re " I know zilch about the science of assays. But I do know the CRL history has led MSB to do a boatload of research on assays that will do a lot to strengthen our moat."
IME a person doesn't really need to 'know' all that much about the science of assays. But in this increasingly fast paced world one really must try as best one can to slow down & read stuff carefully, and that's not easy with all the pressures we face.
For example, during the August 30, 2023 Earnings Call just prior to the AGM, Dr Krause made a quick closing comment, in response to a question from CEO Itescu about whether he had anything to add to Dr Itescu's answer to a question: " What we need to ensure is that we have a potency assay in place that was used precisely in that Phase 3 that continues to demonstrate the same attributes of the existing inventory. Phil, would you add anything to that?".
Dr Krause' response was recorded in transcripts as follows:
" I would not. I think that's exactly right. The manufacturing assay has not changed."
Huh.
My mind said to me: But why didn't he just respond to CEO Itescu " The assay has not changed."? Yep, that's exactly what my mind does.
(NB: I can't find a single post on HC:MSB actually looking at what Dr Krause is saying here. If I've missed it, sorry.)
So, now consider:
1. IMO his choice of words impliedly recognises that there may be multiple assays associated with a drug product;
2. IMO he's differentiating between at least 2 & possibly more assay forms for RYONCIL, specifically 'manufacturing' and something else(s). What might that or those other something/s be? To me, Dr Krause was most likely referring to a separate set of release assays & a set of FIO (for-information-only) assays;
3. he's making the point that - out of all those assays involved over the entire length of the RYONCIL HCT/Ps production and distribution process - the manufacturing assay i.e. the in-process manufacturing assay is 'unchanged'. But, by implication, he's suggesting that other assasys ARE changed; and
4. he's doing all this in the context of comments by CEO Itescu about "a potency assay".
Why did he choose this expression? What was the information he was getting across? To me this was fascinating. I started thinking, so if the 'in-process' assays haven't changed, but 'other' assays may have changed...well that would explain how the RYONCIL 'release' assay could be 'improved' to the FDA's satisfaction while leaving a potency assay in place to demonstrate that the product manufacturing processes would still stay the same in future....and the manufacturing processes would satisfy any method comparability test...and the PLI inspection would verify those processes prospectively....and allow etc etc... but what about the existing stock...etc etc
I won't bore you with the details, & all this may be well known to posters but for me it was the start of an epic personal research project over the last couple of months, which I've now finished to my satisfaction (for now). I now know that there are assays, and there are other assays, & I know a hell of a lot more about the process of manufacturing biologics than I ever wanted to. I took my nascent research with me to the AGM, and it informed some of my questions of CEO Itescu there.
That research enabled me - a decidedly lay person - to come to grips (to my satisfaction) with and reconcile EVERY SINGLE ONE of the comments made by Mesoblast officers about assays & recorded in transcripts since the second CRL, and even earlier. It's like a big lightbulb going off in one's head.
Long story short - I may be completely and utterly wrong, but I agree entirely with your comment about the strengthening of the moat for RYONCIL, & indirectly the other platform indications.
The value of being in the interactive & collaborative relationship with the FDA on the bleeding edge at the same time as FDA implements its new org strucutre, all the new PDUFA VII biologics commitments, and the new Guidance procedures cannot be overstated.
(20min delay)