Newamsterdam Pharma Company N.v. · NASDAQ:NAMS
Newamsterdam Pharma — SPAC Merger (August 2022)
33 slides from Newamsterdam Pharma's SPAC merger presentation, Aug 24, 2022
Slide 1: Patients with high LDL-cholesterol; early combination therapy
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: Lack of goal attainment remains a serious problem in ASCVD patients
Lack of goal attainment remains a serious problem in ASCVD patients • US observational studies suggest that in patients with ASCVD, two- thirds to three-quarters of the patients are estimated NOT to be at their LDL-C goal • A recent observation study across 18 EU countries showed approximately 7 out
Slide 7: How can we improve? Any recent data?
How can we improve? Any recent data? 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 as initial strategy
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: What other options are on the table or under investigation?
What other options are on the table or under investigation? 10
Slide 11: Bempedoic Acid Mechanism Of Action
Bempedoic Acid Mechanism Of Action Converted to ETC-1002-CoA, the Active Form, in the Liver • Bempedoic acid (BA) acts in the same cholesterol biosynthesis pathway as statins • BA targets ATP-Citrate Lyase, an enzyme upstream of HMG-CoA reductase • Upregulates LDL receptors and lowers LDL-C • BA is
Slide 12: Study of Bempedoic Acid or Ezetimibe Alone or in Fixed-dose Combination vs Placebo
Phase 3 Study of Bempedoic Acid or Ezetimibe Alone or in Fixed-dose Combination vs Placebo Ballantyne CM, et al. Eur J Prev Cardiol. 2020;27:593-603. 12
Slide 13: Novel therapeutic modalities: siRNA – The third principal approach
Novel therapeutic modalities: siRNA – The third principal approach 13
Slide 14: ORION-11 Study: Targeting PCSK9 with siRNA
ORION-11 Study: Targeting PCSK9 with siRNA placebo inclisiran n= 1,375 p Ray, KK, et al., Two Phase 3 Trials of Inclisiran in Patients with Elevated LDL Cholesterol, April 16, 2020, N Engl J Med 2020; 382:1507-1519, DOI: 10.1056/NEJMoa1912387 14
Slide 15: Oral PCSK9 Active Clinical Pipeline
Oral PCSK9 ACTIVE Clinical Pipeline Compound MOA/chemistry Admin. Phase CVI-LM001/ CVI Small molecule modulator of oral Ph 2 Therapeutics PCSK9 gene expression NN6435/ Novo Mimetic peptide inhibitor SC: Ph 1 SC SCà oral oral: Ph 2 MK-0616/ Merck cyclic Peptide with predecessor oral Ph 2 DR- to compl
Slide 16: How does CETP fit in this pathobiology?
How does CETP fit in this pathobiology? 16
Slide 17: CETP activity increases circulating LDL-C levels
CETP activity increases circulating LDL-C levels Electron micrograph CETP curves CETP penetrates CETP directly transfers cholesterol esters against HDL HDL surface from HDL to LDL HDL LDL HDL CE PL PL TG CETP C-terminal opening N-terminal opening is where CETPi occurs CETP CE HDL LDL Note: Figures a
Slide 18: What are the consequences of CETP inhibition?
What are the consequences of CETP inhibition? 18
Slide 19: CETPi upregulates LDL-R and improves LDL and ApoB clearance through the liver
CETPi upregulates LDL-R and improves LDL and ApoB clearance through the liver Same mechanism of action as existing LDL-lowering drugs Most current LDL-lowering therapies work by promoting LDL receptor upregulation CETPi PCSK9i STATINS EZETIMIBE OBICETRAPIB Decreases Designed to block Blocks Decrease
Slide 20: Genomic Support that CETP Inhibition Drives CVD reduction through LDL-C Reduction
Genomic Support that CETP Inhibition Drives CVD reduction through LDL-C Reduction 20
Slide 21: 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 protection 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% reductio
Slide 22: CETP, HDL-C, and the risk of CHD
CETP, HDL-C, and the risk of CHD • Initially, it was not appreciated that loss-of-function mutations in the CETP gene do not only lead to increased HDL-C, but also lower LDL-C, non-HDL and apoB • We now understand that inhibiting CETP has the potential to lower CHD risk by lowering atherogenic lipid
Slide 23: REVEAL supports translation from absolute LDL-C reduction to MACE benefit
REVEAL supports translation from absolute LDL-C reduction to MACE benefit A 2.3 year follow-up of the Phase 3 REVEAL study (6.4 years in total) with Anacetrapib showed that CETP inhibition drove a MACE reduction of 20% compared to placebo Decreased Increased MACE risk MACE risk Odds ratio for MACE 9
Slide 24: Obicetrapib
Obicetrapib 24
Slide 25: Phase 2 Dose-Finding Study of Obicetrapib as Adjunct to 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 26: ROSE study: Obicetrapib and High-Intensity Statin therapy
ROSE study: Obicetrapib and High-Intensity Statin therapy (HIS) Objective To evaluate the effect of obicetrapib on top of HIS on LDL-C Inclusion criteria Study design • A stable dose of HIS (A 40 / 80; R 20 / 40) Obicetrapib 5mg (n=38) PK assessment 8 weeks prior to screening Patients(n=114) Mild dy
Slide 27: Baseline characteristics
Baseline characteristics Placebo Obicetrapib 5 mg Obicetrapib 10 mg (N=40) (N=40) (N=40) Mean Age (yrs) 61.3 61.1 62.9 Female % 52.5 42.5 37.5 2 Mean BMI (kg/m ) 30.2 32.2 30.8 Race % White 80.0 75.0 75.0 Black / African American 17.5 25.0 12.5 Statin use (%) Atorvastatin 40mg 50.0 50.0 62.5 Atorvas
Slide 28: 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 10 Placebo Obicetrapib 5mg Obicetrapib 10
Slide 29: 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 29
Slide 30: ApoB & Lp(a) percent change from baseline
ApoB & Lp(a) percent change from baseline ApoB Lp(a) Placebo Obicetrapib 5 mg Obicetrapib 10 mg Placebo Obicetrapib 5 mg Obicetrapib 10 mg 10 10 5 0 4 0 -10 -5 -3 -20 -10 -30 -15 -34 -40 -20 -50 -25 -24 -60 -30 -57 -30 -35 -70 NLA Scientific Session, Late Breaking Sessions, June 4, 2022 30 % change
Slide 31: 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 32: 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 Enrich for higher baseline Stronger expected LDL- Expected to result in more Low Drug showed mod
Slide 33: 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