Aerpio Therapeutics, a clinical-stage biopharmaceutical company,has dosed the first patient in a phase Ib/IIa trial of AKB-9778 for the treatment of diabetic macular edema (DME). AKB-9778 is a first-in-class human protein tyrosine phosphatase beta (HPTPß) inhibitor that works to activate Tie2, a receptor on vascular endothelial cells which promotes vascular stability, preventing abnormal blood vessel growth and vascular leak.

“Recent preclinical and clinical data indicate that decreased signaling through the Tie2 pathway plays an important role in the development of diabetic retinopathy and possibly other diabetic vascular co-morbidities, such as nephropathy and neuropathy,” said Kevin Peters, MD, chief scientific officer and VP of Research and Development, Aerpio. “Based on our preclinical data showing that, through Tie2 activation, AKB-9778 reduces retinal edema and neovascularization in multiple models of retinopathy, as well as data from our phase I study earlier this year, we are optimistic that AKB-9778 could represent an important advancement in the treatment of DME. We look forward to results of this study in DME patients in 2013.”

The 28-day phase Ib/IIa ascending dose study is designed to evaluate the safety and efficacy of AKB-9778 in patients with DME. The study will enroll up to 24 patients at six sites throughout the US. The primary endpoint is safety with secondary efficacy endpoints based on decreased retinal thickness measured by OCT (optical coherence tomography), improved visual acuity and selected biomarkers.

Tie2 is a receptor tyrosine kinase expressed on vascular endothelial cells, which plays a key role in stabilizing blood vessels. AKB-9778 is a first-in-class small molecule that works by inhibiting the Human Protein Tyrosine Phosphatase ß (HPTPß, also known as VE-PTP, or vascular endothelial protein tyrosine phosphatase) enzyme, a negative regulator of the Tie2 receptor. By inhibiting this negative regulator, AKB-9778 restores Tie2 signaling, reducing vascular leak and pathologic neovascularization. Tie2 activators have potential utility in a range of important clinical indications, but Aerpio is currently focusing development of AKB-9778 in diabetic macular edema. In a phase I healthy volunteer study, AKB-9778 was well tolerated through the predicted efficacious dose range, with evidence of on-target pharmacology. Data from a phase Ib/IIa study to explore the safety and efficacy of AKB-9778 in patients with diabetic macular edema is expected in 2013.