Ann: PARADIGM RECEIVES FEEDBACK FROM US FDA ON IND SUBMISSION, page-47

If this news is bad, why do I feel so good?

PAR have just revealed a big shiny green light with a bit of tissue paper in front of it. The FDA have given them explicit guidance on how to remove the tissue paper. We are on.

Start dusting off those previous KOOS and WOMAC scores people, because this is the focus now. The IND will open. PAR will be injecting US Citizens, in the US, with Zilosul (which is apparently the only type of trial data the FDA care about). If the drug produces the same results in Americans as it has in everyone else, then all the PAR hype, and all the PAR hope, starts to become full-blown reality.

For my money, PAR management have navigated the rat issue as well as possible. What a microscopic detail for the company to be delayed by. It must have been hugely frustrating. They could have launched into further expensive time-consuming pre-clinical trials injecting another thousand rats with Zilosul, attempting to show the FDA that the adrenal failure was an anomoly - but they didn't. They backed their exisiting data, they offered an adrenal screening mitigation strategy within the Phase III human trials, and - admittedly after this further 5-week delay - they have a confirmed pathway to IND opening within weeks. It must be also noted that the FDA have now twice offered PAR explicit guidance on mitigation strategies. In my opinion, this shows the FDA are keen to see this trial progress albiet with full and total application of the comprehensive rigour anyone would expect from them.

Having said all of this, we cannot simply brush aside the adrenal failure issue. This is a new, unexpected, out of left-field risk. It will clearly be monitored carefully throughout the trial, but if anything shows up in human trials we are in serious trouble imo.

Despite that, I added 25% to my holding this morning at $1.925. To get a de-facto FDA green light, and then an 8% discount on open, was a gift.