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QCM Speculation: An Act of Throwing Spaghetti on the Wall to See What Sticks

QCM asserted some feckless speculation about this study that I found to be exactly that, mere SPECULATION without a shred of evidence. And they use this speculation to attack a later SAVA study. Before I breakdown this speculatory FUD I found in their report (there are many I have not written on yet) I want to explain some basic concepts in statistics.

A bell curve shows the distribution of a population. For the purposes of this post, consider the bell curve as showing where patients fall in relation to their MMSE score. In statistical analysis the mean is the average represented by this symbol μ. A standard deviation is a measure which shows how much variation (such as spread, dispersion, spread,) from the mean that exists. It is represented by this symbol σ. 99.7 of the entire study population is captured within 3 standard deviations of the mean, 95% of the population is captured within 2 standard deviations of the mean, and 1 standard deviation captures 68% of the population.

Now that with that review out of the way, let's understand the importance of the MMSE or the Mini Mental State Exam.

The Mini Mental State Exam Explained:

During the MMSE, a health professional asks a patient a series of questions designed to test a range of everyday mental skills. The maximum MMSE score is 30 points. A score of 20 to 24 suggests mild dementia, 13 to 20 suggests moderate dementia, and less than 12 indicates severe dementia. On average, the MMSE score of a person with Alzheimer's declines about two to four points each year.

If a person scores 30, it means there were no errors detected and it is EXTREMELY LIKELY with confidence that the person does not have AD. Let's review some important data so we can understand the population in the study. In total there were 64 patients in the study who were randomly put into the placebo, 100mg Simufilam, or 50mg Simufilam cohorts. In the table below you can see how they were distributed.

Placebo Cohort

Simufilam (PTI-125), 100 mg Tablets Cohort

Simufilam (PTI-125), 50 mg Tablets


Population Size





Mini-Mental State Exam Score Mean





MMSE Standard Deviation





A visual understanding of these initial populations, as they were at the beginning of the study, is as follows:

As you can see these groups are nearly identical. QCM asserts that:

....it is almost certain that there will be patients in the study who do not have Alzheimer’s disease (some may have non-Alzheimer’s dementia or simple, age related memory loss). This presents a major problem in the study as any sample of these patients is likely to show better symptoms progression if compared with studies which included exclusively people with certain Alzheimer’s: Cassava may be using exactly this discrepancy in pages 20-21 of its presentation to investors to dubiously claim the efficacy of its drug.

QCM is correct (it feels wrong to say that) that there were very likely people in the study who did not have AD, but it is a very small group in each cohort. In the placebo group (n=22) there are likely at least 3.48 patients who have a MMSE score that does not support a diagnosis of AD. In the 100mg group (n=21) there are likely at least 3.2 patients who have a MMSE score that does not support a diagnosis of AD. In the 50mg group there are likely at least 3.2 patients who have a MMSE score that does not support a diagnosis of AD. So, there's at least 3 patients in each group who have a MMSE score that does not support a diagnosis of AD. Again the groups are showing they are very similar in distribution. The vast majority of people in each group had a MMSE score that is indicative of AD per the guidelines here. The primary purpose of this study was to measure change from baseline in CSF Abeta42. It was not really primarily intended to measure progression, it was study for less than 30 days and it was focused on CSF. I have read every exclusion in this study and each instance it was for extremely logical reasons. Some of those reasons include, patient withdraw, no detectable drug in their plasma (remember the purpose is to measure change from baseline CSF), non-compliance by pill count and other logical and clearly explained reasons. The exclusions were logical and for QCM to suggest they were made to "likely...show better symptoms progression" is ridiculous. In fact, the exclusion criteria for the those who got very few wrong answers on the Paired Associates Learning (PAL) total errors, well that very likely excluded the patients who had a MMSE of 24 or higher. So, it is very likely the patients without AD were trimmed in this manner. Likewise this same exclusion also likely removed those with really low MMSE scores thereby excluding those who did not understand the instructions. Again, excluding patients in all cohorts on the basis of too high or too low PAL results -remember they are extremely similar cohorts in MMSE results- would impact all the cohorts in roughly the same way. In short, these exclusions are not problematic because the exclusion criteria impacts the extremely homogenous cohorts in a similar fashion. Anyone asserting otherwise cannot be taken seriously.

I do not find the exclusions to be for "implausible reasons" or for "other highly dubious explanations" as asserted by QCM. It is my opinion that QCM is attempting to throw a plate of spaghetti against the wall to see what will stick and assist in their short position, if it remains intact at all still. As previously mentioned on this site, there is a letter that suggests QCM may have exited their short position the same day they initiated. If this is true, it shows QCM has no conviction in their short position, in their research, or in the research of the Twitter PhDs. I think it is true, as QCM has refused to denounce the letter. As such, it is another reason I cannot take anything QCM asserts as serious. It is my opinion that authors on Seeking Alpha, InvestorPlace, and other investment websites that do take QCM seriously, have fallen for one of the most sophisticated and coordinated FUD campaigns I have ever seen. This is not investment advice.. This is not medical advice. This is just my opinion.

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