Ann: Trading Halt, page-1236

Yes.

The simple fact of the CRL - and the wording MSB included about what the FDA had said to them pretty much told me all I needed to know. I had already a pretty detailed idea of what had happened - which was how I predicted the outcome - the outcome though, had it been different would have falsified my theory. It didn't falsify it. So that's learning something - its learning I wasn't wrong.

Beyond that SI's conference call made some interesting points that I think amounted to new disclosures about the past - I think you picked up on those quite separately to me as you posted your observations before I made mine and we had similar impressions - SI must have given John Hestor false expectations - SI may have done that because he was genuinely confused himself but there is no way I'm buying from that the goal posts got moved - goal posts would have had to be moved in my opinion or a a whole lot of extra data and support which MSB had not mentioned in their announcements had to have been prepared by them without disclosing it - which sinply didn;t make sense - on the stuff they'd said they'd done to provide new data on potency assays and new data generally it was clear to me that they couldn't have done enough to get read of alternative explanations - the data they had had to be confounded unless they somehow done something extra to remove the confounding - and I think they need to have generated new successful outcomes after changing the potency assay.

I actually don't think they are using different components in the potency assay matrix - its still TNFR1 and IL2ralpha - but I think the TNFR1 levels were measured with a different antibody (they reverted to a previous antibody - I think they had to do that because the FDA was not happy that the results they'd shown the FDA back before ODAC 2020 were behaving consistent with how TNFR1 was supposed to behave) - I do believe that TNFR1 is a good part of a potency assay - I believe it based on the work of Dorosoro (independent of MEsoblast but referred by Mesoblast). But TNFR1 alone (even fixed - and I think MSB did fix that) still isn't enough so they also had to look to IL2ralpha (because that's what they had historical data for - that's what they'd historically measured (and in my opinion = which was also I think the statistician's opinion at ODAC the IL2alpha correlation was quite weak - and to me its stands to reason that it would be - IL2 does a lot) - and the problem with that two part matrix is that its plausible as a mechanism of action but it isn't validated until other explanations for getting good results are excluded.

I reckon they only had a bout 11 GVHD001 patients that could provide single lot in vitro and in vivo measurements of IL2ralpa (aka CD25) in their blood.

Not enough - ergo - they didn't have enough even to validate the potency assay.

I'm reading SI language quite carefully - I agree with the recent post by Techinvestor - where he points out what SI says is not what many readers are reading him as saying. I agree with you post where reasonable approaches and indications are not confirmations.

I think pfeifer1982 has a pretty good understanding of my previous arguments and reasoning - but most of my posts that could have helped holders anticipate this outcome - whist still there - have almost no ticks on them - they weren't understood by most readers. But the arguments are all there.

I don't really have any confusion about what happened as it all fit my theory - I have a bit of frustration that Silviu is still using language that makes it hard for others without the science to see what has happened. I think Silviu is being circumspect with information such that he is not stopping my from understanding but he is stopping many of his shareholders and the market from being clear. I reckon I have more biology for instance than John Hestor to make sense of what the FDA and MSB have said in the public domain - without that knowledge of biology (which anyone can learn - but they have to read - and I'd have helped them if they let me - but there were few takers) the market and holders will be confused.

But this was predictable. I predicted it and my method involved no magic. And others could have as well had they engaged with the science and stats conversations I tried to have with them.