I believe you had cast doubt upon Prof Kurtzbergs potency assay-...

I believe you had cast doubt upon Prof Kurtzbergs potency assay- what would have needed to be added to give you certainty?

1) Its not her potency assay - its MSBs. TNFR1 levels and IL2Ralpha inhibition levels - same two part matrix they've been using all along - they just tweaked the amounts up a bit on the first and did some after the fact data trawling to come up with 60% as a threshold on the second.

2) Certainty isn't necessary - I am not absolutely certain the sun will rise tomorrow - but I am nearly certain we won't have to worry about it if it doesn't.

I''ve already answered you question ages ago - I can't remember now whether it was before or after you got the second CRL because to me the second CRL was expected. Anything else would have been a system failure.

The problem is that too much of MSBs potency and effectiveness data depend on the same small number of patients. The longevity data that Kurtzberg goes on about and Silviu is not wrong its genuinely and believably better (to me) that what would have happened if the patients hadn't been treated or if they'd been treated with Rux. BUT it comes from only three donors. And so its not clear that what was in the doses from those three donors was potent because of just TNFR1 and IL2Ralpha inhibition levels. Those three healthy MSB donors I presume produced healthy MSCs which worked when put into patients - but it might not have been - indeed actually doubt it was - IL2Ralpha inhibition that had anything much to do with what made them potent. But I think something else did. I do think the TNFR1 measure should be in there as a potency assay component. I would add a quick test to ensure that no batch of MSCs increases INF-gamma at the very least because MSB's own data has shown that on at least one occassion INF-gamma increased when cells were added to a PBMC mix (a PBMC mix is like a model of the immune system but its outside the patient - it stands for peripheral blood mononuclear cells - its T cells and B cells and stuff - you can get it as a kit - you can make pools of it from muliple donors - but its used as a test to see what you cells do when exposed to it). Now if you cells increase INF-gamma levels they've actually increased something that even MSB knows - its through their science literature - its a cytokine storm component - it makes the immune response worse when what you want to do is calm the farm down.

So knowing that there were only three donors used in the pivotal trial that got the longevity data but not knowing that they were potent batches specifically because of TNFR1 and IL2Ralpha alone and knowing INF-gamma was a problem - I'd do another trial in adults -exactly as the FDA wanted them to do. Because you'd be using new donors and the same TNFR1 plus INF-gamma plus now a new INF-gamma not increased three way matrix you'd be showing that the matrix would produce good results in as little as 28 or 100 days.

That's what I'd do.

I would not trust Silviu Itescu or MSB who paid $2million to settle a lawsuit about communications to sell circa 300,000 dollar products to sick childrens parents to make sure every dose is potent on his, or MSB's honor alone.

I do not trust the regularors to regulate sufficient well after the decision is made or the company to self police its potency improvement and validation in an after the BLA trial. I think it needs to be before BLA because of the character of the man and of the company (which I don't think are that bad - they are just system game players - they would have taken a BLA from ODAC in 2020 if they could have gotten it - yet as late as May 2022 or 2023, Eric Rose, who was an officer of the company in a position to know was acknowledging the potency assay had problems - thats real problems not imaginary or perceived ones.

So I don't trust MSB enough to think it prudent to let them validate their potency assay after the BLA and I don't think the FDA should either. I think the adult trial (as a proxy for a childrens trial) should go ahead before any BLA.