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Good day for SAVA longs with all indices in deep red. Up almost 100% last 5 trading days. Should continue next week.
Where do you get latest short interest? Nasdaq only shows 6/28/2024. Thanks.
LSXMA is trading at 22.60, SIRI at 3.93. 3.93 * 8.3 = $32.62. Can someone explain the difference, LSXMA is trading at 44% discount ???
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
Pentara was responsible for the statistical analysis of the Phase 2 and Phase 2b trials, focusing on cognitive endpoints and overall efficacy of simufilam in patients with mild to moderate Alzheimer's disease. Wang and Burns were not involved in these trials.
Therefore, the Phase 3 trial was designed to have a high probability of statistical significance based on the untarnished Phase 2 results.
Per trial design the probability of either Rethink(0.63) or Refocus(0.80) achieving statistical significance is (1 -(1-0.63) * (1-0.8)) * 100 = 92.4%
from Matt N. on X
"I believe short sellers and big pharma are using the government to stop a promising and safe Alzheimer's drug from getting to patients. Dr. Wang, as a professor and researcher at a small university, is an easy target for the attack and is all alone to mount a fair defense. "
and more..
"Dr. Wang has dedicated his life to curing Alzheimer's disease, but now his safe, twice a day pill, in phase 3 trials at the FDA is coming under attack by short sellers, big pharma competitors, and the DOJ. The DOJ has indicted Dr. Wang 3 months before the first phase three trial finishes in October of this year.
Families on the drug and clinical trial sites that have run the trials have said that the drug does turn around Alzheimer's disease. "
This is all public information, do your own homework. Go to perplexity AI and ask question. It will tell you everything, beats googling.
P3 excluded vascular dementia and some other conditions. So, the results should be better than P2b. Designed for 80% probability of stat. sig.
You missed the point.
Simufilam binds to and stabilizes filamin A (FLNA), a scaffolding protein in the brain that becomes altered in Alzheimer's disease. Lingering effects of that are to be expected and CMS study confirms that. For the first 3 months there was almost no difference between drug and placebo - simufilam repaired some of the AD damage as was expected. Next 3 months that residual effect gradually disappeared and the study confirmed it. Has nothing to do with stat. significance, that was not the purpose of the study.
P2b data thoroughly reviewed by FDA prior to P3 trial. Board action is a good thing for SAVA, Remi made mistakes. Based on P2b results P3 RETHINK has a great chance of being statistically significant - per study design about 80%. REFOCUS even better, about 90%.
The Cognition Maintenance Study (CMS) was a Phase II randomized withdrawal trial evaluating simufilam, an oral therapy developed by Cassava Sciences, for the treatment of Alzheimer's disease. Here are the key findings from the study:
Study Design:
The CMS enrolled 157 patients with mild-to-moderate Alzheimer's disease.
All patients first received open-label simufilam 100mg twice daily for 12 months.
Patients were then randomized 1:1 to either continue simufilam or switch to placebo for 6 months.
Primary Endpoint:
The pre-specified cognitive endpoint was mean change in ADAS-Cog11 scores over 6 months, comparing simufilam to placebo.
Key Results:
Simufilam slowed cognitive decline by 38% compared to placebo over the 6-month randomized period.
The placebo arm declined 1.5 points on ADAS-Cog, while the simufilam arm declined 0.9 points.
Patients with mild Alzheimer's disease (MMSE 21-26) who continued on simufilam showed no material decline in ADAS-Cog scores over 18 months, indicating stable cognition.
Safety:
Simufilam 100 mg twice daily was reported to be safe and well-tolerated.
There were no drug-related serious adverse events.
No treatment-emergent adverse events occurred in 5% or more of study participants.
The placebo group did better than expected due to the lingering drug effects, especially for the first 3 months.
The chances of Blarcamesine receiving approval in the EU appear promising due to several factors:
Positive Phase 2b/3 Trial Data: The clinical trials have shown significant improvements in dementia symptoms and reductions in amyloid aggregation and brain volume loss, which are key indicators of neurodegeneration in Alzheimer's disease.
Convenient Oral Formulation: Blarcamesine is an oral treatment, which offers a more convenient alternative to existing Alzheimer's treatments that often require complex logistics and monitoring for side effects like amyloid-related imaging abnormalities (ARIA).
Regulatory Encouragement: The EMA has recommended that Anavex proceed with a full approval application, indicating confidence in the drug's potential. Additionally, the Committee for Medicinal Products for Human Use (CHMP) has deemed Blarcamesine eligible for a Marketing Authorization Application (MAA).
Market Need: With an estimated 7 million people in Europe affected by Alzheimer's disease, and this number expected to double by 2030, there is a significant demand for effective and accessible treatments.
Given these factors, Anavex is optimistic about the approval prospects for Blarcamesine in the EU, with a decision expected by the end of 2024
Another round of funding? No, they have more than enough to finish P3 trial. We have to wait till next CC in August to hear more.
Well, the math is very simple if you take Cramer $60 value and multiply with .63 probability of stat. sig. per AI for the first P3 trial. So, the fair value per Cramer and AI is $37.8. So, buying at $18 is a bargain. Of cause, it is a lot higher - we have two P3 trials and value per share should certainly be in high triple digits if successful..
from artificial intelligence (perplexity AI)
The chances of simufilam's Phase 3 results being statistically significant are estimated to be relatively high, based on various analyses and models. Here are the key points:
Quantitative Model Estimates:
An in-house quantitative model calculated the likelihood of achieving statistical significance in the ADAS-Cog score to be around 63%.
For the REFOCUS-ALZ study specifically, the same model estimated an 80% chance of achieving statistical significance.
Historical Data and Expectations:
The REFOCUS-ALZ trial is designed to measure changes in cognitive function and daily living activities over 18 months.
Historical placebo decline rates over 18 months for patients with baseline MMSE scores of 22-24 are typically between +5 to +6 points. For the simufilam arms, extrapolating from previous data, the expected 18-month decline for the 100 mg arm would likely be between +2.5 to +4.5 points.
Consistency with Previous Trials:
The inclusion criteria for the REFOCUS-ALZ trial are consistent with those of the 12-month Phase 3 study, suggesting that similar results are expected, though with potentially slightly higher rates of cognitive decline due to the longer study period.
Safety and Biomarker Data:
Interim safety reviews have shown no significant issues, and the drug has demonstrated a favorable safety profile in previous trials.
Market and Expert Opinions:
Analysts and experts have expressed optimism about the potential for simufilam to show cognitive benefits, particularly in patients with mild Alzheimer's disease.
In summary, while there are inherent uncertainties in clinical trials, the available data and models suggest a relatively high probability (60-80%) of simufilam achieving statistically significant results in its Phase 3 trials. The final outcomes will be crucial in determining the drug's efficacy and potential approval.
Yea, stock price is manipulated by daily churning. This is actually good - retail, including myself, can buy more cheap shares.
Must see...
Interview with Remi Barbier about P3 design, biomarkers, neuroinflammation, beta amyloid plaque, filamin a mutations, simufilam etc.
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
Matt Nachtrab on X - take a look, Short sellers abusing the system.
The Attack of Cassava Sciences (SAVA)
— Matt Nachtrab (@MattNachtrab) June 11, 2024
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…
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)
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
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.
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.
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?
Yahoo MB keeps deleting any links to this board including abbreviated partial links.
Joe Springer Matt Nachtrab interview on utube. Great stuff, I learned a lot. Have to see it.
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)
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.
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.
Prasco was not included. Started selling in January.
I don't think you can short Pink Market stocks.
You have a valid point. Thanks
ELTP Earnings Per Share for quarter ended 9/30/2023 EPS was 0.0149 (rounded off to 0.01 on financial page). Assume 12/31/2023 quarter and next two quarters in 2024 will be the same. So, current EPS is 0.0149 x 4 = 0.0596. Current PE = 0.019 / 0.0596 = 3.19. What is a fair PE for a generic drug company? At least 10, so the share price should be 10 x 0.0596 = $0.596 which is 3 times current share price.
Wait till it hits the fan
You will find out tomorrow after the market closes. Down 6% today with all indices up big time - leaks about earnings or some other bad news?
More than 3% gain in the short trading session on Friday. Market is expecting positive results for the p2 trial, and the results should be out 2nd week in Dec. Any comment on share price upon positive announcement? A pill that cures Covid will make vaccines less relevant.
Yes, should continue to go up. They will file for approval within weeks which will be another boost.