Excellent post, Steady.
The good news is that all of those concerns will be reversed if Anavex can prove effectiveness with their Rett trials. We already have excellent (partial) results from the PDD P2 study.
Now, we wait for the results from our Rett Trials. If proven positive, the MOA will be undeniable.
Biostockclub did an excellent job summarizing how this can happen. See below.
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Am pretty sure that what Missling was saying with regard to the 3 Rett trials boils down to a logically necessary fact:
The US trial which included adult patients on lowest dose (in trials) will read out first. It is necessary that this readout give the lowest limit in order for there there to be proof of a dose correlated response from the ADULT patient trials COMBINED. (Leave peds out for a minute).
The two adult trials can both have significant results (or not) but as long as they show even slight improvement over placebo, and remain safe, and the higher dose AUS reads out greater improvement than the low dose US study - we have demonstrated something noteworthy about our drug and likely actionable if best case - both doses are above placebo, or, even if the higher dose alone shows improvement.
So, look for the side by side after both trials read out to present our case. That’s what the FDA will be looking for and would likely gain an approval.
Additional proofs of theory will occur if the pediatric group performs better than the adults on both low and high dose because it would nail down an age correlation (earlier equals better for this indication, however, existing affected adults still have a drug of benefit).
Also, they will look for the Sigmar wild type to perform better in all groups and dosages respectively in order to show a biomarker correlation (prespecified across 3 indications(!) and doses).
That’s a lot of ways that the data must stack up in order for the theoretical stuff to add up (but not necessary to gain approval for this indication). But, if this all stacks up and proves out within each indication and across indications, would probably be one of the most airtight and convincing things that a regulatory drug agency has seen in a very long time. And - Never(!) in CNS.
That would be a Yahtzee.
So, it’s interesting to look back and see why this all had to be conceived and designed and funded and enrolled each step of the way exactly as it has been.
Across the board correlations will be a watershed moment for:
Patients
Investors - company owners
Partners
Company management and advisors who designed all
A lot of people will have “egg-cellence” on their faces for this set up, imo.
So, no giant individual moment for each declaration of very promising/pleasing trial outcomes (see Dag Aarlsand’s comment) until the market catches up and sees what was done (I’m thinking the market could be seen as the last one in the room to figure out the answer. As my uncle, the mailman, who was the last one to finish his route every day, says, “If you want to know why unions are necessary and good just remember me - I’m the guy the unions are protecting.”)
So the efficient mailcarriers who all finish their routes by noon and never misdeliver are the investors who got in early (it’s still early). At some point down the road, we will watch the “folks the unions protect” come around - they are just a little later than the standard and bring the average down when it all gets tallied. That’s why we are behind the curve of where we could be: we don’t wave red meat (juicy PR’s) in front of the carnivores who jump on anything and are lowest common denominator indiscriminate marketeers - Pavlovian response - run on anything.
Our investment is a true long term arbitrage. You could say it is an accurate correlation of the company’s value as gauged by savvy investors, or you could see that it is in the bin which has accidentally been marked wrong on the price tag. Can be gotten now cheaply due to “market error” which, when corrected, will give you the arb pick up.
Legend: the term “when corrected” means once it’s all been proven and a blind person could see it. Then. That’s when you’ll be glad you owned this underperforming stock. There’s a mental perception gap - people who see what’s going on (Missling is even stating it, but isn’t permitted to “pump”. He simply says we have 3 trials trying to show the same thing in CNS: figure out for yourself how big that will be...?!) and, the people who just don’t see it (yet, but will). That’s when the gap will fill... and, along the way as more people catch on in real time. Market reaction is hair trigger timing from the gut, market understanding/epiphany/wisdom happens in stages as people “wake up”.
Point of focus near term:
Missling isn’t saying that US Rett adult trial results will look bad, only that, whatever they are, even terrific(!), they HAVE to be the very lowest.
If these first Rett results are good - clean out your freezer; venison coming.
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