An FGF21 analog moving towards the market, now with support of one of the big players (Roche)…
Roche becomes MASH player via $3.5B deal for 89bio and its phase 3 drug
September 17, 2025
89bio’s pegozafermin allows for a potentially best-in-disease treatment for moderate to severe Metabolic Dysfunction-Associated Steatohepatitis (MASH), one of the most prevalent comorbidities of obesity
Acquisition supports Roche’s strategy as it enhances the company’s portfolio in cardiovascular, renal, and metabolic diseases (CVRM) and offers optionality for future combination development
Roche to acquire 89bio for US$14.50 per share in cash at closing, representing a total equity value of approximately US$2.4 billion. Stockholders would also receive a non-tradeable contingent value right (CVR) for up to an aggregate of US$6.00 per share in cash, representing a total deal value of up to approximately US$3.5 billion
Basel, 18 September 2025 - Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today that it has entered into a definitive merger agreement to acquire 89bio, Inc. (Nasdaq: ETNB), a publicly listed clinical-stage biopharmaceutical company pioneering the development of innovative therapies for the treatment of liver and cardiometabolic diseases. 89bio’s pegozafermin is a FGF21 analog currently in late-stage development for MASH in moderate and severe fibrotic patients (F2 and F3 stages) as well as cirrhotic patients (F4 stage). The transaction is expected to close in the fourth quarter of 2025.
This acquisition underscores Roche’s dedication to advancing innovative therapies in cardiovascular, renal, and metabolic diseases (CVRM), especially for patients affected by overweight, obesity, and related health challenges such as MASH. Pegozafermin offers a distinct mechanism of action that not only holds the potential for enhanced efficacy and tolerability but also unlocks opportunities for future combination development with incretins, creating synergies with Roche’s CVRM portfolio. Acquiring 89bio, therefore, fosters Roche’s activities to build a robust and differentiated pipeline that targets additional causes of metabolic disease.
“This acquisition further strengthens our portfolio in cardiovascular, renal, and metabolic diseases and offers opportunities to explore combinations with existing programmes in our pipeline,” said Thomas Schinecker, Roche Group CEO. “We are highly encouraged by pegozafermin’s potential to become a transformative treatment option in MASH, one of the most prevalent comorbidities of obesity, and to meet diverse patient needs associated with this complex disease. With its combined anti-fibrotic and anti-inflammatory mechanism, pegozafermin could potentially offer best-in-disease efficacy for all moderate to severe MASH patients.”
89bio’s pegozafermin is a glycoPEGylated analog of fibroblast growth factor 21 (FGF21) specifically designed to address critical unmet needs in MASH. With its anti-fibrotic and anti-inflammatory mechanism of action combined with a favourable safety profile, pegozafermin is positioned to potentially deliver best-in-disease efficacy for patients suffering from moderate to severe liver fibrosis (F2/F3 stages) and cirrhotic MASH (F4 stage).
Current 89bio employees will join the Roche Group as part of Roche’s Pharmaceuticals Division.
Mitochondrial and psychosocial stress-related regulation of FGF21 in humans
Fibroblast growth factor 21 (FGF21) is a metabolic hormone induced by fasting, metabolic stress and mitochondrial oxidative phosphorylation (OxPhos) defects that cause mitochondrial diseases (MitoD). Here we report that acute psychosocial stress alone (without physical exertion) decreases serum FGF21 by an average of 20% (P < 0.0001) in healthy controls, but increases FGF21 by 32% (P < 0.0001) in people with MitoD, pointing to a functional FGF21 interaction between the stress response and OxPhos capacity. We further define co-activation patterns between FGF21 and stress-related neuroendocrine hormones and report associations between FGF21 and psychosocial factors related to stress and wellbeing. Overall, these results highlight a potential role for FGF21 as a stress hormone involved in meeting the energetic needs of psychosocial stress.
New insights into weight-loss hormones: How FGF21 works in the brain
A hormone that reverses obesity in mice appears to work by signaling to a brain region involved in metabolism and appetite regulation, the same area targeted by the popular GLP-1 drugs. The finding, from University of Oklahoma researchers, is published in Cell Reports.
The study provides valuable new insight into the naturally occurring hormone, called FGF21 (fibroblast growth factor 21), which is already involved in drug development. Drugs that target the pathway of this hormone are currently being examined in clinical trials for the treatment of MASH (metabolic dysfunction-associated steatohepatitis), a form of fatty liver disease.
Researcher Matthew Potthoff, Ph.D., is the lead author of the study, which demonstrates that the hormone produces its beneficial effects by signaling to the hindbrain, or the lower back region of the brain.
“In our previous studies, we found that FGF21 signals to the brain instead of the liver, but we didn’t know where in the brain,” said Potthoff, a professor of biochemistry and physiology in the OU College of Medicine and deputy director of OU Health Harold Hamm Diabetes Center. “We thought we would find that it signaled to the hypothalamus (which is widely implicated in body weight regulation), so we were very surprised to discover that the signal was to the hindbrain, which is where the GLP-1 analogs are believed to act.”
Specifically, FGF21 signals to a part of the hindbrain known as the nucleus of the solitary tract (NTS) and the area postrema (AP). The NTS and AP essentially make a “phone call” to a different brain region called the parabrachial nucleus, a signaling process that is necessary for FGF21 to exert its beneficial metabolic effects to reduce body weight.
“This brain circuit seems to be mediating the effects of FGF21,” Potthoff said. “We hope that by identifying the specific circuit, it can help in the creation of more targeted therapies that are effective without negative side effects. FGF21 analogues have side effects like gastrointestinal issues and, in some cases, bone loss.”
Although they target the same area of the brain, FGF21 and GLP-1 act in different ways. GLP-1 works by reducing food intake, whereas FGF21 increases the metabolic rate, which burns energy and leads to weight loss.