NewAmsterdam Pharma Presents Positive Data from BROADWAY Trial Demonstrating Statistically Significant Reductions in Key Alzheimer’s Disease Biomarkers at AAIC 2025

• Pre-specified analysis shows obicetrapib significantly reduced absolute levels of plasma p-tau217, a key biomarker of Alzheimer’s disease pathology, in both the full analysis set (p=0.0019) and in ApoE4 carriers (p=0.0215), supporting CETP inhibition as a potential novel, upstream approach to Alzheimer’s prevention
• In APOE4/E4 carriers, the highest risk category for Alzheimer’s disease, obicetrapib reduced p-tau217 levels by 20.5%, over 12 months, compared to placebo (p=0.010)
• Results build on obicetrapib’s cardiometabolic profile, including multiple clinical trials demonstrating reductions in LDL-C, small dense LDL particles, Lipoprotein(a), and biomarkers associated with diabetes and kidney function

NAARDEN, the Netherlands and MIAMI, July 30, 2025 (GLOBE NEWSWIRE) -- NewAmsterdam Pharma Company N.V. (Nasdaq: NAMS or “NewAmsterdam” or the “Company”), a late-stage, clinical biopharmaceutical company developing oral, non-statin medicines for patients at risk of cardiovascular disease (“CVD”) with elevated low-density lipoprotein cholesterol (“LDL-C”), for whom existing therapies are not sufficiently effective or well-tolerated, today announced full data from the prespecified Alzheimer’s disease (“AD”) biomarker analysis in the BROADWAY clinical trial (NCT05142722). The data were presented today during a Developing Topics oral session at the 2025 Alzheimer’s Association International Conference (“AAIC”) in Toronto.

The BROADWAY trial was primarily designed as a pivotal Phase 3 trial to evaluate LDL-C lowering efficacy of obicetrapib, a potent CETP inhibitor, in adult patients with established atherosclerotic cardiovascular disease (“ASCVD”) and/or heterozygous familial hypercholesterolemia (“HeFH”), whose LDL-C is not adequately controlled, despite being on maximally tolerated lipid-lowering therapy. In connection with this trial, a prespecified analysis evaluated the effect of obicetrapib on plasma biomarkers of AD in 1,515 patients with established ASCVD and/or HeFH whose ApoE status was able to be determined, including 367 ApoE4 carriers. Safety in this population was not evaluated independently from the overall BROADWAY study population, where obicetrapib was observed to be well-tolerated, with safety results comparable to placebo.

ApoE4 is both a risk factor for CVD and AD where ApoE4 carriers generally exhibit higher levels of LDL-C, Lp(a), and reduced cholesterol transport and clearance. Treatment with obicetrapib 10 mg daily for 12 months resulted in statistically significant lower absolute changes in plasma p-tau217, a key biomarker of AD pathology, in both the analysis set (p=0.0019) and in ApoE4 carriers (p=0.0215). Favorable trends were also observed across additional biomarkers, including neurofilament light chain (“NFL”), glial fibrillary acidic protein (“GFAP”), p-tau181, and the Aβ42/40 ratio, in the full analysis set and in ApoE4 carriers, with the greatest effect generally observed in carriers of two E4 proteins.

One of the first biomarkers to provide evidence of neurodegeneration is p-tau217, which can begin to increase more than 20 years before onset of cognitive impairment. In addition, p-tau217 has shown significantly higher accuracy in assessing AD than alternative plasma- or MRI-based analyses, and its performance does not significantly differ from key CSF- or PET-based measures. NFL and GFAP biomarkers are also considered predictive of neurodegeneration and elevated levels in the blood have been associated with AD progression and pathology. These results build on NewAmsterdam’s Phase 2a proof of concept trial and preclinical data, which showed reductions in brain cholesterol metabolites and stabilization of AD biomarkers in ApoE4 carriers.

The Company looks forward to discussing these results with regulatory authorities to determine potential next steps.

Conference Call and Webcast Information

NewAmsterdam will host a live webcast and conference call at 10:00 a.m. ET on July 30, 2025 to review the full AD biomarker data presented at AAIC. To access the live webcast, participants may register here. The live webcast will be available under the “Events & Presentations” section of the Investor Relations page of the Company’s website at ir.newamsterdampharma.com.

To participate via telephone, please register in advance here. Upon registration, all telephone participants will receive a confirmation email detailing how to join the conference call, including the dial-in number along with a unique passcode and registrant ID that can be used to access the call. While not required, it is recommended that participants join the call ten minutes prior to the scheduled start. An archived replay of the webcast will be available on NewAmsterdam’s website following the live event.

Design of the Pivotal Phase 3 BROADWAY Clinical Trial

The 52-week, global, pivotal, Phase 3, randomized, double-blind, placebo-controlled multicenter trial evaluated the efficacy and safety of 10 mg obicetrapib compared to placebo as an adjunct to maximally tolerated lipid-lowering therapies in patients with ASCVD and/or HeFH whose LDL-C is not adequately controlled. The trial was conducted at sites in North America, Europe, Asia and Australia. A total of 2,530 patients were randomized 2:1 to receive 10 mg obicetrapib or placebo dosed as a once-daily oral treatment, with or without food for 52 weeks. The mean baseline LDL-C for enrolled patients in the obicetrapib arm was approximately 100 mg/dL despite high intensity statin use reported by nearly 70% of patients during screening. Females comprised approximately 34% of the trial population and the median age of participants at baseline was 65 years.

The primary endpoint was LS mean percent change from baseline in LDL-C of obicetrapib 10 mg compared to placebo after 84 days which showed a reduction of 33% with imputation. Secondary endpoints also included percent changes from baseline of obicetrapib 10 mg compared to placebo in ApoB, Lp(a), ApoA1, HDL-C, non-HDL-C, total cholesterol, and triglycerides at day 84, and on LDL-C levels at days 180 and 365. Other exploratory outcome measures included time from randomization until the first confirmed occurrence of MACE in the obicetrapib arm compared to placebo. The trial also evaluated the safety and tolerability profile of obicetrapib.

Alzheimer’s Analysis

In BROADWAY, a pre-specified AD analysis was designed to assess plasma AD biomarkers in patients enrolled in the BROADWAY trial and evaluated the effects of longer duration of therapy (12 months) with a prespecified population of ApoE3/4 or 4/4 carriers, based on phenotypic analysis. The analysis included 1,515 patients, including 367 ApoE4 carriers, whose ApoE status was able to be determined. Because this analysis was based on a subset of patients from BROADWAY (which was designed to evaluate LDL-C reductions in an ASCVD and/or HeFH population), the AD analysis was not controlled for baseline differences between the treatment and placebo population. The primary outcome measure was p-tau217 absolute and percent change over 12 months, among patients with baseline and end of study datapoints above the lower limit of quantitation. Additional outcome measures included NFL, GFAP, p-tau181, and Aβ42/40 ratio absolute and percent change over 12 months. NewAmsterdam observed statistically significant lower absolute changes in p-tau217 compared to placebo over 12 months in both the full analysis set (p=0.0019; n= 1,515) and in ApoE4 carriers (p=0.0215; n=367). Although a safety analysis was not performed in the AD study population, in BROADWAY obicetrapib was observed to be well-tolerated, with safety results comparable to placebo.

Design of the Phase 2a Alzheimer's Trial

The open-label and single-arm trial was designed to assess the pharmacodynamics, pharmacokinetics, safety and tolerability of obicetrapib 10 mg in early AD patients carrying at least one copy of ApoE4. A total of 13 patients were given 10 mg obicetrapib and followed for 24 weeks. NewAmsterdam observed reductions in the levels of 24- and 27-hydroxycholestrol in both plasma and cerebrospinal fluid. Overall, obicetrapib was observed to be well-tolerated. No serious adverse events (“AEs”) were reported, nor were any AEs considered to be related to the study drug.

About Obicetrapib

Obicetrapib is a novel, oral, low-dose CETP inhibitor that NewAmsterdam is developing to overcome the limitations of current LDL-lowering treatments. In each of the Company’s Phase 2 trials, ROSE2, TULIP, ROSE, and OCEAN, as well as the Company’s Phase 3 BROOKLYN, BROADWAY and TANDEM trials, evaluating obicetrapib as monotherapy or combination therapy, the Company observed statistically significant LDL-lowering combined with a side effect profile similar to that of placebo. The Company commenced the Phase 3 PREVAIL cardiovascular outcomes trial in March 2022, which is designed to assess the potential of obicetrapib to reduce occurrences of MACE. The Company completed enrollment of PREVAIL in April 2024 and randomized over 9,500 patients. Commercialization rights of obicetrapib in Europe, either as a monotherapy or as part of a fixed-dose combination with ezetimibe, have been exclusively granted to the Menarini Group, an Italy-based, leading international pharmaceutical and diagnostics company.