Anavex Life Sciences Corp (AVXL)

[Investor2014]

Reading this Q&A from the Q1 2024 cc, it seems more than likely a new Rett trial will be required. Although of course Missling does, as he should, leave open the possibility of approval based on completed Rett trials and OLE data. Hard to assign chances of approval in rare indications, but I would say perhaps 25% chance of some kind of approval - perhaps not from the FDA first, as there was no EXCELLENCE patients enrolled in the U.S.

Soumit Roy: I’ll go switching to the Rett program. Two questions. One is, if you can provide us some kind of detail on there was a difference between your trial and Acadia’s trial. The reduction in the – even the placebo arm or the treatment arm is much pronounced in your trial. Does that mean the baseline characteristic was very different in the enrolled patient? And the second is you saw a quick early four week, possibly a clinical benefit, but then it kind of waned away at the 12-week time point. You see as a pharmacokinetics or a dosing issue.

Christopher Missling: No. I think if I can start with the last part, there’s not such a thing actually the trial was really showing an extremely nice improvement score in the active arm with over minus 12.9 in our analysis, which is extremely strong. And trofinetide showed only an improvement in the active arm of minus 5.1. So we showed a stronger signal in the active arm. What happened was in our trial, the placebo also improved and in the trofinetide the placebo did not improve. So that is basically really the difference though the standard error. So the variability of the scores was much higher in our trial than in a trofinetide trial. And we laid out several factors why that is possible and we now understand exactly what happened and we can factor that in, in the explanation very, very nicely.

So it’s really like the variability of the trial, the noise, if you like was much higher in our trial. And let’s not forget, we had a smaller study. We also had a Phase 2/3 was not a pivotal study, Phase 3. And also we had just a two to one randomization with 60 patient or 62 in the active arm and 30 in the placebo arm. And these 30 patients, if a few of them are just basically very noisy, that could derail and increase the noise in the trial and increase the standard error, which we saw in our trial.

Soumit Roy: So should we expect that rate [Rett] still being kind of one of the primary focuses for the company? And maybe one path forward would be to start a fresh pivotal trial with 180 patient, one-to-one randomized, kind of the Acadia size trial.

Christopher Missling: That is a very good point, and it’s exactly a possibility. And again, we would not do that, however, without further get regulatory input, because we might get some feedback, which could be very favorable. But indeed, that is something which could be done very easily. It’s a 12-week study, it’s not too long. And we have, again, a strong interest from the community, given the strong interest, and to continue to stay on study drug and patients in Rett syndrome from our program have been now on this drug for over four years – up to four years. That really shows a very high sticky interest to keep our drug and not to switch to anything else in the meantime.