Tess Romero: I thought I would ask a commercial one today, for PYRUKYND as you grow patients on drug, just trying to get a sense of how you think about trajectory of new patient adds here. It sounds like the drop off is pretty low. And do you think this run rate of 10 or so sequential net patients adds, like you’ve seen in the last couple quarters, is the right way to think about the launch going forward versus something maybe more accelerated given some of the initiatives on analytics, et cetera?
Brian Goff: Yes, thanks. So Tsveta is thrilled to have a question about commercial, so I’m going to let her comment.
Tsveta Milanova: Hi Tess, good morning. So, as you said, we continue to make progress on the launch. Most importantly, we continue to see the strength of the PYRUKYND profile in the real world, especially when it comes to persistency, the positive provider feedback and the payer support. At the same time, we also know that PKD is an ultra rare disease. And as we said through our opening remarks, we would expect to continue to see slow and steady uptake. We will expect to see some variability quarter-over-quarter. But our efforts continue to be laser focused on identifying the right providers, providers who are likely to have patients with PK deficiency and patients who are appropriate for PYRUKYND either today or potentially in the future.
And this is where our efforts in data and analytics continue to support our team as we continue to execute in the field. Very importantly, all the capabilities we are building today serve as a very good foundation for us as we continue to look into the future and potential future indications, expungement for PYRUKUND such as Thalassemia as well.
Brian Goff: Yes, I mean the only thing I will just add, Tess, is that this is a very unique kind of launch. It is pretty far on the ultra rare spectrum. And we are building learnings from it. But I would look at it as slow and steady growth and we always caution to just be a little bit careful over quarter-over-quarter because it will be lumpy for quite some time. But we are very proud of the progress that Tsveta and the team continue to make.
Tess Romero: Great. And if I can just squeeze in a commercial follow-up there, you know, given these dynamics, how do you think about providing longer term PYRUKYND guidance. Is that something you feel like you may be in a position to do as we kind of exit 2023 and get into next year?
Brian Goff: Sure. Thanks. Cecilia, you want to take?
Cecilia Jones: Yes, I can take that. So, you know, as we mentioned before this is for a ultra rare first therapy and we continue to learn data and insights. At this point, we are not going to give guidance. There will come a point, we will continue to evaluate when it is the right time to do that.
Brian Goff: Yes, our anchor point, as we have talked about peak sales, 200 million to 225 million in the U.S., that is where we feel confident. We want to get more quarters under our belt until we give guidance on the revenue for PKD. And of course, the bigger picture for us anyway, is that we are approaching the readout of the Thalassemia data. That is a meaningfully larger launch that has potential in 2025. And we may be in a scenario we start to look at the collective guidance of multiple launches.
Operator: Our question comes from Danielle Brill of Raymond James.
Danielle Brill: I also have a question on the in license asset. So I know there are also antibodies targeting TMPRSS6 in development. I was wondering if you could elaborate on why you think siRNA maybe a superior modality in this indication. Is it just a more convenient dosing regimen or do you think there might be an efficacy advantage as well? Thank you.
Brian Goff: Well, so thanks a lot Danielle, for the question. We think there are, as I noted earlier, potentially multiple opportunities for differentiation. TMPRSS6, we feel is now a well-established pathway. I mean, very simply the 90% knockdown of TMPRSS6 has an uplift effect on hepcidin, which decreases iron, which ultimately lowers the red blood cell production. That thread through that mechanism, we feel through all of our diligence, very confident in, and as I said, I think there will be opportunities for efficacy, safety of course will be — that is one, when you look at some of the current opportunities therapeutically for patients, there is plenty of room for improvement. And then it could wind up also being a meaningful convenience opportunity because siRNA classically and particularly from the Alnylam platform, has proven that, that is a mechanism that has delivered benefit to patients with lower interval of treatment.
But we are going to look at all of that very early, and we will start our IND enabling studies this year, and then we will report out our progress accordingly.
Operator: Thank you. And we are showing no additional questions, so we will turn the call back to Brian Goff for a final comment.
Brian Goff: Alright, well thank you all very much for participating in today’s call, and of course for your continued interest in Agios. As you heard this morning, we are really energized by the tremendous progress we continue to make across our portfolio. We are confident in our potential to deliver significant long-term value for both patients and shareholders. So thank you very much again, and we look forward to speaking with you soon.
Operator: This concludes today’s conference call. Thank you for participating. You may now disconnect. Everyone have a great day.
