For a while now this company has been wrongfully bashed for...

For a while now this company has been wrongfully bashed for reasons that are incoherent by people who's motives are well known. So it is refreshing to have some real concerns prompting positive discussion and I do appreciate your rationality.

First of all, XanADu initial results were only released 12 months ago, not 2 years ago. This is no excuse, 12 months is still a long time without answers but I expect there is a lot to go through especially with XanaHes so I am willing to give them the benefit of the doubt for that. I would like to point out that the difference in plasma concentrations of Xanamem on the 10mg Vs the 20mg. 10mg peaked at approx. 40 ng/mL as opposed to 18mg and 25 mg which peaked at approx. 140ng/mL and 240ng/mL respectively. 20mg was not trialled in this data but you can see that the increases in dosage do not yield linear results. I also understand that increased plasma concentrations differ from enzyme saturation and the vast differences could mean nothing, though we wont have this data until the target occupancy study is complete.

Dr. Sarah Gregory raises concerns about correlative vs causative and concluded the results were mixed but there was promise. Correlations were increasingly apparent with older subjects which I found interesting. The other thing I found very interesting was the fact that the HSD11B gene was prominent among AD subjects compared to controls. As you know the HSD11B gene upregulates the production of the enzyme which would theoretically correlate to higher intracellular cortisone catalysts.

Unfortunately the concerns you have raised are very valid, the investment does involve risk and that's reflected in the share price. However, consider the early study in healthy elderly men which improved verbal fluency with carbenoxolone and the recent trial with healthy elderly subjects at a higher dosage, which yielded terrific results within the expected period of time and somehow showed a level of significance despite the sample size. Investors would speculate it's a coincidence but that is exactly why we have significants values. The reason that I am so confident in the upcoming trials is because they have suggested they will be trialling on mild cognitive impairment. What they are actually trying to do here is replicate XanaHES with a "disease population". I also like the idea of running cognitive trials on other indications as that also very closely replicates our previous successes.

I think we all know that AD is a symptom lagging ailment and by the time you are losing your memory the damage has already been done. Bill has previously mentioned that by the time you begin to show symptoms you are already running on only 30% of your neurons. I haven't fact checked that but I believe that with mild and moderate Alzheimers, unfortunately the horse has already bolted, This could have had something to do with Xanadu's failures.

Also

1. Cushings disease Does show correlation to cognitive decline and Does show correlation to dementia
2. Glucocorticoid treatment Does show correlation to cognitive decline

3. YES. High cortisol cognitive issues are quickly reversible unlike dementia and AD, you are right. And that's the point. Whether its correlative or causative, elevated cortisol has a negative response, that much is well understood. if it is correlative then wouldn't you want to stop that positive feedback loop to potentially buy a few months or years time of remembering who your loved ones are? And if by some chance it does happen to be part of the cause of AD (as the CSIRO have suggested), then we have hit the jackpot.

Cause/Correlation - doesn't matter.