XOMA discovered new classes of fully human monoclonal antibodies that deactivate (XMetD) the insulin receptor, each representing a distinct new therapeutic approach to the treatment of patients with abnormal metabolic states. These programs are highly novel as the antibodies bind to allosteric sites on the insulin receptor, which is different than currently marketed drugs.
XOMA 358 is a fully human allosteric modulating monoclonal antibody that binds to insulin receptors and attenuates insulin action. XOMA 358 is being investigated as a novel treatment for non-drug-induced, endogenous hyperinsulinemic hypoglycemia (low blood glucose caused by excessive insulin production) and other related disorders. A therapy that safely and effectively mitigates insulin-induced hypoglycemia has the potential to address a significant unmet therapeutic need for certain rare medical conditions associated with hyperinsulinism. Positive Phase 1 data was presented at the Endocrine Society’s Annual Meeting in March 2015.
In October 2015, we initiated a Phase 2 proof-of-concept (POC) study to evaluate the safety and ability to prevent hypoglycemia (dangerously low blood sugar) of a single dose of XOMA 358 in patients with congenital hyperinsulinism (CHI). In April 2016, we initiated a Phase 2 POC study of XOMA 358 in patients who experience hyperinsulinism following bariatric surgery (PBS). More information on the XOMA 358 clinical trial may be found at www.clinicaltrials.gov and www.clinicaltrialsregister.eu.
Congenital Hyperinsulinism (CHI) is a genetic disorder in which the insulin cells of the pancreas (beta cells) secrete inappropriate and excessive insulin. Ordinarily, beta cells secrete just enough insulin to keep blood sugar in the normal range. In people with CHI, the secretion of insulin is not properly regulated, causing excess insulin secretion and frequent episodes of low blood sugar (hypoglycemia). In infants and young children, these episodes are characterized by a lack of energy (lethargy), irritability or difficulty feeding. Repeated episodes of low blood sugar increase the risk for serious complications, such as breathing difficulties, seizures, intellectual disability, vision loss, brain damage, coma, and possibly death. About 60 percent of infants with CHI experience a hypoglycemic episode within the first month of life. Other affected children develop hypoglycemia by early childhood. Current treatments for CHI are limited to medical therapy and surgical removal of part or all of the pancreas (pancreatectomy).
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