Anavex Life Sciences Corp (AVXL)

[Steady_T]

From slide 15.

APOE e4 carriers are 2.4 times more frequent in the High AV2-73 concentration cohort compared to Low concentration cohort.

That is very interesting since according to the NIH 40% of the people diagnosed with AD have that gene variant.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3726719/

Why that is interesting is because you would expect the ratio of APOE e4 subjects to be about the same as the general AD population, but according to the CTAD data it is 75% of the High concentration cohort.

The same distortion of distribution is shown in the Low concentration numbers of 30.7% APOE e4 carriers in that cohort. They are under represented compared to the AD population.

With the small numbers of subjects this could be a statistical fluke, but it does stand out.

What this suggests is that possessing the APOE e4 variant somehow affects the blood concentration of 2-73.

To give a little perspective on the statistical impact of such low numbers of subjects. 6 out of 8 patients in the High cohort are APOE e4 carriers. That yields 75% ratio. If just one more APOE e4 subject had been assigned to the low dose group the numbers would shift the 5 of 8 and a 62.5% ratio. The Low concentration numbers would shift from 30.7% to 38.5%

Remember that these people were assigned to drug doses prior to acquiring the genetic data so there was no effort to equally distribute the APOE variants tween groups.

The foot note on slide 13 says Plasma concentration of ANAVEX 2-73 is correlated with the administered dose.
It does not give the strength of the correlation which would allow for an understanding of the dose/concentration relationship. If it was a strong correlation I would expect the wording to be "shows a strong correlation" but they don't use that terminology nor do they give the R^2 number that specifies the strength of the correlation.

Slide 8 lists the administered doses as 10mg,20mg,30 mg,40mg,50mg.
Slide 12 shows the concentration groups as low,medium,high. Again the disconnect between dose and concentration shows up. Are the N=9 people in the low concentration group the ones receiving 10mg,20mg? We don't know and can't tell.

Investor I have to take issue with your interpretation of slide 14 about the meaning of the concentration groups meaning high is the 50mg dose. That link is not clear for the reasons I have stated above.

I have the same argument with your interpretation of slide 15 being the 50mg group for the same reasons. It could be that the APOE e4 people metabolize 2-73 differently.

On 2. The confusion between dose and concentration shows up again.
You say "How else could we still have 8 in the High Dose group at 148 weeks!" That is 8 in the high blood concentration group. We don't know what dose they were taking. Anavex has made this data difficult to interpret by switching from does to blood concentration.

Investor, Thank you for taking the time to make that post. I found it very helpful.