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Patient 2 listed in your post is Jenni. She's not the 4th compassionate use patient, if there even is a 4th, which I don't think there was or Neurotrope would have had to disclose that. How does this Michael Bigger of Bigger Capital know there weren't "super responders" among the 3 (he said 4, which I'm dubious of). Does he have access to insider info that we don't?
Shady of Neurotrope to not list for how long the 3 patients were on bryostatin, what their dosages were, and at what interval the follow up mmse and adcs were performed for the 3rd patient.
Will they be presenting Ph2b results at a scientific conference? I don't think they've ever presented any results at any scientific conferences, which is irregular. The big Alzheimers conference for spring is March 31st in Vienna.
I assume the PPS of NTRP will escalate the closer we get to end of April when they present their Ph 2b results. When results are presented, assuming they are decent to good, do you anticipate the stock will tank, as per AVXL Nov of 2015 and July of 2016 on news, or do you think NTRP will go up? Retail holds little of NTRP. Only 450+ investors and the float is only 1.6 million shares. So, would those factors make it more or less susceptible to a massive sell off and shorting attack on the news?
Assuming bryostatin-1 becomes the new SOC and does indeed reverse Alzheimers Disease, ballpark, what would share price of NTRP eventually be?
Also, how likely is it that it could be given orally at some point in time? I read something saying this is a possibility?
I think this drug will help to mitigate the effects of Alzheimers for a time or to some degree, much like how donepezil helps for up to a year, best case. However, Alzheimers is an aggressive degenerative disease that is 100% fatal. It is one of the most difficult diseases to treat successfully. So, I doubt bryo will reverse or halt the disease permanently or cure the disease. It concerns me both of Neurotropes Ph 2 trials were only 3 months or less. Long term effects of bumping up growth factor are also a concern, but 3 month trials won't reveal much on that front.
Excellent theory Xena. I concur. I think NTRP's bryostatin could help for 3 months, maybe a year, before its usefullness peeters out and/or long term side effects become a problem potentially. Whereas with 273, the initial short term effect isn't as remarkable, its effect is more gradual and more for the long haul b/c it is going after the underlying dysfunction causing Alzheimers and correcting that. NTRP's drug could be given in bursts every so often to regenerate synapes as needed.
How much does it usually drop during these scenarios bUrRpPPP? Think it will go much lower? Hopefully not the basement at $8. Ouch. Wouldn't ya now it I finally drink some of the Kool Aid and took a position and then she tanks even further today. Thanks
Guess what, the multitudes of other companies that have invested millions or a billion into the next best Alzheimers treatment felt really great about their drug too early on. I bet scientists that ran 38 clinical trials for bryostatin to treat cancers and HIV felt really optimistic that the trials would be successful too.
The Ph 2b was originally planned to be 6 months long, but then Neurotrope amended it to just be 3 months long. Seems they doubted scores would hold up long term. Neurotrope will announce good results in April. This board will be going ga ga, intoxicated that Neurotrope is gonna be the next REGN or Acadia. Sustain good scores for a year or more, then we'll talk. Neurotrope is gonna run a PH 3 based on just a 3 month trial? Highly irregular.
Check it out. The list of all the clinical trials for bryostatin 1, all 41 of em. 3 are Alzheimers trials, the rest are completed trials for different types of cancer and HIV. All those ended in failure. Track record in mice, good, track record in humans, not so good https://clinicaltrials.gov/ct2/results?term=bryostatin+1&pg=1
Lol You mean the 6 in Ph 2a? The 6 that got one dose of bryostatin and didn't die so we're gonna crown it the cure for Alzheimers? The 6 for whom Neurotrope has released no hard data some 8-12 months after the trial ended? Neurotrope has given us nothing to sink our teeth into cept for mice studies and them saying, "Trust us". No numbers provided whatsoever. I'll believe its the cure when I see 1 year results. I'm not gonna go ga ga over 3 month data even if its great b/c drugs track record against Alzheimers. I've seen only 1 drug that has shown it can do jack against Alzheimers after 1 year. Stabilization over 1 year I consider a success considering it is a degenerative, fatal disease.
How long is Ph 2b scheduled to last, 6 months at best? Talk about designing trials to avoid revealing failure
If the patient has never been on donepezil before and would start it at same time as 2-73, that is when you would be more apt to see synergy and better gains in test scores for the first 6 months. Early on is when the donepezil helps, after 6 months, its kinda "shot its wad" so to speak and just takes up space on sigma receptor sites, sites which otherwise could be occupied by 2-73. Keep in mind donepezil's sigma affinity is like 1000 and 2-73's is only like 30.
In the Ph 2 trial, not everyone was on donepezil! There were like 6 or 7 that weren't on it. At 6 months, they performed best. Why? Maybe b/c the other patients had been on donepezil for some time when the trial started. At that point, donepezil was prolly just occupying most the sigma receptor sites, but not doing anything of benefit and crowding out the introduced 2-73 from docking onto receptor sites.
So what do we know about bryostatin? It originally looked promising for treating several conditions. Researchers felt it would perform best for treating cancer. So they started there. Mice trials looked good. Failure in clinical trials and side effects noted (#1 was pain).
So what makes you think it will perform differently for neuro disorders? Mice trials? Subjective observations of compassionate use patient Jenni by loved ones? That's all we have to go on at this point.
Warrants. People have told me this will be a big problem for NTRP's shareholders.
Been doing some research, bryostatin was originally thought to work best for cancer, not neuro diseases, so the drug was researched for cancer first. Results with mice were promising so clinical trials were carried out. The drug failed in humans. Main side effect noted was pain. No safety studies done for Alzheimers patients to date.
I've read short term exposure to bryostatin activates PKC, whereas long term exposure inhibits PKC. What does that mean exactly? Does it mean the drug becomes inhibitory if given past a certain length of time, say 3 months? Or, does it mean if the drug is restricted to just being given, for example, once/week, then it activates PKC, however, if it is given everyday and is in the brain constantly, then it inhibits PKC?
Wrong. Neurotrope and Dr. Alkon are hyping this drug, which hasn't even been successfully synthesized, which will be accomplished when exactly? Do we know? Neurotrope says "trust us" that it reverses Alzheimers and will be synthesized (if so, economically?). Yet, all we have to go on is 1 patient whose caregivers believed she made some improvements before she died. Oh yeah, and the mice. Before I invest in a company making such grandiose claims, I've got questions I want answered. I want to go over such a company with a fine tooth comb and do my DD. If that's out of line, "Well, excuuuuuuuuuuuuuse ME!", to quote Steve Martin.
The woman that died, let me get this straight, for an entire year she was getting better and better while on bryostatin. She immediately stopped bryostatin when she got pneumonia, nonetheless, the cognitive benefits of the drug persisted for 8 weeks after she had stopped it. Is that correct?
A for-sure downside of this drug is it has to be given IV every week. Major pain in the butt for someone with Alzheimers that is elderly. If they have to schlepp to the clinic to get the drug administered, that's half a day. Plus they need to arrange transport. In fact, the gal that died contracted pneumonia during a car trip to the clinic to get her treatment. If they can get it done at home, prolly have to pay a nurse to stop by the house every week. Lotta people don't like needles.
At the end of 1 yr of byrostatin was she more improved than the first several months of treatment, or worse off (cognitively)?
Dr. Alkon said none of the other approaches prevent neuron or synapse death. He overlooked Anavex's pipeline of sigma 1 drugs. They are said to be neuroprotective and have hard data to back that up over 15 months. Some patients in their Ph 2a trial have been on the drug for over 2 years. The brain isn't like the liver, once neurons are dead they can't be regenerated.
George Perry is editor of The Journal of Alzheimer's Disease and an Alzheimers Disease researcher himself. He recently said in December that Anavex 2-73 has shown the most promise of any Alzheimers drug to date. He didn't mention bryostatin-1, which was written up in the Journal 2 years ago.
I'd wager the Ph 2b 3 month trial of bryostatin-1 will show some favorable results. But I'm not sure I would invest even if that is the case. Continued improvement, or even continued stabilization, beyond 3-6 months is key. Donepezil shows improvement above baseline for 3-6 months. As I mentioned in an earlier post, bryostatin activates PKC in the short term. Long term, it INHIBITS PKC. Case in point, the compassionate use patient showed, according to subjective observations, limited improvement for 8 weeks. Improvement was not sustained long term. Another compassionate use patient didn't show any improvement from the drug, just observed stabilization, for how long, we don't know. The mice showed improvement, but for how long? >3-6 months?
Look at 10 day chart. IBB up 5% and AVXL up 35%. The sector's performance also something to do with AVXL's performance. I've read 1/2 of a stocks gains have to do with its sector's performance. If biotech were down, these recent gains wouldn't be as much.
Attached link describes the dosing of a 27 year old compassionate use patient that was given bryostatin 1 via iv for an indeterminate length of time. He was given the drug iv for the first 3 weeks of every month that he was on it. I'm assuming 1 iv treatment/week. Patient had very early onset of Alzheimers which ran in his family. Patient severe Alzheimers. Cause of it in this family was a very rare expression of a particular gene. I wonder if the 2 other compasionate use patients were from this patient's same family?
Patient was subjectively judged by others to have experienced limited improvement of symptoms that persisted for 8 weeks. I'm assuming that 8 weeks was for the first couple of months of treatment. Not sure if he was on other Alzheimers drugs at the time. No mention of side effects. No hard data given. Patient's symptoms were so far advanced that I doubt he was capable of participating in typical cognitive assessment tests. No mention of brain scans, P300, erp's, or any testing whatsoever.
The 8 weeks of improvement, was that during treatment, or was that improvement that persisted for 8 weeks after treatment had ended? Did all 3 compassionate use patients have early onset Alzheimers caused by rare expression of the same gene? If so, is the mechanism that caused their atypical expression of Alzheimers related to the cause of Alzheimers in most patients? For instance, does the rare expression of that gene in that family perhaps cause an enzyme (for example, PKC) not to function properly, resulting in this rare, very early onset, expression of severe Alzheimers? Is it unlikely that this is the same mechanism that causes Alzheimers in most patients? If bryostatin targets that mechanism, would it also be expected to work in patients that develop Alzheimers due to a different mechanism?
http://www.j-alz.com/content/severe-alzheimers-patient-responds-bryostatin-treatment
Wrong. A 3 month trial doesn't prove jack. Donepezil keeps cognitive scores above baseline for 3-6 months, so, using your rationale donepezil cures/reverses Alzheimers! Woohoo! But no, after the initial bump, the drug's effect fizzles. This is the problem with all the approved Alzheimers drugs.
Bryostatin 1 is a potent modulator of protein kinase C (PKC). Short-term effects of bryostatin 1 include activation of classical or conventional PKCs and novel PKCs, whereas prolonged presence leads to lowered PKC activation. Bryostatin 1 effects on different isoforms of PKC vary.
We may see a bump from brystatin over several months, such as we've seen with the other drugs. However, whether any improvement or stabilization can be sustained permanently is another story. The above paragraph says bryostatin's effect on PKC is a short term effect, whereas prolonged exposure to bryostatin actually lowers PKC activation! Perhaps this is another reason why Neurotrope has been incentivized to limit trials to just 3 months duration? I want to see a trial that lasts a year.
Phase 2 trials are supposed to primarily examine safety of the drug in patients that have the disease. Phase 1 establishes safety in healthy people. Has Neurotrope established the primary endpoint of safety for Phase 2? They gave ONE SHOT of brysotatin to just 6 patients (3 got placebo) and that's supposed to prove the drug is safe and doesn't produce any adverse events or side effects in people that have Alzheimers? Seriously?
Neurotrope said the secondary endpoint of their Ph 2a trial was efficacy. Yet, no release of efficacy data many months after that trial concluded. No efficacy or safety data for the 3 compassionate use patients either. Hmm. Neverhteless, Neurotrope is confidant the drug will reverse the disease and has said it has reversed the disease in 2 of the 3 compassionate use patients, however, they haven't shown us any data to back up that grand claim. If they are making that claim after just administering the drug to those 2 patients for just 3 months, well, that's just premature.
Soooo, it's not a statin, but just by coincidence they happened to give it the suffix "statin" in its name? Huh?
Check out Donepezil's charts. I think over 200 trials of Donepezil have been run over the years. It improves scores (MMSE, etc) for 3+ months. Then those scores start falling after 3-6 months back to baseline. Then the scores fall below baseline and the drug's effect fizzles. Heck, for many if not most Alzheimers trials, scores typically go up at 5 weeks for placebo groups. Does that mean placebos are Alzheimers cures and reverse the disease? If 3 months is all it takes to prove efficacy, why not 5 weeks?
Wait, hold up, safety, tolerability, and PK/PD all proven from administration of just ONE dose in 9 patients? Seriously? Just one dose? Did they run out the drug? I mean, what the _____? And still, NO data from those 3 compassionate use miracle patients. So, what, are they back to painting masterpieces, playing the piano, and playing golf after their two shots? Man this company seems confident without releasing any human data. 3 month data means nothing. All the approved drugs on the market show improvement at 3 months, even 6 months. Does that make them cures too? I'd like to see how these patients do on the synthetic version, whenever that is completed, for a year or more of administration (do we even know when synthetic version is estimated to be completed? Will these trials have to be redone with the synthetic version before approval?) But Neurotrope's Ph 2b is just 3 months long! What is that, like two shots? Shouldn't they be doing trials that last a year? Where Alzheimers drugs fall down is after the 6-12 month window, after the drug has been started.
Statins are known to actually CAUSE dementia btw. But I'm guessing it takes more than just 1 or 2 doses to see that connection
Limited cognitive enhancement over 3 months for 9 patients? What exactly does she mean by "limited cog enhancements" and where are those results? Where's the beef? And from that Suzanne thinks this current batch of patients will perform much better? Why? Most Alzheimers trials show cognitive enhancement in the short term. Seems presumptuous to insinuate/suggest reversal based on limited cog improvement in just 9 patients over just 3 months.
Neurotrope says its reversed severe Alzheimers! However, conspicuously I can't find the testing results for these 3 patients that have a genetic condition that gave them Alzheimers much earlier than usual. They're not even typical Alzheimers patients. Why did Neurotrope pick these patients that have a variant of Alzheimers instead of garden variety Alzheimers patients? Where are their MMSE scores? If they were any good you know Neurotrope would announce that to get investors. Ironwood did this with their constipation drug Linzess this past year. Said last summer a reduced dose still produced great results in pivotal trial w/fewer side effects. But they didn't release the results, the numbers. Finally did last month and they underwhelmed and the stock tanked. Also, Neurotrope only monitored those 3 patients for 3 months! Based on that, donepezil cures Alzheimers! Donepezil's charts for all its endpoints look great at 3 months! Clear cut improvement with the numbers to prove it! Buuuuut, if you track those Donepezil patients past 3-6 months, their scores and condition plummet. Heck, even placebo groups look improved in most trials at 3 months. That is such a short time frame to say a drug reverses Alzheimers disease. What is Neurotrope basing that on? And this PH 2b trial they're running is again only 3 months! Seriously? It is easy for the existing 5 drugs that are already approved to show improvement at 3 months, sustaining or increasing that improvement beyond 3 months is the tricky part.
By the time an analyst gives the green light to invest in avxl, it's too late. By that late date, the cat's already out of the bag, everyone knows its a winner, aaannnddd all that will have already been priced into the stock by the time he turns bullish. That's why these so called experts suck. They are like Captain Obvious. After Anavex presents its top line Ph 3 results, then the analyst will say to invest. Gee thanks genius, tell us something we don't know, way to go out on a limb. It's easy to tell people to invest after the fact, when everybody knows the company did something good. But by that time the good news has already been priced into the stock and you'll pay premium for it. Often just several months after that time or much sooner the insiders decide its topped and take profits and the stock turns bearish. What these analysts suck at is prediction, precisely what investors want to know and why they read analysts opinions.
But that's just a correlation btw placebo and pain relief. They prolly woulda had pain relief even if they weren't taking placebo just b/c pain varies over time. Good months and bad months. Good days and years, and bad days and years. Prolly 1/3 had pain stay same and 1/3 had pain worse.
No diff btw monotherapy and dual therapy? But you said for months in dozens of posts monotherapy is much better than dual therapy and that Anavex had even switched patients to monotherapy b/c it had become so obvious that monotherapy outperformed dual therapy
PK/PD I don't think is done by Ariana. Missling said Anavex hasn't received the PK/PD results yet.
Most trials fail when going from Ph 2 to Ph 3. Given that, why do you think Anavex will buck that statistic with 2-73?
Whoops, I was using 150 and 50. The 200 is 4.12 and the 50 is 4.06, so the X is about to happen. I'm using the daily frequency and the source I specified is the closing price. I think that's correct?
That happened a week ago
Didn't the President also imply he would have Medicare negotiate drug prices with the drug companies? Most the people that would be taking Anavex drugs are elderly and on Medicare drug plans.
You're saying the enzymes (beta and gamma secretase) that clip a-beta fragments from APP are misfolded? Where are you getting that from? I thought you said the problem is that the enzymes that clean up a-beta become misfolded so they then can't clear a-beta? Now you're saying the cause of amyloid plagues is enzymes that are misfolded clip a-beta from APP?
So which is the cause of amyloid buildup - failure to cleanup a-beta after its been formed, or misfolded enzymes producing a-beta in the first place?
Ah, no HS bio student is taught that. Are you SURE you got your facts straight? It is my understanding that a-beta is formed by correctly folded enzymes (gamma and beta secretase)
a-beta is a fragment cleaved from APP by enzymes (beta and gamma secretase). Gamma secretase inhibiting drugs proved to just make Alzheimers worse. Beta secretase inhibiting drugs (BACE inhibitors) are in development by half a dozen companies. They hope to stop a-beta from being formed in the first place and thus prevent Alzheimers.
Shortly after a-beta is formed, it is expelled out of the cell and into the extracellular environment where it accumulates with other a-beta fragments to form amyloid plagues.
The enzymes packaged by the ER, you say, break down any formed a-beta. You're implying these enzymes somehow move into the extracellular environment to breakdown extracellular a-beta? Or get at the a-beta when it is still inside the endosome before exocytosis releases it into the extracellular environment? Do you know the name of the enzyme(s) that breakdown a-beta?
Watch this 1 minute video to see what I'm talking about.
When the researchers of these neuro diseases say Alzheimers is a protein misfolding disease, they aren't talking about misfolded enzymes, as you allude to, they are talking about misfolded a-beta, and probably Tau too.
AVXL broke out last Nov and now is pausing b/c not much news and biotech is flat. The Retts news at least got us above the channel we've been stuck in, with it serving as support. A biotech breakout would help
When Anavex and white coats talk about Alzheimers as a protein misfolding disease, the misfolded proteins to which they are referring I think are a-beta and tau, not proteins made from a dysfunctional er-mito as you suggest. If you can quote them saying otherwise, I'll rethink
Analysts and brokers are usually down on basing phase stocks, even after they first breakout they still are. Not until the herd floods into avxl will they then change their tune, albeit too late, as per usual
Anavex's drug target mito dysfunction, so isn't a no brainer to trial it for mito disease??? Seems like the obvious choice to me.
Alzheimer's is amyloidosis in the brain. Usually in the absence of Alzheimers, but not always, amyloidosis can occur elsewhere in the body too: the heart, bones, etc. It is a cause of congestive heart failure. Anavex drugs should work for amyloidosis anywhere in the body.
Hold the phone. After further study, I'm thinking it might be insoluble a-beta protein that is misfolded, causing it to clump into amyloid fibriles in the brain and elsewhere throughout the body. FF to the 7:00 mark of this vid clip. The MD is talking about cardiac amyloidosis, but I think the same info applies to amyloid in the brain. https://www.youtube.com/watch?v=o6u-nETEj9M" rel="nofollow" target="_blank" >https://www.youtube.com/watch?v=o6u-nETEj9M[tag]amyloid
Did they compare 3-71 to 2-73?