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The more I look at AXSM, the more I think you've found one of the best comparisons out there to NTRP (if our results are successful).
AXSM has succeeded in Phase 2, still has tremendous upside even at $800M+ MC, continues in an uptrend, and continues to be accumulated by institutions.
We'll likely follow a similar trajectory, but I think NTRP move over a $500M market cap much faster than AXSM did.
I would think the "sell half" strategy would be the better one.
Nothing wrong with riding free shares, especially if it's in a tax-free pension fund.
I don't think I would ever short a biotech in the runup before expected news.
Cyosol gave one good reason.
In addition, any other NTRP news--such as trial startups which are in the works--could cause a significant positive move in the share price.
Nobody knows if these trial startups will happen before the Aug/Sep readout, but it IS a risk for those who are short.
Fair enough. Thanks for your response.
Botox is homeopathy??
For cosmetic purposes (wrinkles), the total botulinum toxin injected in the forehead is about .15 nanagrams (5 injections X 4 units/injection).
That's about 1/100,000th the dose of Bryostatin.
So, I guess Levothyroxine for hypothyroidism is homeopathy?? (doses start at 25 micrograms)
And Fentanyl is homeopathy?? (doses start at 50 micrograms)
Beclomethasone for asthma is homeopathy?? (maintenance dose of 40-80 micrograms)
There is a high likelihood that your "provisional approval" scenario for AVXL would have to involve rogue Australia/EU healthcare workers committing crimes, including:
- breaking privacy laws
- securities fraud
I can't imagine these employees would take such a risk on their own.
Are you saying that someone is illegally paying Australia/EU healthcare workers to break the law, in order to peak at a secondary endpoint on a blinded trial?
I agree coach/antti. There will be a lot of buzz if NTRP is successful in this readout.
If NTRP repeats previous p2 subgroup results:
There are several historical stock comparisons that put NTRP market cap anywhere in the $750M-$2.2B range over the next few years. Any comparisons are many multiples of where we are today.
It will be the first double-blind, placebo-controlled trial that shows reversal of Alzheimer's Disease. And all competitors are at least a few years away from similar results in AD.
Certainly that is worth a higher market cap range, especially if the p-value blows away past Alzheimer's trials (p=.01 or better), as antti points out.
And while we wait for P3, I'm sure progress will be made in other CNS diseases (Fragile-X, MS, etc), and earlier stage Alzheimer's (mild-to-moderate), and synthetic formulation, and an oral version of Bryostatin.
A lot to look forward to, if we succeed in P2 results in 3-4 months!
If p2 is successful, I tend to go with a share count that is somewhere around 20M (fully diluted is 25M). I think a significant number of warrant holders will exercise.
But that would also raise significant capital.
I couldn't agree more--reading the peer-reviewed paper is a must.
Even reading just the discussion of the subgroup analysis is enlightening.
Of course. I was just trying to put complex statistics into simple terms for those few here that may not have bothered to read the peer-reviewed article.
Here's a simple probability exercise on the subgroup analysis:
- Assume a 50% chance of improving in SIB at 13-15 weeks, and a 50% chance of declining in SIB at 13-15 weeks
- 15/16 patients on Bryostatin (non-memantine) improved in their SIB
The probability that the improvement in SIB is caused by Bryostatin is ~99.9%.
"Just look at the data"
Will this repeat in the confirmatory trial? That is the billion dollar question.
I like our chances, too.
*while this is an oversimplification of the data, it does illustrate how unlikely it is that 15/16 patients improved in SIB by chance.
The facts matter:
Theburg:
Use of Contingent Value Rights (CVR) would be the best way for NTRP and a potential suitor to agree on a fair buyout offer, if the phase 2 is successful (if NTRP is even considering a buyout after phase 2).
It would be very difficult to put a dollar value on the potential valuation before a successful Phase 3 is completed (and synthetic as you point out).
Ray:
Have you read the peer-reviewed paper released by NTRP, which explains the subgroup analysis?
Specifically how the non-Memantine 20ug group improved in SIB and was statistically significant vs placebo?
Or maybe the science doesn't matter to you? Perhaps you think it's just another Alzheimer's trial, and because most other Alzheimer's trials fail, this one will too?
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If the results released in Aug/Sep are statistically significant, the stock will be multiples of where we are today.
Whatsupp:
I hadn't thought of a marketing and distribution agreement, but that would make a lot of sense if they want to get cash from a partnership AND maintain control.
Assuming they don't want to go it alone or sell the company, where they go from here comes down to what they need help on, and how a partner can help with that. Their needs:
- Cash
- Trial design and regulatory expertise (Alzheimer's and other CNS diseases)
- Marketing and distribution
- Strategic planning
- Patent expertise (seem to have good coverage here with CEO and new VP)
(assuming this p2 trial is successful)
Coach:
While I'm sure the company has NDA's with several entities (stats consultant, SAB, etc), I don't think it would be to their advantage to sign NDA's with potential partners for that interim period between receiving results from Worldwide Clinical Trials and when NTRP releases them to the public.
Signing NDA's with a few companies for the interim period may accelerate the progress of Bryostatin by a few months, but this also narrows the field of potential partners, and hence the potential monetary value of a partnership agreement.
If the results are positive and if their goal is to partner, I would think they would wait to release the results, then sign NDA's with ALL parties interested in partnering, and then choose the best bid.
Wow. I'd forgotten the memantine dropout was so high.
I know some will...but it would be concerning if that dropout number was too high.
“Buy a stock the way you would buy a house. Understand and like it such that you’d be content to own it in the absence of any market.”
With the placebo-controlled results released by NTRP vs the non-placebo-controlled of AVXL, it's an easy choice to me:
Buy/hold NTRP.
The NTRP MS trial will start when it's ready to go; other NTRP trials will follow when they are ready. But the real value proposition with NTRP is if their Alzheimer's trial results are successful in August/September.
Exactly right, Coach. No double-blind, no placebo.
Also, if I recall correctly, one part of their results was comparing it to historical controls.
Definitely #5 :
"5. External Control (Including Historical Control) (1.3.5)"
Yes, the FDA has no problem with a company running different types of trials. What really counts is what you can ascertain from those trials.
The last 2-73 trial matches closest to "5. External Control (Including Historical Control) (1.3.5)"
From your link:
"External (historical) control groups...are considered together as the fifth type because of serious concerns about the ability of such trials to ensure comparability of test and control groups and their ability to minimize important biases, making this design usable only in unusual circumstances."
Everyone here has been saying the same thing--serious concerns about 2-73 results, since there is no way to minimize or eliminate biases.
Whatsupp:
I think you make a really good point here: Probably 99% of people in Alzheimer's research and development have NEVER worked on a successful Alzheimer's drug.
NTRP has a CEO who has: Dr. Ryan.
Sure it was a success.
P-value = .012 comparing Bryostatin to placebo in a pre-specified analysis.
P-value = .001 in the trend analysis.
Maybe you're right. When we repeat/confirm those results, maybe we WILL get accelerated approval?
Our confirmatory results are in Aug/Sep.
Unlike AVXL, we know we need to run full double-blind, placebo-controlled trials in order to get meaningful results.
NTRP succeeded in their last trial, so that means we don’t need to watch a video of “why traditional Alzheimer’s trials have failed.”
NTRP is all set in the placebo department.
Your webcast seems like something that a company that is data mining in a trial without a placebo could use...let me think on that a bit here...OH, that would be AVXL!
Thank you for thinking of us, though.
All the literature I've read.
Are you stating that "properly designed trial participation" can effectively remove placebo from a clinical trial?
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But, you make a good point:
It's amazing that, in spite of "not properly screening" (which apparently resulted in a high placebo response), Bryostatin STILL produced a highly statistically significant result!
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Here's a recent StudyTalks Webinar: The Power of Placebo in Alzheimer s Research that might be helpful to those that don't understand placebo or the design of an Alzheimer's trial:
"Profound" Alzheimer's patients DO respond in the placebo arm, according to all the literature, so your statement is made without understanding moderate-to-severe Alzheimer's or the issue of placebo (or both?).
A company that doesn't realize that placebo is always a concern--or expects to get meaningful efficacy from a trial without a placebo control--is running a trial that will get crap shoot results (AVXL anyone?).
If it was as simple as "proper screening", I'm sure multi-billion dollar pharma companies would have figured that out years ago, and we wouldn't hear anything about placebo response.
Adding an interim look increases risk, but the risk would probably be small in our case, and a stats expert will certainly help to manage that risk.
You may have a good point, that interim looks are more helpful when the trials are anticipated to take much longer (such as survival in cancer trials).
Agree. >50% improvement in placebo (which we saw in this subgroup analysis) is just off the charts.
I think 20-30% is more likely to be the placebo range for the current phase 2 trial--in your/Doc's range.
I'm hopeful placebo "behaves", lol.
Yes, these would definitely be "good" problems to have, if successful in August/September.
I'm very sorry to hear of your friend/associate's issue with her mother. And, unfortunately, it's far too common in the US. I was scanning an article the past few days, and saw the following stats:
"
- Total payments in 2019 for all individuals with Alzheimer’s or other dementias estimated at $290B (health care, longterm care and hospice). $195B of that comes from Medicare/Medicaid.
- In 2018, [unpaid family or friend] caregivers of people with Alzheimer’s or other dementias provided an estimated 18.5B hours of assistance...valued at $233.9B.
- The total lifetime cost of care for someone with dementia was estimated at $350,174.
- The costs associated with family care make up 70 percent of lifetime dementia care costs.
"
https://www.alz.org/media/Documents/alzheimers-facts-and-figures-2019-r.pdf
Countless families are doing exactly what your friend is doing--caring for a parent/relative with Alzheimer's at home, unpaid and with added stress on the family. And most of this doesn't register as a "cost" on society.
If unpaid care were paid in real dollars, the cost in the US of Alzheimer's/dementia would be almost $525B/year. Staggering!
And this figure is estimated to double by 2050!
I pray that your prayers are answered...this year.
Thanks, coach, for all your efforts! This is outstanding research, and I’m sure it’s the culmination of many, many hours of reading and researching articles on bryostatin and PKC-e and the cascade of downstream effects on the CNS.
Antti:
That is a really good question, as to how the FDA will treat our data, assuming it comes back positive and with similar stunning statistical numbers.
Historically, the FDA has been very conservative, requiring the 2 phase 3’s, etc. But recently the FDA is showing signs of changing, with greater use of Breakthrough Designation, and of course the controversial approval of SRPT’s drug for a very rare DMD disease.
I am in the camp that we will need a phase 3. But given the lack of treatments for AD, the horrible nature of the disease sequelae and short period before death, the cost to our healthcare system, the safety of bryostatin, and outstanding results (if they hold up), I could see a small chance of approval after august/September results.
That is one reason why I would really like to get an update on the synthetic, because I would assume we would need to run a small confirmatory trial of that, since the natural is in short supply.
But regardless of these unknowns, great trial results in August/September will be rewarded handsomely, as you point out.
Thanks Doc, for your insights on the nuances of off-label and insurance coverage. I didn’t realize how much cost plays into off-label. The supporting papers/trials makes sense for getting insurance coverage for off-label.
Yes, PCYC was quite a ride from $1 until buyout at what $260/share?
3 months ago, AXSM was trading at $2, and is now at $16. Most traders probably bought at $2 and sold at $3 on the brief runup before news hit. Great trade, right? Only if you're happy with 50% instead of 400%. AXSM shot up to $8 after the news.
But I thought these stocks were only for trading the pumps??