Current AVI Projects

This project is led by Professor Michael Good, an adjunct Professor in the Faculty of Medicine & Dentistry at the University of Alberta (UAlberta).

His host organization is at Griffiths University in Brisbane, Australia. He has been a leader in the GAS field for many years and has developed a unique GAS vaccine relying on immunogenic, conserved peptide antigens to elicit protective immunity against this highly variable bacterium.

This bacterium causes around 500,000 deaths every year globally from various forms of the disease (rheumatic heart disease, kidney disease, cellulitis, and flesh-eating fasciitis).

It is common among Indigenous peoples of Canada and Australia. LKSAVI has supported this program for the last several years and has used its vaccine and medical and regulatory teams to contribute to an application to Health Canada to perform a phase 1 clinical trial in NACTRC at the UAlberta. Permission to proceed was received from Health Canada in April 2021. This will be the first vaccine phase 1 clinical trial performed by NACTRC.

Under the direction of Dr. Michael Houghton, a world leader in the HCV and vaccine fields for almost three decades, the AVI team of specialists is developing a vaccine against Hepatitis C. Although Hepatitis C can now be treated, there is no vaccine to prevent the infection. Furthermore, due to the high cost of the drugs, and the potential for reoccurrence after treatment, there is still a high unmet need for a prophylactic vaccine, especially in countries with high incidences of infection.

The team has designed a novel vaccine and is currently manufacturing it under high-quality GMP conditions for human use. GMP production is a result of the association of the AVI with the Alberta Cell Therapy Manufacturing (ACTM), both at the University of Alberta. Phase I clinical trials are expected to start mid to late 2019.

Patent:

Houghton M, Hockman D, Law JL, Logan M, Tyrrell DL. “E1E2 HCV Vaccines and Methods of Use” Patent # 2996718; Filed May 15, 2014; issued January 15, 2020

The AVI is working with Dr. Jack Jhamanadas, a Distinguished University Professor in the Division of Neurology with the Faculty of Medicine & Dentistry at the University of Alberta. Dr. Jhamandas is a practicing neurologist and neuroscientist whose research focus includes the study of misfolded proteins in Alzheimer's disease (AD), a progressive neurodegenerative disorder characterized by deposits of β-amyloid. In collaboration with the AVI's strengths in computational drug discovery and medicinal chemistry, the AD research group has identified several compounds that show promise in pre-clinical studies at improving cognitive function and brain pathology in AD mice. This promising research is being actively pursued and developed with the goal of bringing these discoveries to human clinical trials.

Patent:

Jhamandas J, FU W, Kimura R, Tyrrel DL, Clementin A, Sahu K, Belovodskiy A, Hena M, Bai B, Kandadai AS, Nieman JA, Houghton M. “Non-peptidic heterocycle-containing compounds for the treatment of Alzheimer's disease“ USPTO 62/837,845. Filed April 24, 2019

Under the leadership of Dr. James Nieman in LKSAVI, novel antivirals targeting the polymerase encoded by HCMV have been developed and shown to be more potent in cell cultures than the standard-of-care approved drugs. Novel anti-HCMV drugs are urgently needed because many immunosuppressed transplant patients die from HCMV reactivation.

The market size for anti-HCMV therapeutics is more than $1 billion per annum. Our initial aim is to demonstrate proof-of-efficacy and safety in animal models over the course of the next year. This is an achievable goal based on the highly innovative work of Dr. Nieman and his chemistry team, comprising industry-experienced LKSAVI chemists who have filed a patent covering these compounds.

In the following years, the identified clinical candidate will be manufactured under GMP and then tested first in healthy human volunteers before demonstrating antiviral efficacy in immunosuppressed patients undergoing HCMV reactivation.

Patent:

Nieman JA, Hena M, Bai B, Kandadai AS, Belovodskiy A. “Inhibitors of Human Herpesviruses.” PCT Patent # CA2021050275; Filed on March 2, 2021

Non-alcoholic fatty liver diseases, such as NASH, are becoming the most common chronic liver disease affecting 80 to 100 million people in North America alone. There is currently no approved treatment for these conditions, typically resulting in costly liver transplants.

The AVI has innate expertise of this field, our liver disease experts Dr. Michael Houghton & Dr. Lorne Tyrrell (AVI Director and Co-Director, respectively). As a result, the AVI has formed a collaboration among leading global scientists in the same field to develop small molecule inhibitors of protein-protein interactions believed to mediate the NAFLD disease process. Using its leading computational modelling capabilities, the AVI has identified possible inhibitors that are in the process of being tested.

Oncolytic viruses specifically infect and kill cancer cells. In addition, they direct immune responses to themselves and the cancer cells they have infected, leading to highly effective tumor clearance. Dr. David Evans, a world-renowned poxvirus expert, has developed a new oncolytic vaccinia virus.

The LKSAVI is currently co-supporting the manufacturing of the oncolytic vaccinia virus under GMP conditions. Efficacy animal studies show that the clinical oncolytic poxvirus (UAB-211) safely and specifically targets cancer cells and produces long-term remissions in ~50% of the treated animals. Induced anti-tumour immunity is also observed. A phase 1 clinical trial in non-invasive bladder cancer patients is scheduled to begin in 2019.

The AVI is developing a new test for the monitoring of autoimmune hepatitis. Since the current procedures are non-specific, expensive and invasive, the new test (which measures blood cytokine levels) is expected to be well received by the medical community, attempting to evaluate the remission or relapse of this disease. The AVI is currently conducting a validation study to confirm its clinical utility. Upon confirmation, the test's parameters will be validated and standardized to then pursue its commercialization in North America and Europe.

Dr. Tyrrell's research team, in collaboration with the AVI, has developed a novel hepatocyte cell line that can be used in R&D to test hepatotoxicity of novel drugs under development. The cell line has showed promising results in preliminary experiments and is currently being evaluated side-by-side against the standard cell line to demonstrate superiority. The technology has been patented around the world. Drug-induced liver toxicity is a major cause of clinical failure and we anticipate this technology can be of great research and medical value.