Type 2 diabetics suffer from an over-production of sugar within the liver, which contributes to high blood glucose levels in patients. Normally, the liver produces glucose to supply organs during hunger periods, as a response to falling blood glucose levels. In diabetes patients this mechanism is dysregulated and always active, even at already high blood glucose. Glycerol is an important substrate for liver glucose production. Apoglyx has shown in animal models that inhibition of aquaporin-9 (AQP9) can reduce hepatic glucose production and whole body blood glucose.
AQP9 has been validated as a drug target in several inflammatory conditions. These include the inflammatory response following myocardial infarction, as well as skin allergic dermatitis. AQP9 is expressed in several types of leukocytes, and augments a pro-inflammatory leukocyte phenotype.
Apoglyx has developed 191 compounds in the lead series of which 46 have drug-like properties consistent with oral administration. Several of the most promising candidates have been tested in-vivo and we are continuing a program of pharmacokinetics, pharmacology, including multi-dose administration in-vivo efficacy studies. The ultimate aim is to develop a once-daily, oral therapy for diabetes patients.