AlfaDAX-Derived ActRIIA/B Antibody with Semaglutide Enhances Fat Loss and Improves Weight-Loss Quality in DIO Mice

13 Jul 20264 min read0 viewsVerified Feed

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GLP 1 receptor agonists achieve weight loss but are associated with clinically significant reductions in lean mass. Activin type II receptors (ActRIIA and ActRIIB) mediate signaling of myostatin and activin A, both of which negatively regulate muscle growth, suggesting that dual blockade of these receptors may preserve or increase lean mass while promoting fat loss.
In this study, we developed anti ActRIIA/B antibodies using AI driven platforms (AlfaDAX) and selected the lead candidate AB130 165 based on in vitro binding, functional blocking, and developability assessments. Compared with a laboratory prepared bimagrumab analog, AB130 165 exhibited potent dual inhibition of ActRIIA/B signaling, with a 9.5 fold higher functional blocking activity against activin A induced SMAD signaling and 1054 fold improvements in binding affinity for ActRIIA (KD = 0.204 pM), 10-fold for ActRIIB (KD = 0.243 pM), respectively.
In diet induced obese mice, combination therapy with AB130 165 and semaglutide resulted in a 33.4% body weight reduction, which was superior to semaglutide monotherapy (-24.3%) and the bimagrumab combination group (-25.5%).

bioRxiv (Biomedical Preprints) published a clinical update in Research Highlights on 13 Jul 2026.

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bioRxiv (Biomedical Preprints)