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Yeah, I'm not trying to convince you to buy shares, I'm just trying to convince you to look at the company more carefully. But given the limited time we all have in a day, it usually correlates with the ownership, so that's a problem we have here :).
I don't think anybody believes the cognition endpoints yet, otherwise we would surely be around that 1-2 billion valuation by now. And even in that case, a month is just too short interval to have a definitive clinically meaningful answer. At minimum, three months is needed and six months is even better.
But just to quickly remind you, phase 2b had a placebo so their directional improvement on cognition was on top of the placebo.
You are certainly correct that biomarkers can be easily used for cherry picking. And everyone needs to be extra careful about that when we are talking about biotech companies.
With SAVA however, I think you might make yourself a favor if you look more carefully. There's no subgroup picking with their trials. And the p values are so low (even with so tiny amount of patients due to huge treatment effect) that even if there are some biomarkers that they measured but aren't reporting (we don't know), it doesn't chance the big picture.
I don't know if you have looked, but the biomarkers they chose are some of the most used ones. Sure, there are more potential biomarkers, especially related to inflammation. But their set seems to be fairly/very good from what I can tell.
Cognition was also trending in a good direction after only a month. I'm optimistic that the open label interim analysis gives us a nice big positive surprise in that regard, fingers crossed.
For those interested in BBB integrity and AD.
Cassava just released further biomarker data indicating their drug improved also that part of the equation. I think this is something that has been discussed quite a lot in the past since Bryo also has had some effect on BBB in preclinical studies.
https://finance.yahoo.com/news/cassava-sciences-announces-additional-clinical-131500100.html
As many may know Cassava reported extraordinary good biomarker data already before, IMO these new data is just a nice addition to the mix. The entire phase 2b set can be found here:
https://www.cassavasciences.com/static-files/5f96b2d4-46e8-4936-a6cf-8332a56f19b1
P values look great, p<0.001 and p<0.0001 compared to placebo.
Finally had a chance to listen the interview.
To me it sounds very promising. Sure, it will take more time, so the company isn't probably the best short term investment opportunity right now (I would love to be wrong on this one).
I think what Dr Alkon said was that they are still seeing the same thing as always, people who get the right dose (not too little, not too much) are seeing the benefit. But the BIG problem is the optimization and with the current compound it could even be that it has to be done individually and dynamically. Which of course isn't possible in larger scale.
So what they probably need to do is either design one more phase 2 with Bryostatin and use very finely tuned dosing regimen based on baseline characteristics and hope it covers enough people so that they get the stats right. Or start using one of the bryologs which doesn't cause downregulation as easily as Bryostatin does and hopefully also have better PK/PD profile.
And preferably both cases would be done with oral solution which makes it far easier to control and change dosing but could in the other hand bring more complexity to dosing-CNS concentration equation.
In conclusion, I'm happy that there still appears to be a lot of promise here. It will take more time but as of today, I think PKCe hypothesis is still by far the best shot we have to regenerate some of the lost synaptic networks. As Dr Alkon said, some more optimization still needed and I hope they have the resources to make it happen.
I love it. What a logical reply.
Lol
Well, depends on what clock we are talking about :).
The one I meant is the one that starts counting once/if we get good data from the current trial. IMO it's from that point onwards when BP companies really start they engines regarding Neurotrope and PKC epsilon hypothesis. I think so far the talk has been on general level, just like they talk to many other companies. Like "sounds very promising, if you can prove that, let's talk more".
Of course many of us and the company already see that the data collected so far is already extremely compelling. But that's obviously not yet enough for most, including BP, and what we need is to get a successful primary endpoint. And it's not actually so different from many many other biotechs out there. Sub group data is usually cast aside, no matter how good it looks once you look past the headline. It's usually all about primary endpoint.
These are not drugs for AD or CNS indication which were the indications that I talked about and which are of interest regarding Anavex's prospects for getting an approval.
It should be quite obvious that for example cancer indications are handled quite differently by regulators. For example you don't see companies running phase 1 studies in healthy subjects for cancer drugs for obvious reasons.
I think it's not about playing chicken or anything like that. The process should be quite standard actually. It's not like one big pharma suddenly comes forward, makes an offer and Neurotrope accepts it on the spot.
If we get good results, all big pharma companies know about it right away. That starts the clock and I think each of them will contact Neurotrope within couple of weeks latest. After that it's going to be fairly standard process of signing NDAs, Neurotrope delivering entire data package to potential partners/buyers and them researching everything and possibly holding various meetings with Neurotrope.
Then once the deadline is near for leaving offers each interested BP company will submit their offer and then Neurotrope needs to decide which one or ones are best suited for their purposes. And they might still possibly ask for additional clarifications for some details. And there could also be a last minute bidding contest if there are more than one company desperately wanting to make a deal.
I think that would be a nearly ideal process for Neurotrope, patients and investors so that we get the best price and the most motivated partner/partners or buyer/buyers. And it shouldn't take more than maybe three or four months from start to finish.
There's no primary endpoint met for the subgroup option.
The primary endpoint is measured for ALL patients that are enrolled based on inclusion criteria. If the primary endpoint isn't met then you can try to use different secondary endpoints and subgroups to get some meaningful data to be used when defining another phase 3 trial.
It's not that hard to understand really if one has any experience in biotech investing. How many times we see that primary endpoint has failed??
Well, if companies would be allowed to calculate primary endpoint for numerous subgroups, I can assure that almost ALL TRIALS would actually succeed. The reason is that ALL companies would define so many subgroups that there would certainly be at least one that succeeds just due to chance.
Nooooo.
It's under the "Other Outcome Measures:". Meaning that it's one of the predefined subgroup analysis company is allowed to do per protocol.
Remember, these are analyses that the company can run but that cannot be used for approval if the primary endpoint fails. If statistically significant those can be used to get a permission to run another phase 3 trial for the subgroup in order to confirm what was seen in the subgroup during the first phase 3.
In this case, the second phase 3 would be ready around 2026-2027. Hence the original comment that the company's reply didn't make any sense.
And in case you don't believe me, try to find AD or other CNS trials that have gotten approval based on secondary endpoint when the primary endpoint failed. And those who know some statistics or even just basic math can readily understand even without looking why it is almost always so:
If these numerous secondary endpoints could be used to get approval, MANY drugs that don't actually do anything would be approved. The reason is that when you have LOTS of endpoints, it's actually statistically probable that some of them will meat p<0.05 significance just by pure chance!!
And to illustrate it further Anavex has created so many secondary and other outcomes and variables that they are almost certain to get some p<0.05 results. That's what is in the best interest of the company, if the phase 3 fails, they can ALWAYS point out some subgroup that got p<0.05 and collect more money in order to run another phase 3 (if they are allowed to by regulators).
To further highlight one important thing. From some of the comments, it seems that there's some confusion why these trials are run in the first place.
In our case they are run in order to get a FDA approval, first for severe patient population. So the company follows the process that's well documented and FDA approved for that indication. And at the same time other trials can possibly be run to get approval for mild phase and for other indication. AGAIN by following FDA approved process for those cases.
Some other companies might have different reasons for their trials, but I would rather invest in the company looking for a FDA approval.
It's all nonsense. Homeostasis and other terms can be used to try to get investors onboard. But until there's a clear preclinical and clinical proof that something like that is actually happening in any meaningful way, it's just words used for marketing purposes for example to sell shares through ATM. And to really proof something like that in preclinical and clinical phase is actually VERY expensive. Already in preclinical phase it requires lots of time and money to even try to get some proof. Like what Alkon has done when they actually calculated synapses and neurons that were created due to Bryostatin treatment. That alone cost a lot of money and it's not a common type of thing small biotechs do.
Often times the term itself isn't even clearly defined or its meaning to certain indication isn't proven which makes it even more suspect to even use it.
So IMO, it's pure waste of time to consider such things until some real evidence actually exist.
But the problem might be that it's not actually easy to understand many preclinical and clinical studies correctly. Sure, anyone can throw some fancy words around but there's no meaning in it.
Literally every big pharma would want the only effective AD treatment into their pipeline, given the enormous need and the huge market potential. Even without considering all the other potential CNS indications.
So it's the highest bidder who wins and although Biogen has the motivation, I'm not sure they have the biggest wallet to win the bidding contest.
Yes, let's see what happens!
Neurotrope had pre-specified memantine free subgroup analysis and we all know how well most people reacted to that. So expect similar things happening to other companies that possibly are in the similar situation in the future.
Furthermore, Anavex's AD study will end sometime in 2022 and if they fail the primary endpoint and find something interesting from the subgroups, it requires them to run another phase 3 before they have any chance for approval. At that point it would be something like 2026-2027.
Fortunately for us, trials in severe patient population are way shorter and our treatment effect was so big that we managed to run our second trial in one year. The same applies to possible phase 3 once we have the current phase 2b results available.
This was literally the second result on the google search in case some Anavex investors would like to know whether or not she is still a Missling's friend.
https://www.zoominfo.com/p/Nell-Rebowe/-1986038719
"Director, Business Development at Anavex Life Sciences Corp."
Yep, people in general seem to prefer to look at something/everything else except the data in many cases.
It's only once the data becomes so obvious that it's just common sense to accept it when many will actually finally take it into account.
None of this of course means that this trial will succeed, it's just that given the data, the odds look highly promising.
Everyone just look at the data and do whatever one has to do.
The first rule in investing: NEVER invest more that you are willing to lose, NEVER. So personally I would strongly advice against such reckless behavior.
That has nothing to do with Neurotrope and our situation specifically, though. It's just something everyone should always follow, no matter what. Again, it's simple math really. No matter how well you do e.g. with this investment by risking everything, the next one, or the one after that, might wipe you completely out if you always take your chances to the fullest.
If we confirm the previous data then I personally will remember Dr Alkon's "look at the data" catchphrase for quite some time. It's going to be a good memory about how hard it's sometimes for general public to "look at the data". Or perhaps some are looking but not really seeing. Either way, what Dr Alkon has done for the last 40 years is really remarkable, he has basically used his whole career trying to solve some of the greatest mysteries surrounding how you mind works and what makes us human beings.
Whether or not it will pan out financially and how much will be seen in few weeks. For me, it will be a milestone that I have been waiting for 6 or 7 years.
Love it, thanks.
Just look at the data and so on. Every time Alkon speaks and demonstrates the depth of knowledge and data he and the company has, it's just amazing.
Funny world this is, sometimes it's so god damn hard to get people to really look at the data. It should have been obvious to many latest after the CU data, that there's something very interesting happening with this drug and MOA. But noooo, more important to try yet another AB drug and maybe still couple more just to be really really sure.
Fortunately once the confirmatory results hopefully confirm the previous results, we have enough evidence so that (almost) everyone will finally get it.
No, I think the statistics are already calculated at that point according to the protocol. The first patch of results most probably includes the primary endpoint data. And then they get more data later as soon as it's available.
Yes I am. Here's what Alkon said:
Min 6 trading days, max 15 trading days left before we should get the first results from the current trial. Exciting times ahead.
"to initiate a clinical trial"
Great stuff again, thanks.
Even though with confirmatory clinical data coming in few weeks the preclinical data doesn't carry as much near term weight as it used to just few years ago. But it's still very nice to see these research articles were Bryo's multimodal efficacy is demonstrated again and again and again.
ANY small biotech would want this level of preclinical data that we here are used to having. And in vast majority of cases, it's just not possible due to extremely high cost. The cost that someone else has covered for us starting tens of years ago and we can just sit back and start collecting the likely reward soon.
Not a bad situation to be in.
Oh well, at least I tried. But not surprised really.
BTW. I have a minor in applied mathematics so I should know something about statistics and logic.
Some basic knowledge about biotech investing would be beneficial.
- Know what a blinded study means
- Know what kind of placebo effect exist in AD. Yes it really exists.
- Know what kind of sources of errors there are in defining who actually has AD in the first place, especially in early stages.
- Know the variability in measurements.
IMO these are mandatory if one tries to do even a slight amount of DD in any AD biotech stock. Without such basic knowledge, people are sure to lose their money in the long run. No doubt about that.
15% of volume during the second half of July was short sales.
Some clueless people are playing with fire shorting at this point. But what can one do, it's free world. I hope no-one will lose all their money or even worse if/when we confirm the previous results.
I don't think that's going to be a problem.
Some people, for various reasons, will certainly say all sort of things. But if ANY company in the world can produce statistically significant top line data in FDA approved placebo controlled trial for AD, they are going to be golden.
The need is so huge and the lack of any credible results is so clear that all the parties that matter will understand the value of valid results.
These retail focused discussion boards can make it seem like everything might be relative. And it can be for some people. But for professional investors, big pharma companies, FDA and scientific community (at least most of it) the data is what matters. Clean and simple.
So worry not, statistically significant top line results will rule.
For what, wasn't the original study well designed? And what prevents them from adding another 30 or so patients later on to extend the schedule again too buy some more time again?
Usually companies that are confident on the science design and run their studies as fast as possible. To fail or succeed fast. That's the way to get real treatments to market asap.
The chances of success don't increase with slower pace, if anything it's actually the opposite.
With current share price, the company is selling around 50000 shares EACH trading day just to cover the expenses. Just as they did in the past quarter.
The lower the share price goes the more shares they are selling each day.
Lol, the enrollment should have already finished even with steady pace. Usually in well-run studies the enrollment actually picks up the pace during the study.
Since this is the first placebo controlled study ever run for the compound the failure would crash the share price. So it's in the best interest of the company to postpone the completion as long as possible and sell more shares.
In the past quarter around 8 million dollars came from somewhere, most probably from selling shares through ATM. And the pace is probably going to accelerate in H2.
There are some other companies in the field that actually can get their placebo controlled Alzheimer's studies completed in time and in budget. So it can be done.
That's great info, thank you. Were did you find this from?
The whole thing was great but I especially liked this bit:
I have done some calculations based on already reported data about how many patients were dosed (108) and how many completed the study (95). Based on the reported data from the previous phase 2b it can be seen that the 20ug and 40ug memantine free patients had the lowest dropout rates most probably due to best efficacy.
I compared those figures to the reported dropout rate in the current study (88% completed) and this is what I found:
If patients in the current trial were to act similarly to the entire 20ug arm in previous trial we would be actually seeing only 89 patients completing the study. So there are 6 extra patients that have completed the study. But if we take the 20ug memantine free arm from the previous trial then the current 95 patients (88 %) completing the study fits perfectly to the data from the previous trial.
6 patients is IMO quite big difference and it really quite well tells us that patients in the ongoing study are seeing similar efficacy as in the previous trial and therefore are not dropping out. So in essence the reported safety data already "unblinded" the study and we can expect great results soon.
All IMHO and nothing's certain of course. But it's looking god damn good if you ask me. I suspect sooner or later some bigger players will notice the same thing.
Some facts about the trial and the AD market.
1. In the US, FDA is what matters. In our case the current phase 2b is designed to replicate the previous phase 2b results and hopefully show disease reversal for the severe patient population. For that population SIB is the FDA approved measure. It's not that hard really, memantine has been approved before for the same patient population even though their results were quite weak. So the bar is set really low as most know.
2. If the current phase 2b shows disease reversal, it simultaneously shows that PKC epsilon hypothesis is correct. And according to all available data (more is coming in the current phase 2b) PKC epsilon improves cognition in all disease stages.
3. If we get good results at week 13 and/or week 15 showing reversal, all the available data indicates that the effect can be extended far longer. It's NOT however required for the FDA approval, since for this patient population even short interval is enough for approval (already done for memantine). But longer effect, possibly even years and years for some patient population, would naturally be a great news for patients and investors alike.
4. The treatment for severe patient population investigated in the current phase 2b would already be worth at least ten billion in market cap (current drugs with VERY limited treatment effect have sales around 5-6 billion per year). So thinking about other disease stages and longer duration of effect isn't really what's needed for us to be very very wealthy. But in that case the value of the platform would be tens of billions which of course would be an nice addition to already great ROI.
5. If we get good results, it really doesn't matter at all what any of us think about the results!!!! At that point the entire market will know about us, institutions, big pharma, masses of retail investors and so on. And at that point we are finally going to get the correct valuation based on the science and the value of the platform. So anybody trying to convince others that good results either matter or don't matter is just wasting his/her time.
Precisely so. And we already know that there were very few drop-outs during the trial. Even less than in the previous trial in 20ug and placebo arms combined. That's also a positive indicator.
The enrollment criteria and protocol has also remained the same which means that all these statistics from the previous trial can be used to estimate the current trial outcome.
Similar patient population and dosing protocol combined with highly statistical results IMO means that by far the most probable outcome is a success.