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New interview with Dr. Alkon:
I seriously doubt management would want to raise any cash while the price is below fair market value acording to them.
Here's an excerpt from the 10-K:
"The following table sets forth the high and low closing bid prices for our common stock for the fiscal quarter indicated, as reported on The Nasdaq Capital Market beginning on March 29, 2017 and on the OTC Market prior to March 29, 2017. The quotations reflect inter-dealer prices, without retail mark-up, mark-down or commission and may not represent actual transactions. Our common stock has historically been very thinly traded and, thus, pricing of our common stock on the OTC Market does not necessarily represent its fair market value."
Considering that the CEO was involved in developing Namenda, I'd like to think that he's smart enough to delay any further fundraising until after the new trials have commenced later this year. Any future feedback from the FDA will also most likely push up the stock price to more accurately reflect the true potential of Bryostatin.
Personally I think the smartest decision would be to just wait until confirmation trial results are announced before raising further funds, because then no one will be able to deny that this thing actually works.
Look at the Nasdaq competitors page for NTRP, sort by volume, and you'll see that out of about 419 biotech stocks and warrants, only 19 securities are trading at lower volumes than NTRP.
I think the market is still treating this like a failed Alzheimers project without any regard for the latest post-hoc analysis data.
Apparently nobody cares that there was a statistically significant improvement in patients off Memantine.
Yes, it's old news, but Mr. Silverman is still chairman of the board.
Don't you think getting him removed would make investors a lot more comfortable investing in NTRP?
Well, since Mr. Abbe has the highest position possible in Iroquois Capital (Co-Founder and Managing Partner), it would mean that the shares beneficially owned by Ms. Page should be ignored since they are also included in the number of shares beneficially owned by Mr. Abbe. In a way, you can say that the number of shares attributed to him represent the amount of shares that IC owns.
Here's something really suspicious though. Joshua Silverman, the chairman of the board of Neurotrope is also a co-founder and managing partner of IC. This is a man that has proven links to Adam Gottbetter, the guy who was not only arrested for manipulating the stock price of several microcap companies, but who also was responsible for Neurotrope's reverse merger in 2013.
I am firmly convinced that Dr. Alkon is a straight arrow and that Bryostatin 1 will become a huge success, but I question the motives of some people he surrounds himself with.
AbbVie & Voyager partner up to throw more money on a failed anti-Tau approach: https://www.prnewswire.com/news-releases/abbvie-and-voyager-therapeutics-announce-global-strategic-collaboration-to-develop-potential-new-treatments-for-alzheimers-disease-and-other-tau-related-neurodegenerative-diseases-300600889.html
382,412 shares seem to have been sold by Iroquois Capital during 2017 based on their latest 13G/A, leaving them with 335,514 shares.
Or to put it differently, one of Neurotrope's major shareholders sold 53% of its shares last year.
New video interview with Dr. Alkon:
"for use in the treatment of central nervous system disorders, lysosomal storage diseases, stroke, cardioprotection and traumatic brain injury"
I would say MS qualifies as a central nervous system disorder, yes.
In fact, if you look at this page, there are an impressive amount of disorders that fall under that same label: https://en.wikipedia.org/wiki/Central_nervous_system_disease
Dr. Wender and Dr. Alkon seem to be good friends too, so I doubt we have to worry about any license issues.
I think this abstract describes it well: https://www.ncbi.nlm.nih.gov/pubmed/25959522
"Memory therapeutics that target synaptic loss and dysfunction - that is, to slow, halt, or reverse progression of the disorders at the level of synapses, via synaptogenic molecular cascades such as those of protein kinase C (PKC) and brain-derived neurotrophic factor (BDNF) - possess universal therapeutic value for many forms of memory disorder."
The thing that makes Bryostatin 1 so damn incredible to me is that since it enables the growth of new synapses, it single-handledly deals with the root problem that patients with several kinds of neurodegenerative disorders have, which is the loss of synapses.
This isn't just an Alzheimer's drug. It's a drug for repairing the central nervous system.
Not only has Dr. Alkon confirmed that Bryostatin 1 can be used for AD patients across the spectrum (even the early dementia cases that haven't turned into full-blown AD yet), but that low-cost test you're thinking about exists already and is currently being developed by Neurotrope (although it looks like they're more focused on AD trials right now and will wait with the diagnostic test until later).
Dr. Alkons research shows how PKCe levels can be measured in the skin, and how the levels directly correlate with the probability of getting AD in the future.
These two articles show how it can be done:
https://www.researchgate.net/publication/263934332_Fibroblast_Aggregation_Rate_Converges_with_Validated_Peripheral_Biomarkers_for_Alzheimer%27s_Disease
https://www.researchgate.net/publication/230657221_Spatiotemporal_Complexity_of_Fibroblast_Networks_Screens_for_Alzheimer%27s_Disease
The abstract for that first one has a particularly interesting part in it:
"Furthermore, we show that by using a simple majority rule, i.e., two out of the three assays have the same outcome, we significantly increase the agreement with clinical AD diagnosis (100%). Based on the high accuracy of this strategy, the biomarker profile appears to accurately identify AD patients for therapeutic intervention."
Severe stage is never addressed because the industry has pretty much given up on it.
Now imagine how the FDA will react when they see that Bryostatin 1 reverses the disease and doesn't just reduce symptoms or slow the decline.
They are going to be jumping all over this once Dr. Alkon actually shows them the data (which he does not seem to have done yet according to his comments in the latest Noble presentation).
"FDA Opens New Path for Alzheimer's Treatments"
https://www.bloomberg.com/news/articles/2018-02-15/fda-opens-new-path-for-alzheimer-s-treatments-as-failures-mount
Some notable excerpts include:
"U.S. drug regulators wants to let drugmakers test Alzheimer’s disease treatments on patients years before the disease shows outward signs, and could approve the therapies based on subtle biological signals rather than proof they alleviate symptoms."
"In the proposal, the FDA said it could quickly approve a drug for people who haven’t shown outward signs of Alzheimer’s, if the therapy affects a biological marker of the disease -- similar to how lowering blood pressure reduces the risk of a heart attack. Nothing like that currently exists for the disorder, which is the sixth-leading cause of death in the U.S."
"With a drug on the market under the fast-track process, a company would then have to conduct further trials to confirm that the biological change lead to a meaningful benefit, such as slowing patients’ initial decline in mental function, known as mild cognitive impairment."
"There are no approved Alzheimer’s treatments that slow progression of the disease, while almost 200 drugs have failed."
That is true. Admitting you are wrong is a notoriously difficult thing for most people to do, not to mention huge pharmaceutical companies that have poured billions of dollars and decades of work into the wrong approach.
Being the first to get on board NTRP can however offset that embarrassment IMO, considering the consequences will be even worse if those companies spent all that effort on the wrong approach and then miss this train on top of that.
I think a successful confirmatory trial on our side, and a few more failed trials on their side should help get things going in the right direction.
New CEO starts his work as of today FYI
https://www.prnewswire.com/news-releases/neurotrope-appoints-charles-s-ryan-as-chief-executive-officer-300572448.html
Here's another interesting fact:
While companies such as Celgene and Pfizer have an institutional ownership of over 70%, Neurotrope only has an institutional ownership of 12.01% (https://www.nasdaq.com/symbol/ntrp/institutional-holdings).
As the stock price increases, institutions will have to buy more NTRP shares for their index funds, which should move the price up even further, kind of like a snowball effect.
I think once the market cap of this company reaches $300 million or so, we will see lots of institutions start buying more shares for their small-cap funds, which considering the low float of this stock could lead to rather dramatic price swings.
Unfortunate for them maybe. For us this is good news because it further confirms what Dr. Alkon has been saying all along. Just read the articles in my stickied post and you'll find countless examples of how PKC epsilon is the bullseye we should be targeting rather than the Ab/Tau byproducts BP has been going after unsuccessfully all these years (which by the way are eliminated by activating PKC epsilon, according to the articles).
Hopefully BP will soon discover what Neurotrope is doing and cancel all their AD programs, knowing that their billions are better spent investing in this company rather than keep pursuing their usual outdated approach that has never ever worked.
Here are all the relevant full articles I've found so far. If someone could sticky this I would very much appreciate it.
"Bryostatin Effects on Cognitive Function and PKC epsilon in Alzheimer’s Disease Phase IIa and Expanded Access Trials" (2017)
https://content.iospress.com/download/journal-of-alzheimers-disease/jad170161?id=journal-of-alzheimers-disease%2Fjad170161
"Protein Kinase C epsilon (PKC epsilon) Promotes Synaptogenesis through Membrane Accumulation of the Postsynaptic Density Protein PSD-95" (2016)
http://www.jbc.org/content/291/32/16462.full.pdf?with-ds=yes
"Bryostatin-1 Restores Blood Brain Barrier Integrity following Blast-Induced Traumatic Brain Injury" (2014)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5000781/pdf/nihms810689.pdf
"PKC epsilon Deficits in Alzheimer’s Disease Brains and Skin Fibroblasts" (2014)
https://www.researchgate.net/profile/Daniel_Alkon-BRNI/publication/264794792_PKCe_Deficits_in_Alzheimer%27s_Disease_Brains_and_Skin_Fibroblasts/links/565daf2a08aefe619b267c7a/PKCe-Deficits-in-Alzheimers-Disease-Brains-and-Skin-Fibroblasts.pdf
"Common Mechanisms of Alzheimer’s Disease and Ischemic Stroke: The Role of Protein Kinase C in the Progression of Age-Related Neurodegeneration" (2014)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4446718/pdf/nihms659711.pdf
"Fibroblast Aggregation Rate Converges with Validated Peripheral Biomarkers for Alzheimer’s Disease" (2014)
https://www.researchgate.net/profile/Daniel_Alkon-BRNI/publication/263934332_Fibroblast_Aggregation_Rate_Converges_with_Validated_Peripheral_Biomarkers_for_Alzheimer%27s_Disease/links/565db4ae08aefe619b268e9f/Fibroblast-Aggregation-Rate-Converges-with-Validated-Peripheral-Biomarkers-for-Alzheimers-Disease.pdf
"PKC epsilon Promotes HuD-Mediated Neprilysin mRNA Stability and Enhances Neprilysin-Induced Ab Degradation in Brain Neurons" (2014)
http://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0097756&type=printable
"Bryostatin-1 Restores Hippocampal Synapses and Spatial Learning and Memory in Adult Fragile X Mice" (2014)
http://jpet.aspetjournals.org/content/jpet/349/3/393.full.pdf
"Spatiotemporal Complexity of Fibroblast Networks Screens for Alzheimer’s Disease" (2012)
https://www.researchgate.net/profile/Florin_Chirila/publication/230657221_Spatiotemporal_Complexity_of_Fibroblast_Networks_Screens_for_Alzheimer%27s_Disease/links/5757144408ae5c65490423ee/Spatiotemporal-Complexity-of-Fibroblast-Networks-Screens-for-Alzheimers-Disease.pdf
"Apolipoprotein E3 (ApoE3) but Not ApoE4 Protects against Synaptic Loss through Increased Expression of Protein Kinase C epsilon" (2012)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3346146/pdf/zbc15947.pdf
"PKC epsilon Activation Prevents Synaptic Loss, Ab Elevation, and Cognitive Deficits in Alzheimer’s Disease Transgenic Mice" (2011)
http://www.jneurosci.org/content/jneuro/31/2/630.full.pdf
"Postischemic PKC activation rescues retrograde and anterograde long-term memory" (2009)
http://www.pnas.org/content/pnas/106/34/14676.full.pdf
"Poststroke neuronal rescue and synaptogenesis mediated in vivo by protein kinase C in adult brains" (2008)
http://www.pnas.org/content/pnas/105/36/13620.full.pdf
"A structural basis for enhancement of long-term associative memory in single dendritic spines regulated by PKC" (2007)
http://www.pnas.org/content/pnas/104/49/19571.full.pdf
"Bryostatin Enhancement of Memory in Hermissenda" (2006)
http://www.journals.uchicago.edu/doi/pdfplus/10.2307/4134558
"Protein synthesis required for long-term memory is induced by PKC activation on days before associative learning" (2005)
http://www.pnas.org/content/pnas/102/45/16432.full.pdf
"Therapeutic effects of PKC activators in Alzheimer’s disease transgenic mice" (2004)
http://www.pnas.org/content/pnas/101/30/11141.full.pdf
Here's an article on how Bryostatin 1 "Restores Hippocampal Synapses and Spatial Learning and Memory in Adult Fragile X Mice":
http://jpet.aspetjournals.org/content/jpet/349/3/393.full.pdf
For those interested in further reading, here's an article that explains how the process actually works:
http://www.jbc.org/content/291/32/16462.full.pdf?with-ds=yes
Some notable conclusions in the article include:
"PKC Activation Prevents Degradation of Primary Human
Neurons"
"Prolonged PKCe Activation Prevents Loss of Synaptic Proteins"
"Bryostatin 1 and DCPLA-ME Specifically Activate PKCe"
"PKCe Activation Induces Synaptogenesis in Adult Hippocampal Slices"
"Knockdown of PKCe Reduces Synaptogenesis"
You are definitely undervaluing Neurotrope if you think the world's potentially first treatment for not only Alzheimer's, but several other neurological disorders is going to be valued 10% as much as one of many other cancer treatments.
As Dr. Alkon has stated many times before, Bryostatin 1 has the potential to shift the paradigm of how we treat all kinds of neurological disorders, including stroke, which in itself is a ridiculously massive potential market.
When you hear the word "synaptogenic", it doesn't just mean that it fixes Alzheimer's, it means that it quite literally repairs the circuitry in your brain.
Like I've said many times before, I don't think most people have any idea what a stupendously big revolution in medicine this has the potential to be.
That might also explain why so few people believe in it. It just seems too good to be true.
Confirmatory trial results should put all doubts to rest though, and after that, who knows where the stock price is going to land.
All I know is that opportunities like these only appear once in a lifetime, and that the low stock price today shouldn't be seen as a bad thing, but rather as an opportunity to load up on as many shares as possible, because you know deep in your heart how much more they will be worth only a few years from now once the world realizes what Dr. Alkon has uncovered through his amazing research.
Here's an interesting thought:
This stock has a float of about 5 million.
All it takes is about 5000 people holding 1000 shares each in order to wipe the sell side clean.
I don't know if this has been posted here before, but I found two noteworthy paragraphs about the synthetic Bryostatin 1 here: https://news.stanford.edu/2017/10/12/chemical-method-boosts-supply-key-drug-compound/
"The team members have now produced over 2 grams of bryostatin 1, and once production is scaled up, Wender said, they expect manufacturers could produce about 20 grams per year, enough to cover clinical and research needs. That is a bit more than was ever extracted from B. neritina and enough to treat about 20,000 cancer patients or 40,000 Alzheimer’s patients."
"Stanford University has filed a provisional patent application on the technology, which has been licensed by Neurotrope BioScience for the treatment of neurological disorders. An option to license has been granted by Stanford University to Bryologx Inc. for use in HIV/AIDS eradication and cancer immunotherapy. Wender is an adviser to both companies and a co-founder of the latter."
Apparently 1 gram of Bryostatin 1 can treat about 2000 AD patients, which means that if you want to treat the 5+ million Americans suffering from AD right now, you would need 2,5 kilograms of this stuff, or to put it differently, enough to fit inside a big soda bottle and two soda cans.
I'd say the stock price acting funny is just algorithms/market makers doing their usual thing.
What's unusual IMO is the lack of attention this company is getting.
Results like those seen in the post-hoc analysis have never been seen before in history, and yet it seems like nobody is talking about it, and if they do talk about it they don't understand it.
I don't know about you, but I personally think that this stock has a serious liquidity problem.
There have been several days where the daily volume was so low it couldn't even reach a fraction of the size of my position alone.
Now for me that's not anything to be concerned about, since I'm not planning to sell anything for at least another 3-5 years (or until the company gets bought out by BP), but for bigger fish that want to buy in, it must be frustrating to only see 200 shares for sale on the sell side.
Reading about Dr. Wender figuring out how to synthesize Bryostatin 1 (thus eliminating Neurotrope's supply problem) just a few months ago was one thing, but commencing mass production of the stuff not even a year later?
Amazing.
For those of you interested in how it works, here's the article:
http://bryologyx.com/wp-content/uploads/2017/11/17.bryo_.synthesis.wender.science.pdf
You're probably right about the trial length, but if you go to 13:55 in the presentation you can clearly hear Dr. Alkon saying:
"This is a sustained improvement, and shows evidence that we can go further, even long after 15 weeks, which is exactly what we're going to do in our confirmatory trial."
Some noteworthy things I got from the corporate presentation:
- Dr. Alkon says that the SA article is making false claims, that it is inaccurate, misleading, and that he is disappointed by people "throwing out erroneous statements" about Bryostatin
- He says Bryostatin can be administered orally and that this is the next step of their plan
- He says that they are going to the FDA and expecting a fast-track approval
- He says that the confirmatory trial will be longer than 15 weeks
Here's the corporate presentation: http://noble.mediasite.com/mediasite/Play/f9cc934c8a0148f3b6a234de3e4e6f571d?catalog=6f8e7abd-96e3-462f-8035-f48126f80846
And here's the panel presentation: http://noble.mediasite.com/mediasite/Play/911da4f57eff4257a83b9711230158831d?catalog=6f8e7abd-96e3-462f-8035-f48126f80846
I don't think the cheap price is necessarily a bad thing, considering I've been able to average down several times now while accumulating more shares.
Also, Dr. Alkon has said several times that the company has enough funds to complete the confirmation trial on their own, which means that not only will we be able to keep buying shares for an incredible price, but we can sleep well knowing that they won't be diluted until after they announce results, at which point the price movement will be more than enough to offset any dilution.
I've been telling people about how extremely undervalued NTRP is for over a year now, but you can't deny the fact that the market is currently disagreeing with our point of view.
Yes, a positive confirmation trial is going to launch this to the moon, but as of today, NTRP is still worth less than its industry peers, at least according to the market.
Not exactly. NTRP currently has a market cap of about $62 million while AVXL has a market cap of about $115 million.
Also worth mentioning is AXON, which has a $207 million valuation even though they recently failed yet another AD trial with their lead compound.
I sent them an email asking about the missing webcast and if there was a possible partnership on the horizon, but I've received no response so far.
Anyone else have a better idea of what's going on?
110 companies have their webcasts listed on this page but Neurotrope is nowhere to be found: http://noble.mediasite.com/mediasite/Catalog/catalogs/noblecon14
Strange...
I'm pretty sure Pfizer wouldn't have ended their own AD drug development program and started a new venture fund for neuroscience research unless they knew they were going after the wrong approach.
Consider also the fact that Pfizer HQ is only a 20 minute walk away from Neurotrope HQ (They're both based in Manhattan).
Consider also the fact that any signs of an upcoming BP partnership would launch this stock to the moon and make any future deal more expensive for BP.
Then it suddenly starts to make sense why BP wouldn't want to publically express any interest in this company and do everything they can to not say a thing until a deal has been finalized.
Maybe call Neurotrope and ask their PR guy if there's any partnership discussions going on behind closed doors?
Then again, if they are forced to sign an NDA before entering negotiations, that would force their PR guy to claim nothing is going on behind the scenes.
Neurotrope won't have any competition until 2026, considering how US patents generally last for 20 years and Dr. Alkons patents for PKC activators were filed around 2006.
http://google.com/patents/WO2007016202A1
The confirmatory trial will start before June, and let's say it will take twice as long as the previous one, which measured patients for 15 weeks. If the trial takes 30 weeks and starts on the 1st of June, it should be completed around late December 2018/early January 2019.
Now let's say they need a month or two to analyze the data and announce their findings. This brings us to a press release around February/March 2019.
Even if it takes the company all of 2019 to find a distribution partner and get FDA approval, they will still have a guaranteed 6 year monopoly on treating AD patients from 2020 to 2026.
Bryostatin being an IV drug is also not a problem, considering how all other alternatives basically consist out of either slightly delaying the disease (if at all) or letting the disease slowly kill you.
With 5 million people suffering from AD in the US alone, Neurotrope will have access to millions of potential customers they can charge any price they want for an entire 6 years.
Now let's say they'll charge $500 a month (I would gladly pay $500 a month if it meant keeping myself alive and my memories intact).
$500/month x 5 million patients x 12 months = Yearly revenues of at least $30 billion.
Even if they only reach a million patients and charge $300 a month for the drug, that's still $3.6 billion in yearly revenues.
I think this image says it all:
https://www.sec.gov/Archives/edgar/data/1513856/000114420418001210/image_005.jpg
Any idea where I can find that live webcast?
Pfizer knows.
Now watch as the rest of the industry slowly wakes up to the fact that amyloid beta and tau tangles are just the symptoms, not the causes, just like Dr. Alkon has always said.