“Drugs such as AVM0703 that mobilise endogenous supercharged natural killer cells, cytotoxic T cells and dendritic cells provide a potential solution for the treatment of seriously ill COVID19 patients, are available, have safety data, and are registered for the treatment of other diseases. It is in this area that large scale studies should be undertaken as they can be used to immediately treat patients together with other interventions. Such drugs are also potentially useful in other infectious disease settings where vaccines and antiviral drugs are ineffective or unavailable. ”
– Dr. Gary Grohmann
Former Director of Immunobiology and the WHO ERL at the TGA; Director of the Immunisation Coalition; Director and Founder of Environmental Pathogens; and former WHO Advisor and Consultant
Global problems demand global solutions
AVM0703 provides real-world, real-time solutions
AVM0703 can be manufactured in seven hours by a global contract development and manufacturing organization (CDMO), can be stable even at temperatures of 45°C (104°F) in high humidity, and can have a long shelf life of 9 to 24 months which make it a potential global solution for the current pandemic and possible future pandemics.
Strategic advantages of AVM0703 in the battle against COVID-19
AVM0703 is a purer, loaded formulation of dexamethasone that could enable single acute doses to replace chronic repeat dosing. Rapid 6 hour onset of action could eliminate infected monocytes and neutrophils that are driving lung damage. Mobilization of supercharged Natural Killer T and cytotoxic T cells could eliminate the virus and provide long term immunity. Supercharged immune cells are 10X more activatable than ordinary immune cells. This dosing could save more lives than repeat 10-day dosing and could reduce ICU days from 10+ days to 2-3 days, which could be a significant financial impact benefiting healthcare systems and patients. This innovative treatment is approved for human trials in several types of blood cancer and Acute Respiratory Distress Syndrome (ARDS) (ClinicalTrials.Gov, 2020). It is critical that AVM0703 be tested in rigorous controlled clinical trials in severely ill COVID-19 patients.
AVM0703 Treats the Most Vulnerable
The supercharged immune cells mobilized by AVM0703 in mouse models are not normally present in the circulation and are uniquely induced by AVM0703. Therefore, unlike ordinary immune cells which are reduced with age and disease, AVM0703 mobilized supercharged Natural Killer T cells and cytotoxic T cells should not be limiting.
10x More Efficient Super-Charged Natural Killer T Cells
Ordinary Natural Killer T cells and cytotoxic T lymphocytes are known antiviral agents against norovirus, herpesvirus, and influenza. Ordinary NKT cells reduce the accumulation of inflammatory monocytes in the lungs and decrease immune-pathology during severe influenza A virus infection. In preclinical cancer models, AVM0703 mobilized supercharged Natural Killer T cells and cytotoxic T cells are dramatically better than ordinary Natural Killer T cells and cytotoxic T lymphocytes from untreated mice at killing mouse B cell lymphoma and human T cell lymphoma.
AVM has data that demonstrates that this novel NKT homes remarkably to tumors for tumor killing in models in which checkpoint inhibitors are ineffective. Since AVM_NKT are mobilized only after AVM0703 treatment, as opposed to other NK and NKT which circulate continuously, AVM_NKT numbers may not be limiting in any patients.
Based on the cancer research, AVM0703 mobilized supercharged Natural Killer T cells and cytotoxic T cells could be better against viruses like COVID-19 than the ordinary Natural Killer T cells and cytotoxic T lymphocytes, which are known antiviral agents. AVM_NKT also have the potential to directly engulf infected cells. CD3 levels determine how activated T & NKT cells can become for direct killing and Ly6G levels determine how actively they can engulf (eat) and kill viruses and tumors. AVM-NKT are more activatable (higher CD3) and could be even more effective than ordinary NKT.
Increased CD11b high Dendritic Cells (CD) stabilize immune systems and trigger long term immunity
AVM0703 not only increases the number of conventional CD11b DC’s, it also mobilizes a CD11b very high expressing DC not typically observed. Moreover, CD11b positive dendritic cells have been associated with reduced severity of or protection from Influenza A (H1N1) infection, and Respiratory Syncytial Virus.
Asthma protects against influenza severity by increasing conventional CD11b+ Dendritic Cells in lymph nodes draining lungs. AVM0703 increases the number of conventional CD11b+ cells and mobilizes a CD11b very high Dendritic Cell.
Selective reduction of infected monocytes, the underlying pathology of COVID-19
AVM0703 activates a novel receptor that selectively ablates Monocytes, and reduces neutrophils, which could alleviate the pulmonary inflammation that drives the pathology of COVID-19.
Based on these findings and the global search for a cure for COVID-19, AVM Biotechnology has made researching AVM0703’s efficacy in this patient population a concurrent priority alongside cancer-specific research.
Potential Roles of AVM0703 in Future Pandemics
According to promising outcomes in animal studies, AVM0703 could have the potential to change how we respond to viral outbreaks. Once safety and efficacy are determined in clinical trials, AVM0703 could be deployed as a first response.
When a future outbreak of a novel viral infection is identified, teams of trained experts could test candidates. Candidates testing positive could be treated with a single oral, or intravenous dose of AVM0703 which shows action in the laboratory in mouse models within 6 hours. Patients would be re-tested to determine whether immunity or antibodies are produced against the virus.
Once at least 50%-80% of the population in this small defined area has immunity or antibodies, herd immunity would help to effectively stop the spread of the virus. This forward-looking statement is based on outcomes seen in mouse models in cancer testing and will be confirmed in clinical trials once approved.
Supercharged Natural Killer T-Cells
Natural killer T cells (NKT) bridge the innate (rapid) and adaptive (long term immunity) immune systems. They love to kill cancer, viruses, and bacteria. AVM’s supercharged NKT are like an elite special forces unit of killers with long term memory.
Supercharged Cytotoxic T-Cells
Cytotoxic T cells kill cancer and infected cells by forcing the cells to commit suicide (apoptosis). AVM supercharged cytotoxic T cells are like another elite special forces unit of killers with long term memory.
03 CD11b+ Dendritic
Supercharged CD11b+ Dendritic Cells
AVM supercharged dendritic cells are like early warning scouts. They work like a Pac-Man to engulf abnormal cells killed by the AVM-NKT cells and present remnants of the dead cells to other lymphocytes for long term memory.