I am constantly amazed at the seemingly endless capacity for HC...

I am constantly amazed at the seemingly endless capacity for HC posters to whip themselves into a frenzy of negativity over nothing.
The key word everyone seems to be missing in the answer (and, therefore, I assume the question - although we can't even see that) is... INDIVIDUAL



This is completely NORMAL as results from any INDIVIDUAL trial participant are subject to too much variability (due to the heterogeneity of the participant pool) to be able to make any meaningful observations. Put simply, there are so many variables that can influence the ALSFRS-R scores produced by a single patient that it is only by looking at the aggregate results produced by the entire pool that we can see any trend.

Further, it is only when the pool is big enough and the observations span a sufficient time period are we able to assert that what we are seeing is very unlikley to be due to chance variations that occur naturally in the patient population and that the results are statistically significant. Typically, the threshold will be the 95% confidence level (p<0.05). To be clear, the statistics at our disposal from the Phase 1 MEND study are not powered to produce these observations and so we HAVE NOT met this threshold yet - it is what the upcoming larger adaptive Phase 2/3 trial (or more accurately, the registration trial) is all about. (Note: The OST probability produced by comparing trial participants with OST data from matched patients in the PRO-ACT database is different again). Although what we've seen so far is extremely encouraging, the subject pool is too small to be able to definitively assert efficacy.

The variation in individual scores can be seen in the following table, which is taken from the top-line MEND study results presentation released to the market on 27/2/24. I've highlighted the minimum and maximum results recorded for cohort 1 and 2 to show just how much variation exists from one patient to the next.



In regard to Nfl levels, we've already seen as much detail as one could reasonably expect. The following graph is taken from the Singapore Healthcare Day Presentation relesed to the market on 14/3/24 and shows the change in Nfl levels in cerebrospinal fluid samples taken from those patients who consented to this invasive procedure (it's a lumbar puncture - sticking a fairly large gauge needle into the spine). This is why we only have data from 3 patients who - for the greater good - agreed to subject themselves to this procedure.



Keeping in mind everything I've already said about the limitations associated with small data sets, what we can say from these observations is that Nfl levels in these three patients (all from the Melbourne trial site - which we know form the "01" prefix) declined, when what we would normally expect to see is steady or increasing Nfl levels. Additionally, the results (again, a very small data set) are suggestive of a dose-dependent response as the Nfl levels from the two patients in cohort 2 (higher dose) have undergone a larger decline than the patient in cohort 1. As with the ALSFRS-R scores, nothing more can be read into the results than them being SUGGESTIVE of a drug effect - with so few observations it could be due to some other factor.

A long post to deal with a small issue. But let's not start reading into things that which isn't there.

Cheers

Densy