Pfizer’s internal obesity drug R&D stumbled, but the pharmaceutical giant is leaping ahead in this field through the multi-billion dollar acquisition of Metsera, a clinical-stage company whose pipeline of next-generation metabolic medicines could offer multiple points of differentiation in a crowded market of weight loss therapies.
Terms of the acquisition agreement announced Monday call for Pfizer to pay $47.50 in cash for each share of Metsera, valuing the biotech at about $4.9 billion. Pfizer could pay out up to $22.50 more per share if the drugs of New York-based Metsera achieve clinical and regulatory milestones.
Speaking during a conference call Monday, Pfizer Chief Strategy and Innovation Officer Andrew Baum acknowledged that many successful obesity products are on the market, but he said significant unmet medical need remains. He added that obesity’s association with other diseases means Metsera’s pipeline offers the potential for expansion to other indications.
“We evaluated multiple external opportunities in the obesity space and were exhaustive in our analysis and diligence to make sure we identified the optimal opportunity that delivers compelling potential differentiation across key asset attributes,” Baum said.
The most advanced Metsera drug candidate, MET-097i, is a peptide engineered to activate the GLP-1 receptor, putting it in the same class of medicines as the weekly injectables Wegovy, from Novo Nordisk, and Zepbound, from Eli Lilly. While a Phase 2 study is underway evaluating MET-097i as a weekly injection, this drug was designed with proprietary technology giving the molecule a longer half-life to support a longer dosing interval. A separate mid-stage study is underway testing monthly dosing.
In addition to reducing the dosing burden for patients, monthly dosing offers manufacturing advantages by reducing the number of required injector devices, leading to cost and supply chain advantages over weekly injectable products. Preliminary results for weekly and monthly dosing are expected in 2026, according to a Pfizer investor presentation. Metsera is aiming for even less frequent dosing. An injectable GLP-1 candidate with the potential for every-three-months dosing is currently in preclinical development.
Drug companies are also trying to expand metabolic medicines to new targets, such as the amylin receptor. Novo Nordisk has two programs in the clinic addressing amylin. This target has also drawn the interest of AbbVie and Roche, each of which has struck deals this year to add amylin-targeting programs to their pipelines. Metsera’s amylin contender, MET-233i, currently in Phase 1 clinical development. Metsera executives have said this drug has best-in-class potential, a sentiment echoed Monday by Pfizer executives. Preliminary Phase 1 data were presented last week during the annual meeting of the European Association for the Study of Diabetes. A separate Phase 1 test is underway evaluating the combination of MET-233i and MET097i.
The Metsera pipeline also includes pills, which is important as obesity drug research pursues more convenient dosing options that could serve as alternatives to injections for initial treatment or as maintenance therapies after patients achieve target weight loss with an injectable medication. Metsera has oral GLP-1 and amylin drug candidates in preclinical development.
Pfizer had previously identified oral drugs as a way to differentiate and compete against injectable obesity medications. But in 2023, the company discontinued development of the oral GLP-1 drug lotiglipron after a safety signal emerged in Phase 1 testing. The company then turned its focus to a different oral GLP-1 drug, danuglipron. This drug achieved statistically significant weight loss in mid-stage testing, but those results also showed many patients struggled to stick with its twice-daily dosing. Pfizer’s development of once-daily oral danuglipron ended in May after a sign of potential drug-induced liver injury emerged in Phase 1 testing.
Leerink Partners projects that Metsera’s drugs could reach $5 billion in combined peak sales. In a Sept. 9 research note, analyst David Risinger wrote that data so far for monthly injections of lead Metsera program MET-097i suggest efficacy equivalent to weekly injections of Lilly’s Zepbound and potentially better tolerability. Furthermore, development of this weekly injection for initial titration should yield tolerability advantages over competitors and also offer maximum flexibility for patients who want to dose weekly or re-start therapy Risinger said.
Metsera’s amylin candidate also offers the potential for monthly dosing, Risinger said. He added that the company’s oral GLP-1 drug could offer better efficacy and tolerability than Lilly’s oral GLP-1 agonist, orforglipron, which is on track for an FDA submission.
There’s another potential competitive advantage for Metsera’s combination of MET-233i and MET097i, which the company believes will be evaluated as a biologic drug. Risinger said Metsera management noted that a peptide sequence of greater than 40 amino acids would be eligible to be reviewed under a biologics license application (BLA), as opposed to the new drug application (NDA) pathway used for Novo’s semaglutide (Wegovy) and Lilly’s tirzepatide (Zepbound). Classification as a biologic would also give the Metsera drug combo protection against compounders. The Food Drug & Cosmetics Act makes biologics ineligible for compounding.
“We view this as an attractive differentiation from tirzepatide and semaglutide, which underwent an NDA review process, particularly given the favorable positioning for [Inflation Reduction Act] negotiations for BLA over NDA (13 years vs. 9 years, respectively),” Risinger wrote. “MET-097i may also be protected against compounding as the FDA states that ‘Biological products are not eligible for the exemptions for compounded drugs under sections 503A and 503B of the FD&C Act.’”
The $47.40 per share that Pfizer agreed to pay represents a 42.5% premium to Metsera’s closing price on Friday. Metsera’s IPO early this year was priced at $18 each per share. Metsera shareholders could receive more tied to the achievement of clinical and regulatory milestones. A contingent value right in the deal will pay an additional $5 per share after the combination of MET-097i and MET-233i starts a Phase 3 clinical trial. Another $7 per share will be paid upon FDA approval of monthly MET-097i as a monotherapy; $10.50 per share is tied to FDA approval of the MET-097i and MET-233i combination.
The boards of directors of both companies have approved the acquisition, which still needs the approval of Metsera shareholders as well as regulatory approvals. The deal is expected to close in the fourth quarter of this year.
Photo: Dominick Reuter/AFP, via Getty Images
