PERTH, Australia – After a AU$2 million (US$1.4 million) capital raise in April, Perth-headquartered Pharmaust Ltd. will advance its lead compound monepantel into phase I trials in humans.

An Australian researcher discovered that monepantel – an already approved antiparasitic drug for food chain animals sold by Novartis Animal Health – was potent as a cancer drug, Pharmaust CEO Roger Aston told BioWorld. "I looked at it and thought it was a good opportunity for repurposing an already-approved drug that's in the veterinary market and sold in Europe, Australia and New Zealand. The drug is sold for sheep and food chain animals, so it had to be very safe."

Aston, however, did have some questions. "This initially raised some alarm bells for me. How could you have an anticancer drug going into the food chain?" He took the product on board and conducted extensive preclinical work, looking at 40-odd human cancer cell lines that showed the drug was active at both stopping tumor growth and killing tumors.

Monepantel is an oral aminoacetonitrile (AAD) that modulates the mTOR pathway, which plays a role in the pathogenesis of diseases like Alzheimer's disease, Parkinson's disease and other aging disorders. In addition, mTOR inhibitors have been approved for indications including renal cell carcinoma, breast cancer, mantel cell lymphoma and pancreatic neuroendocrine tumors.

The market for mTOR inhibitors is valued at more than AU$2 billion per year.

Aston was previously the CEO of Pitney Pharmaceuticals, which began development of monepantel. Pharmaust acquired Pitney in 2013 for roughly AU$5 million. Pharmaust already had a subsidiary called Epichem that was involved with medicinal chemistry, and the company now has two distinct business units, with Epichem acting as a contract medicinal chemistry company and Pharmaust as a drug development company.

For the last year, Pharmaust has focused on reformulating the drug so it would be practical to give orally as a treatment in both veterinary cancers and human cancers.

Phase I trials positive

The company completed a small phase I trial in solid tumors that achieved primary endpoints in safety and reduction in clinical biomarkers.

Pharmacodynamic analysis showed treatment was associated with a significant reduction in two key biomarkers associated with the disease. Clinical assessment using RECIST 1.1 showed that of the four patients who completed the trial, three had stable disease and one patient had progressive disease.

"In both humans and dogs, monepantel is metabolized to monepantel sulfone, and this metabolite remains in the body for some time," said Pharmaust Chief Scientific Officer Richard Mollard.

"This metabolite appears to have the same, targeted cytotoxic effect upon cancer cells and the same nontoxic effect upon noncancer cells as monepantel. This means that monepantel and its metabolite are predicted to provide an enduring and specific effect through a 'double kick' to cancer cells, while minimally affecting normal cells in the body.

"We have the safety and toxicology data, and we already know we have a very safe drug as we go into the phase I trial," Mollard added, noting that the drug has already demonstrated anticancer activity in humans as far as pharmacodynamic markers and showing stable disease.

"We've been able to give quite high doses, and there hasn't been much evidence of toxicity, and the product exhibited tumor regression or progression-free survival in phase I trials," Aston said.

Because the drug doesn't harm the immune system, it allows a patient's immune system to build up while the tumor is also held in check to give the body time to fight it.

"Our strategy is about protecting the immune system and keeping the tumor in check. The hope is that patients will be able to be treated for years," he said. "The concept is different than normal cancer therapy, which wipes out the immune system. I don't think [this approach] has been considered."

The plan is to focus on cancers that have a poor prognosis such as esophageal, pancreatic and gliomas, since those patients have limited options.

Man's best friend could live longer

Since the drug is already approved for animals, it is also being tested in canines as a cancer therapy treatment for pets. And the path to market for veterinary indications should be quite fast.

"Roughly 80% of dogs that have cancer end up being put down," Aston said, "and we estimate that the animal cancer market in itself is worth about AU$500 million to AU$600 million, and there is a lot of room for a drug that doesn't have toxicity."

The company is beginning a phase II trial in canines, which is part of an agreement with Elantel, a subsidiary of Eli Lilly and Co. If the trial is successful, the product will likely be acquired by Elantel, which has an option on it.

"We're working with a company that owns our product, but we own the methods of use," he said.

"Often what happens in dogs, happens in humans, so the outcome of the dog trial will be an important pointer for us on what's going to happen in humans. If we can show stable disease for long periods of time, we believe we can target several cancers in humans."

In late March, Pharmaust reported that its phase I canine trial showed no adverse effect, toxicity or safety-related observations. Another study showed that one tablet was sufficient to provide blood levels associated with anticancer activity.

Earlier this month, the company announced a capital raise of AU$2 million via a pro-rata non-renounceable rights offer of 80 million new shares priced at AU2.5 cents each.

The funds will allow Pharmaust to begin the larger phase I human trial and the phase II canine trials.

"If you look at the company's share price, we're a microcap, and yet here we are going into a major phase II trial. This is very typical of the Aussie market; they want to see you reach your goal before we get funding," Aston said.

Pharmaust shares on Australia's Security Exchange (ASX:PAA) were trading at AU3.7 cents. Its market cap is roughly AU$10.4 million.