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Not sure if this has been posted here already, but this article has a lot of great details about the beneficial effects of Bryostatin-1:
https://www.frontiersin.org/articles/10.3389/fphar.2018.00625/full
"Multiple sclerosis is still a challenging disease without a curative treatment (Torkildsen et al., 2016). Due to the fact that MS is a complex and multifactorial disease (Esposito et al., 2017), treatment must be multi-purpose and target simultaneously several pathological features of MS. Currently, the available medications have more effects on inflammatory aspects of MS. We suggested here that Bryostatin-1 has enough criteria to be as a choice for the MS therapy. Since it has anti-inflammatory, anti-oxidant, MMP inhibitory, neuroprotective, and neurogenic properties, it can cover many aspects of the pathogenesis of MS. Bryostatin-1 has been positively used in various animal models and clinical trials of neural injury, including auditory neurodegeneration, ischemic stroke, TBI, and Alzheimer’s disease. After global ischemic insult, Bryostatin-1 administration resulted in improvement of cognition, synaptogenesis, and neurogenesis, and decline of necrosis and astrogliosis in infarcted tissue. Moreover, it has direct antitumor effects in lymphoma, sarcoma, leukemia, melanoma, and is used breast, colon, lung, and ovarian cancers (Enna and Bylund, 2009; Tabatabaei Rezaei et al., 2015). In addition, it has several pharmacological actions including functional restoration and cognitive improvement in dementia and depression, a decline in the accumulation of neurotoxic amyloid and an inhibition of tau protein hyper-phosphorylation. Based on the data accessible in the preclinical and clinical studies, pharmacological and toxicological aspects of Bryostatin-1 have been demonstrated. Bryostatin-1 is well tolerated and its adverse reactions are rare, mild, and reversible. A major advantage of this drug is that it can be administered orally. Furthermore, its biological and elimination half-life is suitable. Today, the synthetic form of Bryostatin-1 is available which is cost-effective. Bryostatin-1 can easily cross the BBB, which is an advantage for treating MS in low doses (Sun and Alkon, 2006)."
Looks like the same old information, but at least now we have a story with a fancy headline on the front page of Alzheimers News Today.
https://bionewsfeeds.com/2018/08/08/bryostatin-1-can-reverse-cognitive-decline-in-moderate-to-severe-alzheimers-new-data-shows/
Deadline for the next 10-Q and 13-Fs is a week from now.
Should give us a better look at current institutional holdings and warrants.
That's funny. If you bought 3k shares today then you are responsible for more than 86% of the volume today so far.
The medical community scratches its head and wonders how to treat Alzheimer's as Dr. Alkon casually explains it all in a 2 year old patent while nobody listens.
Great stuff.
About $150 million
I don't think most of the press really cares about whether the Biogen drug really works or not. They're just interested in attracting more viewers with a flashy headline. In fact, even a lot of biotech analysts don't really seem to know much about the drugs they write about.
And while I agree that it's painful to see how ignorant people can be, it's also provided us with a great opportunity to buy shares at bargain prices before everyone realizes what's actually going on here.
Looks like the author of that article not only changed Dr. Alkon's words, but in the process also mixed up NMDA with NDMA.
“Data from many other laboratories over the years implicating [N-Nitrosodimethylamine] in memory processing could now take on new meaning from Neurotrope’s clinical results with bryostatin — in the absence of memantine,” Daniel Alkon, MD, president and chief scientific officer, Neurotrope, said in a press release. – by Janel Miller
N-Nitrosodimethylamine (NDMA) is a human carcinogen that is used to create cancer in rats for cancer research, and has absolutely nothing to do with memory processing.
If Biogen ever partners with Neurotrope, they will almost certainly abandon their old AD pipeline.
Who would ever want to buy a drug that slows the decline when you can buy a drug that reverses the damage?
As has been mentioned before, Neurotrope is the only company on the planet going after severe Alzheimer's patients.
And as for BIIB, prepare for plenty more companies to drop like a rock once their amyloid/tau phase 3 trials fail.
Even a drug that can just slow the decline is worth several billion dollars.
You have to consider the fact that Alzheimer's is the sixth leading cause of death in the US, and as medicines get better at treating heart diseases and cancers, more and more people will live long enough to get dementia and AD instead.
Looks good. Although I have a feeling that critics will keep finding new excuses for why this drug has "failed" until even more significant results are announced next year.
Oh ok, my bad.
To expand further upon my last post, this would also explain why clearing out amyloid and tau doesn't improve patients, since they are just byproducts of the damage that has already been done.
I don't think increasing PKCe levels are what's directly causing the improving SIB scores.
From what I can tell based on the research articles (and all the charts showing consistent PKCe levels), it's more that Bryostatin brings PKCe levels back to normal, which enables the brain to properly engage its own repair mechanisms again.
A normal human brain constantly repairs itself and clears out anything bad throughout its lifespan (For example, researchers think that the reason we have to sleep is because the brain uses that time to clear itself of toxins that have accumulated during the day), but Alzheimer's somehow blocks that mechanism (because of too low PKCe levels probably) and causes the brain to deteriorate over the span of several years.
If you take a look at page 11 in their 2017 report, you can see that Bryostatin 1 research is already being funded by the ADDF:
https://www.alzdiscovery.org/assets/content/static/ADDF-2017-Alzheimers-Clinical-Trials-Report.pdf
Now that you mention it though, I feel like great things could happen if we were to somehow get Bill Gates in contact with Dr. Alkon.
Considering that his own father is suffering from Alzheimer's, I'm sure he would very much appreciate reading some of Dr. Alkon's research.
Let me see if there are any people close to him I can get in touch with.
There are currently 149,772 warrants that can be exercised for $0.32 and 382,887 warrants that can be exercised for $6.40.
And while some investors will certainly wait as long as possible, there are also others that will want to collect their profits rather than hold their warrants through another binary event.
As for the Series E and F warrants, I hope they are used to fund the next fundraiser.
Then there are also over a million options waiting to be exercised, which isn't particularly pretty either.
Personally I hope that management will be able to stay below 20 million fully diluted shares.
There are still a lot of warrants and options waiting to be exercised, so I think there will be plenty of resistance until we reach the 20s again
Here's a TED talk from a few years ago that I believe to be further proof of just how much restoring synaptic connections could do for patients with all kinds of disorders.
"This PET imaging tool is also being used in clinical research studies at Yale for other diseases of the brain where synapse loss is a critical component of the disease, said Richard Carson, co-author and director of Yale PET Center. These diseases include Parkinson's disease, epilepsy, drug abuse, depression, and schizophrenia."
Further proof that restoring synaptic connections with Bryostatin not only could treat AD, but also all kinds of neurodegenerative disorders.
Amazing stuff. Thanks for the link.
Dr. Alkon mentions it around 17:55 in this presentation that they were on the 40µg dose:
http://noble.mediasite.com/mediasite/Play/f9cc934c8a0148f3b6a234de3e4e6f571d?catalog=6f8e7abd-96e3-462f-8035-f48126f80846
Looking at that data makes it clearer how much the Memantine population dragged every other group down.
For reference (SIB scores):
Placebo without Memantine: -1.0
Placebo with Memantine: -3.8
40 µg Bryostatin 1 with Memantine: +0.3
40 µg Bryostatin 1 without Memantine: +4.0
20 µg Bryostatin 1 with Memantine: -1.1
20 µg Bryostatin 1 without Memantine: +6.7
If 11 weeks of dosing is enough to cause a 6.7 point improvement on the 133 point SIB scale, then theoretically speaking, it should take less than 3 years of treatment to bring even the most demented patients back up to moderate levels again (which are at around 92).
This study shows that patients with a mean of 92 on the SIB scale also had a mean of 11 on the MMSE scale, which correlates with moderate dementia.
And then I'm just making a wild guess here, but if we assume that an 80 point increase on the SIB scale equals a 10 point increase on the MMSE scale, then it should take about 7-8 years of treatment to bring even the worst AD patients back to normal cognition levels again (MMSE score equal or higher than 24).
That means 8 years of continuous revenues for Neurotrope until a single patient with severe AD is healthy again.
And don't even get me started on the possibility of patients taking this drug to stop cognitive decline before it has even begun.
They will definitely have to partner with someone at some point (since there is no way a company with 5 employees could ever distribute millions of doses to patients on its own), but I hope it does not happen this year.
Here's how I see it:
1. In about a year, positive results could send this stock soaring and create much better fundraising/partnership conditions
2. Neurotrope will need to raise more funds before the trial is completed to keep the business running
So how do we solve the problem of raising funds in a way that maximizes shareholder value?
You might say that a partnership is the best solution, that is, a different company agrees to fund Bryostatin-1 development until market entry and then receives some sort of compensation for distributing it.
The company could then receive new shares for their investment and/or a share of all revenues from any future Bryostatin-1 doses that it helps distribute to patients.
If done correctly, this type of deal would remove the need for any future fundraisers after the new shares for the partnership have been issued.
However, this would still leave the warrants intact which will further dilute shareholders. It would also give other companies leverage over Neurotrope, since they know it is running out cash soon and needs the money.
A different approach would be to just issue new shares to investors like they did before, but again, this would leave warrants intact and lead to even more dilution.
If they decide to give warrant holders some sort of discount in return for immediately exercising their warrants though, they not only prevent further dilution now, but also give themselves enough time to be able to negotiate better partnership terms after results have been announced.
At least that's what I believe.
Hopefully the full results from the last trial will be published before then.
Then there is also a possible Fragile X study and a fundraiser to look forward to.
Will be interesting to see if they issue new shares or choose to give warrant holders a better deal in return for exercising their warrants immediately.
You are correct in the sense that there are less patients and the trial is simpler this time around, but they still need to enroll and then dose all patients, which could actually take longer now since the requirements for joining this trial are stricter than the last one. I also believe that they will be monitoring the patients for a longer time period this time around.
Either way, we know for sure that this trial will be completed by July 30th, 2019, and by then I'm certain the company will already have put out a statement on when top-line results will be announced.
Estimated study completion date is set for July 30, 2019, so I doubt we we'll see top-line results before October next year (if it takes them 2 months after study completion like it did last time)
WCT is the organization responsible for conducting the trial, so I doubt issues at Neurotrope would affect them fulfilling their part of the contract.
No.
The last trial started in November 2015, but the press release for first dosing didn't come out until February 2016.
If the same happens here, we won't have a first dosing until September/October.
https://clinicaltrials.gov/ct2/show/NCT02431468
http://www.neurotropebioscience.com/neurotrope-doses-first-patients-in-phase-2b-study-of-bryostatin-for-treatment-of-severe-alzheimers-disease/
Maybe it's just an institution desperate to buy in, or another pump & dump.
Either way, I wouldn't worry about it much.
https://www.prnewswire.com/news-releases/neurotrope-appoints-leading-experts-in-alzheimers-disease-to-its-scientific-advisory-board-sab-300679027.html
If the post-hoc analysis wasn't enough to convince you they're onto something, just take a look at the resumes of all the professors joining the company recently.
Just goes to show how desperate the market is for an AD treatment.
What makes this all so much crazier is all the benefits Bryostatin has shown in indications other than AD, such as MS or other neurodegenerative disorders.
AD alone is a huge market. But if Bryostatin treats other kinds of neurodegenerative diseases too, then we're talking about a wonder drug that the industry could never even have thought of in its wildest dreams.
https://www.cnbc.com/2018/07/06/biogen-shares-soar-on-successful-alzheimers-drug-trial.html
"Biogen had a market value of $63 billion as of Thursday’s close."
"Shares of the biotech company were up 15 percent Friday morning, a day after Biogen and Tokyo-based Eisai announced positive results from a Phase II study with BAN2401, an anti-amyloid beta protofibril antibody, in 856 patients with early Alzheimer's disease. The stock move added $9.5 billion in value to Biogen shares."
Up 15% now, which means investors have valued these results at about $10 billion (for a drug which only seems to slow the decline of some early AD patients rather than reverse any damage).
Now imagine if investors treat positive results from our trial the same.
A $10 billion market cap boost would make NTRP shares worth about $1279.
That's more than a 12,900% increase.
Impressive.
Institutions now own 21.25% of the company and the number just keeps increasing.
I'm looking forward to seeing what they will present in London a few weeks from now.
I think another good opportunity to buy will be when the next fundraiser is announced.
Hopefully management will choose to raise money from existing warrant holders rather than issue new shares.
When investing in this company, I always take into account that there will probably be around 25 million outstanding shares after dilution in the future.
Even then, these shares are trading at bargain prices compared to what they will be worth if this confirmatory trial shows positive results.
No, the Series F warrants won't expire until 2021, but some investors might still want to cash out before results are announced.
I know 73,814 of them were exercised last year (presumably before the stock price tanked in May).
If this reaches $13, we might not even need a fundraiser before trial results if enough investors exercise their Series F warrants.
Hopefully it doesn't go over $10 too soon. There's still some shares I want to pick up while this thing is still in the single digits.
Alright, so I've updated the ibox with the new logo, the roth report, and the maxim report.
IR gave me this response about the warrants:
"Thank you for your input regarding the warrants. We are aware of their potential use to raise funds."
Yeah, there won't be much to get excited for this year except maybe a fundraiser and starting the Fragile X trial.
2019 is when the real fun begins.