Antag Therapeutics has dosed the first subjects in a Phase 1a clinical trial evaluating AT-7687, a first-in-class Glucose-Dependent Insulinotropic Polypeptide Receptor (GIPR) antagonist for obesity treatment. The trial marks a significant step forward in addressing key limitations of current obesity therapies.
The double-blind, placebo-controlled study will assess AT-7687's safety, tolerability, pharmacokinetics, and metabolic effects in both healthy lean subjects and individuals living with obesity. Topline results are expected in Q4 2025.
Novel Mechanism Targets Unmet Needs in Obesity Treatment
Despite recent advances in obesity management, many patients struggle to achieve weight loss targets with existing therapies and frequently discontinue treatment due to gastrointestinal side effects such as nausea and vomiting. Clinical data indicates these adverse effects are a leading cause of treatment discontinuation, limiting the long-term health benefits including cardiovascular risk reduction.
AT-7687 is designed to offer a new approach by targeting the GIPR, a mechanism with strong genetic and clinical validation. The compound aims to improve both efficacy and tolerability compared to current incretin-based therapies.
"The initiation of this Phase 1 trial represents a pivotal milestone for Antag and in advancing the chronic weight management paradigm for people living with obesity," said Jörg Möller, Chief Executive Officer of Antag Therapeutics. "While GLP-1-based therapies have transformed treatment options, many patients continue to face challenges with tolerability and long-term adherence."
Promising Preclinical Results
In preclinical models, AT-7687 demonstrated significant potential, achieving substantial body weight reduction in non-human primates over a six-week period. Notably, when combined with a GLP-1 agonist, the weight loss effects were enhanced, suggesting synergistic benefits for patients requiring combination therapy.
The compound has also shown excellent tolerability with substantially lower gastrointestinal side effects than existing therapies, potentially improving long-term adherence and treatment outcomes.
Richard Nkulikiyinka, Chief Medical Officer of Antag Therapeutics, explained: "AT-7687's mechanism targets key metabolic pathways that influence not only weight loss and maintenance, but also broader cardiometabolic health. By improving tolerability and addressing underlying metabolic drivers, AT-7687 has the potential for more sustainable and clinically meaningful outcomes in a much broader patient population than served by currently approved therapies."
Versatile Treatment Approach
AT-7687 is being developed as both a standalone therapy and as a complement to existing treatments. The company plans to investigate AT-7687 as a combination therapy in patients already receiving GLP-1 receptor agonists, with this study expected to commence at the end of 2025.
Beyond weight management, AT-7687 has the potential to deliver additional cardiometabolic benefits, including improved glycemic control and body composition, addressing the complex nature of obesity as a chronic disease.
Scientific Foundation
The development of AT-7687 builds on the groundbreaking discovery of an endogenous GIPR antagonist by Professors Jens Holst, renowned for his discovery of GLP-1, and Mette Rosenkilde. The therapeutic potential is further supported by robust human genetic validation, which demonstrates that reducing GIP receptor activity is associated with leanness.
As obesity rates continue to rise globally, with over 650 million adults affected worldwide according to WHO estimates, the need for more effective and tolerable treatment options remains critical. The current global obesity therapeutics market is projected to reach $54 billion by 2030, reflecting the significant unmet medical need that AT-7687 aims to address.
Antag Therapeutics is a Copenhagen-based biopharmaceutical company committed to discovering and developing novel therapies for obesity and cardiometabolic diseases through GIP receptor antagonism. The company is pioneering the exploration of GIP receptor antagonists to deliver groundbreaking solutions for patients with obesity and related conditions.
