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Atrogi Announces Publication on Advancements in Combatting Obesity and Metabolic Complications

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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
daniel@sciuscommunications.com
Tel: +44 7747 875479

1. ClinicalTrials.gov identifier: NCT05409924

Atrogi Announces Positive Clinical Data from First-in-Class Insulin-Independent Treatment for Type 2 Diabetes

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All endpoints met for novel b2–adrenoceptor agonist ATR-258 treating root cause of T2D

Solna, Sweden 14 March 2024 – Atrogi, a pioneering clinical-stage biotech company advancing treatments for metabolic disorders, announces the full set of results from its Phase 1 a/b trial with ATR-258, its first-in-class treatment for type 2 diabetes (T2D). This clinical trial, conducted on both healthy volunteers and individuals with T2D, underscores the safety of ATR-258 as a novel b2-adrenoceptor agonist, offering a revolutionary approach to type 2 diabetes treatment.

The unique mechanism of action of ATR-258 enables the selective modulation of specific positive intracellular signaling pathways. This innovative approach makes it possible to address the core issue of type 2 diabetes, effectively reversing it to healthy levels as demonstrated in preclinical studies.

Atrogi’s CEO, Alexandra Ekman Ryding, said, “This full phase 1a/b data readout is exactly what we were aiming for, with primary and secondary safety endpoints met. This puts us in a strong position to progress our ground-breaking small molecule compound ATR-258 into a larger multi-centre Phase II trial later this year, underpinned with an upcoming Series B financing. We strongly believe that our novel approach could become a transformative treatment for T2D patients.”

Atrogi´s founder and CSO, Professor Tore Bengtsson, said,“These safety results strongly validate my long-held vision for a more holistic treatment for diabetes that not only treats the underlying cause but also supports overall health and quality of life.  It underscores the therapeutic value of this novel pathway for the treatment of type 2 diabetes. Notably, in the final cohort of people with T2D we had been specifically looking for cardiovascular safety, which is now confirmed.”

Atrogi’s board chair, Anders Ekblom, said, “Diabetes and obesity are major global health challenges. Better treatments are needed that improve glycaemic control while maintaining muscle mass, the latter decreasing more prominently in aging and diabetic populations. Atrogi’s unique discovery of receptor signalling, which treats the root cause of the disease via an insulin independent pathway, has the potential to create unique treatment opportunities and even disrupt the current diabetes market.”

The ‘ATTRACTIVE 1’ trial (1), conducted in Mannheim, Germany, by Clinical Research Services (CRS), was a double-blind, placebo-controlled, randomized trial evaluating the safety of ATR-258 for the treatment of T2D. The complete trial investigated the use of single, and multiple, ascending doses of ATR-258 in 46 healthy volunteers as well as its administration at a fixed dose in 23 T2D patients over 28 days. The final data demonstrated that ATR-258 was safe and well tolerated in healthy volunteers, and, importantly, also in the T2D patients.

Atrogi announces first patient treated with Adrenoceptor agonist

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Atrogi announced today that the first patient has been enrolled in a Phase 1a/b study. Atrogi’s drug candidate, ATR-258 is a first in class novel ß2 adrenoceptor agonist with a unique mechanism of action for the treatment of type 2 diabetes and comorbidities. This approach is supported by data presented in a January 2023 clinical publication in Nature Communications. The trial is expected to be completed by April 2023 with the final report in June 2023.

Conducted in Mannheim, Germany by Clinical Research Services (CRS), the Phase 1a/b study is a double-blind, placebo-controlled, randomized study evaluating the safety of ATR-258 for the treatment of type 2 diabetes (ClinicalTrials.gov identifier: NCT05409924).

The Phase I protocol covers three parts, Part A: Single Ascending Dose of the drug candidate given to healthy volunteers, and Part B: Multiple Ascending Dose administered to healthy volunteers. Both parts A and B have been completed successfully involving 48 healthy volunteers. Preliminary blinded data from the healthy volunteers suggests that ATR-258 was well tolerated without severe adverse reactions. Now the final part of the study with type 2 diabetes patients has commenced: in Part C: daily administration of ATR-258 at a fixed dose during 28 days in 24 type 2 diabetic patients.

This milestone coincides with a clinical publication in Nature Communications (van Beek et al.,) co-authored by Atrogi´s founder Professor Tore Bengtsson. The report describes the beneficial metabolic effects by a ß2 adrenoceptor agonist and the results “highlight the potential of ß2-agonist treatment in improving skeletal muscle glucose uptake and underscore the therapeutic value of this pathway for the treatment of type 2 diabetes.”

”There is a large unmet need for durable and efficient treatments for type 2 diabetes patients. We believe that our first-in-class drug candidate ATR-258 with its unique mode of action, has the potential to not only help these patients manage their blood glucose levels, but also help treat the actual cause of the disease. As of yet, no other type 2 diabetes drug has managed to achieve this.” said Alexandra Ekman Ryding, Ph.D., CEO.

Reference: van Beek, S.M.M., Bruls, Y.M.H., Vanweert, F. et al. Effect of β2-agonist treatment on insulin-stimulated peripheral glucose disposal in healthy men in a randomised placebo-controlled trial. Nat Commun 14, 173 (2023). https://doi.org/10.1038/s41467-023-35798-5