The following is excerpted from the question-and-answer section of the transcript.
(Questions from industry analysts are provided in full, but answers are omitted - download the transcript to see the full question-and-answer session)
Question: Kelly Shi - Jefferies LLC - Analyst
: Okay. Terrific. Maybe let's take a deep dive into that PKU data and the fee reduction looks very, very deep across both mild and the classic PKU
patients. There I have, it sounds like a debate, a recording, that patient at baseline in classic PKU population, it seems a little bit lower if you compared
to the definition of classic PKU patients.
So what is your feedback on that? And what is your selection criteria for the classic PKU patients on this trial and also compared to other trials? And
if you look at a classic PKU patients, how do you think about their [phenitus ray] data actually look like relative to others.
Question: Kelly Shi - Jefferies LLC - Analyst
: Okay. Great. And also, regarding the follow-up time, you now have six weeks data, and the patients are being followed up in a 12-month open-label
extension period. Have regulatory agencies guided on a minimum follow-up time for the NDA filing and also your timeline on that?
Question: Kelly Shi - Jefferies LLC - Analyst
: Okay, terrific. And also, the classical patient data looks very impressive but relatively in a small end. So if regulatory agency ask for additional patient
data, would you be set to start a new trial or the milder patient population opportunities are substantial enough?
Question: Kelly Shi - Jefferies LLC - Analyst
: Okay, great. And let's say FDA agreed on a broad label. And so how do you think phenitus ray position in classical population target, a younger
population compared to Palynziq? How do you think about the market opportunity in classical patient population?
Question: Kelly Shi - Jefferies LLC - Analyst
: Terrific. Just still little bit early, but curiosity of thoughts on the pricing of phenitus ray. I mean, clearly in the Kuvan unresponsive patients and
classical, you have the advantage of setting price. However, for the Kuvan responsive patients, although you have like efficacy superiority, but we
have several generics of Kuvan actually in the market. So how do you think about a sweet spot?
Question: Kelly Shi - Jefferies LLC - Analyst
: Great. And there's a more specific question about the treatment protocol. So in the Phase 3 part two, you have this titration up from 20 milligram
to 60 milligram. Just curious where this titration has to be implemented in the FDA label.
Question: Kelly Shi - Jefferies LLC - Analyst
: Great. And to maximize the market opportunity for phenitusray, after you just touched upon, but I just want to elaborate on this. Besides US and
the EU, what do you think about the other market opportunity because PTC has a very unique, commercial structure, I would say. Are you also
targeting like South America also at populated regions, for example, in Asia and Southeast Asia?
Question: Kelly Shi - Jefferies LLC - Analyst
: Great. And then lastly, on PKU, it's still I'm only talking about the commercialization plan in terms of the size of sales force and the targeted physician
group. But if that occurs, I think you guided a 15% reduction in OpEx for 2023. So does this actually include the sales force building for PKU.
Question: Kelly Shi - Jefferies LLC - Analyst
: Okay. Super helpful. And now switch to another investor super focused program 518. You're going to have the initial 12-week data update in Q2.
First, can you elaborate on what are the specific data to be included in this update?
Question: Kelly Shi - Jefferies LLC - Analyst
: Great. And how should we think about setting a bar on the, let's say, Huntington protein reduction level and to build a strong confidence in you
that we should actually really advance and extend this program, especially given that AMT-130, two-year functional study is going to come this
year as well. And so how do you leverage those data sets in terms of the relationship between function and protein, mRNA level? And I think about
your program development plan.
Question: Kelly Shi - Jefferies LLC - Analyst
: Great. And quickly on the Phase 2 trial and regarding the clinical hold in the US, like I wonder, you expected this kind of lift and what do you think
about a follow-up data FDA require on safety?
Question: Kelly Shi - Jefferies LLC - Analyst
: Great. And moving to vatiquinone. So for MIT-E program, through our proprietary research, we think 40% placebo-adjusted seizure reduction is
really high bar. And how do you think about that? And also given that the patient population is very heterogeneous, just assumption and hypothesis,
if you'd do the trial data actually did not meet the bar primarily. And do you have a Plan B to think about to pursue a path in subgroups of patients.
Question: Kelly Shi - Jefferies LLC - Analyst
: Great. And then lastly, Upstaza. It's a very active drug, and can you give us an update on it's US BLA filing?
Question: Kelly Shi - Jefferies LLC - Analyst
: Terrific. And thank you for a very comprehensive and productive discussion.
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