Technology
Obesity is a chronic disease that occurs when the body stores excess fat due to genetics, physical inactivity, and other related factors. The associated risks of obesity include the development of major health problems such as type 2 diabetes and cardiovascular disease. While lifestyle modifications help to manage or prevent obesity in some individuals, for others additional treatment options are urgently needed to reduce obesity-related health conditions.
Elevation of nutrient-stimulated glucose-dependent insulinotropic polypeptide (GIP) levels can lead to glucose intolerance and insulin resistance that drives obesity. Helicore’s first-in-class therapeutic antibody lowers active GIP in circulation by directly binding to the hormone for functional neutralization. Limiting the actions of GIP can reverse the physiological underpinnings of obesity to lower excess body weight and improve metabolic health.
What is GIP antagonism?
In mammals, appetite and satiety are a function of the incretin hormones. Incretin hormones regulate gastric motility, nutrient absorption, blood flow, and food intake, serving as a proximal step in the communication of food intake to the systems that regulate postprandial metabolic homeostasis. GIP, like GLP-1, is an incretin hormonesecreted from the intestine to regulate circulating glucose levels by stimulating insulin secretion from pancreatic beta cells, which has been termed the “incretin effect.” In obesity, elevated levels of GIP act in coordination with insulin to enhance fatty acid uptake in adipocytes, thereby promoting fat accumulation with overnutrition and undermining the otherwise beneficial effects of GIP in managing glucose and satiety responses. Multiple studies show that decreased GIP signaling results in lower body weight and other metabolic benefits.
What is GIP ligand binding?
GIP ligand binding is a novel approach that Helicore is developing to mitigate the chronic effects of dysregulated GIP signaling that happen in obesity. Functional antagonism of GIP can occur through either directly blocking the GIP receptor (GIPR) or through binding of the GIP ligand in circulation. Ligand targeting is a differentiated strategy that enables durable reductions in the circulating GIP that would otherwise be available for activating the GIP receptor. Additionally, in people with obesity, elevated GIP levels induce leptin resistance and lowered satiety responses resulting from both aberrant adipocyte and hypothalamic signaling. GIPR blockers inhibit GIP signaling in adipocytes but circulating GIP ligand remains elevated and available for CNS signaling due to limited central therapeutic distribution. GIP ligand binding, on the other hand, reduces circulating GIP ligand and thereby blocks GIP signaling in both adipocytes and the CNS. Helicore’s innovative approach to GIP neutralization provides both high affinity and selective target engagement without limiting therapeutic exposures through soluble ligand binding.