Metsera, Inc.

A new type of obesity drug being developed by Novo Nordisk has fallen short of expectations set by the company in a closely watched Phase 3 trial, causing shares to lose nearly a fifth of their value in early trading on Friday.In a statement, Novo said that the drug, a combination therapy called cagrisema, helped people lose up to about 23% of their body weight after 68 weeks, about 20 percentage points higher than placebo recipients and 7 higher than those who received the companys popular weight loss drug Wegovy alone.That weight loss total missed the bar set by Novo executives, who had been hoping that cagrisema would spur about 25% weight loss over the course of the trial. Investors were anticipating as much as 27% weight loss, according to a survey conducted by Jefferies analyst Peter Welford.Additionally, patients were allowed to modify their dosing over the course of the trial, and by its end, only about 57% of patients treated with cagrisema were on the highest dose, versus around 70% of those who got Wegovy and around 83%of participants who got cagrilintide, one of the components of cagrisema. The findings suggest possible tolerability concerns for cagrisema,Welford wrote to investors Friday.Cagrisema is a combination of semaglutide, the active ingredient in Wegovy, and cagrilintide. Its a once-weekly shot targeting multiple gut hormones that regulate metabolism and hunger. Novo has been looking to it as a way to one-up its key weight loss rival Eli Lilly, whose drug Zepbound helped people lose as much as 21% of their body weight in clinical testing.Unlike Zepbound, which targets two gut hormones with a single drug, cagrisemas twocomponents are injected separately with a dual-chamber pen device. That delivery method could limit its commercial outlook given the struggles drug companies have had keeping up with demand for weight-loss medicines. Still, Novo has been hoping cagrisema might prove clearly more effective than its chief rival, even going so far as to test the drug against Zepbound in a Phase 3 trial thats expected to produce results in the second half of 2025.The trial results announced Friday are a blow to Novos obesity ambitions, then,disappointing analysts and investors eager for signs it can continue to dominate a drug class projected to eventually surpass $100 billion in yearly sales. David Risinger, an analyst with Leerink Partners, wrote that, in light of the findings, it is now questionable whether cagrisema will be able to demonstrate weight loss superiority over Zepbound.Novo is not only battling with Lilly, but trying to stay ahead of a host of other biotechnology companies eyeing a share of the market.In the trial, Novo enrolled 3,417 people with a body mass index greater than 30 or above 27 and with one weight-related health condition. Trial investigators randomized them to take cagrisema, semaglutide and a placebo, cagrilintide and a placebo, or two placebo drugs.The main objective was a comparison of cagrisema to the two placebos on weight loss. Secondary study goals included comparing weight loss for people receiving the combination to those who got the single drugs.Shares fell about 20% in early trading on Friday, while Lilly shares climbed about 6%.Still, to Prakhar Agrawal, an analyst with Cantor Fitzgerald, the results had at least one silver lining.The cagrilintide component of cagrisema outperformed investor expectations, leading to 12% of weight loss in those who received it. Thats a sign targeting the gut hormone amylin, as cagrilintide does, could hold promise treating obesity. Zealand Pharma, AstraZeneca and startup Metsera are among the drugmakers with amylin-targeting therapies in development.Novo has a second Phase 3 study of cagrisema called Redefine 2 and thats expected to produce results in 2025. Its also working on another drug combination it calls amycretin as a weekly shot and daily pill.Editors note: This story has been updated with analyst commentary. '

Last year’s Endpoints News winners and losers list was such a hit that we decided to make it a tradition. As always, we’re keeping track of who’s ⬆️ and who’s ⬇️ in biopharma, the ideas, people, drugs and companies that did better or worse than last year, and who has high hopes for 2025. As always, our choices are the product of hours of debate by all of us in the newsroom (really!), a highly rigorous scientific process (not quite) and extensive peer review (define “peer”…). Don’t like our winners? Or our losers? There’s always next year! — Drew Armstrong, Executive Editor 🤝Loser: Megadeals — After 2023’s surge in M&A, there was hope that falling interest rates and a biotech bounce-back would lead to more. That hasn’t happened — there were no $5 billion-plus takeovers of drug developers this year. Instead, pharma buyers focused on licensing deals and early-stage bets. 🤑Winner: Megarounds — Big money public deals may be out, but big money private deals are very in. There were 95 biotech venture investments of $100 million or more in 2024, as investors consolidated their bets. 🏭Winner: Anybody with a drug manufacturing plant — “Hello, yes, I represent a weight loss drug manufacturer. Lovely factory you have here. Any interest in … selling it? For cash? Today?” 🔥Winner: I&I — It was hard to find a hotter therapeutic area than inflammation and immunology in 2024. Multiple mechanisms, tons of new startups and loads of cash have poured into what investors and companies are betting will be a huge market with plentiful indications to carve up. 🐴 Loser: The FDA’s misinformation campaign — Outgoing FDA Commissioner Robert Califf made fighting medical misinformation a major focus of his post-pandemic tenure. But for all of Califf’s speeches, the effort never really caught on. The FDA lost an embarrassing lawsuit that forced it to delete its “You are not a horse” social media post telling people not to take veterinary drugs for Covid-19. And, most notably, the people who hold the anti-vaccine and Covid contrarian views will now be running the US government’s health agencies. 🏔️Winner: Bob Duggan — The former Pharmacyclics CEO could have taken his money and called it a day. Instead, he and his company Summit Therapeutics seemingly came out of nowhere with a drug that threatens to rival Merck’s Keytruda. And the data kicked off an explosion of interest in the PD-1xVEGF category. 💔Loser: Obesity startups — Pharma’s hottest category wasn’t so great for fledgling biotechs. Of almost 100 financing rounds of $100 million or more, only three obesity startups were recipients. No obesity startup was acquired this year (the last major deal announcement was Roche-Carmot in 2023). For all the hype, there seems to be real acquirer and VC questions about how much room will be left by the big players. 🧑‍⚖️Winner: The IRA (at least in court) — So far, the Biden administration’s drug price law is more or less undefeated in court. Of seven lawsuits filed by pharma companies, six have been rejected by federal judges and one is still awaiting a decision. (Whether the law will see changes under the Trump administration — or survives appeals — is a different bet.) 🚪Loser: Retail healthcare — Whether it be at a Walmart store , at a “pod” inside a mall, or online, people didn’t flock to get medical care from retailers this year. It made for an even tougher year for retail pharmacies, which are going through mass closures. 🪞Winner: Me-too drugs — Calling a drug a “me-too” used to be an insult. Now it’s a preferred strategy for targeting potential markets in inflammation and immunology, obesity and cancer. There seems to be plenty of investors who are far more comfortable betting on commercial and market risk than biological or chemistry risk. 👯‍♂️Losers: Ian Read + Frank D’Amelio – The former Pfizer CEO and CFO came at the king and missed. Their short-lived alliance with Starboard Value was a messy episode punctuated by a fat-fingered email that likely damaged the activist investor’s (valid) case that Pfizer had underperformed. And the blundered rollout has made sure CEO Albert Bourla won the first round with the investor. 🔀Winner: Post-Covid BioNTech — The German biotech made the post-pandemic pivot, convincing investors that it’s not just Pfizer’s vaccine partner and has a pipeline of non-Covid assets that are worth the look (a feat that Moderna has yet to pull off). 🤸‍♂️Winner: Regulatory flexibility — What seemed like a one-off with Sarepta now feels a lot more like standard FDA policy, with the agency showing increasing (and increasingly frequent) flexibility with developers of complex therapies for rare diseases, giving a much-needed lifeline to companies developing those products. 🪫Loser: Regulatory authority — It won’t be clear exactly what impact the Supreme Court’s Chevron ruling has until FDA authorities start getting tested in court. But in the early days, it seems like a blow to the power of government bodies to freely set rules for the industry to follow. 🏥Loser (for now): Pharma’s 340B push — Drugmakers’ efforts to halt the ballooning of their 340B drug sales have run into a wall , facing administration rejections and legal battles. But a new Congress and White House always brings new hope for legislative reforms. 🛜Winner: GLP-1.com — Top telehealth companies like Hims, Ro and plenty of others grabbed onto the weight loss trend and didn’t let go. Compounded drugs gave companies like Hims a way into a huge consumer market that seemed like it would be dominated by pharma. And despite drugmakers’ many attempts, they’ve so far struggled to blunt the explosive growth of the compounded GLP-1 market. 🧬Loser: CRISPR stocks — For a technology with such promise, investors sure don’t love the companies that are working on it. Nearly all of the gene editing companies are down this year, as the market has soured on an idea that has yet to show that it can move from a scientific marvel to a commercial one. 📑Winner: RNA editing — Impermanent alternatives to CRISPR that tweak the code of short-lived RNA molecules got off to a strong start in the clinic this year. Wave Life Sciences impressed investors with the first glimpse of human data for RNA editing in the liver, and Ascidian Therapeutics got a green light to start an exon editing trial for a rare eye disease in the US. 😭Loser: The XBI — It was the little index that couldn’t. Every time it felt like biotech stocks were going to show signs of life , they never quite did. Capital kept getting hoovered up by AI companies and crypto, interest rates never really fell, and those deals and IPOs that investors are hoping for seem juuuuuust over the horizon. Maybe next quarter? 🇳🇱Winner: Forbion — The US is home to most of the industry’s blue-chip biotech investors. But nestled in the Netherlands is perhaps the standout firm of 2024. Dutch investor Forbion took part in 10 private megarounds, inked a handful of portfolio company exits to pharma , and raised €2.1 billion for two new funds. 🍂Loser: Sage Therapeutics — Things couldn’t have gone any worse for a company that once seemed poised to bring multiple new neuroscience drugs to market in areas that desperately need innovation. A failure in Huntington’s disease, following their major depression disorder rejection last year, has left the company cutting jobs and with few options in its pipeline. 🤴Winner: Sage Therapeutics co-founder Steve Paul — Sage may be a loser, but co-founding scientist Steve Paul had a better year. Another company he helped start, Karuna, was acquired by Bristol Myers Squibb. And he’s landed at another hot neuro startup, Seaport Therapeutics, with other Karuna vets. 🇨🇳Loser: WuXi — Biosecure may be dead (for now) , but damage has been done to China’s WuXi companies, which had built themselves into the must-use partner for biotechs working on new drugs. Now many companies are looking at alternatives or backup partners, fearful that the government might ban the companies. 🗓️Winner: Long-acting HIV treatments — Gilead’s deals team had a tough year, but the company’s long-acting HIV treatment proved that it could essentially fill the function of a vaccine. It’s a breakthrough that — if the company can get access right — would be a major advancement in stopping the spread of the HIV virus. 💸Loser: The Viking Therapeutics buyout crowd — The obesity biotech has become a day trader favorite for betting on M&A. But so far, and despite plenty of interest from pharma, it hasn’t happened. At least not yet. 🤔Winner: Viking Therapeutics — On the other hand, Viking’s stock is up 160% on the year, which ain’t bad. Who needs a deal when you’ve got returns? 🧠Loser: Alzheimer’s sales — Last year, the amyloid hypothesis was one of our winners, after the approval of one drug and another on the brink. But in 2024, those wins haven’t turned into commercial success , and seem far from doing so. 🪖Winner: Track records — Many of 2024’s biggest venture funding rounds went to teams who have already launched or sold prior companies. Take Mark McKenna raising $400 million for his new autoimmune bet after selling Prometheus, or David Epstein securing $140 million after Pfizer bought Seagen, or Ron Renaud gobbling up $400 million after AbbVie bought his last company. The original Karuna team bagged two megarounds for Seaport, as did the former Medicines Company team with their new obesity company Metsera. The haves are getting more, and the never-hads are forced to do more with less. 🖇️Winner: Molecular glue developers — Several big pharmas bought into molecular glues via licensing deals this year, lured by the technology’s promise of targeting previously undruggable proteins. The approach remains unproven and few projects are in the clinic so far, but with more than $8 billion in biobucks staked on molecular glues in 2024, partners are clearly happy to stick it out and hope they avoid a pasting. 🔎Loser: The Lina Khan-era FTC’s antitrust theories — Biden’s FTC kicked off an expansionary view of antitrust policy, promising to explore new ways of regulating healthcare mergers . But with Donald Trump’s election, that effort seems largely headed for the rearview. What’s less clear is if Khan’s effort to scrutinize PBMs survives. 🙈Loser: Drug price scrutiny — Before Joe Biden dropped out of the presidential race, drug prices had been a top issue for almost a decade. Every news story about a new drug approval had the new product’s price high up. Democrats were campaigning on the IRA. And even Trump was riding the issue. Now? It’s still an issue, but feels like it’s faded — slightly — into the background. 👀Winner: Insurance and PBM scrutiny — While the focus on drug prices has eased, the focus on healthcare costs has stayed hot. That’s particularly true for PBMs, which are facing more pressure in Washington than they have in years. And the shocking killing of an insurance CEO will almost certainly raise the scrutiny on payers, as media and politicians move on from the murder and start spending more time on Americans’ discontent with healthcare. 🥈Loser: Novo Nordisk — If this is what losing looks like, it’s not too bad. But despite Novo Nordisk’s head start in the obesity race, the company is still dealing with product shortages, was the loser in a head-to-head trial against Lilly’s drug, and still doesn’t have a telehealth partner that could be crucial to locking up consumers. 🥇Winner: Eli Lilly — Meanwhile, Eli Lilly has been buying up manufacturing capacity like it’s on “Supermarket Sweep,” has worked through its obesity drug supply issues, and has been bringing telehealth rivals into the fold in what could be a crucial sales channel in the years to come. 🙉Winner: Vaccine hesitancy — One of the US’ biggest vaccine skeptics will be in charge of US vaccine policy. America has faced a simmering vaccine trust problem that only got worse during the tail end of Covid. With Robert F. Kennedy Jr. headed to HHS in the Trump administration, expect to see childhood vaccination rates fall, and rates of preventable disease rise. 🧫Loser: Needing a wet lab — Apparently, that’s mid , as the kids say. That’s it! Thanks for reading, and a Happy New Year to all of you!

Welcome to Endpoints News’ manufacturing briefs, where we bring you essential news on new builds, collaborations, recalls and more. National Resilience is replacing its CEO effective immediately with COO William Marth, who will take over from Rahul Singhvi. Marth previously served as CEO of Curia Global, known then as AMRI, as well as CEO of Teva Pharmaceutical’s US division. Moderna has opened its new mRNA manufacturing facility in Australia within the campus of Monash University. The new site will be able to make 100 million vaccine doses a year, and the first dose is anticipated to be produced next year. Around 140 new “direct” jobs will be created at the site. Reckitt Benckiser is pouring £155 million ($200 million) into a new facility in Wilson, NC, to make its over-the-counter flu and cold drug products, the company said Tuesday. This will be Reckitt’s largest OTC manufacturing site in the US and will create 300 new jobs. CDMO Cambrex is partnering with Eli Lilly’s biotech innovative arm, dubbed Lilly Catalyze360-ExploR&D, to offer its services to Lilly’s biotech partners, according to a Thursday release. Agenus has revealed its planning to make layoffs as a part of its wider plan to reduce costs, the company said Thursday. The company said Monday it is restructuring its manufacturing sites to become a biologics CDMO. Nature’s Toolbox has secured $15 million from JP Morgan to fund the development of its manufacturing platforms to make biomaterials, the company said Wednesday. Altasciences is the manufacturer for several of Metsera’s weight loss candidates, the company said on Nov. 28. The CDMO has produced the biotech’s Phase 1/2 GLP-1 asset, dubbed MET-097i. It is also making two other candidates for Metsera: a long-acting amylin analog (MET-233i) and an oral GLP-1 drug (MET-002). Rallybio is moving its C5 inhibitor into a confirmatory study next year following manufacturing improvements, the company said Monday. After data analysis and changes to the production of the drug, named RLYB116, the study will be completed in the second quarter of 2025. GE Healthcare is gaining full ownership of the radiopharma manufacturer Nihon Medi-Physics by buying Sumitomo Chemical’s 50% stake in the company, according to a Sunday release. The transaction is expected to close early next year. Telix IsoTherapeutics has renewed its supply agreement with clinical-stage radiopharma Plus Therapeutics, according to a Tuesday release. Telix will continue to supply rhenium-186 isotopes for Plus’ lead candidate, obisbemeda, which is being studied for CNS tumours. Eckert & Ziegler is supplying the radiopharma company Ariceum Therapeutics with actinium-225 and lutetium-177 for its lead asset, satoreotide, under study for hard-to-treat cancers. KBI Biopharma will manufacture Alanis Therapeutics’ preclinical antibody that is being investigated for myelodysplastic syndromes and acute myeloid leukemia, according to a Tuesday release. CELLforCURE by SEQENS is partnering with clinical-stage biotech Smart Immune, according to a Tuesday release. The CDMO will make the biotech’s Phase 1/2 asset, SMART101, for acute leukemia or primary immunodeficiencies. NorthX Biologics will make Amarna Therapeutics’ clinical-stage gene therapy called Nimvec AM510, which is being investigated for type 1 diabetes, according to a Tuesday announcement. API manufacturer Antheia will receive $12 million from the US Department of Health and Human Services over two years to manufacture an unnamed pharma ingredient domestically, according to a Tuesday release. Lonza’s ADC company Synaffix has entered a licensing agreement with DNA sequencer Illumina, the companies said Wednesday. Synaffix’s so-called “metal-free clock chemistry” tech will be used by Illumina for its DNA sequencing products. Chemical manufacturer LG Chem is collaborating with microbiology biotech Acies Bio on sustainable commercial production of chemicals in high demand, the companies said Thursday. The UK Health Security Agency has signed a contract with CSL Seqirus to manufacture five million doses of human H5 influenza vaccines for the UK, the agency said Tuesday. The Brazilian research organization Oswaldo Cruz Foundation signed a memorandum of understanding with Belgian companies Quantoom Biosciences and Univercells to boost production of RNA therapeutics in Belgium, according to a Friday release. Gavi, the Vaccine Alliance, is investing $23.4 million to help vaccinate children in Sudan, in partnership with Save the Children and UNICEF, according to a Monday release. The funding will in part be used to improve vaccine storage and cold supply chains. With additional reporting by Katherine Lewin