One day, an mTOR inhibitor drug may be both a fountain of youth and a pot of gold. For now, an ASX firm is using the tech to fight cancer.
PharmAus (ASX:PAA) is developing its lead drug, monepantel (MPL) to treat cancer growth and neurodegenerative diseases such as motor neurone disease (MND).
But the prospects for the technology could have even more widespread effects – even reversing the ageing process. And that would generate billions for its developer.
Ageing is a complex biological progression that involves a combination of genetic, environmental, and lifestyle factors.
The consensus has long been that while some interventions could slow or delay the ageing process, they could not substantially reverse the fundamental changes that occur in the body over time.
But that could soon change, with a kidney transplant drug named rapamycin now becoming the latest fixation of people trying to defy Father Time.
Rapamycin, which belongs to a class of drugs called mTOR inhibitors, was initially developed by scientists at the pharma company Wyeth (now part of Pfizer) as an immunosuppressive drug to prevent rejection of transplanted organs.
The drug works by inhibiting the activity of a protein called mTOR (mechanistic target of rapamycin), which is involved in cellular growth, metabolism, and immune response in mammals, including humans.
Studies have shown that rapamycin could in fact fight ageing too, with recent animal studies yielding encouraging results.
The studies demonstrated that rapamycin can extend the lifespan of yeast, worms and flies. Studies in mice have also shown an increase in lifespan.
Since then, numerous other studies have explored rapamycin’s potential anti-ageing properties, as well as its impact on age-related diseases – although there is still little hard evidence of its longevity benefits in humans.
What is the mTOR pathway?
This development has piqued the interest of investors and put the spotlight on studies being conducted on mTOR inhibitor drugs.
US-based longevity focused biotech Cambrian Biopharma recently signed a licensing agreement with Novartis to advance its novel drug targeting the mTOR pathway.
In a nutshell, mTOR is a protein kinase that plays a central role in regulating our cellular processes – including cell growth, metabolism, protein synthesis, and autophagy.
Autophagy, a mechanism by which our cells remove and recycle themselves, naturally decreases with age and can lead to a build-up of what’s called cellular “junk”.
When this happens, it’s harder for cells to repair themselves and work efficiently, accelerating the ageing process and increasing the chances of getting age-related diseases such as cancer.
These mTOR inhibitor drugs work by regulating and suppressing this mTOR pathway, making them excellent potential anti-cancer agents that could inhibit the uncontrolled growth and survival of cancer cells.
PharmAust’s mTOR inhibitor drug
PharmAust already has a development program focused on an mTOR drug, the monepantel mentioned above.
MPL targets the mTOR pathway to treat cancer growth and neurodegenerative diseases.
Recent research has shown that MPL has broad anti-cancer effects across multiple types including melanoma, lung, breast, brain, colorectal, prostate, and ovarian.
Independent tests also showed that MPL can retain long-term shelf-life (at least 12 months for tablets) and product stability.
The drug has been evaluated in Phase 1 clinical trials in humans, and Phase 2 clinical trials in dogs.
Phase 1/2 clinical trial on MND
For this trial, PharmAust has confirmed that all blood samples from the interim analysis have been collected and submitted for analysis.
PharmAust will continue with MPL dose escalation for Cohorts 3 and 4, to determine the optimum dose for a Phase 2 trial.
A favourable interim analysis will allow the company to prepare for a Phase 2 MND clinical trial, and a human cancer Phase 2 clinical trial on this disease.
Phase 2 trial on canines with B-cell lymphoma
The latest results showed that two dogs had a partial response (more than 30 per cent decrease in cancer tumour), and eight others have enjoyed a stable disease response.
Meanwhile one dog patient has surpassed 280 days with stable disease and continued excellent quality of life, as attested by dog owner testimonials.
PharmAust says assay results from 10 x plasma samples are expected by late May, while the MPL Phase 2 trial itself is expected to be completed by mid-2023.
Phase 2 human trial in Covid-19
PharmAust has been identifying clinical centres capable of sourcing patients with the required Covid-19 progression and vaccination status – focusing on Eastern Block European states such as Poland.
Next steps include providing protocols for the study and qualification of the identified clinical centres.
This content first appeared on stockhead.com.au
At Stockhead we tell it like it is. While PharmAust is a Stockhead advertiser, it did not sponsor this article.
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