Anavex Life Sciences Corporation (AVXL) Options

One wildcard no one is mentioning is other indebted developed countries may follow the U.S. and begin to reduce their government employee headcounts.
That could slow down the EMA among many other things.

Bingo! With Anavex it is always Feb'ish if ever...

NWBO is supposedly in the same sort of approval track with the UK, but we're well beyond day 300 if you want to start with final validation, and around day 400 if you go back to the original submission date.

The point I'm making is that other than the FDA which sets a PDUFA date after they accept a BLA or NDA that's normally 6 months after acceptance, or one year if it's not high priority. A big difference is that if the FDA isn't going to meet their date, they reschedule it. The others don't seem to provide any guidance, at least not anything official that must be released by the companies.

There is no doubt the regulators come to the company with questions or comments that must be answered, so they're aware of the status, but there is no commitment on when they'll finish.

I'm no fan of the FDA but they usually deliver something at the PDUFA date, or before. It may be the dreaded CRL letter, but if you're not approved you know why.

Gary

210 working days = ~10 months (250 total working days in a calendar year in Germany, for example.) So, 10months plus 3 months (Clock Stop 1) plus 1 month (clock stop 2) = 14 months total. This means no MAA approval is likely prior to end of February 2026.

Yes, a miracle could happen and there may be no clock stops but probably people should not invest based on this likelihood.

Per ChatGTP, the List of Questions (LoQ) typically occurs on Day 120, triggering the first Clock Stop. If there are items still unresolved, a List of Outstanding Issues (LoOI) typically occurs on Day 180, which triggers a second Clock Stop.

He is not applying to the FDA until a decision from the EMA. He has never had any discussions with the FDA about AVXL-2-73. He acts like Chicken Little when it comes to the FDA. For the FDA, he has to request a Type B meeting, which takes three months to schedule. He’s not even talking about it.

After 210 calendar days, we will get the LoQ. In the next couple months that follow, we will either get a PR indicating we submitted our responses, or will hear in the next CC that we either submitted or declined to.

Google “what are EMA working days?”

The answer I get is Monday through Friday 8:30 to 6:00

In the EMA language they appear to use active days and working days as the same.

Missling has been vague on when to apply for a NDA
More in terms of future talking to the FDA rather than currently doing so.

Not sure problem is getting past the failed ADL with agency backing down from sticking with it failing a primary objective and recognizing in early AD it is an unreliable marker.

May just be time to get all the paperwork in order.

It's 210 calander days, they just refer to it as "active days" to distinguish from clock stopped days.
90% of apps have a clock stop 1 and on average clock stop 1 lasts around 3 months. In 60% of cases there is a clock stop 2, and these last 1-2 months on average.
With no clock stop 2 looking around Oct, if clock stop 2 then Nov/Dec.

210 “working days” is 42 calendar weeks.
So if no added time at the two stopping points that is 101/2 months from start of evaluation.
That makes it mid October at the very earliest for approval.
My guess late November most likely.

I hope the company will tell us if there is added time at the stop points but I highly doubt they will.

For us the best news will be no news, since if there is early news it probably will be bad.

Anyone thinking we see an NDA come April.

Yes, Avisol is staring to back way from its bearish position. Now he is thinking of taking a small position. In a couple of months he will see a way to come back and mention he has taken a position based on his analysis of the OLE and, perhaps by then, the rejection of Lecanemab upon review by the CHMP. Several months after that he will boldly admit that he is cautiously recommending the stock and buying a more significant position -- albeit will the price much closer to 30 than to 20 -- since Blarcamesine had passed the first clock stop at the EMA and Avavex had gotten the green light to file at the FDA. Should the readout of the Phase 2 trial of 3-71 on Schizophrenia be successful, as many of us believe it likely will, he might even give a full fledged recommendation with the stock at 40...

Great video featuring Dr Marwan Sabbagh and others discussing Alzheimer's effects
https://www.lilly.com/news/stories/reaching-for-the-sun

Blarmamesine needed Now!

Take a small position and make a small profit. This is going to 4 digits. Just a matter of time.

Fair reporting!

"Anavex: Looking At Different Statistical Approaches Before EMA Opinion"

Feb. 14, 2025 6:02 PM ET
Seeking Alpha
Avisol Capital Partners, Investing Group Leader
https://seekingalpha.com/article/4758654-anavex-looking-at-different-statistical-approaches-before-ema-opinion

(It's a long one folks, but pretty comprehensive reporting....positive in the conclusion)

Summary
Anavex Life Sciences Corp.'s stock surged over 50% due to EMA's acceptance of blarcamesine for Alzheimer's review, marking a pivotal moment for the company.
Despite mixed trial results, blarcamesine showed significant cognitive improvements, meeting key endpoints, though it failed in functional assessments.
Financially, Anavex has a market cap of $720M and a cash runway of 8–10 quarters, with ongoing R&D expenses.
Given the EMA review's potential impact, I am considering a small investment, though not right now, acknowledging AVXL stock's high volatility and associated risks.
We are Avisol Capital Partners, a team of medical/biotech experts and finance professionals. We lead the investing group Total Pharma Tracker, where we aim to make the science of biopharma investing easily understandable to regular investors.

I covered Anavex Life Sciences Corp. (NASDAQ:AVXL) in December, after which, I note with some surprise (given the stock’s generally lackluster performance last year), that the stock jumped over 50% between late December and early January. The basis for that surprise positive performance was the company’s announcement that the European Medicines Agency (“EMA”) has accepted for review the application for blarcamesine, the company’s Alzheimer's disease (“AD”) drug candidate. The review period is 7 months, or July 2025.

This is major good news for the beleaguered company, which has been toiling with trial data and confusing market perception for nearly a decade. An even more major news would be an FDA review, but the EMA is a good second place.

Background
In my last coverage, I noted how the company “started” an MAA (the European application for approval over there) in January 2024, and submitted the application in November. It was accepted in December, and this I called a “precipitous” moment. This is because AVXL has a history of confusing and/or poor data in multiple targeted indications.

In the world of small-cap biotech, there is, arguably, no other company which grabs so much investor attention — both bullish and bearish — over its every announcement and every real or perceived problem. All of that long history comes to a head with a regulatory event like an MAA approval, and acceptance of an application is the first unchangeable step towards such clarity. There is no turning back from here. This will end in either an approval or a rejection — there can be no confusion about that.

The MAA was based on a Phase 2a and a Phase 2b/3 trial in Alzheimer’s. The phase 2a trial had two co-primary endpoints, in one of which the company succeeded, and in the other, it failed. According to a particular statistical analysis which I discussed at length earlier, such an outcome has to be considered an overall trial failure — so the phase 2a trial failed.

As to the phase 2b/3 trials, the data announcement was fraught with many errors, including basic Math errors and so on which, when corrected, could have an impact on the endpoint analysis. While the company said that the trial met the primary endpoint of improvements in cognitive function as measured by ADAS-Cog (and ADCS-ADL, see below), these errors I alluded to make the claims confusing. The company claims, among other things, that a) as to efficacy, they have numerical clinical efficacy compared to approved therapies, b) as to safety, the treatment does not need MRI monitoring and is safe and well-tolerated, and c), as to dosing, blarcamesine is an oral small molecule with a convenient route of administration. The CHMP will be the final arbiter of these claims. Recall that both trials had two co-primary endpoints and in both trials, the molecule failed the ADCS-ADL endpoint while succeeding with the ADAS-Cog endpoint.

Alzheimer’s: what clinical trials measure
There are three basic impairments in Alzheimer’s disease — cognition, function, and behavior. If you draw a line with these three metrics, and you mark the 6 stages of AD researchers have identified, you will see there is a progression in the stages according to those three impairments. Thus, preclinical AD, or stage 1/2 AD, does not produce obvious impairments in any of these three metrics, but can be detected through biomarkers in a research setting. Stage 3 is MCI (Mild Cognitive Impairment) due to AD, where the first early signs of cognitive impairment occur, but the patient can compensate for functional and behavioral impairments. In Stage 4, which is early-stage AD with mild dementia, patients can still compensate for functional and behavioral impairments as long as their cognitive decline is mild. Therefore, it is more difficult to measure functional impairment in early-stage AD than it is to measure cognitive decline.

Blarcamesine targets early Alzheimer’s. Its clinical trials have used both the ADAS-Cog13 and the ADCS-ADL scores. Now, the ADAS-Cog13 score covers all cognitive areas in dementia, while the ADCS-ADL is designed to evaluate daily functioning. It considers both BADL and iADL, or basic activities of daily living and instrumental activities of daily living. However, since there is progression from cognitive to functional/behavioral decline in AD patients through the 6 stages of AD, functional scoring may not be suitable to detect early AD. As research says:

Patients with early AD have subtle cognitive deficits and do not present with functional impairment; patients who are closer to the onset of dementia may have noticeable functional deficits that progress slowly, creating sensitivity issues with currently available scales. Furthermore, the extent to which an individual compensates for cognitive deficits and adjusts for daily activities is very variable. It is thus challenging to establish a clinically meaningful effect during a trial of reasonable duration.

In its draft guidance for trials in early AD, the FDA notes the following:
Historically, studies to support approval for drugs in the overt dementia stages of AD (Stages 4 through 6) have used an approach which required the assessment of both cognitive and functional (or global) measures as co-primary endpoints. The co-primary endpoint approach was used, in part, because the cognitive assessments used in the studies were not considered inherently clinically meaningful.

Recall that the AVXL phase 2b/3 study used this co-primary endpoint approach, although the trial was in early AD patients.

Thus, as the FDA concludes:
Additionally, many of the assessment tools typically used to measure functional impairment in patients with later dementia stages of AD (Stages 4 through 6) would not be sensitive to detect subtle functional changes in early AD. Therefore, FDA may consider other approaches, including endpoints based on cognitive assessments or surrogate endpoints, which may allow for shorter trial durations as a basis for approval in the earliest stages of AD (i.e., Stages 1, 2, and early 3).

It is under this light that Blarcamesine’s failure to succeed with ADCS-ADL despite consistently doing well with ADAS-Cog13 in a pair of trials which ultimately aims to treat early AD patients becomes interesting. Despite my complete neutrality to the debate surrounding this company, the above discussion, I am sure, will produce some doubts in honest AVXL bears. Maybe functional assessment is not a metric where Blarcamesine can succeed with early AD patients, despite having visible treatment effect in halting cognitive decline? That is a debate only the EMA and the FDA can settle.

Multiple statistical approaches to the same data
Thus, as we see in recently published data from the phase 2b/3 study:

Among 462 randomized participants in the intent-to-treat population (mean age, 73.7 years; 225 [48.7%] women), 338 (73.2%) completed the trial. The co-primary outcome was met under the multiplicity control rule, since the differences in the least-squares mean (LSM) change from baseline to 48 weeks between the prespecified blarcamesine and placebo groups for ADAS-Cog13 was significant at a level of P < 0.025 and for CDR-SB was significant at a level of P < 0.025, while ADCS-ADL did not reach significance at Week 48 (ADAS-Cog13 difference of -2.027 [95% CI -3.522 to -0.533]; P = 0.008; CDR-SB difference of -0.483 [95% CI -0.853 to -0.114]; P = 0.010; ADCS-ADL difference of 0.775 [95%CI -0.874 to 2.423]; P = 0.357).

The ADCS-ADL endpoint was not met, while the ADAS-Cog13 endpoint was met with statistical significance (P < 0.025). Now, the company also brings in a third endpoint, CDR-SB (Clinical Dementia Rating – Sum of Boxes), and invokes the multiplicity control rule. There are various types of multiplicity adjustments, and in prior discussions, I have cited two of the more conservative ones which are designed to reduce Type I errors (false positives). These are Bonferroni and Hochberg. While Hochberg's is less conservative, it can still preserve control of Type I errors while allowing some non-significant results. Using these conservative tests, the phase 2b/3 trial does not become successful.

However, if we use a less conservative Hierarchical Testing (Gatekeeping), we get to order the endpoints by their degree of significance. Here, the common-sense concept we have discussed about the relative importance of cognitive metrics over functional ones in early AD becomes relevant. Thus, if we order the 3 endpoints in the order of importance for early AD, we develop the following scenario:

1. Pre-specified Order: Let us assume the endpoints were ordered as follows given the early stage of the disease:
1st: ADAS-Cog13
2nd: CDR-SB
3rd: ADCS-ADL

2.Now, using Sequential Testing:
ADAS-Cog13: Significant (P = 0.008 < 0.025) ? Allows testing of the next endpoint.
CDR-SB: Significant (P = 0.010 < 0.025) ? Allows testing of the next endpoint.
ADCS-ADL: Not significant (P = 0.357 > 0.025).

So we can say that since the first two endpoints (ADAS-Cog13 and CDR-SB) were significant, the trial is considered successful, demonstrating efficacy on cognitive and clinical outcomes. Although the ADCS-ADL results were non-significant, they do not invalidate the positive findings for the other two endpoints, as they were tested in sequence and met their significance levels. This is just a big worded scientific way of saying that in early AD patients, detecting cognitive decline gets precedence over detecting functional decline, and hence a trial which halts cognitive impairment is successful.

Financials
AVXL released earnings recently, and their market cap is now $720mn, while the cash balance is $120mn. Research and development expenses were $10.4 million for the quarter, while general and administrative expenses were $3.1 million. That $13.5 per quarter cash burn gives them an 8 quarter cash runway.

Looking at an FCF model, we have CFO of ($12.1mn) while there was no capital expenditure, which now gives them a 10 quarter runway.

Risks
AVXL has always been a super risky stock whose price movement follows market sentiment like no other. An EMA approval will take this stock way up beyond what logic should indicate, while any indication of rejection, even if tenuous and temporary, will similarly destroy it more than it may probably deserve. I am very wary of investing in such stocks.

Bottom line
It is tempting to take a small position in Anavex Life Sciences Corp. based on the EMA outcome later this year. The stock is down considerably from its latest peaks, and while it was way more down in October, the MAA filing in November has derisked it from October, so the added expense may be worth it. I am strongly considering taking a position, albeit a very small one.

power--thanks much for your response--I'm a believer also--been here it'l be 10 years this coming May--all indications say WGT---let it happen !!!!!

Why should anyone pay attention to him at any time?

RFK has reportedly pledged to fire anyone involved in the fixation on the anti-amyloid dead end. 

plex, if there were a drug before EMA that should receive approval upon first review (and no stop), Blarcamesine is it ... the end of June, if no stop.


Anavex Now ... Right Now ... Anavex for Everyone!!!

Your prognostications are uncanny..
Let be clear no EMA filing, no peer review paper ever coming.

kund
I think the word "potential" means he is waiting for clock stop one success or approval.

Just back and the doctor removed the bandages and although she still has cloudy vision, he said the operation was successful with the cataracts out the glaucoma pressure has dropped sharply. He put in stitches which we did not know about until today most of which will just fade away. We have another follow up on Wednesday morning. So relieved! Thanks all for your well wishes!

COGS aside, my question may have been misplaced.
PW's post more in line with my thoughts when posting originally.

Margins seemed to be addressed in the extended discussion
and I believe (accounting terminology aside) costs against 2-73 revenue
are considerably more than 10%. For accumulated losses to properly
apply the IRS MUST consider them in pursuit of the product.

And YES I fully agree with you about the tax treatment/benefit going forward.

No, Bourbon, there is not 65% of revenues going to Anavex. The 65% operating profit is split evenly between Anavex and the respective partner.

One Billion $$ buy-in is reasonable for the three partners.


Anavex Now ... Right Now ... Anavex for Everyone!!!

You must do more follow up. Product labeling requirements are carefully controlled and verified by regulatory bodies WW. Such unauthorized product ID would certainly present as a labeling non compliance

Way more important than what a stock does!

Yes, I missed another golden opportunity to sell. You probably did too. Thanks for the ride offer -

So funny that you put kund and I in the same basket. I very much want kund to go away but the only thing that will make that happen is AVXL stock going UP - which it NEVER seems to do. If it ever does go UP you will see a very different reaction between the two of us. As I've stated MANY times, I will be here until either AVXL becomes successful or totally fails. I'm rooting for it to be successful, kund is not. It's kind of strange though that the closer AVXL looks to be successful the lower the stock goes.

Yes but kund don't understand that, that waaaaaaaay over what he can comprehend, you have to start with something much more simple.

k9uwa:

Thanks, John....so grateful for this outcome after the doctor said he was extremely happy with this long procedure; it started late in the day (around 3:30pm and she was released around 6 pm). My wife said they must have been working on her for more than 1 1/2 hours and he fit her in as an emergency that day! Let's get those bandages off this morning!

Steve

Potential is what you say before the drug is approved.

In case you forgot, there are class action law firms that would jump all over that if anything didn't go perfectly, if he didn't use the word potential.

Mikey and Kund got their assignment for the week. Their sponsor feels the short position slipping away. It's a dead end job but somebody's gotta do it. 

Seriously, develop some skills, though. Come up with some substance. It offends me, as an American, that you don't give value for your compensation. 

Good Evening,
Realizing of course I’m not supposed to not respond to the FUDS. Apologizing to the believers as I know I am feeding into the BS by replying to this IMBECILE that probably makes $.25 for each post.
I asked you weeks ago if you’re so miserable here with your investment why don’t you just sell and go away? and your response was you’re waiting for a run up. My response to you would be why didn’t you sell at $14 or are you in this opportunity north of $14? would like you to come and visit Texas? I would love to take you for a ride in the country.

He used the word "potential" three times in one paragraph. WTF is wrong with this PhD, MBA guy? I seriously doubt he got his MBA from Kellogg—must be a fake degree.

We are receiving growing support from stakeholders for the potential to advance a novel treatment for early Alzheimer’s disease with convenient oral dosing with potential clinical meaningful benefit,” said Christopher U Missling, PhD, President and Chief Executive Officer of Anavex. “We are excited to potentially making a difference for individuals suffering from Alzheimer’s disease, by presenting a scalable treatment alternative alongside the ease of oral administration.

Along with its 42 percent figure, Fintel also oddly references a two percent drop in institutional ownership that seems quite inconsistent with its Q3 32 percent institutional ownership figure.

I went to ChatGTP to see what I could find, and I was not getting a reasoned answer. So I started cross-examining it. In the end, here's what I got: "Apologies for any confusion in my previous responses [then conceding the strong Q3 to Q4 increase]. . . . The reported decrease of approximately 2.02 million shares (5.48%) in Q4 likely refers to a reduction within that quarter, following an initial increase from Q3. This suggests that institutional holdings peaked during Q4 before experiencing a slight decline."

Whether this speculation is true or not, I thought it was interesting enough to post here.

Looks like TGD doesn’t have much work to do, just like his employees. He’s spending way too much time on LinkedIn posting useless content. If he really wants to spread the word, he needs to improve his presentation skills and PR skill or hire someone else to do the job. LinkedIn is not the platform for a company that thinks it has a blockbuster drug.

Recent PR; WTF is potential:

We are receiving growing support from stakeholders for the potential to advance a novel treatment for early Alzheimer’s disease with convenient oral dosing with potential clinical meaningful benefit,” said Christopher U Missling, PhD, President and Chief Executive Officer of Anavex.

Excellent Steve Hope all is well with your wife when bandages come off!!!
John k9uwa

Got home around 7pm after picking up 2 prescriptions....Doc called me in waiting room and said that it went very well, we have follow up tomorrow (Sat) in the morning....we arrived at 11 am and my wife was released around 6pm...quite a long day for both of us & certainly pray that when the bandages come off she can see more than the gray blank emptiness! I'm up past my bedtime which is around 7:30 and exhausted, happy too! I see $AVXL had a pop and drop, but the higher slant down has been broken...needs conviction buying....yeah, same story needs VOL

Nope, decision will come by year end or later, even Misleading believe that. For once he told the truth.

Approval of Blarcamesine A2-73 could come at anytime.

Check out LABELING requirements

Now up to 42% with 35.6 million shares held by institutions, per Fintel.

Hey power--how confident are you we get 2-73 approved this year (2025)????? TIA

So 65% of revenues to AVXL. Reasonable if partner is doing production marketing and distribution.

I am thinking 10% each for production, S&M, and distribution with a shared 10% for administrative. These %'s are on the high side after the first two years.

Just throw in a $1 billion upfront cash payment as well.

Could be over 50% tutes by May 15th

2/13/2025 Fintel Institutional Owners 295 total, Institutional Shares (Long) 34,928,873 up 887,505 from yesterdays numbers 41.04%

So ridiculous we have to wait 45 days to know. Should be public filings available ater 5 trading days updated continuously.

It is not the Victorian Era.

It closed GREEN. You may not have noticed.

Time to shut this political thread down. This is the AVXL board. Unless the political actions directly affect AVXL it is off topic.

What do you think the EMA approval timeline would be if we had 2 clock stops and they both ran toward the long side timewise?