Yatin Suneja: I have a question on the Sjogren disease. Could you just talk about the disclosure that you expect to make? And given the composite nature of press, will you decide to move forward, even if you don’t see a strong signal or even if you just see a signal on other domains? And then maybe along the same line, from a regulatory standpoint, is there a well defined regulatory path here or is there an endpoint of choice from registration standpoint?
Karl Gubitz: I want to call out that Sjogren is a signal finding study where we will look at the totality of data across multiple clinical endpoints not just CRESS, but also ESSDAI actually ClinESSDAI and ESSPRI and then a string of biomarkers, which we are carefully monitoring. And what we want to see is consistency between the clinical endpoints and the biomarkers in order to get conviction and march forward. And from a regulatory point of view or endpoint point of view, we will need to have of course an interaction with the regulators. But mind you that there are a number of Phase 3 registration trials running, but actually the primary endpoint is ESSDAI. So, we assume this is the endpoint the FDA would like to see and CRESS is [indiscernible]. So stay tuned, if and when we will have positive signal data and we will entertain a conversation with the FDA on this topic and afterwards communicate.
Operator: Your next question comes from the line of Yaron Werber from TD Cowen. Your line is open.
Yaron Werber: Tim, maybe just a follow-on Yatin’s question also on Sjogren. So, your study is 36 patients J&J were in three on three arms, you have two, and they obviously had 163 patients. So they obviously had a much bigger study and sounds like it was stat as you mentioned. The endpoint is a little different, but you have a composite that includes their endpoint. So I guess my question is, it’s a pretty good trial design and so give us a little bit of a sense. Is it completely underpowered to show any statistics at all? And is there a certain threshold of an effect that you want to see that you consider to be positive to move forward?
Tim Van Hauwermeiren: I want to call out as an overlap between our endpoints and the J&J endpoints. The reason, of course, they’re doing three arms is because they still need to sort out a dose, which is not something which we have to do. You know that you can dose this product at full power without paying the safety penalty. We will look at consistency of data. So it is defined what a clinically meaningful improvement is on an entire score, on a press scale, on an SP scale and then of course we want to see the biomarkers move in the right direction. The biomarkers are a combination of biomarkers from the circulation, but also from the biopsy. And it is important to see the needle move on the clinical endpoint that we are going to pay special attention to what’s happening in the biomarker section, what’s happening in the biopsy and are these moving in a consistent fashion.
So conviction on biology, we have also stratified for high and low IgG levels, about 50% of Sjogren’s patients have high IgG types, 16 grams per liter or more. I think that’s a very interesting stratification factor. The other way we look at the data is looking for patients which are positive for the raw antibody or not. So I think it’s going to be a small sample with a very deep look into patients and a very rich look so way beyond the P value on an endpoint.
Operator: Your next question comes from the line of Allison Bratzel from Piper Sandler. Your line is open.
Allison Bratzel: So just to follow up on some of the discussion on the prefilled syringe. Could you just expand on the expected cadence of updates on that this year and just what gives you confidence and potential approval of the prefilled syringe in 2024? And then just more broadly, given competitive updates in the field, how important do you see self-administration via syringe or auto injector in determining your competitive positioning in a market with multiple FcRn agents approved?
Tim Van Hauwermeiren: So, I’ll take the first one and I will hand over to Karen to explain how we seek to continue to lead the space also from a patient’s accompanying point of view. But first at least in syringe, it is high on the strategic agenda of the Company this year that we decided to launch the first generation subcu as fast as we could with the patient in mind. This is our second generation of prefilled syringe and our two important data sets we need to collect in order to be ready to submit the dossier with the FDA. The first data set is a bioequivalence study. The second data set involves a human factor study and we are on track to give you an update during the first half of this year in terms of the progress we are making with collecting these data points. It is of high priority for the Company to be in a position to submit this year with the FDA. And maybe, Karen, you can continue on part two of the question, please.
Karen Massey: Absolutely, I’m really excited, for the prefilled syringe and the potential, to bring that to patients. Look, we talked earlier about there’s a significant unmet need, in this market, and we can see that patients are looking for innovation. And I think our revenue last year demonstrates that, in just our second year of launch. MG patients want to get their lives back, and PFS and self-administration help them to do that. So I think that’s the real reason that the innovation of PFS is important. And then and I think for us, from a VYVGART perspective, it just reinforces our leadership in the market. But first thing, FcRn, I talked earlier about how we’re demonstrating that real world efficacy, continued safety, and then this just brings another product presentation potentially to the market. So we’re confident that we’re bringing the innovation to the market that the patients really need.
Operator: Your next question comes from the line of Vikram Purohit from Morgan Stanley. Your line is open.
