Cassava Sciences Inc (SAVA)

[ranchhand71]

8:30 AM on November 7--will Rick provide an important update on SAVA FDA progress????
Expect short sellers could have a bad week post election for several reasons. Seat belts on...

[investingdog]

Simufilam, an experimental drug for Alzheimer's disease, interacts with amyloid beta (Aß) through its mechanism involving filamin A (FLNA). Here are the key points regarding its relationship with amyloid:
Mechanism of Action
Binding to Filamin A: Simufilam binds to an altered form of filamin A, which is implicated in Alzheimer's pathology. This binding disrupts the interaction between FLNA and the a7 nicotinic acetylcholine receptor (a7nAChR), a pathway that is activated by soluble Aß42 and leads to neurodegeneration through tau hyperphosphorylation.
Effects on Amyloid Beta
Reduction of Aß42 Binding: Research indicates that simufilam significantly reduces the binding affinity of Aß42 to a7nAChR. It has been shown to decrease this binding with a potency measured at 10 picomolar IC50, effectively disrupting the toxic signaling associated with amyloid.
Disruption of Toxic Signaling: By interfering with the FLNA-a7nAChR linkage that is critical for amyloid's toxic effects, simufilam may help mitigate the neurotoxic consequences of amyloid accumulation in the brain.
Impact on Inflammation and Neurodegeneration
Anti-inflammatory Effects: Simufilam has also been shown to reduce inflammatory cytokine release from Aß42-stimulated human astrocytes, suggesting it may have anti-inflammatory properties that further support brain health.
Neuroprotective Potential: In animal models, simufilam has been reported to reduce tau hyperphosphorylation and amyloid deposition, indicating a potential neuroprotective effect against the pathological features of Alzheimer's disease.
Conclusion
Simufilam's approach to modulating the interactions between amyloid beta and cellular receptors represents a novel strategy in Alzheimer's therapy. By targeting these interactions, it aims to disrupt toxic signaling pathways associated with amyloid accumulation, potentially offering a new avenue for treatment in Alzheimer's disease.

[runncoach]

For a disease no one knows the cause of....no

[investingdog]

Have you ever use it? Try, you may learn something. It does biostatistical calc very well. Try Perplexity.ai
You feed it P2 results and P3 sample size and ask to calculate p, probability of stat. sig., etc.

[sunspotter]

Artificial, yes.

Intelligence? Not so much.

[runncoach]

AI simulations? Lol

[investingdog]

Sixty bucks before the Rethink readout?
The general consensus is that a run-up rally is about to start. Being short now, knowing that the share price is likely to double in the next 45 to 60 days, is a losing proposition.
If I were short and believed in a Phase 3 failure, I would exit my position now, stop paying interest, and short at twice the price just before the readout.
Of course, the shorts are entrenched in their positions and beliefs and may not do what they should.
The probability of a statistically significant Rethink readout is estimated at 65% based on a very conservative trial design, 80% for Refocus, and 93% for the combined Rethink and Refocus trials. According to AI simulations, this probability ranges from 95% to 98%.
Considering these facts, $60 before the readout seems low given the risk/reward potential.

Let me add that insiders haven't sold a single share. If there were a problem with the Phase 2 trial data, Remi wouldn't hold his 2 mil. shares. He was involved in the process and knows best.

[ranchhand71]

Talk to the families of patients in the trials-the best due diligence available

[AMA]

43.3% short cost to borrow over 100% now

[janice shell]

Um, I don't think you understand how shorting works.

[investingdog]

Shorts keep borrowing shares and shorting more - over 50% of the float not counting phantom shares and synthetic short positions. Totally insane.

[FooBarAndGrill]

Last Patient, Last Visit is an expected milestone. Always appreciated as material information. Squeeze? No.

[ranchhand71]

Will this good progress news cause a short squeeze?

https://www.cassavasciences.com/static-files/d46ee533-09d3-42d8-ba76-5b62d9332720#page4

[janice shell]

Really? Did you read the article I posted?

The committee, however, said it could not draw definitive conclusions about the integrity of Wang’s work because he could not or would not provide original data from his experiments. The panel nonetheless declared that he had engaged in “long-standing and egregious misconduct in data management and record keeping.”

He also stole money, according to the DOJ.

https://www.science.org/content/article/u-s-levels-fraud-indictment-cuny-scientist-who-helped-alzheimer-s-drug-developer

[investingdog]

"Is he unaware that the DOJ has brought criminal charges against Wang?"

Nonsense. Did you read his stuff on X. He spent hours and hours talking to Wang about Simufilam, visiting him etc. DOJ charges are for some money transfers related to grant if I remember correctly. Nothing to do with P2 and lab analysis.

[janice shell]

I believe Barbier is gone for good, but am not sure if his wife--who did stay on--went with him. In a PR from a few days ago, both were described as "former employees":

https://www.cassavasciences.com/news-releases/news-release-details/cassava-sciences-resolves-sec-investigation

Barry, the new CEO and Chairman, also said:

In connection with the previously-disclosed investigation by the Department of Justice (“DOJ”), the Company does not currently anticipate that DOJ’s Criminal Division will bring charges against or seek a resolution with the Company.

We'll see.

[investingdog]

"All three of them have left the company."
No, Barbier and Burns are back. They plead no contest because Burns violated unblinding procedure in an email. There is no proof Wang actually use the info to unblind some patients, but he could have. That was enough for SEC to pass the verdict.

[janice shell]

See the post on X by Matt Nachtrab. SEC concluded that based on some email information Wang could have unblinded about 30% of P2 patients and SEC made the ruling based on that.

Is he unaware that the DOJ has brought criminal charges against Wang?

[janice shell]

This raises the question: could the SEC be mistaken?

No. The company, Barber, and Burns settled:

The SEC’s complaint, filed in the U.S. District Court for the Western District of Texas, charges Cassava, Barbier, and Burns with violating antifraud provisions of the federal securities laws and charges Cassava with violating reporting provisions of the federal securities laws. Without admitting or denying the allegations, Cassava, Barbier, and Burns consented to civil injunctions against future violations and agreed to pay civil penalties of $40 million, $175,000, and $85,000, respectively. Barbier and Burns agreed to be subject to officer-and-director bars of three and five years, respectively.

And:

In a related order, the SEC charged Cassava consultant, Dr. Hoau-Yan Wang, an associate medical professor at the City University of New York’s Medical School and the therapeutic’s co-developer, for manipulating the reported clinical trial results.

https://www.sec.gov/newsroom/press-releases/2024-151

Wang has also been criminally charged by the Department of Justice:

https://www.science.org/content/article/u-s-levels-fraud-indictment-cuny-scientist-who-helped-alzheimer-s-drug-developer

All three of them have left the company.

[investingdog]

Insiders are not selling, they actually bought more - they wouldn't be doing that on questionable P2 data.

[investingdog]

Reply to runncoach
I don't believe they did. See the post on X by Matt Nachtrab. SEC concluded that based on some email information Wang could have unblinded about 30% of P2 patients and SEC made the ruling based on that. A number of patients were excluded - they did not screen P2 for vascular dementia so they excluded them later. That is correct decision because Simufilam does not help those and they are not in P3 trial. Once again see X (twitter) for complete explanation by Matt.
On your second point it is always wise to sell some into a strong rally.

[runncoach]

The question is if the drug worked so well, why did company employees have to manipulate the data per the SEC? I personally would sell into any rally. Jmho

[investingdog]

Now that the SEC episode is over, there are no more hurdles ahead. A significant rally into Phase 3 readouts could happen at any time, driven by fundamentals and FOMO (fear of missing out).

[investingdog]

The SEC's litigation release appears bad for Cassava. However, insiders have not sold a single share in the last five years. This raises the question: could the SEC be mistaken?

[investingdog]

Reducing Filamin A Restores Cortical Synaptic Connectivity

https://pubmed.ncbi.nlm.nih.gov/39164108/

[investingdog]

Rich Barry Cassava CEO interview

[runncoach]

If the trial fails can you imagine the class action?

[FooBarAndGrill]

Here was the basis for all my support, all I can say at this time is "poof".

Cassava claimed that Phase 2b bioanalyses were conducted under blinded conditions

[janice shell]

Well well well. Richly deserved. Here's the SEC's litigation release:

https://www.sec.gov/newsroom/press-releases/2024-151

The Order:

https://www.sec.gov/files/litigation/admin/2024/33-11311.pdf

The Complaint:

https://www.sec.gov/files/litigation/complaints/2024/comp-pr2024-151.pdf

[runncoach]

Oops.
https://finance.yahoo.com/news/cassava-pay-40-million-sec-231145794.html/

[runncoach]

Man it's getting close!

[TechandBio]

Sava Simufilam looks like a best in class for Alzheimer’s disease Loaded for some calls early 2025!
Also been accumulating a under the radar gem IceCure 97% Complete Response Rate for Breast Cancer for 5 Years out Peer Published will run hard soon FDA Panel Meeting early November.

$SAVA

[FooBarAndGrill]

Cassava up on DSMB review.

“We are pleased to have satisfactorily completed this safety review, the last before the expected top-line read out for our first Phase 3 study.” said Jim Kupiec, Chief Medical Officer. “We look forward to announcing top-line efficacy, safety and biomarker data for our 12-month Phase 3 study before the end of 2024.”

[Stockexpertpro]

PCRX 113% institution owned with 25% Float sold short Reminds me of SAVA

Buy some out of the money upside calls if there cheap

PCRX is Profitable huge revenues and growth

Income Statement
Revenue (ttm) 690.31M
Revenue Per Share (ttm) 14.88
Quarterly Revenue Growth (yoy) 5.00%
Gross Profit (ttm) N/A
EBITDA 175.34M
Net Income Avi to Common (ttm) 63.59M
Diluted EPS (ttm) 1.34

Company has over 400 Million in Cash

Book Value Per Share (mrq) 19.07 getting it for 11$ back down here all time lows for this stock with 113% institution ownership
Cash Flow Statement
Operating Cash Flow (ttm) 194.36M
Levered Free Cash Flow (ttm) 153.5M Cash flow positive

Stock reminds me of SAVA Dropped down to like 11$ then ran to 42$

[runncoach]

Quite the ride here. Smart move

[joyceschoice]

Sold 1/2 from my most recent buy near $10.
GLTA

[Schmiggins]

Smithy...What other diseases has SAVA talked about tackling with their FLNA fix?

Seems like there would be a few. And have they done patent coverage on them if there are any? I'll check out their patents over the weekend, but perhaps someone can give me some motivation?....

[Schmiggins]

Good discussion. Seeing as they are favoring the "Milds" at 71% (even though the mean is right in the middle), they've designed it to make a strong case for a "Milds" approval. The "Moderates" - though there are less of them - will include some pretty advanced cases, and they are probably looking to see some good signs in that group but they are not relying on them to help much overall. I think they'll succeed for what they want and maybe there's a chance they luck out with the "Moderates". But if not, not a deal breaker.

The trial wrapping up 6 months later will possibly show that over more time the "Moderates" start to do better as the corrected proteins come in at higher numbers in their brains compared to the damaged ones. Also there will be data on the differences between the doses to look at.

I think the second trial may help the first trial if it needs it. Between the two trials, there will likely be enough positives to see to warrant approval, it seems reasonable, to me, to expect that approval.

The new seriousness seen in management - (I think Nicaise (Alexion) was brought in at the end of last year to become the CEO....He's been on the Sarepta board with Barry for years) - and the rising stock price and a whole bunch of new "lookers and likers" is going to keep the stock in focus up until the climactic moment at year's end. If ambiguity still ensues and a buying opportunity arises, take it .... The second trial will fix everything.

I bought in on Tuesday at 19. Had bought all the negativity for a year previous and didn't dive in deep until this week. I've been with Anavex for a year and Sarepta for 19 years. I sure wish Anavex had a Robertson, a Barry, a Nicaise, and this Matt N guy routing for it and helping it. Anavex does have the bad press that Cassave has had, so maybe that's one thing going for it! ....It's got the same screwy enemies!

[investingdog]

Good day for SAVA longs with all indices in deep red. Up almost 100% last 5 trading days. Should continue next week.

[runncoach]

Praying for success and in 5 short months we'll know one way or another. Never bet more than one can afford to lose

[Mrs. Smith the Third]

EVERYONE wants on board this train before the FDA gives the nod on simufilam AND before the market cap explodes or before simufilam sets fire across the globe.....Suffering alzheimer's victims in need of a treatment that works is the reason for all of the above.......

Big Pharma will be in the crosshairs (BUYOUT)........i am counting on it!!

[Monksdream]

Early Barchart 100
https://www.barchart.com/stocks/performance/percent-change/advances?timeFrame=today&viewName=main&screener=overall&orderBy=percentChange&orderDir=desc

[Mrs. Smith the Third]

I have followed sava trading closely for years now. Watching order flow and there are a lot of larger buys on green bars. 10k+ share buys. 40%+ of share volume is medium to large orders. Before the recent powerful bounce off of the $9 range I tended to see much more small orders on the buy side.

Matt Nachtrab on X

[Mrs. Smith the Third]

for a very long period (years), i have cheered on the FDA for standing behind SAVA/SIMU.......starting with the SPA then to the dismissal of the Citizens Petition just months later in 2022.......I have always eluded to the fact that it is extremely prudent to adopt a bullish bias on the FDA/SAVA........Today, this is elevated with yesterday's announcement on the extended trials.......the subtle HINT i take away is the FDA has a sharp interest in Simufilam >>> taking the drug to approval.....yes, yes and YES!

we are on our way to triple digits testing the all time high......PH3 Strong!!

[Mrs. Smith the Third]

delayed reaction to yesterdays confirmatory news on the extended trials which allows those on simu to stay on simu and even more importantly simufilam WORKS unlike the brain bleeders that do little but compromise the suffering AD patient......this rally on this great news is worth a new 52 wk high....how about triple digits high!!

[investingdog]

Simufilam (PTI-125) is a small molecule that targets an altered form of filamin A (FLNA), which is implicated in Alzheimer's disease. By binding to this altered protein, simufilam aims to reduce neurodegeneration and neuroinflammation, and it has shown potential in disrupting the binding of amyloid-beta to neuronal receptors, which is a hallmark of Alzheimer's pathology.
To put it in a plain language - triple digits after P3 readout

[Monksdream]

SAVA

[runncoach]

Nice move today for the bulls!

[runncoach]

How would 30% of patients not being helped make for great results? And no 90% isn't unheard of. Does mean it's safe and that's why FDA hasn't stopped trials even with company management stepping down or indicted and is great news compared to MABs for sure

[runncoach]

Thanks Doc! Hoping for the best here but 92% is just nuts!