And yes, again, very excited to get going on this. For your second question around Phase 3 dose selection for sickle cell disease, obviously, we are very excited about the data of the Phase 2, and we are very fortunate to have both doses show benefit risk. Profile that was favorable. We have pre-specified criteria in the protocol and the team had time to now look at all of the data. So we followed that framework and selected the 100 milligrams. We have not disclosed further details on the data. We mentioned that we have submitted the abstract to ASH, and so are now awaiting the outcome of that. And then we are hopeful to be able to provide all that detail at that conference.
Brian Goff: And Greg, maybe I will just tag on too and say, I always love to take the opportunity to speak with pride about Sarah and her entire R&D team. This is just a great example of the excellence operationally that we have and the efficiency of the design of the RISE UP Phase 2/3 trial and the fact that we were prepared for both doses. We were thrilled to see that both doses were effective. And now that we have the 100 milligram dose, the fact that we can proceed in the fourth quarter with the first patient dosed in the Phase 3 trial, I think is again, just a mark of excellence and a real point of pride for the organization.
Operator: Our next question comes line of Divya Rao from TD Cowen.
Divya Rao: Just two from us. We are just curious, what do you define or how do you define success in the MDS trial? I know that there are other, you know, several mechanisms that are being tested in this space. Do you view those as competitive or do you see those more as opportunities maybe to build combinations with AG-946. And then I have a follow-up.
Brian Goff: Yep. Thanks Divya. I will just start by saying, as is the case with all the disease areas that we are focused on, we have a very different mechanism of action with pyruvate kinase activation. And of course, you know, the question for low risk MDS, this is with our other PK activator AG-946, and I know Sarah will be eager to talk about what we are awaiting in terms of the Phase 2a data.
Sarah Gheuens: So, yes, thanks for the question. So I think for the MDS program, one, I want to highlight here again that the team has done an amazing job on enrollment of that Phase 2a program. I think it also highlights the enthusiasm of the investigators for this mechanism of action for MDS patients. We have not declared our framework for MDS to define success, but it is a Phase 2a. So we are indeed looking for a signal of efficacy and favorable safety and then our setup if that is there, then we are set up to move fast into a Phase 2b in which we will do a proper dose finding. It is indeed a market that is evolving, and it is, I think it speaks to that this is also a market that is ripe for a change. And we do believe that with this very differentiated mechanism of action, which is not being currently studied by, or not assessed far advanced by others, that we really are set up for success there as well.
And then I think what cannot be underestimated is that ours is also an oral therapy, which provides a convenience of use for a patient population that is typically an older patient population.
Divya Rao: That is really helpful. And then just a quick question on the sickle cell program, could you remind us on if you just closed the powering assumptions for the Phase 3 trial and then have you discussed the 100 milligram dose with the FDA or is that just mostly based on internal discussion and analysis of the data?
Brian Goff: So for the sickle cell disease program, the 100 milligram dose, so right now, this is the internal framework that we have applied and all of the data that have assessed, we are very excited about an end of Phase 2 meeting with the FDA. We always look forward to our, the constructive dialogue that we have together. And, you know, it is always great because I do feel like we are all wanting the same thing, right. For across all of our programs we are really shooting to deliver medications that have a favorable benefit risk and can provide change to patients. So we are always very pleased with the constructive dialogue that we have. In regards to the powering assumptions. So obviously the Phase 3 is much bigger sample size than the Phase 2.
