Drugs that activate the GLP-1 receptor transformed the treatment of obesity, but biotech company Metsera contends that limitations keep them from expanding their reach. The weekly injections and gastrointestinal side effects pose challenges for adherence to a chronic therapy. GLP-1 drugs are also engineered peptides, which are expensive to manufacture. Metsera has technologies and drug candidates intended to improve on these limitations. With key clinical trial readouts expected this year, the company took its story to investors through an IPO.
Metsera initially planned to offer more than 17.1 million shares priced in the range of $15 to $17 each, which would have raised $275 million at the pricing midpoint. The New York-based company reached that sum by pricing more than 15.2 million shares at $18 apiece. Metsera began trading on the Nasdaq Friday under the stock symbol “MTSR.” The stock showed some pop, finishing its first day of trading at $26.50 per share, up 47.2% from the IPO price.
The most advanced Metsera program is MET-097i, a subcutaneously injected, long-acting GLP-1 agonist drug. A Phase 1/2 test is underway in the U.S., enrolling participants who are obese or overweight but otherwise healthy. At the beginning of January, Metsera reported preliminary Phase 2a data showing the drug led to dose-dependent weight loss. At the high dose, the average placebo-adjusted weight loss from the weekly administered drug was 11.3%. No plateau of effect was observed, which suggests the potential for greater weight loss with longer treatment. Regarding the gastrointestinal side effects that are associated with the GLP-1 drug class, Metsera said these problems were classified as mild or moderate and short-lived.
Though weekly doses of MET-097i were tested in the Phase 1/2 study, this injectable drug was engineered with technology intended to give it a longer half-life. Metsera said this capability could support monthly dosing, offering a less burdensome dosing regimen compared to weekly injections. A longer dosing interval also provides a manufacturing edge. Reducing the required active pharmaceutical ingredient required improves scalability and reduces manufacturing costs compared to other GLP-1 drugs, Metsera said in its IPO filling. The company describes these engineered peptides as next-generation injectable and oral nutrient stimulated hormones (NuSH).
“Our goal is to develop a broad, scalable and combinable portfolio of injectable and oral NuSH analog peptides for the treatment of obesity, overweight and related conditions,” Metsera said in its IPO filing. “We believe our product candidates have the potential to reduce the barriers to adoption as a chronic therapy, while raising the ceiling of effectiveness, and improving manufacturing scalability.”
Like many biotechs working in metabolic medicines, Metsera is pursuing targets beyond GLP-1. The company’s next product candidate, MET-233i, is an analog of amylin, a different hormone that plays a role in regulating blood sugar and appetite. Metsera is developing this ultra-long acting, subcutaneously injectable drug as a standalone treatment and for potential combination with other drugs, including MET-097i. A Phase 1 test is underway; preliminary data are expected in mid-2025. If this study demonstrates sufficient safety, Metsera plans to start a clinical test of MET-233i in combination with MET-097i. That study could yield preliminary data by the end of the year.
Metsera is also joining its metabolic medicines peers who are developing oral GLP-1 drugs. The biotech’s candidate is MET-224o, an ultra-long acting GLP-1 receptor agonist made with technology that enables oral bioavailability and stability in the gastrointestinal tract. The company said preclinical research showed robust activity comparable to MET-097i and no significant toxicity.
Population Health Partners and Arch Venture Partners founded Metsera in 2022. The following year, the young company struck two pipeline-defining business deals. The first was a license and collaboration agreement with D&D Pharmatech, which had a platform technology for developing metabolic disorder drugs. Months later, Metsera acquired Zihipp, a company developing peptide therapies for diabetes and obesity. Zihipp’s research was licensed from Imperial College of Science, Technology and Medicine in London.
Last April, Metsera emerged from stealth with $290 million in financing. According to the prospectus, the company had raised $536.4 million prior to the IPO, most recently a $215 million Series B round announced this past November. Arch Venture Partners is the largest shareholder with a 23.5% post-IPO stake, according to the filing. Metsera said it will use its cash on hand to finance the Phase 2 test of lead program MET-097i through completion. The company will also advance MET-233i through preliminary Phase 1 results.
The IPO was done with the lead program’s near future in mind. About $250.8 million of the proceeds will finance a planned Phase 3 test through the readout of preliminary data as well as the related milestone payments associated with the program, Metsera said in the filing. Per terms of the agreements that brought Metsera its drug candidates, the company must make payments tied to development milestones. Metsera expects its cash will last into 2027.
Two other life science companies went public this past week. Here’s a look at those IPOs:
Maze Therapeutics Finds Way to $140M IPO for Chronic Kidney Disease Drugs
Drugs currently used to treating chronic kidney disease drugs mainly slow disease progression. Maze Therapeutics aims to address underlying causes of the disease. Maze has two kidney disease drugs currently in the clinical, and the biotech was able raise $140 million in IPO cash to support those programs and more in its pipeline. Maze’s shares now trade on the Nasdaq under the stock symbol “MAZE.”
The drugs of South San Francisco-based Maze come from Compass, a platform technology that the company said identifies and characterizes genetic variants in disease. By linking those variants to disease-driving biological pathways in specific patient groups, the technology provides insights for drug R&D, from discovery all the way through clinical testing.
The most advanced Maze program is MZE829, a small molecule designed to inhibit apolipoprotein L1, or APOL1. This protein is associated with a higher risk of kidney disease. People of African descent carry variants that make them more likely to develop APOL1-kidney disease. In its IPO filing, Maze said that although the link between APOL1 variants and renal dysfunction has been known for more than a decade, the company has identified a new protective variant that underpins MZE829’s approach and brings the potential to reach more patients. A Phase 2 test underway is expected to post proof-of-concept data in the first quarter of 2026.
Maze’s MZE782 is a small molecule inhibitor of SLC6A19, a gene that encodes a protein that transports amino acids. In the kidney, SLC6A19 is key to minimizing excretion of amino acids in the urine by transporting these nutrients back into the bloodstream. Maze said it identified this gene as a potential target for treating chronic kidney disease based on finding that loss-of-function variants in SLC6A19 were associated with improved renal function and protection from kidney disease. The company believes SLC6A19 inhibition also offers the potential to treat phenylketonuria, a rare, inherited enzyme deficiency that can lead to impaired kidney function. MZE782 is currently being evaluated in a Phase 1 trial enrolling healthy volunteers; preliminary data are expected in the second half of this year.
Compass previously produced MZE001, a drug in development for Pompe disease. The oral small molecule was initially licensed to Sanofi, but the pharma giant walked away after the Federal Trade Commission opposed the deal as anticompetitive. Last year, Shionogi licensed rights to the drug candidate for $150 million up front.
Prior to the IPO, Maze had raised $499 million from investors, including a $115 million Series D round announced in early December. Third Rock Ventures is the largest Maze shareholder with a 16.4% post-IPO stake followed by Arch Venture Partners’ 9.6% stake, according to the filing.
Maze initially planned to offer 7.8 million shares in the range of $15 to $17 each, which would have raised nearly $125 million at the pricing midpoint. Maze boosted the deal size to $140 million by offering 8.75 million shares for $16 each. Combining its existing cash with the IPO proceeds, Maze plans to spend about $100 million to fund MZE829 through the completion of Phase 2 testing. For MZE782, the company is budgeting $70 million for a planned Phase 2 test in chronic kidney disease and $40 million for a planned Phase 2 test in phenylketonuria. Another $50 million is earmarked for development of other programs in cardiovascular-renal-metabolic indications currently in preclinical development. The company will also continue developing the Compass platform.
Beta Bionics Brings in $221M for Diabetes Device R&D
Beta Bionics, a company that has commercialized an insulin delivery device for patients with type 1 diabetes, raised $221 million in its stock market debut as it looks to expand its portfolio beyond its flagship product. Beta Bionics’ shares now trade on the Nasdaq under the stock symbol “BBNX.”
Irvine, California-based Beta Bionics initially planned to offer 10 million shares in the range of $16 and $17 apiece. The company upsized the offering to 12 million shares priced at the top of its targeted price range, which raised $204 million. Concurrent with the IPO, Beta Bionics also sold to private investors 1 million shares at the IPO price, raising another $17 million.
The commercialized Beta Bionics device, named iLet, received FDA clearance in 2023 for patients age 6 and older. Unlike traditional insulin pumps that require users to keep track of their carbohydrate intake or make calculations to determine the correct insulin dosage, iLet employs adaptive algorithms that learn a user’s insulin requirements and make adjustments as needed, the company said in its IPO filing. Beta Bionics generates revenue from iLet purchases as well as sales of single-use products associated with the device, such as insulin cartridges and infusion sets. In the first nine months of 2024, Beta Bionics reported $44.6 million in revenue.
Beta Bionics is continuing to innovate. According to the IPO filing, the company is in the early stages of developing a “patch pump,” a pump that adheres directly to the skin and does not require tubing to administer insulin. The company is developing a configuration of iLet that combines automated delivery of insulin and glucagon, a blood glucose-raising hormone. This version of iLet uses algorithms to determine the doses of both hormones. Beta Bionics also aims to develop iLet for more patients and indications, such as type 2 diabetes.
As of the end of the third quarter of 2024, Beta Bionics reported its cash position was $60.9 million. That capital, combined with the IPO proceeds, will support the company’s R&D plans. Beta Bionics plans to spend about $50 million to develop the bihormonal configuration of iLet and submit an application seeking FDA clearance. Another $50 million is budgeted for taking the patch pump through FDA regulatory submissions. Beta Bionics said in the filing it expects its capital will last into the first half of 2028.
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