN Trial BROOKLYN Ph
Slide 33: Projected exclusivity timelines in the EU and US
Projected exclusivity timelines in the EU and US Assumes EU approval on June 1, 2025 and US approval on July 1, 2027 2023 2024 2025 2026 2027 2028 2029 2030 2031 2032 2033 2034 2035 2036 2037 2038 2039 2041 2042 2043 SPC max EU approval EU 6/35 6/36 Data exclusivity (8 + 2 years) 2/41 6/1/25 Regulat
Slide 34: NewAmsterdam Pharma
I” NewAmsterdam Ab Pharma
Slide 35: Appendix
NewAmsterdam /Y % Pharma ’ Appendix L
Slide 36: Obicetrapib development history
Obicetrapib development history Preclinical—Phase 1b (2008-2012) o Mitsubishi Tanabe (MTPC) is a Japanese pharmaceutical company, invented obicetrapib in late 2000’s o MTPC completed development through Phase 1b and thereafter deprioritized any lipid-lowering therapeutics o Dr. Kastelein was a consu
Slide 37: Menarini partnership overview
Menarini partnership overview Partnership with Menarini brings in significant non-dilutive capital and could enable NewAmsterdam to simultaneously launch obicetrapib in different markets with the ideal partner to optimize the commercial opportunity in the EU R I GHT PARTNER R I GHT T I ME R I GHT D
Slide 38: LDL-C, ApoB and Lp(a) are causal in atherosclerosis and heart disease
LDL-C, ApoB and Lp(a) are causal in the development of atherosclerosis and heart disease ApoB is a molecule that envelopes LDL in a 1:1 ratio LDL-C ApoB: Each LDL-C particle contains one ApoB molecule • ApoB-containing particles can become trapped in the arterial wall • High ApoB levels lead to athe
Slide 39: Genetic support that CETPi drives CVD benefit through LDL reduction
Genetic support that CETPi drives CVD benefit through LDL reduction Analysis of >1mm patient-years’ shows loss-of-function equivalent to targets of other LDL-lowering drugs Odds ratio for CVD Decreased Increased per decrease in LDL-C CVD risk CVD risk of 10 mg/dL (95% CI) • A 16% reduction in CVD ri
Slide 40: REVEAL long-term follow-up identified risk enhancers important for PREVAIL
REVEAL long-term follow-up identified risk enhancers important for PREVAIL HIGHER RISK subgroups have higher event rates & larger treatment effects REVEAL total study population 15.6% 11.9% RR decrease RR decrease Best 15.5% 18.1% risk RR decrease RR decrease enhancer 11.3% shows RR decrease highest
Slide 41: Obicetrapib does not show an effect on blood pressure
Obicetrapib does not show an effect on systolic and diastolic blood pressure • In the TULIP study, obicetrapib did not show any effect on blood pressure, aldosterone and electrolytes • A dedicated meta-analysis of the obicetrapib ROSE, TULIP and OCEAN study did not reveal any signal in systolic and
Slide 42: Consistent LDL-C lowering and HDL-C increase across three Phase 2 studies
Consistent LDL-C lowering and HDL-C increase observed across three Phase 2 studies of obicetrapib HDL-C levels increase LDL-C levels decrease 200 184 -5 180 165 157 160 -15 135 140 127 121 120 -25 100 -30 80 -35 60 -41 40 -45 -46 -46 20 -51 -51 0 -55 5mg 10mg 5mg 10mg 5mg 5mg Obi + 5mg 10mg 5mg 10mg
Slide 43: OCEAN: Phase 2b of obicetrapib with ezetimibe
OCEAN: Phase 2b evaluating 5mg obicetrapib in combination with 10mg ezetimibe Objective To evaluate the effect of obicetrapib in combination with ezetimibe compared to placebo on LDL-C Inclusion criteria Study design Obi 5mg + eze 10mg (n=25) • Mild dyslipidaemia • Fasting LDL-C levels >2.5 mmol/L a
Slide 44: OCEAN: LDL-lowering additive with ezetimibe
In OCEAN, obicetrapib was observed to have LDL-lowering efficacy that is additive with ezetimibe LDL-C in mg/dL by PUC & Percent change from baseline Median (min, max) LDL-C levels (mg/dL) at baseline and E0T Placebo Ezetimibe 10mg Obicetrapib 5mg Obi 5mg / Eze 10mg 10 Ezetimibe Obicetrapib Obi 5 +
Slide 45: OCEAN: ApoB in mg/dL and percent change from baseline
OCEAN: ApoB in mg/dL & percent change from baseline Median (min, max) ApoB levels (mg/dL) at baseline and E0T Placebo Ezetimibe 10mg Obicetrapib 5mg Obi 5mg / Eze 10mg 10 Ezetimibe Obicetrapib Obi 5mg + 5 Time Placebo 10mg 5mg Eze 10mg 0 105.5 103.0 102.0 105.0 Baseline -1 (74, 141) (79, 133) (74, 1
Slide 46: OCEAN safety: TEAEs, TESAEs and withdrawals overview
OCEAN safety: TEAEs, TESAEs and withdrawals overview Obicetrapib 5mg well tolerated compared to placebo Placebo Ezetimibe 10mg Obicetrapib 5mg Obi 5mg / Eze 10mg TEAEs (%) TEAEs, total 6 (21.4) 8 (28.6) 4 (14.3) 9 (33.3) TEAEs, related 4 (14.3) 3 (10.7) 1 (3.6) 3 (11.1) TEAEs, severe 0 1 (3.6) 0 0 T
Slide 47: TULIP Phase 2a trial results
TULIP Phase 2a trial results TULIP clinical trial design Percent change of LDL-C levels from baseline • Randomized double-blind placebo-controlled Placebo 1mg 2.5mg 5mg 10mg trial, once daily dosing P<0.0001 0.8mg • Endpoints: • Percent change in LDL-C at week 12 compared to baseline -27.4 -32.7 -45
Slide 48: TULIP: HDL-C, ApoA-1, ApoE and nascent HDL increases
TULIP: HDL-C, ApoA-1, ApoE and nascent HDL levels increases observed 200% 100% 180%* 180% 161%* 160% 77% 80% 140% 65% 122%* 58% 120% 60% 57% 56% 100% 48% 76%* 80% 40% 38% 37% 35% 33% 32% 28% 60% 25% 40% 20% 19% 20% 3% 2% 1% 0% 0% placebo 1 2.5 5 10 placebo placebo 1 2.5 5 10 1 2.5 5 10 5 10 5 10 5 1
Slide 49: Obicetrapib potential to impact diabetes risk
Obicetrapib bears significant potential to also beneficially impact diabetes risk CETP validated both genetically and clinically to reduce/reverse diabetes risk 1 • While statins increase diabetes risk by 11-15% , CETP inhibition is clinically demonstrated to reverse existing diabetes, decrease new-
NewAmsterdam Pharma — Investor Presentation (March 2023) on 6ix