Karl Gubitz: Yes. It wouldn’t be unusual to see C5 blocker failure in indication, but then other complement intervention works. Complement is not one size fits all. Complement is a very complex system. There are multiple pathways involved and depending on the disease, different arms of complement are involved and at different stages. MMN for example is an example in case and C5 blockade failed in MMN, C2 blockade is a homer. So, the same I think is valid for DM and it’s not because of C5 blocker fails that upstream complement blocker defector would fail. So we need whole biology. We think the complement activity is upstream of C5 and therefore I think we need to do this experiment without over prior to C5 work. Thanks for the question.
Unidentified Analyst: Awesome. And then one quick follow-up, just could you comment on any relative design differences between your Phase 2 and Phase 3 and then the ULTOMIRIS trial, if you happen to know?
Tim Van Hauwermeiren: Yes. We don’t have enough details about the ULTOMIRIS trial to really do a head to head comparison between, you know, study details. So, we don’t have that information, and I’m not in a real position to comment on that.
Operator: Your next question comes from the line of Myles Minter from William Blair. Your line is open.
Myles Minter: Just back on the ROE study, I think we’ve seen like 50% SI response rates in prior Sjogren’s trials at Phase 2 on placebo. Just wondering whether that’s the expectation for the 12 patients that you have on placebo in that trial? And then also how important is it to show efficacy on the totality of data at the 24-week endpoint versus efficacy over the entirety of the trial. Again, just pointing to recent trials in the space that have shown variability between 20 and 24 weeks on efficacy?
Karl Gubitz: So yes, we have been studying precedent trials. There is some consistency in placebo response. It’s about a 40% response. You have an outlier study, but we think we understand why there is an outlier. So, I think you do see a reasonable consistency in historical placebo responses and that is the incoming assumption for our trial two. In terms of endpoint, we have an endpoint to choose, but we are actually looking at multiple endpoints. So it’s a 24 week study, that we have multiple time points where we will basically assess the patients and look at the dynamic evolution of the disease symptoms and the biomarker. So it’s not just going to be a photo finish at week 24. We’ve been looking at the evolution of the data over time.
Operator: Your next question comes from the line of Xian Deng from UBS. Your line is open.
Xian Deng: So I have a question on 119 in ALS, please. I was just wondering if you could elaborate a bit more about the biological rationale for ALS please. I mean, given ALS is a very complex disease, I mean, there’s like protein degradation, autoimmune, genetic factors involved. So just wondering for benign, are you coming from the angle that mask is sort of a key factor in neuromuscular synapse formation? And if that’s the case, I’m just wondering, are you after disease modification here or it’s more sort of like a symptom relief, a bit like levodopa in Parkinson’s?
Karl Gubitz: So, muscular is a very interesting target. It’s not just organizing the formation and the maturation and the functioning of the neuromuscular junction and the signal also goes in the other way. So, not can signal through LRP4 back to the neuron, and one of the hallmarks of ALS is that in the initial stage we go through a phase which we call a phase where we have repeated denervation and reinnervation, and there must be communication between the nerve cell and the muscle cell in that process and we think that happens through retrograde signaling musk to LRP4 to the neuron. So, if you can keep the innovation longer through activating musk, we think that could have a meaningful impact on ALS patients. So despite some biology thinking going on behind the program, we do realize ALS is high risk, but also high reward.
And therefore, there is a ton of translation biology going into the ALS thinking. Also the way we set up the initial clinical experiment is such that we will have a very deep look into these patients, almost happens on that reinnervation, denervation process. So stay tuned. It’s an exciting experiment and we’re looking forward to seeing the first data.
Operator: Your next question comes from the line of Joon Lee from Truist Securities. Your line is open.
Unidentified Analyst: Good morning. This is Asim on for Joon. Thanks for taking the questions. On the TED trial, I believe it was previously slated to begin in the fourth quarter last year. Just wondering what was behind the delay. And then my other question is on the pre-filled syringe, just wondering if you could just provide some details on your manufacturing capacity or your preparations. Thank you.
Karen Massey: Thanks for the questions. For the TED trial, we made a decision to wait to start that trial so that we could use the PFS and that trial is on-track now. For the second question, we’ve invested in manufacturing capacity and confident in the manufacturing capacity for IV, subcutaneous and PFS at this stage.
Operator: Your next question comes from the line of Douglas Tsao from H.C. Wainwright. Your line is open.
Douglas Tsao: Hi. Good morning and thanks for the questions. I’m just curious in terms of how you’re thinking about reimbursement in CIDP or just sort of contracting with payers. I suspect you had some early conversations and just given the fact that, IVIg is already on label, the dosing frequency is greater in CIDP. Do you see the same opportunities to have access and same success with access that you’ve had in gMG and will it sort of have different outlines and same opportunities for value based reimbursement? Thank you.
Karen Massey: Yes. Thanks for the question. We think a lot about how do we maximize access to patients, through our innovation and we’re thinking deeply about it for the CIDP launch. What I can share is that, we’ll take the same approach that we did with the gMG launch. We’ll be transparent once we have a decision and we’ll make responsible decisions that really give patients the greatest access to our innovation that we can, but more to come. Thanks for the question.
Operator: Your next question comes from the line of Andy Chen from Wolfe Research. Your line is open.
