There does appear to be differences is FTO variants between...

There does appear to be differences is FTO variants between different human populations, but that does not matter for what we are doing in this trial. We are not measuring FTO activity directly, but the level of m6A in the RNA before and after treatment with bisantrene. We are looking to see if bisantrene changes the m6A in levels in RNA (we expect that it would increase), not inhibition of FTO directly.

The reason for this is it is the effect on m6A levels that matters, not if bisantrene directly inhibits FTO or not. You could imagine a scenario where bisantrene inhibits FTO, but the patient's cells compensate for this by decreasing the amount of METTL3 produced (i.e. decrease the amount of m6A methylation going on in the cell). If this were to happen then the level of m6A in the RNA might not change, or might even go down. Dynamic systems like the m6A regulatory system are very complex so it is important to measure what matters (m6A levels), not just intermediate effects upstream (i.e. FTO inhibition).

Of course this is just an exploratory first step to see if we can change the m6A levels in humans. If it is positive then we would look to do much more work in this and possibly look to run specific m6A trials where we expect this to have a significant therapeutic effect on the cancer the patient has. By doing things in careful steps we can maximise the return on our shareholders capital - I could spend $200m tomorrow on bisantrene studies, but I am not sure any of you would like the effect us raising $200m would have on the SP and your investment.