Ann: Update on FDA Meeting for Remestemcel-L in Paediatric GvHD, page-61

My take:

1. Potency assay agreed - check.
2. Data to support in vitro immunomodulatory activity of Rem-L (SI advised data in hand) - likely check at next meeting (SI is confident).
3. By demonstrating the relevance of the in vitro potency assay to in vivo clinical outcomes (Point 2 above) MSB believes this will suffice in demonstrating Rem-L consistency in their Phase III study (i.e. standardised to identity, strength, quality, purity, and dosage form).

In other words, if SI can check off Point 2 (demonstrating in vitro immunomodulatory activity) then this can be linked to in vivo Phase III clinical outcomes demonstrated, therefore addressing the need for another trial (i.e. no need for another trial).

This checks off the CRL points previously:
* Potency assay (agreed in announcement)
* Another trial (probably not needed if SI can demonstrate Point 2 and authorities agree Point 2 can be linked to actual clinical outcomes via way of standardised measures of strength, purity etc.

From memory our trials were based on different products so to say. Initial Rem-L and then improved Rem-L after manufacturing improvements - resulting in product being more effective. Therefore not all our data compares apples to apples so to say (may make the FDA uncomfortable). It seems SI has addressed this by comparing patient outcomes on the two different batches and found the improved Rem-L had better patient results (and now has potency data to support this finding). From memory phase III primarily used improved Rem-L after manufacturing improvements (and a smaller amount of the older product pre-manufacturing improvements).

IMO it is this improved potency Rem-L data post-manufacturing improvements that SI now has in hand after further interrogation of the trial data (which goes a long way to explaining why the Phase III data in phase III is superior to former trials (when looking at the under 18 population only) and is about to present this to FDA/OTAT to justify that the improved efficacy is meaningful and the primary reason for better in vivo activity (as a result of manufacturing improvements). The way I read the announcement is that if this can be accepted then the FDA/OTAT will not need another trial before BLA re-submission and potential approval.

Good news if SI has data on hand to support POINT 2 above (sounds like he does) and (FDA/OTAT accepts linkage between POINT 2 above and POINT 3 - makes sense in theory - improved product biomarkers lead to better in vivo outcomes - and FDA/OTAT comforted that the improved manufacturing process is the reason the results were better in Phase III - and therefore outcomes not an inconsistency with other trials ).

Therefore this will address the need for another trial requested in BLA - in other words if above points can be established then SI believes there is no need for another trial.