A Perth-based company is developing solutions to combat the worldwide threat of antimicrobial resistance.
A drug being developed in Western Australia is showing promise in the international fight against antimicrobial resistance.
The overuse or incorrect usage of antimicrobials, such as antibiotics, can reduce their effectiveness, with the microbes they are meant to treat becoming resistant to their effect.
It’s a microscopic problem with macroscopic implications.
A 2019 report commissioned by the US government’s National Center for Biotechnology Information – titled Global burden of bacterial antimicrobial resistance in 2019 – identified antibiotic resistance as one of the leading public health threats of the 21st century.
A 2016 report commissioned by the UK government, The Review on Antimicrobial Resistance, argued AMR could kill 10 million people a year by 2050.
While that figure has been disputed, the World Health Organisation and other groups agree AMR is an urgent issue requiring global attention.
The high rate of antibiotic use in Australia has raised concerns, therefore.
In 2015, only seven of 28 European countries surveyed had a higher rate of antibiotic usage than Australia. Notably, Australia’s rate was more than three times that of Netherlands.
In a survey of usage in hospitals, only Scotland had a higher rate.
Those figures were released five years after a strategy to combat AMR was implemented in Australia, which resulted in a 9.8 per cent drop in usage between 2010 and 2015.
Research, results
However, AMR remains a serious problem, a constantly evolving threat to which the scientific community is struggling to adapt.
Among those seeking a solution is Nedlands-based Lixa, which in 2021 began development of its universal antimicrobial resistance breakers (uARBs).
Developed at the The University of Western Australia and led by worldrenowned drug developers Maud Eijkenboom and Andrew Barker, the lead development candidate of Lixa’s uARBs, NeoX-101, has shown some promising results.
Usually, bacteria prefer to live in communities protected by a slimy biofilm coating. The film increases the bacteria’s survival rate by shielding it from antimicrobials and the immune system.
NeoX-101 is a proprietary, non-antibiotic, small molecule that causes rapid collapse of the biofilms and sensitises bacteria to accessible, affordable existing therapies.
“For too long we’ve been in an AMR arms race, developing new antibiotics as the old ones become obsolete. But we’re struggling to keep up in the race, the development of new antibiotics has slowed,” Lixa’s chief executive, Dr Eijkenboom, said.
“Instead of trying to make new weapons, NeoX is taking away AMR’s weapons and making our old tools more effective.”
It’s currently in preparation to enter clinical development as an inhaled therapy, NeoX-102 for respiratory infections, with the hope results observed in laboratory and animal studies can be replicated in humans.
In laboratory tests, the drug-resistant Methicillin-resistant Staphylococcus aureus – which was previously untreatable with antibiotics and one of the most problematic bacteria often found in hospitals – was successfully treated with the lowest dose of a generic antibiotic, if the antibiotic was applied together with a small amount of NeoX-101.
The lab results were confirmed in subsequent animal studies, in which a single oral dose of NeoX-101 enhanced the survival rate of mice with septicaemia by 67 per cent when compared with treatment using antibiotics alone.
With ethics approvals for its phase one trial to be run at Linear Clinical Research, the company is now opening an investment round for $6 million to fund phase one and two clinical trials for the inhaled formulation.
Dr Eijkenboom said the company was also exploring fast-track US Food and Drug Administration approvals.
If granted, the designations could provide tax credits for clinical trials, exemption from user fees, and a potential seven years of market exclusivity after approval.
The biofilms targeted by NeoX affect countless industries globally, including agriculture and livestock, meaning the potential use cases for NeoX are wide-ranging.
Dr Eijkenboom said the company was already in advanced discussions with a number of multinationals to identify partnerships for uses beyond the medical.
One of the multinationals has been involved with Lixa for 10 months.
“During (the ten months) we completed a technology due diligence process and a technology feasibility assessment,” Dr Eijkenboom told Business News.
“We have agreed on the philosophy underlying co-development projects [non-medical] and a budget, and the multinational is drafting the legal documents.”
Dr Eijkenboom said she expected legal negotiations with the multinational to be completed soon.
“The co-development projects are designed to integrate the Lixa non-medical active ingredients to their existing consumer product formulations for enhanced performance against resistant bacterial biofilm contamination,” she said.
“The partner stands out for its market leadership in the specific target segment with ten billion dollars of revenue in this segment in 2023.”
Applications
Plant disease caused by microbial biofilms contribute to the loss of an estimated 10 per cent of global food supply.
Biofilms also lead to livestock infections such as bovine mastitis, which was estimated in 2016 to cost the US diary industry around $2 billion through an estimated 11 per cent loss of the country’s total milk production.
The effects of these biofilms even extend to the global energy market.
Studies have shown fuel consumption of large ships with hulls contaminated by colonies of microorganisms is 18 per cent higher than that of ships with clean hulls.
Similarly, biofouling – the process where micro-organisms, plants or algae attach themselves to surfaces that are in water – has been shown to reduce hydropower turbine efficiency by 40 per cent and clog pipes and membranes.
Dr Eijkenboom believes NeoX could be used to combat these and other problems.
“[T]his technology can be used in almost every single industry in some way,” she said.
“It really is groundbreaking, and if we can garner support through partnerships then I hope to see the medical side of this technology become almost a philanthropic cause.
“After our cap raise, the company will seek to expand our capacity to leverage our technologies in multiple additional non-medical co-development deals, such as cosmetics, agribusiness, food preservation, hygiene and marine anti-fouling, while continuing the clinical development in the exceptionally lucrative and important pharmaceutical markets.”
Phase one clinical trials will involve eight volunteers – six on NeoX-101 and two on placebo – taking small, inhaled versions of the drug to test how their lungs respond, and whether a cough develops.
“We’re not looking to test its toxicity as we already know it’s extremely safe for humans,” Dr Eijkenboom said.
“From there, we will move to a trial in bronchiectasis patients. It will be a dose escalation trial where these patients get a standard-of-care antibiotic, plus our ingredients.
“We’ll be looking there first for safety endpoints, so we’ll check in again how these patients deal with this as an inhaled form, but we’ll also be looking at anti-inflammatory biomarkers, microbial reduction and for clinic wellbeing.”
Earlier this year, Lixa received an Innovation Booster Grant from the state government’s New Industries Fund.
The company has also been invited to take partnership in a new training centre led by the University of Queensland to tackle AMR: the Australian Research Council Centre for Environmental and Agricultural Solutions to Antimicrobial Resistance.
