Atrogi, a Swedish clinical stage biotech company, has announces that the first subjects have been dosed in a human trial for its lead candidate, ATR-258. The company is pioneering novel GPCR pathway-signalling modulators to transform metabolic and muscle health, and the phase 1 trial will evaluate the muscle physiological effects of the candidate’s highly selective GRK-targeted β2-adrenergic signaling pathway.
The first-in-class oral therapy ATR-258 mimics the effects of exercise – driving fat loss, increasing muscle and improving metabolism – with broad potential as a novel treatment for muscle-sparing weight loss.
Morten Hostrup, Associate Professor at the University of Copenhagen and Principal Investigator of the study, said: “This trial will allow us to rigorously interrogate targeted downstream effector signalling associated with the β2-adrenergic receptor in human skeletal muscle using a highly selective next generation modulator.
“By combining detailed muscle physiological measurements with advanced molecular readouts, we aim to better understand how biased β2-adrenergic signalling regulates muscle growth and function, and how it can potentially be harnessed to preserve, or even augment, muscle function in various conditions of muscle wasting, such as immobilisation, ageing and weight loss.”
The 8-week, investigator-initiated, interventional study will examine biased β2-adrenergic receptor (β2-AR) signaling in human skeletal muscle, in overweight male volunteers. The volunteers will be given daily oral dosing of ATR-258, Atrogi’s GRK-selective long-acting β2-agonist. The study aims to measure the extent to which the candidate recapitulates the muscle physiological effects of classic β2 agonists, as well as its potential across a range of muscle atrophic conditions.
Professor Tore Bengtsson, Chief Scientific Officer and Founder of Atrogi, added: “Professor Hostrup is widely recognised…in the field, and we are excited about his commitment to investigate the muscle signalling effects of ATR-258. We look forward to sharing the results later this year.”
The trial follows the publication of a landmark study in Cell in June 2025, validating Atrogi’s novel GRK2-biased signalling pathway approach in unlocking the therapeutic potential of muscle-targeted β2-agonists while avoiding the cardiovascular side effects typically associated with this approach.
The paper also detailed first-in-human trial data from a 69-subject phase 1 trial, demonstrating the safety and tolerability of ATR-258 in both healthy volunteers and patients with type 2 diabetes.
Paul Little, CEO at Atrogi, commented: “The initiation of this study, and dosing of the first subjects, marks an important milestone for Atrogi. With safety established in phase 1 and a validated mechanism of action, the generation of key muscle physiology data from this trial will underpin ATR-258’s further development across metabolic and muscle-wasting conditions.”