Ann: Exceptional Results in Second Valve-in-Valve Case, page-33

And I always appreciate your thoughts as well, Eire.

My comparison regarding compassionate use between drug and device companies was merely on the basis of those procedures being used to shortcut the path that the FDA has laid out for us, which is FIH, EFH then pivotal. Of course I am very aware of the differences between drug and device approvals and Wayne has been speaking to that recently when discussing how the DurAVR is derisked.

Replacement heart valves are life-sustaining devices though, and while I agree with Wayne that the chances of a trial failure is much, much, much less than with drugs, I'd say his 99.9% number for the chance of pivotal trial success is accurate, when it comes to safety the FDA is very likely not going to allow shortcuts around the 900-1100 procedures we'll need for an approval to sell the DurAVR commercially. Will ViV be included in FDA sanctioned trials? That's up to the FDA to decide but I'm sure Wayne is pushing for it.

I don't see the history of the CardioCel tissue having any real impact when it comes to trial size or a HDE though and I'm aware of the studies that have been performed on implants using the tissue. I have copies of 6-7 of them. It's about data needed to be produced from the DurAVR as a functioning valve in humans along with the delivery system.

Maybe you're correct and I'm wrong, I'd love for you to be, but when it comes to safety the FDA is predictable and Wayne himself has spoken of the need for around 1000 patients to get to an approval quite a few times.

And again, I hope folks don't think I'm being pessimistic, just trying to give my sincere thoughts on what I think is realistic. As I've said before (with calculations), I think the economics are great and AVR will be a very lucrative investment even if we don't get an approval until 2028.