PharmAust (ASX:PAA), a clinical-stage oncology company, has announced an extension of work for ONJCRI researchers to continue to investigate the mechanism of action of monepantel (MPL) upon cancer cells.

Researchers in our Cell Death and Survival Laboratory led by A/Prof Doug Fairlie and Dr Erinna Lee conducted a comprehensive RNA-Seq (RNA sequencing) screen investigating how the entire genome of cancer cells responds when treated with MPL. A select subset of genes was found to be either switched on or off by MPL in cancer cells, but not in non-cancer cells. The tested non-cancer cells’ mRNA profiles were relatively unaffected by MPL treatment.

Using state-of-the-art techniques, the team will now examine these genes in greater detail and match changes in their activity with changes in associated protein signalling pathways. These experiments are aimed at determining what happens within the cancer cell once MPL interacts with its primary molecular targets, and then exerts its downstream and definitive anti-cancer activity. Establishing MPL’s mechanism of action in this detail will enable differentiation of MPL’s effects upon cancer cells compared to other anti-cancer drugs, thus assisting with regulatory submissions and marketing moving through Phase III and IV trials.

Doug says “This is an exciting opportunity for us to move this study into its next phase and help us better understand the anticancer activity of MPL”.

“This is important for the progression of the drug through the approval process so that it may eventually have real benefit for cancer patients.”

The work will be funded by PharmAust. PharmAust’s Chief Scientific Officer Dr Richard Mollard stated, “PharmAust is pleased to continue this productive relationship with ONJCRI. PharmAust is looking forward to seeing at the molecular level how MPL works in cells to combat disease, especially in terms of how MPL’s mechanism of action differs to other mTOR inhibitors presently in the clinic.”


About PharmAust (PAA):
PAA is a clinical-stage company developing therapeutics for both humans and animals. The company specialises in repurposing marketed drugs lowering the risks and costs of development. These efforts are supported by PAA’s subsidiary, Epichem, a highly successful contract medicinal chemistry company which generated $3.5 million in revenue in FY 2020.

PAA’s lead drug candidate is monepantel (MPL), a novel, potent and safe inhibitor of the mTOR pathway – a pathway having key influences in cancer growth and neurodegenerative diseases. MPL has been evaluated in Phase 1 clinical trials in humans and Phase 2 clinical trials in dogs. MPL treatment was well-tolerated in humans, demonstrating preliminary evidence of anticancer activity. MPL demonstrated objective anticancer activity in dogs. PAA is uniquely positioned to commercialise MPL for treatment of human and veterinary cancers as well as neurodegenerative disease as it advances a reformulated version of this drug through Phase 1 and 2 clinical trials.