Matthew Klein: Yes. I think we’re — it’s really luxury. The Friedreich ataxia community has really been a model community in doing the necessary hard work of creating a robust patient registry. The FA [Indiscernible] natural history registry is a robust repository of patient data that has several years’ worth of data on things like the mFARS, including upright stability scale. And this is something that Reata was able to leverage as part of the NDA, and we would look forward to doing the same. I think the FDA acknowledges that. I think the FDA has publicly acknowledged the geo that the Friedreich ataxia community they’ve done in building this registry and obviously, it’s something that’s incredibly useful to develop — drug developers like us, like Reata and others who can now leverage that natural history database to contextualize the long-term beneficial effects of therapies.
So, I think there’s no question that this is the registry. We will has needed to develop a statistical analysis plan and precisely details how we’ll do what will be a propensity score match with — to ensure that we have an apples-to-apples comparison between the patients in MOVE-FA and vatiquinone and the natural history patients, and that should provide us the necessary natural history data — or the long-term treatment data needed to provide that confirmatory evidence of the NDA.
Peyton Bohnsack: Great. Thank you so much for taking our questions.
Operator: Thank you One moment for our next question, please and it’s from the line of David Lebowitz with Citi.
David Lebowitz: Thank you very much for taking my questions. Could you compare the regulatory process for 505(b)(2) and 505(b)(1)? And talk about how the data to this point for sepiapterin fits into the submission? And what additional components — or different ways of looking at the data might be required by the FDA?
Matthew Klein: Yes. Thanks David. I think just for context, as we’ve talked about, the initial sepiapterin development path was 505(b)(2), which was a decision made by Sensa when they were developed in the compound, I think it was likely thought to be a path that would be maybe faster or less resource intensive. But when we license the therapy, and it’s very clear, it is not the appropriate path. That’s more — it’s really for a molecule like sepiapterin. sepiapterin has novel composition, novel mechanism of action, novel biodistribution, novel pharmacology, and clearly differentiated therapeutic benefit. So, it doesn’t fit into the sort of need to 2505(b)(2) paradigm. It’s a novel therapy that is and should be part of the 505(b)(1) development pathway.
As such, it’s a necessary then to provide a full slate of nonclinical studies, including things like right pharmacology studies, toxicology studies, internal fetal studies, all those types of juvenile toxicity, all of those studies then become necessary to be part of our program, all of which we’ll have. And in terms of being ready to submit the NDA and the 505(b)(1), as we said, the only outstanding item is the study, which I mentioned earlier in the call. So, it’s really a matter, I think, it was probably not appropriately started in 505(b)(2) pathway, and it was really not a clinically prolongs for a novel differentiated therapy like sepiapterin 505(b)(1).
David Lebowitz: Does the FDA require any type of head-to-head comparisons in this particular process?
Matthew Klein: Not at all. I think the one thing we could say is — I think we’re in a situation that is precedented. There have been approved therapies for PKU. There’s a well-established clinical trial endpoint and what the FDA likes to see and that’s exactly what we follow. Including the sepiapterin registration program looks a lot like the Kuvan program in terms of having a responder analysis to identify those that responded, then having a placebo-controlled study and then having the necessary data to demonstrate durability and long-term safety, all of which we have. I say the only different a program is a significantly greater responder rate, significantly greater magnitude of treatment benefit. So, those are the components of the data needed to support the NDA submission is for the efficacy. It’s the evidence of effectiveness that the evidence of effectiveness that we have, and we look forward to be able to submit that NDA as soon as possible.
David Lebowitz: Got it. And just jumping over to FA. Have you received the minutes from the meeting yet? And what are the next steps?
Matthew Klein: Yes. So, I think at this point, where we are is we’re still, as I mentioned, having some back and forth with FDA regarding whether this could be an accelerated approval or full approval. That’s something that we look forward to getting to correspondence on in the near future. And I think for us right now, it’s also moving forward, collecting the open-label data and getting together physical analysis plans that can support the confirmatory evidence. And so that’s what all our team is focused on right now.
David Lebowitz: Got it. Thank you for taking my questions.
Operator: Thank you. One moment for our next question, please and it comes from the line of Gena Wang with Barclays. Please proceed.
Gena Wang: Thank you. I would just ask one more question regarding vatiquinone in FA. So, did FD suggest any specific statistical methodology to analyzing data since this will be comparing to the history data as well as open-label extension study?
Matthew Klein: Yes. Thanks Gina. They were not prescriptive. I think we’ve gone to them and that we would look to do a propensity analysis approach. Again, we’re in a realm here of precedent. They recently approved an NDA for SKYCLARYS based on a study — the placebo-controlled study along with open-label data compared to the FA natural history data and seasonal propensity score matching. So, we have a lot we can follow here. And — but to be sure, we’ll submit the fiscal analysis plan that will fully detail our approach not only in the propensity model, but also into what likely to be a mix effect modeling to provide the appropriate longitudinal estimate of treatment benefit relative to natural history.
Gena Wang: Okay. And very quickly, if we give a guidance, what type of data you need to hit in order to could be approvable?
Matthew Klein: From the open-label registry?
Gena Wang: For FA?
