Antag Therapeutics Reports Promising Phase 1 Results for Novel GIPR Antagonist AT7687 in Obesity Treatment
Key Insights
Antag Therapeutics (search) announced positive Phase 1 results for AT7687, a first-in-class GIPR (search) antagonist, demonstrating excellent tolerability with no serious adverse events or GI-related side effects in 102 participants.
Preclinical studies showed AT7687 combined with cagrilintide achieved enhanced weight loss in the low double-digit percentage range without plateauing, superior to either monotherapy alone.
The combination therapy improved body composition by preferentially reducing fat mass over lean mass and enhanced insulin sensitivity, positioning AT7687 as a promising combination partner for obesity (search) treatment.
Antag Therapeutics (search) has reported compelling Phase 1 clinical data for AT7687, its first-in-class GIP receptor (search) (GIPR (search)) antagonist, demonstrating excellent tolerability and promising efficacy signals for obesity (search) treatment. The biotechnology company also announced positive preclinical results showing enhanced weight loss when AT7687 is combined with amylin receptor (search) agonist cagrilintide.
Phase 1 Clinical Trial Demonstrates Excellent Safety Profile
The Phase 1 randomized, double-blind, placebo-controlled study evaluated the safety, pharmacokinetics, and early pharmacodynamics of AT7687 in 102 individuals with a body mass index below 40 kg/m². The study utilized a combined single ascending dose (SAD) and multiple ascending dose (MAD) design, with participants in the MAD cohorts treated for four weeks.
The study demonstrated a favorable safety and tolerability profile across all doses tested. Notably, no serious or severe adverse events were reported, and no participants discontinued treatment due to adverse events. AT7687 showed an excellent gastrointestinal-related tolerability profile, with all GI adverse events being mild and equally distributed between the AT7687 and placebo arms.
Multi-organ target engagement was observed from the lowest tested doses, including reductions in LDL-cholesterol and resting heart rate. The pharmacokinetic data supported once-weekly subcutaneous dosing, which could enhance patient compliance in clinical practice.
Combination Study Shows Superior Weight Loss Effects
In a separate preclinical study conducted in obese, insulin-resistant non-human primates, the combination of AT7687 and cagrilintide demonstrated robust and sustained weight loss in the low double-digit percentage range without evidence of plateauing over the 42-day treatment period. This weight loss effect was superior to either monotherapy treatment.
Importantly, the additional weight loss observed with the combination was independent of appetite suppression. Total energy intake was similar between animals receiving the combination and those treated with cagrilintide alone, indicating that the enhanced weight loss was not driven by reduced food intake.
The combination therapy was also associated with favorable changes in body composition, including preferential loss of fat mass relative to lean mass, as well as improvements in insulin sensitivity. These findings support a differentiated and synergistic profile versus amylin treatment alone.
Building on Previous GLP-1 Combination Data
These results build upon previously reported positive data demonstrating AT7687's additive effect on weight loss, body composition, insulin sensitivity, and cardiovascular risk biomarkers when combined with GLP-1 agonist liraglutide. This positions AT7687 as a versatile combination partner across different obesity (search) treatment mechanisms.
Jörg Möller, Chief Executive Officer of Antag Therapeutics (search), commented: "These combination data with cagrilintide, building on those already reported with liraglutide, demonstrate AT7687's leading combination partner of choice status in the obesity (search) field. The potential for AT7687 to not only enhance weight loss, but also have strong additive effect on both healthier body composition and insulin sensitivity without increasing the tolerability burden, is especially compelling in this insulin-resistant study group."
Novel Mechanism Targeting GIP Receptor
AT7687 is specifically designed to target and deactivate the GIP receptor (search), a genetically-validated pathway that contributes to fat storage, insulin resistance (search), and metabolic dysfunction. Based on decades of research by GLP-1 pioneer Professor Jens Holst, this mechanistically distinct approach represents a potential paradigm shift in obesity (search) treatment.
The peptide is specifically engineered for straightforward and versatile formulation properties, uniquely positioning Antag to develop AT7687 as monotherapy or as co-formulation with other obesity (search) therapies. This approach aims to enable more personalized, adaptable care for patients with overweight or obesity.
Clinical Development and Funding
AT7687 is currently in Phase 1 clinical trials, with topline data expected in Q4 2025. The company plans to advance this asset into Phase 2 development based on the positive results reported. Data from both studies will be presented at a future medical congress and submitted for publication.
Antag Therapeutics (search) has raised €80 million in a Series A financing led by Versant Ventures (search) with participation from Novo Holdings (search), SR One, Dawn Biopharma, Pictet, Longview Ventures, and the Export and Investment Fund of Denmark (EIFO), providing the financial foundation to advance AT7687 through clinical development.