The final point, obviously, we know very well from the Translarna experience is to be able to be able to demonstrate that you can collect more data on patients to support the sport conditioning or approval and to confirm that you have a favorable benefit balance. We obviously believe there’s many sources of additional data that we could generate to confirm the benefit is profile. So again we believe we need all of the necessary criteria to additional authorization, and we look forward to discussions with the EMA to gain alignment within on this point.
Jeff Hung: Great. Thank you.
Operator: Thank you. One moment please. Our next question comes from the line of Alexander Xenakis of Truist Securities. Your line is open.
Alexander Xenakis: Hi. Thanks for taking my questions. Congrats, first of all, on securing the royalty financing deal. That’s great. Maybe two for me. One on sepiapterin. When might we see another cut of the Phe tolerance data? And then one on Translarna. And if you are able to overturn the conditional marketing — these ongoing conditional marketing motorization and have that ongoing study, but you don’t have the official sold marketing authorization. Have you done any market research to see how that would affect referencing countries worldwide and if they would be required to whole sales or not? Thanks.
Matthew Klein: Thanks for the questions, Alex. So first on the Phe tolerance, as we shared, we gave an update on the Phe tolerance data at the sepiapterin IEM meeting in Israel in September. Those were again really great data showing now with over 40 patients enrolled in the Phe tolerance protocol that we’re seeing patients move through and get to levels get to levels of Phe tolerance beyond the recommended daily labs. These are incredibly important data. As we said all along, the Phe tolerance component is brilliant for regulatory purposes necessarily, we have the sufficient efficacy data for that and we’re able to show in the long-term extension that we’re adding important durability of sepiapterin treatment effect as well as long-term safety.
This is really quite important one for differentiation is something Kuvan is never able to demonstrate and for physician adoption and for payer discussions, particularly outside of the US. On the Translarna front, the — look, again, we see the ability to keep the conditional authorization as a big win, not only how is doing for us, but really most importantly for the patients. I turn it over to Kylie, a few comments, Kylie, on the — what you think the global payer, in fact, could be a conditional authorization.
Kylie O’Keefe: Yeah. I think from a paper impact, I think it will be quite minimal, Alex. I think one of the things that the team has done an incredible job is with the conditional authorization that we’ve had over the last nine years is being able to secure a favorable pricing corridor and reimbursement and being able to maintain that over the years. So I think at this stage, where we stand, we don’t see any sort of negative impact from the continuing conditional authorization. And of course, we’ll continue to focus on it.
Alexander Xenakis: Okay. Thanks for taking the questions.
Operator: Thank you. One moment please. Our next question comes from the line of Joseph Schwartz of Leerink Partners. Your line is open.
Joseph Schwartz: Hey, thanks very much. I was wondering if you could talk about your publication plans for the APHENITY sepiapterin data. Will we see that published in a peer-review journal any time soon? And then I believe you have the option to go up to a 20-milligram dose of PTC518 in PIVOT-HD patients outside the US. So where do you stand on implementing that decision?
Matthew Klein: Yeah. Absolutely. I’ll take the — I think let me take the second question first, and then I’ll let Kylie answer the first question, second. So on 518. So we — as we talked about we shared the results from the 5 and 10-milligram dose groups, the first cohort of 32 in June. Those data from our standpoint were as good as they can be. We achieved every objective of that 12-week portion study in that first cohort of patients demonstrated a dose-dependent lowering of Huntington protein in the blood, seeing the differential exposure of PTC518 in the CSF relative to the plasma as a 10-milligram dosing seeing that, that ratio is 1.5:1 suggest that we’re getting even greater exposure, 518 in the brain and even potentially higher levels or greater lowering of Huntington proteins in the brain all of which is very, very important.
And of course, the other key plan is that we are doing all of this safely. The safety profile of the drug was quite strong in those first 12 weeks. We had no terminated serious adverse events. There were no NFL spikes, all very, very important, particularly given concerns that were raised over other HTT lowering therapies that have drawbacks that we’ve talked a lot about in the past. We said based on those data, we believe we may have the dose levels we need right now to get us where we want to be in terms of the ultimate goal of the program, which is being able to lower brain cell Huntington protein levels 30% to 50%. And so with the decision with those early data, while we had the ability to go up to 20 milligrams, the DSMB has supported us starting 20-milligram cohort.
The regulatory authorities and local ethics communities have approved us going into 2020. We’re still in a holding pattern. We want to understand a little bit more what the biomarker effects are with the dose levels we have now 5 and 10, but those very well may be sufficient to forget they want to be. So we haven’t issued those — the 20-milligram dosing yet. I’m not sure we’re going to need to, and we want to better understand the longer-term bile marker effects of the current levels before revisiting that decision. Why don’t I turn it over to Kylie to answer your questions around publication strategy for PKU.
Kylie O’Keefe: Yeah. Thanks Joe. We are absolutely getting the APHENITY study published in a peer-review journal. The team is working on that as we speak and is looking to target a high impact journal. And so the timeline for getting that published is obviously driven by the journal of choice. So we work — this is work in progress. The team is moving through this and we expect it to be published during 2024 pending the journal chosen.
