AV-101, our lead drug candidate, is an orally-available, non-sedating, non-hallucinogenic prodrug that is rapidly and enzymatically converted in vivo
into 7-chlorokynurenic acid (7-Cl-KYNA), one of the most well-characterized, potent and selective antagonists of N-methyl-D-aspartate (NMDA) receptors, at the glycine-coagonist (GlyB) site within the NMDA receptor, after crossing the blood-brain barrier and reaching brain glial cells. Targeting the glycine coagonist site of the NMDA receptor may bypass potential adverse effects without direct impact on efficacy, making AV-101 a potential new treatment for multiple diseases and disorders involving the central nervous system (CNS), including Major Depressive Disorder, chronic neuropathic pain, epilepsy and neurodegenerative diseases, such as Parkinson’s disease and Huntington’s disease. When compared with classic NMDA receptor antagonists, AV-101 has displayed a much safer profile in animal testing. In addition, we have successfully completed Phase 1 clinical development of AV-101, demonstrating that AV-101 is safe, well-tolerated and has good bioavailability. We are currently preparing for Phase 2 clinical development of AV-101 in the U.S. for the treatment of Major Depressive Disorder and other CNS-related conditions.
We apply our proprietary human pluripotent stem cell (hPSC) technology to produce VSTA-CMs
™, our mature, adult human cardiomyocytes (human heart cells) differentiated from hPSCs Using our VSTA-CMs
, we have developed and validated CardioSafe
3D™, our suite of novel, customized in vitro
bioassays for predicting the cardiotoxicity profile of small molecule drug candidates, including promising drug rescue candidates and drug rescue variants, long before they are ever tested in animals or humans. We believe CardioSafe
3D is capable of predicting the in vivo
cardiac effects, both toxic and non-toxic, of small molecule drug candidates more comprehensively and efficiently than conventional surrogate safety models often used in drug development, including the FDA-required in vitro
hERG assay and other preclinical models using live animals or animal, transformed or immortalized cells. Our CardioSafe
3D drug rescue activities are focused on producing for our internal drug development pipeline new safer variants of promising drug candidates previously discovered, optimized and tested for efficacy by pharmaceutical companies and others but terminated before FDA approval due to unexpected heart toxicity. We are currently preparing to begin our initial CardioSafe
3D drug rescue program.
We also apply our proprietary hPSC technology to produce VSTA-heps
™, our highly-functional, non-transformed, mature, human hepatocytes (human liver cells) derived from hPSCs. We believe our VSTA-heps
have more functionally useful life-span in culture than, and overcome numerous problems related to, commercially-available primary (cadaver) hepatocytes currently used in FDA-required in vitro
hepatocyte assays for drug metabolism, including limited supply, unknown health status of the donor and genetic differences. We are using our VSTA-heps
to develop LiverSafe
3D, our second novel customized bioassay system for drug rescue and development. We believe LiverSafe
3D will enable us to assess new drug candidates, including drug rescue candidates and drug rescue variants, for potential liver toxicity and metabolism-based safety issues resulting in adverse drug-drug interactions, early in development, long before animal and human testing. Drug-related liver toxicity and adverse drug metabolism, as a group, represent one of the top-two reasons for safety-related drug failure during clinical development.