Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
You must be misreading my posts--I said If Bryostatin/NTRP is approved and If it's the only approved drug to reverse Alzheimer's, and then gave a potential market cap under that scenario.
I'll make a counter-offer to you. Sell me your shares for .50 each right now, since YOU'RE the one who doesn't think Bryostatin will succeed.
I know...that offer would be just as crazy as you offering your shares to me for $200/share, when they are trading for $5.88.
I saw a recent quote on another board:
"Know what you own and understand what the market is willing to do and say in order to make a buck.
Hold Longs!"
That was YOUR post/quote, in regard to AVXL. I agree with your sentiment, but I would change the symbol to NTRP.
I'm happy to help you out here: Biogen/Eisai lost > $20B in market cap when they announced they were discontinuing their phase 3 Aducanumab drug trial.
Further, Aducanumab had no reversal properties like Bryostatin. Aducanumab only slowed the decline of Alzheimer's.
If I qualified my last post by stating, "If Bryostatin is approved", then you wouldn't view my post as "a pump", right?
Here's your chance to give your opinion:
If Bryostatin IS approved as the only drug that reverses moderate-to-severe Alzheimer's (which was the point of my post) what do you think it's worth?
Finally, I've never co-ordinated with anyone what I say on this board...so how is that "orchestrated"?
For those who are concerned that ONLY treating moderate-to-severe AD patients will limit the upside, here are my very conservative numbers:
My estimate: 1 to 1.5 million US citizens have moderate-to-severe AD (~6M US citizens are estimated to have all stages of AD).
If market penetration of Bryostatin is only half, that is 500,000-750,000 patients treated per year.
If Bryostatin still controls 100% of the drug, I believe a $5,000/pt/yr profit is doable.
Annual PROFIT = $2.5B-$3.75B/yr
X 15 PE = market cap of $37.5B-56.25B
An FDA "label" for a drug is very specific and thorough, including dosage, side-effects and clinical trial results. For Bryostatin, it would list the trial results which will probably be run in the moderate-to-severe category.
So, my guess is that it will need to be prescribed "off-label" for mild-to-moderate AD, even though it is the same disease.
But, most docs are more than willing to go the extra mile for their patients. So, if a doc saw there was a drug whose MOA would probably reverse the disease regardless of cognitive state (severe AD or mild AD), and the side-effects are negligible, most of them would prescribe off-label for their mild-to-moderate AD patients. Whether insurance companies would cover that is another matter.
Theburg:
It's not likely to be a black market per se.
If Bryostatin is approved, and if you can convince your physician to prescribe it off-label, and if you're willing to pay full-cost out of pocket, then you would be able to receive Bryostatin.
I know of several people who have done exactly that with Vascepa, which is a synthetic fish-oil pill taken daily.
The truth is that just about everything you've stated about 2-73 and their trials is "A logical non sequitur", because everyone is STILL waiting for results from a well-controlled trial.
Without larger trials...and lawsuits if the treatment is inappropriate for a significant percentage of people.
...overcome the limitations of traditional symptom- and sign-based phenotypic diagnoses and clinical “one-size-fits-all, magic bullet drug development” in these largely heterogeneous target populations.
NTRP (Neurotrope)
Several years back, 3 or 4 patients were treated with Bryostatin in FDA approved compassionate use (CU) trials.
There was an article just published by the Wichita Eagle April 19, describing CU #3 (Frank Carney, co-founder Pizza Hut):
https://www.kansas.com/news/business/biz-columns-blogs/carrie-rengers/article229253744.html
(In addition to the print article, the video interview of Ms. Carney in article above is worth listening to)
The company summarizes this CU patient as follows:
Patient 3 – 76 y/o white ? (FC)
Course: MMSE: 2-3, improved to 10-12; recognizes, vocalizes words. ADCS-ADL-severity score: 18 improved to 33; hallucinations: reduced; Return of complex motor skills — e.g. swimming, billiards.
------------
There was also a great article written up on CU patient #2 (Jenni Spencer), in 2015 in the Charleston Gazette:
https://www.wvgazettemail.com/news/rockefeller-institute-drug-provides-hope-for-alzheimer-s-treatment/article_bf5bab5f-e40e-5f47-95ca-666f14b795e0.html
Her summary:
Patient 2 – 38 y/o female (JS)
Familial Early-Onset AD due to PSEN1 mutation, Non-verbal, drooling, unable to swallow (fed with gastrostomy), attention grossly impaired, spasticity, inability to move
Course: Return of some language and vocalization, swallowing, increased attentiveness to environment & persons, increased range of motion
RE: IV delivery.
When patients are faced with deadly diseases such as Alzheimer's, they will take extraordinary measures. IV delivery, although it may be less convenient than IM or oral, is not very difficult, and patients use it chronically for several diseases.
Examples of IV drugs taken chronically and their disease?
Benlysta for systemic lupus erythematosus
Tysabri for multiple sclerosis
cytoxan for CLIPPERS syndrome
etc.
IV delivery is NOT "too complex for the masses".
Not for a drug (Bryostatin) that, with a successful readout in August, will be the most significant breakthrough drug in Alzheimer's in 20 years. And potentially the only drug that reverses Alzheimer's.
As far as whether 2-73 will be successful in their trials, it seems like a longshot to me until they have results from a well-controlled trial that definitively shows reversal.
You're absolutely right, coach.
Both Ms. Spencer and Mr. Carney's stories are remarkable, highlighting the long-term potential to reverse Alzheimer's with Bryostatin.
And this was early in the development of Bryostatin, so the company was experimenting with various doses and sequence of doses, which I think they have a much better handle on.
Good find Antii! Great article on Frank Carney.
About 2 years back, the following summary was given for this compassionate use (CU) patient:
Patient 3 – 76 y/o white ? (FC)
Course: MMSE: 2-3, improved to 10-12; recognizes, vocalizes words. ADCS-ADL-severity score: 18 improved to 33; hallucinations: reduced; Return of complex motor skills — e.g. swimming, billiards.
The article you found:
https://www.kansas.com/news/business/biz-columns-blogs/carrie-rengers/article229253744.html
------------
There was also a great article written up on CU patient #2 (Jenni Spencer), in 2015 in the Charleston Gazette.
Her summary:
Patient 2 – 38 y/o female (JS)
Familial Early-Onset AD due to PSEN1 mutation, Non-verbal, drooling, unable to swallow (fed with gastrostomy), attention grossly impaired, spasticity, inability to move
Course: Return of some language and vocalization, swallowing, increased attentiveness to environment & persons, increased range of motion
The Jenni Spencer article:
https://www.wvgazettemail.com/news/rockefeller-institute-drug-provides-hope-for-alzheimer-s-treatment/article_bf5bab5f-e40e-5f47-95ca-666f14b795e0.html
Yes, AVXL has 20 patient's worth of data in Alzheimer's until they unblind in 2 years.
Everywhere I look, AI requires big data.
Breadth and Depth.
20 patients won't suffice for the breadth. I would imagine this would require on the order of 300-1000 patients to get the breadth of patient data required to get a sufficient signal out of the data using AI.
Looks like AVXL will have that breadth in about 2 years.
Luke timmerman, reporting from SF Cancer Summit:
“Hal Barron: in 4 years at Calico, a Google co, I learned a bit about large data. We don't have it yet in biology. Tech laughs at us. For now, AI in drug discovery over hyped. #SFCancerSummit”
Thanks, whoopddew. Wishing the same for you and everyone else.
You state:
Unfortunately for Neurotrope investors, there is no indication that Bryostatin can do anything that Anavex 2-73 isn't able to do.
Anavex does this with a MOA of restoring cellular homeostasis, which may turn out to be a real "cure" in the end, but it's too early to know.
Anavex is looking at possible approval within a year
Thank you. Great contributions.
Doc328:
Thanks for your richly descriptive post--very informative. I was having difficulty understanding the various categories, but your post helped with that.
You honed in on the active/pure SPMS for a proposed trial, and seemed to avoid the PPMS altogether. Is this because PPMS is considered the worst form of the disease, and is considered too difficult to treat? Or is it not well understood in terms of the characteristics of the disease? Would there be a reason to run your 1 year proposed trial with an additional arm of PPMS patients, or are the SPMS vs PPMS disease characteristics too distinct from each other?
Thanks
This is one of my favorite quotes from this abstract, which has been peer-reviewed:
The established clinical safety profile of bryostatin-1 in humans could expedite its development as a therapeutic agent in MS.
A+ explanation, Coach. Thanks!
Coach:
I don't know too much about MS; but I do know there are different stages, and I know it is a prolonged disease.
If Bryostatin does have an effect on MS, which stage would show something the quickest? How long would patients have to be followed to determine that Bryostatin is an effective treatment, such as slowing the decline or reversing?
Is it a disease that we will have to go outside the company for expertise?
Thanks
Coach: Great explanation of why we are using IV...when the time is right, the company will make the push for oral formulation. For all we know, they're already working on it.
Further, IV is used all the time for delivery of drugs, for various reasons. For example, early in Jenni Spencer's treatment (a Bryostatin compassionate use patient with early-onset Alzheimer's), there was no way she could have taken an oral formulation! She had lost the ability to swallow.
For many patients, IV is cumbersome, but I don't see anyone refusing IV treatment if we prove that Bryostatin reverses Alzheimer's.
Whatsupp: Thanks for the follow-up, and I agree. I was just giving the poster a chance to explain a technical reason why oral formulation will have a problem.
Nobody on this board has been able to state a specific reason why oral formulation of Bryostatin won't work in clinical trials.
Do you have experience in reformulations of drugs that you can share with us?
What do you think the issue will be? Absorption? PK/PD? Or will the problem relate to preprandial/postprandial?
I think we both believe in the same trajectory, but we differ on the timeline to get to the endpoint.
Cheers!
IMO, we need to (1) convincingly succeed in August, (2) have an FDA sanctioned pathway to approval for AD, (3) prove something in another indication (MS?) and (4) show that the synthetic works before getting in the $5-10B range.
I think the chances of (1) are quite good (>80%). $1B-$3B seems doable.
(2), (3) and (4) will take time.
Of course, a partnership or buyout would change everything...
This twitter thread is a GREAT story about disabilities (5 min read):
I’m waiting on kitty ultrasound results and trying to distract myself a little bit so I’d like to tell you a story about something that happened last night, in the hopes that I can process my feelings around it.
— Erynn Brook (@ErynnBrook) April 4, 2019
I met a girl on the train last night.
No matter how long it's been extended--3 years, 5 years, whatever--it's still data gathered from an uncontrolled trial.
And all that AVXL has to compare to NTRP isn't worth much until AVXL has data from a well-controlled trial.
Last time I checked, AVXL will have data to compare to our Alzheimer's trial in 2 years.
Coach:
Funny how those with uncontrolled trials (AVXL)--and hence suspect data--try to compare all their preclinical data to what we (NTRP) has shown in a well-controlled trial.
They (AVXL) try to project their preclinical findings as though it's going to be the cure of the century without real-world (well-controlled) trial data to back it up.
I think you're misunderstanding/mischaracterizing the goal of the Cortellis report. It's not reviewing "drugs to watch in 2019" as you state.
It's coverage is of drugs set to enter the market in 2019:
"Seven drugs are set to enter the market in 2019 and achieve blockbuster status by 2023. Immune-related and genetic disorder products dominate the list, with a strong showing by orphan drugs and breakthrough treatments"
I don't think any of the bulls here thinks Bryostatin will enter the market in 2019. Do you?
You are exactly right about SOC, coach...Donepezil is a key drug in the standard of care for moderate-to-severe Alzheimer's in the US and most other countries.
As an example of standard of care: I've seen a pancreatic cancer drug get approved that only extended the average survival rate of patients a few months, say from 6 months to 8 months. This means that many of the patients still die before 8 months. But, if that is the best drug available, then that becomes the standard of care.
The point is, people still die even though they are taking a drug that is the standard of care.
Depending on the state of an Alzheimer's patient, a doctor could actually get sued if they don't offer the standard of care drug (donepezil) through the caregivers of an Alzheimer's patient. Even if that patient is likely to die in 5-8 years, and that drug only slows the decline.
Won't matter if Bryostatin wasn't recognized as a CNS drug for many years, until Dr. Alkon discovered it's important properties.
What will matter is results from our well-controlled trial in late August.
NTRP hands-down leader.
AVXL...not so much.
2-73 for Parkinson's? A graveyard for drug trials. Good luck with that trial. Maybe the placebos are outperforming and asking for extension? Won't know until the trial reads out.
Good luck using a drug (2-73) that is in the same class as drugs (S1R) that have failed in placebo-controlled Alzheimer's trials.
NTRP is the leader in potential Alzheimer's treatments, hands-down. NTRP has the most advanced positive results in clinical trials.
AVXL? It is of no concern to NTRP and meaningless:
- AVXL has good preclinical results? Who cares...prove it in a real trial.
- AVXL reported results from an open-label phase 2 trial? Now do a real double-blind placebo-controlled trial; readout of that trial in 2 years?
Who cares for the next few years.
- AVXL has a cost-effective drug? Could be worthless, until it can prove something in trials. Who cares if it's cost-effective, until it proves something in clinical trials.
Sorry, omitted what I thought was obvious:
"Perhaps this author views us as the only serious contender because NTRP is the only one that has been peer-review published, backed up by a successful double-blind placebo-controlled trial?"
Perhaps this author views us as the only serious contender because we're the only one that has been peer-review published?
Nice to be recognized as the only company showing signs of life in Alzheimer's in this recent Seeking Alpha article.
https://seekingalpha.com/article/4251846-nanostring-technologies-fundraising-signals-inflection-point-strategy
There is a virtual graveyard in AD with only one company showing any sign of life. Neurotrope (NTRP) is the last company standing in AD with a highly anticipated readout in the summer of 2019. NTRP actually showed an improvement in Severe Impairment Battery (SIB) in a subset of patients that didn't take Memantine.
All AD trials measure the rate of decline in SIB, so for even a subset of patients in a clinical trial to show an increase is quite exceptional. NTRP uses a different target than plaque, the big pharmas' focus. Many trials involving amyloid plaque have failed. Any big pharma will need to play catch up and fast to stay in the race for AD therapy.
Oh, back to AVXL...right. Seemed like there was some accurate information in that article you're referencing. If I recall, they pointed out that the class of drugs that AVXL is testing (S1R) had failed in previous Alzheimer's trials. If you wish to discuss those facts, we certainly could.
But, if you want some facts on NTRP (other than those provided by a click-bait site like motley fool), check out the recent key opinion leader interview in which 2 Alzheimer's disease KOLs highlighted Bryostatin as having a decent shot. I'll be glad to provide that interview for you if you're really interested.
At this point, while NTRP isn't getting the big media attention, I'd much rather listen to key opinion leaders--wouldn't you?
This motley fool article can't be taken seriously.
The first 2 companies/drugs only treat the symptoms (agitation) of Alzheimer's, not the cause of the disease. The 3rd company/drug treats Amyloid-Beta, but even the article admits that BACE inhibitors haven't been successful in Alzheimer's trials, so there's not much hope this drug will work either.
Just like the mainstream media, motley fool has no new ideas on Alzheimer's disease treatment.