Ann: Investor Presentation, page-609

so my idear that a patients data could be entered onto the chart that received say two lots is more about the more robust analysis of old data that SI has mentioned.

But unless you gave them both lots at the same time (which makes no sense) you'd have to give one lot first to patient John Smith then the other lot to the same patient John Smith some amount of days later. Which means your measurement for patient John Smith is either not taken at 28 days after first treatment (so you can't use it -when that's a condition of collecting the data for that specific time period in the first place) or you use if an muck up the measurement because its impossible to tell what would have happened if John Smith only got lot 2 in the first place instead of lot 1 in the first place.

7 days after first treatment, or 21 days or 28 days or 100 days or 3 days - any of those might arbitrarily be chosen as the period of time to check out a patients blood readings for T cell activation after their first treatment and compared with their reading at day zero (just before they got treatement) - but mixing up the days makes so John Smith is measured at 3 days and John Doe is measured at 21 is absurd.

Also measuring 28 days after giving patient Sarah Jane her second dose after she had only a slight improvement in the first dose around day 14 also makes no sense as you are muddying up the effect of the second treatment with the possible effect of the first one.

I think you should be able to see that sensible comparisons between two variables - varable 1 being how much the lot caused interleukin 2 receptor alpha levels to be inhibitted (your horizontal plot point) and variable 2 being how much any particular patients blood decreased in the T cell activation levels after 28 days, (your vertical plot point for the same patient-lot pairing) can't involve mixing other things in at the same time.


I did say the data was from perhaps 40 patients. Could it be done ? 40 is the absolute maximum if none had received multiple lots - that didn't happen - I believe the FDA said at ODAC MOST received multiple lots. But even if they did. Even if there were 40 - that's about 4 times 11. You could easily plot 40 points on the same X Y graphic we'd been talking about. The Y axis is measuring decreasing T cell activation in percentage terms there would be plenty of room for 4 different patients on average (assuming 40) to show up as 4 different dots in a vertical line below the X axis at whatever value matched the lot level of inhibition that came from the ILRalpha metric they shared in common. It simply makes no sense to bunch together patient blood readings for John and Sarah and Brian and Tracy after 28 days (they each have their own immune systems however compromised) to average those simply because they got treated by the same lot.

Is it not time to admit that you were wrong, perhaps the FDA has also admitted that they were wrong.

Absolutely not - all of this is the same as it was prior to the second CRL - I wasn't wrong then. The time to admit to being wrong is when one is shown an error in one's calculations or line of reasoning or when one sees ones predictions did not come true. I was wrong on a minor matter applying 25 as a filter recently (but I do think 40 down to about 11 is about right without the 25).

If the FDA have changed - either the data has changed

(if there was new EAP data Silviu could have combined it on a new X versus Y chart and given up no intellectual property it wouldn't be labelled Study001 it would have to be labelled something like in vivo versus in vitro measurements in patients receiving a single lot of remestemcel from the improved version (ie TNFR1>= x pg/mil and IL2RAlpha inh >=60%))

or those at the FDA doing the assessing have changed (perhaps to be wrong now where their colleagues before were not. So giving Silviu hope when he shouldn't have been given hope but should have been told to do the damn adult trial.

or Silviu is confused. Either he is confused in that he did give them new data not just a re-analysis of old data or he is confused in that they haven't changed their mind.

The scenario I think pfeifer is holding out for - is that there is new EAP data - based on Extended Access Protocols going into 2023 in some cases so after the ODAC period - but that data, being EAP data would normally be data gathered by treating physicians (likely confounded) and Silviu could have reported it if he had it and helped calm the market - he hasn't done that.