Gilmore O’Neill: Thanks very much, Phil. With regard to recruitment, no, we do not expect any change. We believe that our enrollment will continue to be robust. I’ll pass that to Baisong, who can tell you about his personal experience and conversations with sites and investigators.
Baisong Mei: Thanks, Phil, for your question. Really that I’ve been continuing to visit and study sites, I see really very strong momentum and feedback about it and we actually have many patients on our list for this trial. So we actually do not see the impact. So we continue to see the positive momentum. And not only now, but I will see it for next year and we will continue to see the momentum on that.
Gilmore O’Neill: And indeed, the investigator has said that notwithstanding approvals, this is still an area that they are particular with regard to our therapy and the trials. You asked the other question about differentiation and with regard to the time to actually see differences in total hemoglobin and then what some of the more downstream clinical impacts would be around fatigue or other outcomes. And I’m going to ask Baisong to talk about that.
Baisong Mei: Yes, yes. Yes, so this is actually a very important question we are looking into that is as I mentioned, we look into three categories of clinical endpoints for this differentiation. Certainly, that for hematological parameter you will be taking shorter time to see and for the patient portal outcome for example, you specifically mentioned the fatigue, usually based on my experience in other studies that when you do this kind of convert — when you do this kind of see this patient with reported outcome usually takes six months for the severe disease, you see something then usually takes six to one year, you’ll see some kind of improvement, but you monitor longer, you will see much more impact for compared to the baseline.
So we are very optimistic and confident that we’ll be able to see something in that direction for patient reported outcome on that. And the other category I mentioned is also for the end organ damage and we actually look into the cardiac, pulmonary, liver, CNS, and as well as the kidney. So we’ll also see that looking forward to see the improvement. This area is quite relatively new, but there are publications for allogeneic bone marrow transplant for sickle cell patients, for example in the brain, blood vessel, the vascular system in brain and also in cardiac system. So there are some reports relatively limited see that allogeneic transplant for sickle cell patients could potentially actually improve organ function. So we’re looking forward to that direction.
Gilmore O’Neill: Yes. Phil, one of the things I would say is that, you know Baisong and I have been around the block long enough as drug developers to know that when you start applying new outcomes measures in clinical trials using potent new medicines that have sort of have an unprecedented potency in disease, your ability to absolutely firmly predict the absolute time point, the number of patients, et cetera, needed to actually demonstrate that benefit can vary and require additional work. So while we are very enthusiastic about the work that we’re doing here, we also are pragmatic and experienced enough to know that we will see hematologic parameters quickly. We may see end organ functional physiologic parameters in a slightly longer-term and then with regard to other outcomes, some of that will be, as I say, we’re optimistic, but we have to just temper that with the realism that it may take somewhat longer.
Phil Nadeau: That’s very helpful. Thanks again and congratulations on the progress.
Gilmore O’Neill: Thanks very much.
Operator: The next question is from the line of Yanan Zhu with Wells Fargo. Please proceed with your question.
Yanan Zhu: Hi, thanks for taking my questions. So I was wondering a focus at the AdCom was the adequacy of the number of patient samples tested for off-target and whether that’s enough to characterize the risk in certain patients with genetic variants. I think I was wondering in your work — in your off-target analysis work, are you targeting again single-digit sample numbers or are you targeting a number significantly higher than that? The next question is about percent fetal hemoglobin as a differentiator I think you talked a lot about total hemoglobin, but I was wondering based on the data you have reported so far and also in abstract at ASH, seems like you had three patients of your first four patients who had greater than 50% fetal hemoglobin.
So I was wondering about your confidence of that being replicated in additional patients and also that being a differentiator. And lastly, I was wondering about your thoughts on whether there is a correlation between total hemoglobin and hemolytic markers and whether you can comment on your thoughts there. i.e. higher — maybe at a patient level, whether a higher total hemoglobin is correlated with better hemolytic marker observations. Thank you.
Gilmore O’Neill: Thanks very much, Yanan. So I’m going to try and choreograph a set of answers to a complex set of questions, if you will, or quite diverse set of questions. So with regard to the advocacy sample, I think the first thing we should do is just remind ourselves that the discussion the very what I would say the informed discussion at the AdCom demonstrated that a robust evaluation of at risk really showed that from an off-target point of view, the risk management, even with the data set presented the AdCom was actually very good. I will say that we are using additional and a multiplicity of orthogonal in silico and vitro and need some in vivo that’s on the iconic state, but in silico and in vitro assessments, which go well beyond what was shown at the AdCom in our data package.
I’m not going to go into the specifics of the numbers of patients just to say it’s more and obviously we share more detail about that at an appropriate time in the future. I think the other thing about the variants again, I just want to reaffirm I thought actually that the discussion by the geneticists at the AdCom was very illuminating. I thought both parties, the experts on the panel as well as in the sponsor, really articulated very clearly how the nature of variation, the nature of common ancestry for all humanity, and how we can really manage and identify variants and the risks associated with that. I think it was a very robust discussion and again, it gave us great confidence in our management of risk and the data package that we’re generating there.
Linda, I don’t know if you wanted to answer that.
Linda Burkly: No. I think that was a very good summary. I think that was a very good summary, Gilmore. I’m not going to add it.
