Evercore notes:
(These are my rough notes, not word for word, and not complete. Feel free to add. My comments are in parentheses.)
Q. Dr.M please give us an overview of S1 Receptor?
S1 has no immediate function for day to day activities in our bodies. It can be left out and animals have no different life. It seems to only be useful later in life, for activation by certain small molecules.
(Wow. This seems amazing to me that there is little known about it, as is apparently not used. This raises lots of questions... How does a S1R evolve to exist, when it is not used? Why would it be designed into the system?)
It is so upstream and affects so many biological processes, is there a sweet spot for S1R agonism?
A. Unknown sweet spot, but it is similar to oncology immunostimulation. Where cancer is fought by activating the bodies defense mechanism.
Dr.M referred to the US Rett Low Dose trial readout being this quarter, and very soon, and forthcoming, and imminent. (not just soon!)
Overseas adult study, AVATAR, is a high dose study, as FDA likes trials showing dose response. First or second quarter 2021.
EXCELLENCE pediatric trial will readout second half of 2021.
The two adult Rett studies potentially, depending on data, can be taken to FDA. If the data is good, it bodes well for pediatrics.
US Rett adult study is 10 placebo and 15 drug. Focus on FDA request of RSBQ with its 45 rigorous questions. Also testing CGI-I and ADAMS. Focusing on consistency of data, for example between RSBQ and ADAMS.
We are hoping for MOA validation for pursuit of other diseases.
Will there be an interim analysis for the ALZ trial?
A. It is a possibility, but we are using intelligence from the PDD study, which uses the same doses as ALZ study, which has strong episodic memory signal.
Is the P3 Alz trial long enough at 48 weeks?
A. Yes, we saw high dose improvement in PDD. Enrollment should end early 2021 so add 48 weeks for completion.
