Eric Joseph: Thank you. I just wanted to touch on vatiquinone and FA. It’s nice to see that opportunity back on the table. Can you just talk a bit more about sort of what has got FDA a little more constructive? Were they — was any new data from the open-label extension discussed? Or is it more about just sort of getting them on board with stability of a key functional endpoint? And just to — just kind of looking back on your commentary where they previously seem to want a confirmatory study. If you proceed with an NDA submission here, that would be for full approval or accelerated approval? Thanks.
Matthew Klein: Yes. Thanks for the question, Eric. So, the discussion with the agency really focused on the upright stability scale. I think as we’ve talked about when we started the MOVE-FA study, what wasn’t quite appreciated was that for the population you were looking at ambulatory patients, the only sensitive portion of that scale is the upright stability scale. Now, over the past couple of years, there have been several publications, and there’s also been an FDA-funded study looking at Friedreich ataxia patients. All of these studies have shown clearly that if you want to assess the treatment effect in a young adolescent ambulant patient population that the upright stability is the only way to do it. In fact, if you even look at the placebo data in our trial, you see that the placebo group barely changed on any of the other parts of the mFARS.
It was really only on upright stability that you see disease progression in that population over 72 weeks. And so when you are able to show those data and talk about those data and provide evidence to the agency, including evidence from the study they funded, it becomes very clear that while the primary endpoint itself at mFARS didn’t hit, we demonstrated a significant benefit on the only thing you possibly could show significant benefit on disease progression and that’s the upright stability of scale. So, I think those data and that understanding along with the supported evidence of the fatigue scale, which had also statistical significance is well-recognized as the most burdensome symptom for FA patient some correlation with walk test, all of that together, I think, was very helpful in having a constructive discussion with the agency and being able to talk about a path forward to NDA-based on the MOVE-FA data.
We have not done the analysis yet of the open label beta. Those weren’t shared. We’ll obviously prepare an analysis plan for those data and share with the agency kind of doing those analyses. In terms of this being accelerated or full approval, we’re still having those discussions at this point. But what we’re most excited about, obviously, is being able to have the potential to submit an NDA based on the MOVE-FA study and still — what is still a significant unmet need for pediatric and adolescent Friedreich ataxia patients and also to be able to have a therapy that would provide that 50 ambulatory patients who are young adults or an adult age as well.
Eric Joseph: Okay. I appreciate the commentary there. Maybe just on the sequencing of the open-label incision analysis and showing those data with FDA. I guess, will you be updating the Street with those data ahead of further interactions with the agency?
Matthew Klein: Yes. So, we expect those open-label data to be collected over the next several months and would expect them to complete the analyses once they collect all the data. We’ll also be doing an analysis of the original study. As you know, we’ve previously shown in the long-term follow-up from the initial vatiquinone study, we had a highly significant benefit when comparing those patients treated for 24 months versus an age-stage natural history match. We’ll be updating that analysis as well, including that as a source of confirmatory evidence. To the exact sequencing of having the data share in the FDA and updating The Street, we’ll certainly keep The Street posted as we move towards the NDA, including a pre-NDA.
Eric Joseph: Okay, great. Thanks for taking the questions.
Operator: Thank you. One moment for our next question, please and it’s from Jeff Hung with Morgan Stanley. Please proceed.
Jeff Hung: Thanks for taking my questions. For Translarna, are you aware of any communication between the EMA and the Brazilian health regulatory agency after the recent EMA decision given their data sharing agreement? Roughly how much you come from Brazil? And then I have a follow-up.
Matthew Klein: Yes, Jeff, we’re not aware of any correspondence. I think Brazil has traditionally been quite independent. We expect that to continue to be the case. And the indications we’ve had is that they will continue to act independently and making their assessment of the benefit of Translarna.
Jeff Hung: Okay. Thanks. And then for the sepiapterin NDA commission, what other data might be needed to be on the tox data? Could the FDA look for clinical data versus Kuvan in classical PKU patients? Or have they ever asked you or sense about running ahead study against Kuvan? Thanks.
Matthew Klein: Yes, as we’ve previously talked about, the only outstanding or the only gating item for the NDA submission was the completion of the mouse study. We started that as expected in December. Now, that we have visibility on those timelines, we look forward to discussing being able to possibly submit the NDA sooner than the third quarter. So, we’ll obviously look forward to those discussions. In terms of comparison to Kuvan, I think we — that’s something we’ve never been asked for. In fact, what we’ve been able to show FDA and other regulatory authorities as well that we had in the Phase 2 study, which was a head-to-head comparison with Kuvan which shows statistically significant benefit of sepiapterin over Kuvan. And then, of course, the APHENITY study, where we had a number of patients, 27 patients who came in the study on Kuvan we had washed out of it, and then we had a 50%, roughly 50% greater lower phenylalanine [ph] once those patients pushed over to sepiapterin, again, clearly demonstrating that we’re able to provide significant greater benefit to these patients.
