Sarah Gheuens: Sure. So, in regards to PK activation and the differences between mitapivat and some other PK activators, so we indeed, well, while we stimulate PK, different PK isoenzymes amongst which the PKR, which is important for the red blood cell, but then also PKM2 is important, then we understand more and more the relevance of this specific isoenzyme in the context of the diseases that we are studying. And as you know, thalassemia, sickle cell disease, MDS, there is different components to these diseases in which stimulation of PKM-2 may be relevant as it is expressed in immature red blood cells. It is expressed in other tissues that are also touched by these diseases. We are planning to further study this clinically as well, specifically in sickle cell disease in the kidney.
As we know, kidney is such an important organ in the context of sickle cell disease, and now many patients suffer from kidney disease, and we believe that PKM-2 may have an added advantage there. In regards to how that compares to other PK activators, specifically at our Etavopivat that is, they, this is the drug that used to be Forma’s drug, they always spoke about being a PKR selective agent in regards to how they translate into other isoenzymes, they have not spoken about that. They have just highlighted their selectivity message.
Operator: Our next question comes from the line of Salveen Richter with Goldman Sachs.
Unidentified Analyst : Hi, this is Lydia on for Salveen. Thanks so much for taking our question. Just one on sickle cell. Could you just discuss where you see PYRUKYND fitting into the current commercial landscape just broadly? And then can you also speak to the enrollment progression and any physician feedback you’ve gotten so far? Thanks so much.
Brian Goff: Sure. And maybe I will just start and then quickly turn it over to Tsveta and then Sarah can pick up on the enrollment aspects. I mean, the fundamental premise of what we’re driving towards with sickle cell disease is we believe that mitapivat, PYRUKYND has the potential to be what we refer to as foundational therapy. This is a very different mechanism of action as we’ve talked about. Very unique from currently available options. We’re increasingly convinced that the benefits on making the red blood cells healthier really position it as such. And then the fact that this is an oral treatment only adds to that potential. But I’ll let Tsveta speak a little bit more about not just how we’re thinking about sickle cell disease, but the bridge as we go from PKD to thalassemia and then the sickle cell.
Tsveta Milanova: Thanks, Brian. I’ll start with sickle cell disease for us, but as you said, we have a very important milestone with the thalassemia launch ahead of that, which we believe will be an important point from growing the commercial capabilities executing on the thalassemia launch. And after that capitalizing on sickle cell disease. When we think about sickle cell disease, Brian mentioned that and Sarah mentioned that already the prevalence of the disease is 100, 000 patients in the US, which is a significant step up from where we are today with PK deficiency. It’s a disease where patients are diagnosed and the burden of disease is well characterized. At the moment, the adult patient population with sickle cell disease has very limited treatment options available.
They are either improving hemoglobin levels, which is the case of a brighter or improving VOCs based on the Phase 2 data and the target product profile, we have for a PYRUKYND for launch. We believe that we’ll be very well positioned with PYRUKYND to provide a treatment option, which will bring benefits to physicians, patients, and ultimately, payers as well by improving hemoglobin, reducing VOCs, and ultimately improving the way patients feel and function. And that’s going to be a unique value proposition if we were to deliver on that profile. So we are very excited about that opportunity to come. But before we get to sickle cell disease, we are actually very excited to progress with our launch preparations for thalassemia as well. After we saw the results from the ENERGIZE data in the year, we have definitely pressed the button and are actively preparing for thalassemia launch to come in 2025.
Similar to sickle cell disease, I think the thalassemia launch will be meaningfully differentiated in terms of market characteristics compared to PKD and that will position us well for adoption of PYRUKYND, assuming approval in 2025, including again, these patients are diagnosed, it’s 6, 000 diagnosed patients in the US with thalassemia, and well-established ICD 10 own, a stronger concentration of the prescribed base and all of these elements gives us confidence on our ability to commercialize the product and drive adoption at launch. And similar to sickle cell disease, there is a better understanding of the thalassemia unmet needs across both the transfusion dependent but also the non-transfusion dependent patients as well. So we’re gearing up and getting ready to commercialization to go, launch in thalassemia in 2025 potentially, followed by back to back launch in sickle cell disease in 2026.
Brian Goff: And then, I was just going to say that’s great, Tsveta. And I think everybody can sense of excitement about what we have in front of us and I was just going to ask Sarah to make a comment about the progress with RISE UP Phase 3 for sickle cell.
Sarah Gheuens: Exactly because we’re equally excited to move towards those launches, so we are heavily focused on our Phase 3 enrollments of course right now. The trial is progressing as we are anticipating, there’s a lot of enthusiasm both within our teams and of course by the investigators as well, and so everything is on track to deliver to the milestone that we have set out for this year.
