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NTRP still shorted up the ying yang, get ready for AF & friends to do their thing come Monday PM or Tuesday AM
I wouldn't worry about AF. He and his friends have no influence whatsoever on stock prices. Lol
Shoddy research by the author. Notice the table at the bottom of page 1. Completely wrong assessment of the current trial phase for one of the stocks and also its market cap. That alone makes me dubious of everything else he wrote.
Is a-beta protein misfolded protein?
If so, where and how does a-beta become misfolded?
Well that flies in the face of conventional wisdom. Every Wall Street guru says to always set a stop loss, usually immediately after you stake a position.
If your focus is share price, AVXL has done really well lately. The price was 2.43 last September and is 5.82 now. That's well over a 100% increase in only 7 months. Stock continues its uptrend.
Misfolded proteins have a tendency to aggregate. Is an example of this phenomenon a-beta protein aggregating into amyloid plagues? If we assume that a-beta is a misfolded protein, where does it get misfolded? I watched the linked 2' video and it doesn't show a-beta becoming misfolded. It shows APP, residing across the cell membrane, being clipped by enzymes to form a-beta, which is promptly expelled from the cell via exocytosis. This is happening at the cell membrane, not at the MAM.
The video leads one to believe all a-beta that is produced is immediately expelled from the cell; however, I have read or heard that a-beta can be found inside the cell too. I haven't verified to my satisfaction that a-beta can also be found inside cells. If it in fact does occur, I don't know how that happens.
To my knowledge, all amyloid plague is extracellular, whereas Tau is intracellular.
Considering the aforementioned, what does the MAM have to do with formation of a-beta?
"The sell on the news theory has no application to the unique circumstances surrounding this stock."
^Oh I beg to differ. The circumstances surrounding this stock are indeed "unique". I'd choose a different word, perhaps peculiar, suspect, odd, unorthodox, strange, or concerning. NTRP, bryostatin, and most of all, this trial are ripe for criticism. Investors shall see that happen shortly on a broader, more public scale than ihub.
Wrong. Higher volume and a 8.11% drop already today b/c this might be the start of the multiday NTRP takedown b/c news is expected this week. Sell the news can happen the day news is released, a few days before news is released, or a few days after news is released. When NTRP crashed on March 14, that wasn't the day of uplisting. But is was near the expected uplisting day/week. NTRP then continued to crash on March 15 and 16 too. Hasn't recovered since. Yet NTRP has further to drop before it reaches a bottom below $10. I plan buying at $9.
The above scenario is what happened to a stock I was tracking November of 2015. Good news was expected on Sat, yet it started to break down on a Wednesday and had red days on Thurs and Friday too. Sat the news was released. It was positive, as expected. The stock started to recover Mon morning. Then a hit piece was released that morning by a well-known analyst/writer and the stock almost immediately crashed hard. Hasn't recovered since despite still posting good news.
What is wholly missed by traders/investors is that it doesn't matter what the results of this Ph 2 study are. Much of the time, micro cap biotechs crash on news period. There's an excellent chance that will happen to NTRP. Happened already surrounding NTRP's NASDAQ uplisting. NTRP is on AF's radar and it will not go unnoticed. If you think he's neutral towards NTRP, you are mistaken. AF is a protege of Cramer, whom owns The Street. Cramer's featured in the 3rd link down explaining the ruse.
http://smithonstocks.com/illegal-naked-short-selling-appears-to-lie-at-the-heart-of-an-extensive-stock-manipulation-scheme/
http://smithonstocks.com/illegal-naked-short-selling-appears-to-lie-at-the-heart-of-an-extensive-stock-manipulation-scheme/www.deepcapture.com/wp-content/uploads/2009/10/story-of-dendreon.pdf
Prion disease usually happens in elderly people. It is neurodegenerative disease. It is disease of protein misfolding, which is its relevance to Alzheimers, Parkinson's, etc.
Dr. Corinne Lasmezas is on the scientific advisory board of Anavex. She is a world expert on prion dieases. So why is she on Anavex's board? She describes Alzheimers, and the like, as protein misfolding diseases. The MAM (connection btw mito and ER where proteins get folded, or misfolded). Anavex's sigma 1 drugs target the MAM so proper folding is preserved. This is pertinent for prion disease and other neurodegenerative diseases.
You can google Dr Lasmezas' research and watch her Ted Talks. Here's her bio from Anavex website:
Corinne Lasmézas, DVM, PhD
A member of the Scientific Advisory Board, Professor at The Scripps Research Institute for the past 10 years and frequent TED Speaker, Dr. Lasmézas is an internationally recognized expert in the field of neurodegenerative diseases with a focus now on studying the mechanisms of neurodegeneration. Since her appointment at Scripps in 2005, Dr. Lasmézas has focused on how misfolded proteins lead to neuronal dysfunction and loss in diseases including Alzheimer’s, Parkinson’s and prion diseases. Additionally, Dr. Lasmézas is a reviewer for national and private funding agencies worldwide, including the US National Institutes of Health (NIH) and the UK Medical Research Council, and an advisor for the US Food and Drug Administration (FDA), the US Environmental Protection Agency (EPA) and the US Department of Agriculture (USDA). She has published more than 60 original scientific papers. Earlier in her career, Dr. Lasmézas’ research provided the first experimental evidence that the prion disease “mad cow disease” had been transmitted to humans, causing variant Creutzfeldt-Jakob disease. This fatal disease belongs to the same group of age-related neurodegenerative diseases as Alzheimer and Parkinson’s diseases, caused by aggregates of misfolded proteins. At the peak of the mad cow crisis, Dr. Lasmézas became an advisor to the World Health Organization (WHO) as well as several governmental and public health committees. Dr. Lasmézas holds a PhD in Neurosciences from the University Pierre & Marie Curie in Paris and obtained her Doctorate of Veterinary Medicine and Diploma of Aeronautic and Space Medicine from the University of Toulouse, France.
Buy stop in place at $9 to take on a trading position.
What are y'all setting your stop losses at?
No. Everything takes longer than expected in biotech, shareholders have to wait years before the price rises, if at all. Takes patience. Half the shareholders didn't even know a vote was taking place.
high pucker factor for shorts these days. low volume, low liquidity, with upcoming short squeeze
$10 eom
Do you still think that donepezil is a drag on 2-73 or did the last Anavex trial update disuade you of that notion?
Please. Anavex has MD's and biochem PhD's as investors, they just don't post on ihub. The world's foremost expert on sigma receptors is the co inventor of 273. The editor of The Journal of Alz Disease, himself a respected Alzheimers researcher, said last Dec that 273 has posted the best Alzheimers trial results to date. I'll take his word over AF's thank you very much. Call me crazy.
Anavex has employees and a board of advisors that have impressive credentials. They've run thorough, efficient, cost effective trials and received the financial backing of foundations and the Australian govt. Biogen has shown interest in their compounds
Anyone that's been around micro cap biotech knows that news, especially highly anticipated news, usually brings a sell off, regardless if the news is good or bad. And, FYI, NTRP is on AF's poop list.
The country's drug czar wants to criminalize medicinal use of marijuana unless clinical trials can show it is effective (this has been shown already I believe) and it can be delivered in pill form. A synthetic mimic of marijuana's active ingredients has been made that can be delivered in a pill; however, it comes with a lot of side effects. Will the synthetic version of byrostatin also come with a host of additional side effects? Who knows? I expect separate clinical trials will have to be run to find out, and for more than 3 friggin months. I mean cmon, 3 months? Gimmee a break
Anyone that asserts that Anavex's pipeline results are tenuous doesn't understand the science or drug trials. This stock has doctors and lab researchers investing in it and I'll take the word of them and Dr George Perry, editor of The Alzheimers Journal, over any anonymous person on social media or AF et al.
If the interest rate is 125%, that means the dump to this pump is in the offing.
I concur. Have NTRP investors looked at the track record of drugs seeking to boost growth factors? Case in point, M3 Biosciences out of Washington state. Back in 2014 there was a lot of hype surrounding this privately held company, much like there is now surrounding NTRP. Its Alzheimers drug had/has same MOA as brysotatin, boost growth factor levels. NIH and a foundation were funding its early trials. A trial enrolling, I believe, 450 patients flamed out. The company hasn't given up on the drug, although its been stalled. Their website is a joke, no listing their pipeline or trial progress.
Bryostatin fails to correct the cause of the Alzheimers, mitochondrial dysfunction. The first thing to show up in pre Alzheimers patients is mitochondrial dysfunction, not low levels of PKE epsilon. Anavex's sigma 1 drugs correct mitochondrial dysfunction, as well as stimulating regulated synaptogenesis
It dumbfounds me that the goal of Neurotrope is to stimulate synaptogenesis yet they don't bother to include P300 testing in their trials.
I think there is a 50/50 chance NTRP will crash post Ph 2b results no matter the results.
You're mistaken. There were/are two parts to Anavex's Phase 2a trial. There is Part a and Part b. Part a was 36 days. Part b was 52 weeks after Part a ended. Part b was extended for an additional two years. Total trial length for Ph 2a if you include the 2 year extension will be 3 years and 36 days.
Anavex's clinical trial designs are what the FDA now desires. They are the FDA's preference. Anavex is wise to design their trials per the FDA's preferences. Many trials fail b/c drug companies don't follow the FDA's advice and preferences.
Did the FDA request and prefer that Neurotrope design their Ph 2b and Ph 3 trials to be only 3 months? Or was it Neurotrope that requested the FDA approve their abbreviated trials? I'm guessing the latter was the case?
Dr Alkon firstly is looking to get paid, just like everybody else in capitalist America. That means getting bryostatin FDA approved to treat Alzheimers, by hook or by crook.
What you need to remember is that the current Anavex 2-73 trial is only a Ph 2a trial. A primary endpoint to the trial, which I believe is typical for most Ph 2a trials, is placing patients on different dosages to find out what the maximum tolerated dose is for patients that have different characteristics. For instance, maybe the trial will discover that the mild Alzheimers patients could tolerate a higher dose whereas the moderate patients could only tolerate a lower dose. Patients that dropped out due to dizziness etc..........probably were on too high a dose, given their particular circumstances.
The trial also seeks to correlate the different dosages with therapeutic effect. The trial has found that 14mg seems to be the minimum dose that gives some benefit.
3 months is short term use of a drug, not long term. When I say long term, I'm thinking 1-2 years or more. Take steroids, someone can take them and be OK short term, but 1 or two years down the road significant side effects may appear. Exactly when should we expect side effects to appear in Alzheimers patients on byrostatin? IDK and these trials won't do anything to bring clarity b/c they are of such very short duration. What I like about the Anavex trial is that patients can continue on the drug for two years beyond the 52 week trial. During those 2 years, they'll be tested every 3 months or so to track their long term progress and any side effects.
After the bryostatin Ph 2b results are reported, my guess is, a widely read article(s) will appear that is critical of the trial and Neurotrope, regardless of what the results are. One widely read biotech writer has it in for NTRP. This will coincide with a massive sell off of the stock and maximum shorting (both legal and illegal). The stock will crash to below $10. In a crash of this type, stops afford little protection. These severe drops on news are typical of micro cap biotechs.
Despite all the hype surrounding bryostatin, I have significant doubts. It seeks maximum synaptogenesis by strongly increasing levels of growth factors. I've been informed by a neurologist that unregulated synaptogenesis has a downside, increased incidence of seizures and behavioral/psyche issues for people that have Alzheimers. Long term, I believe bryostatin will produce a lot of side effects and adverse events in people with Alzheimer's. The track record for drugs that increase growth factors is not good. Bryostatin does not at all address/correct mitochondrial dysfunction. Many Alzheimers experts describe Alzheimers as a "mitochondrial dysfunction disease". The short term results for bryostatin I expect to be good. However, I see this drug as neurorestorative but not neuroprotective, so I don't see it as a long term solution for treating Alzheimers. The sigma 1 drugs show correction of mitochondrial dysfunction (neuroprotection) and also boost synaptogenesis (neurorestoration), tho their synaptogenesis is more measured and regulated for when the neurons need it. Sigma 1 drugs stimulate PKC via M1 receptor stimulation and via releasing calcium from IP3 channels as needed. Sigma drugs treat microglial cells and oligodendrocytes, not just neurons. Not aware that bryostatin does this. That is crucial b/c those brain cells are effected by Alzheimers. Bryostatin given for the treatment of Alzheimers reminds me of anabolic steroids, such as testesterone. In the short term, they work great, you see a huge response intitially. However, long term, problems arise (side effects and adverse events). 80's NFL football player Lyle Alzedo is an example of long term use of steroids. Neurotrope is wise to keep their trials to the unheard of length of just 3 months, which I've never seen before in a Ph 2b or Ph 3 Alzheimers trial. It is incorrect to compare Anavex 273's Ph 2a trial to Neurotrope's Ph 2b trial for bryostatin. There is a difference between Ph 2a and Ph 2b. Different end points. Neurotrope did run a Ph 2a trial for bryostatin, but I can't find the full top line results for that trial. Weird. They admined ONE DOSE of the drug and that was the extent of their Ph 2a to "prove" safety of the drug in Alzheimers patients Lol.
Was it bryostatin's Ph 2b or Ph 3 or both that were initially planned to be 6 months but then were shortened to just 3 months? That is a red flag imo. Are the Ph 2a patients still on the drug? If not, why wasn't this option given to the patients if the drug is so great? Are the compassionate use patients all on the drug still? If not, why not, if the drug is so great long term? I heard the Ph 2b patients will be tracked for one month after the trial ends but those patients won't be able to continue on the drug until AFTER the drug is FDA approved. Is that correct? If so, that is strange and concerning. Is Neurotrope afraid if they continue on the drug side effects may pop up which might interfere with the drug gaining FDA approval?
Flurizan was an amyloid reducing drug. Everyone now knows that approach sucks. Alzheimers is a mitochondrial dysfunction disease. Only 1 drug in clinical trials addresses that - Anavex 2-73. That is what makes 2-73 neuroprotective, not just neurorestorative (cough bryostatin). 2-73's safety profile can't be touched by the competition. The current 2-73 trial is Ph 2a. It's not the same as Ph 2b or Ph 3. Its patients have mild TO MODERATE Alzheimer's Disease. The patients in this trial aren't on optimized dosages. This is a small trial not powered for statistical significance, tho a bunch of the results have been statistically significant. Dr George Perry of the Alzheimers Journal said 2-73's scores are the best he's ever seen, better than Flurizan, donepezil, and bryostatin.
Well the company and its shareholders talk like they have, even tho the 3 month results haven't been released yet. I don't think much stock can be put into 3 month results with regard to safety or efficacy, but they think otherwise.
This is Ph 2a trial, not Ph 2b nor Ph 3. It isn't powered for statistical significance and the dosages given aren't optimized. Efficacy isn't a primary endpoint. Nonetheless, there were favorable efficacy scores over time, which was unexpected.
Unfortunately the trial didn't show cure of Alzheimers after just 3 months like one of Anavex's competitors has demonstrated.
Networks only to be eventually destroyed as the neurodegenerative process continues. Microglia and oligodendrocytes upon which neurons depend also malfunction in Alzheimers too and bryostatin doesn't fix them.
Why? To see the full spectrum of side effects and adverse events that may develop over time. 3 months is too short to assess that fully. I'm most concerned about seizures. I suspect bryostatin will increase an Alzheimers patients chances of developing seizures. Remember, Jenni Spencer developed seizures after going on bryostatin. A seizure is what eventually lead to her developing pneumonia and dying. I don't know how soon the severe seizures developed after she went on bryostatin. Within a 3 month window, or after?
I also want to see if any improvement is short lived (<6 mos). The approved drugs keep patients above baseline for <6 mos typically and then nosedive. Donepezil can be of benefit out to a year, best case. You can't tell if the drug is disease modifying in just 3 months, so don't assume when the 3 month results are good that they're gonna stay at that level permanently or improve further.
Bloomberg radio this week talking about long trials that last >1 yr are necessary for Alzheimers trials. Why has Neurotrope conspicuously designed extremely short clinical trials for a disease that necessitates longer trials to rule out noise? Why did they reduce their Ph 3 from 6 mos to 3 mos? Why are they gonna wait til after bryostatin is FDA approved to put their Ph 2b patients back on the drug?
https://assets.bwbx.io/av/users/iqjWHBFdfxIU/vmq6OggMFIkM/v2.mp3
Within 5 yrs 3-71 will get patent and fda approved and everybody knows it's superior to 2-73
Review of bryostatin-1 by amstocks82:
1) "bryostatin-1" is given as an intravenous infusion. This means that there is significant expense associated with dosing patients. Due to bryostatin-1 being an infusion, it makes it more difficult to get an appropriate dosage. That is because an infusion goes directly into the blood. It is difficult to give infusions every day. That means that sufficient bryostatin-1 must be given to last several days each time it is given but they can't give so much that it causes severe side effects. In the study, they gave 7 doses in 12 weeks. They started with a dose every week for two weeks (loading phase) and then one dose every two weeks. This was administered by an IV over 45 minutes. See the clinicaltrials.gov summary of the trial:
https://clinicaltrials.gov/ct2/show/NCT02431468?term=Neurotrope+Bioscience,+Inc&rank=1
2) The dosage and method of infusing bryostatin-1 has been studied since the early 1990s when it was given to cancer patients and has been studied for Alzheimer's disease for over 14 years
http://www.tandfonline.com/doi/abs/10.1081/CNV-120025095?scroll=top&needAccess=true&journalCode=icnv20&;
3) Brystatin-1 has been found to have several adverse side effects. The side effects are one of the reasons that bryostatin-1 requires a much longer testing period. The side effects of bryostatin-1 are age dependent getting worse as the patient ages. http://onlinelibrary.wiley.com/doi/10.1111/j.1527-3458.2006.00001.x/pdf,
( http://www.tandfonline.com/doi/pdf/10.4161/cbt.1.4.17see page 411 for toxicity summary )
( https://rd.springer.com/article/10.1023/A:1020694425356 )
A2-73 works well as a tablet or pill taken by mouth and does not have similar negative side effects as does bryostatin-1. There is no question that if bryostatin-1 and A2-73 had similar beneficial therapeutic impact on patients Alzheimer's disease and other diseases of the brain and nervous system, that A2-73 would be the blockbuster drug and bryostatin-1 would be something doctors would regrettably have to try if A2-73 didn't seem to be working.
The lack of major side effects makes testing A2-73 much simpler. With bryostatin-1, the side effects mean that months of follow up are needed to verify that the drug has not caused adverse side effects to each patient. Additionally, side effects limit the amount of time it can be given for.
The fact that A2-73 is given by mouth reduces the costs hugely. An infusion center will charge $800 to $1200 just to give an intravenous infusion. With A2-73, the patient or patient care giver can be issued a bottle of pills with the typical instructions printed on the bottle and on a handout.
Bryostatin-1 is typically given for a short time only due to side effects that get worse over time. In this case, it was given for 12 weeks. If Bryostatin-1 works as well as A2-73 for those 12 weeks, it would not be as effective as A2-73 in the long run simply because A2-73 can be given for much longer periods and can therefore be benefiting patients over a longer period of time.
The next reason that I think bryostatin-1 probably does not have the same impact is because bryostatin-1 is a natural product that scientists/doctors noticed seemed to have a positive neurological impact. It was not created to have an impact on Alzheimer's disease. The impact it does have is an accident of nature just as the side effects are accidents of nature.
I do think the phase 2 results show bryostatin-1 show it has some utility but I think Anavex2-73 is as good or better with fewer side effects and a much more cost effective treatment.
The company is working on an oral version of bryostatin-1 but it is not yet ready. And they can now synthesize the drug in the lab. If they get an oral version working, they will have to restart in the Phase I trials.
No mention of bryostatin-1 or stem cell therapy? https://seekingalpha.com/article/4054680-alzheimers-disease-next?page=3
That's the beauty of AVXL, they ran just a small non-optimized Ph 2a trial to find optimal dosing and max tolerable dose, yet they've unexpectedly been getting very good efficacy results at every 3 month interval for, what will be, 15 monnths.
They had patients on different dosages. Assuming all the drop outs reason for dropping out was related to the Anavex drug, the drop outs that cited dizziness, they were prolly on too high a dosage, whereas that same dosage on another person in the trial was/is fine. The Ariana and PK/PD analysis is sussing that all out (what dosages are tolerated and most effective for different types of people). Ph 2a wasn't even optimized or powered, yet Anavex saw unexpected, stat sig efficacy results; that's unprecedented at 57 weeks (and soon 15 mos). I like how Anavex is using biomarkers in their trials. Is Neurotrope for Ph 2 and Ph 3? They should be b/c P300 is correlated with synapse function, which is the entire focus of bryostatin. I'll assume they are. I also like how Anavex attracts others to help fund their trials: the Australian govt and a couple different foundations. Biogen's studying Anavex's drug and if they like it for MS there will be a deal struck at some point. Anavex has a nice pipeline and their drugs are targetting so many different, both related and unrelated, diseases from insomnia to depression to MS to epilepsy to cancer, etc. And their drug 3-71 is even a better drug than 2-73
NTRP dilution. More to come
Is BP subject to the gross manipulation perpetrated upon small and micro cap biotechs? Or is their share count and stock structure just too immovable for the manipulators (funds and perhaps competitors)? Are large caps relatively spared this unrelenting, unpredictable, artificial volatility?
On another note, with most stocks, the 200MA is a key indicator of support or resistance, but with the volatility and swings of small caps during bull and bear runs, the priceline leaves that MA in the dust. Is it better to use a MA with a shorter period that hugs/tracks the price closer, such as the 50MA or even 20MA?
Why a 3 month Ph 3 trial Antti to prove bryostatin's safety and efficacy in Alzheimers patients? Why not just give one dose, like the joke that was the Ph 2a trial, and then follow up for testing 3 hrs later and call it a day/trial (apparently in the compassionate use patient that's only how long it took for improvement. A "miracle"! to quote Alkon. Case closed, cure found! Lol). Why drag things out for 3 long months? Shareholders should be complaining about unnecessary waste and delay!
According to Antti's logic, Aricept reversed/cured Alzheimers years ago based on its 3 month trial results! Why isn't this news? Some kinda Russian conspiracy? Sorry Neurotrope, Phizer's Aricept beat you to the punch :(
Anavex 273 has posted unprecedented clinical trial results each time its given them over the past two years at major Alzheimers scientific conferences, which is the expected venue to present trial results of a substantive nature. Why? So results and trial design can be subject to peer review and discussion. George Perry, Alzheimers researcher and editor of the Journal of Alzheimers Disease, said last December that 2-73 is the best Alzheimers drug he's seen. Funny he didn't mention bryostatin given that his journal did run an article on it. Smart of Neurotrope to stay away from the scrutiny of the scientists at those conferences when they put out their spin/PR. Keep things on the down low and pray Trump's corporate friendly, soon to be gutted, FDA plays along.
Bryostatin's motto, "If at 1st, 2nd, 17th, 25th, 39th, you don't succeed, try try again!" Lol Sink another $2 million into it, gotta be good for something right? Head lice maybe?