Unidentified Analyst: Yes, thank you so much.
Operator: Thank you for your question. Please stand by for our next question. Our next question comes from the line of Brendan Smith of TD Cowen. Your line is now open.
Brendan Smith: Great thanks very much for taking the question. Maybe just another quick one on pulmonary and then I have a broader follow-up. So first I actually just wanted to see if there’s anything else specifically that you’re seeing in the asthma patient data that’s giving you more confidence and movement to Phase 2. Maybe more to the point if you’ve seen any of the high FeNO patient data yet like if you’re seeing good FeNO knockdown or anything like that. And then more broadly I just wanted to check and see if there’s any update on potential licensing or commercialization partnerships or maybe when we might get an update there and what that’s looking like? Thanks very much.
Bruce Given: Sure. I think the biggest driver in moving in not waiting and moving you know towards that Phase 2 is the safety and tolerability that we’ve seen so far and the and the target engagement we’re seeing good rage knockdown. We’ve seen we’ve seen a lot of excitement from KOLs for the rage pathway and so it just makes sense just makes sense. So we’re moving as quickly as we can there. On the on the partnering side we have we are we are always or virtually always in discussions as you can imagine. We have no control over timing and so I have nothing to report at this point other than the fact that this is an important part of our business and we do expect to execute additional transactions.
Brendan Smith: Okay. Thanks very much.
Bruce Given: You’re welcome.
Operator: Thank you for your question. Please stand by for our next question. Our next question comes from the line of [indiscernible]. Your line is now open.
Unidentified Analyst: Thank you. First question. Is there a rationale for the different sample sizes between SHASTA-3 and 4 as one deliberately over sampled?
Bruce Given: Not really. The so the design of the SHTG program was in many ways a result of our discussions with FDA about their overall expectations for what they wanted to see in efficacy, database safety, database, et cetera. And it just turned out that it could have been 350 in both. In the end, practically, it made sense to have one be 401, 300, but it was really largely just driven by practicalities to get the patient population that the agency was requesting. So it really is accidental, you might say, that they’re different size.
Unidentified Analyst: Okay. And then in terms of the…
Bruce Given: Yes, they’re both way overpowered for efficacy. If you saw the results from SHASTA-2, they’re both way overpowered for efficacy.
Unidentified Analyst: Okay, well, that’s great to hear. Just in terms of the mix CVOT, since you have a design you’re ready to submit for review, have you selected one of the two? And then based on the feedback, you still, I guess, have the option to switch or how should we think about where you’re at with this?
Bruce Given: Yes. So until we get. Until we have feedback in alignment with regulators, it makes sense for us just to stand pat on this. We’ll give you, of course, all the information that we can, once we have confirmation from the regulators that we are all aligned on what this study looks like. So stay tuned on that. We’re still working.
Unidentified Analyst: Okay thanks.
Operator: Thank you for your question. Please stand by for our next question. Our next question comes from the line of William Pickering of Bernstein. Your line is now open.
William Pickering: Hi good evening congrats on the progress and thank you for taking my question. On SHTG, in SHASTA-2, you had a fairly sizable placebo effect of 17% at 24 weeks. Could you comment on whether you think that’s a reasonable proxy for what to expect in the pivotal and if there are any strategies to potentially limit that?
Bruce Given: Yes. Well, it’s kind of interesting because if you actually look at the data, placebo was essentially plugging along at, right around zero change. And then, at week 20, it was like zero. And then at week 24, it dips down to, whatever, you know, minus 17, I guess. And then it was halfway back, up to zero, you know, four weeks later. And then eight weeks later, it was right back to where it had been for the first 20 weeks. So it’s just one of those weird deals that, this is what makes it hard to do placebo-controlled studies. Placebo just behaves strangely at unpredictable times. And all of us, you know, just have to put up with that. We did things in the trial to try to minimize placebo, changes in placebo. But, but in the end, it’s always difficult to, to really manage that.
William Pickering: And if I could just squeeze in a very quick follow-up, you know, what led you to pick the 25 milligram instead of the 50? And do you think that you’ll be able to demonstrate a more compelling efficacy profile versus plozasiran at that dose?
Bruce Given: Yes, well, 50 and 25 were very similar with respect to, with respect to activity, with respect to efficacy. And that was not only in SHASTA-2, but that was also in MUIR. They just looked really close. And yet there was a difference in tolerability. And so, it really was a benefit-risk decision in the parlance of, the regulatory parlance, but in our parlance as well. You look for, you know, we put up with side effects in this business, when we have to. But if, in fact, there’s a dose available that essentially gives you full efficacy and has, better safety and tolerability, you take that one. I mean, our overall assessment of the 25 milligram dose in both of those two large Phase 2s in which it was in is that it’s, kind of indistinguishable from placebo.
The difference between active and placebo is so small as to be, not convincingly different at the 25 milligram dose. In terms of safety? In terms of safety and tolerability, right. And that mattered a lot, when the efficacy looked basically the same. And 50 milligrams looked a little different from placebo. So we took advantage of the fact that we were at the top of the dose response curve for efficacy and we had, a better safety and tolerability profile.
William Pickering: Makes sense. Thank you very much.
Bruce Given: You bet.
Operator: Thank you for your question. Please stand by for our next question. Our next question comes from the line of William Pickering. I’m sorry. Our next question comes from the line of Patrick Trucchio of H.C. Wainwright & Company. Your line is now open.
Patrick Trucchio: Thanks. Good evening. Just a couple of follow-up questions on the complement programs. Just first, I appreciate that dosing in the Phase 1 2a trial began last month. I’m wondering, though, if you can talk about potential timing of initial data in this trial evaluating AROCFB and kind of what you’d be looking for in that initial data and later data give confidence in advancing this program. And then secondly, if you can talk more broadly about the potential advantages of CFB relative to existing treatments for various complement media disease, and how you envision CFB fitting in these, the different treatment paradigms. And then lastly, how should we think about this complement program relative to AROC3? And can you talk in more detail how these programs may progress in parallel?
Chris Anzalone: Yes, sure. Maybe I’ll take the last one first. Thanks for the question. So I think we will make a data-driven decision for C3 versus CFB. We think there are maybe some indications where C3 might work better, something like C3 glomerulopathy where the disease is really driven by the accumulation of, excessive C3, and then others where CFB might work better. But I think that’ll be really data-driven. And then in terms of advantages over some of the other therapeutics out there, I mean, I think the dosing advantage is really significant that we would have for both of these in terms of duration of effect for AROC3, we’re getting 88% knockdown that can be essentially maintained for three to four months after a single dose.
So I think if you’re, again, looking at dosing quarterly versus other therapies that require either, daily oral dosing or frequent subcutaneous dosing, I think there’s a big advantage there. We’ll see what the dosing regimen looks like for AROCFB, but based on preclinical data, that’s a very potent molecule. And so, I’d expect something similar in terms of duration of effect. And then data timing, the CFB study just got started. It’s a healthy volunteer study. And so, the biomarker knockdown of circulating plasma CFB, that’s the main efficacy or activity biomarker of interest. And we could potentially have something by year end for that.
Patrick Trucchio: Great. Thanks so much.
Operator: Thank you for your question. This does conclude our question-and-answer session. I would now like to turn the call back over to Chris Anzalone for some closing remarks.
Chris Anzalone: Thanks, everyone, for joining today, and we look forward to seeing you at the Summer Series starting later this month.
Operator: This does conclude today’s conference. You may now disconnect.
