Carmot Therapeutics, Inc.

The once-fledgling field of MASH drug developers is now one of the few areas of consistency in the biotech industry. And another late-stage startup is gaining traction. Boston Pharmaceuticals, advancing a once-monthly liver disease drug, is exploring both an IPO and an acquisition, looking to capitalize after a successful mid-stage trial and a comparable company’s positive data. “We are focusing on being de-risked and fast, but we’re also doing [a] dual track,” Boston Pharma CEO Sophie Kornowski told Endpoints News in an interview. “It’s important for us to have smart investors at the table. You want to maximize the asset for the patients.” Mayank Mamtani, senior managing director and group head of healthcare at B Riley Securities, compared Boston to the cardiometabolic biotech Carmot Therapeutics. In 2023, that company raised $150 million in May, filed paperwork to go public in mid-November, and was swiftly acquired by Roche two weeks later. “They could kind of do these parallel processes and see what makes sense from a timeline to value creation,” he said in an interview. Boston’s plans underscore just how much momentum biotechs have gained by looking to treat metabolic dysfunction-associated steatohepatitis, a form of advanced fatty liver disease also known as NASH. A few years ago, the treatment landscape was a graveyard. Now, there’s an approved drug in Madrigal’s once-daily pill Rezdiffra, and a number of followers that confidently feel there’s enough of the market that awaits them. Boston Pharma launched 10 years ago with $600 million when megarounds genuinely were a dime a dozen. It had the backing of Gurnet Point Capital, led then by current Biogen CEO Chris Viehbacher, and was helmed by former Eli Lilly executive Robert Armstrong. Not unlike many bright-eyed biotechs, Boston Pharma wanted to win at everything. It strove to have 20 clinical assets, and licensed a handful from GSK and Novartis in 2018. Another asset separately licensed from the Swiss pharma in 2020 was what became efimosfermin alfa, now the only asset in its clinical pipeline. Kornowski, a dealmaker in her own right after previously leading Roche’s BD team, said “the economics are really favorable to Boston Pharmaceuticals.” Board chairman Elias Zerhouni told Endpoints that when he got involved, he convinced investors that the company had to focus. “You can’t afford to not be best-in-class in at least one category, if not two,” he recalled telling Ernesto Bertarelli, an Italian billionaire whose asset management firm includes Gurnet Point. So the company focused on the MASH treatment. Boston Pharma reported Phase 2 data in November showing statistically significant improvements in both fibrosis without worsening of MASH, and resolution of MASH without worsening of fibrosis. Fibrosis is a type of liver scarring that’s a hallmark of the disease. Its drug got another boost after Akero Therapeutics reported in late January that its own candidate with a similar mechanism was able to better reverse advanced fibrosis in patients compared to placebo. Zerhouni says that those data not only validated the broader FGF21 class, but they informed how vital the duration of therapy is. “They set up a threshold for everybody,” he said. “We think we have what it takes to equal or better this particular threshold that they came up with.” Akero is testing its drug as a once-weekly treatment, and fellow FGF21-targeting biotech 89bio is testing weekly or every two-week dosing. Mamtani compared Boston’s once-monthly efimosfermin alfa to Amgen’s obesity drug MariTide, which is similarly leaning on convenience to compete with other weight loss drugs. “Longer-acting mechanism, very potent fat reduction, less drug exposure, maybe that bone [toxicity] risk can be kind of ruled out,” Mamtani said. “So those are things that, from a clinical profile standpoint, make the case” for the drug, he added. Boston Pharma has some catching up to do, with Akero and 89bio both in Phase 3 studies. It expects to work with the FDA on trial plans by the middle of this year and could start its Phase 3 study in patients with F2 or F3-stage fibrosis as early as the third quarter of this year. A separate trial arm, in more severe F4 patients, would launch “very soon after that,” according to Zerhouni. That program will also include a subgroup analysis for patients who enter the study on a GLP-1 drug, a key feature that some other MASH biotechs have already incorporated into their trials. Akero found that the combination of its drug and GLP-1s made “substantial differences to the liver,” according to an exec in an earlier interview . Boston did not include a similar subgroup analysis in its Phase 2 study. For Kornowski, keeping up with competitors isn’t daunting. “I’m extremely motivated to do it well, and to do it fast,” she said.

Zealand Pharma has finally found a partner. And according to the Danish company, the licensing deal it announced with Roche on Wednesday for its amylin analog petrelintide is the biggest ever for an obesity candidate to date. The companies said the Swiss pharma is paying Zealand $1.65 billion upfront in cash. $1.4 billion of that will be given once the deal is closed, which is expected to be in the second quarter of this year, and $250 million over the next two years every time the partnership celebrates an anniversary. Importantly, Roche and Zealand will also investigate petrelintide combinations. The first on the list for co-administration is Roche’s GLP-1/GIP agonist candidate CT-388, which Roche obtained from its acquisition of Carmot Therapeutics in late 2023. CT-388 has shown effectiveness in early trials but had high rates of gastrointestinal side effects; combining it with amylin could allow a more potent weight loss effect, allowing lower, safer doses. The ghost at the feast is Novo Nordisk’s amylin-incretin combo CagriSema, which has disappointed in late-stage trials in patients with obesity and with obesity and diabetes . CEO Adam Steensberg told Endpoints News in an interview that Zealand can do better. CagriSema combines equal 2.4 mg doses of Novo’s amylin analog cagrilintide and GLP-1 semaglutide, and Steensberg suggests this ratio is “suboptimal.” “We think you need to max out on amylin … then just add a little bit of GLP-1/GIP on top,” he said. In Zealand’s ongoing Phase 2b monotherapy trial in obese patients, petrelintide is being dosed at up to 9 mg . Data from this trial are due by mid-2026. Steensberg said that having Roche on board as a partner does not alter its plans for Phase 3 trials of petrelintide, but could accelerate them. “We look very much forward to also having their input into the details of the program,” he said. “The key focus will be on obesity as a first indication, with an ambition of rapidly expanding into additional indications,” Steensberg said. These are yet to be confirmed, but he did not rule out research in diabetes and the liver disorder MASH. Zealand believes that petrelintide monotherapy and the incretin combo will eventually be used to treat different populations. The former “will be a product for the majority of obese individuals,” Steensberg said, whereas “the most morbidly obese patients, they could benefit from a combination therapy.” The combo could also be of use in patients with both obesity and type 2 diabetes. On Zealand’s side, the collaboration is strictly on petrelintide — its other obesity candidates, such as the GLP-1/GLP-2 drug dapiglutide, are not involved. But other injected Roche assets might be used in future combinations, Steensberg said. Roche’s weight loss portfolio mainly stems from its $2.7 billion acquisition of Carmot. Roche has another GLP-1/GIP agonist, CT-868, and one of the brightest oral obesity hopes, a pill called CT-996. The company also has an anti-latent myostatin product called GYM329. Including milestone payments, the companies estimate the deal to be worth up to $5.3 billion. As part of the deal, Zealand will pay Roche $350 million for its share in studying CT-388 as a combo with petrelintide. The companies said they will split revenues — and losses — on their first monotherapy and combo drugs on a “50/50 basis” in the US and Europe. Steensberg described the profit share as the “true value” of the deal. Zealand could get royalties on net sales in other countries. Another major aspect of this deal is Roche’s manufacturing network and commercial reach. With the leading weight loss drug companies Eli Lilly and Novo Nordisk having to find ways to scale up manufacturing quickly, others yet to enter the market are mapping out commercial production plans much earlier in the process. Zealand has not been shy in declaring it was looking for a partner to study and commercialize its lead weight loss candidate. It has been on the hunt for a year or so now, and three weeks ago Steensberg told Endpoints the biotech was “exactly where we want to be.” Zealand is up 35% on the Danish stock exchange. Additional reporting by Reynald Castaneda. Editor’s note: This article has been updated throughout after an interview with Zealand CEO Adam Steensberg and stock reaction.

Zealand first announced that it was seeking a development partner in August 2024. Credit: Liudmila Chernetska via Getty Images. Zealand Pharma has named Roche as a development and commercialisation partner for its lead obesity candidate petrelintide, after a seven-month search. Under the deal, Zealand will receive an upfront payment of $1.65bn, with the potential for milestone payments bringing the total deal value to $5.3bn, depending on Phase III trials and commercial performance. Zealand and Roche will co-develop and co-commercialise Zealand’s amylin analogue petrelintide as a monotherapy, and in combination therapies. The first planned combination will pair petrelintide with Roche’s glucagon-like peptide 1/gastric inhibitory polypeptide (GLP-1/GIP) agonist candidate CT-388. Inherited by Roche through its $2.7bn acquisition of Carmot Therapeutics, CT-388 has demonstrated efficacy in early trials . In a Phase Ib trial (NCT04838405), participants taking the therapy achieved a mean placebo-adjusted weight loss of 18.8% at 24 weeks. CT-388 is currently being studied in two Phase IIb clinical trials in people with overweight/obesity with (NCT06628362) and without type 2 diabetes (NCT06525935). As part of the collaboration, Zealand will contribute $350m to support the study of the CT-388/petrelintide combo. The companies will share profits and losses on a 50/50 basis in the US and Europe while Zealand will receive tiered royalties on net sales in other global markets. Zealand first shared that it was eyeing up a partner to study and commercialise its lead weight loss candidate back in August 2024. However, its failure to announce a deal in its February earnings report last month disappointed investors . At the time, CEO Adam Steensberg reassured stakeholders that the company was “exactly where it wants to be in the process”. Zealand has delivered this promise with the Roche partnership now secured. The collaboration marks Zealand’s progression into the obesity space, which is dominated by GLP-1 receptor agonists (GLP-1RAs) such as Novo Nordisk’s semaglutide (branded as Wegovy and Ozempic), and Eli Lilly’s tirzepatide (branded as Mounjaro and Zepbound). Petrelintide is currently being investigated in the Phase II ZUPREME clinical trial (NCT06662539). While GLP-1RAs such as semaglutide work by stimulating insulin secretion, reducing glucagon levels, and slowing gastric emptying, amylin analogues such as petrelintide act through a different mechanism. By mimicking the hormone amylin, they suppress glucagon secretion, slow gastric emptying, and restore sensitivity to the satiety hormone leptin. Zealand believes this distinct mode of action could position petrelintide as a best-in-class therapy in obesity and diabetes. “We strongly believe that petrelintide holds potential as a foundational therapy for weight management,” said Steensberg in the 12 March announcement accompanying the deal. Investor confidence in Zealand’s obesity pipeline has remained high. In June 2024, the company raised $1bn through a share offering, surpassing its original target of $900m. In January 2024, Zealand secured an additional DKr1.45bn ($204m) in funding for its obesity pipeline through a private placement and directed share issue to US investment firms. Zealand’s other major obesity candidate , survodutide, a glucagon/GLP-1 receptor dual agonist developed with Boehringer Ingelheim, is already in Phase III trials for obesity and metabolic dysfunction-associated steatohepatitis (MASH). Rates of obesity across populations are increasing, and the market for obesity drugs is set to reach $37.1bn across the seven major markets (US, UK, Germany, France, Italy, Spain, and Japan), by 2031, according to a GlobalData report. GlobalData is the parent company of Pharmaceutical Technology.