From your post - all the boldbelow some of it is you quoting me. Why am I bringing this up again here and now? Because I think the post line of interest to me went off track with a misinterpretation about what I was referring to about not needing to save face - and I do think had it not been for that we might have had a useful conversation - because you understand I got the CRL call correct and I think you understand it wasn't luck there was reasoning and method behind that call. Reasoning which is still on the record and could be faulty or which could be used by an impartial reader to convince themselves my current view that another CRL is coming (unless MSB changes tack) will be similarly correct.
"[...] but if you have a batch of MSCs that for any reason increase the INF gamma levels when they are added (in vitro) to a mix and then you see interferon gamma levels in the mix go up - then something is going wrong. You've got a batch of product that is actually acting counter too what you want on the interferon gamma dimension which is a cytokine storm component.
If I recall correctly you have previously found in my comments with dachopper an example of me showing that MSBs own data shows that inf gamma increased on at least one occasion the measured levels of interferon gamma."
That's exactly what I was referring to. The issue you have highlighted between CRL #1 and CRL #2 as being at least one confounding factor that was in the absence of a well-controlled trial what led the FDA to overrule the 9-1 ODAC recommendation.
If the FDA had been convinced that the trial was well-controlled, I dare say they would have approved it at the time.
CRL #2 and still without a well-controlled but supposedly new clinical data (same data but sliced differently), was again not enough to convince the FDA and again, you correctly and this time before the CRL pointed at the slide showing interferon gamma levels to increase when you'd expect them to reduce (it was one batch of five from five different donors if I recall correctly), and given that the slicing has turned the clinical data into pieces simply too small to overpower the FDA's previous concerns, it wasn't enough to gain approval.
Again, had the trial been well-controlled in the eyes of the FDA, we likely wouldn't be talking about this in 2024.
Now I think the FDA has agreed that the trial in hindsight could be considered well-controlled given the emphasis in MSB's releases (or at least that is MSB's interpretation), and with the primary endpoint being met, plus improvements made to the potency assay they have "reverted back" to and a demonstrated intention to obtain more data with a partner like BM CTN lined up, I believe that this time the FDA will approve it, albeit likely conditional. That is an opinion - mine. Nothing else. No financial benefit on my end either since I am not invested in MSB.In your sentence which I've highlighted you say "I think" and also "or at least that is MSB's interpretation" - I am actually interested in what you think based on what you understand about what I have written in the past and what you have read that MSB have written whether they can - without another trial or without doing something that they are proposing to do different (I think they are proposing to try to again not do a further GvHD trial prior to re-applying for a BLA - to be clear) be successful in obtaining a biologic license application (BLA)?
I'm asking because I think all my old reasons still apply and still preclude MSB being successful and I don't want to have to go over them over and over - BUT something could be missing and you might see somewhere where MSB could find a way through without doing bad science or bad stats or without trying to essentially special plead like "oh please, please let us have an application this time".
I'm interested in what you think because I'll then see where I'm either wrong or where I have been unclear.
(20min delay)