Joon Lee: Hey, thanks for the updates and for taking our questions. For the Angelman program, are you talking to CBER or the Neurology Department? And if it’s not CBER, would it be possible to request GTX-102 be reviewed by CBER? And the Phase II meeting, how strongly would you be advocating for MBRI as an approvable endpoint or has that ship already sailed? Thank you.
Emil Kakkis: Well, we’re under CBER. We’re actually in we said before in the psychiatry part of the neurology sciences group. And that’s where we’ve been the whole time. So, and they’re actually doing a great job. Tiffany is the leader of that group, but then we’ve had good meetings and she’s great to work with. So, I’m actually we’re very happy with the setting we’re in and how it’s going. So, they’re in CBER and there’s really no purpose. It’s not it’s really well characterized drugs. It’s not really gonna fit within the CBER mantra and there’s no benefit to us to doing that at this point. So, we’re comfortable where we are with that one. With regard to MDRI, we like MDRI, but it is something very different. While we had it in our Mepsevii program and it was used and had helped support the program, It’s still a methodology that’s new for FDA.
And we’ve had a lot of meetings. I’ve presented a lot of conferences. I think there’ll be growing support with it if we use it. So our plan rather than press our case is probably to put in a single primary validated type endpoint for them and then put our MDRI in as key secondary. That way we get the best of both. We manage what FDA may want or prefer and at the same time we get MDRI in there, which allows us to support the product. I do believe and my belief in the long run is that the MDRI will be a fundamentally new way and better way of doing particularly heterogeneous neurological disorder analysis. And once the FDA sees that in a large randomized trial, see how it performs and understand it, I think they’ll start gaining more appreciation why it’s a superior approach to analyzing clinical outcomes.
Operator: Our next question comes from the line of Joseph Schwartz with Leerink Partners. Your line is open.
Joseph Schwartz: Great. Hi, all. This is Will on for Joe today. Thanks for taking our questions and congrats on the progress this quarter. So, one for us on the DTX401 program. We recently saw the updated data in the ASGCT abstracts, which suggests that the cornstarch benefit rebounded favorably compared to the data shared last year. So just wondering if you could provide some comments on how you’re thinking about the durability of this treatment and how this may change your expectations, if at all, for the cornstarch reduction that we might see in the pivotal study later this quarter?
Emil Kakkis: Well, I don’t think that’s changed our opinion very much on that at all. I think the what we are noting over time is that the reduction in starch happens very quickly, but to get all the way down takes time and there’s some secondary factors. It does depend a little bit in the long run on how the doctor manages the starch. They have to get the starch down and get the glucose to come down, so that the gene therapy actually expresses. That the expression of the gene therapy is dependent on stimulating the promoter, because we’re using the normal GSD1a Glucose 6 Phosphatase promoter. So, there are some interesting features of how that operates, but we’re comfortable with where we are. We haven’t changed our expectations for the study.
We think that — we saw something like 50% reduction within a short period of time. But if you looked, it took a lot longer to get down and it was highly more dependent on how doctors were titrating in individual patients. But we’re very comfortable with what we’re seeing and we haven’t we don’t have concern yet on durability. We think it’s been good over the long haul.
Operator: Next question comes from the line of Brendan Smith with TD Cowen. Your line is open.
Brendan Smith: Great. This is Brendan on for Yaron. Thanks for taking the question, guys. Just a quick one from us on the gene therapy pipeline. I think you correct me if I’m wrong, but I think you recently said that you might file for GSD1a around the end of this year or early next year. Totally understanding that this is somewhat in flux. But I guess in light of the transition to the manufacturing, should we expect kind of similar timing between top line data and filing for OTC? Or would you expect that to potentially go more quickly after the manufacturing is in house? And then kind of along the same line, on pricing, is it fair to assume that both GSD1a and OTC would be priced similarly? And I guess, if not, what might be dropping the differences? Thanks.
Emil Kakkis: Yes. Well, the BLA, I don’t want to predict exactly the timing of filing. We have transitioned manufacturing internally. We’re running those — we’ll be running those runs. And we have to go meet with FDA to make sure, for example, whether they require of our manufacturing to be in the filing, right, at the time of filing versus can be submitted at, let’s say, during the filing. So those are factors that will impact the exact timing of filing. And we need to get the data and season in a pre BLA meeting and get that straight. So, we’ll put out a little bit more data. Our expectation though is probably going to end up being if it’s late in the year, it would be actually more likely next year to get all the pieces early next year.
But right now we don’t want to make a prediction because of some pieces we have to get straight. With regard to OTC timing, well, it’s a bit further out. I’m not sure I want to predict whether we’re going to how fast that’s going to go. What I can say is that if you look at everything we have and we don’t know that everything will be successful, but we have in front of us six BLA filings over the next three years or so, so something like that. So, we’re going to be busy, including three within the next year or so, right? So, we’ll be busy, and I’m sure OTC will have to be fit in once the Phase III is out. With regard to pricing, I don’t think there’s a big difference in how we price GSD1a and OTC. They’re very similar population sizes and severity of diseases.
OTC happens to have very expensive drugs like [INDISCERNIBLE], which a lot of patients use that you probably could justify pricing easier with regard to the cost reduction, assuming patients were getting off their other drugs. But right now, we haven’t put any stake in the ground regarding pricing. We’re listening and watching what’s going on and we’ll come up with a plan we get closer in.
