Metsera, the well-funded obesity biotech from Population Health Partners and ARCH Venture Partners, has unveiled its first clinical data just a few months after emerging with $290 million and a broad pipeline of weight loss drug candidates.
The New York City startup said its GLP-1 receptor agonist, a long-acting injectable known as MET-097, was able to reduce some patients’ weight from baseline by 7.5% at day 36 in a Phase 1 study.
That measurement came one week after a cohort of patients received their fifth and final dose of 1.2 mg. Looking farther out, four weeks after the final dose was given, Metsera said the cumulative weight loss grew to 8.1% for that group in the 125-person placebo-controlled trial.
“We have a feeling that we can be really quite competitive with this,” CEO Clive Meanwell told Endpoints News in an interview Monday night.
Doses ranging from 0.16 mg to 1.6 mg were tested in the single-ascending and multiple-ascending dose trials. At 1.6 mg, there was “quite a lot of nausea, vomiting, and would not be suitable for standard of care,” Meanwell said. At the 1.2 mg dose, the CEO said side effects were “very, very similar to the class.” Almost all of the adverse events were mild, with a “few hours at most” of nausea. Less than a handful of patients had diarrhea, he said.
The study was conducted in the Kansas City area by the CRO Altasciences. Novo Holdings — the controlling shareholder of one of the market leaders in obesity, Novo Nordisk — owns the contract research company and also runs some early-stage testing for the Danish drug giant, Meanwell said.
Metsera’s results are early and will need to be replicated in a larger and longer Phase 2b study, which Meanwell expects to be 13 weeks in duration and could potentially test Metsera’s drug candidate head-to-head against leading obesity medications. The startup is still internally debating which dose to test in the upcoming trial, whether that be 0.8 mg or 1.2 mg, Meanwell said.
Once-monthly goals
Other companies have recently reported higher levels of weight loss, albeit with different types of drugs and longer time frames. Zealand Pharma’s GLP-1/GLP-2 receptor dual agonist notched up to 8.3% placebo-adjusted mean weight reduction at 13 weeks, and Roche’s once-daily pill saw up to 7.3% weight loss within one month.
In long-term studies for GLP-1 receptor agonists, Meanwell said that “you’ve got to get into high-teens, low-20s.” The company also has an earlier-stage amylin-calcitonin receptor agonist being combined with its GLP-1 that would be “very competitive” if it induces 25% to 30% weight loss, Meanwell said.
While Metsera’s far behind the well-entrenched first-movers of Novo Nordisk and Eli Lilly, the company thinks it can carve a lane in the obesity market with a once-monthly option that has a much longer half-life. It said MET-097, which comes from its acquisition of UK startup Zihipp, had a half-life of 380 hours. Novo cut a Phase 1 trial studying a once-monthly GLP-1/GIP agonist due to “portfolio prioritizations,” it said last month.
The market leaders, Novo’s Wegovy and Lilly’s Zepbound, are indicated for once-weekly injections. Those behemoths are also testing longer-duration treatment options and have bought up a few obesity startups to get access to muscle-preserving medicines or other mechanisms of action. Novo’s bet on a second iteration of a previously shelved class, CB1, hit a speed bump last week with neuropsychiatric effects that overshadowed efficacy.
Meanwell said the goal is also to get rid of the need for a titration schedule that gets patients acclimated to the higher doses.
Metsera is still finalizing its Phase 2b trial, which will begin next quarter and will be conducted in the US. The trial is slated to have data by next summer, meaning the startup could quickly start a Phase 3 as soon as the second half of next year, Meanwell said.