Neurocrine Biosciences Initiates Phase 1 Trial for Novel CRF2 Agonist NBIP-2118 in Obesity Treatment
Key Insights
Neurocrine Biosciences has launched a Phase 1 first-in-human clinical study evaluating NBIP-2118 (search), a potential first-in-class corticotropin-releasing factor type 2 receptor agonist for obesity (search) treatment.
The investigational drug targets a novel non-incretin mechanism designed to promote weight loss while preserving lean muscle mass, addressing a key limitation of existing obesity (search) therapies.
NBIP-2118 (search) demonstrated high selectivity and potency in preclinical models, with weight loss primarily driven by fat reduction while maintaining or increasing skeletal muscle mass.
Neurocrine Biosciences has initiated a Phase 1 first-in-human clinical study evaluating NBIP-2118 (search), an investigational corticotropin-releasing factor type 2 receptor (CRF2 (search)) peptide agonist representing a potential first-in-class therapy for obesity (search). The announcement marks a significant milestone in the company's expansion into metabolic disease treatment.
Novel Mechanism Targets Muscle Preservation
NBIP-2118 (search) targets a new, non-incretin mechanism for weight loss with lean mass preservation, addressing a critical limitation of current obesity (search) treatments. "CRF2 (search) agonism is a promising and differentiated mechanism with the potential to address key limitations of existing therapies, including the loss of lean mass during weight reduction," said Sanjay Keswani, M.D., Chief Medical Officer at Neurocrine Biosciences.
The investigational drug is designed for once-weekly subcutaneous administration. In preclinical models, NBIP-2118 (search) demonstrated high selectivity and potency, with weight loss primarily driven by fat reduction while preserving or increasing lean mass, including skeletal muscle. This differentiated profile could be particularly beneficial for patients at risk of muscle loss, as existing therapies often attribute a significant proportion of weight loss to lean mass.
Phase 1 Study Design and Timeline
The Phase 1 study will initially evaluate the safety and tolerability of single ascending doses of NBIP-2118 (search) compared to placebo in healthy-weight adult participants, as well as those who are overweight or obese. Initial data from the trial is expected in 2027.
"This program represents an important step in applying Neurocrine's expertise in CRF biology to treat metabolic disease," Keswani noted. The company believes the program could play a meaningful role both as a standalone therapy and in combination with other mechanisms, including incretin-based approaches.
Comprehensive Obesity Pipeline Strategy
Neurocrine's integrated obesity (search) strategy extends beyond NBIP-2118 (search), encompassing multiple programs in preclinical development. NBIP-1968 (search), an internally discovered investigational triple agonist targeting GLP-1 (search), GIP (search), and glucagon receptors (search), is intended for use in combination with NBIP-2118, with the goal of achieving greater weight loss while maintaining muscle-sparing benefits.
The company is also advancing a single-molecule incretin mimetic-CRF2 (search) agonist conjugate and developing a long-acting triple-agonist targeting GLP-1 (search), GIP (search), and glucagon receptors (search) conjugated to an antibody Fc domain. This approach could potentially extend half-life and enable once-monthly or even less frequent dosing.
Addressing Global Health Challenge
Obesity (search) represents a significant global health challenge, characterized as a chronic disease driven by complex biological, environmental, and genetic factors. The condition is associated with serious health complications, including type 2 diabetes (search), cardiovascular disease (search), and certain cancers. Despite recent advances in treatment, there remains a substantial need for additional therapies that support safe, effective, and sustainable long-term weight management.
The initiation of NBIP-2118 (search)'s clinical development represents Neurocrine's strategic expansion into metabolic diseases, leveraging the company's three decades of expertise in neuroscience and the interconnections between brain and body systems to address complex conditions.