Ann: Bisantrene shows potent anticancer activity in AML models, page-59

Hi Dr. T,

A few questions from the results presented in the poster:



1. What is the current understanding of the independent inhibitive effect on CHK proteins? Is this somehow related to FTO? Everything I have read so far is that ALKBH5 regulates this pathway, though I do note one paper lamenting that an FTO inhibitor was not found to have 'crossover effects' into ALKBH5 inhibition.

2. If CHK inhibition is occurring through bisantrene, do we have any idea how selective this is?

3. Would you be able to expand on the synergistic MYC activity? A recent paper that has received some media attention highlights the community's interest in this pathway and it would be interesting to see how our results compare (though I am unsure how to do this).

4. Many of the pathways are measured in the combination condition, but not in either of the independent condition. Is this due to limitations in the ability to measure some of these, changes to the experiment, or resources?

5. I note that the dosing frequency for bisantrene was twice per week. Is this the preferred frequency based on past results or will this be further explored prior to the P1 trial?

Apologies if these questions are way off-base, I've been trying my best to understand all the great new information from these results from a layman's perspective.