Neurocrine Biosciences (Nasdaq: NBIX) has dosed the first participants in a Phase I first-in-human study of NBIP-1968, an internally discovered glucagon-like peptide-1 (GLP-1)/glucose-dependent insulinotropic polypeptide (GIP)/glucagon receptor triple agonist for obesity. The study evaluates single ascending doses in adults across a range of body mass index categories, with safety and tolerability as the primary endpoint. No efficacy or safety data have been reported
NBIP-1968 is designed for once-weekly subcutaneous administration and targets all three receptors simultaneously to influence appetite regulation, energy balance, and glycemic control. The company said the molecule was engineered with balanced glucagon receptor activity — an attempt to capture the metabolic benefits of glucagon agonism, including energy expenditure, while managing the tolerability concerns that have complicated earlier glucagon-containing combinations
The trial’s strategic relevance extends beyond NBIP-1968 itself. Neurocrine intends NBIP-1968 as one component of a fixed-dose combination with NBIP-2118, a corticotropin-releasing factor type 2 receptor (CRF2) agonist that entered Phase I in May 2026. NBIP-2118 targets a non-incretin mechanism and demonstrated fat-preferential weight loss with lean mass preservation in preclinical models. The combination strategy — pairing incretin-based weight loss with a muscle-sparing mechanism — reflects an attempt to address one of the recognized limitations of current GLP-1-class therapies, which reduce lean mass alongside fat.
The obesity pharmacotherapy market has shifted rapidly. Eli Lilly’s Zepbound (tirzepatide), a dual GIP/GLP-1 receptor agonist, and Novo Nordisk’s Wegovy (semaglutide 2.4 mg) currently anchor the injectable market, with tirzepatide demonstrating the highest mean weight loss of any approved agent. Eli Lilly’s Foundayo (orforglipron), the first oral non-peptide GLP-1 receptor agonist approved for obesity, received FDA approval in April 2026, expanding the competitive field further. Adding a glucagon receptor component to GLP-1/GIP agonism is a mechanism several developers have pursued as a potential route to greater weight loss, though clinical validation of the triple agonist approach in obesity remains limited.
Neurocrine is primarily known for its neuroscience and endocrinology portfolio, which includes approved treatments for tardive dyskinesia, Huntington’s disease chorea, and classic congenital adrenal hyperplasia. The obesity pipeline represents a deliberate expansion into metabolic disease, drawing on the company’s existing expertise in CRF biology — the same pathway underpinning NBIP-2118. The company said its broader obesity research also includes a single-molecule incretin mimetic-CRF2 agonist conjugate and a long-acting triple agonist conjugated to an antibody Fc domain intended to extend the dosing interval to once monthly or less frequently.
Initial data from the NBIP-2118 Phase I study are expected in 2027. No timeline for NBIP-1968 Phase I data has been disclosed
Access the AllSci platform to explore the science behind the news
Spot something wrong? Report an issue with this article
