Clinical-stage oncology company PharmAust (ASX: PAA) has received early positive results from a phase I trial of its reformulated monepantel anti-cancer tablets.
The canine-based trial commenced last month using a new version of the tablet following earlier difficulties in administering the drug to human and dog cancer patients due to its poor taste.
The trial was designed to test the absorption and pharmacokinetic parameters of monepantel in suppressing tumour markers and tumour regression.
It will be used as a precursor to a phase II dog cancer trial.
Following a single dose administration of one tablet to the phase I trial cohort of nine healthy dogs, blood concentrations of monepantel were found to exceed those observed in the phase I clinical trial in humans, which were associated with reduced tumour marker levels in blood.
Further, the serum concentrations from one tablet in dogs also exceeded monepantel levels observed to achieve anti-cancer activity in mice bearing the human cancer xenografts.
“This preliminary data set provides early evidence that a single dose of monepantel can provide sufficient drug levels in serum to achieve anti-cancer activity,” said PharmAust chief scientific officer Dr Richard Mollard.
“This is a pleasing result as it means dosing of canines by their owners will be much less of a challenge using these tablets.”
Dr Mollard said the company will investigate dose escalation and repeat dose administration to align long-term administration frequency of monepantel with these same blood levels, anti-cancer activity and the “very good safety setting” established for the drug.
Modulating the mTor pathway
Monepantel is a small-molecule drug currently being developed as a novel, safe and potent treatment for cancer.
It employs an oral aminoacetonitrile compound which modulates the mTOR pathway recognised as a key driver of many cancers and a contributor to the pathogenesis of diseases such as Alzheimer’s, Parkinson’s and various ageing disorders.
The market for human mTOR inhibitors is valued at over $2 billion per year, with many inhibitors already approved to treat various human indications including renal cell carcinoma, breast cancer, mantle cell lymphoma and pancreatic neuroendocrine tumours.
Treating canine cancer
With an estimated six million dogs diagnosed with cancer each year in the US, PharmAust is also evaluating monepantel for treatment of lymphomas and other cancers in companion animals.
The company aims to develop monepantel as a novel therapy to treat common cancers in dogs and use the information to inform and de-risk its human clinical development program.
To date, PharmAust has completed phase 1 clinical trials with monepantel in human and dog patients diagnosed with solid tumours, with all trials achieving their primary endpoints in terms of safety and reduction in key clinical biomarkers.
PharmAust has also initiated a phase 2 pilot study in dogs diagnosed with lymphoma.
At mid-afternoon, shares in PharmAust were up 15.63% to $0.037.