Hot Copper post
Clearly the ground breaking and pivotal areas of investigation for Novogen centres around cancer treatment; but something which has flown under the radar is the non oncology areas of opportunity.
After research and conversations with Professor Graham Kelly, I’ve collated the 5 core areas of opportunity for Novogen.
Non Oncology Opportunity 1:
By way of background, within the Yale collaboration into TRXE-002, a curious observation was made; in very low doses, TRXE-002 stopped killing the cancer stem cells and started making them grow.
Clearly this news was met with angst and frustration, until it was discovered that the cancer stem cells started looking and behaving like normal stem cells.
This is now one of the matters Novogen and Feinstein are examining with great enthusiasm; having a drug with the ability to transform cancer cells into normal stem cells.
Which leads into the first non-oncology opportunity – whether Novogen can “make” other badly behaving stem cells behave "normally".
To do this Novogen is working with Sydney based Genea Biocells, who has a large library of stem cells extracted from human embryos carrying a range of genetic abnormalities. After screening different stem cells, the Yale observations (of being able to make badly behaving stem cells act normally), were validated within some of the compounds.
The compounds that show this effect have no anti-cancer activity.
This is a major achievement in itself, but leads into
Non Oncology Opportunity 2:
In collaboration with Genea Biocells, Novogen has a program currently running on a muscular dystrophy condition known as FSHD. A grant from the global FSHD Foundation has been granted, with the aim of finding SBP’s that have the ability to make affected muscle stem cells make normal muscle fibres.
Take a second to let that sink in. Developing a drug that will reverse the muscle wasting that goes with the different forms of muscular dystrophy. Professor Graham expressed that the team believe they are on the cusp of doing this.
Non Oncology Opportunity 3:
The next logical step was to see what other applications could be applied to the stem cell developments, which leads us to the brain.
Genea Biocells have normal embryonic brain stem cells and the objective was to see if it was possible to make these stem cells proliferate and produce fully mature brain cells.
Novogen identified three compounds with potent ability to do so, and all three are currently at the University of Melbourne being tested in an animal model of brain injury.
By way of background, brain stem cells are exceptionally slow and lazy at repairing brain injury, which is why stroke victims are slow to recover (can anyone else see where this is going, and the potentially massive market on just this one non oncology opportunity).
The aim is to be able to encourage brain stem cells to come to the site of the injury and stay long enough to repair the injury. Professor Graham has indicated that a read out of this study will be in 2 months time.
If this proves to be positive, Novogen will have an entirely novel approach to the problems of brain trauma, stroke and spinal injury.
Non Oncology Opportunity 4
Another program concerns a group of paediatric diseases known as lysosomal storage diseases. There are about 30 different conditions here, all genetic. One of them is SanFilippo Syndrome. Currently this is being treated with genistein, the same compound that is the heritage for the whole benzopyran family. We have a collaboration happening in Poland and the UK intended to identify the active pharmacophore.
Non Oncology Opportunity 5
Professor Graham is empathic that this opportunity is the big one – so I’ll take a bit of time to explain the details as much as I can.
There is a growing understanding of the role of a cell’s cytoskeleton; the cytoskeleton serves many functions, the main one being how a cell divides. 30 years ago the scientific world thought that the role of the cytoskeleton was fairly limited, with the main purpose being to give the cell its shape, its ability to move, and providing the means for the cell to divide.
The cytoskeleton is composed of two completely different structures:
microtubules (hollow structures)
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&
microfilaments (solid, rope-like structures)
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When a cell prepares itself to divide, the microtubules and the microfilaments combine to form a structure known as a mitiotic spindle.
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Here’s where things get interesting – the micotubules make up the main framework of the mitiotic spindle. The family of anti-miotic drugs has become the most widely prescribed drugs in chemotherapy because they stop the microtubules from forming the mitotic spindle.
The chromosomes attach to the microtubules via a structure known as the kinetochore. The kinetochore is composed of microfiliments; this is what Anisina targets and the combined effects of destroying both components is through to be behind the 20-fold increase in anti-cancer potency of the anti-miotic (chemo) family of drugs in animals what we see when we combine Anisina with them.
Now that we’ve got that clear, I can move on to the final opportunity (if the above is unclear, read through it a few times so the next part makes sense).
This opportunity relates to Novogen’s ATM technology platform, and the opportunity for a whole new range of therapeutics targeted to the cytoskeleton and it’s fundamental functions (cell signaling, glucose metabolism).
The cytoskeleton plays a role in virtually every aspect of cell function – they are the means by which signals are received and sent by the cell. It regulates the receptors on the cell’s surface and also plays a role in general metabolism such as glucose use and energy production; in short, the nucleus of the cell is the brain and the cytoskeleton is the body.
One of the many such areas of investigation, for example, is Ulcerative Coilitis (a form of IBD – Inflammatory Bowel Disease). Novogen has an advantage over anyone else in the field, they know how to target the microfilaments in a highly selective way; the microfilaments are made up of over 40 different forms of tropomyosin (known as isoforms), and Novogens expertise lies in building drugs, which block specific isoforms.
The pivotal part of this opportunity is as follows; Cancer is associated with the over-expression of one particular isoform, and that is what Anisina attacks, and that same isoform is implicated in Ulcerative Coilitis. Let that sink in for a moment.
It takes a few reading attempts to let the above sink in, but take the time to really digest it. Novogen believes that they will eventually identify other specific isoforms associated with almost all forms of degenerative disease, thus allowing the experience gained from developing Anisina to develop drugs for other specific indications.
In summary, in my eyes it makes perfect sense why Novogen have sought to raise money – they are embracing a platform approach to their offerings. It’s not simply “We have one drug and we are trying to make it work” – they have multiple offerings, all of which are actively being investigated.
If just one pays off, the current sub 100m market cap will seem a pittance.
Also, even the core offerings are spectacular – Anisina is a complementary drug to standard anti-miotics – it’s not in competition with the current suite of drugs.
Put simply, the aim is to prove that Anisina makes standard chemo better, more potent, with fewer side effects. If this is proven to be true, we’re looking at a company not in the millions, but the billions as a market cap.
Kelly explains these apparent conflicting observations through the Novogen theory that they have stumbled on a family of molecules that function in a housekeeping role in the cell, particularly the stem cell. Where the stem cell is behaving abnormally (either because it has developed mutations or has inherited a genetic fault), then this family of compounds have the ability either to correct the fault, or where correction is not possible, to kill the damaged cell. In the case of stem with normal, but tardy, function (as with brain stem cells), they appear to have the ability to stimulate them to lift their game.
Kelly says he believes that this discovery will revolutionise how we look at and how we treat many diseases.
The above is written with information provided from Professor Graham Kelly, and public domain information – it is not investment advice, and you should seek professional advice before making any investment decisions.
