PharmAust lays out market strategy for lead drug monepantel

PharmAust ASX PAA monepantel 2020 anti cancer drug Epichem
PharmAust is increasing its focus on COVID-19 with EU and US collaborators expressing interest in preparing the ground for clinical evaluation of monepantel in humans.

Oncology company PharmAust (ASX: PAA) has provided a timely update to the market concerning developments of its lead drug candidate, monepantel (MPL).

PharmAust is currently progressing the drug in a trifecta of pathways including treating cancer in dogs, a repurposed treatment for COVID-19 and as a drug treating neurodegenerative disease.

In an interview last week, the company’s executive chairman Dr Roger Aston outlined its business strategy of focusing on repurposing and commercialising MPL for new indications, including COVID-19.

To date, the drug has been shown to have anti-cancer activity in various cancer settings, with PharmAust focusing on canines and humans for the time being. In most recent news PharmAust published positive early results showing that MPL can inhibit the progression of SARS-CoV-2, according to research conducted by the Walter and Eliza Hall Institute of Medical Research in Melbourne, Australia.

According to PharmAust, MPL’s strong historical background makes future regulatory hurdles more expedient to clear although to make further progress, the company is seeking to attract development partners.

Into battle with COVID-19

Given MPL’s effect on the mTOR metabolic pathway – a complex network of cell signalling and transduction pathways in mammals – PharmAust is keen to repurpose the drug to treat patients with COVID-19.

According to the oncology company, mTOR controls a variety of cellular functions including cell growth, autophagy (lysosomal degradation of a cell’s contents) and protein translation. Therefore, MPL “lends itself to manipulation for other diseases”, an idea that was, to some extent, demonstrated by PharmAust in recent SARS-CoV-2 testing.

“MPL’s impact on viral replication in both human and monkey cells leaves little doubt that PharmAust needs to pursue the therapeutic value of MPL in the treatment of this devastating viral disease,” PharmAust said.

The company is now in dialogue with both European and US laboratories that can undertake preclinical work in preparation for a phase 1 human trial.

One of the potentially lucrative advantages that underpins PharmAust’s ambitions for MPL as an anti-COVID medication is its formulation and how it compares to current go-to COVID drug Remdesivir.

The US drug has been shown to reduce patient recovery time from 15 to 11 days and has quickly amassed predicated annual sales of between US$2-8 billion (A$3-11 billion) by 2022.

Remdesivir is administered intravenously which means only hospitalised patients can ever hope to receive it. PharmAust believes that if it can prove MPL’s efficacy, the drug’s oral form means COVID-19 positive patients could potentially take the medication before their symptoms have exacerbated to the point of needing hospitalisation.

Animal applications

Having initially began development of MPL for a range of cancers, PharmAust remains confident it can develop a commercially viable drug, for both canines and humans, despite recent setbacks.

The company’s recent phase 2 trial in canines with B-Cell Lymphoma, the most prevalent canine cancer, showed both tumour regression as well as stable disease.

PharmAust considered this data as a sound platform to springboard into undertaking dose optimisation and eventually phase 3 trials. Dose optimisation expected to increase efficacy in animal trials and seen as a pivotal factor that will ultimately secure final approval.

“If our strategy is correct and we can demonstrate that MPL is consistently effective in tumour regression in most canine patients, this will likely strengthen our negotiating position with both third-party veterinary and human pharmaceutical companies,” the company said.

Dr Aston confirmed that “alternative parties” had already approached PharmAust for discussions in terms of identifying different cancer treatments using MPL and collaboratively funding research and development.

PharmAust ASX PAA Monepantel trial anti-cancer treat anive B cell lymphoma MPL tablet pet dog
In PharmAust’s recent phase 2 trial in canines with B-Cell Lymphoma both tumour regression and disease stabilisation was observed.

The company provided multiple reasons why it thinks a focus on MPL as an anti-cancer drug is worthwhile. First and foremost, the drug has been shown to affect B-cell lymphoma in dogs with early studies indicating a great than 60% reduction tumour burden and complete regression of one cancerous lesion in one dog.

Moreover, PharmAust has also demonstrated MPL’s activity against a key cancer marker in humans and canines, with a good safety profile, during as part of a clinical trial conducted at the Royal Adelaide Hospital. MPL is already approved for the treatment of parasitic infections in food chain animals, confirming that the drug has received extensive regulatory scrutiny.

Last week, PharmAust received a significant update with respect to developing MPL for animal use. Development partner, vet company Elanco, declared it would not exercise an option to negotiate an exclusive worldwide royalty-bearing commercial licence to use PharmAust’s intellectual property in the field of treatment of cancer in animals.

Dr Aston characterised the news as “disappointing” but said the news would not affect the company’s commercialisation strategy or the final outcome of MPL.

At the right dose, MPL demonstrates significant tumour regression which spells an effort to “optimise” dosage moving forward.

Neurodegenerative disease application

According to PharmAust, MPL could potentially be repurposed into an anti-neurodegenerative disease drug, stating that previously published literature implicates mTOR pathways in the control of neurological diseases.

With mTOR pathways playing a major role in several biochemical functions and processes in both animals and humans, MPL can be formulated into inhibiting functions that affect cognitive capacity.

In the past, the company has published pre-clinical research demonstrating that MPL impinges upon molecular cascades “relevant to correct induction of autophagic flux relevant to the clearance of misfolded neurodegenerative causing proteins”.

Also, very importantly, clinical research has demonstrated MPL’s capacity to cross the blood-brain barrier, making MPL a rare drug that inhibits mTOR signalling while being able to act directly on the brain following oral administration as a tablet.

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