Operator: Our next question comes from the line of Tess Romero with JP Morgan.
Tess Romero: Great. Good morning, Brian and team. Thank you for taking our question. So, switching gear a little bit to commercial PKD. Do you still think that PKD could be a $200 million to $250 million peak opportunity here in the US? And if so, how long do you think it could take you to get there? And then my second question is, we know that you’re moving AG-946 forward and lower risk MDS. But we were curious, have you formally deprioritized the program in sickle cell disease, as we hadn’t heard anything on this in a while? Can you confirm if that’s the case or not? Thanks so much for taking our question.
Brian Goff: Thanks a lot, Tess. Actually, the second question, we can handle that very quickly, which is no. And we have not deprioritized anything with AG-946. I think we’re inspired by the potential. And at the right time, we’ll provide updates about the progress, not just in our pursuits of low risk MDS, but also where we stand with respect to sickle cell disease. Cecilia, do you want to comment on the first one?
Cecilia Jones: Yeas sure. Thanks, Tess, for the question. So we definitely remain excited about the opportunity in PKD, and we continue to expect those peak sales at $200 million to $225 million for the US. We continue to make progress each quarter, and we’re learning, and as Tsveta said, this is helping also build those capabilities for that launch. We think it’s going to be slow and steady, continuing to see the trends we’ve seen in 2023 for the next few years. But we do still maintain our peak of $200 million to $225 million.
Brian Goff: Yes, I mean, with PKD, and we’ve talked about this previously, but in the deep commercial experience that both Tsveta and I have across multiple rare disease cases, this one’s tough. It’s a challenge. It is ultra rare. It’s diagnostically intensive. There are long lead times for patients. So slow and steady is the right phrase. What were continue to be inspired by each quarter is that persistency, which is something we saw relatively early with the launch of PYRUKYND and PKD, that is a really important feature as we think about chronic rare disease launch is to come that are in our sites. And so we’ll take the slow and steady path and we’re going to continue to expect that going forward. But the way PYRUKYND is performing is what we believe really puts us in a position of strength as we approach ENERGIZE, sorry, keep seeing ENERGIZE, as we approach thalassemia as well as sickle cell beyond that.
Operator: Our next question comes from the line of Greg Harrison with Bank of America.
Greg Harrison: Hey, good morning. And thanks for taking the question. Also, just wanted to follow up on AG- 946. How are you thinking just generally in development, about development and potentially overlapping indications with mitapivat that could be improvement? For example, in sickle cell, like you discussed, or even thalassemia. And what would you need to see from 946 in order to make that decision?
Brian Goff: Yes, I’ll start and then Sarah can jump in. First of all, Greg, I hope we’re in that position where we have multiple indications, just as we have right now with PYRUKYND. One of the key advantages of, at Agios, of having really a leading PK activation franchise is we have not one, but two products that we’re developing. And that allows us to have different economics, different pricing dynamics across the indications in between the products. I think there’s a wide enough space for us right now, given where we are in the development program with AG-946 that we can tailor the appropriate target product profiles, whether it’s for sickle cell disease or for low risk MDS. And in the case of low risk MDS, as I think folks know, we just reported out last year very encouraging proof-of-concept from our Phase 2a study.
And we’re in the process right now of making enhancements in the design so we can pursue Phase 2b. I feel very good about the work the team has done and that’ll be the next step. And as I mentioned before, at the right time, we’ll also report out the progress on sickle cell disease. Anything you want to add, Sarah?
Sarah Gheuens: Just high level, I think what you can expect from development is that we always try to design our trials to meet multiple stakeholders, their needs, meaning we take our target product profile very seriously. So that is something that for 946 is the same. We take that very seriously and we incorporate, we will be incorporating patient voice and the regulatory feedback obviously as well.
Brian Goff: Yes, and a great example of that is in the case of sickle cell disease, a point that we are very proud of at Agios is we have deeply involved the community. In fact, Sarah and I attended the conference last year where we won an award from the community about how carefully and thoughtfully, we involved sickle cell disease warriors and caregivers in how we think about designing the trials, recruiting for the trials, and ultimately what the commercial profile should look like. And we will do the same thing with AG-946.
