Ok, now that I've had time to digest both lunch, the meaning of life and the information in the announcement. These two slides are starting to stand out significantly...... like Nexus event significantly.
This data which was provided by an external study demonstrates the link between an immune response and the severity rating for the Covid -19. The Green response you would say is someone who gets Covid who probably does not know they even have Covid - ranging to the dark brown which is someone ventilated / on the cusp of death.
You can see that there is a definitive link here, where the sicker someone is, the less Naive T cells they will have, and the more Activated T cells they will have. Note this is not age stratified, this is just factual for any age group who were positive for covid.
If you look at the Naive T cell graph - the ' healthy' people with covid have around 60% , where as the ventilated group are in the 15-20% range........ now....
Here you can see again, there is a clear link between the age of the Covid patient, and the % of these Naive T cells alive. Therefore, if you are older you will have less Naive T cells therefore expect you will get sicker unless you are an outlier. There are obviously outliers here in the 20 - 50 age group, and my hunch is that these are likely the same group that also have comorbidities like Cancer, Obesity, Renal failure, and the list goes on.
You can also see in the graph, that no-one above the age of about 55, has a Naive CD8 count above 60%, and above 80, nobody is above approximately 30% at all........ now where have I seen a graph like this before.
Looking at this chart which is death stratified by age for
mechanically ventilated patients, you can see that the 0 - 40 group had approximately 50% survival rate and from the previous graph the same age group had 40 - 60% Naive CD8 count. If we skip up to the over 80 age group, the survival rate was 15%, and the over 80's Naive CD8 count from the previous slide looks about the same... around 15%.
Coincidence? I think not... Look at those P values.... P = 0.0004, and P = 0.00001 that is 99.96% and 99.998% certain of the correlation between age and reduction in Naive CD8 cells.
So, why all the fuss?
The FDA are going to ask mesoblast why did your treatment not reduce mortality in over 65's, because if it did then primary end point would have been a massive success. Mesoblast will likely prove using the data above and probably more data from other trials that there is indeed a definitive link between age and naive T cell counts.
They then need to prove the link between treatment and an increase in the naive T cell, or a reduction in the activated T cell count or both (this information was not provided, but I think they must have it in hand).
All mesoblast may then need to do is provide a manufacturing assay that demonstrates activated T cell knock down and naive T cell proliferation,..... provided this was observed and they have the 'proof' from the previous paragraph in hand.
What I'm also wondering is, the over 65's showed remarkable improvement for the first week post treatment, almost on par with the under 65's (40% improvement vs 49% ). Is this indicative that the treatment for the first week in the over 65's, did in fact raise the Naive T cell counts, and / or reduce the activated T cell counts? Does mesoblast even have this data? I really don't know, but based on where the presentation was headed, you would bet your ass they would want / need that data for FDA approval, and if indeed it shows that, then maybe they can take live T cell readings and vary dose based on what they are observing in patient responses.
What else could come of this? It could play a factor in GvHD, and also explain why an adequate dose was never found in the over 65's for that indication either. If they moved to a model where they administer an initial dose and then observe the T cell effect to then administer the next dose..... one would imagine this is the future way of administering the 'correct' cause and effect dose to give equal treatment to any age group and any level of immuno deficiency.
Exciting!
(20min delay)
