We are a clinical-stage biopharmaceutical company headquartered in South San Francisco, California and focused on drug development, rescue and discovery, as well as regenerative medicine.
Our lead drug candidate, AV-101, also known as “L-4-chlorokynurenine” or “4-Cl-KYN”, is an orally-available, non-sedating prodrug that is converted in the brain into an active metabolite, 7-chlorokynurenic acid (7-Cl-KYNA), which regulates the N-methyl-D-aspartate (NMDA) receptors. 7-Cl-KYNA is a synthetic analogue of kynurenic acid (KYNA), a naturally occurring neural regulatory compound, and is one of the most potent and selective blockers of the regulatory GlyB-site of the NMDA receptor. 7-Cl-KYNA does not cross the blood-brain barrier. In preclinical studies, AV-101 is rapidly and efficiently transported across the blood-brain barrier, and is converted into 7-Cl-KYNA in the brain and spinal cord, preferentially, at the site of seizures and potential neural damage.
We have successfully completed Phase I development of AV-101, demonstrating that AV-101 is well tolerated without any significant safety issues. AV-101 is a candidate for the treatment of multiple diseases and disorders involving the central nervous system (CNS), including, Major Depressive Disorder (MDD or refractory depression), refractory epilepsy, neuropathic pain, and neurodegenerative diseases such as Parkinson’s disease and Huntington’s disease. We believe our AV-101 IND application on file at the U.S. Food and Drug Administration, and the safety studies we have completed successfully in Phase I development of AV-101, will support our development of AV-101 for the multiple CNS indications noted above.
To date, the U.S. National Institutes of Health (NIH) has awarded us $8.8 million of grant funding for our preclinical and Phase 1 clinical development of AV-101. We are now preparing to begin Phase 2 clinical development of AV-101 with the NIH.
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 focused on 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 drug rescue applications.
Our stem cell technology platform, which we refer to as Human Clinical Trials in a Test Tube, is based on a combination of proprietary and exclusively licensed technologies for controlling the differentiation of human pluripotent stem cells into multiple types of mature, functional, adult human cells that we use, or plan to develop, to reproduce complex human biology and disease. We are currently producing heart cells and liver cells for our drug rescue applications. Upon completion of this offering, we intend to focus on the drug rescue applications utilizing human heart and liver cells, and further advance, through collaborative research projects, pharmaceutical applications of stem cell-derived blood, bone, cartilage, heart, liver and pancreatic beta-islet cells, including exploring opportunities to leverage our stem cell technology platform for regenerative medicine purposes. Our emphasis in the regenerative medicine arena will be on developing novel human disease models for discovery of small molecule drugs and biologics that activate the endogenous growth and healing processes enabling the body to repair tissue damage caused by certain degenerative diseases.
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. Detailed information is often available in the public domain regarding the efficacy, pharmacology, formulation and toxicity of promising drug candidates which already have been tested extensively in in vitro studies, live animal models and even humans, but subsequently have failed due to unexpected toxicity. “Drug rescue” refers to research and development using small molecule drug 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. We refer to these drug candidates as Drug Rescue Candidates™. We have designed our drug rescue model to leverage publicly available information and substantial prior investment by pharmaceutical companies and others in Drug Rescue Candidates. The key commercial objective of our drug rescue model is to generate revenue from license, development and commercialization arrangements involving Drug Rescue Variants™ that we develop having improved safety characteristics. These are proprietary, new, safer small molecule variants of Drug Rescue Candidates we are focused on producing with our medicinal chemistry collaborator and validating internally in our bioassay systems prior to license. 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 stem cell technology-based drug rescue, we intend to become a leading source of proprietary, small molecule drug candidates to the global pharmaceutical industry.
Using VSTA-CMs™, our mature human cardiomyocytes (human heart cells) derived 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 with greater speed and precision than long-established, surrogate safety models most often used in drug development, including the FDA-required in vitro hERG assay and models using animal cells or live animals, and cellular assays using transformed cells. Our VSTA-CMs and CardioSafe 3D are key components of our Human Clinical Trials in a Test Tube platform and our drug rescue programs.
Using VSTA-CMs™, our mature human hepatocytes (human liver cells) derived from pluripotent stem cells, with adult functional properties, we are currently validating LiverSafe 3D, our second novel, customized bioassay system for drug rescue and development. We believe LiverSafe 3D will enable us to assess new small molecule 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 or 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. We plan to use LiverSafe 3D, and the clinically predictive liver biology insight we believe it provides, to expand the scope of our commercial opportunities related to drug rescue and development.
Regenerative medicine and drug discovery
Although we believe the best and most valuable near term commercial application of our stem cell technology platform is for small molecule drug rescue and development, we also believe stem cell technology-based regenerative medicine has the potential to transform healthcare in the U.S. over the next decade by altering the fundamental mechanisms of disease and help slow rapidly rising healthcare costs in the U.S. We plan to explore opportunities to leverage our stem cell technology platform for regenerative medicine purposes, with emphasis on developing novel human disease models for discovery of small molecule drugs and biologics with regenerative and therapeutic potential. Our regenerative medicine focus will be based on our expertise in human biology and differentiation of human pluripotent stem cells to develop functional adult human cells and tissues involved in human disease, including blood, bone, cartilage, heart, liver and insulin-producing pancreatic beta islet cells. Among our key objectives will be to explore regenerative medicine opportunities through pilot nonclinical proof-of-concept studies, after which we intend to assess any potential opportunities for further development and commercialization of therapeutically and commercially promising regenerative medicine programs, either on our own or with strategic partners.