Are there any arguments against approving Blarcasamine besides for?
-trial may be too small and may be a little too short
-it was only a 2b/3 after a very tiny 2a

Seems that the arguments for approval vastly outweigh. The above can be answered with a confirmation trial after full approval. OLE can put some of that to bed as well.

Also for those that are more knowledgeable, it is my understanding that OLE data can be complied and gathered as patients finish making it a much faster process. Also, other measurements aside from the Adas and CDR can wait as they are less important at this time in terms of confirmation. If Adas and CDR are not what is expected, then the other OLE data will rise in importance and take much longer to flush out.

Either way, it is also my understanding that MAA is moving forward without waiting for any OLE data.

Thoughts?

For now, the MAA is like the peer review. It’s fake news until we see it.

Once we see it/them, sentiment will change rapidly.

I pray we are not reliving the past, where Missling was promising all of these catalysts by year end and achieved none. Déjà vu?

Even one of our analysts was like. Ugh. That’s a lot. Do you think all these are possible. Oh yeah. Missling said. And then flop. Missling learned his lesson and then stopped putting dates on our future catalysts.

No it seems he is back to his old ways. He didn’t say this year but is intimating a lot. Possibly too much. One of our posters listed 10. Can even half of these really be achieved?

Are getting stretching our resources again? Focus man!!

Our non published data might be our best hiring tool.

Missling: We can’t pay you much, but you will get some good options.

New Hire: uhm, I’m not sure. Wait you don’t even have an office?

Missling: No. but we’re doing some great things.

New Hire: uhm. Let me think about this for a bit.

Missling: Here is our unpublished Alz data. Take a look.

New Hire: Holy Fxxk! Where do I sign??

New hire skips down the hallway humming his favorite tune and dreaming of new mansions.

Varying degrees of being pulled in after being shown most of the data. Most means the most important parts without hiding anything.

-The data looks good. We think you should take a chance and file. And if the rest is good, you may have a shot.

-You should definitely file. Although not a slam dunk, we’ve never seen data like this especially in brain atrophy. We think you have a really good chance.

-This data is quite impressive. We are desperate for something safe and effective. The upstream MOA and peripheral benefits is what we need. Let’s get it going. We’ll support you along the way. What are you waiting for?

I’m guessing somewhere between 2 and 3. Being pulled is pretty strong language. Stronger than suggested. Pulling almost indicates a little convincing.

Maybe I’m reading too much into the word. Missling also seemed optimistic about the MAA profess. Almost as if they were ahead for once.

Insider purchases don’t bother me much as a 5-10k share purchase would be a token symbol. Living in NY is not cheap. Why toss 30k dollars down when you have options and time?

Peer review still annoying as hell. I’m not reading into the delayed ASM as anything unusual. He is definitely annoyed about how long it’s taking.

The company did a good job hiding the COO departure as the analysts would have surely asked about it if they knew. Would Toutain leave for a better package knowing what coming down the pike? There’s definitely more to his departure. High level people don’t leave at a time like this if they don’t have to. Forced to.

There’s writing on the wall. He saw it and left on his own terms. Career flop averted.

This golden parachute proposal is interesting. A proposal made by a shareholder/s. Inside knowledge of something brewing or just someone that doesn’t want to get bent over?

I wonder what Toutain’s package was. Anyone?

Strange that COO leaves and there’s no immediate replacement. Maybe someone got promoted? Our operations are still small potatoes so maybe we can do without one for a while.

Still an unusual move done in the down low. Not sure how much of an asset he was anyway.

I put COO leaving in the Super Duper AI Fantastical Speculator Machine and it said - Anavex will partner with a large pharma and one of their executives will come in to be the COO.

One can dream!

I think they know that and it’s something they can’t do on the fly if they want to succeed.

All the expertise will be brought in through a partnership. Hopefully very soon. That’s most likely the reason we haven’t seen any new hires in this area. Like you said there is a lot of pre commercial activity that needs to be done in order to ramp up properly.

Last years ASM was on May 23rd so we’re not late yet. For those who are speculating that something is in the works.

Missling is sloppy with his timing. He doesn’t think when he picks dates for CCs. Several times he had CCs on strange dates like before holidays and weird times like switching to an 8am on a Monday, not thinking investors read into these moves.

They all have been a nothing burger, while we all got excited expecting something since he telegraphed.

I hope there’s something here this time.

Or maybe he was just like, oh crap, we got to do the ASM. Shiit, I knew I should have never fired my secretary.

Pretty sad to be here at this level. Not much else to say about it.

Hope our chess master has a plan other than attend conferences.

I wonder what file as early as possible in 2024 means. Clear as mud.

I wonder what Kun’s probability of a successful filing is. Since it’s almost solely Missling’s decision to determine whether to try to file right away, wait for more data or do another trial.

I imagine that Kun’s input weighed heavily on the decision.

If it was, I think we have a good shot Chris, they would have filed immediately. They didn’t.

It was probably more like, it’s good, but if we get this and this, it will be better. And we eventually got what we needed. So here we are. Whether or not that includes some OLR data, I don’t know.

If it was, it’s not good enough or we have a small chance even if we get extra data, I think we would have seen all the data by now and plans to do another trial would be in the works.

Kun knows the data presented thus far is incomplete. They have “heat” on them already with the pending lawsuit. The truth will come out eventually. Obviously for now they’ve “fooled” the EMA into letting them proceed.

Do we/they really think all these inconsistencies pointed out will not come to light? Do we really think that maybe if they just try to proceed that maybe no one else will notice? I don’t think so.

Or do we think the data driven Chris Missling said, I don’t care, let’s move forward anyway. They’ll never catch us. Ha ha! Evil laugh. I’m guessing no.

So we’re in the dark a little longer and that’s ok cuz I’m pretty confident the smart people at Anavex aren’t trying to be middle school slick here.

Common sense tells me things are moving along nicely but slow as F

Although I agree with you, removing Missling at this time may do more harm than good.

Unfortunately we are stuck for the foreseeable future.

It’s difficult to play armchair CEO without knowing all the facts even though I’m often guilty of doing it.

Hope the peer review brings several, “oh now I get it” moments.

Peer review drop right before Needham.

Ha! Someone had to say it.

I’m gonna sue these mofos. Can’t let them get away with this.

Oh look honey they were actually sued before.

Let’s call them to see if we can get them to do it again since they’re familiar.

Ring ring. Ok. We know the recipe

Or it could be the short hedges. Either way it’s not fun and doesn’t change what we need to or can do about it.

At this point, even those of us trading to make a little extra coin are in a tough spot.

For now

It’s just a coincidence that all these events happened so close together. I don’t see any hidden agendas by any “secret cabal” trying to destroy our company.

Someone thinks they have a legitimate grip and is angry about losing money.

Peer review is sorely needed to increase morale and put to bed some silly assumptions.

Sad to have this lawsuit overhang in what arguable could be the most important time in our history.

Words matter and you can’t just blurt out whatever you want. Hope he’s learned that by now. I see this as just an annoyance in our path to success. Missling is a rule follower. I have no doubts that everything was done by the book. And if he needs to throw outa few Benjis to get rid of these pests, so be it.

It doesn’t take away from what we have. This little mini PR campaign if that’s what you want to call it may be a sign that the peer review is close. A little teaser if you will.

I don’t think it’s just one of his bright ideas that he thought of while playing battleship thinking it could make a difference to anyone.

Is Missling capable of any surprises?

We see the road ahead. The timelines are predictable with the ema and will be once it starts with the fda.

The peer review will shed light. I believe better than we expect. However, the predictability means no parabolic moves and an easily manipulated SP considering our low float.

Rett could be a surprise. Hopefully something else unexpected in the works.

It’s amazing how slow the peer review process is especially for small companies. Maybe AI can help speed up the process soon on all fronts of drug development.

It’s almost gonna be painful to hear Missling repeat himself at Needham.

I guess we’ll search for nuggets. Oh yeah. And hope some more.

How about some out-licensing? Missling spoke about that once many moons ago.

It’d be a good way to speed up the science, trials, revenue potential, etc.

I doubt the regulators will make the perfect an enemy of the good.

Especially when our good is already much better than the mediocre that was already approved.

Thanks. I would imagine that since it’s open label, the data at various time points have already been collected and crunched.

Why wait for the complete OLE when a 6 month view can give us a head to head comparison with Lecanamab and others?

I wonder if the 6 month will be part of the MAA. Waiting til July will delay a little more for no reason unless the 6 month was not as good as they thought.

When will the OLE be completed? TIA

Yep, a lot of good stuff happening. The Rett was an unexpected hiccup that we will muscle through. There’s a plan there and it will be revealed in time. Our rare disease franchise is too valuable and Rett gave us a lot to work with.

Everyone is shatting themselves with the silence and the low SP. Yep, it doesn’t feel good with no clear timelines. However an FDA nod to file will change everything.

We always say that Missling keeps things close to the vest. Before it was a little too close and I thought more transparency was needed. However, now at this moment, it may actually be wise to keep things close. We are in striking distance for a real seismic shift in how Alz and other CNS diseases are treated and viewed.

We have a solid platform with a boat load of Sigma one research backing our theories. We’re stepping on some big toes and we need to be selective on what we release and when.

We still don’t know what the peer review will reveal. If it does reveal some super responders as many here have speculated for some time then it might be better to make it a surprise. If QOL and other RWE measures are anything like we’ve seen the the 2a then watch out.

Patience and Perspective as one of our posters would often say. Steady?

Maybe that rebuke of the Alz Asoc in the Journal of Alz Disease is a precursor to the release of our peer review.

Timing is ripe with everything that’s happening in MAB and regulator land.

I’ll use Missling’s favorite word. Intriguing

It’s intriguing to see the lecanemab launch failure.
The slowing of brain atrophy is intriguing.
The very nice correlations between everything we have done is quite intriguing.

Missling pisses me off too but the unfolding events are intriguing to say the least.

It’s a gift for people getting in at this level. The Blank Check Preferreds help keep the vultures at bay.

I vividly remember that full page colored mailing about that vote. On nice card stock.

EMA. Uhm should we grant approval to this better, safer, cheaper, easily accessible drug that can given to ALL Alz patients while we face a huge economic burden that’s only getting worse with not many other available options is sight?

I vote no.

Ha!! Sure. That might happen in Bizzaro World but not on Earth.

Missling will bring this home and it will pay off handsomely despite his faults and past blunders.

I was referring to complete vs conditional MA. I thought Missling said they were going for “complete” MA through the centralized procedure, meaning we have more comprehensive data.

Did he? Can anyone confirm? Maybe I imagined it.

Complete Marketing Authorization (MA) and Conditional Marketing Authorization (CMA) are two different pathways for obtaining approval to market and sell medicinal products within the European Union (EU) and European Economic Area (EEA). Here's a comparison of the two:

1. **Complete Marketing Authorization (MA):**
- Process: Under the complete MA pathway, pharmaceutical companies submit comprehensive marketing authorization applications to regulatory authorities, such as the European Medicines Agency (EMA), for review and approval.
- Data Requirements: Companies are required to provide extensive data on the quality, safety, and efficacy of the medicinal product, including results from preclinical studies and clinical trials, manufacturing processes, and pharmacovigilance plans.
- Approval Criteria: The regulatory authority evaluates the application and assesses whether the medicinal product meets the necessary standards for safety, efficacy, and quality. If the criteria are met, the regulatory authority grants full marketing authorization, allowing the product to be marketed and sold in the EU/EEA.
- Conditions: Full marketing authorization is granted without specific conditions or obligations, although post-authorization surveillance and monitoring may be required.

2. **Conditional Marketing Authorization (CMA):**
- Process: Conditional marketing authorization is granted for medicinal products that address unmet medical needs and provide a significant benefit to patients, but for which comprehensive data are not yet available.
- Data Requirements: Companies must provide preliminary data on the quality, safety, and efficacy of the medicinal product, but additional confirmatory data may be required to support full approval.
- Approval Criteria: The regulatory authority evaluates the available data and assesses whether the benefit-risk balance justifies granting conditional marketing authorization. If the criteria are met, conditional marketing authorization is granted, allowing the product to be marketed and sold in the EU/EEA.
- Conditions: Conditional marketing authorization is granted with specific conditions or obligations, such as the requirement for the company to complete additional studies to confirm the product's efficacy and safety. Risk management measures and pharmacovigilance activities are also required to monitor the product's safety and effectiveness once it is on the market.

In summary, while both complete MA and conditional MA pathways allow medicinal products to be marketed and sold in the EU/EEA, they differ in terms of the data requirements, approval criteria, and conditions associated with marketing authorization. Conditional MA is intended for products that address unmet medical needs and provide a significant benefit to patients, but for which additional data are needed to support full approval.

The slow pace is agonizing.

One thing that’s for sure is we are not going away like many one trick pony companies with horrible balance sheets.

Thankfully our pipe is rich and our coffers are full with a low share count. We continue to attract new talent and are still moving forward as slow as it may seem.

Our science is real and continues to be explored, developed and hopefully partnered with to produce even better drugs/effects.

The SP has me sad and frustrated like everyone else here. I will let the story unfold knowing it’s gonna take much much longer than we want.

Any idea what items are being voted on in the next ASM? Hopefully we can send a clear message with our votes.

The FDA and EMA have similar views and processes on drug approvals. With our nod to move forward with a complete MA, it’s hard to believe the FDA would view our data so differently.

With two reg bodies giving us the go ahead, the SP should react accordingly. Missling would not go to the FDA if Kun said we are not ready. Kun’s view holds a lot of weight and most likely helps to drive Missling’s decisions.


The European Medicines Agency (EMA) may recommend a company pursue a complete marketing authorization (MA) rather than a conditional MA for several reasons, depending on the specific circumstances and characteristics of the medicinal product. Here are some potential reasons why the EMA might make such a recommendation:

1. Adequate Benefit-Risk Profile: The EMA may determine that the benefit-risk profile of the medicinal product is sufficiently well-established to support a full MA, without the need for additional data or conditions. This could be the case if the product has demonstrated significant clinical benefits with an acceptable safety profile in pivotal clinical trials.

2. Robust Clinical Data: The EMA may have reviewed comprehensive and robust clinical trial data demonstrating the efficacy, safety, and quality of the medicinal product, providing confidence in its overall benefit-risk assessment.

3. Unmet Medical Need: If the medicinal product addresses an unmet medical need or provides a significant therapeutic advance in treating a particular disease or condition, the EMA may prioritize granting a full MA to ensure timely access for patients.

4. Manufacturing and Quality Assurance: The EMA may assess that the manufacturing and quality control processes for the medicinal product meet the necessary standards for ensuring consistent quality and safety, supporting a full MA.

5. Public Health Considerations: In some cases, granting a full MA may be deemed more appropriate from a public health perspective, particularly if the product addresses a significant public health issue or if conditional approval could introduce uncertainty or risks for patients.

It's important to note that the decision to grant a full or conditional MA is based on a comprehensive evaluation of scientific data, regulatory criteria, and public health considerations by the EMA. The agency aims to make decisions that balance the need for timely access to medicines with the requirement for robust evidence of efficacy, safety, and quality.

If Missling is waiting for some OLE data to include in our package/meetings, how much is sufficient?

6 months? or maybe just long enough to compare with the mabs?

I think we’re almost at the point where the amyloid hypothesis becomes laughable.

Too much proof that shows it doesn’t work. Scientists soon or even now have no choice but to refute it. And the ones that still tout it will be ridiculed.

Even the Alz Association will need to pivot soon to something else as this time has become quite old. The problem is that big money donating BP have nothing else to fall back on.

No marching orders to start pumping this or that approach as the new idea because there not much to pump. Maybe they jump on removing tau bandwagon? Do they risk egg on their face by being g sideswiped with the sigma one? How foolish and behind will they look if Anavex sneaks by without them saying a word about it/us

The pivoting will need to happen or they risk losing face, money, influence, etc. Too much to lose by staying with the same horse. If not us and our science then who?

Once we file MAA, the SP should get a nice pop. It’s gonna be filed. Only way it doesn't is if our data is suspect and doesn't pass the smell test when the curtain is lifted.

Already passed the Kun test. No doubt he would have bolted if the data was suspect, if we didn’t follow sap or if the trial didn’t follow the acceptable protocols. I’m pretty confident they will be able to answer all questions satisfactorily.

No doubt Sabbagh and the gang of new hires have also seen, critiqued and verified.

Once filed, partners and smart money’s ears perk up. Hopefully before then we get some FDA guidance. Maybe in close proximity. 2 very big SP moving events. It will make this wait, pan, etc. worth it.

No, in gatekeeping procedures with two primary endpoints, each endpoint is typically assessed separately against a predetermined significance level, often set at 0.05. The requirement for statistical significance is applied to each endpoint individually, rather than their combined significance. If both primary endpoints individually meet the predefined significance level, they are considered statistically significant.

However, it's essential to consider the overall Type I error rate control when interpreting the results of multiple hypothesis tests. Gatekeeping procedures are designed to control the overall risk of making a Type I error across all hypothesis tests in the trial, including multiple endpoints. Therefore, the overall significance level is typically adjusted to maintain the desired overall Type I error rate, often using methods such as Bonferroni correction or hierarchical testing approaches.

In gatekeeping procedures, if one primary endpoint does not meet its predefined significance level, it's generally not appropriate to combine the other primary endpoint with the secondary endpoint in a statistical analysis. Each primary endpoint is typically evaluated independently to maintain the integrity and validity of the trial results.

However, if one primary endpoint does not achieve statistical significance, it may still be informative to explore the relationship between the other primary endpoint and the secondary endpoint in secondary analyses or exploratory investigations. These analyses could provide additional insights into the overall treatment effect or potential subgroup effects within the study population. However, such analyses should be interpreted with caution and considered exploratory rather than confirmatory.

In gatekeeping procedures, the combination of primary and secondary endpoints is generally not recommended for hypothesis testing if they were not predefined to be combined in the study protocol or statistical analysis plan. Each endpoint, whether primary or secondary, is typically evaluated independently based on its predefined significance level.

If one primary endpoint and one secondary endpoint individually meet their predefined significance levels (typically set at 0.05), they are considered statistically significant on their own merits. However, the decision to combine them for analysis should be carefully considered and justified based on scientific reasoning and prior planning in the study protocol or analysis plan.

Combining endpoints post hoc without prior justification can increase the risk of Type I error and compromise the validity of the study results.

“It's essential to adhere to the predefined analysis plan and statistical methodology to ensure the integrity and reliability of the findings.”

Serious question. Why would he say ADL met if not true? Others have stated that the 2 primaries, ADL and Cog need to add up to less than .05 and that each may have been under that threshold alone but when added together it wasn't.

I have not found anything that says that is a requirement. Anyone? And if the ADL was under .05, he definitely would have released it.

Missling - Oh crap, I really screwed up telling everyone ADL met. Why the F did I do that? Ok, I won't release the number and just wait for the peer review. Maybe if I stall long enough, I can get EMA approval before the real number comes out.

Then when it comes out, no one will care. If EMA doesn't approve, then I'm really F'd.

I've gotta believe Missling knows shareholder disappointment has reached an all time high. This is our first filing and it's a big one. He knows he needs to get it right. Not much news on the horizon, so we stay in limbo until further notice.
-Rett Guidance
-Peer Review
-FDA Alz Guidance
-MAA

That's all. Wait, complain, hope, wait, get angry, hope, wait, complain, etc.. Not much else to do or talk about.

Hopefully Missling will learn from this experience, grow and take us into the next chapter.

His learning curve is painful though.

It seems that our PDD data will/should be included in our MAA. The genetic data which has our patients returning to a more healthy state should be eye opening.

Our cumulative data is quite powerful and this current landscape makes it that much more appealing.

Yes, data from other relevant trials can be used to support a Marketing Authorization Application (MAA) submitted to the European Medicines Agency (EMA). These additional data can include results from previous clinical trials, pharmacovigilance data, real-world evidence, and other studies that provide relevant information about the safety, efficacy, and quality of the medicinal product.

When including data from other trials in an MAA, it's essential to ensure that the trials are adequately designed, conducted, and documented to meet the regulatory standards set by the EMA. The data should be relevant to the indication and patient population for which the marketing authorization is sought, and they should be appropriately analyzed and presented to support the application.

EMA evaluates all submitted data as part of the MAA review process to assess the benefit-risk profile of the medicinal product and determine whether it meets the necessary regulatory requirements for approval. Including data from other trials can provide additional evidence to support the overall assessment of the product's safety, efficacy, and quality.

There is no specific requirement for companies to list statistical methods in a Statistical Analysis Plan (SAP) from "best" to "worst." Instead, the selection and presentation of statistical methods in a SAP should be based on scientific principles, the objectives of the study, and the characteristics of the data collected in the clinical trial.

In general, the statistical methods outlined in a SAP should be selected based on their appropriateness for addressing the research questions and analyzing the data collected in the trial. The SAP should provide a clear rationale for the chosen methods and describe how they will be applied to achieve the study objectives.

While some statistical methods may be considered more appropriate or commonly used for certain types of analyses (e.g., regression analysis for examining associations between variables), the concept of ranking statistical methods from "best" to "worst" is not standard practice in clinical trial analysis.

Instead, the focus should be on selecting the most appropriate statistical methods to address the research objectives and ensure the validity and reliability of the study findings. It's also important for the SAP to provide transparency and detail regarding the planned statistical analyses to facilitate understanding, replication, and interpretation of the study results.

No mention of a hierarchy. From the bot at least. Maybe others have better sources.