The following are some questions generated by last Thursday’s announcement.
Q: Why are we planning on running 7 clinical studies?
A: Because we want to be in a Phase 3 registration study in 2019, and that means knowing by the end of 2018 what that study will look like. We also want that Phase 3 study to involve the fewest number of patients and to be conducted in the shortest possible time. Each of the planned 7 clinical studies is putting NOX66 to the test under different clinical conditions involving chemotherapy or radiotherapy or both. A broad approach widens our choices and increases the chances of identifying the best approach to a Phase 3 registration study.
Q: How can we afford to run such a large clinical program?
A: Simple. Allocate resources judiciously. Minimise the size and duration of studies. Have others share some of the costs (Investigator Initiated Trials). Keep overheads to a minimum. Use government funding where available. After 23 years of running biotech companies, I have some idea of how to extract as much value as I can out of a shareholder’s dollar. I believe we probably do more than most other biotechs with the cash we have.
Q: When will the Company know if NOX66 is working and when will the market hear about it?
A: Each of the studies has a series of in-built review points that will allow us to release news on a progressive basis. I have consistently said that I am confident that we (and therefore the market) will know before the end of this year whether or not NOX66 holds the promise that we believe it has. I don’t know of another ASX-listed biotech that could make such a claim within 15 months of listing.
Q: Will the Company need to raise more money, and when?
A: Of course it will…it is just a matter of when, and that will be at a time that maximises shareholder value. Raising only $6M at the IPO was a deliberate strategy. We chose to take the minimum amount that we believed was required to reach a key inflection point that would enable us to raise further funds at a less dilutive price. That remains the strategy.
Drug development is an expensive business, and successful drugs cost even more to develop. We currently have sufficient cash to keep the current program running into 2018. But it would be reckless in the extreme to not replenish our cash position before then. The timing is an equation of more news, more progress, and more market appreciation of the potential significance of what we are doing.
The past quarter’s activities can be summarised in the following statement.
We believe we are about to see for the very first time what happens in humans when you selectively switch off resistance mechanisms in their cancer cells at the same time as treating them with chemotherapy or radiotherapy.
The following is for those interested in drilling down a bit more into what it means to cancer therapy to ‘switch off resistance mechanisms’.
Resistance mechanisms are what allows cancer cells to ignore chemotherapy and radiotherapy, either by shielding the cell from being damaged in the first place or by allowing the damage to occur and then ramping up its ability to repair the damage. It is because of these mechanisms that the poor outlook for many forms of cancer hasn’t changed much over the last 40 years. We almost invariably die from late-stage cancers because of these resistance mechanisms.
Science has a pretty good understanding of what these resistance mechanisms look like. They generally involve proteins that go by such names as PI3 kinase and Akt/mTOR and MAPK/ERK, all clearly identified as potential drug targets based on the simple rationale ….. disable these proteins and the cancer cell won’t be able to fight back.
Drugs have been made against some of these proteins, PI3 kinase (PI3K) being the most popular one. A number of PI3 kinase inhibitors currently are being evaluated in the clinic. But here’s the problem. First, PI3K isn’t just responsible for drug resistance mechanisms…it plays a key role in the overall survival of any cell. So, unless your drug can differentiate between PI3K in good cells and PI3K in bad cells, the end-result is not going to be good. And that is the problem with all PI3K inhibitors developed to date – they have serious side-effects, which means their dose needs to be limited, which means that they end up being used at doses not able to kill all cancer cells. But there is a second and even bigger problem…and that is that PI3K is but one of a number of proteins involved in resistance mechanisms. Knocking out PI3K simply leads to another resistance mechanism taking over.
What marks NOX66 as being different is that it overcomes both problems: first, by knocking out the master control switch that is responsible for turning on all virtually all the resistance proteins including PI3K; and second, it knocks out this master switch in cancer cells only.
We currently are asking a question that medicine has long wanted to ask but has not been able to.
It is in this context that I recommend people view our clinical trial program and the coming 9 months.