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Correct. Nobody knows about the preliminary data until all of it has been collected and sent to the company in November. After that they need to make sense of that data and prepare an announcement for December.
Double-blind means not even the doctors or patients know what they're getting. These trials are run by a serious and independent third party CRO, not by the company itself.
They are completely blind until they receive all the preliminary data at once around early November and it would be foolish to attribute stock price movements to "leaks" before then.
Patients only receive the drug for 6 months. I think the 10 month data won't be as relevant because it will show how both groups do after 4 additional months on no drug.
As for the valuation, you could be right that a lot of angsty investors will take their money and run as soon as possible after results, but those will then be replaced by new investors that may not be as eager to sell until the valuation reaches a more appropriate level.
There's a reason for why the company is worth $60 million right now and it's because of the risk and uncertainty of not knowing whether the drug actually works. Maybe it doesn't, but if it does, why would you sell it for less than $1 billion?
Even Haywood thinks good results are worth at least $5 billion.
They're not going after severe patients. Those were removed from the current trial because of wonky results in the last trial.
Moderately severe (moderate) is what they're going after.
It's a 6 month trial (10 months for full data) with about 40+ completer patients in each group.
If the drug works as expected, the results should be crystal clear and remove most doubts about its efficacy, and then the question is:
How much do you think a statistically significant improvement in moderately severe AD patients is worth? Would you look at a company like Cassava and say it's worth less than that? Would you sell shares at a $500 million valuation because you think it's not worth $1 billion?
Don't forget that it would be a positive signal for the other diseases they're pursuing too.
There's nothing else to communicate. If you're looking for constant stock promotion from the company then you're in the wrong place.
This will continue to track the market until new data is out.
Placebo results for the #202 trial aren't statistically significant (p=0.546). Neither are the combined placebo results (p=0.160).
The 2 point placebo increase in the #203 trial however is statistically significant (p=0.014).
The #203 groups are about twice the size of the memantine-free #202 groups which makes their results more reliable than the #202 results.
Compare the two trials to the combined data and you'll see the #203 data is closer to combined data than the #202 data.
I wouldn't be surprised if placebo patients show a 1 to 2 point improvement at 13 weeks in the current trial with bryo patients showing a 4 point improvement. The real question is how things look after 6 months now that both groups are finally big enough and have been adjusted to start from the same baseline.
Memantine works by binding to NMDA receptors and has a half life of about 3 days. After 20 days of not taking it there's less than 1% of the drug left. After 40 days it's less than 0,01%.
Study protocol says 90 days. That means less than 0,0000001% of the drug is left, if there even is any.
Just saying. I really don't think this is an issue.
I don't think Memantine plays any role in this. Both groups were Memantine-free.
What's more likely is that the trial was too short and that a 2 point improvement on a 100 point scale after 3 months doesn't mean anything when the standard deviation is between 4 to 8 points.
#203 moderate placebo group got about -0,24 to +4,54 points.
#203 moderate bryo group got about +0,04 to +7,84 points.
IMO the trial wasn't long enough for cognitive decline to happen and on top of that it was underpowered because of too small patient groups.
Statistically significant improvement over placebo and baseline is definitely worth a triple digit stock price.
It depends on how convincing the data is though. The last time they posted "positive" results in 2017 the market didn't believe them and decided to drop the price by 60%.
The uncertainty is what makes this stock so risky, but it's also what gives it such a massive upside potential.
Great for gambling, not so much for putting your life savings into it.
There's actually nothing wrong with the placebo result itself. The problem was that placebo patients started out with a higher baseline, which makes it hard to compare against the bryo group that started out lower.
Severe patients did so bad that they were excluded from the current trial. I recommend reading the 2022 paper about the latest trial that I added to the ibox if you want to learn more about the details of it.
I don't think there's only a 1% chance of success and I doubt the NIH thinks that either, but even if you eliminate the 40mcg dose, Memantine, severe patients and adjust for baseline imbalance, the fact of the matter is that this is still a unique trial that will deliver unique results. The drug has never been tested for an extended period in humans like this and the risk of failure is very much real, contrary to what some may think about this being a sure thing.
I doubt that's gonna happen in a blood red market like this, but hey, maybe I'm wrong.
Investors back then only had the P2a and CU data. Current valuation includes data from both P2b trials.
Good luck finding buyers at a 250 million market cap when the last trial showed placebo outperforming the drug.
Of course the benefit of having a lower valuation means there's much more potential upside this time around.
I can't imagine this staying below triple digits for long if results look good.
Before it quickly dropped to about $16 and then ran up to $19 the day before results, yes. Market was more optimistic back then and the company was worth maybe 5x more than today.
Last trial the price started dropping two months before results and never recovered.
Not that I think history is going to repeat itself but it's worth mentioning that approaching new results doesn't always mean a higher stock price.
From the P2b paper:
"As an exploratory trial, three separate doses were identified to define a range of dosing efficacy : zero (placebo), 20 µg, and 40 µg. The 40 µg dose corresponded approximately to the 25 µg / m² doses that were used in Compassionate Use protocols [ 18 ] . These doses were derived from three sources of extensive prior data collection : pre - clinical in vitro studies with isolated PKC enzymes and their substrates , pre clinical in vivo studies with AD transgenic mice , and compassionate use patients .
These studies and the relevant data are all described in several publications that are referenced in this article . The range of 0 to 40 µg was not arbitrary , but instead was directly derived from empirical experience . In the Phase II A study [ 18 ], Compassionate Use protocols used doses that approximated the 40 µg ( 25 µg / m² ) with frequencies that apparently were too high , thus causing downregulation after 3 consecutive weekly doses . Inference of downregulation was based on direct measurement of PKC epsilon in a patient's blood samples . For this compassionate use patient , it was possible to measure blood PKC epsilon levels [ 18 ] rise in close association with the patient's initial improvement with weekly dosing , followed by a decline in this improvement as the PKC epsilon levels fell , in fact , showing downregulation ( inhibition ) . These and other compassionate use results guided our selection of alternate weekly doses - to avoid this observed downregulation in moderately severe to severe AD patients .
These compassionate use results also suggested that too frequent bryostatin over time would produce downregulation and not the activation of PKC epsilon that our pre - clinical studies indicated was associated with cognitive , synaptogenic , and anti - amyloid benefit . On that basis , therefore , we anticipated that the 40 µg dose might be too high a dose and weekly might be too high a frequency ( e.g. , weekly ) . Given those possibilities , we believed that we should test an intermediate dose of 20 µg , also administered at a lower frequency than that of the compassionate use protocols . A similar sequence of PKC activation followed by prolonged downregulation had been previously demonstrated in a clinical oncology trial [ 20 ] with a dose level and frequency of bryostatin administration comparable to that of our Compassionate Use protocols for AD .
The biochemical data presented in Fig . 1 A , B illustrates in vitro PKC epsilon activation that follows an inverted U - shaped dose - response curve . Such an inverted U - shaped dose - response curve was , in fact , suggested by the improvement signals in the SIB scores that were observed in the present trial ."
From the P2a paper:
"Sterile injectable bryostatin 1 and diluent were manufactured by Lyophilization Technology, Inc., Ivyland, PA.
Bryostatin 1 was produced as a sterile lyophilized cake in 10ml lyophilized sterile vials containing 50g bryostatin 1 and 2.5mg Povidone C17, USP. Placebo was prepared identically except that bryostatin 1 was omitted. Sterile PET Diluent was made in 10ml sterile vials and contained 1ml solution of polyethylene glycol 400 (60%), dehydrated ethanol, USP (30%), and Polysorbate 80, USP (10%), v/v. Povidone C17 was a generous gift of Ashland Chemical Co., Wayne, NJ.
Pure bryostatin 1 was stored at–20?C. The bryostatin 1, placebo, and PET diluent drug product were stored in controlled access chambers at +2 to +8?C. The identity, purity, and stability of the drug substance and drug product were confirmed by mass spectrometry [36], HPLC, UV spectroscopy, and IR spectroscopy at 6-month intervals. The identity, ethanol content, and viscosity of the PET diluent were also confirmed at 6-month intervals. Moisture content was measured at 6-month intervals by pulsed coulometric KF titration using Hydranal Coulomat AK (Sigma-Aldrich) in a Mettler Toledo C20 titrator. Sterility and endotoxin content were confirmed every 6 months by Alcami, Wilmington, NC.
Bryostatin 1 or placebo was administered by dissolving the contents of one vial in 1ml PET diluent, followed by dilution with 9ml of 0.9% sodium chloride injection, USP. This solution was then injected into a 250-ml Baxter non-DEHP-non-PVC Intravia polyolefin-lined saline IV bag. Hospira polyethylene lined tubing was used. The bryostatin 1 was administered to the EA patient by drip infusion over a period of 1h. PVC tubing and bags were avoided because previous research showed that bryostatin 1 could bind to PVC.
Stability tests showed that the bryostatin 1 concentration thus prepared was stable at room temperature in PVC-free infusion bags for at least 21 days. Bryostatin was stable in glass vials containing 9ml saline for at least 10 days at room temperature. Aqueous solutions of bryostatin were found to bind to PVC containers but not to polypropylene or glass. Bryostatin dissolved as 10% solutions in ethanol or DMSO was stable for at least 30 days in glass containers."
Not really. Bioequivalence trials will sometimes fail because of a company testing two different solutions against each other.
In this case they're testing Bryostatin against Bryostatin, and AFAIK they're both dissolved into the same solution.
Yes, you make a valid point.
Now read my post again but this time replace the V with something more inappropriate.
lol
Maybe it's V-shaped, in which case it's a matter of finding how far up the V to go before getting the right response.
It's meant to further inform the company about how to design the next trial rather than prove anything to the public or the FDA, hence no need for a placebo or statistical significance.
The current 20mcg dose is only used because it outperformed a 40mcg dose in 2017 and not because they found it to be the optimal dose.
They're only announcing topline data in December while full data will take at least another 4 months, so there's plenty of time for the open label trial to produce results before they launch a larger P3 trial based on those results.
There should be a link to a scientific paper in the ibox about their earlier compassionate use trial that show graphs of how they switched between different doses and intervals to see what works and what doesn't. Before that all they had was mouse data for efficacy and cancer patient data for safety.
We'll just have to ask for details in the next conference call lol
Market started climbing in June and we caught up to it in July, then it reversed course last week and we have been flat ever since.
Could it go to $12? Sure it could, but I don't see anyone wanting to buy into a risky biotech microcap on no news when you have the Fed actively working to bring down asset prices so they can get inflation under control.
jmho
Count your blessings and don't gamble with money you can't afford to lose.
Depends on how the current trial goes. If you're convinced they're all fools you can always just short this into results and make money off them.
Hard to move anything forward when you barely have enough money in the bank to keep the lights on.
NTRP was probably dumped to give the company a fresh start under a new name after two trial failures. Makes it easier to raise new cash and keep the lights on I guess.
Looking forward to seeing how it performs commercially.
That trial is scheduled to begin later this year and I'm pretty sure they're using their natural supply for it.
I think they're planning to use all of their natural supply before switching to synthetic, even if they already have some in their inventory.
Because bioequivalence trials are usually short and more of a formality to satisfy the FDA rather than an actual test to see if it's the same molecule.
There's a scientific paper that explains the Bryostatin synthesis process and how the end product is the same as the natural version.
Already been launched? I must be deaf or something then because I only remember the dose optimization trial being launched in July, not the bioequivalence one.
I never said it wasn't a big deal. I just think the statement is too vague to consider it a confirmation. If they had solid plans to launch a bioequivalence trial within a few months I would expect them to be more specific about it instead of giving a caller a vague answer about it being a possibility.
Maybe you're right, but I'm still skeptical.
"It would not be unreasonable to think that."
Doesn't sound like a confirmation imo. I can see why some would see it that way though.
You sure about that? I remember it being mentioned in the call but not that a specific timeline was given for it.
Maybe in 2023? Hard to know for sure when there's no information about how long the trial will be.
I'm sure they would. I just don't see it happening this year. There's not even a mention of it in the latest 10Q.
The only important news this year will be the AD data. FXS, MS and bioequivalence data is not coming out this year and I don't see how launching an FXS trial that everyone knows about will move the price in any meaningful way.
Until the AD data is announced, I expect market forces to have the biggest influence on price.
If the market goes down it's going to drag this stock down with it.
Lots of talk about an upcoming recession lately, so I'm guessing we'll be below $7 within a month if the bear market continues.
Probably means stock price is heading lower before results.
We'll just have to agree to disagree then.
If you look at older analyst reports about this company you'll see that they were all wrong, and they would still be wrong if the drug had succeeded because their price target would've been set too low.
Those reports are still included in the ibox though because they contain interesting information that investors can use to get a more informed opinion about the company, and hopefully they will combine it with other data and opinions to get a better understanding of how to trade this stock in the best way possible.
Information from multiple sources is key, and restricting yourself to what an analyst says means you're restricting the amount of information you collect.