Small Caps | Jul 17 2023
Tim Boreham highlights the potential for cancer treatment biotech Arovella Therapeutics.
By Tim Boreham
ASX code: ((ALA))
Share price: 4.8 cents
Shares on issue: 899,149,698
Market cap: $44 million
Chief executive officer: Dr Michael Baker
Board: Dr Tom Duthy (chair), Dr Baker, David Simmonds, Dr Debora Barton, Dr Elizabeth Stoner, Gary Phillips
Financials (March quarter 2023): receipts $19,000, net cash outflows $1.83m, cash on hand - about $8m post-raising.
Identifiable major shareholders: Merchant Funds Management 11.3%, Richard Mann (Mann Beef Pty Ltd) 6.4%
Little by little, investor purse strings are re-opening and biotechs are raising capital again. But their efforts are in dribs and drabs and no-one is aiming too high.
An exemplar is Arovella Therapeutics, the cancer immunotherapy play that raised $4.1 million and strived for an additional $1 million by way of a share purchase plan (SPP).
As it happened, on Tuesday the company announced the SPP had raised $2.2 million and - yes - the company would keep the over-subscription bestowed by the biotech gods.
Formerly the oral drug delivery developer Suda, Arovella has re-invented itself with a singular focus on the sexy immunotherapy discipline of Car-T therapies.
The Monty Python catchphrase - “and now for something completely different” - comes to mind. Put another way, the company is like grandpa’s axe with a new management, new board and a new raison d’etre within the old entity.
With a long-time interest in immunotherapies, Paul Hopper took over as chair of the then Suda in 2019. The country’s busiest biotech entrepreneur declared the company was pursuing too many small programs without a commercial focus.
Still, little did we know that Suda/Arovella would ditch its spray mist delivery program completely, in favour of the Car-T program. But it did.
But one must angle where the fish are biting and investors have been lured by the pre-clinical results pertaining to Arovella’s lead compound, called ALA-101, which targets a cancer marker called CD19.
Don’t quiver, it’s Arovella
The name Arovella derives from arrow (as in targeted drug delivery) and novel (as in new therapies).
Arovella plays in Car-T therapies alongside the ASX-listed Chimeric Therapeutics ((CHM)), Imugene ((IMU)) and Prescient Therapeutics ((PTX)). (All of which just happen to be, or were, Paul Hopper-related companies.)
‘Car’ stands for chimeric antigen receptor and T refers to T-cells.
Arovella’s program revolves around invariant natural killer T-cells (iNKT) assets, acquired from Imperial College London.
The company also has technology that targets a cancer marker called DKK1, acquired from the Houston, Texas-based MD Anderson Cancer Centre. The idea is eventually to use this in conjunction with the iNKT platform.
Arovella was initially known as Eastland Medical, which was incorporated in 1999 and listed in 2001, developing the sublingual Artimist as a treatment for malaria.
The troubled Eastland changed its name to Suda in 2012, with a remit to develop spray-based oral delivery Oromist platform.
Mr Hopper’s appointment resulted in the departure of chief executive Stephen Carter after nine years at the helm, to be replaced by Dr Michael Baker.
Dr Baker was an investment manager with Bioscience Managers and is on the board of the Mr Hopper-chaired nuclear medicine play Radiopharm Theranostics ((RAD)).
In October 2021, Suda changed its name to Arovella.
A year later, the company said it would cease development of Oromist and close its Perth facility.
Mr Hopper quit the board in June 2022, with Dr Thomas Duthy eventually taking his place as chair.
Mr Hopper continues to chair Chimeric Therapeutics, which is also Car-T driven.
With about five staff, Arovella operates on a pure virtual model by which trials and pre-clinical work are outsourced.
Fighting the scourge of cancer - and acronyms
In June 2021, Arovella signed a deal with Imperial College London to acquire a cell therapy platform called invariant natural killer T-cells, or iNKT.
The body’s strongest immune cells, iNKTs are a rare variant of T-cells.
Dr Baker said the program appealed because of Imperial College’s lofty status and the laboratory-ready nature of the asset.
Separately, the MD Anderson Cancer Centre delivered a poetically monikered asset called DKK1-Car/mAb. This peptide is the first to target DKK1, a biomarker of several forms of blood and solid cancers.
Dr Baker describes iNKT cells as “one of the most potent, naturally occurring immune cells.” (A mAb is a monoclonal antibody.)
Tackling blood cancers
Arovella’s lead program, ALA-101, is showing early promise as a treatment for CD19- expressing blood cancers.
In April this year, the company’s shares went on a mini-run after pre-clinical data was aired at the American Association of Cancer Research (AACR) in April.
In the mouse study, the rodents were infused with CD19-expressing, aggressive B-cell acute lymphoblastic leukemia cells. At the 90-day mark, only the 38 mice treated with ALA-101 (Car19-iNKT cells) and other Car-T therapies survived.
Of the 19 mice treated with ALA-101, the 90-day rate was 1.5 times better than the other Car-T mice and 90 percent of them were still squeaking.
An interesting twist is that four of the ALA-101 mice developed subsequent brain tumours, but they cleared up without further treatment. This suggests the effect of ALA-101 is enduring and that the molecule can cross the blood-brain barrier.
Crucially, the studies have shown the iNKT cells can be expanded by a factor of 5,000 without losing their potency.
“The data has given us great comfort that our proprietary manufacturing process allows for sufficient expansion of the iNKT cells that retain their functionality,” Dr Baker says.
He adds that the first-generation Car-T therapies have resulted in significant relapses and safety risks such as cytokine release syndrome, neurotoxicity and infection.
“We believe there is a significant unmet need and ALA-101 is well placed to fill that need by having an off-the-shelf strategy to treat B cell lymphomas and leukemia.”
. … and solid cancers
Arovella also has a joint program with the ASX-listed Imugene, which combines ALA-101 with Imugene’s Oncarlytics therapy (more formally known as CF33-CD19).
This effort is relevant for solid cancers which - unlike blood cancers - do not exhibit the CD19 marker.
As Dr Baker says the Oncarlytic virus infects the cancer cells and forces them to express CD19. “Our iNKT cells will come along like heat-seeking missiles and find and destroy them,” Dr Baker says.
The Imugene therapy also aims to kill the tumour cells. So, like Harpic Flushmatic dual action cistern blocks, there is a two-fold efficacy by combining both therapies.
This collaboration is in proof-of-study, in-vitro stage, with animal data expected in the second half of 2023.
Bespoke versus off-the-shelf
The usual Car-T manufacturing process involves blood being taken from a patient’s arm. The T-cells are collected and are genetically reprogrammed to produce millions of chimeric antigen receptors.
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