PERTH, Australia – The Australian Government is providing AU$13 million (US$8 million) to fast-track research into treatments for COVID-19, and a number of promising candidates are about to enter the clinic.
The funding from the Medical Research Future Fund will support rapid development of treatment options for COVID-19, with AU$8 million to identify and develop antiviral therapies for people infected with COVID-19, and AU$5 million for clinical trials to better treat and manage COVID-19 patients with severe acute respiratory distress.
Melbourne-based Starpharma Holdings Ltd.’s antiviral dendrimer, SPL-7013, has been shown to have significant activity against COVID-19.
SPL-7013 inhibited the infection of cells with the SARS-CoV-2 virus, and the finding was validated by replicate testing against Gilead Sciences Inc.’s remdesivir, which is considered a leading candidate for the treatment of COVID-19.
SPL-7013 is the active ingredient in Starpharma’s Vivagel products. The Vivagel condom has an antiviral coating that inactivates up to 99.9% of HIV, HPV and HSV-2 and provides "near complete" protection against the Zika virus, Starpharma CEO Jackie Fairley told BioWorld.
SPL-7013 was originally developed as an antiviral but it is also approved for the treatment and prevention of bacterial vaginosis.
“Given its antiviral activity, when the COVID-19 issue emerged, we were interested to know if it was active against that virus,” Fairley said, noting that the active molecule inactivates virus particles by binding to the virus and rendering it incapable of invading human cells.
The Starpharma compound was tested against a panel of other compounds, including Gilead’s remdesivir, and SPL-7013 “was the most active compound out of all of them that were tested,” she said.
Fairley said she couldn’t provide additional details on the study, but the company will publish the results at a later date. The testing was conducted by Melbourne-based 360Biolabs, which has developed SARS-CoV-2 assays to support antiviral discovery and development.
Given SPL-7013 is already approved as the active component of two approved Vivagel products that are marketed in Europe, Canada, Japan, Australia and Southeast Asia, the CEO said she expects the development path would be quite fast.
Starpharma will now conduct additional short-term preclinical studies, and it will be exploring different routes of administration.
“We’ll be looking at a nasal spray and an inhaled version and eye drops as a preventative against COVID-19 infection.
“By all accounts, it will be quite some time before a vaccine is available, so you could see a product like this for front-line workers but also for people who want another level of defense. Everyone who is wearing a mask is a potential candidate for something like this,” she said.
Starpharma's underlying technology is built around dendrimers – a type of synthetic nanoscale polymer that is highly regular in size and structure and well suited to pharmaceutical and medical uses.
She said the company was well placed with AU$36 million in cash and its operations running normally.
Noxopharm’s idronoxil blocks STING pathway
Meanwhile, Sydney-based Noxopharm Pty Ltd. has discovered that its lead candidate idronoxil, the active ingredient in Veyonda, inhibits the STING (Stimulator of Interferon Genes) signaling pathway and has potential to block the hyper-inflammation stemming from the COVID-19 infection.
STING is part of a primitive defense mechanism that detects the presence of invading pathogens and plays important roles in the clearance of damaged cells and tissues. Both responses involve the production of cytokines that coordinate immune and inflammatory responses.
In COVID-19 patients, a trigger for this cytokine storm or septic shock is mounting tissue damage associated with poor oxygen levels stemming from poor lung function, with this tissue damage believed responsible for triggering a toxic STING response. High levels of cytokines and clotting factors are proving to be a predictor of mortality in COVID-19 patients.
“With the emerging possibility that an abnormally high STING response is a factor in COVID-19 death, having an inhibitor of STING signaling ready to be tested in COVID-19 patients is both a considerable responsibility and opportunity, said Noxopharm CEO Graham Kelly.
“The need to prevent the phenomena of cytokine storm and septic shock in COVID-19 patients looks likely to remain for some considerable time and may even remain a long-term need should development of an effective vaccine prove challenging.”
For Noxopharm, Veyonda is first and foremost an oncology drug, with end-stage prostate cancer remaining its primary focus. Any clinical studies in non-oncology patients will require nondilutive funding, something that the company believes should be achievable once it receives the go-ahead to conduct a clinical study.
CSIRO testing first COVID-19 vaccines
Australia’s national science agency, the Commonwealth Scientific and Industrial Research Organization (CSIRO), has begun the first stage of testing potential vaccines for COVID-19 at its high-containment biosecurity facility, the Australian Animal Health Laboratory (AAHL) in Geelong, Victoria.
To prepare for disease outbreaks, last year CSIRO partnered with the Coalition for Epidemic Preparedness Innovations (CEPI), a global group that aims to derail epidemics by speeding up the development of vaccines.
In January, CEPI requested the University of Queensland (UQ) to use its rapid response vaccine technology to develop a vaccine, and the candidate was produced within the first three weeks. The vaccine was developed using UQ’s molecular clamp technology that locks the spike protein into a shape which allows the immune system to recognize and then neutralize the virus.
That vaccine candidate will now move to further testing at CSIRO’s biologics production facility in Melbourne where scientists have begun small-scale testing.
CSIRO’s Dangerous Pathogens Team worked with the first strain of SARS-CoV-2 isolated outside of China by the Peter Doherty Institute. The team was the first to grow sufficient stocks to investigate the physical and molecular characteristics of the virus to find differences and similarities with other known coronaviruses.
This team was also the first to show that ferrets are susceptible to COVID-19 and developed an animal model for evaluating the efficacy of multiple COVID-19 vaccine candidates.
The UQ team will partner with the Dutch company, Viroclinics Xplore, on preclinical studies.
“These protection studies must be done in specialist biosecurity facilities as they use the live virus, and our long-standing partnership with Viroclinics Xplore gives us the confidence that this can be achieved as quickly as possible,” said Keith Chappell said, vaccine program co-leader.
“This work will establish a critical package of data that will take us through to human clinical trials in the third quarter of 2020.”
CSIRO has a long history of developing and testing vaccines since the opening of the AAHL in 1985. It is the only high biocontainment facility in the southern hemisphere working with highly dangerous and exotic pathogens, including diseases that transfer from animals to people.
CSIRO was the first research organization outside of China to generate sufficient stock of the virus – using the virus strain isolated by the Doherty Institute – to enable preclinical studies and research on COVID-19.
“CSIRO has been commissioned to develop a system so that anyone with a candidate vaccine can just plug it into our system and make the process of testing faster,” said Trevor Drew, director of CSIRO’s AAHL.
Stem cell treatments cleared for trials
Two Australian stem cell companies are testing their stem cell therapies in people with acute respiratory distress syndrome (ARDS), which is the body’s immune response to the COVID-19 virus in the lungs, causing the immune system to overreact.
Australian stem cell therapy company Mesoblast Ltd. is evaluating its allogeneic mesenchymal stem cell (MSC) therapy remestemcel-L in patients with ARDS caused by COVID-19 in the United States, Australia, China and Europe.
Cynata Therapeutics Ltd. is also studying the utility of its Cymerus MSCs as a treatment for ARDS associated with COVID-19 with the Critical Care Research Group at Prince Charles Hospital in Brisbane.