Xoma 129, a Novel Insulin Receptor Negative Modulator, Is Efficacious in Treating Insulin- Induced Hypoglycemia in Minipigs

Presentation Number: SAT 583
Date of Presentation: April 1st, 2017

Ou Li*1, Daniel Bedinger1, Jenny Rao1, Jessica Chen1, Lynn Webster1, Kiran Ahluwalia1, Paul D. Rubin2, Toshihiko Takeuchi1 and Kirk W. Johnson2
1XOMA Corporation, Berkeley, CA, 2XOMA (US) LLC, Berkeley, CA

Abstract

Hypoglycemia has become one of the most complicated challenges of diabetes management. These events can be acute, e.g. insulin overdose, prolonged, e.g. oral ingestion of a sulfonylurea drug, or even undetected, e.g. nocturnal hypoglycemia. Severe hypoglycemia can lead to irreversible damage to vital organs, even death. There is a need for a safe and well-tolerated treatment for the different forms of hypoglycemia. XOMA 129 is a fully human, high affinity Fab antibody fragment that specifically targets the human insulin receptor. It binds to an allosteric site on the receptor, distinct from the insulin binding site, and dampens insulin signaling. Previously, we reported that XOMA 129 can promptly reverse hypoglycemia in rats. Here, we extend the characterization of XOMA 129 in minipigs. XOMA 129 – at ≤10 mg/kg – significantly modulates glucose levels for several hours via three administration routes (IV, IM and SC). When minipigs were challenged with insulin bolus, IV XOMA 129 at 2 mg/kg reversed hypoglycemia within 15 min without causing hyperglycemia. XOMA 129 at 5 mg/kg via intramuscular administration effectively blunt the glucose drop within 15 minutes. When given prophylactically, XOMA 129 via subcutaneous administration at 9 mg/kg was preventative in a model of nocturnal hypoglycemia. Thus, XOMA 129 has potential as a novel treatment for many hypoglycemic conditions.

 

Disclosure: OL: Employee, XOMA Corporation. DB: Employee, XOMA Corporation. JR: Employee, XOMA Corporation. JC: Employee, XOMA Corporation. LW: Employee, XOMA Corporation. KA: Employee, XOMA Corporation. PDR: Management Position, XOMA Corp. TT: Employee, XOMA Corporation. KWJ: Vice President, XOMA Corp.