There is not enough data to argue that TUSP is less effective at the higher doses. Is it possible? Yes. I am not too concerned either way. We have active doses.
Regarding the sub-saturationl dose (hypothesis), it is not proven, but makes the most sense. Over the past years I have done literature searches on the individual TK's that Lux and TUSP inhibit. You can find papers that talk about syk, Jak, aurora, met, PDGFalpha, flt and other targets having roles in AML. Hitting multiple pathways or MOA's simultaneously is the premise behind drug combinations. Having multiple targets within one molecule is fortuitous. It is not a big leap to imagine that hitting several of these simultaneously my have synergistic effects.
If you look at the Lux IC50 AML plasma cell dot plots in vitro you can clearly see that the addition of venetoclax lowers the median IC50 of Lux significantly. Without checking, I recall the the median Lux IC50 alone was around 1 microM (for the plasma samples tested). With venetoclax the median Lux IC50 was around 0.6 microM.
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