We believe better cells lead to better medicines™ and that the key to making better cells is precisely controlling the differentiation of human pluripotent stem cells, which are the building blocks of all cells of the human body. For over 15 years, our stem cell research and development teams and collaborators have developed proprietary methods for controlling the differentiation of pluripotent stem cells to produce multiple types of mature, functional adult human cells, with emphasis on human heart and liver cells for our drug rescue programs. We believe drug rescue is the highest-value, near-term commercial application of the human cells we produce and our novel in vitro bioassay systems, CardioSafe 3D™ and LiverSafe 3D™, the foundation of our Human Clinical Trials in a Test Tube™ platform.

“Drug rescue” refers to research and development using small molecule drug candidates (Drug Rescue Candidates™) previously discovered and validated in efficacy studies by pharmaceutical companies, but terminated during development prior to FDA approval due to unexpected heart or liver safety concerns. Our drug rescue model leverages publicly available information and substantial prior investment by pharmaceutical companies and others in Drug Rescue Candidates to generate Drug Rescue Variants™. These are proprietary, new, safer small molecule variants of Drug Rescue Candidates validated internally in our bioassay systems. We anticipate that each validated lead Drug Rescue Variant will be a proprietary, new molecular entity (NME), suitable as a promising drug development program, either internally or in collaboration with a strategic partner. Through our stem cell technology-based drug rescue programs, we intend to become a leading source of proprietary, small molecule NMEs to the global pharmaceutical industry.

ImageOur lead drug candidate, AV-101, is an orally-available, non-sedating prodrug that is rapidly converted in vivo to its active metabolite, 7-chlorokynurenic acid (7-Cl-KYNA), one of the most well-characterized, potent and selective synthetic blockers of N-methyl-D-aspartate (NMDA) receptors at the glycine-coagonist (GlyB) site. However, 7-Cl-KYNA does not cross the blood-brain barrier, making it a poor drug candidate. AV-101, the prodrug of 7-C1-KYNA, readily gains access to the CNS after systemic administration and is converted to 7-Cl-KYNA by astrocytes that are activated at sites of neuronal injury or excitotoxic insult, making it a potential treatment for multiple diseases and disorders involving the central nervous system (CNS), including Major Depressive Disorder (refractory depression), refractory epilepsy, neuropathic pain and neurodegenerative diseases such as Parkinson’s disease and Huntington’s disease. We have successfully completed Phase 1 development of AV-101, demonstrating that AV-101 is well tolerated, without any significant safety issues. AV-101 is a now potential Phase 2 development candidate for the treatment of multiple diseases and disorders involving the central nervous system (CNS), including, Major Depressive Disorder (refractory depression), refractory epilepsy, neuropathic pain, and neurodegenerative diseases such as Parkinson’s disease and Huntington’s disease.
ImageUsing VSTA-CMs™, our mature human cardiomyocytes (human heart cells) differentiated from pluripotent stem cells, we have developed CardioSafe 3D™, a novel, customized in vitro bioassay system for assessing new small molecule drug candidates, including drug rescue candidates and drug rescue variants, for potential cardiac toxicity, long before they are 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 hERG assay and models using live animals or animal, transformed or immortalized cells.
ImageUsing VSTA-heps™, our mature, human hepatocytes (human liver cells) derived from pluripotent stem cells, we are developing LiverSafe 3D, our second novel customized bioassay system for drug discovery, 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.