Gene Kinney : Yeah, maybe – thank you for the question and maybe I can just take this one. I think, what we’re looking for is to really have a fulsome understanding of the exposure response relationship and we believe that evaluating dose levels, from 45 milligrams to 400 milligrams provides us with a pretty comprehensive overview of that. And obviously that exposure response relationship is something that we’re interested in both in terms of amyloid reduction, but also in terms of Aria rates to understand that therapeutic index. So that’s that’s really what defined it. I think as Hideki has already mentioned there has been very high level of interest in this study. So we’ve been affording also the opportunity to include a number of cohorts and we’ve been able to enroll those cohorts in a pretty favorable way.
So I think that that really is the rationale for it. And other than that, I would just say that these were the dose levels that we had pre-planned on testing as we saw the first dose level cohort at 70 mg dose level cohort data, the decision was to continue to conduct this study in the way that had been previously evident.
Operator: Your next question comes from the line of Michael Yi from Jefferies. Please go ahead.
Michael Yi: Hey guys. Thanks for the question. I know there’s been a lot of questions around Aria and we just wanted to ask more specifically when you say consistent with placebo, was there actually one case of Aria in the placebo and whether you would have expected that? And then if so, would you have expected Aria in that type of range in the drug arm given you had very little exposure to whereas the IV drugs inclusion can have Aria rates that are around 12% to 20%. So, could you tie those two together and what would drive confidence today for those listening that you can go to 200 mg and three times the dose and still thread the needle. Thank you.
Gene Kinney : Yeah. Thanks for the question, Mike. I mean, obviously this study is double-blind placebo-controlled and as we reported as a 70 mg dose level. The Aria rates as you say were consistent with placebo and I think that’s I think the statement around where we are from a therapeutic index perspective and what we think that therapeutic index then provide is the ability to move up and dose range as you’ve indicated. So I think Hideki has already mentioned that the 200 milligram dose level cohort, in fact, all dose level cohorts are active. And so we’re moving forward and exploring a full exposure response relationship ranging all the way from 45 to 400. So I think what that could indicate is that we believe that the therapeutic index provides us with the sense that we have the potential for a best-in-class molecule.
And again for us a best-in-class molecule is a function of the three variables. The convenience factor, which is really around patient burden. The efficacy which indicates case here, we’re talking about really reduction of amyloid. And then of course the safety, which I think everyone is very focused on Aria. But we’ll talk about safety in general as being permissive from therapeutic index perspective to continue to explore this fulsome exposure response relationship rank.
Operator: Your next question comes from the line of Jason Butler from Citizens JMP. Please go ahead.
Jason Butler : Hi, thanks for taking the question. I guess I wanted to switch gear here and just ask a question about Prasinezumab. Can you just speak to us about how we should think about magnitude of benefit or clinical meaningfulness around the primary endpoint? And then how do you envisage the product being incorporated into clinical practice? Thanks.
Gene Kinney : Yeah, no, thanks for the question. Yeah, so like, just maybe just a quick refresh of what Roche has already shown with this molecule. So, starting with the Movement Disorder Society data last year where they showed the three year open-label extension data from the prior Phase 2 PASADENA study and importantly relative to the PPMI demographic matched group, it showed a 63% flowing of progression as measured by MDS S-UPDRS Part III. And more recently, we’ve seen the abstract publish for the ADPD meeting which will occur here in early March where that presentation hasn’t happened yet. They have published the abstract and they have been talking now about four year open-label data and then based on UPDRS – the MDS-UPDRS Part III scale 117% less progression than that PTMI data base group.
And that’s like even on the activity of daily living, scale of the MDS-UPDRS Part II are 39% less progression in that PTMI data group. So, we’re very interested in this. Obviously the PADOVA study is fully enrolled as per Roche. This is a large study that is being run with high integrity. You got 586 patients in this study randomized on a one-to-one basis. So we’re excited to see those results. I think it’s based on strong science, it’s based on previous clinical data. I think the way they’re thinking about the endpoint is informed by the prior studies and then ultimately, that the go-forward regulatory path and I think to your question, how this will ultimately be positioned will be determined by the data. And obviously also continued conversations between our partners at Rocha and the regulators and we have very high confidence that Roche will be as a aggressive as is appropriate based on the data set that they have today.
Hideki Garren: But I think one thing to add to in terms of the time to event endpoint is that it captures a five-point or greater increase right progression in the scale, which ended up self Roche for these to be clinically meaningful. They’re also working on other clinical functional endpoints within the trial to correlate. So we look forward to the continued discussion with regulators. And of course the data later this year.
Operator: And we have time for one more question today and it comes from an Ananda Ghosh from H.C. Wainwright. Please go ahead.
