Ann: FDA Notifies Clinical Data Sufficient for Refiling aGVHD BLA, page-545

Hi @JB1975 ,
Your comments suggested Si could be swinging his emphasis onto IL2 alpha . Yes is the answer.
Si- as per the annual report-
Further, to support approval for the pediatric indication,
we are currently generating additional data using the
IL-2R alpha inhibition potency assay which was in place
during the pediatric Phase 3 trial to provide the needed
link assuring consistency between the RYONCIL product
that was used in the pediatric Phase 3 trial and available
commercial inventory.
In parallel with the additional assay work needed for refiling,


OK. I haven't checked that - I'm taking your word its in the annual report.
SI swinging again behind IL2Ralpha rather than introducing something completely new into the
matrix fits better - ie - there is time for him to do something in that scenario - something like measure the Il2Ralpha levels in vitro and in the blood of new EAP patients. And it would be consistent with the sort of stuff he has tried to argue before.

The trouble is (one of them - there are probably about three at least) EAP patients are treated at physician discretion - and physicians tend to treat their patients differently from one to another which introduces confounding variables. It was the need to get confounding variables out of the data that necessitated the MSB-GVHD001 trial in the first place - Dr Kurtzberg already had EAP data (for kids) - it couldn't be used because of the confounding.

You put me back to me - (highlighting yellow, ie - the yellow you added - the green is me)

Your comments

Troublefor me is that two matrix components TNFR1 and IL2Ralpha were bothshown to some extent to the FDA, but when SI has described orabbreviated what he’s done in less formal than ODAC contexts he hasused language that obscures. I believe prior to the BLA 2 SI and Cowere stressing, and folk like otherperspective here were seeminggetting excited about and amplifying, that there was a bunch of extradata about IL2Ralpha and that Dr J Kurtzberg’s follow up worth washighlighting that. So SI’s loose talk sometimes makes it hard toknow what he is actually specifically saying. I’m not sure he isnot just talking about more data (that at CRL1 or CRL2) to do withIL2Ralpha. He could be talking about something additional (andtreating TNFR1 plusIL@Ralpaas onepotency assay only though it has two parts) or he could be justswinging his emphasis onto the IL2Ralpha stuff again.Do you consider that IL-2R alpha inhibition could be used to demonstrate the trial was well controlled? It appears that the FDA has considered this new data sufficient enough to agree to refiling the BLA. Would this mean they have seen the logic behind Si's attempt to rise from the dead? Albeit they will pull apart the new data with fresh eyes once filed.

Thankyou for your consideration

Reg

Reg, Off course the FDA will take a look at resubmited BLA's that is their job. Of course presented something that looks prima facie plausible (in a meeting outside a BLA) they would naturally say, (probably amongst other things that MSB may elect not to emphasis when what is reported is at their discretion and the FDA doesn't comment) because considering BLA's is their job, discouraging third time lucky wild ass punts isn't their job, that they'll consider the details when they get the details or words to that effect and that what is being put to them, I imagine, is not impossible.

Do you consider that IL-2R alpha inhibition could be used to demonstrate the trial was well controlled?

I really don't think so - but right now I'm not absolutely sure.
I don't think so because - (a) they've tried that before - it was, I understood a big part of what they were trying in BLA number 2 (b) - what I've already said about EAP data - it tends to be confounded (c) I doubt IL2Ralpha is specific enough. (d) The timeline looks a bit cooked to me in that just a few weeks before the announcement that seemed to please the market SI had been interviewed by s har e ca fe and had stressed the potency assay stuff as being what they were going to go to the FDA about - then the announcement didn't even mention potency assay stuff at all - that looks like a big switch in emphasis without a sufficient explanation - I personally see that as highly suspicious as being putting on a spin.

But the bottom line is - I am not currently certain (your greened question - though I'm pretty certain)- I would think it an extreme long shot.

I actually think you should be asking Silviu for more detail - I think there should be meetings minutes and I think you should as a shareholder and long term holder be looking for more detail.

At present I'm probably just going to wait and see if meeting details come out - I wouldn't be amazed if SI doesn't say anything more about meeting minutes or that shareholders don't ask him.

But I think its a silly approach for small shareholders to take - to just keep not asking questions and to keep hoping this time will be different.

You may end up with the assets that are mortgaged in the hands of someone else - Oaktree or be taken over opportunistically.

Perhaps asking questions (of Silviu - not me - about IL2Ralpha or about the status of the potency assay or about meeting minutes) would get you a better chance of keeping value for small shareholders that have long held.