Hi @omnisearch, yes, it was a great roundtable paper to read,...

Hi @omnisearch,

yes, it was a great roundtable paper to read, published October 2023 but - importantly - in relation to the Annual Meeting held in Paris in May 2023.

I think you're correct about future patient stratification benefits, but I just enjoy seeing Mesoblast personnel, such as Mr Schuster, collaborating in round-table leading (or shall we say, 'bleeding') edge discussion groups. It shows enormous respect for Mesoblast's position at the highest levels in the international MSC industry i.e. the Scientific Committee of ISCT. It also provides a respectful forum in which colleagues (and potential competitors) can raise issues which Mesoblast may not have under control - altho' there don't appear to be any, as I read the paper.

And OK, yes the investor in me likes reading about MSB's existing MSC/MPC platforms apparently generating beneficial outcomes when other products experience difficulties or failures, as with dexamethasone (cf. Shi's lab results).

So, one might ask, what else happened to give Mr Schuster such confidence to open up & talk on May 30, 2023 with confidence about Mesoblast's assay processes? Yep, it was the FDA inspectorate's verification of MSB's validated processes, up to & including release:



I'm sure you also read with pleasure @omnisearch, as did I, that:

" Schuster discussed Mesoblast's use of a potency assay as a CQA to measure the immunomodulatory fitness levels of MSC(M) lots based on inhibition of interleukin-2RA expression in co-cultures with activated lymphocytes"

This seems, to me, to indicate that the FDA has at least confirmed its acceptance that IL-2Ra expression is associated with RYONCIL's MOA (which the FDA will accept as being 'immunomodulatory' and not simply 'anti-inflammatory'). Otherwise, there'd be no basis on which the inspectorate could have verified and signed off on the release processes in Singapore.

I also noted Mr Schuster's confirmation that Mesoblast has correlated the improved OS outcomes with improved product and improved processes using the IL-2Ra measures & then went on to alter future release assay specifications for RYONCIL presumably to ensure the maintenance of that correlation can be demonstrated in future, i.e.

" Historical manufacturing changes that augmented the immunomodulatory fitness of the product were captured by the potency assay and correlated to improved survival outcomes.

As such, Mesoblast set new specifications for release of the commercial product based on the potency assay readouts and clinical data. Notably, the August 2023 complete response letter from the FDA cited no issues with the updated data on this potency assay".

As there are now some new specs for prospective release, they'll need to be captured certifiably by measurement at the time of all future lot releases (NB: not as in-process manufacturing).

The underlined words are, IMO, important. These were obviously added to the Roundtable summary notes after the May 30 meeting in Paris. That would seem to suggest that the ISCT members are VERY interested in the FDA's response to the next BLA resubmission, & are following the remaining FDA requirements and being kept in the loop to a certain extent by Mesoblast. Everyone is leaning forward in their seats, as I see it.

It's direct reinforcement of the comments previously made by CEO Itescu during the 2023 Earnings Calls, and being made before such an august scientific body, I think we can safely assume the members understand the implications of the matters disclosed by Mr Schuster, even if mere ordinary shareholders such as me may miss some of the nuances.

All good IMO.

Cheers
GLTA(LT)H