Phil Nadeau: Good afternoon. Thanks for taking our questions and let us add our best wishes to song as he moves on. Two from us. So, first, as you just highlighted, durability response is a key question that’s going to be answered by with the Estel and Q4 updates. Is there any reason to worry that the effect could be lost for the combination regimen or monotherapy regimen over time? Any preclinical signs that resistance could develop in hepatitis Delta? And then second, totally unrelated on business development with $1.5 billion in cash. Can you talk a bit about the environment you’re seeing in business development and what your most recent thoughts are on priorities for investing externally? Thanks.
Marianne De Backer: Thank you for those questions, Phil. And maybe we’ll get to your second question first. Yes, we have shared, we are in a great position that we can really use our strong balance sheet to fund our priorities and of course that is hepatitis Delta and hepatitis B in our pipeline. However, we also have the opportunity to look for extra external innovation and especially early clinical programs would be of interest there. And we continue to be very thoughtful and strategic in looking at those opportunities and discerning whether those would be a great fit for us and creating value for the company and our shareholders. I will ask Carrie to answer your question related to durability of response.
Carrie Huang: Thank you, Marianne, and thank you, Phil, for the question. So your question around durability of response, would we expect to see any resistance or loss of durability with our chronic hepatitis delta regimen? So I think based on what we’ve seen to date, we have some in vitro data. We haven’t seen any resistance to date. We have a lot of hepatitis B data, like looking at surface antigen, and we haven’t seen rebounds in hepatitis surface antigen over time with a combination of ellipsoid and Hibabar given together. And I think, as with other chronic infectious diseases, both ellipsoiran and Tobivabar work through two different mechanisms. And because we’re working through two different mechanisms in terms of inhibiting levels of surface antigen and then hdbrna, the likelihood of developing resistance is much less compared to if you were going forward with a monotherapy.
So time will tell. But based on what we know so far from hepatitis be some of our in vitro work and what the expectations are with having two different independent mechanisms against the virus, my guess is that rebounds and resistance would be rare.
Operator: Your next question comes from the line of Patrick Trucchio of H.C. Wainwright. Your line is now open.
Patrick Trucchio: Thanks. Good afternoon. Just a couple of questions from me. The first is just on the Delta program. Given the lack of treatments available, I’m wondering if you can talk about if there’s a possibility for an accelerated pathway to approval, depending on the outcome from SOLSTICE and what that might look like in terms of potential phase three and pathway to approval. And then just on the HBV program, I’m wondering if you can talk about whether you expect to have data segmented based on surface antigen levels at baseline, and if so, at what levels at baseline would you expect to report this data? And related to this, how important is it to demonstrate loss of surface antigen in all comers relative to patient cohort with relative lower baseline surface antigen, especially as you consider potential advancement of the program to phase three?
Carrie Huang: Thank you, Patrick, for the questions. So in terms of hepatitis delta and possibilities for accelerated pathways, as you know, there’s no therapy that’s currently approved in the United States at this time. And so based on the strength of our data, we will look for any of those mechanisms that we can accelerate paths to approval such as fast track, breakthrough prime and these other methods that are available to us from regulatory agencies. So we will be looking at those pathways to move forward and to facilitate discussions with regulators as we develop and get alignment on our registrational pathway going forward. And then in terms of your second question, around hepatitis B, will we be looking at segmented data by surface antigen levels?
So, yes, in our trials, actually, to date, in our hepatitis B trials, we have taken all comers, not just enrolling participants with surface antigen, less than 3000 or 1000. We’re taking a broader view, but we will be able to look at subgroups within our data sets to see whether certain cutoffs would increase serial clearance rates and surface antigens. So those will be areas that we will be evaluating and looking at in our data set.
Operator: Your next question comes from the line of Roanna Ruiz of Leerink Partners. Your line is open.
Rosa Chen: Hi, this is Rosa Chen on for Roanna Ruiz at Leerink Partners.Thanks so much for taking your question. First, a couple on hdv. So, for SOLSTICE, what level of alt normalization are you expecting to see in the upcoming data? At easel, given that we didn’t really see meaningful normalization in the early data that you presented last year?
Carrie Huang: Great. Thank you. Thank you, Rosa, for the question. So I think the data set from our ASLD set was small numbers. We only had six participants. We had two out of six that achieved alt normalization. But of the participants who did not achieve alt normalization, a majority of those were just around that upper limit of normal. And so I think with potential longer treatment, we may see more and more normalization. With this dataset coming out at easel, we will have a more robust data set. And so that will help inform us further in terms of what we would expect to see in terms of alt mobilization with this regimen going forward.
Rosa Chen: Okay, got it, thanks and then another one on Hdv. So we haven’t heard too much recently about Hepcludex’s resubmission in the US. So can you share how you guys are thinking about maybe the competitive positioning of your regimen versus hapcludex? How are you thinking about maybe the patients who could be more responsive to your regimen versus hapcludex if both are available?
Carrie Huang: Yeah, thanks for that question. So I think, as you said, it’s not approved in the US, but as I mentioned in my prepared remarks, that we would plan to have Oliver tide as our comparator in our trials going forward. And based on at least what we’ve seen from the first six participants and our ability to really get to undetectable levels very quickly only after twelve weeks of combination therapy. I think that is the potential differentiator for us going forward. As I mentioned, the goal is always to achieve virologic suppression for any therapy in chronic viral diseases. And if we’re able to demonstrate that in a larger data set, then that gives us further confidence in moving forward. In addition, I think the regimen that we are developing is also being administered [ph]subcu once monthly, which is also a potential differentiator there as well, because, as I mentioned previously in a previous answer, we are attacking the delta virus through two different mechanisms.
There’s less of a concern with resistance or non response in different patient populations.
