Ann: Investor Presentation, page-532

Cynata's market value would probably rise on FDA approval for a Mesoblast therapy and likewise decline if there's another failure. But that's not what I'm interested in uncovering.

Firstly, thank you for your thoughtful reply.

Matching patients and then following them is actually better than a RCT because it takes into account current standard of care.

I'm not convinced this is true. In a clinical trial, the patients are monitored at the same intervals across the drug and control arms, thereby creating a more consistent way of comparing response rates. The FDA also recommend including a control arm (refer lines 437-440 on the document referred below).

FDA may have even made a similar mistake to what JB has
Yes, the FDA have clearly managed to have their head turned and now accept what was provided initally was acceptable.

Probably the most interesting document I have seen is the FDA's GvHD Guidance for Industry release in September last year: https://www.fda.gov/media/172524/download

The FDA do appear to want randomised trials for dose escalation studies:



It is also notable that the Phase 3 Trial in paediatric GvHD did include a dose-escalation, whereby if a patient incurred a partial response after the first dose, they received a second. While if they had no response, they got nothing.

Despite that, Mesoblast are clearly relying on this:




Since Jakafi is not approved in children <12 years old, there is certainly an argument to be made that they meet this criteria.

I am very surprised the FDA completely changed their mind on the adequacy of the paediatric trial - it will be interesting to see the approval process play out. Has it been announced if anything has been submitted yet?