NewAmsterdam Pharma Holding BV

Dive Brief:An experimental heart drug from biotechnology company NewAmsterdam Pharma met its main goal in the first of several Phase 3 trials, but the results fell short of investor and analyst expectations.In the trial, people with an inherited condition called heterozygous familial hypercholesterolemia who received the drug alongside other medicines saw their levels of LDL, or bad, cholesterol fall by 36% after three months, when adjusted for placebo, and by 41% after one year. The drug, obicetrapib, reduced other markers of heart disease while its safety was comparable to placebo, the company said.On a conference call, NewAmsterdam CEO Michael Davidson said the results raise the companys confidence in other ongoing studies. But shares fell by as much as one-third in premarket trading before opening down 4% Monday morning, as investors had anticipated more powerful cholesterol-lowering effects.Dive Insight:NewAmsterdams study is part of the biotechs effort to change the narrative surrounding a class of heart drugs known as CETP inhibitors.These drugs were once seen as a possible breakthrough in heart medicine, as companies bet that raising high-density lipoprotein, or HDL, could have stronger effects than reducing the LDL cholesterol associated with heart problems.Poor clinical performance and safety concerns caused several pharmaceutical companies to abandon research, however. Among them was Amgen, which had picked up obicetrapib in a 2015 acquisition of biotech Dezima but suspended development shortly after.Amgens decision created an opportunity for NewAmsterdam, which was launched by Dezima founders in 2019 and licensed obicetrapib from Amgen a year later. The company claims obicetrapib may be more potent and safer than previous CETP inhibitors. Early- and mid-stage studies showed promise, with the drug safely raising HDL as well as lowering LDL cholesterol. Four late-stage trials are now underway and, ahead of the results, some analysts predicted the drug could become a blockbuster if successful.Yet myriad other therapies, among them generic statins and potent, injectable drugs called PCSK9 inhibitors, are available to lower cholesterol. PCSK9 blockers can reduce LDL levels by about 50% to 60% in heterozygous familial hypercholesterolemia patients and even they havent met analysts once-lofty financial projections. Jefferies Dennis Ding, in a Friday note to clients, wrote that investors were generally looking for obicetrapib treatment to lead to at least a 40% difference in LDL levels after three months, a mark it missed.NewAmsterdam executives claimed the results show the consistency of obicetrapibs effects. They noted how the drugs LDL-C lowering appeared to strengthen with time, which could bode well for a longer, ongoing study designed to test whether obicetrapib can reduce the risk of cardiovascular events. They also highlighted the drugs safety, noting that, in the study, a higher percentage of placebo recipients discontinued treatment. Trial investigators also didnt observe the types of side effects seen in testing of other CETP inhibitors.This was a very, very well tolerated drug, and that, to me, at the end of the day, is going to be a big part of our story for clinicians and for patients, said Davidson, on a conference call.Jefferies analyst Ding also defended the findings, writing Monday that the few percentage points difference in LDL reduction versus expectations isnt overly relevant given placebo recipients initially overperformed and the drugs effects improved.NewAmsterdam will present detailed results at a medical meeting in November. Meanwhile, a study in people with atherosclerotic cardiovascular disease, a more common heart condition, will read out results by the end of the year. '

The first phase 3 data drops on NewAmsterdam Pharma's obicetrapib are due next year. NewAmsterdam Pharma has advanced its bid to write a new chapter in the story of an Amgen castoff by linking the CETP inhibitor to reductions in LDL cholesterol when used as an adjunct to high-intensity statin therapy. The Dutch biotech plans to start a phase 3 trial on the strength of the data. Amgen acquired the CETP inhibitor, obicetrapib, for $300 million upfront in its 2015 takeover of Dezima Pharma. By 2017, the Big Biotech had given up on the drug. The failure of Merck & Co.’s rival candidate drove the final nail into the coffin by seeming to confirm doubts raised by earlier setbacks at Eli Lilly, Pfizer and Roche. Yet, key players in the Dezima story kept the faith, leading them to license obicetrapib from Amgen and pump money into further development.   Now, operation save obicetrapib has delivered more phase 2 data. The placebo-controlled trial tested the CETP inhibitor as a monotherapy and in combination with ezetimibe, a cholesterol-lowering drug that Merck sold as Zetia. All participants stayed on high-intensity statin therapy after enrolling in the study. The trial enrolled 119 patients with LDL cholesterol above 70 mg/dL and triglycerides below 400 mg/dL. After 12 weeks of daily dosing, LDL levels in the obicetrapib-ezetimibe combination cohort had fallen by 59%, compared to a 6% drop in the placebo arm.  NewAmsterdam is yet to share data on the patients who received obicetrapib as a monotherapy. A meta-analysis of earlier clinical trials linked the addition of single agent ezetimibe to high-intensity statin therapy to a 14% reduction in LDL cholesterol. The meta-analysis suggests obicetrapib made a significant contribution to the 59% drop but the current lack of monotherapy data leaves questions unanswered. Obicetrapib lowered median LDL by 51% when given without ezetimibe in an earlier clinical trial. The biotech plans to release full data in a publication or presentation at an upcoming medical meeting but has privately seen enough to commit to further development of the combination, as CEO Michael Davidson, M.D., said in a statement. “We are now focused on selecting a formulated fixed-dose combination tablet of obicetrapib plus ezetimibe to advance into a definitive bioequivalence study and a phase 3 trial,” Davidson said. “If positive, the results from these trials, coupled with our ongoing BROADWAY, BROOKLYN and PREVAIL studies, if also positive, have the potential to support an application for approval of obicetrapib as an adjunct to maximally tolerated statin therapy and in a fixed-dose combination with ezetimibe.” BROADWAY, BROOKLYN and PREVAIL are phase 3 trials that are testing obicetrapib as a monotherapy. The current phase 3 program consists of two assessments of the effect on LDL cholesterol of giving the CETP inhibitor as an adjunct to maximally tolerated lipid lowering therapy, and one evaluation of its effect on the risk of major adverse cardiovascular events. The first phase 3 data drops are due next year.

Once an industry staple, so-called blank-check deals in biotech were all but left for dead at the start of 2022. Once the hottest ticket for an ambitious biotech to go public, special purpose acquisition company (SPAC) deals almost died out earlier in the year. But there has been a steady trickle in recent months, with NewAmsterdam Pharma Co. the latest to take the blank-check route. The Dutch biotech, which is focused on developing an Amgen reject drug for major cardiometabolic diseases, has merged with SPAC company Frazier Lifesciences Acquisition Corp. The combined entity, led by NewAmsterdam’s CEO Michael Davidson, M.D., and his management team, began trading on the Nasdaq this morning. With $490 million to play with, the enhanced NewAmsterdam expects to have a sufficient cash runway to last into 2026. This will take it past readouts of its three ongoing phase 3 trials for its sole candidate obicetrapib. The cholesteryl ester transfer protein (CETP) inhibitor is being studied as an adjunct to maximally tolerated statin therapy for patients with high-risk cardiovascular disease. Data from two of the trials—in patients with established atherosclerotic cardiovascular disease and those with heterozygous familial hypercholesterolemia—are due to read out in 2024. A third trial in patients with a history of atherosclerotic cardiovascular disease with inadequately controlled low-density lipoprotein cholesterol is due to report back in 2026. Meanwhile, a phase 2 trial in combination with ezetimibe—the generic version of Zetia—is expected to read out next year. “Following the close of this transaction, we are well-positioned to execute on [our] vision, with late-stage trials ongoing across the globe, a leading pharmaceutical partner to support commercialization efforts in Europe, if our product candidate is approved, and what we believe to be sufficient capital to fund our business through all expected key phase 3 data readouts for cardiovascular disease,” Davidson said in a release Nov. 23. Obicetrapib has a colorful history, having been acquired by Amgen for $300 million upfront in its 2015 takeover of Dezima. The CETP class had already been tarnished by failures at Pfizer and Roche at that point, before Eli Lilly and, most critically, Merck dumped their programs amid disappointing data. Amgen exited the field weeks after Merck in 2017 and three years later off-licensed obicetrapib to NewAmsterdam, which has a number of links back to Dezima. More recently, NewAmsterdam sold the European rights for obicetrapib to Italy’s Menarini Group in June this year in a deal worth over 1 billion euros, but retained the license for other markets as well as the rights to develop the drug for Alzheimer’s disease and certain other conditions. The Dutch biotech was founded in 2019 by venture capital firm Forbion and Chief Scientific Officer John Kastelein, M.D.—a backer and co-founder, respectively, of Dezima. NewAmsterdam's recent clinical work on obicetrapib was boosted by a $196 million series A round in January 2021. Once an industry staple, so-called blank-check deals in biotech were all but left for dead at the start of 2022, with zero SPAC mergers occurring in the first quarter. But the last few months have seen a steady, if shallow, stream of SPAC deals, including Oculis, Estrella Biopharma and Aum Biosciences all announcing their intentions in October.