About Us

We are a clinical-stage biopharmaceutical company located in South San Francisco committed to developing novel medicine for depression, cancer and diseases and conditions involving the central nervous system.

AV-101 (L-4-chlorokynurenine or 4-Cl-KYN)

AV-101 is an orally-available, non-sedating, non-hallucinogenic, non-addictive prodrug candidate in Phase 2 development for Major Depressive Disorder. AV-101 also has additional potential in chronic neuropathic pain, epilepsy and neurodegenerative diseases, such as Parkinson’s disease and Huntington’s disease. AV-101 prodrug efficiently crosses the blood-brain barrier and is rapidly converted into 7-chlorokynurenic acid (7-Cl-KYNA) by astrocytes, which is released into the synaptic spaces. 7-Cl-KYNA is a well-characterized, potent and highly selective antagonist of N-methyl-D-aspartate (NMDA) receptors due to its antagonistic binding to the glycine-coagonist site of the NMDA receptor.

Current evidence suggests that AV-101’s antagonism of NMDA signaling may provide fast-acting antidepressant effects in the treatment of Major Depressive Disorder. In addition, as confirmed in Phase 1 clinical studies, targeting the glycine-binding site of the NMDA receptor does not have the adverse effects typically associated with classic NMDA receptor antagonists, such as ketamine and other NMDA channel blockers. The fact that AV-101 is a safe, well-tolerated, orally-available drug, with preclinical data in three animal models of depression, suggests that AV-101 has the potential to become a transformative advancement in the treatment for Major Depressive Disorder.

We have completed IND-enabling preclinical studies and two Phase 1 clinical safety studies supporting Phase 2 clinical development of AV-101 in multiple CNS indications. To date, the U.S. National Institutes of Health (NIH) has awarded us $8.8 million of grant funding to complete our successful preclinical and Phase 1 clinical development of AV-101. In addition, in early-2015, we entered into a Cooperative Research and Development Agreement (CRADA) with the NIH regarding Phase 2 clinical development of AV-101 in Major Depressive Disorder. Under the CRADA, the NIH will fully-fund and conduct a randomized, double-blind, placebo-controlled Phase 2 efficacy study of AV-101 in patients with Major Depressive Disorder beginning in 2015. The World Health Organization (WHO) estimates that “depression is the leading cause of disability worldwide, and is a major contributor to the global burden of disease.” Major Depressive Disorder affects approximately 350 million people worldwide, including nearly 7% of adults in the United States.

In NIH studies, the NMDA receptor channel blocker ketamine produced fast-acting, robust antidepressant effects in patients with Major Depressive Disorder. These NIH studies introduced a new paradigm for the research and development of antidepressants with rapid-onset action, in stark contrast to all FDA-approved antidepressants. Despite the promising results in the NIH studies, however, ketamine’s potential to become long-term, widely-used antidepressant medication is severely limited due to its well-established addictive nature, anesthetic properties, capacity to produce dissociative side effects, and the invasiveness and inconvenience of required intravenous administration. AV-101 and ketamine both regulate the NMDA receptor. However, AV-101 selectively targets the glycine-binding site within the NMDA receptor and does not precipitate the serious adverse effects of ketamine or other NMDA channel blockers. As a result, we believe orally-available AV-101 has the potential to deliver the fast-acting antidepressant effects of ketamine in Major Depressive Disorder, without ketamine’s side effects or required i.v. administration, making AV-101 a potential transformative advancement in the treatment of Major Depressive Disorder.

Stem Cell Technology and Drug Rescue

We believe better cells lead to better medicines.™
We use our stem cell-derived human cardiomyocytes (heart cells) in CardioSafe 3D™, our new generation, customized in vitro bioassay system for predicting potential heart toxicity of new drug candidates. We believe CardioSafe 3D is more comprehensive and clinically predictive than the hERG assay, currently the only in vitro cardiac safety assay required by FDA guidelines. We use our stem cell-derived hepatocytes (liver cells) in LiverSafe 3D™, our second novel, customized bioassay system for predicting potential liver toxicity of new drug candidates, including potential drug metabolism issues and adverse drug-drug interactions. We believe our stem cell-derived hepatocytes, 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 believe CardioSafe 3D and LiverSafe 3D offer a new paradigm for evaluating and predicting potential heart and liver toxicity of new drug candidates, including drug rescue candidates, early in development, long before costly, high risk animal studies and human clinical trials.

We are using CardioSafe 3D and LiverSafe 3D for our internal drug rescue programs. We are focused on producing proprietary new chemical entities (NCEs) for our internal drug development pipeline. We have identified in the public domain promising drug candidates that were discovered, optimized and tested for efficacy by pharmaceutical companies and others but terminated before FDA approval due to unexpected heart toxicity. We refer to these still-promising new drug candidates as Drug Rescue Candidates™. Our drug rescue strategy involves using CardioSafe 3D to assess the cardiac toxicity(ies) that caused a Drug Rescue Candidate to be terminated, and then apply our human biological insight to produce an effective and safer Drug Rescue NCE for our pipeline. We intend to develop each optimized Drug Rescue NCE internally to establish in vitro and in vivo preclinical proof-of-concept (POC), as to both efficacy and safety, using both established in vitro and in vivo models, as well as in CardioSafe 3D.

Regenerative medicine
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 two decades by altering the fundamental mechanisms of disease and help slow rapidly rising healthcare costs in the U.S. We plan to explore nonclinical opportunities to apply 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. 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.