🔥 THIS WEEK’S KEY DEVELOPMENTS
Roche to acquire 89bio for MASH drug pegozafermin.
[Partnerships/M&A]
Roche has commenced a tender offer to acquire all outstanding shares of 89bio for $14.50 per share in cash, plus a non-tradeable contingent value right (CVR) of up to $6.00 per share. The acquisition includes 89bio’s lead candidate, pegozafermin, a Phase 3 asset being developed for MASH and severe hypertriglyceridemia (SHTG). The transaction is expected to close in the fourth quarter of 2025.
Press | Mechanism: fibroblast growth factor 21 (FGF21) analog | *See Mechanism Explained below for why this is relevant to GLP-1s
🆕 NEWLY REGISTERED TRIALS (8 in last week)
HM15275 Phase 2 evaluating the drug for weight management in obese or overweight adults without diabetes (Hanmi Pharmaceutical, n=250) [Weight Loss/Efficacy] Trials: [NCT07205900]
Orforglipron Phase 3 trial investigating its effect on stress urinary incontinence in women with obesity or overweight (Eli Lilly, n=1000) [Weight Loss/Efficacy] Trials: [NCT07202884] (RESTRAIN-SUI) | Mechanism: Oral GLP-1 agonist
Survodutide Phase 2 trial evaluating the dual GLP-1/glucagon agonist for reducing albuminuria in patients with kidney disease (University Medical Center Groningen, n=120) [New Indications] Trials: [NCT07206290] (ARTIST-CKD) | Mechanism: GLP-1/Glucagon dual agonist
TIRZSITA-CVOT Observational study comparing the cardiovascular effectiveness of tirzepatide versus sitagliptin in individuals at cardiovascular risk (Brigham and Women’s Hospital, n=49065) [New Indications] Trials: [NCT07203677] (Observational) | Mechanism: GLP-1/GIP dual agonist
XTL6001 Phase I evaluating the safety and tolerability of a new injection in both healthy and obese subjects (Shanghai Xitaili Biomedicine, n=80) [Weight Loss/Efficacy] Trials: [NCT07205432]
Glutide for Ending Methamphetamine (GEM) Phase 2 investigating a GLP-1 agonist for treating methamphetamine use disorder (San Francisco Dept. of Public Health, n=25) [New Indications] Trials: [NCT07204249] (GEM)
IMPACT-ADT Trial Phase 2 investigating if time-restricted eating, a GLP1 agonist, and diet can improve cardiometabolic health in prostate cancer patients on ADT (City of Hope Medical Center, n=60). [New Indications] Trials: [NCT07202247]
Oral Semaglutide Phase 2 trial investigating its effect in patients with Alzheimer’s disease (Imperial College London, n=60) [Oral Formulations] Trials: [NCT07200622] | Mechanism: GLP-1 agonist
💡 TRIAL SPOTLIGHT
Educational spotlight selected by editors
A Study of Orforglipron in Female Participants With Stress Urinary Incontinence Who Have Obesity or Overweight (RESTRAIN-SUI)
Eli Lilly is launching a large Phase 3 trial, NCT07202884, to investigate its oral drug, orforglipron, for treating stress urinary incontinence (SUI) in women with obesity or overweight. The study operates on the hypothesis that significant weight loss, induced by the drug’s mechanism as a GLP-1 receptor agonist, will reduce intra-abdominal pressure on the bladder and pelvic floor, thereby alleviating SUI symptoms. With a target enrollment of 1000 participants, this pivotal trial is moving into the final stage of clinical development before a potential request for regulatory approval for this specific use. Strategically, this trial is significant as it aims to expand the application of GLP-1 agonists beyond diabetes and weight management into a common and impactful quality-of-life comorbidity. A positive outcome would not only provide a novel, non-surgical treatment for SUI but also differentiate orforglipron as a convenient oral option in a market dominated by injectables, tapping into a substantial unmet medical need.
🔬 MECHANISM EXPLAINED
Understanding the science behind the therapeutics
fibroblast growth factor 21 (FGF21) analog
Fibroblast growth factor 21 (FGF21) analogs like pegozafermin represent a distinct approach to treating metabolic diseases, particularly metabolic dysfunction-associated steatohepatitis (MASH). As an engineered version of the naturally occurring FGF21 hormone, pegozafermin binds to FGF21 receptor complexes in tissues like the liver and adipose tissue, activating pathways that enhance insulin sensitivity, boost fatty acid oxidation, and reduce fat production. This mechanism is significant because it directly targets the key drivers of MASH by reducing liver fat, inflammation, and fibrosis. In a therapeutic landscape dominated by GLP-1 agonists, which primarily regulate glucose and appetite, FGF21 analogs offer a complementary and more direct liver-focused action. This positions them as a potentially crucial therapy for patients with advanced liver fibrosis, addressing a critical aspect of metabolic disease that is not the primary target of GLP-1s.
*This newsletter compiles publicly available information from company press releases and ClinicalTrials.gov. Not investment advice.*