PERTH, Australia – Australia’s largest health care venture capital firm, Brandon Capital, announced the launch of Australian biotech company Ena Respiratory Pty Ltd., which has developed a nasal treatment to boost the natural immune system to fight common colds and flu and has proved successful in reducing COVID-19 viral replication.

The Melbourne, Australia-based company has developed a series of synthetic Toll-like receptor (TLR) 2/6 agonists for topical delivery via nasal spray to target the primary site of most respiratory infections, including influenza and SARS-CoV-2. The pegylated TLR 2/6 agonist INNA-051 reduced viral replication by up to 96% in an animal study in ferrets led by Public Health England.

One of the biggest benefits of the compound is that it stops the virus in its tracks at the point of infection and cuts it off before it gets into the body, Chris Smith, Ena Respiratory board director and senior investment manager at Brandon Capital, told BioWorld.

Chris Smith, Ena Respiratory board director and senior investment manager at Brandon Capital

In the study, INNA-051 was administrated as prophylaxis. After five days post-exposure to COVID-19, INNA-051-treated animals had statistically significant reduction of virus in throat swabs (96% reduction) and nasal washes (93% reduction) compared to untreated animals, despite high levels of virus exposure.

The therapy restricts initial replication of the virus in the upper respiratory tract and reduces the level of viral RNA in the nose and throat.

TLRs are key microbe-recognition receptors with a crucial role in activating host defense and protection from infections and are attractive drug targets against infectious diseases, study authors said.

“However, their success in the clinic has been limited, due to short-duration of benefit or induction of adverse effects related to the release of pro-inflammatory cytokines and activation of the type-1 interferon pathway. TLRs expressed on the cell surface such as TLR2 offer an alternative approach,” they said.

Importantly, TLR2 agonists don’t bring on a cytokine storm or type-1 interferon response, Smith said.

“When other people have tried to do this in the past, they’ve done it with molecules that aren’t quite safe enough to do for an application like we’re talking about. We’ve been working on this for about six years to make sure that it doesn’t do that, and that’s really critical, because not all the ways you recognize pathogens are the same.

“The real difference is that these molecules don’t induce flu-like symptoms,” he added. “That’s a type-1 interferon response, and our molecule doesn’t do that, which makes it really different to what’s been done in the past.”

When asked what makes the treatment different than a prophylactic like a mask, Smith said that a mask will protect other people from getting infected, but it doesn’t do much to protect the person wearing the mask.

Christophe Demaison, co-founder and managing director, Ena Respiratory

“But it is sort of like a PPE layer, especially if you’re in a hospital setting where we know the rates of infection are really high, and the place that you get infected and where the virus gets replicated is all in the nose and throat.”

“We’ve been amazed with just how effective our treatment has been,” said Ena Respiratory’s co-founder and managing director, Christophe Demaison. “By boosting the natural immune response of the ferrets with our treatment, we’ve seen a rapid eradication of the virus.

“If humans respond in a similar way, the benefits of treatment are twofold. Individuals exposed to the virus would most likely rapidly eliminate it, with the treatment ensuring that the disease does not progress beyond mild symptoms. This is particularly relevant to vulnerable members of the community,” Demaison said. “In addition, the rapidity of this response means that the infected individuals are unlikely to pass it on, meaning a swift halt to community transmission.”

Clinical trials to start soon

Ena Respiratory has raised an AU$11.7 million (US$8.26 million) series A round from Australian investors and, subject to successful toxicity studies and regulatory approval, the company could be ready to test INNA-051 in clinical trials in the next few months.

The series A round was led by Brandon Capital-managed Medical Research Commercialization Fund (MRCF) and a coalition of investment partners, including the MRCF Biomedical Translation Fund, four leading superannuation funds – Australiansuper, HESTA, Hostplus and Statewide Super – and biotech giant CSL Ltd. University commercialization fund Uniseed also participated in the round.

The company is seeking additional funding to accelerate clinical development and global distribution.

“We are doing all we can to support Ena Respiratory and its quest to secure additional investment to accelerate the development and testing of the therapy in humans, said Chris Nave, CEO of the MRCF and co-founder of Brandon Capital.

“While a vaccine is ultimately the key solution to combatting COVID-19, governments need to be developing different treatment approaches to ensure they have a range of options, in the event that a vaccine proves elusive or takes longer to develop,” Nave said.

“The treatment offers significant potential to protect the most vulnerable, including those with pre-existing respiratory conditions and the elderly, where vaccines can be less effective,” Smith said, noting that the compound was in development before the outbreak of COVID-19 to promote resistance toward broader respiratory viral epidemics.

“As an original investor alongside Uniseed, the MRCF saw great potential in INNA-051, before the COVID-19 era, to manage respiratory viral outbreaks, exactly like we are currently experiencing, although our initial focus was against influenza,” Brandon’s Nave said.

Unlike vaccines which are targeted to a specific strain, INNA-051, is designed to be effective for all types of respiratory infections.

“We really see this as part of a toolkit that the world will have,” Smith explained. “This is certainly not the last pandemic, unfortunately, and it’s going to happen again, and we need to be prepared, which means having something that is broad spectrum, not necessarily specific, because we don’t know what it will be next time.”

As a broad-spectrum treatment, Ena’s compound would prevent most respiratory viruses and has been tested in influenza, rhinoviruses and coronaviruses.

“Even with a vaccine, the virus is likely to mutate, so having other therapeutics would provide additional value,” Smith said.

In addition, INNA-051 could be much safer than vaccines because it’s not actually administered into the body; it’s a topical administration and stays on that topical surface.

The authors of the study include scientists from Public Health England, Ena Respiratory and leading Australian research organizations, including the Hunter Medical Research Institute, Newcastle and the University of Melbourne.

INNA-051 is based on discoveries made by David Jackson and his team at the Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity at the University of Melbourne.

No Comments