Padmanabh Chivukula: Yeah. This is Pad. And based on our Phase 1 data, obviously, we’ll be looking at the lowest dose and the top dose. And when we decide to — when we go into Phase 2, we can probably eliminate some of the lower doses, and we’ll pick a dose where we feel comfortable with, that has a good safety margin to start with.
Yanan Zhu: Great. Very helpful. Thank you.
Joseph Payne: Thanks, Yanan.
Operator: Our next question comes from the line of Yigal Nochomovitz with Citi. Please proceed with your question
Ashiq Mubarack: Hi, team. This is Ashiq Mubarack on for Yigal. Thanks for taking my questions. On the OTC program, you had some earlier comments on enrollment and how that’s going. Can you comment at all on the rate of enrollment, in particular, site activation and if there are still outstanding challenges there or if was more or less an solved? And in terms of the OTC data itself, you’re planning on sharing. Can you comment at all on your expectations for kinetics of response, meaning as in how long do you need to dose and follow these patients before accumulating enough response data that would be meaningful enough to share? Thanks.
Joseph Payne: Sure. So, I can update the market that we have now onboarded nine active sites for OTC deficiency. The bulk of that effort was last year. This is the year where we’ve initiated enrollment officially. So, with respect to the pace of enrollment, it’s nothing that is out of the ordinary for a rare liver disease in Europe. So that’s the only comment I can provide there. All we’ve disclosed is multiple patients being enrolled so far. With respect to the kinetics, it’s helpful to understand that this is a six-administration trial. So these doses are separated by two weeks. So there’s six administrations. And what we’ve seen preclinically is that OTC is additive in our preclinical animal studies. So we may see this in humans as well. So that with respect to kinetics, we are collecting blood draws after each administration over these half a dozen doses.
Padmanabh Chivukula: Yeah. Again, this is Pad. Just to point out that, we’re the first protein replacement therapeutic that’s going after this indication and specifically for protein replacement using mRNA. So there’s a lot of unpaved road that we’re trying to tackle. What we envision, of course, that we could see something in the first few doses. And if we do — because of that, we are measuring a handful of biomarkers. So, we hope that we see something very soon, and we’ll report on that.
Ashiq Mubarack: Got it. That’s very helpful. And if I could ask one more on the cystic fibrosis program. Do you think it’s possible we could get some initial healthy volunteer data this calendar year or is that you think that’s more likely to be a 2024 event? Maybe once you have that data in hand, how do you think you can pivot into treating actual cystic fibrosis patients? Thanks.
Joseph Payne: Yeah. The study is being conducted in New Zealand, the Phase 1 study for CF because we’ve already dosed a pair of cohorts, there may be some initial feedback from, and we haven’t had any serious or severe adverse events, right? We have to report on that. So after the first survey after the first couple of cohorts, it does present the potential opportunity to end Phase 1 to add CF patients. But whether we add CF patients to the Phase 1 trial itself or quickly pivot to a more traditional Phase 2 regulatory process is yet to be determined and communicated.
Ashiq Mubarack: Very helpful. Thanks very much.
Joseph Payne: Thanks.
Operator: Our next question comes from the line of Pete Stavropoulos with Cantor Fitzgerald. Please proceed with your question
Pete Stavropoulos: Hello, Joe, Andy and team. Thank you for taking my questions. So I have one on 810, the OTC deficiency program. What type of patients are you enrolling? Can you speak to their baseline characteristics? Are you kind of enrolled patients are stable on stable background meds? And are they controlled uncontrolled? And can you speculate in which type of patients you may be able to see the most pronounced effects in?
Joseph Payne: Yeah. These are stable adult and adolescent subjects. That will be the initial focus. So, both adults and adolescents in the European Phase 2 multiple ascending dose trial. So I can comment on that. With respect to the other, and what was the other aspect of your question?
Pete Stavropoulos: Can you lay on which type of patients you may actually see the most pronounced effect?
Joseph Payne: Okay. Well, I think this therapeutic has the opportunity to have a biological impact on every patient injected. However, if they are already on ammonia scavengers, for example, the other biomarkers will be more meaningful, like, urea genesis and OTC itself. But if they are not on ammonia scavengers then, of course, ammonia will be looked at erotic acid and other amino acids are going to be investigated on, so the collective body of data should be sufficient to negotiate the regulatory path efficiently with regulatory agencies.
Pete Stavropoulos: Okay. Sorry go ahead.
Joseph Payne: No. That’s it.
Pete Stavropoulos: Yeah. I have a couple of questions. So if you can give a sense of how many subjects have gone through the full dosing cycle in the Phase 2 MAD study? And are you — is there like a safety look built in by, let’s say, the SMD (ph)?
