Preclinical data shows precision modulation of beta-2 and beta-3 signaling boosts metabolism and enhances body recomposition
STOCKHOLM, Sweden, May 24, 2024 (GLOBE NEWSWIRE) -- Atrogi, a pioneering clinical-stage biotech company advancing treatments for metabolic disorders, announces a publication in the Journal of Molecular Metabolism (1). The research paper validates the mechanism of action of the company’s first-in-class, small molecule, ATR-127, in combating obesity and metabolic complications.
Unlike existing anti-obesity therapies that compromise lean muscle mass, ATR-127 induces significant weight loss while preserving crucial lean body mass. ATR-127 binds to both the beta-2 and beta-3 adrenergic receptors in a unique manner, allowing for precise modulation of downstream signaling cascades. Unlike conventional approaches, ATR-127's innovative binding mechanism enables selective activation of specific signaling pathways. This unlocks the full therapeutic potential of beta-2 and beta-3 receptor agonism, maximizing beneficial effects on metabolism and body composition while mitigating the cardiovascular side effects commonly associated with indiscriminate receptor activation.
Atrogi’s CEO, Alexandra Ekman Ryding, said, “This publication highlights strong pre-clinical data relating to ATR-127 and validates our approach for the development of a novel modality for the treatment of obesity. We are now advancing our next generation small molecules for the treatment of obesity to IND preparatory studies in H1 next year and expect to enter the clinic in 2026.”
Atrogi´s founder and CSO, Tore Bengtsson, a Professor of Physiology at Stockholm University, said, “There is a high demand for novel treatments of obesity without the current debilitating side effects and muscle loss. We believe our pioneering dual receptor beta-agonist approach has the potential to transform the obesity treatment landscape. Our vision is for a more holistic treatment for diabesity and steatohepatitis that not only treats the underlying cause of disease but also supports overall health and quality of life.”
The study found that ATR-127 enhances energy expenditure and promotes beneficial metabolic changes by inducing skeletal muscle glucose uptake and the concomitant activation of brown and beige adipose tissue. This results in healthy weight loss - decreasing fat mass but preserving muscle, whilst reducing hepatic inflammation and lipid content. ATR-127’s ability to deliver precise signaling modulation prevents excessive cAMP production thereby lowering cardiac force production and mitigating risks of cardiovascular side effects.
This study was a collaborative international effort involving Atrogi AB, and institutions in Europe and Australia, including Stockholm University, Monash University, University of Nottingham, Karolinska Institute, Maastricht University Medical Center, Latvian Institute of Organic Synthesis, Excellerate Bioscience, Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Tübingen University, University of Copenhagen, University of Queensland, and Queensland University of Technology.
Atrogi’s unique platform enables the synthesis of compounds capable of modulating signaling downstream of adrenergic receptors in novel ways. By measuring the specific activation of numerous downstream signaling events, Atrogi has created a proprietary library of compounds that engage discrete signaling pathways, each tailored to enhance beneficial effects while mitigating potential side effects in different therapeutic areas. Atrogi's iterative approach to drug development allows for the generation of compounds with optimized signaling profiles and improved efficacy.
References
(1) Paper: “The novel adrenergic agonist ATR-127 targets skeletal muscle and brown adipose tissue to tackle diabesity and steatohepatitis”
Notes to Editors
About Atrogi AB
Atrogi is a clinical-stage biotech company developing first-in-class, insulin-independent treatments for type 2 diabetes (T2D) and related metabolic disorders, including obesity and muscle-wasting disorders. Atrogi’s lead compound, ATR-258 for T2D, completed a Phase 1a/b clinical trial in March 2024, with Phase II trials planned by the end of 2024. Atrogi also has compounds in pre-clinical development for the treatment of obesity and muscle wasting disorders.
ATR-258 binds to the beta-2 adrenoreceptor, initiating a process that mediates the transportation of glucose into skeletal muscle, lowering blood glucose levels and positively affecting several organs affected by T2D. The proprietary small-molecule compound activates the receptor in a novel manner, causing selective modulation and a distinct signaling profile.
Atrogi’s platform extends beyond the adrenergic receptor system, offering the potential for application to other GPCRs. By leveraging the signaling complexity of GPCRs, Atrogi aims to develop tailored compounds that engage specific pathways relevant to different clinical conditions, paving the way for safer, more effective therapies.
The company has raised over EUR 24 m in total since inception from investors, including Flerie Invest, Korea Investment Partners (KIP) and private investors. This includes a SEK 90 million (approx. EUR 7.6 m) rights issue. The company has also been awarded non-dilutive grants of over EUR 1.5 million from international organizations such as Eurostars, as well as grants from SweLife in recognition of the company’s unique discovery of receptor signaling.
The company is based in Solna, near Stockholm, Sweden. Follow the company on LinkedIn and visit its website.
Media Contacts
Atrogi
Alexandra Ekman Ryding, CEO
alexandra@atrogi.com
Scius Communications (for Atrogi)
Katja Stout
katja@sciuscommunications.com
Tel: +44 7789 435990
Daniel Gooch
Tel: +44 7747 875479
daniel@sciuscommunications.com
