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And yes, all 3 compassionate use patients improved in a clinically meaningful manner (both physically and cognitively):
"Bryostatin infusion produced clinically relevant improvements in assessed behavior in all three patients (Table 3)."
I believe they were dose-loaded at 40ug for the first 3 weekly infusions, and then subsequent doses were lowered and doses were spaced further apart:
"...we hypothesized that an optimal bryostatin treatment protocol would be a dose of 25 µg/m2 for 3 successive weeks followed by several lower doses of gradually increased spacing."
Two important papers on the dosing subject:
The Compassionate Use & P2A safety peer-reviewed paper:
https://content.iospress.com/articles/journal-of-alzheimers-disease/jad170161?resultNumber=0&totalResults=3&start=0&q=neurotrope&resultsPageSize=10&rows=10
The last Phase 2b peer-reviewed paper:
https://neurotrope.com/wp-content/uploads/2018/12/JAD180759.pdf
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From the Phase 2b paper:
"The 40ug dose [in the last phase 2b] corresponded approximately to the 25ug/m2 doses that were used in Compassionate Use protocols [18]."
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CU subject #3 dosing:
"Subject was infused with the indicated doses on 26 occasions over 46 weeks with bryostatin 1 as indicated by the arrows. The dose rate was gradually lowered from 25 to 10 µg/m2/week" (Note: this equates to ~40ug to ~16ug used in the last phase 2b)
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In the Phase 2A safety:
"...randomized double-blind Phase IIa trial with 6 subjects receiving a single i.v. dose of bryostatin 1 at 25 µg/m2 and 3 subjects receiving a placebo"
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In the Compassionate use trial:
"In contrast to the Phase IIa trial, in which subjects received a single infusion, EA subjects [compassionate use] received up to 26 infusions over a period of up to 46 weeks (Table 3). Based on earlier pre-clinical studies of cognitive enhancement and neuroprotection in three different AD transgenic mouse strains, and also based on earlier clinical studies for oncologic indications, we hypothesized that an optimal bryostatin treatment protocol would be a dose of 25 µg/m2 for 3 successive weeks followed by several lower doses of gradually increased spacing. These doses are 4.8–12×lower than many doses given previously in some cancer trials [23, 24] but comparable to others [40–42]. Bryostatin infusion produced clinically relevant improvements in assessed behavior in all three patients (Table 3)."
Cyosol:
I saw that the KOL call on Friday is available live (a call-in number was given).
Do you know if Dr. Ryan's presentation tomorrow will be webcast?
Yes, SIGNIFICANT changes, with the subgroup analysis done by NTRP.
The analysis “Andy” did was comparing donepezil to ALL patients in the previous phase 2, most of whom were taking namenda, which interferes with the uptake of bryostatin at the NMDA receptor.
This post by doc might answer your question:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=149017815
It still will likely take at least 6 weeks after the end of study visit. The slight simplification in the protocol won't really speed analysis up by more than a few days, maybe just a few hours. All data must be verified, all final visits must be reviewed and signed off by the site/PI and the CRO's. Then data is cleaned to remove errors and adjusting for dropouts. Finally, the data can be locked and analyzed by the statisticians, then checked and rechecked to ensure analysis is correct and the database is accurate. Using SAS or other analytical tools, the actual calculations just take seconds. Then the company can see the data and write the press release. 8 weeks will be fine. Wall Street will not expect a faster analysis. Maybe they can do 6 weeks if the sites are super quick in signing off on the final visits but I doubt they can do any faster.
Janney says they expect the NTRP results due this quarter to succeed. Interpret that how you want, and put whatever chance you want on that outcome (70%? 80%?).
And, even those with a bearish perspective say this will go up 10X if we get statistically significant results in the next 8 weeks.
Seems like a good bet to me, and Coach is in at much lower than current prices.
Alzheimer's (pre-clinical & clinical):
https://www.jneurosci.org/content/31/2/630.long (BDNF)
https://neurotrope.com/wp-content/uploads/2018/12/JAD180759.pdf (phase 2 peer-reviewed; BDNF, NGF, IGF)
MS (preclinical):
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5834718/
Fragile-X (preclincal):
http://jpet.aspetjournals.org/content/349/3/393 (abstract)
The scientific literature bolsters NTRP's claim that Bryostatin upregulates PKC-e, which affects BDNF, IGF and NGF. These CNS pathways restore synpapses, clear Amyloid-Beta and Tau, and are neuro-protective.
Can you show me an Alzheimer's trial that improved SIB scores by 4-8 points vs placebo in moderate-to-severe patients at week 13 (the final SIB test)? That is the goal.
This is a phase 2 trial, so if successful, I expect the FDA will require a longer (30 week) phase 3 trial. My hope is that management will partner to take this to the next level.
It sounds to me you're saying that, with statistically significant results in Q3 (efficacy proven), Neurotrope should be trading at 10X where we are.
Sounds like a good prediction to me.
Neurotrope Concludes Data Collection in Confirmatory Phase 2 Clinical Trial of Moderately Severe to Severe Alzheimer's Disease
Top-line efficacy data expected to be announced during the Third Quarter of 2019
https://www.prnewswire.com/news-releases/neurotrope-concludes-data-collection-in-confirmatory-phase-2-clinical-trial-of-moderately-severe-to-severe-alzheimers-disease-300884499.html
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Neurotrope/Oppenheimer KOL Call
Dear Fellow Neurotrope Investors,
We are looking forward to the Alzheimer's Association International Conference in Los Angeles being held July 14-18th 2019. Chief Executive Officer, Dr. Charles Ryan, will be presenting Neurotrope's poster on Wednesday, July 17th at 1:00p Pacific time. The poster will be available from 9:30 AM-4:15PM that day.
Following the AAIC, Neurotrope's Chief Scientific Advisory Board members Dr. Martin R. Farlow and Dr. Marwan Sabbagh will be hosting a KOL call with Oppenheimer's Biotech team. Dr. Farlow is a Professor Emeritus in the Department of Neurology and co-director of the Alzheimer's Disease Center at Indiana University. Dr. Sabbagh is the director of the Cleveland Clinic Lou Ruvo Center for Brain Health.
The call will take place immediately following the AAIC meeting.
Oppenheimer's Biotech Team invites you to a Conference Call:
Alzheimer Experts Provide Insights on Recent Data
When: Friday July 19, 2019
Time: 11:00 AM Eastern Time
Dial in Numbers:
US/Canada (800) 344-0695, passcode 2687039
International (706) 679-5238, passcode 2687039
Sincerely,
Susan Roberts
sr@roberts-communications.com
202-779-0929
NTRP had a pre-specified subgroup no less. And compared to placebo. They did it the way the FDA approves of.
Ad hoc subgroups? Now those are the ones to be wary of.
Or trying to compare a non-placebo subgroup to historical data (yikes!). I know I've heard of some company doing that? lol!
Coach:
That cancer-Alzheimer's inverse relationship IS fascinating. Thanks for pointing it out.
SF:
I think that's a good point, that nobody was looking specifically for cognitive issues.
I think it's also important to note that most of the cancer trials were run at much higher doses which would be expected to downregulate PKCe. With downregulation of PKCe we would not likely see engagement of any of the beneficial cognitive cellular pathways (BDNF, IGF, etc.).
Yes...news lady. Apparently a news anchor at one point in her career.
Just noticing at the bottom of the PR: this is the first time in one of our PR's that I've seen a "Public Relations" contact listed (usually just investor relations):
Public Relations
Susan Roberts
sr@roberts-communications.com
I like that addition to the team, leading into results in Aug/Sep.
BattleReady/Red:
And Vanguard knows how to add after great results:
In Q1 '19, Vanguard Group increased their holding of AXSM by ~563,000 shares (166%) to hold ~902,000. The impetus for this buying by Vanguard was because of Phase 2 results released by AXSM in early January. Further, the share price of AXSM has increased by almost 1000% over the last 6 months.
If/when positive results in NTRP's phase 2 are released in Aug/Sep, we can expect similar buying by institutions (as coach has been pointing out), and NTRP share price will be multiples of where it is today within months.
Coach:
Further, most analysts initiate coverage with conservative estimates in both share price and chances of program success.
Gives them plenty of room to up their estimates if/when positive results are released!
The real notable thing, to me, about this Janney report is that this PhD analyst basically went on record that she expects the confirmation results to repeat the subgroup analysis.
Doesn't mean the Aug/Sep results are a slam dunk, but certainly bodes well that an analyst is willing to go on record that they expect positive results.
The fda approves drugs oftentimes knowing they have bad side-effects. These drugs are approved because the benefits outweighs the risks. If the drugs, after approved and marketed are later deemed to be more risky than their benefit, they are usually pulled from the market.
Fortunately, bryostatin has been studied In long-term trials and NO SAE’s have been found, so drug toxicity is a moot point for Neurotrope.
Again, you're welcome to your opinion, as wrong as it is.
Fact: All peer-reviewed papers state "established clinical safety"
Fact: These are long-term, life-long chronic diseases (Alzheimer's, Multiple Sclerosis, Colitis)
Fact: If these researchers and experts had any doubt about the long-term chronic safety of Bryostatin, they wouldn't have said "established clinical safety" for the use in long-term, life-long chronic diseases.
Don't let the facts get in the way of an opinion.
You are certainly welcome to your OPINION, as wrong as it is.
Meanwhile, most here will trust the research scientists and experts, who do the leg-work and put their reputations on the line.
3 independent labs studying long-term, life-long chronic diseases, now confirming "Established clinical safety".
- Alzheimer's
- Multiple Sclerosis
- Colitis
Nice to see the research scientists and experts AGAIN confirm the long-term safety of Bryostatin-1
I agree, Babaji. I think anyone stating that Janney put a 20% chance on success in the Aug/Sep readout isn't reading that report correctly, and therefore has a flawed investment thesis.
I enjoyed reading your commentary on the Janney report.
...According to janney...in the PROGRAM...
...and they say likely success in the phase 2b. What does likely success mean to you? 80% chance of success in the 2b results in aug/sep? Sounds like a good bet to me
Well stated, doc--thanks for explaining the biochemical reasons for why the diluents are inert! Makes perfect sense now.
Occam's razor. Placebo is a well-known phenomenon in running trials, including Alzheimer's Disease.
Seems to me this history professor is making stuff up just to fit his bias.
Your reply is the only fail here.
The diluents are deemed "inactive" for a reason, lol
More on placebo and the seeking alpha article:
Author claims Povidone, Polyethylglycol and Polysorbate 80 (the diluents used in the IV Placebo used in the Bryostatin trial) may explain why some of the placebo patients improved.
It's important to not that these diluents are an inactive ingredient in many other common drugs. So if they actually do something to help treat Alzheimer's, I'm sure someone would have discovered this:
Povidone is an inactive ingredient of Tylenol 500mg.
Polyethylglycol is also an inactive ingredient in Tylenol 500mg.
Polysorbate 80 is an inactive ingredient in gabapentin 600mg/800mg.
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https://www.drugs.com/imprints/l484-10944.html
https://www.drugs.com/inactive/polysorbate-80-372.html
https://www.drugs.com/inactive/polyethylene-glycol-177.html
https://www.drugs.com/inactive/povidone-169.html
Agree BattleReady:
The placebo comments alone are unfounded and bizarre. Placebo is a well-known phenomenon, even in Alzheimer's disease (see memantine trial results).
Ray: First, the shorts don't "know" anything.
Second, Occam's razor applies here--the most obvious answer is usually the right one: The market maker may hold the majority of the short position in NTRP stock, in order to offset other inventory, such as calls/puts.
https://www.tradingacademy.com/lessons/article/hedges-and-market-makers/
"In fact, that is what the market maker wants. He is in business for the sure profits on the wholesale-retail spread. He does not really want to deal with the changes in prices of the products in his “inventory.”
"To that end, to be perfectly hedged, the option market maker uses the stock itself to offset the risk on his option positions. Each option position can be translated into an equivalent number of shares of stock. Every time a market maker sells a call to a customer, he buys a number of shares of the underlying stock such that the profits on the stock and the short call exactly offset each other. When he buys a call, he sells stock [shorts]. When he sells a put, he sells stock [shorts] , and when he buys a put, he buys stock. At all times, his net stock position equals and offsets his net option position. He does not care what the price of the stock does. The tool that lets the market maker know how many shares of stock are required for each option is the calculation called Delta, which is one of the products of the option pricing model, or formula."
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Finally, as we increase in price, there WILL be some retail/institutions that open temporary unhedged short positions for a quick turnaround, usually when they see weakness in the book. But these are experienced traders that will use tight stop losses. That drop 10 days ago of 10% on 23,000(?) shares may have been exactly this type of move.
Also, some owners of warrants may temporarily short the stock (a "covered" short) at points that they think are short-term highs.
But anyone who carries an unhedged short into results needs to have their heads examined.
I thought it was stuck at $7, and nobody would buy it above that? Currently at $8.30, so I guess that was wrong.
I thought something leaked (bad news?) when it dropped from $7s to low $6s 10 days ago? So by the same logic, that means good news must have leaked, now that it's trading at $8.30?
Shaking my head...
I could care less about Janney's long-term model at this time. Their long-term model has no bearing on the chances of success in the current trial.
And, the fact is that if we are successful in Aug/Sep results, we will have a new treatment paradigm that actually reverses Alzheimer's Disease.
With success in Aug/Sep results, we will likely see:
- A market cap in the $500M to $1B range within a few months. More after that.
- Numerous companies looking to partner with NTRP.
- Upfront money of several hundred of million dollars, if we decide to partner.
- Buyout in the billions if we decide to sell.
- FDA granting Breakthrough Designation.
Everything else is just noise at this time.
Shaking my head, too.
Medicare always denies use of Aricept. NOT
Medicare always denies use of Namenda. NOT
Medicare always kicks patients out of nursing facilities. NOT
A new treatment paradigm:
- REVERSING Alzheimer's not just slowing the decline.
- Market cap should see $500M-$1B within a few months. More after that.
- The number of companies looking to partner with NTRP will be dozens.
- Upfront money will be in the 100s of millions.
- FDA will surely give Breakthrough Designation.
What's not to like if we succeed in Aug/Sep?
This is false:
Doc said something like $30-$50 after they succeed in Aug/Sep.
Sounds good to me.
This is false:
Absolutely right.
The hard part is done: engineering the chemical process and successfully completing a prototype run of synthetic Bryostatin.
It's now a matter of scale-up manufacturing and streamlining the process.
If the projections I see here of multi-billions of dollars in sales per year work out, our contract manufacturer (Wender) will be highly compensated--on the order of $10's of millions per year. Wender's group is motivated to get this right.