Pfizer has agreed to acquire Metsera for up to $7.3 billion, the companies said, in a deal that returns the pharma giant to the obesity and metabolic drug space from which it retreated this past spring following a clinical setback.
Pfizer effectively exited the next-gen obesity drug scramble in April when it halted development of danuglipron (PF-06882961). The company acted after a single patient treated with the once-daily oral chronic weight management therapy candidate in one of two Phase III dose optimization studies (NCT06568731 and NCT06567327) developed what Pfizer called a “potential drug-induced liver injury which resolved after discontinuation of danuglipron.”
That setback came nearly two years after Pfizer ended development of another obesity candidate, lotiglipron (PF-07081532), in June 2023 after an unspecified number of patients showed elevated transaminases in the Phase II C3991004 trial (NCT05579977) and two Phase I drug-drug-interaction studies, C3991040 (NCT05671653) and C3991047 (NCT05788328).
Pfizer emphasized at the time that none of the participants reported liver-related symptoms or side effects, none needed treatment, and there was no evidence of liver failure.
“Obesity is a large and growing space with over 200 health conditions associated with it. The proposed acquisition of Metsera aligns with our focus on directing our investments to the most impactful opportunities and propels Pfizer into this key therapeutic area,” Albert Bourla, Pfizer’s chairman and CEO, said in a statement.
The deal would add Metsera’s portfolio of oral and injectable incretin, non-incretin, and combination therapy candidates to a Pfizer pipeline that includes a Phase I obesity candidate (PF-07999415, a biologic with an undisclosed mechanism of action); a Phase II chronic weight management drug (PF-07976016, a GIPR antagonist new molecular entity); and three new molecular entity candidates designed to treat metabolic dysfunction-associated steatohepatitis (MASH).
Pfizer’s three MASH candidates are ervogastat (PF-06865571), a Phase II Diacylglycerol O-Acyltransferase 2 (DGAT2) inhibitor; the Phase II combination therapy of ervogastat and clesacostat (PF-05221304), an Acetyl CoA-Carboxylase (ACC) inhibitor; and PF-07853578, a Phase I PNPLA3 modulator.
Fewer injections
Metsera’s pipeline aims to address key unmet needs via fewer injections while achieving improved efficacy and tolerability. The pipeline includes four preclinical programs in IND-enabling studies, and four clinical-stage programs:
- Weekly and monthly dosing of injectable versions of MET-097i, glucagon-like peptide 1 (GLP-1) receptor agonists that are both in Phase II trials.
- MET-233i, a monthly dosing, ultra-long acting, subcutaneously injectable amylin analog candidate being evaluated as monotherapy and in combination with MET-097i in a Phase I trial. Metsera reasons that the combination will show enhanced weight loss and metabolic benefits.
- MET-224o, an ultra-long acting GLP-1 RA being developed to be administered at lower dose levels than other oral peptides developed through Metsera’s Nutrient Stimulated Hormone (NuSH) platform, to improve scalability. MET-224o—which is being developed alone and in combination with MET-097o, an oral version of MET-097i—is a successor peptide to MET-002o, now being evaluated in a Phase I study as a prototype to identify an optimal clinical formulation for MET-224o/MET-097o.
Last week, Metsera highlighted positive initial Phase I clinical results for MET-233i, showing what the company called a potential best-in-class profile as the first analog peptide to be developed using its NuSH platform for once-a-month dosing.
In a late-breaking presentation during the 61st Annual Meeting of the European Association for the Study of Diabetes (EASD), Metsera researchers reported that MET-097i showed competitive and durable weight loss, including a 7.5% reduction in body weight from baseline at day 36. MET-097i, which incorporates Metsera’s HALOTM platform technology, showed an approximate 380-hour half-life, an outcome that, according to Metsera, supports potential once-monthly dosing and dosing regimens without titration.
Metsera investors applauded the deal with a stock surge that sent its share price soaring about 61%, to $53.58 from $33.32 at Friday’s close of trading. Pfizer shares gained a penny, advancing to $24.04 before rising 11 additional cents or 0.5% to $24.15 in after-hours trading as of 7:38 p.m. ET.
>$5B sales forecast
“PFE’s planned acquisition of MTSR [Metsera] is set to add differentiated obesity drug candidates that we estimate could generate >$5B in combined peak sales potential,” David Risinger, a senior managing director and senior research analyst at Leerink Partners covering diversified biopharmaceuticals, wrote in a research note.
Earlier this month, Risinger initiated coverage of Metsera with an “Outperform” rating and a 12-month price target of $77.
“Our investment thesis is that the company’s platform and pipeline of novel obesity peptide-based therapeutics offer key advantages relative to competing assets,” Risinger wrote in a research note. “We believe that Wall Street underappreciates the company’s monthly injectable GLP-1, monthly injectable amylin, daily oral GLP-1 peptide, and peptide manufacturing scale advantages relative to competitors,” Risinger said.
Risinger cited several examples:
- MET-097i data to date, he said, suggested equivalent efficacy and possibly slightly better tolerability compared with Eli Lilly’s weekly-dosing tirzepatide, marketed as Mounjaro® for type 2 diabetes and Zepbound® for obesity and weight management.
- MET-233i has shown a 19-day half-life and potential for monthly dosing, differentiating the drug from competitors.
- MET-097o could deliver better efficacy and tolerability than Lilly’s historic and potentially blockbuster oral GLP-1 orforglipron, with potentially no food or water effects due to enteric coating.
- Metsera’s IND-enabling pipeline includes MET-815i, a prodrug of MET-097i that could potentially be dosed in patients quarterly; a GIP agonist, MET-034i; and MET-067i, a glucagon analog.
- Metsera’s platform offers significant peptide manufacturing cost advantages by allowing its candidates to require far smaller amounts of active pharmaceutical ingredient than leading competitors.
Pfizer agreed to acquire all outstanding shares of Metsera common stock for $47.50 per share cash at closing, representing approximately $4.9 billion in enterprise value.
Up to $2.4B in milestones
In addition, Metsera shareholders will receive a non-transferable contingent value right (CVR) entitling them to potential additional payments of up to $22.50 per share cash—adding up to $2.4 billion to the value of the deal—tied to three specific clinical and regulatory milestones:
- $5 per share upon the start of Phase III clinical trials for Metsera’s MET-097i+MET-233i combination
- $7 per share upon FDA approval of Metsera’s monthly MET-097i monotherapy
- $10.50 per share upon FDA approval of Metsera’s monthly MET-097i+MET-233i combination
The acquisition transaction is expected to close in the fourth quarter, subject to satisfying customary closing conditions, including receipt of required regulatory approvals and approval by Metsera’s shareholders.
Pfizer said it will offer any updates to its financial outlook related to the Metsera acquisition during upcoming quarterly earnings releases.
Should Metsera terminate its deal with Pfizer under specified circumstances that include accepting a superior offer from another company, Metsera has agreed to pay a fee equal to $190 million, the company disclosed in a regulatory filing.
“Since our founding in 2022, Metsera has worked tirelessly to reduce the physical, emotional, and economic burdens of obesity with a portfolio of next-generation nutrient-stimulated hormone therapeutic candidates,” stated Whit Bernard, Metsera’s co-founder and CEO.
“[Monday]’s announcement sets a path for our portfolio to potentially transform the lives of hundreds of millions of people and represents an excellent outcome for our shareholders,” Bernard added. “We look forward to joining forces with Pfizer to leverage their global clinical, regulatory, manufacturing, and commercial capabilities to realize the promise of improved human health at scale.”
