Anavex Life Sciences Corporation (AVXL) Options

Really!

With falsified data, everyone can make it look good until discovery!

But in the end of the day; a pig is still a pig no matter how much lipstick you put on it, even I could see that and stayed far away from it.

We got 3-4 self-proclaimed experts on here that likes to sow a bit of doubt into people, I am not sure what their movies are?

Wrong!!! He did not answer my question because he liked SAVA and dislikes AVXL

GOD bless and have a wonderful Easter

He didn't answer your question because it is a troll question.

With the caveat, that if the share price drops below the put price you wind up buying the shares at higher than the market price.

I have been on the wrong end of that with AVXL on one occasion.

Christos anesti! Alithos anesti!
Easter blessings to all!

FWIW, I was referring to your asking if I had to purchase 49,900 shares on Friday, which i did. Add that to the as existing pile. Am planning on selling covered calls against these ST shares to generate cash (been selling options monthly and it has worked out pretty well - and this is a good time to use this strategy in terms of life sciences company life cycle.)

What you wrote may or may not be true in terms of DPZ MOA. It doesn't matter. Both placebo and drug groups were receiving SOC so it equalizes out. If what you wrote were true then you would expect very little difference between drug and placebo arms, but in fact we saw the best results ever seen - more so in wild type and more so in COL24A1 subgroups. You just wouldn't those enormous differences if DPZ was providing the same benefit - in fact you DPZ clinical trials would have shown great and sustained effects (and they didn't.) Why make up this crazy theory - it is wrong, makes no sense...and don't you own shares? Why make up FUD about a company you own shares in?

“Lastly, there are currently 74 participants receiving blarcamesine within the Compassionate Use Program, who continued treatment with blarcamesine subsequent completion of respective preceding open-label-extension studies from both ANAVEX®2-73-AD-EP-004 in early AD and from ANAVEX®2-73-003 in mild-to-moderate AD. Including the start of the respective preceding studies, some participants are on oral blarcamesine once daily for over 9 years. Importantly, no severe or life-threatening adverse events were attributed to blarcamesine.”

Yes, he never answered my question because he liked SAVA.

Good luck and GOD bless,

Mayo
Everything I read about now is all about the belly.....even Dr. Berg has so many ways to approach this and I have never seen so many people on "X" mentioning it!

Happy Easter! Thanks for your findings, extremely helpful

yes, George....that's now how Anavex is going.....early treatment and I remember you asking Doc328 this question often; he never answered you

OLE for me plus 58 scientists

Last paragraph is golden

selling a put is actually like buying a stock for less than the going price.....10 minjus 2 = $8

" and impaired autophagy as key drivers of Alzheimer’s pathogenesis"---Thanks Jesse for your input !!! Appreciate it !!! As always !!

Dropouts.....during COVID I think

Doc328
I am catching up....wouldn't those experts (peer group) be able to analyze everything you have mentioned?

Seems like they all came to the same idea of favorable; are they all uninformed?

Leo
On that you might be right!

I did not search for the open interest on that Friday expiration $10 strike put!

New research continues to shift focus away from the amyloid hypothesis, highlighting mitochondrial dysfunction, DNA damage, and impaired autophagy as key drivers of Alzheimer’s pathogenesis. This week, new data published in the International Journal of Molecular Sciences and insightful commentary in Nature further support this evolving perspective.

https://www.linkedin.com/posts/jesse-silveira-1a366927b_alzheimer-mitochondrial-lysosomal-activity-7319485407912419328-Y48z?utm_source=social_share_send&utm_medium=member_desktop_web&rcm=ACoAAERDW8sBlyrV0QeJz43ptIXjxOLSEnCDyqA

He sold the $10 strike put for appx $2.00 or more....that's his effective cost after those share were put to him. Capisce?

Alzheimer's disease is easier to treat at the earliest stage possible. See the image below to understand why this is true.

The above is especially true if you are targeting upstream MOA with precision medicine.



The Anavex Blarcamesine Phase 2b/3 trial is for early stage Alzheimer's disease with baseline MMSE scores of 20 to 28 inclusive

Prevention of Alzheimer's disease via Blarcamesine or Anavex 3-71 would be the earliest stage possible.

Good luck and GOD bless

Speaking of Annovis, what many here forget in their judgement of Dr. Missling is that we would be exactly where Annovis is financially and needing more funding to finish their programs. You watch, a large secondary will be announced (the “paying of the piper”) and the hype machine will “up cycle ” the shares into the “fair and balanced” market until they are done and then they will short them back down. The timing of this is based on shen the Ph 3 will end and either the comps y will be bought out or will crash and burn. The market, or gatekeeper, will control it all through the exertion of pressure.

I for one appreciate $8-$9 and look at it as a blessing mostly because with our measly MC we still have 4+ years of runway money and the sharks know they cant stop us from succeeding.

Happy Easter to all and may this be a fruitful Pentecost season for all and always remember “ "Tempus Fugit. Memento Mori".

Blessings

Tred

That is not what the Ki data shows.

Read the specific post I was replying to. The example you give is unrelated to the PW post.

Steady, Think again!!!

You posted:

If that was true, then you would expect 2-73 to have no effect. The DPZ would have all the docking sites occupied and 2-73 would never agonize the S1 receptor.

A bet that Anavex 2-73, blarcamesine, and donepezil were taken once per day at exactly the same time therefore sone of blarcamesine and some of donepezil would agonize the sigma-1 receptor depending on which got to the individual binding site first.

GOD bless.

PW has it right on this point Steady!

Sorry to inform you that you have your key 'fact' upside down.
Some drugs have a stronger affinity for a particular docking site than others. I think it has been shown that 2-73 has a strong affinity for S1 docking site and Don... has a moderate affinity for the docking site.

Except so far that is only based on an Open Label scenario and is just one of the factors that may lead to a P3 RCT confirmatory trial being required designed with the P2b/3 trial's shortcomings in mind.

The Donepezil vs. A2-73 and their concomitant administration is entertaining, so based on the paper I read back when here is the ChatGPT answer that PW may not favour.

Note that below is based on just the one paper mentioned. It does not take into account the original claim Anavex made regarding AnavexPlus, quoted again here:
Anavex Life Sciences Corp. (www.anavex.com) is a clinical-stage biopharmaceutical company engaged in the development of novel drug candidates to treat Alzheimer’s disease, other CNS diseases and various types of cancer. ANAVEX 2-73, an orally available drug candidate developed to treat Alzheimer’s disease through potential disease modification, has undergone an initial Phase 1 human clinical trial and was well tolerated in doses up to 55mg. Results from preclinical studies indicate that ANAVEX 2-73 demonstrates anti-amnesic and neuroprotective properties. A highly encouraging synergistic effect has also been observed between ANAVEX 2-73 and donepezil (Aricept®). The combined therapeutic, called ANAVEX PLUS, produced up to 80% greater reversal of memory loss in Alzheimer’s disease models versus when the drugs were used individually. Anavex is a publicly traded corporation quoted as AVXL.

This was likely complete BS based on the preclinical lab mouse research. Mice are not men or women! and don't let anyone here tell you otherwise.

Based on the 2017 paper titled “Sigma-1 Receptor Agonists Induce Oxidative Stress in Mitochondria and Enhance Complex I Activity in Physiological Condition but Protect Against Pathological Oxidative Stress” by Goguadze et al., we can extract and compare the distinct effects of Anavex2-73 (blarcamesine) and donepezil as Sigma-1 Receptor (S1R) agonists in mitochondrial function, particularly in the context of Alzheimer’s disease models.

⚖️ Comparison of Anavex2-73 and Donepezil as S1R Agonists

Feature Anavex2-73 Donepezil
Primary pharmacological role Mixed muscarinic/S1R ligand Acetylcholinesterase inhibitor with S1R affinity
S1R binding affinity 860 nM 14.6 nM
Effect on mitochondrial ROS (baseline) Did not increase ROS under physiological conditions Increased ROS (+12% at 3 µM) under physiological conditions
Effect on ROS under Aß1–42 toxicity Reduced Aß-induced ROS, though less effectively than PRE-084 Moderately reduced Aß-induced ROS
Effect on Complex I activity (baseline) Increased Complex I activity (statistically significant) Not specifically noted for Complex I increase
Protection of ETC in Aß1–42 conditions Partially reversed Aß1–42-induced decline in Complex IV activity and restored respiratory control ratio (RCR) Mild ROS reduction; no noted protection of Complex I/IV or RCR recovery
Effect on oxidative respiration (RCR) Prevented Aß-induced decrease in RCR No significant data reported for RCR impact
🧠 Key Takeaways
✅ Anavex2-73
Selectively enhances mitochondrial Complex I activity under physiological conditions via S1R activation.

In pathological (Aß-exposed) conditions, it:

Reduces ROS burden,

Preserves mitochondrial respiration (RCR),

Protects Complex IV function, and

Shows specific neuroprotective potential targeting mitochondrial dysfunction relevant to Alzheimer’s disease.

Unique advantage: Anavex2-73 shows S1R-driven mitochondrial restoration effects without elevating ROS under normal conditions — a potentially safer profile.

✅ Donepezil
Primarily an acetylcholinesterase inhibitor, but also binds S1R with higher affinity than Anavex2-73.

In this study:

Increased ROS under normal conditions,

Moderately attenuated Aß1–42-induced ROS,

But did not significantly affect complex activity or restore respiration under Aß stress.

Limitation: Donepezil's S1R-related mitochondrial effects are less pronounced, and it lacks evidence for restoring ETC function under stress.

📌 Conclusion
Anavex2-73 acts more selectively and beneficially on mitochondrial complex I and IV activity, with protective effects in Aß-induced oxidative stress models — supporting its candidacy as a neuroprotective drug.

Donepezil, while an S1R ligand, shows less robust mitochondrial protective activity and increased physiological ROS, suggesting it may not share Anavex2-73’s therapeutic mitochondrial profile.

Would you like a visual side-by-side chart or a summary suitable for a slide presentation?

You said:
Is there any suggestion that concomitant administration of Donepezil with A2-73 reduces the effectiveness of A2-73 due to both molecules binding to S1R?

ChatGPT said:
Based on the paper "Sigma-1 Receptor Agonists Induce Oxidative Stress in Mitochondria and Enhance Complex I Activity in Physiological Condition but Protect Against Pathological Oxidative Stress" (Goguadze et al., 2017), there is no direct experimental evidence or statement suggesting that concomitant administration of donepezil with Anavex2-73 (blarcamesine) reduces the effectiveness of Anavex2-73 due to competition for Sigma-1 Receptor (s1R) binding.

However, here are a few relevant observations that might inform the hypothesis:

🔹 1. Binding Affinities and Competition Potential
Donepezil has a relatively high binding affinity for s1R: 14.6 nM

Anavex2-73 (AN2-73) has a lower affinity: 860 nM

This suggests that donepezil would preferentially occupy the receptor in a competitive scenario if both drugs are present at similar concentrations?
.

🔹 2. ROS and Efficacy in Pathological Conditions (Aß1–42 Model)
Donepezil moderately reduced Aß-induced ROS at concentrations of 1 and 3 µM.

Anavex2-73 showed no significant reduction in ROS under the same Aß stress conditions in isolated mitochondria, while other Anavex compounds (e.g., AN1-41) did?
.

This could mean Anavex2-73's beneficial effect may already be context-dependent, and potentially sensitive to receptor competition — though not proven.

🔹 3. No Reported Synergy or Antagonism in the Study
The study did not test co-administration of donepezil and Anavex2-73, so there is:

No observed synergistic or antagonistic interaction.

No confirmation of functional interference at the receptor level.

🔹 4. Theoretical Consideration: Potential for Interference
Since both drugs are s1R agonists with different affinities:

Co-administration could theoretically result in competitive binding.

Donepezil might occupy receptors that Anavex2-73 could otherwise activate, possibly blunting Anavex2-73’s effects if s1R activation is the key mechanism.

But this depends heavily on in vivo pharmacokinetics, dosing, and tissue penetration — not addressed in this study.

🧠 Summary

Aspect Donepezil Anavex2-73
s1R affinity High (14.6 nM) Moderate (860 nM)
ROS suppression under Aß1–42 Moderate Minimal
Evidence of interference ❌ None reported ❌ None reported
Potential receptor competition ⚠️ Possible ⚠️ Possible
🧪 Conclusion: There is no direct evidence that donepezil reduces the effectiveness of Anavex2-73, but competitive binding at s1R is plausible and merits in vivo pharmacodynamic studies.

The July 10 PUTS have over 3,200 contracts open interest. Should AVXL close under $10 the 3rd Friday in July, whoever sold those contracts will be acquiring a boat load of shares at $10 minus the premium they received.

That’s how an institution can quietly acquire more shares without driving up the price.

Of course if the share price is above $10, they just keep the premium.

Since AVXL closed under $9, It could have been a $9 PUT that was put to him.

That’s how institutions acquire shares without raising the price.
Whoever bought the put will lose their shares.

Selling a PUT is like placing an order to buy shares at a certain price and getting a premium while waiting.

If that was true, then you would expect 2-73 to have no effect. The DPZ would have all the docking sites occupied and 2-73 would never agonize the S1 receptor.

Lilly is not the only qualified pharma buyer. Smaller pharmas would produce a higher share price increase over the long run from the acquisition. Maybe you are unwilling to run that risk.

Well, yeah, the delayed start group was not getting the same efficacy from blarcamesine as the early start group; that was demonstrated quite clearly by the OLE, so that will have adversely affected the dropout rate. And the early start group was not getting the slower titration schedule that later knocked down the incidence of dizziness.

Neither arm experienced the combination of higher efficacy and slower titration that will minimize dropouts going forward, or the foreknowledge of efficacy upon an approval.

Perhaps a little understanding of molecular dynamics would be helpful.

Each drug and protein combination has a residency time which varies from short to long depending on the drug, the target, other factors of the environment in the body. It has also be shown that in some cases the ligand (drug) detaches from the protein and then reattaches repeatedly. The rate of reattachment depends the drug concentration and the shape of the molecular docking site among other factors.

Some drugs have a stronger affinity for a particular docking site than others. I think it has been shown that 2-73 has a strong affinity for S1 docking site and Don... has a moderate affinity for the docking site.

So there are several possible processes that could replace Don... with 2-73.

There is the docking, undocking and redocking process that would leave the S1 receptor available for 2-73 to replace the Don...
There is the straight up undocking that occurs when the normal residency time is up.

There is also the relative difference in ligand concentration which governs the exposure rate to the S1 receptor each drug. That suggests that there are open S1 receptors for docking by other ligands. The percentage of open receptors would likely vary with the drug dosage and its half life etc.

And I didn't leave the appropriate space in may be so it was maybe. Sue me.

Trial completion set for May 15 so my guess is by July.

Reread it again Leo

He said he had 499 contracts PUT to him. that means he sold the puts and they were exercised. When exercised, you have to buy 100 shares each at the contract price. since it was worthwhile exercising the put, it is reasonable to assume the put price was $10 a share. 100 x $10 x 499 = $499,000, approximately half a million.

Not a huge amount if other peoples money, but pretty big addition for someone spending their own coin.

"Not very many". Slower titration and qHS dosing likely helps but......still about 30% (29/99) patients who switched from placebo to blarcamesine dropped out during the first year of rolling over to OLE. Meanwhile only 16% (26/158) of patients staying on blarcamesine (i.e. those not needing a titration) dropped out the first year.

https://www.anavex.com/_files/ugd/79bcf7_4e15217c129541228327838b534afe4d.pdf
slide 20

The larger mab trials killed people without showing anymore benefit. I think were good

Febish.

It's always Febish despite any promised dates.

Dr. M is a Febishsist.

LOL excitable, eh?

I want a pharma that will pay in shares, but not overpriced shares, and I want it to grow the Sigma1 platform well.

So Lilly, which is the only BP that seems to be able to grow its business internally is a bad choice? 🙄

any Anavex long that has stuck it out will be better off than getting a much smaller slice of Lilly.

Again, SLOWLY. The price is the price, whether paid in shares of Pfizer or Lilly. The only difference is cash, which brings an immediate tax liability.

With Pfizer, you settle for what is essentially a bond return after the transaction. With Lilly, the record indicates a growth stock with major internal product development potential. Like I said, the first choice is for risk-adverse bureaucrats. The second is for growth capitalists.

Excellent point! That pretty much minimizes the key downside.

Anavex used a slower titration protocol in its OLE to drop the transient dizziness rate to 9.6 percent from about 25 percent. That, plus nighttime administration and the foreknowledge that the drug works should ensure that not very many patients will discontinue blarcamesine due to tolerability issues.

As has been reported, Anavex used a slower titration protocol in its OLE to drop the transient dizziness rate to 9.6 percent from about 25 percent. That, plus nighttime administration and the foreknowledge that the drug works should ensure that not very many patients will discontinue blarcamesine due to tolerability issues.

I read H's answer and he said I am correct.

So redirecting for you to reread 😏

Thank you Doc, I do appreciate your thoughts on this. My interest in the relationship between dpz and A273 is based on a layman’s idea that Ideally we should affect multiple pathways simultaneously .
My next thought is really outside the general conversation occurring now but a new therapy combining a.small molecule sr1 agonist with small molecule mitochondrial agonists and antagonists if even possible

The Phase 2 Part b top line results for the schizophrenia trial using Anavex 3-71 could be released between May 2025 and October 2025. A good possibility could be just prior to the mid June 2025 ASM, Annual Shareholders Meeting.

Good luck and GOD bless,

Tolerability is always important --- I usually start donepezil at 5 mg and after a month increase to 10 mg. If very ell tolerated will sometimes increase to 20 or 23 (2x10 or the 23 mg). Main side effect is GI. Some don't tolerate and discontinue. I would guess 8/10 tolerate 5 mg and 7/10 tolerate the 10 mg. 10 mg has been shown to be more effective then 5 mg. I only have s couple patients on 20-23 mg shown to be a little better than 10 mg.

Seems like dizziness is main tolerability issue for blarcamesine. Obviously no personal experience but this was a reason for dropouts in the study - hence tolerability has different symptoms but discontinuation rates would likely be somewhat similar.

As I have said multiple times, I would definitely write blarcamesine if it ever got approved in US (which will most likely take a larger longer P3)

As I recall, while donepezil is an S1R agonist, it apparently cannot be tolerated at what would be a clinically effective dose -- in contrast to blarcamesine. That makes all the difference, it seems.

Well above my head from the viewpoint of the Science,
But certainly makes intuitive sense if your assumptions are factual.

More than I can say for many other offerings....not yours.

THAT I can figure. Controlling 50K shares with 500 contracts.
I just could not find the Market or trade
AND
paying $10 premium for the Put Option @ $10
does not resemble any Open Interest view I have
Even May 11s are only $3.

Just interested in the time strategy and Premium.