Target Occupancy Study (TOS), page-11

Hi II,

I haven't had a chance to look over the results, but interesting to see the %'s you have listed.

I will be completely honest, I don't know much about TOS, and I could never find any literature to support what % is required for cognitive improvements, especially in disease population.

in 2018, I spoke with Ketelbey via email. At the time he told me that the technology for TOS did not exist before they commenced XanADu, but mid enrolment, it did. He told me this before they announced the TOS. He told me this because I raised concern about the change in dosage from 60mg/day to 10mg/day. He assured me that based on the phase one method of identifying the level of inhibition, 10mg inhibits 50% (I would need to double check this, I'm going off memory). He also went on to tell me that 50% was adequate for cognitive benefits.

so to answer, I don't know why the 2016 one was not used, but management at the time alluded to a new technology in circa 2019. As for percentages, the advisory board must theorise 5-10mg is enough based on these percentages, but I don't know what evidence supports this. The only evidence I have seen that supports anything to do with % of inhibition is the (going of memory again) abt trial that tried to use their drug to inhibition 11bhsd, but it did not penetrative the BBB. I think the % of inhibition was under 30%.... if memory is serving me correctly

apologies for not actually checking my correspondances and relying on memory.