Newamsterdam Pharma Company N.v. · NASDAQ:NAMS
Newamsterdam Pharma — SPAC Merger (August 2022)
34 slides from Newamsterdam Pharma's SPAC merger presentation, Aug 24, 2022
Slide 1: Addressing the unmet needs in LDL-C lowering; what can we expect?
Filed by NewAmsterdam Pharma Company B.V. Pursuant to Rule 425 under the Securities Act of 1933, as amended, and deemed filed pursuant to Rule 14a-12 of the Securities Exchange Act of 1934, as amended Subject Company: Frazier Lifesciences Acquisition Corporation Commission File No. 001-39765 The fol
Slide 2: Conflicts of interest
Conflicts of interest • Dr Kastelein reports consultancies with 89Bio, CiVi Biotech, CSL- Behring, Draupnir Bio, Menarini Ricerce, Madrigal, North Sea Therapeutics, Novartis, Silence Therapeutics, CinCor, Scribe Therapeutics • Dr Kastelein is acting Chief Medical Officer (CMO) of Staten Biotech and
Slide 3: Legal disclaimer
Legal disclaimer About NewAmsterdam Pharma NewAmsterdam Pharma is a private clinical-stage biopharmaceutical company whose mission is to improve patient care in populations with metabolic diseases where traditional therapies have not been sufficiently successful or well-tolerated. NewAmsterdam Pharm
Slide 4: Elevated levels of LDL-C are the root cause of cardiovascular disease
Elevated levels of LDL-C are the root cause of cardiovascular disease • Cardiovascular disease (CVD) is the leading cause of death among adults worldwide • Hyperlipidemia nearly doubles the risk of developing CVD • Elevated levels of LDL cholesterol (LDL-C) are the root cause of atherosclerosis, the
Slide 5: How well are we treating our ASCVD patients?
How well are we treating our ASCVD patients? 5
Slide 6: Europe Da Vinci Study: LLT use and LDL-C goal attainment
Europe Da Vinci Study: Overall LLT use & risk-based LDL-C goal attainment 100 100 80 80 54 60 60 52 33 40 40 28 20 20 9 6 4 1 0 0 Moderate- High- intensity Ezetimibe Other LLT Low- intensity PCSK9i 2016 LDL-C goal 2019 LDL-C goal intensity statin statin combination statin combination monotherapy mon
Slide 7: How can we improve?
How can we improve? 7
Slide 8: Moderate-intensity statin with ezetimibe non-inferior and better tolerated than high-intensity statin
Moderate-intensity statin with ezetimibe observed to be non-inferior and better tolerated than high-intensity statin, suggesting better adherence and less relevance of the MOA for lowering LDL-C • Primary Endpoint = Composite of cardiovascular death, major cardiovascular event, or non-fatal stroke •
Slide 9: Rationale to treat very high-risk patients with combination therapy initially
Rationale to treat all very high- and extremely high-risk patients with combination therapy as the initial strategy Simplified treatment algorithm for very high-risk patients with ASCVD Cardiovascular risk assessment if if VERY HIGH CVD RISK EXTREMELY HIGH CVD RISK then then Start statin + ezetimibe
Slide 10: How can we improve?
How can we improve? 10
Slide 11: Effect of bempedoic acid on LDL-C after weeks of treatment
Effect of bempedoic acid on LDL-C after 12 weeks of treatment Persistent Hypercholesterolemia Despite Maximally Hypercholesterolemia But Unable to Tolerated Statin Therapy Tolerate Statins 5.0 10 2.4 1.6 0 -1.3 –10 –20 –15.1 –16.5 Placebo-corrected Placebo-corrected difference (95% CI): difference (
Slide 12: Bempedoic Acid / Ezetimibe Combination Non-Statin Mechanisms of Action
Bempedoic Acid / Ezetimibe Combination Non-Statin Mechanisms of Action (MOAs) Ezetimibe Bempedoic Acid • Inhibits NPC1L1 (sterol transporter) • Inhibits ATP Citrate Lyase (ACL) • Primary • Active in liver cells • Inhibition of gastrointestinal • Acts in the same cholesterol cholesterol absorption bi
Slide 13: Phase 3 Study of Bempedoic Acid or Ezetimibe Alone or in Combination vs Placebo
Phase 3 Study of Bempedoic Acid or Ezetimibe Alone or in Fixed-dose Combination vs Placebo ▪ Patients at high risk due to ASCVD or HeFH with LDL-C ≥100 mg/dL, or multiple CVD risk factors Placebo Ezetimibe Bempedoic acid BA + EZE FDC (n=41) (n=86) (n=88) (n=86) with LDL-C ≥130 mg/dL –38.0 (–46.5, –2
Slide 14: ANGPTL3 inhibition: LDL-R-independent hepatic uptake of remnant particles
ANGPTL3 inhibition LDL-R-independent hepatic uptake of ‘remnant’ particles 14
Slide 15: ELIPSE HoFH Study: evinacumab added for homozygous FH
ELIPSE HoFH Study: The addition of the ANGPTL3-inhibitor, evinacumab, for homozygous FH (n=65) 28 21 14 7 0 Placebo IV Qw3 -7 -16 -21 -28 Evinacumab 15 mg/kg IV Q4W -35 -41 -49 -56 Number of patients 22 19 20 21 20 29 20 21 Placebo IV Q4W Evinacumab 15 mg/kg IV Q4W 43 39 43 42 42 40 43 43 BaselineWk
Slide 16: ELIPSE HoFH Study by mutation status
ELIPSE HoFH Study Mutation 0 Null/Null -6 Not Null/Null -12 -18 -24 -30 -36 -42 -48 -54 -60 Wk 24 Wk 8 Wk 12 Wk 16 Wk 20 B Wk 2 Wk 2 Number of patients 15 15 15 15 14 15 14 14 Null/Null 28 27 28 25 28 28 24 24 Not Null/Null Raal FJ et al. New Engl J Med 2020;383:711-20 16 LDL-C LS mean (±SE) change
Slide 17: Treatment algorithm for HoFH
Treatment algorithm for HoFH HoFH patients Initiation of high-intensity High intensity statin statin monotherapy is standard of care Ezetimibe is added when Cholesterol patient is not at LDL-C absorption inhibitor threshold (ezetimibe) Add a PCSK9 inhibitor PCSK9 inhibitor Add lomitapide or ANGPTL3-
Slide 18: How does CETP fit in this pathobiology?
How does CETP fit in this pathobiology? 18
Slide 19: HDL-C initial target for CETP inhibition
HDL-C initial target for CETP inhibition CETP inhibitors were initially developed based on the premise that increasing HDL-C would prevent CHD CETP, HDL-C and the risk of CHD CHD= Coronary Heart Disease Emerging Risk Factors Collaboration, Di Angelantonio E, Sarwar N, Perry P, Kaptoge S, Ray KK, Tho
Slide 20: Dalcetrapib: Dal-OUTCOMES Study
Dalcetrapib: Dal-OUTCOMES Study CVOT with ~16,000 patients with recent MI on lipid- lowering therapy randomized to dalcetrapib or placebo CVOT= Cardiovascular outcomes trial MI= Myocardial Infarction Schwartz, GG, et, al., Effects of Dalcetrapib in Patients with a Recent Acute Coronary Syndrome, Nov
Slide 21: HDL-C increase in Dal-OUTCOMES did not lower CHD risk
HDL-C increase in Dal-OUTCOMES did not lower CHD risk; the end of the HDL hypothesis HDL cholesterol levels increased from baseline by 4 to 11% in the placebo group and by 31 to 40% in the dalcetrapib group Dalcetrapib did not alter the risk of the primary end point* Dalcetrapib had a minimal effect
Slide 22: Dalcetrapib did not move LDL-C
Dalcetrapib did not move LDL-C 22
Slide 23: Evacetrapib: ACCELERATE Study
Evacetrapib: ACCELERATE Study CVOT with ~12,000 patients with recent ACS, or other vascular disease, on lipid- lowering therapy randomized to evacetrapib or placebo CVOT= Cardiovascular outcomes trial ACS= Acute coronary syndrome Lincoff, AM. et al,. Evacetrapib and Cardiovascular Outcomes in High-R
Slide 24: ACCELERATE; LDL-C was measured by a direct assay
ACCELERATE; LDL-C was measured by a direct assay Wrong assay! LDL-C was measured using a direct assay vs preparative ultra-centrifugation which is more sensitive at low absolute LDL-C levels Lincoff, AM. et al,. Evacetrapib and Cardiovascular Outcomes in High-Risk Vascular Disease, May 18, 2017, N E
Slide 25: Kaplan-Meier curves for ACCELERATE, REVEAL and IMPROVE-IT studies
Kaplan-Meier curves for ACCELERATE, REVEAL and IMPROVE-IT studies 35 With only modest absolute ApoB lowering in all 3 studies (-15 mg/dl), Simvastatin curves show separation later than the point in time that ACCELERATE Simvastatin-Ezetimibe 30 stopped, indicating necessity of longer duration studies
Slide 26: Evacetrapib's CVOT was underpowered and too short
Evacetrapib's CVOT was underpowered and too short 26
Slide 27: Anacetrapib: REVEAL Study
Anacetrapib: REVEAL Study CVOT with ~30,000 patients with occlusive vascular disease on lipid- lowering therapy randomized to anacetrapib or placebo CVOT= Cardiovascular outcomes trial The HPS3/TIMI55–REVEAL Collaborative Group, Effects of Anacetrapib in Patients with Atherosclerotic Vascular Diseas
Slide 28: REVEAL study results were initially misinterpreted
REVEAL study results were initially misinterpreted based on the reported 41% LDL-C reduction At 4.1 years, two important learnings: Learning 1: Predictable MACE benefit Learning 2: Baseline levels were too low • 9% drop in MACE is exactly predicted by the CTT metaregression • Baseline 60 mg/dL alrea
Slide 29: Phase 2 Dose-Finding Study of Obicetrapib 5 and 10 mg with High-Intensity Statin
Chemistry A Placebo-Controlled, Double-Blind, Randomized, Phase 2 Dose-Finding Study to Evaluate the Effect of Obicetrapib 5 and 10 mg as an Adjunct to High-Intensity Statin Therapy Stephen J Nicholls, Marc Ditmarsch, John J Kastelein, Scott P Rigby, Douglas Kling, Danielle L Curcio, Nicholas J Alp,
Slide 30: ROSE Phase 2b: robust LDL-C lowering as adjunct to high intensity statins
In ROSE Phase 2b clinical trial, obicetrapib demonstrated robust LDL-C lowering as adjunct 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 10mg
Slide 31: ROSE waterfalls: LDL-C % change from baseline
ROSE waterfalls: LDL-C % change from baseline at Day 56 LDL-C reduction of >60% was observed in LDL-C reduction of >60% was observed in 20% of obicetrapib 5mg patients 40% of obicetrapib 10mg patients Note: Each bar represents one subject in the trial. NewAmsterdam Pharma Data on File 31
Slide 32: ROSE safety: AEs, SAEs and withdrawals overview
ROSE safety: AEs, SAEs and withdrawals overview Positive safety profile observed, and no drop-outs due to AEs Placebo Obicetrapib 5mg Obicetrapib 10mg (N=40) (N=40) (N=40) AEs (%) 19 (47.5) 15 (37.5) 8 (20.0) AEs, total 4 (10.0) 2 (5.0) 1 (2.5) AEs, related 1 (2.5) 0 0 AEs, severe SAEs 2 (5.0) 0 0 S
Slide 33: 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 34: Conclusions
Conclusions • Driving statins to their highest dose as monotherapy has many downsides, of which failed goal attainment is the worst • Emerging data support the rationale for the option of combining early with ezetimibe, bempedoic acid, monoclonals against PCSK9 or inclisiran makes the most sense • N