Neena Bitritto-Garg: Hey guys. Thanks for taking my question. Just to kind of piggyback on the Aria discussion here, I’m just wondering if you can tell us a little bit about was the comment on Aria being consistent with placebo? Is that true for both the cohort A and the cohort B patients so far. So both the APOε4 non-carriers and heterozygous as well as the homozygous, And then I was just wondering if you could also talk a little bit about some of the differences in activity that you’re expecting between the 70 mg dose versus 200 and 400 and why you selected 200 and 400 for both SAD and MAD? I know you talked a lot about collection of 70 mg as being based off of the see C average to 10 mg per [Indiscernible] but just wondering how we should think about the higher doses. Thanks.
Gene Kinney : Yeah, thanks Neena for the question. Maybe I can start then hand it to Hideki can again jump in here. I think first with respect to your question about the data that informs what we’ve said about this molecule to-date which just again as a reminder, I think what we’ve indicated is that with the A cohort which is the 70 mg monthly cohort, we’ve seen evidence of what we would characterize as encouraging reduction in amyloid beta. Obviously, that helps us to understand that we believe this is a once-monthly subcutaneous drug. And obviously Aria rates as you had mentioned consistent with placebo, what goes into informing that is obviously the data from a single dose study, as well as the cohorts – that 70 mg cohort I am referring to in the multiple dose study.
The additional ongoing cohorts remain blinded. So there is a it is a double-blind placebo-controlled study. I think the other question was really just around the selection of the dose levels and I think maybe I’ll just ask the Hideki to speak to that other than to say that these dose levels that are being explored are the dose levels that were anticipated to be explored and that we are continuing to conduct this study as we had anticipated and it’s moving forward in an encouraging pace as Hideki indicated. Hideki?
Hideki Garren: Yeah, thanks Gene. So as you mentioned we are continuing explore in a Phase 1 study and that’s the purpose of Phase 1 study is and I just remind you that 7 mg is encouraging Amyloid reduction and consistent Aria rate with placebo and that allowed us to really explore the full dose sponsor modify all of this 400 mg, And again just to remind you that high binding – once monthly subcu administration and potential be best-in-class and [Indiscernible]
Operator: Your next question comes from the line of Yasmeen Rahimi from Piper Sandler. Please go ahead.
Unidentified Analyst: Hi team, this is [Indiscernible] for Yas. Thanks for taking our questions. Just kind of diving more into the details of the Aria rates given that you’re enrolling both APOε4 homozygous and heterozygous. We know that this drives sometimes differences in Aria rates. How do the – expectations regarding both safety and efficacy across these populations?
Gene Kinney : Yeah, no. Thanks for the question. I think there is kind of two questions built into that one in terms of how we’re thinking about Aria just across the entirety of the patient population. And I think the second is really just around how we think about this trial design. So let me start with Aria and obviously, as we talked about Aria rates were being specific to our patient level cohorts we are reporting data out as one would in a Phase study relative to placebo. And I think that’s what we indicated in our release in January that Aria rates in the 70 mg cohort after six months of treatment were consistent with placebo. I think your – the point you’re making about testing separately APOε4 homozygous carriers in these B cohort is something that we’re learning from the field.
So, as we continue to iterate in this field across multiple companies, it does take a village to develop therapeutics in this space. We are learning from each other I think on the clinical side as well as the preclinical side. And one of the lessons I think that’s become clear that APOε4 homozygosity does tend to lead itself to a higher Aria rate and in the context of clinical trials that can lead to in some cases misdosing or skip dosing. Obviously that’s less than ideal as we start to think forward to efficacy-driven studies and registrational studies. We want doses that are optimized for the entirety of the population, not just portions of the population. So we chose in the context of the Phase 1 Study to be a little bit more deliberate in evaluating these APOε4 homozygous patients.
So that when we bring this entirety of the patient population back together in a clinical study that we’re selecting dose levels and approaches that are optimized for the entirety of the population. So that’s kind of how we think about it from an Aria perspective and not just from an Aria perspective, but from a therapeutic index perspective gut obviously with the convenience factor we think that’s quite important with respect to patient burden and as we’ve indicated in January relative to the data that we have came to date, we’ve given some directional guidance in terms of where we are in all of those encouraging levels of amyloid reductions once monthly Sub-Q we believe is supported based on the data we’ve seen to-date. It is the approach.
We’re continuing to take moving forward in our trial as planned. And then of course, we’ve just talked about the Aria being comparable with Placebo.
Operator: Your next question comes from the line of Rudy Li from Leerink Partners. Please go ahead.
Rudy Li: Hi, thanks for taking my questions. Just a quick follow-up on your dosing selection. So can you maybe talk about the rationale including the 45-mg dose in ascent 2 which was not tested in ascent 1. I am trying to get a better safety and any color will be helpful. Thanks.
