Replies to post #354361 on Anavex Life Sciences Corp (AVXL)

[falconer66a]

But after 14 weeks...?

Yes, the four data plots show very significant score improvements for the 14 weeks of the trial. Those, alone, when confirmed in the Phase 3 study, will prompt FDA approval of blarcamesine for Parkinson's disease dementia.

But two related considerations. First, the trial ran for only 14 weeks. But the therapeutic dose (50mg) was not attained until it was titrated up to that level, starting in third week. Simply, the targeted 50mg dose level occurred only for the final 11 weeks. But even in that shorter period, the favorable therapeutic scores were dramatically increased.

However, secondly, what evidence is there that this 14/11-week dosing period is optimal? In the trailing weeks were the score increases tapering or leveling? Or, had the trial continued for another three months or more, would the scores have continued to improve?

Favorably changing neuron physiology takes time. In this trial, 14 weeks were allocated, with incontrovertible success. But in chronic dosings, over much longer periods, months, even years, there is the prospect that healing (sorry, had to use that term; it applies) might continue; all the way to normalcy.

Four questions for blarcamesine:

1. Can it slow the progression of various CNS diseases?
2. Can it stop the progression of various CNS diseases?
3. Can it reverse progression of various CNS diseases?
4. Can it prevent the onset of various CNS diseases?

In this study blarcamesine not only slowed or stopped the progression of Parkinson's disease dementia (PDD), it reversed it. People taking the drug got better.

It stands to reason, therefore, that were there an early, pre-symptomatic detector of PDD vulnerability, blarcamesine dosings could be prophylactic, preventing the onset of the disease altogether.

What, then, are the probabilities or possibilities of similar effects of blarcamesine in Alzheimer's disease? Will it be shown to not only slow or stop Alzheimer's progression, but, in fact, reverse it? Even better, will it actually prevent the disease?

Very likely, on all accounts. Let the trials begin.

[end2war]

Thank you for you analysis. I especially liked your comments quantifying the results and your comparison with ANVS.

[RedShoulder]

My notes on Misslings CC this morning:

Rett Excellent in 2nd half of year.

He was grilled pretty good on the change in end points for Rett.

Meeting with the FDA on the Rett adult, and will consult on the Excellent trial. Sounds like he is open to what they suggest, maybe going for approval on the adult and miss the voucher (IMO I think he will wait for the Excellent study to complete and get the voucher since it will be so close in timing).

Will discuss Rett and adult with the FDA around the middle of the year and before Excellent completes.

Does not think addition pediatric studies will be required.

Will move forward for approvals in parallel of not only FDA studies but also other countries where the study was performed.

AD last patient dosed in the middle of the year, and "data released definitely in the 2nd half of the year, and there will be no delay - absolutely".

PD "extended data" is still ongoing will be completed in the next few months .

They are going for 2 separate studies PDD and PD.

"We are currently designing the PDD and the PD studies as we speak" and do not have to wait on the extension data to design the trials, they have all the data they need to do that.

PDD/PD The gut microbiota was measured before and after the trial. It will be measured in the extension part of the trial.

Will be moving forward with Fragile X next, because of the robust data done on animal models. Plus the Fragile X correlates well with the Rett Syndrome.

"We have other indications that we have not mentioned yet." "Right now we want to focus on the indications we have right now."

With 3-71 we be moving forward with Fragile X, schizophrenia, and Alzheimer in Ph-2 studies.

2-41 we are waiting on 2-73 data before moving forward.

10-66 showing reduction in visceral and Neuropathic pain. Currently adding preliminary data to this drug.

"Building up a team for marketing and sales for Rett especially in the US and considering other regions."

Will be to partner for Parkinson and Alzheimer.

"We are already in in midst of execution this expansion" "We are open to partnering international areas like Asia where they cannot reach quickly, or build up quickly".

"We are broadening our scope with additional expertise which helps us moving forward in the direction."

"We have on going partner dissuasions but don't want to expand on that yet because it is premature, and also because it is an advantage to Anavex and shareholders to partner when they have the full data, that when we get the most featured outcome and beneficial out come and the most benefit in a partnership, other than doing it too early."

The moderator did a good job with the questions. I thought this was Missling's best CC to data IMO.

(I may have errors, it is difficult to listen and take notes at the same time, feel free to correct nay misquotes.)

[RedShoulder]

Peter, thanks again for you outstanding analysis:

Conclusions

The improvents in all four parts of the UPDRS are consistent across all measures and are well separated from placebo.

Parts I and II are much more easily affected than parts III and IV, yet the most significant therapeutic effect can be found in the latter measures for Blarcamesine. A very or the only effective drug.

This status of Blarcamesine is corroborated by the results from $ANVS ‘s Posiphen with lack of significant response in parts III and IV.

Parts III and IV show very stable characteristic for the patients over time. Nevertheless, Blarcamesine (mean of improvement of the sample) can improve them over 10 times better than current drugs. All in short duration of 14 weeks.

Parkinson’s is etiologically connected to atrophy of motor neurons in the brain and periphery. By restoring or ameliorating the motor skills of patients, Blarcamesine seem to address the disease as understood by now, not just the symptoms.

The implications from all the parts suggests disease altering therapeutic effects for the patients. The unanswered question is “Would Blarcamesine administered earlier stop the progression of the disease or even reversed it, at least for some?”

Link for full analysis:
https://piotrpeterblog.com/2022/03/16/looking-under-the-hood-of-pdd-phase-2-blarcamsine-results-avxl-anvs/