GPR75 antagonist
A small molecule GPR75 antagonist program for the treatment of obesity.
Phase
Lead Optimization
Target
GPR75
Modality
Small Molecule
Approach
Antagonist
Development rights
Confo
1
Billion +
people globally are currently living with obesity (1)
54
%
lower risk of obesity in humans with loss of function variants in the GPR75 gene (2)
Our program to treat obesity
Obesity is a chronic disease with a profound and growing global impact. It is a major driver of cardiometabolic disease, contributing to type 2 diabetes, cardiovascular disease, liver disease, and reduced life expectancy.
Despite recent advances in therapy, many patients remain inadequately treated due to variety of factors including limited durability, tolerability challenges, and insufficient response. There is a clear need for additional mechanisms that can broaden treatment options and support long‑term disease management.
GPR75 has emerged as a compelling obesity target based on strong human genetic and mechanistic evidence. Our program is focused on the discovery and development of GPR75 antagonist molecules designed to support meaningful, durable weight management.
Obesity is a chronic, relapsing disease that disrupts metabolic health and increases the risk of a variety of diseases including type 2 diabetes, cardiovascular disease, and multiple cancers. Once considered a lifestyle issue, obesity is now recognized by the World Health Organization as a global medical condition rooted in genetics, neurobiology, eating behaviors, access to healthy diet, and an obesogenic environment.
Today, more than one billion people worldwide live with obesity, making it one of the most urgent health challenges of our time. Its impact extends beyond health and places a substantial burden on healthcare systems, productivity, and quality of life, underscoring the urgent need for transformative therapeutic approaches.
GPR75 (G protein–coupled receptor 75) is an orphan class A GPCR that has emerged as a genetically validated regulator of body weight.
Interest in GPR75 accelerated following large human studies showing that rare loss‑of‑function human variants are associated with significantly lower BMI and reduced risk of obesity. Carriers of these GPR75 variants weigh several kilograms less on average and do not show obvious adverse health effects, making GPR75 a compelling therapeutic target.
Therapeutically, GPR75 represents a non‑incretin, disease‑modifying obesity target. Antagonism of GPR75 could complement current obesity therapies and offers the potential for effective, well‑tolerated weight management grounded in human genetics.
Obesity remains a major unmet medical need despite recent therapeutic advances.
Current treatments do not work effectively or sustainably for all patients, with wide variability in weight loss, tolerability, and long-term adherence. Most patients who newly initiate treatment with GLP-1 R agonists treatment within 1 year. Most individuals experience weight regain after treatment discontinuation, highlighting the need for durable disease modification.
Existing therapies may inadequately address obesity related complications in all patients. Safety, gastrointestinal side effects, and injection burden limit broader use.
Critically, obesity is biologically heterogeneous, yet therapies targeting distinct mechanisms and patient subtypes remain largely unavailable.