Excerpt on dosing taken from the recent investor briefing transcript (
https://actinogen.com.au/wp-content/uploads/2018/05/20185030-Transcript-KOL_ACW_ID_300518.pdf):
Mark Pachacz: (Bioshares, Analyst) Hi Bill, thanks for your time everyone. This is a question for Jeff. Jeff, you talked about the dosing regime being or the dosing strategy being reasonable. I just wanted to, from a publication on this drug, the recommendation was that a dose of 20 mg a day is what would be effective even though you're trialling 10, so maybe do you think the current dose is a little bit low and are there plans for subsequent trials at a higher dose?
Bill Ketelbey: Perhaps Mark, was that - I just need to clarify which Geoff that was…
Mark Pachacz: (Bioshares, Analyst) That was for Jeff in the US.
Bill Ketelbey: Oh Jeff in the US, go ahead, otherwise I'll certainly add in my commentary there.
Jeffrey Cummings: Sure, be glad to hear from you Bill. Mark, dosing is one of the biggest challenges in these trials. The thing that gives me some confidence here is that the dose in the CSF is ninefold higher than the IC50. So even if - of course you're measuring in the lumbar space, not in the brain space, but ninefold should give us an adequate margin to know that we're achieving the IC50 or above in the brain.
So I think the 10 mg dose, as it has played out in the pharmacologic measures in the CSF, gives you a fair amount of confidence that the dosing strategy is fine. You always would like to explore a higher dose range and also to find a dose response curve, but I would say that 10 mg dose is not in jeopardy of under-dosing.
Mark Pachacz: (Bioshares, Analyst) That's very helpful. Bill, can you elaborate perhaps on just with this funding, what other trials you might be doing and whether you will be exploring the higher doses?
Bill Ketelbey: Sure and the answer is yes, we will be exploring higher doses. So we're doing a target occupancy study and a higher dose safety study really to optimise the dose. So while we have modelled and Jeff has already alluded to the fact that 10 mg appears to be a correct dose, an appropriate dose, obviously it may not be the optimal dose and to ensure that we have a comprehensive dataset in time to initiate Phase III, we are undertaking safety - we will undertake safety studies at higher doses along with the target occupancy to ensure that we can optimise the dose of Xanamem.
