AT-7687 / Antag Therap - LARVOL DELTA

Amylin combination study (The Manila Times) - "The study was conducted in high-fat-fed obese, insulin-resistant NHPs which were randomized to placebo, cagrilintide, AT7687 or the combination for 42 days followed by a 15-day wash-out whilst fed ad libitum....AT7687 and cagrilintide combination regimen showed robust and sustained weight loss, in the low double-digit percentage range, without evidence that the effect plateaued over time. This weight loss effect was superior to that of either monotherapy treatment. Total energy intake was similar between animals receiving the combination and those treated with cagrilintide alone, indicating that the additional weight loss was not driven by reduced food intake. AT7687 alone or combined with cagrilintide was well tolerated."

Preclinical • Obesity

Phase 1 clinical study (The Manila Times) - "The study demonstrated a favorable safety and tolerability profile across all doses. No serious or severe adverse events and no discontinuations due to adverse events were reported. Notably, AT7687 demonstrated an excellent GI-related tolerability profile: all GI adverse events were mild and equally distributed between the AT7687 and the placebo arms. In addition, multi-organ target engagement was observed from the lowest tested doses, including reductions in LDL-cholesterol and resting heart rate. PK data were consistent with once-weekly subcutaneous dosing."

P1 data • Obesity

Antag Therapeutics initiates Phase 1a trial of AT-7687, a first-in-class GIPR antagonist designed to address key gaps in obesity treatment (GlobeNewswire) - "Antag Therapeutics...today announces the initiation of its first-in-human Phase 1 clinical trial evaluating AT-7687, a first-in-class Glucose-Dependent Insulinotropic Polypeptide Receptor (GIPR) antagonist....The Phase 1a trial is a double-blind, randomized, placebo-controlled study designed to evaluate the safety, tolerability, and pharmacokinetics of AT-7687. It will be conducted in healthy lean and healthy subjects living with obesity, with topline results expected in Q4 2025....Following this study, the Company plans to investigate AT-7687 as a combination therapy in patients treated with a GLP-1 receptor agonist, with the study expected to commence at the end of 2025."

Trial status • Obesity

GIP receptor antagonism eliminates paradoxical growth hormone secretion in some patients with acromegaly. (PubMed, J Clin Endocrinol Metab) - "Of 25 patients with acromegaly, seven had paradoxical GH secretion during OGTT, and pharmaceutical GIPR blockade abolished this secretion in four. Corresponding somatotroph adenomas abundantly expressed GIPR, suggesting a therapeutic target in this subpopulation of patients. In vitro and ex vivo analyses confirmed the role of GIP and the effects of the antagonist."

Journal • Acromegaly • Endocrine Disorders • Pituitary Gland Carcinoma