It doesn't matter what "MSB have to do, exactly, to tripple the...

It doesn't matter what "MSB have to do, exactly, to tripple the TNFR1 count, and almost tripple the IL2Ra inhibition." Even "Trade secrets" don't matter.

The question about MSB's potency assay (matrix) is not the count (increase) of TNFR1 or IL2Ra inhibiton increase, it comes down to:

Has MSB generated enough data generated in multiple patients that received cells from only one donor to eliminate any confounding factors including (but possibly not limited to) IFN-γ, which literature (including Danilkovitch) believes to be of some importance to say the least, to show that trippling the TNFR1 count and having achieved "almost tripple the IL2Ra inhibition" (based on "threshold minimum value") are the Mechanism of Action used to measure potency of MSB's product?


Short answer is no, they haven't.

It would not be fair to compare any statements made by yourself or other posters in favour of MSB's argument that they have generated enough data. CRL#2 says otherwise:


https://investorsmedia.mesoblast.com/static-files/422cd6da-a0b9-49cf-a177-7fd106f111f2



Long answer (for anyone interested):

The product improvement which you mention (tripple x2) is in comparison to the original product.

Dr Bauer however goes into great detail on why he finds the comparisons provided are challenging:



1.



2.



2a.



2a1.



2b2.




2b3. (although mostly a summary of the above)





He then discusses the improvement process, to which you are referring to and what your "Case in point" is based on, by discussing the "knockdown" (which I found to be very impressive when I watched Dr Itescu's presentation back in 2020):



And that is obviously a big problem. He continues:




About confounding factors such as IFN-γ, he had the following to say:



(pages 89 and following)
https://web.archive.org/web/20210305082200/https://www.fda.gov/media/143337/download

The fact that it could induce greater amounts of immunosuppressive activity puts the onus back to MSB to show that IFN-γ as a confounding factor must be ruled out didn't, doesn't and won't affect the efficacy of the cells.

Now re-read @JB1975's posts in the context of the above and you will find that they didn't have enough data to convince the FDA.

They may have now developed a potency assay (matrix) that can satisfy all of the FDA's requirements, but that is yet to be seen in a clinical study to confirm it.

If you can't rule out all confounding factors and subsequently can't guarantee that the cells work independently of the starting material used, you are not selling (and charging a sick patient for) a therapy, but a lottery ticket of getting the final product that is derived from the donor that in this example had high IFN-γ levels, adding also a financial burden (think about whi has health insurance in the US and consider that SR-aGvHD doesn't only affect people that have insurance) in addition to a very unforgiving and devastating disease.