Anacetrapib

Jan. 14, 2021 11:00 UTC Founding investor Forbion joined by co-lead investors, Morningside Ventures and Ascendant BioCapital, and other leaders in global biopharmaceutical investment Funding will support initiation and finalization of Phase 3 development of obicetrapib, a potent ApoB and LDL-c lowering small molecule drug, intended for patients not well-controlled on statins NewAmsterdam Pharma welcomes Jason Dinges of Morningside and Gaurav Gupta, MD of Ascendant BioCapital to its board of directors NAARDEN, the Netherlands--(BUSINESS WIRE)-- NewAmsterdam Pharma (NAP), a clinical stage company focused on the research and development of transformative therapies for cardio-metabolic diseases, today announced completion of a $196M (€160M) Series A funding round. The financing will support the full Phase 3 development of its ApoB and LDL-c lowering small molecule drug, obicetrapib. The drug, a cholesteryl ester transfer protein (CETP) inhibitor, is being developed for patients who are not well-controlled on statins. Forbion, NAP’s founding investor, was joined by Morningside Ventures and Ascendant BioCapital as co-lead investors in the Series A financing. Also participating in this funding round were Kaiser Foundation Hospitals, BVF Partners L.P., Population Health Partners, LSP Dementia Fund, Peter Thiel, Janus Henderson Investors, Medpace, GL Capital, JVC Investment Partners, and Presight Capital. “This is an important milestone in the advancement of obicetrapib and the growth of NewAmsterdam Pharma,” said Michael Davidson, MD, chief executive officer of NewAmsterdam Pharma. “The tremendous support of our investors allows us to initiate a large, Phase 3 development program as we work to create a new option for the millions of high cardiovascular risks patients globally who, despite maximally tolerated statin therapy, require additional LDL-c lowering options.” “Effectively inhibiting CETP to reduce atherosclerotic risk in patients is something Dr. Davidson and I have been endeavoring to achieve in our field of research for more than two decades,” said John Kastelein, MD, PhD, FESC, chief scientific officer of NewAmsterdam Pharma. “Long term follow up from the 2017 REVEAL study validated CETP as a target to lower LDL-c and reduce major adverse cardiac events (MACE).1 We believe that in obicetrapib, based on clinical studies to date, we have a molecule which is well tolerated and has not shown any of the safety issues of previous CETP inhibitors. Furthermore, based on the surrogate endpoints of the REVEAL study, obicetrapib was shown to be more effective at lowering LDL-c at a 5 mg dose in comparison to a 100 mg dose of anacetrapib.” “We are very pleased to support the development of obicetrapib and contribute to the success of NAP,” said Jason Dinges of Morningside. “We believe that obicetrapib has a unique efficacy and safety pro will further demonstrate not only a potent LDL-c lowering ability but other key attributes which could potentially benefit the large and underserved number of patients at risk of cardiovascular disease. We have confidence in the deep expertise and proven track record of Dr. Davidson and Dr. Kastelein to deliver these results.” “Cardiovascular disease remains the leading cause of disability-adjusted life years globally, and tens of millions of patients struggle to reach LDL-c goals on current therapies, demonstrating a clear need for novel agents,” said Gaurav Gupta, MD of Ascendant BioCapital. “CETP-silencing mutations correspond to lower cardiovascular risk, and given the potent pharmacology demonstrated in the TULIP study2, we expect obicetrapib to become a significant part of the treatment paradigm for dyslipidemia globally.” Two Phase 2b clinical trials for obicetrapib are underway with targeted completion in Q2 2021. NAP is looking to initiate Phase 3 clinical trials in Q4 2021. About Obicetrapib Obicetrapib is a cholesteryl ester transfer protein (CETP) inhibitor which targets Apolipoprotein B (ApoB) and low-density lipoprotein cholesterol (LDL-c) in the body. Millions of people globally have cannot achieve LDL-c goals despite maximally tolerated statin therapy.3 A Phase 2b study called TULIP, published in The Lancet, showed that obicetrapib significantly reduced the number of ApoB-containing particles that constitute LDL-c and was well tolerated in patients with mild dyslipidemia. The randomized, double-blind, placebo-controlled study tested the drug in 364 patients, to assess the safety, tolerability, and efficacy of the potential therapy. Two Phase 2b clinical trials for obicetrapib are underway with targeted completion in Q2 2021. NAP is working to initiate Phase 3 trials in Q4 2021. About NewAmsterdam Pharma Founded in 2019 by the venture capital firm Forbion and John Kastelein, NewAmsterdam Pharma is a privately held, clinical-stage company focused on the research and development of transformative therapies for cardiometabolic diseases. Its mission is to improve patient care in populations where traditional therapies are not tolerated or have been unsuccessful. In April 2020, NewAmsterdam acquired Dezima Pharma from Amgen, including all rights for obicetrapib (formerly AMG 899, now TA-8995) a selective cholesteryl ester transfer protein (CETP) inhibitor. The Company is investigating obicetrapib as the preferred ApoB and LDL-c lowering therapy for patients with ASCVD/FH on the maximally tolerated dose of statin therapy. NewAmsterdam Pharma is headquartered in Naarden, The Netherlands. For more information, please visit: 1 2 Hovingh GK, Kastelein JP, van Deventer SJH, Round P, Ford, J, Saleheen D, et. al. Cholesterol ester transfer protein inhibition by TA-8995 in patients with mild dyslipidemia (TULIP): a randomized, double-blind, placebo-controlled phase 2 trial. The Lancet 2015.386(9992): 452-460. DOI: (15)60158-1 3 Ray K et al. EU-Wide Cross-Sectional Observational Study of Lipid-Modifying Therapy Use in Secondary and Primary Care: the DAVINCI study, European Journal of Preventive Cardiology 2020 View source version on businesswire.com: Contacts Media and Investor Inquiries: NewAmsterdam Pharma McDougall Communications on behalf of New Amsterdam Pharma Elizabeth Harness, P: +1 585-435-7379, elizabeth@mcdougallpr.com Christopher Knospe, P: +1 716-440-5580, chris@mcdougallpr.com Source: NewAmsterdam Pharma View this news release online at:

Amgen inherited the drug after acquiring Dezima Pharma in a $1.2 billion deal in 2015. In 2015, P.K. Shah , director of atherosclerosis research at Cedars-Sinai Heart Center in Los Angeles, declared that CETP inhibitors were “dead” as legitimate drug targets. Shah said CETP inhibitors are a cardiologist’s dream that has not come true. Fast forward to today and it seems that Amgen may finally be in agreement with Shah’s statement. In its Third-quarterly report, Amgen announced it has scrapped internal development of AMG 899, an oral CETP inhibitor it acquired in the $1.2 billion deal for Netherlands-based Dezima Pharma BV. Amgen finally pulled the plug more than a year after it had suspended development of the CETP product. This morning, Amgen provided no details in its report as to what prompted the final decision to terminate the program, but that result further realizes Shah’s prediction. Amgen’s decision may have been linked to rival Merck ’s decision earlier this month to not submit regulatory filings for its cholesterol drug anacetrapib. In August, the company announced overall positive results for a four-year clinical trial of CETP drug anacetrapib. At the same time though, the company said the drug appeared to accumulate in fat tissue after extended dosing, which could hinder efficacy or create some unwanted adverse effects. At the time of Amgen’s 2015 acquisition of Dezima, analysts were already questioning if the cardiac drug was worth the cost. Two days after Amgen acquired AMG 899, Eli Lilly scrapped its Phase III CETP program that was testing if evacetrapib was a suitable treatment for high-risk atherosclerotic cardiovascular disease. Lilly pulled the plug on the CETP program following the recommendation of an independent data monitoring committee that said there was a “low probability” the study would achieve its primary endpoint based on results to date. CETP is a “cholesteryl ester transfer protein” which transfers cholesterol from HDL to VLDL Shah made the comment that CETP inhibitors were dead in an interview with Reuters following Lilly’s decision. Now with Amgen and Merck pulling out of the CETP development, it seems that the once-great hope for cholesterol treatment is, as Shah said, dead. Merck and Amgen are the two latest companies in a line who have shuttered their programming. In 2006, Pfizer terminated its trials for torcetrapib over safety concerns and in 2012, Roche discontinued studies of dalcetrapib for efficacy. Despite Roche’s failure, London-based DalCor is testing dalcetrapib in a subset of patients with a certain genotype, Endpoints News noted. Although AMG 899 is closed, Amgen still has other cholesterol treatments in its arsenal, such as Repatha, its PCSK9 drug. In its Q3 report, Amgen said Repatha sales increased “riven by higher unit demand.” And Repatha could continue to drive revenue. A Phase III study of Repatha on top of “maximally tolerated statin therapy in type 2 diabetic patients with hypercholesterolemia” met its co-primary endpoints of the percent reduction from baseline in LDL-C at week 12, and the mean percent reduction from baseline in LDL-C at weeks 10 and 12, with no new safety findings, Amgen reported. Amgen filed a supplemental Biologics License Application (sBLA) to include risk reduction of major cardiovascular events based on data from the large Repatha cardiovascular outcomes study. The U.S. Food and Drug Administration has set a Prescription Drug User Fee Act (PDUFA) target action date of Dec. 2, 2017.