Nicotinic Acetylcholine Receptor (nAChR)

nACh receptors exist both in the CNS and in the vasculature. nACh receptors in the brain can be stimulated to increase cognition and are useful in CNS disorders such as Alzheimer’s disease, attention-deficit hyperactivity disorder (ADHD) and schizophrenia. 

In the vasculature, the nAChR pathway can be stimulated to promote angiogenesis (termed cholinergic angiogenesis). By creating small molecule inhibitors that act upon this novel angiogenic pathway, we develop drug candidates with potential uses in angiogenesis-dependent diseases such as neovascular age-related macular degeneration (also known as “wet’ AMD) and cancer.

Cholinergic angiogenesis was discovered and characterized at Stanford University by two of the scientific founders of CoMentis, Drs. John Cooke and Ken Kengatharan and colleagues. Interestingly, this novel pathway synergizes with other growth factor dependent angiogenic pathways such as that mediated by the vascular endothelial-derived growth factor (VEGF).

In August 2006, CoMentis’ lead product from this program, ATG-3, became the first topical ophthalmic drug candidate to enter clinical development for AMD where existing treatments have to be frequently injected into the eye. ATG-3 is currently being evaluated for safety and efficacy in a Phase II clinical trial enrolling 330 patients with neovascular AMD (OPTIMA) with results expected in Q3 2009.

In addition, in June 2008, CoMentis initiated a Phase II clinical trial evaluation ATG3 in combination with anti-veaf αβ in patients with neovascular AMD. Data from this study is expected in Q3 2009.