Hello @RaceOncology, I have a few questions regarding the...

Hello @RaceOncology, I have a few questions regarding the announcement and trial that I hope you can help with.

Firstly, could you please clarify what is meant when you say that Extramedullary AML patients have no clinically approved treatments but that azacitidine is a standard of care drug. Does this mean that azacitidine is approved for other indications but its use in Extramedullary AML is off label, and it's standard of care even though not approved because there is nothing else? My limited googling was unable to provide me with an answer that I could understand.

Secondly, inferring from the announcement, is there are essentially three groups of patients that make up the patient base?

1. Patients who are able to tolerate high intensity chemotherapy in general. These are probably people early in the treatment of their cancer, having undergone minimal previous cycles of chemotherapy.
2. Patients who have reached the limit of non-Bisantrene chemotherapy due to heart damage, or perhaps have pre-existing cardiac damage from other causes, but could tolerate further high intensity treatment with Bisantrene alone but not other chemotherapy. These patients would probably be further down the road with having tried other treatments and their disease has likely progressed further than group 1)
3. Patients who are unable to tolerate a high intensity of any chemotherapy (anthracyclene, Bisantrene or other), as they would be unable to withstand even the less severe symptoms that these drugs cause. I assume these are probably people in a very late stage of treatment and overall very unwell with limited options going forward.

Based on those groups, would Stratum 1 patients for the Extramedullary trial be composed of people from group 1) above, group 2) above, or both groups 1) and 2)? I am wondering whether group 2) would be excluded due to the use of azacitidine in the consolidation treatment which (again from my limited googling) seems to have some potential to cause heart damage itself and so may not be able to be used if the patients have already undergone extensive chemotherapy previously. If the patients for Stratum 1 then are going to be primarily from group 1) above, am I right in assuming then that these patients would on average be in a better starting state, and therefore hopefully more responsive to treatment, than those patients who were treated and responded in the Sheba trial last year?

Lastly, for the patients in Stratum 2 (which are coming from group 3 above), is it fair to assume that these patients would on balance be in a relatively worse state than the patients treated in the Sheba trial, who obviously were able to tolerate high intensity chemotherapy in that trial? If this is the case, is it a double-edged sword in that it is potentially the hardest group of patients to try to evaluate how effective FTO targeting is, however if positive results are achieved it would mean so much more precisely because of that? If that is true, what is the risk that this first attempt at FTO targeting is less successful due to the very difficult patient base that it is being evaluated on? I do realise we have to start somewhere of course.

Thank you for your time.