Cassava Sciences Inc (SAVA)

[FooBarAndGrill]

I know my previous post was a bit mysterious but perhaps the following video will help to clarify.

[FooBarAndGrill]

Filamin-A is a scaffolding protein. Here is page 13 from the latest Cassava corp presentation.
Do you see that Destabilized Microtibule? That may be playing a role in ALZ.
The relationship was first conjectured by Roger Penrose (physicist) and Stuart Hameroff (anesthesiologist) .
Recently this conjecture has advanced to become a hypothesis

[investingdog]

😃

[investingdog]

Interview with Remi Barbier about P3 design, biomarkers, neuroinflammation, beta amyloid plaque, filamin a mutations, simufilam etc.

[investingdog]

From .tube:
This is how low the bar is for approval:
Leqembi (lecanemab) was granted accelerated approval in January 2023 based on its ability to clear amyloid plaques in early Alzheimer's patients in Phase 3 trials.
Confirmatory trials were ongoing.
Aduhelm (aducanumab) received accelerated approval in June 2021, though its clinical benefit remains controversial due to mixed Phase 3 data.
The FDA converted Leqembi to full traditional approval in July 2023 after its confirmatory trials showed it slowed cognitive decline (no cog improvement, just slowed decline "*in 27% of it's patients**), an unprecedented achievement for an Alzheimer's drug...
So in addition to the safety concerns, like brain bleeding and death, ONLY 27% of the EARLY to MILD patients had their Alzheimer's rate of decline SLOWED or 73% receive ZERO positive benefits!
Now imagine if this drug shows anything close to the P2 data (47% cognitive improvement and 23% slowed decline over 12

[investingdog]

Matt Nachtrab on X - take a look, Short sellers abusing the system.

The Attack of Cassava Sciences (SAVA)
Stock Market Short Sellers Abusing the System, Again.

A 3 year saga of shorts seller’s allegations of scientific misconduct by $Sava, a company fighting to develop and bring a life saving drug for Alzheimer’s patients. These short sellers…

— Matt Nachtrab (@MattNachtrab) June 11, 2024

[investingdog]

From 10Q filing, page 28. :

P-values shown below are baseline vs. 6-month levels by paired t-test:
?
CSF biomarkers of disease pathology, t-tau and p-tau181, decreased 38% and 18%, respectively (both p<0.00001)
?
CSF biomarkers of neurodegeneration, neurogranin and neurofilament light chain (NfL), decreased 72% and 55%, respectively (both p<0.00001)
?
CSF biomarkers of neuroinflammation, sTREM2 and YKL-40, decreased 65% and 44% (both p<0.00001)

[investingdog]

Look at some trial results:
There was no exclusion for vascular cognitive impairment in these trials. In some neuropathologic studies, mixed vascular and Alzheimer pathology has been found to have a prevalence of 20% to 27%, others have shown a prevalence of up to 38%, with pure vascular pathology seen only in 12%.
Patients with mild Alzheimer’s disease who received simufilam treatment continuously for two years (n=47) had no decline in ADAS-Cog scores (± 1.51 SE) as a group.
ADAS-Cog scores improved in 47% of patients; this group had a mean change of -4.7 (±3.8) points (lower is better).
In the mild sub-group, ADAS-Cog scores improved, from 15.0 (±6.3) to 12.6 (±7.8)
CSF biomarkers of disease pathology, t-tau and p-tau181, decreased 38% and 18%, respectively (both p<0.00001).
CSF biomarkers of neurodegeneration, neurogranin and neurofilament light chain (NfL), decreased 72% and 55%, respectively (both p<0.00001).
CSF biomarkers of neuroinflammation, sTREM2 and YKL-40, decreased 65% and 44% (both p<0.00001).

Current P3 trials have exclusion for vascular cognitive impairment

[investingdog]

Here is another one from different AI
Answer
To calculate the statistical significance of the clinical trial results, we need to perform a hypothesis test comparing the mean ADA-cog scores between the drug and placebo groups. Given the information provided, we can conduct a two-sample t-test assuming equal variances.

Assumptions:
• The data follows a normal distribution.
• The standard deviation of 13 is the same for both groups.
Null Hypothesis (H0): There is no difference in mean ADA-cog scores between the drug and placebo groups.
Alternative Hypothesis (H1): There is a difference in mean ADA-cog scores between the drug and placebo groups.

Let's define the variables:
• n1 = sample size of the placebo group = 320 (assuming equal group sizes)
• n2 = sample size of the drug group = 320 (assuming equal group sizes)
• µ1 = mean ADA-cog score for the placebo group = 20
• µ2 = mean ADA-cog score for the drug group = 16
• s = standard deviation = 13 (assumed to be the same for both groups)
The test statistic for the two-sample t-test is calculated as:

t = (µ1 - µ2) / sqrt[(s^2/n1) + (s^2/n2)]
t = (20 - 16) / sqrt[(13^2/320) + (13^2/320)]
t = 4 / sqrt(0.5294)
t = 4 / 0.7275
t = 5.50

With 638 degrees of freedom (n1 + n2 - 2 = 320 + 320 - 2 = 638), the critical value for a two-tailed test at the 5% significance level is approximately 1.96.

Since the calculated t-value (5.50) is greater than the critical value (1.96), we reject the null hypothesis. This means that the difference in mean ADA-cog scores between the drug and placebo groups is statistically significant at the 5% level.

Therefore, based on the given information, the clinical trial results show a statistically significant difference in mean ADA-cog scores between the drug and placebo groups, with the drug group having a lower (better) mean score of 16 compared to 20 in the placebo group.

In summary, a t-statistic of 5.5 corresponds to an extremely small p-value, indicating that the null hypothesis can be rejected with a high degree of confidence. The exact p-value depends on the degrees of freedom, but is certainly less than 0.00001 for any reasonable sample size.

[investingdog]

This is from BING AI

Copilot
Certainly! Let’s calculate the p-value for the difference in means between the placebo and drug groups using a two-sample Z-test.
Here are the details:
Group A (Placebo):
Sample size ((n_A)): 320
Mean ((\bar{x}_A)): 20
Standard deviation ((\sigma_A)): 13
Group B (Drug):
Sample size ((n_B)): 320
Mean ((\bar{x}_B)): 16
Standard deviation ((\sigma_B)): 13
We’ll use the following formula for the Z-score:
[ Z = \frac{{\bar{x}_A - \bar{x}_B}}{{\sqrt{\frac{{\sigma_A^2}}{{n_A}} + \frac{{\sigma_B^2}}{{n_B}}}}} ]
Substituting the values:
[ Z = \frac{{20 - 16}}{{\sqrt{\frac{{13^2}}{{320}} + \frac{{13^2}}{{320}}}}} ]
Calculating the pooled standard error:
[ \text{{Pooled standard error}} = \sqrt{\frac{{\sigma_A^2}}{{n_A}} + \frac{{\sigma_B^2}}{{n_B}}} ]
[ \text{{Pooled standard error}} = \sqrt{\frac{{13^2}}{{320}} + \frac{{13^2}}{{320}}} ]
Now, let’s find the Z-score:
[ Z = \frac{{20 - 16}}{{\text{{Pooled standard error}}}} ]
Once we have the Z-score, we can find the p-value associated with it. If the p-value is less than the significance level (commonly set at 0.05), we can conclude that the difference in means is statistically significant.
Using an online calculator, I found that the p-value for this scenario is approximately 0.000011. Since this p-value is much smaller than the significance level of 0.05, we can conclude that there is a statistically significant difference between the placebo and drug groups in terms of Ada’s cog mean score.

[Mrs. Smith the Third]

up 10 cents.....there are better ways to start the week like a short covering pop for the obvious reason 'simu' is the real deal.......lets go!!

[investingdog]

Here's the lowdown on our friendly shorts and hedge funds: They've got 13 million shares shorted, plus some phantom shares in the mix, all hitting $250 or more after Phase 3. Crunching those digits, we're talking 13,000,000 * 250, ringing in at a staggering $3,250,000,000—yeah, over 3 billion straight down the toilet. That's one heck of a motivator to hustle harder, ain't it?

[FooBarAndGrill]

Yeah Yahoo doesn't want you clicking off-site. They lose ad revenue.

[investingdog]

Yahoo MB keeps deleting any links to this board including abbreviated partial links.

[Mrs. Smith the Third]

AND the best from the 2 most informed advocates for simufilam and the company that pioneered and is bringing to market the first drug to treat Alzheimer's that actually works........a big Shout Out to Matt Nauchtraub and Joe Springer!!

[investingdog]

Joe Springer Matt Nachtrab interview on utube. Great stuff, I learned a lot. Have to see it.

[Mrs. Smith the Third]

Imagine a world without the brain bleed drugs or the MABs.......that could be coming via the playbook the FDA brings to Lilly's drug doneonemab.......Imagine how this stirs up the shorts who may now see the light shining on SAVA this close to the readout on PH3........we are entering extremely exciting times for a potential blockbuster Alzheimer's drug coming to the market 2025.......go go go,,

[Mrs. Smith the Third]

the Ghetto Circus @ the Hush Money Trial in NYC has concluded and succeeded for TODAY.......what lies beneath has not played out similar to what has not played out with Simufilam trials that conclude in just months meaning Readout 2024 for Simufilam in just months........shorts will not wait to get out upon PH3, i think they will start leaving in advance.......HOLD your shares tightly!!

[Mrs. Smith the Third]

and an obvious bullish bias depicted by Team SAVA.......

[WebSlinger]

Okay, I'm done taking my victory lap for 2023. Now it's time for my next public-facing prediction.

Cassava Sciences $SAVA is my top short-squeeze candidate for 2024.

There are a ton of catalysts on the horizon here; most notably the results of its fully-enrolled Phase 3… https://t.co/ddMlC9ieek pic.twitter.com/Q5sRaj8Xhh

— Simon Erickson (@7Innovator) January 22, 2024

[FooBarAndGrill]

It’s T+1 time!

[investingdog]

From AI
Simon Erickson is the founder and CEO of 7investing. He is one of the stock market’s most forward-looking investors, focused on identifying disruptive innovation and finding developing trends before others may even be aware of them.
Cassava Sciences $SAVA is my top short-squeeze candidate for 2024. There are a ton of catalysts on the horizon here; most notably the results of its fully-enrolled Phase 3 simufilam trial (expected completion by EOY 2024)

[FooBarAndGrill]

May Employee Stock Option disclosures. All options granted vest over 48 months at 1/48th each month. All options have a cost basis of $22.10
10,000 James Kupiec Chief Medical Officer
10,000 Robert Cook SVP & General Counsel
25,000 Eric Schoen Chief Financial Officer
50,000 Remi Barbier President & CEO

[Mrs. Smith the Third]

How about a Post Holiday Rally long overdue based on the backlog of superb trial data for simufilam AND the fact that we are nearing the completion of PH3 in just months......AND lets put this rally in overdrive!!

[investingdog]

Copilot
The U.S. Food and Drug Administration (FDA) will convene an in-person meeting of the Peripheral and Central Nervous System Drugs Advisory Committee (PCNS) on Monday, June 10, 2024, to discuss Donanemab. Eli Lilly and Company has submitted Donanemab for the treatment of early symptomatic Alzheimer’s disease. The Phase 3 study submitted as part of this application, TRAILBLAZER-ALZ 2, evaluated the safety and efficacy of Donanemab in participants aged 60-85 years with early symptomatic Alzheimer’s disease (mild cognitive impairment or mild dementia due to Alzheimer’s disease) who had confirmed Alzheimer’s disease neuropathology. The trial enrolled 1,736 participants across eight countries, selected based on cognitive assessments in conjunction with amyloid plaque imaging and tau staging by positron emission tomography (PET) imaging. Donanemab selectively targets existing amyloid plaques, potentially improving disease progression.

[investingdog]

Bing AI comparison of Aducanumab and Simufilam:

Copilot
Certainly! Let’s compare the test results for Aducanumab and Simufilam in the context of Alzheimer’s disease:
Aducanumab:
Aducanumab (marketed as Aduhelm) is an antibody-based treatment that targets amyloid-beta plaques in the brain, which are associated with Alzheimer’s disease.
In a Phase 3 clinical trial, Aducanumab demonstrated a reduction in amyloid plaques and a potential impact on cognitive decline1.
However, its approval has been controversial due to mixed results and concerns about safety and efficacy.
Simufilam:
Simufilam is an experimental oral therapy developed by Cassava Sciences. It aims to improve cognition in people with Alzheimer’s disease.
Two Phase 3 clinical trials are currently evaluating Simufilam:
RETHINK-ALZ (NCT04994483): Testing Simufilam (100 mg twice daily) against a placebo for a year in people with mild to moderate Alzheimer’s. Results are expected by the end of this year.
REFOCUS-ALZ (NCT05026177): Testing two doses of Simufilam (50 or 100 mg twice daily) against a placebo for 76 weeks. Results are due in 2025.
Interim safety reviews have not raised significant issues, and MRI data from REFOCUS-ALZ showed no cases of ARIA-E (amyloid-related imaging abnormalities edema) after 40 weeks2.
Notably, two-thirds of participants in a study funded by the National Institutes of Health improved their cognition scores after nine months on Simufilam3.
In summary, while Aducanumab has faced controversy, Simufilam shows promise in slowing cognitive decline and improving cognition in Alzheimer’s patients. We await further results from ongoing trials to better understand their effectiveness and safety profiles.

[investingdog]

link for Simufilam data

https://delta.larvol.com/NewsItemImages/783f89d3-b973-4bdc-a1ca-21382490911e/8bc9f883-bba5-4b08-892e-6f992fdf51f5.jpg

[FooBarAndGrill]

Yeah. The whole play was to halt sava's clinical trials. Obviously that play didn't work.

[ranchhand71]

Reposted from X:
Rapport Therapeutics filed an S1 on May 17th to go public.

The genesis of Rapport Therapeutics is unequivocally linked to an effort to stop the Cassava Sciences Alzheimer's therapy trial. They seemed to put a competitor through HELL to gain an advantage and profit from a short position in the stock.

David Bredt founded Rapport Therapeutics a Delaware on February 11 2022, the same day that his citizen's petition against $sava was denied by the FDA.

I believe David Bredt,
@JNJNews
, Rapport Therapeutics, Jordan Thomas, and
@ThirdRockV
participated in a massive fraud to stop a competitor in the exact same research area of Receptor Associated Proteins (the RAP in Rapport). David Bredt departed Johnson and Johnson in March of 2021. He worked with Jordan Thomas and filed a Citizen's Petition and Whistleblower complaints against Cassava in August of 2021. The Citizen's Petition was denied on the same day he started Rapport. SEC and DOJ investigations still linger with no charges against $sava. How could that happen if all these events are not linked by collusion between these people and companies?

[FooBarAndGrill]

Annual meeting notes.
All measures passed.
Decision to close the warrant distributions after conversions dried up. May or may not do another at some point.
735 P3 completers. 20% dropout rate with reasons all over the board (lost their ride, etc.) 90% conversions from P3-blinded to OLE
OLE is very expensive but they're happy to continue it.
Total focus on AD at this point. Research in other areas (cancer, Parkinson's) is on-going but AD is THE THING.

[FooBarAndGrill]

Today 10:00 AM Central
https://apps.computershare.com/MeetingsShareholderWeb/Home?Code=MXKUQLX&Invitation=&Locale=en

[FooBarAndGrill]

WOW! $125M Cash! P3 trials are covered.
Cassava Sciences Announces Over $125 Million Raised from Warrant Distribution

[runncoach]

125 million....that's real money. Brilliant strategy from company management it would seem to me. 6ish months to go!

[FooBarAndGrill]

$22 cap removed.

[Monksdream]

Reports 5/8

[FooBarAndGrill]

Proxy
https://www.cassavasciences.com/static-files/3efd35a5-e3ba-41ea-be8b-a99d20c9c835

[FooBarAndGrill]

Thursday, May 9 10:00 AM Central
https://apps.computershare.com/MeetingsShareholderWeb/Home?Code=MXKUQLX&Invitation=&Locale=en

[FooBarAndGrill]

These PK trial results will be used to complete a section of the NDA.

[FooBarAndGrill]

SAVA will run another Pharmacokinetics (PK) trial for patients with impaired liver function.
A Pharmacokinetic Study of Simufilam in Subjects With Impaired Hepatic Function

Pharmacokinetics (PK) is the study of how the body interacts with administered medications for the entire duration of exposure.

[runncoach]

These guys are closer than anyone else in the alternative AD space. They aren't pretending like some thanks to the SPA. let's pray that it's an improvement over current SOC

[FooBarAndGrill]

The cash burn for the two P3 Clinical Trials Is represented by a Bell Curve. The peak of the Bell Curve was reached upon full enrollment in the trials. We are now on the down slope of that P3 cash burn. Patients are completing the P3 trials and transferring to the P3 OLE..

[FooBarAndGrill]

Cassava updated Corporate Presentation.
https://www.cassavasciences.com/static-files/2e5fa90d-4e73-4b96-8d19-57edabe08130

[FooBarAndGrill]

SAVA Clinical Trial Completed April 29. Pharmacokinetics ...

Pharmacokinetics (PK) is the study of how the body interacts with administered medications for the entire duration of exposure. This is closely related to but distinctly different from pharmacodynamics, which examines the drug's effect on the body more closely.

Open-label Study of the Absorption, Metabolism, and Excretion of [14C]-Simufilam Following a Single Oral Dose in Healthy Male Subjects

[FooBarAndGrill]

April Insiders Warrant Transactions.
Richard Barry Director spent $3,873,870 of his own cash to add 176,085 shares to holdings.

Sanford Robertson Director spent $1,518,000 of his own cash to add 69,000 shares to holdings.

James Kupiec CMO spent $33,000 of his own cash to add 1500 shares to holdings.

Eric Schoen CFO spent $33,000 of his own cash to add 1500 shares to holdings.

[FooBarAndGrill]

My thoughts on warrants.
(1) Capped share price at $22
(2) Exercise was not a click away, so they just sat there.
(3) I have no idea how many were actually exercised.

[FooBarAndGrill]

Warrant announcement Apr 15.
https://www.cassavasciences.com/news-releases/news-release-details/redemption-date-announced-warrants

[FooBarAndGrill]

Bonus warrant status page.
https://www.cassavasciences.com/static-files/5b796146-4e6a-41e6-9909-5e084bcacfec

[Biggeoff]

Rumors might be true

[Biggeoff]

If Carl Icahn took stake. This should moon shot.

[FooBarAndGrill]

This thread has some thoughts:

I wonder why $sava is moving the last couple days. High volume move up despite a market that is not up. Shorts always seem to be in the know. It doesn’t seem like a bull trap as those on $sava tend to be a couple hours of action.

I’m wondering if the shorts got a heads up…

— Matt Nachtrab (@MattNachtrab) April 9, 2024