@Davisite, firstly congratulations on your appointment to CEO. Similar to many others I was very glad to see your appointment coincident with the updated strategy, and I truly hope you can keep the team together for the next couple (or more) years and steer Race to a successful conclusion, in whatever form that may pan out to be. It's a big responsibility, and a lot of expectations are riding on your shoulders (as I'm sure you know), so thank you for taking on the job.
Now that's out of the way, I have a few questions about the strategy update that I haven't seen answered yet (apologies if I have missed it somewhere).
1) The pre-clinical cardio-protection studies demonstrated a cardio-protective effect against doxorubicin specifically, however the Phase 1a/b all-comers trial will admit any solid tumour patient where anthracycline use is indicated, not specifically doxorubicin. I'm not sure how many anthracyclines are in widespread use that will likely be encountered, but do all cause anthracyclines cause a similar level of cardio damage by a similar mechanism to doxorubicin? Do we know that Bisantrene will work as well against cardio damage caused by anthracyclines in general as we do against doxorubicin specifically?
2) Are there any types of cancer that we know of where Bisantrene has a 'negative synergy' with anthracyclines? For example, perhaps cancers that 'underexpress FTO' (if there is such a thing). i.e. is it possible in the all-comers trial that any patient may be worse off (from a cancer perspective at least, not cardio) with having Bisantrene included in their treatment regime? Do we have a way on screening out these patients if so and if not could it cause an issue with gaining ethics approval?
3) Is the VO2Peak 'revelation' the reason that the non-interventional arm of the cardio-protect trial was abandoned? I ask, because at the time this decision was initially floated in one of Damien's updates, you seemed sceptical and unsure of how they could cancel it. You were awaiting on further detail to be provided in the (first) strategy update (which then actually didn't mention VO2Peak at all from memory) before commenting further. However, recently you elaborated that the VO2 peak information was around at the time you were CSO (i.e. prior to your departure). Was it that the full impact of the VO2 discovery was determined after you left (perhaps you did not fully appreciate it at the time?), or did they have some other reasoning for the initial cancellation of the non-interventional arm?
Thanks in advance.
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