This may be a disputable source however the 30% being the...

This may be a disputable source however the 30% being the minimum required was a quote in an email from Bill 2 years ago. I will put in his full response because the Insulin degrading enzyme answer may be interesting to some.


"The IDE hypothesis is just that, a hypothesis that brings together a number of threads of data. We have yet to definitively prove it, and demonstrate the same results in humans as we saw in the Tg2576 rodents. Also, this speaks to an unexpected finding related to amyloid mobilisation that is not the primary mechanism of action of Xanamem. To detail this amount to science on the website will overwhelm the average non-scientific reader. The point you make about us lacking confidence in the data is fair enough – this is after all a hypothesis that still requires verification. As to your question about ABT384 – this was an AbbVie 11B-HSD1 inhibitor that was developed as a treatment for diabetes, and as such targeted the enzyme systemically in the liver and adipose tissue. ABT384’s enzyme inhibition alibility isn’t in question, however, when the drug was studied in Alzheimer’s disease, it was quite clear that its brain penetration was inadequate for the purpose. On current published data the estimate is that the amount of ABT384 that crossed the blood-brain-barrier was adequate to inhibit the 11B-HSD1 enzyme in the brain only up to 11%. We know that 30% inhibition of the enzyme is the minimum required. Xanamem, in contrast, crosses the blood-brain-barrier in concentrations that achieve a 50% inhibition of the enzyme, with the 10mg dose used in XanADu."

Regarding the significance, it bothered me somewhat also, however keep in mind reaching any level of significance on objective outcomes is quite difficult given the small group of 32(?). I recall Bill saying in the 2018 investor roadshow that Data and Statistical analysis advisors seemed to think that the population size needed to be over 160 to achieve significance. I'm sure you know this already but for those who don't, significance is simply to prove that the positive results did not happen by chance. It is quite impressive that in the small sample size, it was that overwhelmingly positive among the group that it received less than 0.01 and less than 0.05. keep in mind the 0.09 is not classed as statistically significant. 0.05 is the minimum standard. therefore we only achieved 2 statistically significant outcomes out of 6. but the 0.09 would likely trend to a statistically significant number given a larger cohort.

And lastly, I agree, it is completely backward the way that it had been done. Though the target occupancy study is only very new, so this could not have been done earlier. My number one concern is that 10mg/day is in fact a sufficient dose as proven by the TOS. So there goes the narrative that the dosage was too low in XanADu. In hindsight I think Mild AD is too far gone for a 12 week trial. It is quite difficult to combat a decline in brain mass with nothing more than a 12 week cycle of cortisol reduction. I am much more hopeful with xanaMIA over 24 weeks.