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Damn you're fast. I can't get past the paywall if the article was uploaded too recently lol
I don't know if Parkinson's works that way, but if repairing synapses helps those patients get better then sure, why not?
I see the new data as a milestone rather than the finish line.
Sure, a good readout will likely cause the price to pop, but both the FDA and various institutions will still need their time to look over the data before making any big decisions.
As I've mentioned previously though, if the MOA is confirmed we're not just talking about an AD treatment worth tens of billions of dollars on its own, but a drug that regrows synapses and repairs brain damage caused by all kinds of diseases or accidents.
I'm not going to pretend I can value something like that, so instead I'll wait for the big fish to come up with a proper acquisition offer somewhere down the line.
Not much use speculating anyways when results are only a few weeks away.
To understand the shorts here, all you need is to look at Twitter:
$NTRP $6.40 today. Is this a good short? @juliaskripkaser
— Kevin Wolcott (@Kevin_W81) August 8, 2019
Data anytime in Aug - Sep 2019. This company found something in the ocean & thinks it can be used to treat Parkinson's 😬
👉🏼~$20M cash left
👉🏼Previous P2 data failed, 39% dropout
👉🏼Moved from OTC to Nasdaq in 2017 pic.twitter.com/NTtETUkEK1
$NTRP has targeted a placebo-adjusted improvement in the SIB of 2.6 points at 3 months for bryostatin (clinically meaningful?) By comp, the PFE's Aricept showed a pbo-adj chg in SIB of 5.9 points after 6 mth. So $NTRP is chasing an endpoint which will not be rewarded by investors
— MayaMatrixMuktiManifestor (@NohupMy) August 8, 2019
What's funny is that the current CEO worked on the last drug to be approved for AD, Memantine.
Now he's working for a company specifically not allowing Memantine in its trials.
He's been interviewed plenty of times already. At this point I think there's nothing they can do to convince people except release the new data and hope people don't misinterpret that one too.
I think what's more exciting is the part that isn't about AD.
"Mammalian brains have a certain capacity to regenerate/remodel synapses/neural networks when facing injury, disorders, and cognitive challenges. Cognitive impairment becomes evident only when injury/damage/cognitive demands reach a threshold by which the brain can no longer initiate and sustain the required responses. This threshold is lower with neurotrophic hypoactivity."
"Memory impairment and dementia are the consequences of synaptic/neuronal deficits. The intrinsic neuro-regeneration capacity in the mammalian brain has been shown to be very limited, even after eliminating multiple known inhibitory signals [47]. In the adult mouse brain, most axons cannot regenerate sufficiently, even with precise laser-mediated lesions that produce minor scarring [48]. This low endogenous capacity for neuro-regeneration in mammalian brains does not mean, however, that this capacity cannot be enhanced to achieve dramatic outcomes. Spines are highly dynamic and capable of remodeling and restoring their original structure, location, and function [49], when triggered with appropriate therapeutics, such as neurotrophic activators (see below). Therapeutic strategies aimed at the reactivation of these pathways in injured CNS neurons might be successful in enhancing our capacity to revitalize neurons and regenerate synapses."
What these people are really discussing is the regeneration of synapses and repair of brain damage in general, and they have 119 different references to back up their claims in just this one paper.
Why nobody is talking about this is a complete mystery to me.
Still very cheap considering how much a data release can move the price.
My guess is that they release it late September and that investors betting on results with August/September options are going to be left disappointed.
Open interest for October calls covers almost 700k shares now.
Incorrect. The synthetic version has the exact same chemical structure as the natural version, which makes it bioequivalent, not biosimilar. These are two different terms that mean two different things.
They will run a pivotal P3 for approval and then a short bioequivalence study, nothing more.
To clarify further:
Not only does Bryostatin help restore autophagy by indirectly degrading amyloid and tau waste products, but the last trial also used ANCOVA, MMRM and mITT analysis to better understand results, which I would say are "21st century" methods that help us see what exactly may have caused the patients to react the way the did. Additionally, the study design was not only approved by the FDA, but also the Copernicus IRB, a well known independent review board with a 20+ year track record of ethical, independent study and protocol review.
As for homeostasis being maintained, I think patients still improving after drug administration has stopped is a very good signal for just that.
And what if I told you that PKCe activation degrades amyloid through Neprilysin and ECE? And that it inhibits tau phosphorylation through GSK3 inhibition?
Sure, clearing out the trash doesn't seem to help patients get better, but it's something that Bryostatin seems to do anyways.
Would that still worry you? And if so, why?
If dysfunctional autophagy in patients is what worries you then you probably also know that the brain luckily enough has a built-in mechanism for clearing out and recycling waste products such as amyloid and tau.
Neprilysin and ECE helps to restore autophagy by degrading amyloid.
Inhibiting GSK3 helps restore autophagy by preventing tau phosphorylation.
The problem with just restoring autophagy however is that it only helps clear out and recycle waste products. It does not grow back the synapses that have been lost over the years.
In fact, plenty of drugs have managed to fix the autophagy problem. The real problem is that patients still did not improve cognitively.
So I have to ask, why are you worried about autophagy if Big Pharma has burned through billions of dollars fixing just that problem without any measurable cognitive improvement in patients?
Or to put it more simply, why are you worried about taking out the trash instead of repairing the damaged house that's about to collapse?
Alright, so what specifically do these "21st century" methods find out about long-term safety that were missed in the previous trials?
What specific method or technology do you think is going to invalidate years of research in hundreds of patients?
We're talking about several trials though. Are you saying that all of them missed something that could pop up later that has never popped up before in any of the several trials that have been conducted so far?
What about the lack of serious adverse effects in patients taking the higher doses for several years?
We're not trying to cure cancer here after all. You said you were worried about long-term safety.
Would you say that the planned pivotal P3 trial will be enough to prove long-term safety that the past year-long cancer trials with 9x higher doses couldn't?
Less than two months left before all cards are on the table.
If a drug is believed to work by regrowing synapses, and it shows human synapses growing back in vitro, and it shows rat synapses growing back in vivo, and it shows improved cognitive abilities in CU patients, and it shows improved cognitive abilities in phase 2a patients, and it shows improved cognitive abilities in phase 2b patients, and it shows improved cognitive abilities in an even bigger group of phase 2b patients...
...why wouldn't it work in mild patients who are suffering from the exact same disease as their more severe counterparts?
8 weeks really isn't that long. At this point we're pretty much right in front of the finish line.
No need for more speculation when results are right around the corner.
Or maybe just some random market maker making a quick buck off a thinly traded stock.
I don't believe in conspiracies and hidden agendas.
It does feel a bit strange though to see the price decline in such a straight and controlled manner for about a month now. No sudden drops or anything, almost as if someone is doing it on purpose.
The same happened on the way up. Completely straight line day after day until it stopped.
Daily movements don't have to mean anything. Sometimes the price goes down and that's just how it is.
If someone is freaking out about 10% drops they should really just stay away from this stock so they don't accidentally give themselves a heart attack.
I see you have found the list of research articles lol
For everyone else that's interested:
https://justpaste.it/4frnd
So they know what the optimal dose is without ever testing it in patients because of "precision medicine"?
Then how come this precision medicine didn't find the optimal dose before they gave patients the wrong dose?
There weren't? Then how would they know they have the optimal dose now if it hasn't been tested in patients before?
Seems like it. Took about two months last time to get the PR out, so if the same applies here we're looking at a mid-September PR.
If they have collected the data it's not blinded anymore.
The database may be a big mess that needs to be scrubbed and checked and tested and what not, but they can obviously see the data if they have collected it.
As for the shareholder meeting, it's just a shareholder meeting, not a press event. Just like they refuse to speak about which firms they're talking to about partnering, so too can they refuse to speak about what little information they have about the data so far.
Shareholders can ask any questions they want during the meeting but the executives are under no obligation to reveal any confidential information to them.
It's been unblinded since last week actually.
https://www.prnewswire.com/news-releases/neurotrope-concludes-data-collection-in-confirmatory-phase-2-clinical-trial-of-moderately-severe-to-severe-alzheimers-disease-300884499.html
The next month or two will be used to run statistical tests on the data and turn it into something that can fit inside a press release.
Contrary to what some are saying on this board though, the current stock price has nothing to do with "leaks" since that would be considered insider trading, which is a big no no for the SEC.
Yes, they found it was safe and found the optimal dose, but the patients on the optimal dose still did not improve over baseline.
See, this is where I get confused. Some patients responded better than others, but even those declined over time.
We're still not talking about an improvement, and the doses in the current trial are the same as the well-responding patients in the last trial, which again, did not improve over baseline.
So again, what makes you think this time will be different?
Thanks for that. What makes you think the data will be different this time?
Correct, it is a P2a safety trial.
I'm not saying the drug is dangerous or bad, or that they're not studying the gut. I'm saying it's clearly not showing any improvement in patients. Their scores are below baseline even after being treated for 148 weeks.
Or would you disagree with that?
Please correct me if I'm wrong, but I'm seeing a chart showing a significant difference between the high dose group and the low dose group. I'm also seeing both groups decline over time. Both slopes are pointing down and end up below 0.
Now maybe I'm blind and stupid and don't know what I'm talking about, in which case could you please explain for me what I'm supposed to see instead?
We're not talking about just one drug though, and the case for muscarinic agonists doesn't look much better either:
https://www.ncbi.nlm.nih.gov/pubmed/3524514
To further demonstrate my point, take a look at page 8 in the document you've linked in your post:
https://i.imgur.com/mp2oeXz.jpg
Both slopes are clearly not pointing up, at all. There is no improvement over baseline, and that's even without using a placebo group. They are claiming that scores have improved when clearly they have not.
What's even more alarming is their attempt to find an improvement in patients by looking at gut microbiomes and DNA sequences in hopes of finding a subgroup of patients that might show something they can use as a target.
Now you might say that non-memantine patients are a subgroup as well, which is true, but in this case the subgroup is based on a drug that patients were not taking. This means that any AD patient can get these results just by not taking Memantine for a month first.
It just sounds extremely fishy to me, and I'm having a hard time understanding why you have so much faith in this drug.
Put simply, I fail to see the logic in your logic.
What's interesting about that SA article is that even shorts seem to agree that this is a $10 billion dollar drug if it works.
Fully diluted that would make each share worth about $370.
Sigma-1 activation having no effect in human patients has no bearing on a sigma-1 activator?
It certainly looks very promising in treating Mouseheimer's, but again, activating sigma-1 in human patients showed no difference from placebo:
https://www.alzforum.org/news/research-news/epilogue-edonerpic-it-does-not-work-alzheimers
As previous Bryostatin trials have shown, you can't just activate PKC. You need to specifically activate PKCe in a way that doesn't downregulate it.
The goal may be right in front of you, but if you kick the ball too hard it's going to fly out into space and award you no points.
Like they did in this trial?
https://www.alzforum.org/news/research-news/epilogue-edonerpic-it-does-not-work-alzheimers
Now you might say that a competitor could just come up with a PKC activator that isn't a fatty acid, but then you're ignoring the fact that PKCe in healthy people is being activated by DAG, which is also a fatty acid.
You would have to come up with a completely new structure that can somehow bind to PKC that isn't a fatty acid, for which there is absolutely no research today at all.
By the time anyone figures that out and brings it to market, our patents will already have expired long ago.