Concerning the dosing restrictions, I still think it probably has to do with the lack of 3 month monkey tox data (the original 3 month studies being in rats and dogs). This deficiency would be especially glaring if the histo "finding" was seen in the acute monkey study.
Seeing the histo problem in the original acute monkey data, the FDA asked to see that acute monkey study repeated, which Cortex did. Now they want to see longer term 3 month data in monkeys, which wasn't part of their original request. Luckily, Cortex's consultants recommended getting the 3 month monkey study started back in the summer, figuring correctly that this might be the FDA's next request.
In trying to read the current tea leaves, one related question is whether the acute tox data from the repeated studies was - 1) totally clean, 2) ambiguous in some way, or 3) clearly not clean. We can almost certainly rule out #3, since if the histo problem was clearly repeated in the new data, we'd be looking at the "CX-717 is toast" scenario, which would have been a material event. It's possible that the repeated study data was ambiguous in some way, leading to the FDA's decision to place dosing limits on CX-717 pending further monkey data. It's also possible that the repeated study data was totally clean, but that the FDA is being extremely cautious and wants to see the additional 3 month monkey data anyway (particularly since they know the next logical step in CX-717's development will be 3 month human trials).
Call it a semi-educated guess/intuition, but I think CX-717 will get the dosing restrictions lifted once the new 3 month monkey data is delivered to the FDA. However, this delay has thrown a wrench into the BP deal timetable, most likely making a PIPE necessary, and thrown off the non-Ampakine in-license plans. All in all, the FDA has wreaked some havoc, but if CX-717 gets a clean bill of health, it'll have been worth it.
