Dae Gon Ha: Good morning, guys. Thanks for taking our question. I apologize. It’s actually a two-part question. But just to clarify on the reni-cel progress in RUBY, if I heard you correct 18-dosed, I thought the prior conversation was 20-dosed by January. So can you talk about sort of the dropouts there? What was the reason behind that? And then another clarification on the FDA side, when you talk about differentiation, have you guys actually engaged them on the angle you’re taking on the differentiation, whether total hemoglobin, or end organ function? How are they perceiving that in terms of the conversation? Thanks so much.
Gilmore O’Neill: Thanks very much, Dae Gon. First of all, I think we’re actually very happy with where we are with our dosing, 18 patients dosed. And that really has us on track with that dosing pace to get us on track for a presentation of a substantial data set in the middle of the year. And actually, with regard to our driving towards BLA. We have not had dropouts. So I just want to be sure that there’s no confusion about that. And I think the final thing is that, you know, Baisong and myself with our clinical development experience, and particularly when you’re dealing with complex therapeutics like that, you’re going to get some waves, ups and downs and waves of not just enrollment, but dosing, particularly around scheduling, around holiday periods, et cetera.
So as they saw and also said we have many more patients scheduled for dosing in the coming months. And as I say, remain on track for a substantive data set in the middle of the year. With regard to differentiation and our conversations with the FDA, we have actually highlighted our potential differentiation, the mechanistic differences behind that, et cetera. But I think it’s too soon to comment on where the FDA and where our discussions with the FDA are on that.
Dae Gon Ha: Great. Thank you very much.
Operator: Our next question is from Debjit Chattopadhyay with Guggenheim. Please proceed with your question.
Ry Forseth: Good morning. This is Ry Forseth from Debjit’s team. Did the alignment with the FDA include any feedback on off-target editing, profiling akin to sort of the AdCom’s criticism around CASGEVY’s characterization for the breadth of genetic diversity? And our second question is, so the yet to be disclosed progress are you going to offer proof-of-concept I mean what characteristics of this program are you most excited about? The market size, the opportunity for first-in-class, the specific editing chemistry, et cetera?
Gilmore O’Neill: Thanks very much, Debjit. So let me actually pass the first question to Baisong.
Baisong Mei: Yes. Well, we have continuous engagement with FDA. So we are looking, the engagement is scientifically driven, is to understand the science of our molecule, the data we have, and then how the patient will manage it. And we have a whole range of engagement with FDA, from preclinical, CMC, to clinical. So because, as Gilmore mentioned, we have an armed response destination, and we have a lot of leverage and a lot of opportunity to actually engage with FDA. So we are very happy with the collaborative nature of the engagement. And can I just add to that is that, as we said before, when we actually watched the AdCom discussion, we were very gratified, by what we heard and saw, because our confidence, both in the comprehensive nature of our off-target editing, oversight package, was actually very robust relative to the discussion of the AdCom.
And frankly, our off-target editing data package is actually very good, and not surprisingly, because we are using our own engineered AsCas12a enzyme, which is a high fidelity, as well as high efficiency enzyme. And it’s worth saying that in our hands and in the hands of others, off-target editing is not detectable across a genome wide screen as opposed Cas9. So feel very good about that. And then with regard to the in vivo characteristics, I think I just want to say, as I said before, that the key things, or factors that we are focusing on is to select a set of targets that are high conviction based on their potential for critical differentiation from the current standard of care. And it actually does include a number of variables, including the probability of technical success, as well as regulatory success and commercial success.
Ry Forseth: Thanks for the rundown.
Baisong Mei: Thank you.
Operator: Our next question comes from Phil Nadeau with TD Cowen. Please proceed with your question.
Phil Nadeau: Good morning. Thanks for taking our question. Our question is on manufacturing. Can you remind us where you are in the scale of process in commercial, manufacturing scale process? And in your discussions with the FDA, have you agreed upon CMC package? And in particular, is there a requirement for patients in RUBY to be dosed with the commercial material? Thanks.
Gilmore O’Neill: Thanks very much for your question. From a CMC point of view, we actually are in a very good place. We have, as you know, had discussions with the FDA and are actually progressing very well along that line. We actually are, as we have our building, our commercial capacity, and obviously that capacity will be ready for the demand that will exist at the time of our launch and is ready for supporting demand beyond that launch. And then with regard to the processes, I would say we’re making excellent progress there in support of our BLA so that we would be BLA ready and inspection ready at that time.
Phil Nadeau: Thank you.
Operator: Our next question comes from Jay Olson with Oppenheimer & Co. Please proceed with your question.
Jay Olson: Oh, hi, congrats on all the progress and thank you for providing this update. Our question is about your In vivo program. Can you talk about how and when you’re planning to share preclinical proof-of-concept? And since it seems like there’s two undisclosed targets in your corporate deck, are you planning to share preclinical proof-of-concept for both programs? And also, any thoughts you could share on your choice for editing tool and delivery tool? Thank you.
