I mentioned in a post prior to our announcement of the PDD approval in Spain this:
From post 156646 on 7/8: “If the PDD trial in EU comes to fruition, we are back in the driver’s seat. Don’t be surprised to see us move on that indication hot and heavy - we are racing on foot now”
The next day, we announced approval of our PDD trial in Spain (7/9/18), so I posted 156808 thanking our CEO for this move and stating it was the next chess move, no accident.
On 7/18/18, post 158337, I posted one reason I thought this was our key strategy: “I’m sure I posted this link twice, here’s a third try - Not sure why this one isn’t getting across? Please read the article even though it is long and scholarly. I believe it’s the lynchpin in this whole standoff. The KEY is that once PDD gets approval by EMA, our AD drug can VERY EASILY be approved based on the extension alone! NOT A DRILL! The larger trial being set up down under will be a post-approval confirmatory trial! Do yourselves a favor and read this. And second original post #154479 “
And, the link to drugs approved with and without Random controlled trials (RCT’s) in EMA vs FDA. Once a drug is approved for any indication, it can easily be approved for another indication without another RCT based on an extension of another trial alone. (That gets us AD.)
This same post also addressed the reason DZP was being included in the PDD trial: because according to the article linked, the EMA approves drugs much more readily if they are a component in combination with a drug which has already been approved. It is assumed that some efficacy is already built in and that as long as the new component is safe, the combo will have some effect which has already been proven. So, that was in response to the discussion as to why we would include Anavex plus in the PDD trial which was a much discussed point on the message board. (This gets us approval and IP protection - more on that in another post...it happened again! Biogen was awarded IP rights in a case for Avonex- their big MS drug, last week, when a judge overturned a decision by a Federal Jury from March which ruled in favor of Serono and Pfizer for the IP rights.)
Now, as to the reason this trial is the best chess move on the board at this particular point in the game:
The PDD in Spain is an ideal starting point for all 3 trials. I had not thought this in the beginning but as Missling reportedly said I think I am seeing why he is doing what he is doing. Many here have correctly suggested that the crux of the matter begins with our finances and share price. Missling must work within this including grants which offset expenses as he is well aware. This is no easy task. I believe that by trying to recruit for 3 separate trials of varying sample sizes, in various locations, with different numbers of sites participating, and with differing lengths, means timing is key. The thought about Rett is: would the benefit it would bring us in revenue or a partner be enough to support the other 2 trials if Rett concluded first? I think Missling decided that the cost of doing that trial versus what it would signify about our drug’s capability (transferable to AD/PD) might not have been the best use of bootstrapping us to approval without dilution, nor might it be convincing enough to tempt a partner or buyout. I’m just guessing but I could see where it might fall short of hoisting our entire objective for the other indications for A2-73.
But, PDD is correlative to AD in the dementia component and it has crossover into motor skills for the knowledge of how it might help our Rett girls. So, it, being another short trial, which touches on both of the others, should be a great indicator of both if not either of them. Also consider, if we glean from the PDD trial that motor skills improve but cognition does not, we still have an indicator of our success with Rett. If it improves cognition but not motor skills, we know what AD may look like. If it helps both... we have tremendous leverage using one short trial with the moderate sample of 120 pts. Not extremely costly and should get help from the Fox Foundation so this would be where we want to start - in the middle and go in the direction of greatest success - hopefully both. But, we should have very great interest at that point.
My thought is, does it even make sense to begin the AD trial or the Rett trial before we have some idea of the PDD outcome. As we know, it could be negative for both endpoints - but, Missling has always believed in failing fast - why prolong the inevitable? In which case perhaps we begin safety on 3-71? Just a thought.
However, if we begin dosing the PDD and AD trials, we could be in for a negative outcome which would not bode well for the ongoing AD trial. I’m pretty sure Missling said that the same gene variants would be used in all three indications which would leave no room to suggest that it might work for one indication if it has failed for a previous one. However, it gives every reason to believe that it WILL work for others if it does succeed in the first one. In fact, if so, we could gain approval for other indications simply by demonstrating they have the same biomarkers - precision medicine. This is the point of including those with and without the gene variants we identified in the trial. It is to enrich them to be used to establish biomarkers, in addition to efficacy, in order to save duplication in future indications - short cut. At which point I think we will be in the best position possible.
Also, with the rolling recruitment and dosing, although we estimate the entire length of trial and enrollment, we could well know something a little sooner based on the performance of the earliest enrollees. Interesting and important to note: we have already enrolled on 9/9/18, without a PR...we are racing on foot now. Look for some swift actions out of nowhere, imo.
Another thing I mentioned in my post regarding Illumina’s database which I now know is the UK’s Biobank: in the webinar on their site they mentioned that there where an incredible number of genetic matches for Parkinson’s disease when compared to those for Alzheimer’s and rare diseases. Also, they stated there was very little overlap between PD and AD genetic mutations. I have to think that the fact that Missling is confidently pursuing the AD/PD and Rett with the same mutations must be very strong evidence that these 3 matched up on the SIGMAR1 wild type and COMT genes. He could not be so encouraged about the findings if they did not.
I think we will know about all 3 indications once the PDD early enrollees are up to the MTD and have been dosed for 6-8 weeks. Improvement should be observable and although the trial will continue, I believe that is what I referred to in one of my posts as having “runners in scoring position”. We will know much more about what the outcome will be and I think at that point all potential deals will come forward and we should see our big run up which will continue until we have a very nice deal in place. I think we could be looking at something be end of this calendar year or early in 2019. Based on Sept. 9 enrollment begun, if you allow 14 weeks for total enrollment, we should have half enrolled and dosed by end of October and observable results will be seen by end of year although the trial will not be fully concluded. I think at that point - maybe early October, if we have responders, Missling would begin the AD trial with the knowledge that it would be a success. He said in late July that he hoped to have these trials running within a couple of months. So, early October would be just about 3 months and not off the mark. And it would still allow him room to decline going forward with AD if PDD did not look promising. However, there is really every reason to believe it will be because of the progress of the patients already and still in the AD extension.
Folks, I think we got this. I would not get up and type this on a Saturday morning if I did not think it had merit - I have way too much regard for my sleep than to squander it, scout’s honor .)
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