Bidding for Innovation
WEEK OF OCTOBER 25 – OCTOBER 31, 2025
This week I want to highlight one ongoing business deal and the science involved. Novo Nordisk submitted an unsolicited proposal to acquire Metsera. This was after Pfizer announced a definitive agreement to acquire Metsera just over a month ago. Pfizer didn’t take too kindly to Novo Nordisk’s proposal. Pfizer’s response statement started like this: “Pfizer Inc. (NYSE: PFE) is aware of the reckless and unprecedented proposal by Novo Nordisk A/S (NYSE: NVO) to acquire Metsera, Inc.” Metsera didn’t see it that way. Metsera’s board called Novo’s offer “superior”, and Pfizer has four days to respond.
What are these giants fighting over? What is the science and the promise behind Metsera’s portfolio?
Metsera is developing next-generation obesity drugs with once-monthly dosing and combination therapy potential. Metsera’s lead program, MET-097i, is an ultra-long-acting GLP-1 with a 15-day half-life that showed 14.1% placebo-adjusted weight loss at 28 weeks in its Phase 2b VESPER-1 trial -- all from monthly injections without dose titration. The company’s broader strategy involves combining incretin and non-incretin mechanisms (GLP-1, amylin, glucagon, GIP) using proprietary HALO™ lipidation technology, plus oral GLP-1 peptides via their MOMENTUM™ platform. In short, orals and injectables are in the pipeline as part of a platform approach with the promise of better characteristics than existing medicines. You can see why Novo Nordisk might think that Metsera’s portfolio might breathe extended life (no pun intended) into their GLP-1 offerings.
This week’s Trial Spotlight below touches again (like last week’s opener) on the potential role that addressing inflammation plays as part of incretin-based trials.
🔥 THIS WEEK’S KEY DEVELOPMENTS
Novo Nordisk bids up to $9B to acquire Metsera.
Novo Nordisk confirmed it submitted an unsolicited proposal to acquire Metsera, Inc. The proposed acquisition is valued at approximately $6.5 billion in cash, plus up to $2.5 billion in contingent value rights (CVRs) based on clinical and regulatory milestones, totaling up to $9 billion in potential value. The primary justification for the acquisition is Metsera’s portfolio, which includes early and development-stage incretin and non-incretin analog peptide programs, aligning with Novo Nordisk’s long-term strategy of developing innovative medicines for obesity and diabetes.
Press | Mechanism: incretin and non-incretin analog peptide programs
Novo Nordisk to present new Wegovy data in MASH.
Novo Nordisk announced it will present 11 abstracts for Wegovy® (semaglutide 2.4 mg) at the 76th Annual AASLD The Liver Meeting® from November 7-11, 2025. The presentations will feature post-hoc analyses from the ESSENCE trial investigating the effects of Wegovy in metabolic dysfunction-associated steatohepatitis (MASH) in relation to weight loss and across diverse patient populations.
Press | Trials: NCT04822181 | NCT03574597 | NCT04971785 | Mechanism: glucagon-like peptide-1 receptor agonist (GLP-1 RA)
Viking to present VK2735 obesity data at upcoming medical conferences.
Viking Therapeutics announced it will present data on its VK2735 obesity program at ObesityWeek® 2025 and the American Heart Association (AHA) Scientific Sessions 2025. One presentation will feature an exploratory analysis from the Phase 2 VENTURE trial evaluating the impact of 13 weeks of VK2735 treatment on prediabetes and metabolic syndrome. The company will also present the study designs for its ongoing Phase 3 VANQUISH-1 and VANQUISH-2 trials.
Press | Trials: NCT06068946 | NCT07104500 | NCT07104383 | Mechanism: dual agonist of the glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors
Roche acquires 89bio and its Phase 3 MASH drug.
Roche announced it has accepted for payment all validly tendered shares for 89bio, Inc. at a price of $14.50 per share in cash, plus a contingent value right (CVR) of up to $6.00 per share. Approximately 94.1 million shares, representing 60.49% of 89bio’s outstanding common stock, were tendered. Through this acquisition, Roche gains 89bio’s lead candidate, pegozafermin, a Phase 3 FGF21 analog for metabolic dysfunction-associated steatohepatitis (MASH) and severe hypertriglyceridemia (SHTG).
Press | Mechanism: fibroblast growth factor 21 (FGF21) analog
PRESS RELEASES
• Lilly raises guidance on strong Mounjaro and Zepbound sales. Press | Mechanism: incretin portfolio
• Lilly invests $1.2B to expand orforglipron manufacturing in Puerto Rico. Press | Mechanism: oral, small molecule GLP-1 receptor agonist
• Lilly partners with Walmart for Zepbound retail pickup. Press | Mechanism: incretin (GLP-1) medicines
🆕 NEWLY REGISTERED TRIALS (5 in last week)
BMF-650 Phase 1 trial evaluating the new drug in otherwise healthy overweight or obese adults (Biomea Fusion Inc., n=80)
[Weight Loss/Efficacy]
Trials: NCT07223216 | Mechanism: oral non-peptide GLP-1 receptor agonist
Survodutide Phase I study comparing two different formulations in healthy volunteers to assess how they are absorbed by the body (Boehringer Ingelheim, n=100)
[New Indications]
Trials: NCT07221591 | Mechanism: Dual GLP-1/glucagon agonist
GLP-1 receptor agonists Phase IV trial to reduce alcohol consumption and cardiovascular risk in people with HIV (Vanderbilt University Medical Center, n=200)
[New Indications]
Trials: NCT07221214 (GL1DER HIV RCT) | Mechanism: GLP-1 receptor agonist
Tirzepatide Phase 2 trial investigating its potential to slow biological aging in healthy adults (UT Medical Branch, n=90)
[New Indications]
Trials: NCT07220473 | Mechanism: Dual GLP-1/GIP agonist
RESOLVE-2 Phase 2 investigating NT-0796 as an add-on therapy to semaglutide for participants with obesity (NodThera Limited, n=80)
[Weight Loss/Efficacy | Safety/Tolerability]
Trials: NCT07220629 (RESOLVE-2) | Mechanism: Non-incretin mechanism
💡 TRIAL SPOTLIGHT
Educational spotlight selected by editors
Study to Explore the Safety and Efficacy of NT-0796 as an Adjunct to Semaglutide in Participants With Obesity (RESOLVE-2)
This Trial Spotlight focuses on RESOLVE-2, a Phase 2 study evaluating if adding an investigational oral drug, NT-0796, can improve weight loss in patients already taking semaglutide. The trial is a randomized, double-blind, placebo-controlled study where all ~80 participants with obesity receive semaglutide, with half also receiving NT-0796 and the other half a placebo for six months. Unlike semaglutide, a GLP-1 receptor agonist, NT-0796 works through a novel mechanism by inhibiting the NLRP3 inflammasome, which is believed to reduce chronic inflammation associated with obesity. NodThera, the sponsor, is currently recruiting for the trial and anticipates completion by the third quarter of 2026. Strategically, this trial is significant as it tests whether a combination approach can enhance the effects of established incretin therapies and potentially address key challenges like weight regain after treatment discontinuation. Preclinical data suggests this combination may drive greater weight loss and limit regain, representing a new strategy that targets both metabolic pathways and underlying inflammation.
🔬 MECHANISM EXPLAINED
Understanding the science behind the therapeutics
Dual GLP-1/glucagon agonist (Example drug: Survodutide)
Dual GLP-1/glucagon agonists like survodutide represent a multi-faceted approach to treating metabolic diseases. These unimolecular drugs activate two distinct receptors: the GLP-1 receptor to suppress appetite and improve blood sugar control, and the glucagon receptor to increase energy expenditure and promote fat metabolism. This dual mechanism is designed to create a synergistic effect, tackling both calorie intake and calorie burning for potentially greater weight loss than GLP-1 agonism alone. This approach matters because the added glucagon activity directly targets fat in the liver, making these drugs promising candidates for treating metabolic dysfunction-associated steatohepatitis (MASH), a severe form of fatty liver disease. In a competitive landscape dominated by GLP-1 and GLP-1/GIP agonists, the unique addition of glucagon agonism may provide a key advantage for treating liver-related comorbidities.
This newsletter compiles publicly available information from company press releases and ClinicalTrials.gov. Not investment advice.