Newamsterdam Pharma Company N.v. · NASDAQ:NAMS
Newamsterdam Pharma — Investor Presentation (January 2023)
43 slides from Newamsterdam Pharma's investor presentation, Jan 9, 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: NewAmsterdam is developing oral obicetrapib as CETPi to address major unmet need
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: 30mm+ 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 David Topper Marc Ditmarsch, M.D. CEO CSO COO CBO CFO CDO SANDER SLOOTWEG JULIET JAMIE NICHOLAS LOU MICHAEL DAVIDSON JOHN SEASONED BOARD AUDET TOPPER DOWNING LANGE KA
Slide 5: Net proceeds expected to fund obicetrapib development through several value-creating milestones
Net proceeds expected to fund obicetrapib development through several value-creating milestones 2022 2023 2024 2025 2026 1H 2H 1H 2H 1H 2H 1H 2H 1H 2H Phase 3 BROADWAY Trial Lipid Mono Study BROADWAY Ph3 (ASCVD; LDL-C ≥ 55 mg/dL; n=2,400) LDL regulatory filing Phase 3 BROOKLYN Trial BROOKLYN Ph3 Lip
Slide 6: Obicetrapib to Treat Cardiovascular Disease
Obicetrapib to Treat Cardiovascular Disease 6
Slide 7: Despite availability of 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 (2) 84 million Treated with prescription medication (3) <1 million post- statin Key factors limiting penetration 22 million (3) 8 million (4) Still above patie
Slide 8: Current post-statin LDL-lowering products all fall short of the profile patients need
Current 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 180mg ~140
Slide 9: ~50% LDL-C reduction efficacy virtually identical 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 10: Obicetrapib has potential to solve a substantial unmet medical need in dyslipidemia
Obicetrapib has potential to solve a substantial unmet medical need in dyslipidemia (1) 231mm Patients with >30mm 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 11: 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 12: Disease background and summary of clinical data
Disease background and summary of clinical data 12
Slide 13: LDL-C, ApoB and Lp(a) are causal in the development of atherosclerosis
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 14: In ROSE Phase 2b, obicetrapib demonstrated robust LDL-C lowering
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 1
Slide 15: 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 16: 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 Ap
Slide 17: 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 (1) (2) Obicetrapib Pooled ROSE Safety Pooled Safety (3) (4) Comparator 5mg + 10mg Placebo Obice
Slide 18: Target biology and class overview: Key lessons learned
Target biology and class overview: Key lessons learned 18
Slide 19: 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 20: 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 21: Absolute reduction of LDL-C and ApoB, and duration, are key to reducing cardiovascular 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 22: 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, leading to 1 OFF-TARGET TOXICITY, INCREASED BLOOD T O R
Slide 23: ACCELERATE, REVEAL and IMPROVE-IT show CVOT duration should be long enough
(1) (2) (2) 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 stoppe
Slide 24: MACE benefits in REVEAL observed as expected, informing 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 25: 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 26: 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 27: PREVAIL designed to be better positioned for success versus prior CETPi CVOTs
Applying lessons from prior CVOTs, PREVAIL trial is designed to be better positioned for success versus prior CETPi CVOTs ü Superior LDL-lowering activity anticipated • Obicetrapib 10mg observed to lower LDL by 51% in a Phase 2b clinical trial ü Target higher baseline LDL patients for greater potent
Slide 28: Therapeutic area expansion opportunities
Therapeutic area expansion opportunities 28
Slide 29: HDL and apoA1 effects offer pipeline 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 30: Clinical development and exclusivity timelines
Clinical development and exclusivity timelines 30
Slide 31: Net proceeds expected to fund obicetrapib development through several value-creating milestones
Net proceeds expected to fund obicetrapib development through several value-creating milestones 2022 2023 2024 2025 2026 1H 2H 1H 2H 1H 2H 1H 2H 1H 2H Phase 3 BROADWAY Trial Lipid Mono Study BROADWAY Ph3 (ASCVD; LDL-C ≥ 55 mg/dL; n=2,400) LDL regulatory filing Phase 3 BROOKLYN Trial BROOKLYN Ph3 Lip
Slide 32: 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 2022 2023 2024 2025 2026 2027 2028 2029 2030 2031 2032 2033 2034 2035 2036 2037 2038 2039 2041 2042 SPC max EU approval EU 6/35 6/36 Data exclusivity (8 + 2 years) 2/41 6/1/25 Regulat
Slide 33: NewAmsterdam Pharma
I” NewAmsterdam Ab Pharma
Slide 34: Appendix
NewAmsterdam /Y % Pharma ’ Appendix L
Slide 35: 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 36: Obicetrapib does not show an effect on systolic and diastolic blood pressure
Obicetrapib does not show an effect on systolic and diastolic blood pressure (1) • 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
Slide 37: 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 38: OCEAN: Phase 2b evaluating 5mg obicetrapib with 10mg 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 39: In OCEAN, obicetrapib LDL-lowering efficacy 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 40: OCEAN: ApoB in mg/dL & 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 41: 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 42: 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 43: TULIP: HDL-C, ApoA-1, ApoE and nascent HDL levels increases observed
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
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