For Biogen the Alzheimer’s programme would have risk adjusted revenue expectations built into the shares price. That risk has now materialised wiping away any expectations of future Alzheimer’s earnings. Not sure $BIIB have much else of similar earnings potential in the pipeline.

Doubt it brings any immediate benefits to $AVXL, but longer term should Anavex trials prove successful the stages is more set for the winner takes it all or least facing much less competition.

Maybe Statnews has hired AF to do proper journalism?

Bigger fish to fry, so he assigned some 3rd graders to $AVXL?

There is always the unknown and unexpected, like some form of deal, but in the main the dead money scenario seems the more likely.

The answer to both of your questions is conceivably yes, but I can't really tempt a confidence interval on those presumptions.

My sense is though that not getting the preferred voted through was a spanner in the works of something.

There was a time when the PR focus seemed to shift towards A3-71, which might be the better drug compared to A2-73 perhaps because it would require lower dose - who knows.

Time will tell.

Well back at my computer and could skim through the animal models of epilepsy reference you provided.

Also I believe your calculation is right. That is, 100mg/kg in a mouse would mean 160mg/kg A2-73 in a human of 20Kg.

Given below paragraph it seems the MECP2 mouse model may not be a reliable indicator of dose translation to humans. That is the mouse model tends to over estimate the equivalent human dose, whereas a Rat model might be better.

Dose could be a potential issue and if so we'll have to see how Anavex chose to deal with it and what the FDA will approve. There may be several options I imagine e.g:
1) dose level may not be as big an issues as feared ref. mouse model issues
2) administer a lower dose more often
3) different scenario in combination with existing seizure control drug

At a mouse dose of 100mg, it would mean 8.1mg in a human.

If that is really true there seems no tolerability issue.

Good and so some are presuming 30mg scaled down to little girls is not tolerable, on what basis?

All I know is that the bulk of research into Sig-1R agonism highlights it is safe and tolerable. Why this should be any different with a faulty MECP2 gene is a good question.

Reduction in seizure frequency.

based on Xena's post 30mg looks good, which I presume is a mouse scaled human equivalent.

We really do not have any concrete data to suggest that 30mg was not well tolerated in frail old AD patients.

I still have an enquiry out with IR and Clayton from Trout Group, repeated today, just see if we can clear up the dosing questions relating to Part B.

Why base the dosing of Rett girls on mouse data when we have data from multiple dosing schemes in humans?

You are not and I should have posted as a new message.

I wanted the comment broadly aimed at the proposals that A2-73 is much less tolerable than all the data presented tells us and that this is forcing Anavex to reduce doses below the threshold that gets the most patients into the 4ng/mL therapeutic window.

If that turns out to be the case, we have been mislead.

Well in agreement with the FDA the A2-73 P2a trial met all it's endpoints and offered unexpected therapeutic bonuses. All patients then opted for continuing on A2-73 going on for 3 years, so not quite sure how you would reach a conclusion that the data does not support a P3 and the rest of the pipeline holds more promise.

The other pipeline compounds are all pre-clinical, don't we know less about them than A2-73?

Ok thanks.

Just a belief or substantiated in some research and reasoning?

You must have done some interesting science DD, care to share?

The scientists at Lund university, Wayne State and several others, it turns out have just researched and published about the life and whereabouts of red herrings.

The quest to promote the idea that A2-73 is not tolerable forcing low dose in the P2a Part B trial and beyond has no basis in fact.

Wow, that ripoffreport website looks really reputable and informative with awesomely effective red font. Another piece of astoundingly good DD, thank you!

Likely a little less than in the AD and PD trials in adults.

Here is slide 24 from the Jan 2018 presentation wit the full AE info.

Grade 1 AEs require no intervention!

based on this I find it unlikely that Safety and Tolerability is a major issue and, as you probably have heard, Missling tends to highlight the safety of the drug also supported by the bulk of Sig-1 research.

The above quote in the light of the data published can hardly be taken to infer that patients broadly struggled with dosage levels therefore making it hard to reach 4ng/mL.

I continue to content, perhaps wrongly, that patients were kept in 4 groups pre-assigned to 10m, 20mg, 30mg and 50mg respectively throughout Part B. The population dosing and response data thus gathered is perfect for finding the standard minimum dose to use in future trials. That dose will likely be adjusted for age/body weight for the young participants in the Rett trial. Thus, it just means that the company needs to find the standard minimum dose, not the standard maximum dose that will get the most patients into the therapeutic window.

None of us knows what feedback the FDA had on the Rett IND, but anyone is free to promote that it was something approaching a doomsday scenario.

GREAT presentation. M sounded like he had just had a great nights sleep and a freshly brewed coffee. It was a coherent story, with compelling investment thesis and M had excitement in his voice. A CEO who believes his company is on the cusp of a major breakthrough in CNS diseases and tried hard not to sound too pumped. The applause from the people sitting in the room said it all. (BP is worried.)

Can you substantiate the above statement, or is it your conjecture?

Was the Rett IND put on hold? No don’t think so. The FDA had feedback or perhaps in fact Anavex withdrew the IND to amend it for inclusion of genetic findings to the protocol.

That’s because Alfred Health does not have any need or wish to disclose what it cost them to run their trial. If you examine the annual reports of Alfred Health you will see they do not breakdown their CRO cost to individual trials.

Missling can’t tell cause he doesn’t know.

I would think it the norm rather than an exception that Alfred Health would again use their budget to run a confirmatory trial with an AD drug they found promising in the P2 trial they paid for. I mean what would be the point of stopping at P2?

As I understand it the Australian government through Alfred Health running the trial has pay whatever that cost.

Anavex have borne the cost of the drug supply and probably some other smaller overheads for which they receive a tax incentive.

Presumably that tax incentive only becomes useful if some day Anavex makes a profit in Australia.

I predict it will be either fine or game over this year.

Some have remembered to take profit along the way.

If our bags starts filling again this year remember to take some profit along the way.

I meant roughly 1/5 - 1/4 doing well out of the remaining overall trial population i.e. 25.

Hence we might assume a good proportion, with the right inclusion genetics, will do well once all on optimal dose.

It does and we also heard that the presentation embargo will not hold up any clinical plans.

It is not granted that the genetic inclusion profile is very narrow.

In the AD trial just under a 1/4 of patients responded well in the therapeutic window of 4ng/mL, but there were outliers. One responding well with low A2-73 blood contraction and 3 or 4 not responding on therapeutic concentrations.

If we assume, as I do, that the patients were in 4 groups each staying on their pre-assigned dose of 10mg, 20mg, 30mg and 50mg throughout Part B, then with everyone on a higher dose perhaps the percentage of patients in the exclusion group may be quite low, say 20 - 50%.

We know from the conf call that the genetic profiling is to understand response to therapeutic concentrations, not to understand differences in blood concentration - at least that is how I have read what is known.

Missling stated that the analysis is complete, so the question is which next scientific meeting will it be presented at.

So I guess we do not have any real evidence for or against, just assertions of opinion.

We will just have to wait for the presentation of the genetic biomarkers as that scientific meeting.

Grateful if you could explain why a genetic profile more likely to respond to A2-73 in AD would not be relevant for other indications such as Rett?

Check the 10Q and let us know.

Anavex has a monthly running rate eating into cash and tapping the LPC facility has allowed the cash position to stay more or less steady.

Once the share price again reach over $3, hopefully when the Rett trial starts, Anavex will likely resume tapping LPC to take the remainder of the first $50M facility.

Always enjoy your well researched and informative posts.