Gilmore O’Neill: We designed our discovery group and scientists designed and selected the combination of Cas12a with the specific targeting of the HBG1/2 promoter using a set of empirical experiments to determine what was the best approach to driving not just fetal hemoglobin expression, but robust erythroid output that would be — or red cell output for the bone marrow that would be independent of erythropoiesis or anemia. And those empirical experiments really determined that approaching or directly targeting the HBG1/2 promoter would be better. And that was the original design hypothesis. The nonclinical data — preclinical data actually supported that, showing robust erythroid output in comparison to other approaches as well as robust fetal hemoglobin expression.
And indeed, that is what we have seen as we disclosed in our first sharing of the data or cut of the data from our RUBY study. And so, obviously, it is — we haven’t seen enough data in our EDITHAL patient. But what I can say is that RUBY has certainly demonstrated data that are consistent with both, the preclinical data, which were supportive of the original biological and therapeutic hypotheses.
Operator: Our next question is from Phil Nadeau with TD Cowen.
Ernie Rodriguez: This is Ernie Rodriguez for Phil. Thanks for taking my question. On the on the sickle cell program, have you met with the FDA to gain better visibility on the regulatory path? And then, a second question on the TDT program. For the year-end update, would that include only the sentinel patients that you initially dosed, or will you disclose additional patients? And if you will be disclosing additional patients, are you planning on reporting when you switch from sentinel dosing to parallel dosing?
Gilmore O’Neill : So I think what I’ll do is ask Baisong. I’ve actually — I’ll keep track of the question. Baisong, if I’d ask you just to answer the question on the FDA and the regulatory interactions.
Baisong Mei : Yes. Thanks for your question. So, we certainly have a lot of engagement with FDA. As you see that recently, we have the orphan drug destination. And from the registration perspective, we previously announced that we actually have the alignment on the potency assay with the FDA, which FDA will consider this efficacy data can be supporting registration. And we will have further engagement with the agency to align on the total registration package for the BLA submission, which is also planned. And your second part of the question is about the beta-thal data. So, we are moving really along with the EDITHAL study, and we expect that we will have data by year-end, more than sentinel patient. And so, we’re looking forward to share that data by the year-end.
Ernie Rodriguez: And you are — more than sentinel patient, so are you planning to disclose when you going approve to continue parallel dosing before then?
Gilmore O’Neill: So, what we are actually planning to do is — I think the key thing is we’re on track to get the data for readout at the end of the year for that initial readout at the end of the year. We haven’t determined if we’re actually going to share that. But I think the important point is that we are well on track to disclose good initial data for the end of the year.
Operator: Our next question comes from Rick Bienkowski with Cantor Fitzgerald.
Rick Bienkowski: I guess, I’ll expand a bit on the last question on the path towards registration for EDIT-301. 20 patients is a pretty substantial cohort size in sickle cell disease. So, do you have any sense of how many patients’ worth of data you will need for a registrational filing?
