Comparison of Intensive Lipid-Lowering Therapy Without Aspirin vs. Moderate-Intensity Lipid-Lowering Therapy With Aspirin in Asymptomatic Patients With Coronary Artery Calcification (GUIDE-CAC Trial)

A multicenter, randomized, open-label, non-inferiority trial evaluating the efficacy and safety of intensive lipid-lowering therapy without aspirin compared to moderate-intensity lipid-lowering therapy with aspirin in asymptomatic patients with coronary artery calcification.

Start Date01 Apr 2025

Sponsor / Collaborator

Asan Medical Center

NCT06686615

/ Not yet recruitingNot Applicable

Effectiveness and Safety of Bempedoic Acid in Combination With Ezetimibe and Either Rosuvastatin or Atorvastatin in Patients With Primary Hypercholesterolemia or Mixed Dyslipidemia: an Observational Study

Data on the real-world use and effectiveness and safety of bempedoic acid combined with both a statin and ezetimibe in clinical practice is limited. There is an increased focus on using combination therapy to lower LDL-C.

Start Date03 Mar 2025

Sponsor / Collaborator

Daiichi Sankyo Europe GmbH

NCT06742853

/ RecruitingPhase 1

A Phase 1, Randomized, Single-blind, Placebo-controlled Study to Investigate the Pharmacokinetics, Safety, Tolerability, and Efficacy of AZD0780 in Combination With Ezetimibe, Ezetimibe/Rosuvastatin, or Ezetimibe/Bempedoic Acid in Healthy Male and Female Participants 18 to 75 Years of Age With Elevated LDL-C.

The main aim of this study is to assess the effects of AZD0780 when added on top of ezetimibe or ezetimibe and rosuvastatin or ezetimibe and bempedoic acid.

Start Date20 Dec 2024

Sponsor / Collaborator

AstraZeneca PLC

100 Clinical Results associated with Ezetimibe

100 Translational Medicine associated with Ezetimibe

100 Patents (Medical) associated with Ezetimibe

6,241

Literatures (Medical) associated with Ezetimibe

01 Apr 2025·SEPARATION AND PURIFICATION TECHNOLOGY

Using artificial neural networks to elucidate retention interactions on stationary phases with amine moieties dedicated to supercritical fluid chromatography

Author: Plachka, Katerina ; Gazarkova, Tatana ; Plachká, Kateřina ; Pilarova, Veronika ; Nováková, Lucie ; Pilařová, Veronika ; Svec, Frantisek ; Švec, František ; Garrigues, Jean-Christophe ; Novakova, Lucie ; Gazárková, Taťána

The retention mechanisms of small mols. on a wide range of stationary phases using different mobile phase compositions are one of the most discussed topics in current state-of-the-art supercritical fluid chromatog. (SFC).Although various theories have been published on retention behavior, prediction, and stability over time, an in-depth insight into the mechanisms is still lacking.Our study focused on the description of the retention mechanisms on columns with amine moieties, i.e., 2-ethylpyridine, 2-picolylamine, 1-aminoanthracene, and diethylamine, dedicated to SFC, using three different compositions of organic modifier, i.e., methanol, methanol + 10 mmol/L NH₃, and methanol + 2 % H₂O, in CO₂.An extensive set of analytes characterized by more than 200 mol. descriptors was used.The importance of the effect of each mol. descriptor on the retention behavior was determined by artificial neural networks.Thus, the descriptors increasing and/or decreasing retention on individual columns using different mobile phase compositions were defined.The data collected over one year of column use were statistically evaluated to describe the retention behavior of small mols. on the tested stationary phases using three organic modifiers and to describe the changes in retention behavior over time.As the development of the SFC method can be laborious and time-consuming, this publication offers a detailed description of the interactions taking place between the analyte and the SFC stationary phase.Understanding these fundamental processes will enable faster development of SFC methods using quality-by-design principles.

01 Mar 2025·CANCER LETTERS

Dual targeting PPARα and NPC1L1 metabolic vulnerabilities blocks tumorigenesis

Article

Author: Hu, Xi ; Yuan, Shenli ; Fan, Yuchen ; Huang, Tao ; Yin, Jilong ; Liu, Lanlan ; You, Xiaona ; Wang, Juncheng ; Zhang, Yingjie ; Sun, Zenghui ; Zhang, Zhiyue ; Xu, Wenwen ; Wang, Limei ; Wang, Hao ; Xu, Wei ; Liu, Fabao

Dysregulated lipid metabolism is linked to tumor progression. In this study, we identified Niemann-Pick C1-like 1 (NPC1L1) as a downstream effector of PKM2. In breast cancer cells, PKM2 knockout (KO) enhanced NPC1L1 expression while downregulating peroxisome proliferator-activated receptor α (PPARα) signaling pathway. PPARα and nuclear factor-E2 p45-related factor 1/2(Nrf1/2) are transcription factors regulating NPC1L1. In vitro PKM2 KO enhanced recruitment of Nrf1/2 to the NPC1L1 promoter region. Fenofibrate, a PPARα activator, promoted NPC1L1 expression; ezetimibe, an NPC1L1 inhibitor and effective Nrf2 activator, also elevated NPC1L1 expression. Combined administration of fenofibrate and ezetimibe significantly induced cytoplasmic vacuolation, and cell apoptosis. Mechanistically, this combined administration activated inositol required enzyme 1α(IRE1α) and produced the spliced form of X-box binding protein (XBP1s), which in turn enhanced lysine demethylase 6B (KDM6B) transcription. XBP1s interacts with KDM6B to activate genes involved in the unfolded protein response by demethylating di- and tri-methylated lysine 27 of histone H3 (H3K27), consequently increasing H3K27 acetylation levels in breast cancer cell lines. Fenofibrate and ezetimibe synergistically inhibited tumor growth in vivo. Our findings reveal that dual targeting of PPARα and NPC1L1 may represent a novel therapeutic regimen for breast cancer therapy.

01 Mar 2025·SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY

Eco-friendly synchronous spectrofluorimetry coupled with chemometrics for simultaneous determination of ezetimibe and propranolol in pharmaceutical formulations and spiked plasma samples

Article

Author: Alqahtani, Taha ; Alshehri, Adil ; Fatease, Adel Al ; Almrasy, Ahmed A. ; Alqahtani, Ali ; Almrasy, Ahmed A

In this study, synchronous fluorescence spectroscopic methods coupled with chemometric techniques were developed and evaluated for the simultaneous quantification of ezetimibe and propranolol, two commonly prescribed cardiovascular drugs. Both drugs exhibit overlapping native fluorescence, posing a challenge for their selective determination. To address this, chemometric models including partial least squares (PLS) and genetic algorithm-based variable selection (GA) were constructed using a calibration dataset based on a 5² factorial design resulting in 25 synthetic mixtures. The developed method has been optimized to account for factors such as solvent composition, micellar systems, and excitation/emission wavelengths that affect the fluorescence signals. The PLS and GA-PLS models were validated using an independent test set of 13 samples based on central composite design revealing the GA-PLS model provided improved quantitative performance with relative root mean square error of prediction (RRMSEP) values of 1.3939 and 1.0005 % for ezetimibe and propranolol, respectively, compared to 2.2502 and 2.3526 % for the PLS models. Hence, the GA-PLS models were successfully applied for the determination of ezetimibe and propranolol in pharmaceutical formulations and spiked plasma samples. Furthermore, the greenness and blueness of the proposed methods were compared against reported HPLC procedures using the AGREE and BAGI tools, revealing a greener analytical footprint for the developed method and higher analytical practicability posing as an environmental-friendly alternative to the standard HPLC technique.

135

News (Medical) associated with Ezetimibe

10 Jan 2025

·www.globenewswire.com

NewAmsterdam Pharma Highlights 2024 Achievements and Outlines 2025 Strategic Priorities

-- Additional data from BROADWAY, BROOKLYN, and TANDEM to be presented throughout 2025; expected to support global regulatory filings for obicetrapib, including EMA submission in 2H25 by our partner Menarini – -- Data from Phase 2 VINCENT trial expected by 2H25, which explores effect of obicetrapib alone and in combination with a PCSK9i on Lp(a) – -- Focus on commercial readiness with manufacturing capacity establishment and inventory build-out -- -- Year end, unaudited, cash balance of $835 million following oversubscribed public offering in December 2024 -- NAARDEN, The Netherlands and MIAMI, Jan. 10, 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 provided an update on the obicetrapib clinical development program and outlined its strategic priorities for 2025. NewAmsterdam is developing obicetrapib, an oral, low-dose, once-daily, and highly selective cholesteryl ester transfer protein (“CETP”) inhibitor, alone or as a fixed-dose combination with ezetimibe, as preferred LDL-C lowering therapies to be used as an adjunct to statin therapy for patients at risk of cardiovascular disease with elevated LDL-C, for whom existing therapies are not sufficiently effective or well tolerated. The Company’s global, pivotal Phase 3 clinical development program consists of four trials in over 12,250 patients. "2024 was a landmark year for NewAmsterdam, underscored by exceptional clinical and operational execution. We announced positive topline results from three pivotal Phase 3 trials, BROOKLYN, TANDEM, and BROADWAY, which will form the foundation for our planned global regulatory filings for obicetrapib,” said Michael Davidson, M.D., Chief Executive Officer of NewAmsterdam. “We were particularly excited to announce results from BROADWAY, which demonstrated greater than expected reduction in the exploratory outcome measure of major adverse cardiovascular events (“MACE”) after only one year of treatment with obicetrapib, with a safety profile that was comparable to placebo. These data not only reinforce obicetrapib’s potential to both lower LDL-C and address critical cardiovascular risks, but also support the approach we have taken for our ongoing PREVAIL Phase 3 cardiovascular outcomes trial (“CVOT”), which is designed to assess MACE benefit as its primary endpoint.” “As we move into 2025, we are focused on sharing additional scientific findings on obicetrapib’s therapeutic potential through presentations at leading medical meetings and publications in high-impact journals, and on advancing PREVAIL toward a successful data readout. Importantly, following our recent financing, we are operating from a position of financial strength, with capital to support operations through the anticipated PREVAIL CVOT readout and, pending regulatory approval, the commercial launch of obicetrapib. We believe we are at the precipice of a major transformation for CVD care globally and remain steadfast in our mission to unlock the full potential of obicetrapib for the millions of people living with dyslipidemia and at heightened risk for CVD,” continued Dr. Davidson. Key 2024 Achievements: NewAmsterdam announced positive topline results for three Phase 3 clinical studies, each with safety comparable to placebo: BROADWAY evaluated obicetrapib in 2,530 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 December, NewAmsterdam reported positive topline data from the BROADWAY study. The primary endpoint was the least-squares mean of the percent change in LDL-C from baseline to day 84 for obicetrapib 10 mg compared to placebo. The primary endpoint was achieved with statistical significance with an LDL-C reduction of 33% (p<0.0001). Mean and median reductions in LDL-C at day 84 were 33% and 36%, respectively. As part of the safety analysis, the trial adjudicated MACE, including death, non-fatal myocardial infarction, non-fatal stroke and coronary revascularization, and in an exploratory analysis, a 21% reduction in MACE favoring obicetrapib was observed. NewAmsterdam expects to report additional data at an upcoming medical conference and to publish the data in a major medical journal.TANDEM evaluated obicetrapib as part of a fixed-dose combination tablet with ezetimibe, a non-statin oral LDL-lowering therapy, in 407 patients with established ASCVD or multiple risk factors for ASCVD and/or HeFH, whose LDL-C is not adequately controlled despite being on maximally tolerated lipid-lowering therapy. In November, NewAmsterdam reported that the TANDEM trial met all co-primary endpoints, including the obicetrapib-ezetimibe fixed dose combination achieving an LS mean reduction of 49% (p < 0.0001) compared to placebo at day 84. Mean and median reductions in LDL-C at day 84 were 52% and 54%, respectively. NewAmsterdam expects to report additional data at an upcoming medical conference and to publish the data in a major medical journal.BROOKLYN evaluated obicetrapib in 354 patients with HeFH, whose LDL-C is not adequately controlled despite being on maximally tolerated lipid-lowering therapy. In July, NewAmsterdam reported that the BROOKLYN trial met its primary endpoint, achieving an LS mean reduction of 36% (p < 0.0001) compared to placebo at day 84, with additional data presented at the American Heart Association Scientific Sessions 2024 in November. Mean and median reductions in LDL-C at day 84 were 36% and 39%, respectively.PREVAIL is a cardiovascular outcomes trial evaluating obicetrapib in patients with a history of ASCVD, whose LDL-C is not adequately controlled despite being on maximally tolerated lipid-lowering therapy. NewAmsterdam completed enrollment of over 9,500 patients in April 2024 and the trial continues in line with expectations. In addition, NewAmsterdam announced that the United States Patent and Trademark Office (“USPTO”) issued a new patent covering the solid form that will be used in the Company’s products. The issuance of this composition of matter patent provides intellectual property protection for obicetrapib until July 2043 in the United States. The USPTO has now issued or allowed a total of nine patents covering obicetrapib and its uses. Key 2025 Milestones and Ongoing Trials: Over the course of 2025, NewAmsterdam plans to announce additional data from its Phase 3 studies, including BROADWAY, TANDEM, and BROOKLYN. NewAmsterdam also plans to publish data on a significant number of topics that support the overall benefit and differentiation of obicetrapib and the fixed dose combination of obicetrapib plus ezetimibe, compared to other lipid lowering therapies. In addition to PREVAIL, NewAmsterdam continues to enroll two studies of obicetrapib, including: VINCENT, a Phase 2 clinical study to evaluate the effects of obicetrapib alone and in combination with evolocumab on lipoprotein (a) (“Lp(a)”) in patients with mild dyslipidemia. The single arm study will treat patients with obicetrapib 10mg daily for 8 weeks followed by obicetrapib 10mg daily plus evolocumab 140 mg/dL every other week for 8 weeks. The study is expected to complete in the second half of 2025 and to enroll 30 patients with baseline Lp(a) levels above 50 mg/dL.REMBRANDT, a Phase 3 cardiovascular computed tomography angiography imaging trial to evaluate the effect of obicetrapib plus ezetimibe FDC on coronary plaque. The placebo-controlled, double-blind, randomized, Phase 3 study is being conducted in adult participants with high-risk atherosclerotic cardiovascular disease (ASCVD) who are not adequately controlled by their maximally tolerated lipid-modifying therapy, to assess the impact of the obicetrapib 10 mg + ezetimibe 10 mg FDC daily on coronary plaque and inflammation characteristics. The study is expected to complete in 2027 and to enroll 300 patients. An additional focus for the Company throughout 2025 will be on commercial manufacturing and readiness. The Company plans to scale up and build inventory sufficient for both the U.S. and European launches, if approved, which will be supported by the approximately $835 million of unaudited cash on hand at year-end 2024. About Obicetrapib Obicetrapib is a novel, oral, low-dose, and highly selective 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 is currently conducting the Phase 3 PREVAIL cardiovascular outcomes trial, which is designed to assess the potential of obicetrapib to reduce occurrences of major adverse cardiovascular events, including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke and non-elective coronary revascularization. NewAmsterdam 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, for cardiovascular diseases have been exclusively granted to the Menarini Group, an Italy-based, leading international pharmaceutical and diagnostics company. About Cardiovascular Disease Cardiovascular disease remains the leading cause of death globally, despite the availability of lipid-lowering therapies (LLTs). By 2050 more than 184 million US adults are expected to be affected by CVD and hypertension, including 27 million with coronary heart disease and 19 million with stroke. In the United States from 2019 through 2022, CVD age-adjusted mortality rates increased 9%, reversing the trend observed since 2010 and undoing nearly a decade of progress. Despite the availability of high-intensity statins and non-statin LLTs, LDL-C target level attainment remains low, contributing to residual cardiovascular risk, and underscoring a significant clinical need for improved therapeutic regimens. Even with 269 million LLT prescriptions written over the last 12 months, 30 million under-treated US adults are not at their risk-based LDL-C goal, of which 13 million have ASCVD. Less than 1 in 4 patients with ASCVD achieve an LDL-C goal of less than 70mg/dL and only 10% of very high risk ASCVD patients achieve the goal below 55 mg/dL. In addition to the 30 million under-treated US adults, there are 10 million patients diagnosed with elevated LDL-C who are not taking any LLTs including statins. Beyond LDL-C, additional factors are at play, such as lifestyle choices, tobacco use, and obesity, as well as inflammation, thrombosis, triglyceride levels, elevated Lp(a) levels, and type 2 diabetes. About NewAmsterdam NewAmsterdam Pharma (Nasdaq: NAMS) is a late-stage, clinical biopharmaceutical company whose mission is to improve patient care in populations with metabolic diseases where currently approved therapies have not been adequate or well tolerated. We seek to fill a significant unmet need for a safe, well-tolerated and convenient LDL-lowering therapy. In multiple Phase 3 trials, NewAmsterdam is investigating obicetrapib, an oral, low-dose and once-daily CETP inhibitor, alone or as a fixed-dose combination with ezetimibe, as LDL-C lowering therapies to be used as an adjunct to statin therapy for patients at risk of CVD with elevated LDL-C, for whom existing therapies are not sufficiently effective or well tolerated. Forward-Looking Statements Certain statements included in this document that are not historical facts are forward-looking statements for purposes of the safe harbor provisions under the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements generally are accompanied by words such as “believe,” “may,” “will,” “estimate,” “continue,” “anticipate,” “intend,” “expect,” “should,” “would,” “plan,” “predict,” “potential,” “seem,” “seek,” “future,” “outlook” and similar expressions that predict or indicate future events or trends or that are not statements of historical matters. These forward-looking statements include, but are not limited to, statements regarding the Company’s business and strategic plans, the Company’s commercial opportunity, the therapeutic and curative potential of the Company’s product candidate, the Company’s clinical trials and the timing for enrolling patients, the timing and forums for announcing data, the achievement and timing of regulatory approvals, and plans for commercialization. These statements are based on various assumptions, whether or not identified in this document, and on the current expectations of the Company’s management and are not predictions of actual performance. These forward-looking statements are provided for illustrative purposes only and are not intended to serve as and must not be relied on as a guarantee, an assurance, a prediction, or a definitive statement of fact or probability. Actual events and circumstances are difficult or impossible to predict and may differ from assumptions. Many actual events and circumstances are beyond the control of the Company. These forward-looking statements are subject to a number of risks and uncertainties, including changes in domestic and foreign business, market, financial, political, and legal conditions; risks related to the approval of the Company’s product candidate and the timing of expected regulatory and business milestones, including potential commercialization; whether topline, initial or preliminary results from a particular clinical trial will be predictive of the final results of that trial and whether results of early clinical trials will be indicative of the results of later clinical trials, or whether projections regarding clinical outcomes will reflect actual results in future clinical trials or clinical use of our product candidate, if approved; ability to negotiate definitive contractual arrangements with potential customers; the impact of competitive product candidates; ability to obtain sufficient supply of materials; global economic and political conditions, including the Russia-Ukraine and Israel-Hamas conflict; the effects of competition on the Company’s future business; and those factors described in the Company’s public filings with the Securities Exchange Commission. Additional risks related to the Company’s business include, but are not limited to: uncertainty regarding outcomes of the Company’s ongoing clinical trials, particularly as they relate to regulatory review and potential approval for its product candidate; risks associated with the Company’s efforts to commercialize a product candidate; the Company’s ability to negotiate and enter into definitive agreements on favorable terms, if at all; the impact of competing product candidates on the Company’s business; intellectual property related claims; the Company’s ability to attract and retain qualified personnel; and ability to continue to source the raw materials for the Company’s product candidate. If any of these risks materialize or the Company’s assumptions prove incorrect, actual results could differ materially from the results implied by these forward-looking statements. There may be additional risks that the Company does not presently know or that the Company currently believes are immaterial that could also cause actual results to differ from those contained in the forward-looking statements. In addition, forward-looking statements reflect the Company’s expectations, plans, or forecasts of future events and views as of the date of this document and are qualified in their entirety by reference to the cautionary statements herein. The Company anticipates that subsequent events and developments may cause the Company’s assessments to change. These forward-looking statements should not be relied upon as representing the Company’s assessment as of any date subsequent to the date of this communication. Accordingly, undue reliance should not be placed upon the forward-looking statements. Neither the Company nor any of its affiliates undertakes any obligation to update these forward-looking statements, except as may be required by law. Company ContactMatthew PhilippeP: 1-917-882-7512matthew.philippe@newamsterdampharma.com Media ContactSpectrum Science on behalf of NewAmsterdamJaryd LeadyP: 1-856-803-7855jleady@spectrumscience.com Investor ContactPrecision AQ on behalf of NewAmsterdamAustin MurtaghP: 1-212-698-8696austin.murtagh@precisionaq.com

Phase 3Clinical ResultPhase 2AHA

16 Dec 2024

·www.prnewswire.com

Menarini Group announces Positive Topline Data from Pivotal Phase 3 BROADWAY & TANDEM Clinical Trials Evaluating Obicetrapib and the Fixed-Dose Combination Obicetrapib with Ezetimibe 10 mg

– Both pivotal studies achieved primary endpoints of LS mean reduction in LDL-C on top of maximally tolerated lipid-modifying therapies with high statistical significance (p<0.0001) – Approximately 50% of patients in BROADWAY (Obicetrapib monotherapy) and over 70% of patients in TANDEM (Fixed Dose Combination Obicetrapib with Ezetimibe) achieved LDL-C target below 55 mg/dL – In BROADWAY a 21% reduction in major adverse cardiovascular events favoring Obicetrapib was observed at one year -- In both studies, Obicetrapib monotherapy and the fixed dose combination with Ezetimibe were shown to be well tolerated FLORENCE, Italy, Dec. 16, 2024 /PRNewswire/ -- Menarini Group today announces positive topline data from the Phase 3 BROADWAY (NCT05142722) and the Phase 3 TANDEM (NCT06005597) clinical trials sponsored by 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. The Phase 3 BROADWAY clinical trial (NCT05142722) was designed to evaluate 10 mg Obicetrapib in adult patients with heterozygous familial hypercholesterolemia ("HeFH") and/or established atherosclerotic cardiovascular disease ("ASCVD"), whose LDL-C is not adequately controlled, despite being on maximally tolerated lipid-lowering therapy. The phase 3 TANDEM clinical trial (NCT06005597) was designed to evaluate 10 mg Obicetrapib and 10 mg Ezetimibe fixed-dose combination in adult patients with HeFH and/or ASCVD or multiple ASCVD risk factors, whose LDL-C is not adequately controlled, despite being on maximally tolerated lipid-lowering therapy. The primary endpoint in BROADWAY was the least-squares mean of the percent change in LDL-C from baseline to day 84 for Obicetrapib 10 mg compared to placebo. The primary endpoint was achieved with statistical significance with an LDL-C reduction of 33% (p<0.0001). The observed changes in other biomarkers, including increase of high-density lipoprotein cholesterol ("HDL-C") and reduction of non-HDL-C, lipoprotein(a) ("Lp(a)"), apolipoprotein B ("ApoB"), and Apolipoprotein A1 (ApoA1) were positive and consistent with data reported from prior clinical trials. As part of the safety analysis, key adverse events ("AE") of special interests were monitored. Among these AEs, glycemic control and renal function favoured Obicetrapib. In addition, the BROADWAY trial adjudicated MACE, including death, non-fatal myocardial infarction, non-fatal stroke and coronary revascularization showing a 21% reduction in the first 4-point MACE favoring Obicetrapib. Overall, Obicetrapib was also observed to be well tolerated, with safety data, including blood pressure, comparable to placebo. The treatment discontinuation rate for the Obicetrapib arm was 11.1% versus 12.4% for placebo. The incidence of treatment-emergent adverse events ("TEAEs"), study-drug related TEAEs, and treatment-emergent serious adverse events ("TESAEs") are summarized in the table below. The co-primary endpoints in TANDEM were percent change from baseline in LDL-C of the fixed-dose combination compared to each monotherapy arm after 84 days and Obicetrapib 10 mg compared to placebo after day 84. Secondary endpoints incorporated percent changes from baseline in other biomarkers, including Lp(a), non-HDL-c and APO B. The TANDEM trial met all co-primary endpoints, including the fixed dose combination Obicetrapib with Ezetimibe achieving an LS mean reduction of 48.6% (p < 0.0001) compared to placebo at day 84. LDL-C percentage change at Day 84 In the trial, the fixed-dose combination of Obicetrapib and Ezetimibe was observed to be well tolerated, with safety data comparable to placebo. The below table summarizes study drug-related treatment emergent adverse events ("TEAEs") and study drug-related treatment emergent serious adverse events ("TESAEs"). "Cardiovascular diseases (CVDs) are the leading cause of death globally, taking an estimated 17.9 million lives each year. Despite the widespread availability of lipid lowering therapies, CVD-related deaths have risen and patients remain above LDL-C targets, many patients failing to achieve guidelines recommended LDL.C target goals. Patients and their doctors need additional options. We are very pleased that BROADWAY and TANDEM data and previously announced BROOKLYN data confirmed the ability of Obicetrapib as a monotherapy or in a fixed dose combination with ezetimibe to significantly reduce LDL-C and help patients achieve recommended target goals. This represents a key milestone in our commitment to offer patients suffering from cardiovascular diseases in Europe, a potential first in class, low dose, once daily oral treatment in the fight against cardiovascular diseases, a mission of over 30 years for our company" said Elcin Barker Ergun, Chief Executive Officer of the Menarini Group. Design of the Pivotal Phase 3 BROADWAY Clinical Trial The 52-week, global, pivotal, Phase 3, randomized, double-blind, placebo-controlled multicenter study 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 study 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 study population and the median age of participants at baseline was 65 years. The primary endpoint was 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 (-34% and -24%, respectively with p<0.0001). Other outcome measures include 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. Design of the Pivotal Phase 3 TANDEM Clinical Trial The pivotal, Phase 3, randomized, double-blind, four-arm, placebo-controlled multicenter study evaluated the effect of 10 mg Obicetrapib and 10 mg ezetimibe as a fixed-dose combination on LDL-C levels, compared to both ezetimibe 10 mg and Obicetrapib 10 mg monotherapy and to placebo. The study was conducted at sites across the United States, and a total of 407 patients with HeFH and/or ASCVD or ASCVD risk equivalents, who had a baseline LDL-C of at least 70 mg/dL, were randomized 1:1:1:1 to receive 10 mg Obicetrapib and 10 mg ezetimibe fixed-dose combination, 10 mg Obicetrapib, 10 mg ezetimibe or placebo for an 84-day treatment period. The mean baseline LDL-C for enrolled patients in the obicetrapib-ezetimibe arm was 97 mg/dL despite high intensity statin use reported by approximately 74% of patients during screening. In addition to measuring the co-primary endpoints and secondary endpoints, the trial also evaluated the safety and tolerability profile of Obicetrapib. Obicetrapib's Global Pivotal Phase 3 Program Obicetrapib global, pivotal Phase 3 clinical development program consists of four studies in over 12,250 patients, three for obicetrapib monotherapy and one for the fixed-dose combination ("FDC") with ezetimibe: BROOKLYN evaluated Obicetrapib in patients with HeFH, whose LDL-C is not adequately controlled, despite being on maximally tolerated lipid-lowering therapy (NCT05425745). Study enrollment of over 350 patients was completed in April 2023. Topline data reported in the third quarter of 2024. BROADWAY evaluated Obicetrapib in adult patients with established ASCVD and/or HeFH, whose LDL-C is not adequately controlled, despite being on maximally tolerated lipid-lowering therapy (NCT05142722). Study enrollment of over 2,500 patients was completed in July 2023. Topline data reported in the fourth quarter of 2024. TANDEM evaluated Obicetrapib as part of a FDC tablet with ezetimibe, a non-statin oral LDL-lowering therapy, in patients with established ASCVD or multiple risk factors for ASCVD and/or HeFH, whose LDL-C is not adequately controlled despite being on maximally tolerated lipid-lowering therapy (NCT06005597). Study enrollment of over 400 patients was completed in July 2024. Topline data reported in November 2024 PREVAIL is a cardiovascular outcomes trial ("CVOT") evaluating Obicetrapib in patients with a history of ASCVD, whose LDL-C is not adequately controlled, despite being on maximally tolerated lipid-lowering therapy (NCT05202509). Study enrollment of over 9,500 patients was completed in April 2024. About Obicetrapib Obicetrapib is a novel, oral, low-dose CETP inhibitor under development to overcome the limitations of current LDL-lowering treatments. In each of the Phase 2 trials, ROSE2, TULIP, ROSE, as well as the Phase 3 BROOKLYN, BROADWAY and TANDEM trials, evaluating Obicetrapib as monotherapy or combination therapy, it was observed statistically significant LDL-lowering combined with a side effect profile similar to that of placebo. The Phase 3 study cardiovascular outcomes trial PREVAIL commenced in March 2022 and is designed to assess the potential of Obicetrapib to reduce occurrences of major adverse cardiovascular events, including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke and non-elective coronary revascularization. The enrollment of PREVAIL was completed in April 2024 and randomized over 9,500 patients. About The Menarini Group The Menarini Group is a leading international pharmaceutical and diagnostics company, with a turnover of $4.7 billion and over 17,000 employees. Menarini is focused on therapeutic areas of high unmet needs with products for cardiology, oncology, pneumology, gastroenterology, infectious diseases, diabetology, inflammation, and analgesia. With 18 production sites and 9 Research and Development centers, Menarini's products are available in 140 countries worldwide. For further information, please visit . About NewAmsterdam NewAmsterdam Pharma (Nasdaq: NAMS) is a late-stage biopharmaceutical company whose mission is to improve patient care in populations with metabolic diseases where currently approved therapies have not been adequate or well tolerated. We seek to fill a significant unmet need for a safe, well-tolerated and convenient LDL-lowering therapy. In multiple phase 3 studies, NewAmsterdam is investigating Obicetrapib, an oral, low-dose and once-daily CETP inhibitor, alone or as a fixed-dose combination with ezetimibe, as LDL-C lowering therapies to be used as an adjunct to statin therapy for patients at risk of CVD with elevated LDL-C, for whom existing therapies are not sufficiently effective or well tolerated. Logo - SOURCE Menarini Industrie Farmaceutiche Riunite WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Phase 3Clinical ResultAHA

13 Dec 2024

·www.globenewswire.com

NewAmsterdam Pharma Announces Closing of Upsized $479.0 Million Public Offering of Ordinary Shares and Pre-Funded Warrants, Including Full Exercise of the Underwriters’ Option to Purchase Additional Shares

NAARDEN, The Netherlands and MIAMI, Dec. 13, 2024 (GLOBE NEWSWIRE) -- NewAmsterdam Pharma Company N.V. (Nasdaq: NAMS; “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 the closing of the previously announced underwritten public offering of (i) 14,667,347 of the Company’s ordinary shares, nominal value €0.12 per share (the “Ordinary Shares”), at a public offering price of $24.50 per share, which includes the exercise in full of the underwriters’ option to purchase an additional 2,550,000 Ordinary Shares, and (ii) to certain investors that so choose in lieu of Ordinary Shares, pre-funded warrants to purchase 4,882,653 Ordinary Shares at a public offering price of $24.4999 per pre-funded warrant, which represents the per share public offering price for the Ordinary Shares less the $0.0001 per share exercise price for each such pre-funded warrant (such offering, the “Offering”). All of the securities sold in the Offering were sold by the Company. The net proceeds to the Company from the Offering, including the proceeds from the exercise by the underwriters of their option to purchase the additional shares, were approximately $452.6 million after deducting underwriting discounts and commissions and estimated offering expenses payable by the Company. Jefferies, Goldman Sachs & Co., Leerink Partners, TD Cowen, Guggenheim Securities and William Blair acted as joint book-running managers for the Offering. The Offering was made pursuant to a registration statement on Form S-3, including a base prospectus, that was initially declared effective by the U.S. Securities and Exchange Commission (the “SEC”) on July 12, 2024 and a related registration statement that was filed with the SEC on December 11, 2024 pursuant to Rule 462(b) under the Securities Act of 1933 (and which became automatically effective upon filing). A preliminary prospectus supplement and accompanying prospectus relating to and describing the terms of the Offering were filed with the SEC and are available free of charge by visiting EDGAR on the SEC’s website at www.sec.gov. Copies of the final prospectus supplement and the accompanying prospectus may also be obtained free of charge from: Jefferies LLC, Attention: Equity Syndicate Prospectus Department, 520 Madison Avenue, New York, NY 10022, or by telephone at (877) 821-7388, or by email at Prospectus_Department@Jefferies.com; Goldman Sachs & Co. LLC, Attention: Prospectus Department, 200 West Street, New York, NY 10282, or by telephone at (866) 471-2526, or by email at Prospectus-ny@ny.email.gs.com; Leerink Partners LLC, Attention: Syndicate Department, 53 State Street, 40th Floor, Boston, MA 02109, or by telephone at (800) 808-7525, ext. 6105, or by email at syndicate@leerink.com; TD Securities (USA) LLC, 1 Vanderbilt Avenue, New York, NY 10017, or by telephone at (855) 495-9846, or by email at TD.ECM_Prospectus@tdsecurities.com; Guggenheim Securities, LLC, Attention: Equity Syndicate Department, 330 Madison Avenue, New York, NY 10017, or by telephone at (212) 518-9544, or by email at GSEquityProspectusDelivery@guggenheimpartners.com; or William Blair & Company, L.L.C., Attention: Prospectus Department, 150 North Riverside Plaza, Chicago, IL 60606, or by telephone at (800) 621-0687, or by email at prospectus@williamblair.com. This press release shall not constitute an offer to sell or the solicitation of an offer to buy any securities, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction. Van Lanschot Kempen N.V. acted as a financial adviser to the Company. About NewAmsterdam NewAmsterdam Pharma (Nasdaq: NAMS) is a late-stage biopharmaceutical company whose mission is to improve patient care in populations with metabolic diseases where currently approved therapies have not been adequate or well-tolerated. We seek to fill a significant unmet need for a safe, well-tolerated and convenient LDL-lowering therapy. In multiple phase 3 studies, NewAmsterdam is investigating obicetrapib, an oral, low-dose and once-daily CETP inhibitor, alone or as a fixed-dose combination with ezetimibe, as LDL-C lowering therapies to be used as an adjunct to statin therapy for patients at risk of CVD with elevated LDL-C, for whom existing therapies are not sufficiently effective or well-tolerated. Company ContactMatthew PhilippeP: 1-917-882-7512 matthew.philippe@newamsterdampharma.com Media ContactSpectrum Science on behalf of NewAmsterdamJaryd LeadyP:1-856-803-7855jleady@spectrumscience.com Investor ContactPrecision AQ on behalf of NewAmsterdamAustin MurtaghP: 1-212-698-8696 austin.murtagh@precisionaq.com

Phase 3

100 Deals associated with Ezetimibe

External Link

KEGG	Wiki	ATC	Drug Bank
D01966	Ezetimibe	C10AX09	DB00973

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Hyperlipidemias	US	Organon & Co.	05 Jun 2008
Hypercholesterolemia	US	Organon & Co.	23 May 2006
Cardiovascular Diseases	AU	Organon Pharma Pty Ltd.	23 Jun 2003
Heterozygous familial hypercholesterolemia	AU	Organon Pharma Pty Ltd.	23 Jun 2003
Homozygous familial hypercholesterolemia	US	Organon & Co.	25 Oct 2002
Primary hypercholesterolemia	US	Organon & Co.	25 Oct 2002
Sitosterolemia	US	Organon & Co.	25 Oct 2002

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Coronary Disease	Phase 3	-	Schering-Plough Corp.	12 Jul 2005
Coronary Artery Disease	Phase 3	-	Organon & Co.	01 May 2003
Coronary Artery Disease	Phase 3	-	Merck Sharp & Dohme Corp.	01 May 2003
Hyperlipidemia, Familial Combined	Phase 3	-	Organon & Co.	01 Dec 2002
Hypertriglyceridemia	Phase 3	-	Organon & Co.	01 Dec 2002
Atherosclerosis	Phase 3	-	Organon & Co.	01 Jun 2002
Hyperlipoproteinemia Type II	Phase 3	-	Organon & Co.	01 Jun 2002
Diabetes Mellitus, Type 2	Phase 3	-	Organon & Co.	01 Dec 2001

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04826354 (SaveSAMS, Pubmed) Manual	Phase 4	Atherosclerosis	561	Moderate-intensity statin with ezetimibe combination therapy (rosuvastatin 5 mg with ezetimibe 10 mg)	wbehmfksag(eqwtukoggc) = thkctjnork rfegxbuenn (lukzkkkjfz ) View more	Positive	22 Dec 2024
				High-intensity statin monotherapy (rosuvastatin 20 mg)	wbehmfksag(eqwtukoggc) = upqgsklknr rfegxbuenn (lukzkkkjfz ) View more
NCT04369664 (CHORD, CTgov)	Phase 4	Diabetes Mellitus, Type 2	151	PCSK9 inhibitor+Ezetimibe 10mg+Statin (Type 2 Diabetes Group)	wxzwpspkuw(lmgayynang) = dzbsxsexyg btgafxvacj (wgjlosgefs, etifuyveup - ezsgbldjut) View more	-	17 Oct 2024
				PCSK9 inhibitor+Ezetimibe 10mg+Statin (Control Group)	wxzwpspkuw(lmgayynang) = ajrfafvxin btgafxvacj (wgjlosgefs, kawtbtklzf - iclfzoplfd) View more
ESC2024	Not Applicable	Myocardial Infarction	-	Ezetimibe use	cinpvannam(qlhefgkroi) = rcndtynczs exezrceexl (mamczxxdoc )	Positive	31 Aug 2024
				No Ezetimibe use	cinpvannam(qlhefgkroi) = flyhzzdtbd exezrceexl (mamczxxdoc )
ATS2024	Not Applicable	Idiopathic Pulmonary Fibrosis	-	Ezetimibe users	pisiamjmzj(vkttjdogdc) = qsvtdpzkcu avkxnsbayy (fuvxrbezis )	Positive	19 May 2024
				Non-users	pisiamjmzj(vkttjdogdc) = jsftsuepwf avkxnsbayy (fuvxrbezis )
NCT04638400 (CTgov)	Phase 4	Inflammation \| Atherosclerosis \| Obesity ... View more	10	Simvastatin 40mg (Simvastatin)	hpwufckcbm(fsnthbxjpa) = larfaemkgh kqlvkgixod (tkmsozrcil, xkawpnexzi - fqtgrkvmgk) View more	-	23 Jan 2024
				Ezetimibe 10mg (Ezetimibe)	hpwufckcbm(fsnthbxjpa) = yixqefjxtq kqlvkgixod (tkmsozrcil, qiswwjkhki - cbwjbqmjla) View more
NCT00988364 (Merck-123, CTgov)	Phase 4	Metabolic Syndrome	30	ezetimibe (Ezetimibe)	iuqzsjnekr(kfymqknkpq) = khgrckznso rtbxqynmho (cgnswedlwk, umszjphwjd - gvosveyiue) View more	-	30 Nov 2023
				Simvastatin (Simvastatin)	iuqzsjnekr(kfymqknkpq) = qlzgwutoxv rtbxqynmho (cgnswedlwk, hqthftescg - pyfvsszuud) View more
AASLD2023	Not Applicable	-	88	Glecaprevir/pibrentasvir + Ezetimibe	gjsujzbtre(qgqcdjyauq) = 27 (46%) patients developed HCV antibodies that persisted post-treatment omolpramsz (dkzxhfofsi )	-	10 Nov 2023
FRI094 (ENDO2023)	Not Applicable	Sitosterolemia	1	Ezetimibe 20 mg daily	uuwgeruclm(yzmvelgwhn) = kszkrofvkj irzwgplaoh (kqqvhpjfqm ) View more	Positive	05 Oct 2023
				Atorvastatin 20 mg daily	uuwgeruclm(yzmvelgwhn) = kkhbqqrcdr irzwgplaoh (kqqvhpjfqm ) View more
IMPROVE-IT (ESC2023)	Not Applicable	-	-	Ezetimibe	iofiwftpze(myfpeqqrqa): RR = 0.77 (95% CI, 0.62 - 0.96), P-Value = 0.018	Positive	26 Aug 2023
				Placebo
ADA2023	Not Applicable	Diabetes Mellitus, Type 2	-	Moderate-intensity statin with ezetimibe combination therapy	gscxafnqti(odwfglowvb): HR = 0.7 (95% CI, 0.52 - 0.93), P-Value = 0.014 View more	Positive	20 Jun 2023
				High-intensity statin monotherapy

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