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PTC Therapeutics, Inc. (PTCT) Q4 2022 Earnings Call Transcript

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PTC Therapeutics, Inc. (NASDAQ:PTCT) Q4 2022 Earnings Conference Call February 21, 2023 4:30 PM ET

Company Participants

Kylie O'Keefe - Chief Commercial Officer

Stuart Peltz - Chief Executive Officer

Matthew Klein - Chief Operating Officer

Eric Pauwels - Chief Business Officer

Emily Hill - Chief Financial Officer

Conference Call Participants

Kristen Kluska - Cantor Fitzgerald

Brian Abrahams - RBC

Joseph Thome - Cowen

David Lebowitz - Citi

Kelly Shi - Jefferies

Tazeen Ahmad - Bank of America

Gena Wang - Barclays

Mike Riad - Morgan Stanley

Paul Choi - Goldman Sachs

Danielle Brill - Raymond James

Operator

Good day, and invited to nan PTC Therapeutics Fourth Quarter 2022 Corporate Update and Financial Results Call. At this time, each participants are successful a listen-only mode. After nan speakers' presentation, location will beryllium a question-and-answer session. Instructions will beryllium fixed astatine that time. As a reminder, this telephone is being recorded.

I would now for illustration to move nan telephone complete to Kylie O'Keefe, Chief Commercial Officer. You whitethorn begin.

Kylie O'Keefe

Good afternoon, and convey you for joining america coming to talk PTC Therapeutics' 4th fourth 2022 firm update and financial results.

I'm joined coming by our Chief Executive Officer, Stuart Peltz; our Chief Operating Officer, Matthew Klein; our Chief Business Officer, Eric Pauwels; and our Chief Financial Officer, Emily Hill.

Today's telephone will see forward-looking statements based connected our existent expectations. Please return a infinitesimal to reappraisal nan descent posted connected our Investor Relations website successful conjunction pinch nan call, which contains our forward-looking statements. Our existent results could materially disagree from these forward-looking statements, arsenic specified statements are taxable to risks that tin materially and adversely impact our business and results of operations.

For a elaborate explanation of applicable risks and uncertainties, we promote you to reappraisal nan company's astir recent yearly study connected Form 10-K revenge pinch nan Securities and Exchange Commission, arsenic good arsenic nan company's different SEC filings.

We will disclose definite non-GAAP accusation during this call. Information regarding our usage of GAAP to non-GAAP financial measures and a reconciliation of GAAP to non-GAAP are disposable successful today's net release.

With that, fto maine walk nan telephone complete to our CEO, Stuart Peltz. Stu?

Stuart Peltz

Thanks, Kylie. Good afternoon, and convey you for joining nan call. I'm proud to stock PTC's 4th fourth and afloat twelvemonth results and our expectations for continued beardown capacity successful 2023.

PTC treats uncommon diseases by modulating cistron and macromolecule expression. Our strategy is to discover, create and commercialize products to build a robust pipeline of imaginable caller therapy. Our extremity is to present 1 caller therapy each 2 to 3 years.

I'm honored to study that PTC has been named nan victor of nan 2023 EURORDIS Black Pearl Company Award for Innovation. This grant recognizes and celebrates companies who person undertaken groundbreaking subject to beforehand uncommon illness investigation and improvement and is simply a testament to nan ngo and strategy of PTC.

We are readying a very breathtaking twelvemonth successful 2023, including nan ceremony of our 25th anniversary. And we're proud of what we've achieved to date. Our commercialized portfolio has 5 marketed products, positive a sixth merchandise for which we cod collaboration and royalty revenue.

In 2022, we achieved $699 cardinal successful full revenue, which is simply a singular 30% maturation complete full gross successful 2021. This gross accomplishment was contempt important FX headwind. And erstwhile calculated astatine changeless speech rate, it was $740 million, representing a 37% year-over-year growth. In nan 4th fourth of 2022, we achieved $167 cardinal successful full revenue.

We expect our maturation to proceed to accelerate successful 2023. As announced successful January, we expect our full gross guidance successful 2023 to beryllium betwixt $940 cardinal to $1 billion, which would correspond much than 30% year-over-year growth. We are continuing to beforehand nan wide and heavy pipeline of caller therapies that we expect to supply important maturation to our commercialized portfolio successful nan coming years.

I'm proud that these efforts person led to 7 promising improvement programs focused connected treating uncommon illness pinch precocious unmet aesculapian need, from which we'll person 4 important readouts successful nan first half of 2023, 3 of which are registration-directed studies. We expect results from nan APHENITY study for sepiapterin for PKU, for vatiquinone successful some mitochondrial illness associated seizures of Friedreich ataxia and nan 12-week information for PTC518 successful Huntington's disease. Matt will spell into this successful much item shortly. We're very excited astir Part 1 information for APHENITY study pinch sepiapterin and look guardant to nan results from Part 2 shortly.

In summation to these studies, we proceed to advancement enrollment successful our SunriseLMS proceedings for unesbulin successful leiomyosarcoma patients and our CardinALS proceedings for utreloxastat for ALS patients.

With coagulated maturation crossed our commercialized portfolio and galore caller therapies advancing successful our pipeline, we proceed to make beardown momentum for galore years to come.

I'll now manus complete to Matt for an update connected our improvement programs. Matt?

Matthew Klein

Thanks, Stu.

Our teams proceed to make advancement successful advancing important caller therapies from our pipeline to patients successful need. As Stu noted, successful nan first half of 2023, we will person results from 4 of our ongoing objective trials, 3 of which are registration-directed studies.

Let maine statesman pinch an update connected APHENITY, our world Phase 3 proceedings of sepiapterin successful patients pinch PKU. As a reminder, APHENITY is simply a double-blind placebo-controlled study successful which subjects are randomized to person sepiapterin aliases placebo for six weeks pinch nan superior endpoints being simplification successful humor phenylalanine level.

To enrich nan randomized organization for sepiapterin responders, location is simply a run-in shape during which each surface subjects person sepiapterin for 2 weeks. Only those subjects who show a simplification successful phenylalanine levels of 15% aliases much from baseline will beryllium randomized, pinch nan superior study organization consisting of those who person greater than 30% reduction. Importantly, each subjects entering nan placebo-controlled shape will acquisition a washout play of astatine slightest 14 days.

In January, we shared information from nan Part 1 run-in shape for nan first cohort of subjects pinch greater than 30% simplification successful phenylalanine levels. I will now supply an update connected Part 1 preliminary information for each subjects.

Overall, 156 subjects passed screening and completed nan Part 1 run-in phase. Of these 156 subjects, 102 aliases 65% had greater than 30% simplification successful phenylalanine levels from baseline. This is simply a very precocious responder rate, complete 3 times nan responder complaint recorded successful nan Kuvan responder study. When looking astatine nan magnitude of Phe simplification successful nan 30% sepiapterin responder group, location was a mean simplification of 66%, which is much than doubly that recorded successful nan Kuvan placebo-controlled phase.

Also, I want to constituent retired that nan 30% responder group includes 15 classical PKU patients, who had a mean phenylalanine simplification of 61.5%, which is simply a very awesome result. I'll adhd that location are further 5 classical PKU subjects who had a 15% to 30% simplification successful Phe levels during nan run-in phase. These Part 1 results including nan precocious responder complaint and nan mean phenylalanine reductions successful non-classical and classical patients proceed to support nan premise that sepiapterin tin perchance meet nan persistent unmet aesculapian request of PKU patients.

With nan precocious proportionality of subjects achieving an complete 30% phenylalanine simplification successful Part 1, nan superior study organization for Part 2 will beryllium over-enrolled by astir 25%, beyond nan first target of 80 subjects. Given nan clip required for these further subjects to acquisition washout and complete nan placebo-controlled information of nan study, past diligent past sojourn is planned to hap successful March and we expect results of Part 2 successful May.

Let maine now move to nan 2 registration-directed tests of vatiquinone, MIT-E and MOVE-FA. The MIT-E and MOVE-FA studies are based connected some nan beardown technological rationale arsenic good arsenic information from respective erstwhile studies successful which we person recorded grounds of curen use crossed cardinal illness endpoints.

The MIT-E study is simply a world registration-directed proceedings of vatiquinone successful patients pinch mitochondrial illness associated pinch seizures. The study includes a 24-week placebo-controlled shape pinch a superior endpoint of alteration successful observable centrifugal seizures from baseline. The placebo-controlled shape will beryllium completed successful March, and we now expect results successful nan 2nd 4th to let for information cleaning and database lock.

The MOVE-FA proceedings is simply a world registration-directed study of vatiquinone successful patients pinch Friedreich ataxia. The study includes a 72-week placebo-controlled shape and nan superior endpoint is nan alteration successful nan validated mFARS standing standard from baseline. Last diligent past sojourn for nan placebo-controlled shape will besides beryllium successful March, and we proceed to expect results of nan MOVE-FA study successful nan 2nd quarter.

Moving to our PTC518 Huntington's illness program. Enrollment is ongoing astatine our world sites for nan Phase 2 PIVOT-HD trial. As a reminder, PIVOT-HD is simply a 12-month placebo-controlled proceedings successful 2 parts. Part 1 is 12 weeks successful long and focuses connected PTC518 medicine science and pharmacodynamic effects, arsenic good arsenic biodistribution. Part 2 9 months successful long and focuses connected blood-based, CSF-based and radiographic biomarkers of disease.

The study initially includes 2 dose levels, 5 milligrams and 10 milligrams, pinch nan expertise to see a 3rd dose level of up to 20 milligrams leveraging nan titratability of nan molecule. As we shared astatine nan J.P. Morgan convention successful January, we person initiated further 5 milligram and 10 milligram dosing cohorts successful early Stage 3 patients. We expect results from nan 12-week information of nan proceedings successful nan 2nd 4th of 2023.

Turning now to Translarna. We precocious had an informal gathering pinch nan FDA during which we discussed nan imaginable way to an NDA resubmission. Based connected nan gathering discussion, we scheme to petition different Type C gathering to reappraisal nan totality of information collected to-date including dystrophin and different mechanistic information arsenic good arsenic further analyses that could support nan use of Translarna. We scheme to hole a petition for this gathering successful nan adjacent future.

Lastly, for Upstaza, arsenic we antecedently shared, nan FDA requested further bioanalytical information successful support of comparability analyses betwixt nan supplier merchandise utilizing nan objective studies and nan commercialized supplier product. We person completed these analyses and person provided nan results to nan FDA for reappraisal up of a BLA submission, which we proceed to expect to hap successful nan first half of 2023.

I will now manus nan telephone complete to Eric to supply an update connected our commercialized portfolio. Eric?

Eric Pauwels

Thanks, Matt.

It is breathtaking to spot nan awesome advancement of our late-stage objective pipeline and nan world commercialized squad is surely fresh to leverage our expertise and wide geographic footprint to bring these important treatments to patients. Our world customer-facing squad has delivered yet different beardown quarter, continuing nan important momentum built passim nan twelvemonth and closing retired what has been a very singular twelvemonth for PTC.

Our motorboat of Upstaza successful Europe is building momentum. The world DMD franchise continues to strengthen, and we spot our world commercialized description delivering important growth.

With nan 5th merchandise added to our commercialized portfolio, we delivered $128 cardinal of gross successful nan 4th fourth and an awesome $535 cardinal for 2022, which represents 25% year-over-year maturation for our marketed products.

Let maine commencement pinch Upstaza. We are pleased pinch nan first motorboat of Upstaza pursuing nan support successful nan EU. Last year, we treated commercialized patients successful Germany and patients successful France done nan early entree program. Importantly, we are pleased pinch nan first interactions pinch wellness exertion bodies successful France and Germany, which will further support pricing and reimbursement successful nan future. We expect continued maturation successful 2023 by treating patients successful different European countries, besides enabling cross-border curen options.

Lastly, to proceed nan growth, we will further attraction connected geographies extracurricular of Europe pinch further registration submissions and named diligent programs successful Latin America, nan Middle East and Asia Pacific.

Our DMD franchise continues to present robust results pinch $114 cardinal successful gross successful nan 4th quarter, which brings our 2022 DMD franchise to $507 million, an awesome 20% year-over-year maturation complete 2021. This singular accomplishment is contempt beardown FX headwinds and, erstwhile calculated successful changeless speech rate, it is $539 cardinal and 27% growth.

The fundamentals of nan Emflaza business continued to beryllium solid. Revenue successful nan 4th fourth of 2022 for Emflaza was $58 million. This brings full yearly Emflaza gross to $218 million, which is simply a singular 17% maturation complete 2021. Operational excellence drove continued caller diligent starts, wide entree and continued attraction connected precocious compliance and little curen discontinuations.

Turning to Translarna. We achieved $56 cardinal successful gross this quarter, which brings our 2022 gross to $289 million, which is an outstanding 22% maturation complete nan erstwhile year. Again, contempt important overseas speech headwinds, we proceed to spot maturation successful our main markets now that Translarna is successful its eighth twelvemonth of commercialization. Additionally, we proceed to push guardant pinch our geographic description into caller markets successful Latin America, Middle East, Northern Africa and Asia Pacific.

Now turning to Tegsedi and Waylivra successful Latin America. The attraction we person had connected building nan instauration of these therapies is delivering results. We person strengthened our position successful Latin America arsenic nan pioneers successful uncommon diseases pinch our caller support successful Brazil for nan 2nd denotation for Waylivra successful familial partial lipodystrophy, aliases FPL. This is nan first curen for FPL successful Brazil and nan first support globally for Waylivra for nan FPL indication.

As a reminder, Waylivra was antecedently approved for familial chylomicronemia syndrome and received Category 1 innovative supplier pricing successful Brazil.

For Tegsedi, we person received our 2nd group acquisition bid from nan Brazilian Ministry of Health, which we expect to fulfill successful nan first half of this year. And our discussions pinch CONITEC continues to progress.

Across nan region, we besides proceed pinch our geographical description pinch MAA filings for some Tegsedi and Waylivra, and we proceed to support and turn our diligent guidelines done early entree programs.

2022 was a awesome twelvemonth for our world customer-facing squad and has group america connected a coagulated trajectory for 2023. This has been a transformational twelvemonth arsenic we proceed our motorboat efforts for Upstaza, ample FPL successful Brazil and proceed to turn our DMD franchise up of our near-term pipeline readouts.

Now, fto maine move nan telephone complete to Emily for a financial update. Emily?

Emily Hill

Thank you, Eric.

I will return a fewer minutes to reappraisal our 4th fourth and afloat twelvemonth financial results. Please mention to nan net property merchandise issued this day for further detail.

Beginning pinch top-line results. Total revenues for nan 4th fourth were $167 million. This consisted of nett merchandise gross crossed nan commercialized portfolio of $128 cardinal and Evrysdi royalty gross of $40 million.

Translarna nett merchandise revenues successful nan 4th were $56 million, reflecting beardown maturation successful astir geographies, contempt important overseas speech headwinds. Emflaza had nett merchandise revenues of $58 million, representing 22% maturation year-over-year.

Non-GAAP R&D expenses were $175 cardinal for nan 4th fourth of 2022, excluding $14 cardinal successful non-cash stock-based compensation disbursal compared to $136 cardinal for nan 4th fourth of 2021, excluding $13 cardinal successful non-cash stock-based compensation expense. This year-over-year summation successful R&D expenses reflects further finance successful investigation programs and advancement of nan objective pipeline.

Non-GAAP SG&A expenses were $79 cardinal for nan 4th fourth of 2022, excluding $13 cardinal successful non-cash stock-based compensation disbursal compared to $74 cardinal for nan 4th fourth of 2021, excluding $13 cardinal successful non-cash stock-based compensation expense.

Our full gross for nan afloat twelvemonth 2022 was $699 cardinal for year-over-year maturation of 30%. This was impacted by important FX headwinds, which were calculated astatine CER was $740 cardinal and 37% year-over-year growth. This included DMD gross of $507 million, which represented 20% year-over-year maturation aliases 27% maturation astatine CER. Evrysdi royalties for nan twelvemonth grew 108% to $114 cardinal year-over-year.

Cash, rate equivalents and marketable securities totaled astir $411 cardinal arsenic of December 31, 2022, compared to $773 cardinal arsenic of December 31, 2021.

I will now move nan telephone complete to nan usability for Q&A. Operator?

Question-and-Answer Session

Operator

[Operator Instructions] Our first mobility comes from Eric Joseph pinch J.P. Morgan. Your statement is open.

Unidentified Analyst

Hi, bully afternoon. This is Hannah connected for Eric. Thanks for taking nan questions. Just a fewer from us. So, first, tin you break down conscionable immoderate of nan gross components successful your afloat twelvemonth 2023 gross guidance extracurricular of your DMD franchise? Just wondering really you're reasoning astir nan equilibrium betwixt Evrysdi and Upstaza? And I person a follow-up aft that.

Stuart Peltz

Yes. Thanks, Hannah, for nan question. Emily, do you want to return that?

Emily Hill

Yes, sure, I'm happy to return nan question. Thanks. We're looking guardant to our guidance for 2023 of $940 cardinal to $1 billion. That evidently reflects continued maturation expected successful nan DMD franchise. As you alluded to besides maturation successful Upstaza, Evrysdi, some royalty and milestone. There's a $100 cardinal milestone expected for crossing a income period for Evrysdi. And then, continued publication of Tegsedi and Waylivra. We haven't surgery retired specifically nan contributions of Upstaza and Evrysdi, but obviously, you tin spot now that Roche has Evrysdi approved successful complete 90 countries, quickly becoming nan modular of attraction successful SMA, and we expect important maturation going into adjacent year.

Unidentified Analyst

Okay. That's helpful. And then, conscionable moving connected to APHENITY. Thanks for providing updated information from nan run-in portion. Just wondering if you're capable to speak to nan variance of humor phenylalanine lowering that you're seeing successful that run-in study? And then, should we expect immoderate stratification mechanisms aliases criteria successful spot based connected magnitude of Phe simplification arsenic portion of nan Phase 2 diligent randomization?

Stuart Peltz

Yes. I deliberation that's a bully point. And I mean, 1 of nan things that we ever opportunity is that nan bully point astir this endpoint is nan biochemical marker, truthful we measurement nan magnitude of phenylalanine, and it's a comparatively unchangeable measurement.

Matt, you want to talk a small spot astir nan stratification and nan measurement?

Matthew Klein

Yes, absolutely. Hannah, acknowledgment for nan question. So, first conscionable obviously, we're really excited astir nan updated Part 1 data. I think, from what we reported successful January, we are seeing nan wide consequence complaint up from 61% to 65% and magnitude of Phe simplification for some nan non-classical and classical PKU patients is besides higher, which continues to springiness america a batch of assurance going into Part 2.

In position of your mobility astir familial variance, I judge that was your question, nan enrollment includes really nan afloat spectrum of familial variance, non-classical and classical. We didn't do immoderate circumstantial stratification aliases removal based connected immoderate circumstantial familial subtypes.

In position of nan stratification for Part 2, we did stratify nan randomization for supra and beneath 600 micromolar per liter, truthful that was nan 1 strata, arsenic good arsenic stratifying for greater than 30% consequence successful nan run-in shape and 15% to 30% consequence to run-in shape with, of course, nan greater than 30% organization being nan superior study organization for nan study.

Unidentified Analyst

And wrong nan greater than 30% patients that are moving connected to nan superior study population, should we presume that there's nary further stratification based connected what was seen successful nan run-in portion?

Matthew Klein

Correct. We predefined nan strata arsenic greater than 600 astatine baseline aliases beneath 600 astatine baseline, arsenic they participate nan placebo-controlled phase.

Unidentified Analyst

Great. And possibly conscionable 1 much if I could. Just wondering astir nan request aliases nan liking successful over-enrolling nan study comparative to your first study design. Wanted to cognize if that was borne retired of feedback from immoderate regulatory agencies.

Stuart Peltz

Yes. No, we were -- spell ahead, Matt.

Matthew Klein

Yes. That had thing to do pinch regulatory interaction. That was agreed upon -- nan protocols agreed upon pinch nan FDA and EMA anterior to nan commencement of nan study. This really reflected important liking connected portion of nan patients and nan physicians. I deliberation arsenic we've talked astir this clear unmet aesculapian request and desire for safe and effective therapies and what we saw was conscionable really important liking from centers passim nan world. And arsenic nan over-enrollment and nan delays successful getting to information really comes from nan truth that [indiscernible] there's still a ample number of investigators, cardinal KOLs who had patients, they really wanted to get into nan study. And of course, we judge that nan greater number of patients ever strengthens aliases heightens that probability of occurrence successful nan trial.

Unidentified Analyst

Okay. Very helpful. Thanks for taking nan question.

Operator

Thank you. Our adjacent mobility comes from Kristen Kluska pinch Cantor Fitzgerald. Your statement is open.

Kristen Kluska

Hi, everyone. Thanks for taking my questions, and congrats connected nan 25-year milestone. First mobility I had was, for PKU, tin you springiness america your consciousness aliases preliminary thoughts connected what nan payer's consequence mightiness be? Whether location mightiness beryllium a generic Kuvan measurement edit aliases possibly really it could disagree crossed different populations specified arsenic those pinch classical?

Stuart Peltz

Yes. So, yes, this -- I deliberation this is simply a bully point. And I deliberation you request to retrieve that while Kuvan was nan first drug, it had a ample diligent organization that it was ineffective to. And what we spot is that astir if you look astatine possibly Palynziq and Kuvan together, it's still astir apt close, but not precisely 10% of nan wide population. So, you person a immense diligent organization of patients that are not satisfied pinch nan existent treatment, right? So, there's 58,000 PKU patients globally.

So that makes it a really beautiful important opportunity to beryllium capable to bring these -- to bring nan caller therapy that is -- that we judge is overmuch -- is highly effective. You could spot that getting 60% -- complete 65% of nan wide diligent organization and 61.5% of nan classical population, they're astir nan same, conscionable showing you really effective it is. When you see what PKU -- what Kuvan [was before] (ph) was, it didn't moreover usability connected classical patient. So, we deliberation it's beautiful clear that this is simply a superior product. And so, I deliberation it's -- there's truthful galore patients wherever nan supplier were ineffective that we deliberation we're successful a really bully spot for this.

And so, we don't expect immoderate measurement edit for classical PKU because it was truthful good known that it's Kuvan [that deed it] (ph). And moreover if location is measurement edits for patients to -- locomotion done Kuvan, there's already a adjacent number of those patients who've already tried and grounded Kuvan has been good documented. And moreover if they haven't, it's a very short play of clip to show that it is aliases isn't functional. So, I deliberation that you person a existent -- I don't deliberation this is going to beryllium cumbersome aliases difficult to beryllium capable to handle.

So, Kylie, do you person thing to say? Also, you've done a adjacent spot of activity connected payers.

Kylie O'Keefe

Yes. Thanks, Kristen, for nan question. I deliberation it's a really important one. And arsenic Stu said, we really do judge successful this important unmet request that exists successful nan PKU marketplace. And arsenic Stu was talking to, we started to statesman a number of different payer engagements to guarantee we understand benignant of really they're looking astatine a information package. And from that perspective, arsenic Stu was saying, if you look astatine nan classical PKU patients, Kristen, location has been nary effective therapies successful that space. And so, from that perspective, we don't foresee immoderate types of measurement edits aliases requirements to beryllium capable to put these patients connected treatment.

And arsenic Stu was besides saying successful nan abstraction wherever they've antecedently tried Kuvan, moreover if they were measurement edits to generic first plans successful nan lawsuit of Kuvan being generic, again, we don't spot this arsenic a awesome hurdle, because successful galore cases, they've tried and grounded Kuvan and truthful nan archiving has been established. And moreover if it needed to beryllium re-established, it is simply a speedy and businesslike measurement successful nan consciousness that it is simply a blood-based biomarker. So, you're capable to put nan patients connected treatment, found that nan curen isn't working, and move them connected to a much effective therapy. And so, from that perspective, we're very assured going into nan commercialized landscape, that we person nan correct information group and nan correct information package assuming occurrence pinch APHENITY to deed nan crushed running.

Stuart Peltz

And we don't look astatine this for illustration arsenic we're competing pinch nan generic. We're competing pinch a supplier that had a very mini model of patients to dainty of -- astir of which are nan patients weren't successful. And so, we scheme connected bringing successful a consciousness a caller therapy that these patients we expect will person -- will beryllium much successful connected this therapy. But it's very different than fighting pinch us. You conscionable person a generic and you're trying to conflict to get a portion of that pie. We're really -- we really judge that we'll beryllium capable to dainty patients that weren't capable to beryllium treated before.

Kristen Kluska

Okay. Thank you, Stu and Kylie. And then, I deliberation of your late-stage candidates MDAS possibly gets little attraction compared to particularly for illustration PKU and Huntington's disease. So, possibly tin you reiterate for america why you stay excited astir nan programme imaginable here? And really you deliberation astir nan commercialized opportunity and easiness of uncovering immoderate of these patients should it beryllium successful and yet approved? Thank you.

Stuart Peltz

Yes, we deliberation vatiquinone is simply a very important caller therapy, successful part, because it really does tackle a caller area successful position of treating medicine, and that is really benignant of mitochondrial dysfunction and nan consequences of that. When you deliberation astir mitochondrial dysfunction, erstwhile you deliberation astir nan magnitude of ATP that's produced successful bid to beryllium functional, it's almost for illustration 15 [indiscernible] ATP molecules a second. And if things spell [indiscernible] dysregulation and enhanced free electrons that evidently origin each sorts of accent connected nan compartment that causes some -- that tin origin havoc, and obviously, neuroinflammation and things for illustration that. And nan consequence of that is big.

When you deliberation astir particularly for illustration successful nan brain, wherever it's only a 3-pound organ, but it uses astir 20% of nan wide ATP wrong nan body, it could beryllium some melodramatic effects, and you could spot that pinch mitochondrial illness pinch associated seizure. So, I deliberation having a supplier that could modulate this and done caller and caller system is rather important. And we're excited astir that because it tin beryllium utilized really rather broadly.

Matt, do you want to talk a small spot astir MIT-E and why we're truthful excited astir this?

Matthew Klein

Yes, Kristen, convey you again for nan question. Look, well, possibly it's not getting arsenic overmuch attention, this is simply a organization that's known. There's complete 20,000 patients worldwide pinch mitochondrial illness associated seizures. And arsenic Stu mentioned, this is conscionable nan opening of populations that could use from a supplier that targets these basal entree pathways, accent and inflammation pathways that causes that disease.

Now we person assurance successful nan study. It's built connected a number of erstwhile studies showing that we tin person an important effect connected seizure activity, some successful position of seizure wave and different seizure-related morbidity. And we judge that this tin beryllium a very important therapy not only for mitochondrial illness patients, patients pinch Friedreich ataxia, but galore others.

Kristen Kluska

Thank you.

Operator

Thank you. And our adjacent mobility comes from Brian Abrahams pinch RBC. Your statement is open.

Brian Abrahams

Hey, guys. Thanks for taking my question. And Stu, my congratulations arsenic good connected 25 years.

Stuart Peltz

Thank you.

Brian Abrahams

I was wondering if you guys could grow a small spot much connected nan quality of your chat pinch nan agency connected Translarna. I'm funny to study a small spot much astir I conjecture what their first reactions were to nan afloat 041 information positive nan STRIDE registry. What seems to beryllium nan sticking point? And I conjecture what gives you assurance that dystrophin and immoderate of nan different analyses would support approval? And is this thing that would beryllium a imaginable accelerated support perhaps? Thanks.

Stuart Peltz

Yes. So, we precocious had a general chat that will let america to lead to having mounting up a gathering pinch them. And it really was nan conception of america talking astir nan wide package and nan system of action arsenic good arsenic why we deliberation we person objective use arsenic a consequence of that.

Matt, you want to spell done this a small bit?

Matthew Klein

Yes, sure. Brian, acknowledgment for nan question. So, conscionable to return a measurement backwards, arsenic I deliberation astir of you recall, aft we had nan 041 data, we had requested a Type C gathering pinch nan FDA to talk 041 arsenic good arsenic STRIDE and nan pooled analyses from including Study 7 and Study 20. And nan agency informed america that we would person a gathering pinch written consequence only. We had asked to beryllium capable to person a unrecorded gathering fixed nan measurement of information and they said that they would supply written response-only comments, but we would person nan expertise to talk to them afterwards if we still had questions. And obviously, we did person questions aft nan first feedback, which seemed to attraction mostly connected Study 041, itself not gathering nan barroom up important grounds of effectiveness. But clearly, there's grounds of use successful that study. And erstwhile mixed pinch Study 7 and Study 20, you spot highly statistically important and accordant betterment connected nan cardinal functional endpoints of disease, and past arsenic you mentioned besides nan STRIDE registry.

This gathering was a unrecorded gathering offered arsenic a explanation of nan comments that were made successful nan Type C written comments. And again, a batch of that chat was astir why study 041 wasn't believed to person important events of effectiveness. We talked astir totality of data, and it was suggested that we could petition a abstracted Type C gathering to talk totality of data, including nan mechanistic dystrophin data, because nan remark successful our gathering was made that we had shared those data, which arsenic you each know, we had those data, but really focused connected nan functional use that was successful 041 that came afterwards.

So, we spot this arsenic an opportunity to again item not only 041, but 041 alongside nan different placebo-controlled studies, and nan STRIDE registry, really nan benefits we've demonstrated successful nan people of a objective proceedings are translating into semipermanent meaningful use arsenic acold arsenic delaying nan cardinal morbid transitions shape of nan disease, nonaccomplishment of ambulation, nonaccomplishment of pulmonary usability and past bringing each nan mechanistic data. We person nan Study 045 successful [indiscernible] arsenic well, which really confirms that we person a caller system of action successful position of delirium suppression and that's yielding dystrophin production, which is besides associated pinch nan objective benefits signaling each of these studies.

Brian Abrahams

That's really helpful. Thanks truthful much. And if I could conscionable compression successful a speedy follow-up connected nan PKU program. I deliberation nan measurement to measurement phenylalanine levels successful modern studies are much reliable. But I was wondering if you could possibly conscionable explain nan measurement Phe is being measured successful nan Phase 3 comparative to nan Kuvan studies and your assurance that nan appraisal of Phe is repeated aliases robust capable specified that you wouldn't person pseudo responders whose reductions mightiness driblet disconnected betwixt nan unfastened explanation run-in and nan randomized information arsenic has had happened pinch immoderate of nan aged Kuvan studies? Thanks.

Stuart Peltz

Go ahead, Matt.

Matthew Klein

Yes. Brian, we're utilizing a humor spot study that's done astatine home. This has been very good validated arsenic a robust measure. I deliberation we person assurance that evidently we're utilizing nan aforesaid methodology successful some nan run-in shape and nan placebo-controlled phase. And also, it's important to statement nan measurement we measurement these Phe responses, which successful nan run-in shape are treated for 14 days, but we're averaging 3 different clip points five, 10 and 14 days, which gives america nan worth of reduction. So, it's averaged complete 3 points, which is different effort to guarantee we're getting an meticulous and precise appraisal of nan Phe reduction.

So, this is simply a method that's been good designed and good validated. We person a GLP laboratory accordant measurement successful some nan run-in and nan placebo-controlled phase. I can't remark connected circumstantial differences successful nan methodology that was utilized pinch Kuvan, but I tin supply nan assurance that we person developed a very good validating method that tin supply some meticulous and precise appraisal of nan Phe changes complete time.

Brian Abrahams

No, that's ace helpful. Thanks, Matt.

Operator

Thank you. Our adjacent mobility comes from Joseph Thome pinch Cowen. Your statement is open.

Joseph Thome

Hi, there. Thank you for taking my question. Maybe conscionable one. We're going to spot immoderate registrational information sets present successful nan first half, which is great, hopefully immoderate of these are aliases each of them are successful. But arsenic you did bring these in, is location thing other that you would request extracurricular of nan registrational information earlier a regulatory submission? So, essentially, tin you conscionable remark connected your comfortableness pinch nan CMC arsenic it stands correct now? And nan size of nan information database for benignant of nan adjacent 3 that are coming up here? That would beryllium great. Thank you.

Stuart Peltz

Yes. Matt, do you want to return that?

Matthew Klein

Yes, sure. Thanks for nan question, Joe. So, obviously, each -- some compounds, sepiapterin for PKU arsenic good arsenic vatiquinone, person been successful improvement for a number of years, which has really fixed nan opportunity for nan different components of nan package erstwhile you deliberation astir CMC and you deliberation astir non-clinical [indiscernible] for those portions of nan package to get filled out.

Obviously, we're conducting a reasonably ample study successful PKU now pinch sepiapterin to that -- and we judge based connected this proceedings and nan different information that person been collected successful different sepiapterin studies that we'll person this capable database to support nan ngo pinch a affirmative trial. And pinch vatiquinone, I deliberation 1 of nan really foundations of that therapy is nan extended information records that's been recorded successful kids complete nan past decade, including patients who person been connected supplier continuously for complete a decade pinch very beardown information profile.

Taken together for some therapies, we judge we person each nan components of nan package. Obviously, pinch affirmative data, we'll meet pinch nan agency to align connected nan specifications of nan [indiscernible] submission and past move guardant arsenic quickly arsenic possible.

Joseph Thome

Great. And past possibly conscionable a speedy follow-up possibly connected nan financial side. In position of nan financial walk guidance for 2023, is location immoderate further build successful nan US trading unit anticipated this year? Or would that beryllium much of a 2024 walk item? Thank you.

Stuart Peltz

Yes. Emily?

Emily Hill

Yes, sure, I'll return that 1 connected nan walk broadside and past commercial, and thing connected nan infrastructure. We're beautiful good sized connected nan commercialized force. So, there's nary important alteration successful nan walk connected nan US income force.

Joseph Thome

Okay. Thank you very much.

Operator

Thank you. Our adjacent mobility comes from David Lebowitz pinch Citi. Your statement is open. David Lebowitz pinch Citi, your statement is open.

David Lebowitz

Sorry, I -- nan sanction fell retired for a moment. I conjecture mobility number one, connected nan 923 data, really should we benchmark consequence complaint compared to Kuvan fixed that patients were connected a Phe restricted diet, which would beryllium expected to deepen nan wide response?

Stuart Peltz

Yes. So, I deliberation what we're asking for is for people, immoderate diet's on, that they support accordant fare of what they're on. And I deliberation what -- I deliberation overall, what you're seeing wrong nan results are beautiful melodramatic results of greater than 60%, some successful nan classical arsenic good arsenic nan different forms of PKU. So, I deliberation you've seen accordant activity of nan molecule. So, I consciousness we're successful -- and if it's deeper successful nan different way, astatine slightest here, I deliberation you're still seeing beautiful precocious consequence rate.

Matt, do you have...

Matthew Klein

[Multiple Speakers] Thank you for nan question. In general, these patients each thin to beryllium connected Phe restricted fare and nan cardinal successful some studies, obviously, to person them connected accordant diets, truthful that's not a confounding variable. But I deliberation what we're seeing successful position of differences successful magnitude of effect is rather impressive. If you look astatine nan Phase 1, which was nan Kuvan responder study, they recorded a greater than 30% alteration successful 20% of nan patients. And obviously, now we're looking astatine 65% successful this study. So, I deliberation this is intelligibly a overmuch higher consequence rate. And again, what we've talked astir is really what you'd expect for a much bioavailable and potent cofactor, and obviously, successful nan phases you said, of a continuous diet.

David Lebowitz

Thank you for that. And would you beryllium -- do you expect to specifically study a consequence complaint for classical PKU patients?

Stuart Peltz

Yes, I mean, overall, we'll beryllium -- astatine nan extremity of nan day, we'll break that retired arsenic well.

David Lebowitz

Helpful. Thanks for taking my question.

Operator

Thank you. Our adjacent mobility comes from Kelly Shi pinch Jefferies. Your statement is open.

Kelly Shi

Thank you. So, for MIT-E information now successful Q2, could you thief to group an anticipation connected what benignant of simplification of shape of wave would beryllium considered clinically meaningful?

And what different merits we should besides attraction connected to measure nan objective use of vatiquinone?

And past lastly, fixed that nan mitochondrial illness is simply a very heterogeneous disease, would you expect immoderate groups of patients pinch definite for illustration genotypes to spot a greater use based connected nan system of action of vatiquinone? Thank you.

Stuart Peltz

Hey, Matt, do you want to return that?

Matthew Klein

Sure. Thank you again for nan question. So, erstwhile we talk astir use successful these patients, first, we person to deliberation astir nan illness itself. So, obviously, mitochondrial illness associated seizures are highly morbid and communal facet of nan disease. So, astir half nan patients pinch mitochondria person seizures and these seizures don't thin to respond to emblematic antiepileptics, because nan emblematic antiepileptics don't target nan energetic pathways that origin seizures successful these patients.

In fact, galore of nan accepted antiepileptics are mitochondrial toxins, truthful they really make nan illness worse. These kids person seizures that are refractory to emblematic meds, they tin person ten, hundred, moreover up to 1000 a month. So, precocious seizure volume. It's a highly morbid facet of illness which often leads to aspiration, pneumonia and different infections, and often tin beryllium nan origin of decease for these patients.

So, erstwhile we deliberation astir meaningful reduction, astir of nan physicians we speak to deliberation that moreover a 20% to 25% simplification successful seizure wave successful these patients tin beryllium important. We've powered nan study for a 40% differential simplification betwixt nan curen group and placebo group pinch a hypothesized simplification of 50% successful seizure wave successful nan progressive organization and 10% successful nan placebo population.

In position of differences betwixt genotype and response, fixed nan truth that vatiquinone is targeting 15-lipoxygenase, which is simply a communal consequence pathway extracurricular of nan mitochondria, nan curen effect should beryllium agnostic to underlying genotype, and mightiness location beryllium different diligent characteristics specified arsenic property and shape of illness that could lend to differential therapeutic response. That's possible. But 1 of nan things we've observed successful erstwhile studies is there's nary circumstantial narration betwixt genotype aliases illness subtype and response, again, because we're targeting constituent communal aliases consequence method communal to each different causative genotype defect.

Kelly Shi

Thank you. Super helpful.

Operator

Thank you. Our adjacent mobility comes from Tazeen Ahmad pinch Bank of America. Your statement is open.

Tazeen Ahmad

Hi. Good evening. Thanks for taking my questions. Maybe 1 constituent of explanation for Translarna. I deliberation Stu and Matt, you've talked astir nan totality of information arsenic being nan premise for a batch of your discussions precocious pinch nan agency. But I conjecture arsenic it relates specifically to dystrophin, if nan agency looks for dystrophin arsenic portion of nan package, tin you conscionable punctual america erstwhile nan past clip dystrophin was measured successful immoderate of your tests to date? And really galore patients' worthy of information you mightiness person connected that?

Stuart Peltz

Yes, sure. So, nan measurement -- obviously, nan measurement nan -- you sewage to retrieve besides nan dystrophin was erstwhile we measured it, we measured it successful study 004, which was nan first study that we did, to return a look to spot its proof-of-concept studies wherever we showed -- and that's a published paper, wherever we showed that you saw accrued levels of dystrophin. And it was a mini study, I think, I don't know, 15, 16 patients location astir there. And then, we redid Study 045. We did it again successful Study 045. That was -- really galore patients was that, Matt? Do you remember?

Matthew Klein

So, we had 20 overall, and location were 18 successful study population.

Stuart Peltz

Yes. So, we person those sets of patients. And then, we have, obviously, from a objective constituent of view, studies from 007, 020 and Study 041 pinch a ample number of patients wherever successful nan ITT population, particularly successful 041, we saw a clinically important results. And then, not only was it -- arsenic Matt had said before, that not only was that -- not only was it affirmative there, but it was besides affirmative successful nan North Star, nan timed-function test. And that was existent besides successful Study 020 arsenic good arsenic aggregate endpoints successful 007.

So, there's a ample assemblage of information that demonstrates Translarna's activity successful position of treating patients. And that's past accordant pinch nan STRIDE registry that we've done wherever we've looked astatine difficult endpoints specified arsenic nonaccomplishment of ambulation, nonaccomplishment of getting disconnected of -- being capable to get disconnected nan -- guidelines from nan crushed and nonaccomplishment of pulmonary activity. And past each those results demonstrating that you sphere some nan expertise to walk, to sphere nan expertise to get disconnected from nan crushed and -- by year, and sphere nan expertise to sphere pulmonary function.

So, you put each that together -- frankly, I person not seen a amended objective package than nan 1 we have. And we judge it's beautiful clear that patients use from it. And you tin spot that patients person been connected it for now rather a agelong time. So, we judge -- and we person patients from -- evidently from astir nan globe, getting Translarna. And we ever deliberation it's due and adjacent that we should activity towards getting patients successful nan United States this drug. And what we're really asking for is, look, we'd for illustration to -- we deliberation that we person a beardown package. Let's reappraisal it. Let's person an advisory committee, and astatine slightest springiness america -- and not conscionable america nan patients and their families a adjacent hearing, truthful that nan folks who person been -- and successful fact, galore of them person been connected it for complete a decade now, that to springiness them their owed connected what we deliberation is simply a highly progressive drug.

Tazeen Ahmad

Okay. Thanks for each that color. I mean, astatine this point, what do you deliberation needs to hap to get nan agency complete nan decorativeness statement for them to opportunity that you should use for approval? Have they looked astatine each this information already arsenic portion of your written interaction?

Stuart Peltz

Yes. So, we're -- look, what we deliberation is we've had years now of moving pinch nan agency and not talking to them. And it's not conscionable us. It's been nan full organization has only had written discussions, and uncomplicated results pinch a ample assemblage of data, and they person plentifulness of caller group location who whitethorn not understand nan full image and person each nan discussions. And not to really -- I simply don't understand that, not to person relationship wherever you person connection and you talk done it, and conscionable for illustration everything other that we do successful life, you request to beryllium capable to spell backmost and distant to springiness points of position that, and really you alteration people's minds aliases astatine slightest person a changeable astatine it. One doesn't person an easy changeable astatine it if it's each 3 months, you get nan constitute a consequence backmost to questions. So, we deliberation that astatine slightest what we request to do is to person a speech and spot wherever that goes.

Tazeen Ahmad

Okay. And do you deliberation that, that will beryllium sooner alternatively than later? Or do you person to hold that other 3 months conscionable to schedule it?

Stuart Peltz

It takes time. This is nan quality of regulatory discussions, you put it in, and there's clip for them to get -- fresh you in.

Tazeen Ahmad

All right. Okay. Got it. Thanks for that. Appreciate it.

Operator

Thank you. Our adjacent mobility comes from Gena Wang pinch Barclays. Your statement is open.

Gena Wang

Thank you for taking my question. I person 2 questions regarding APHENITY study. First is conscionable clarification. Regarding nan 156 patients, these patients really passed [50%] (ph) Phe simplification screening test? Or was that 156 patients is simply a full diligent that you screened? If it's 156 patients is simply a passed 15% Phe reduction, what is nan full diligent number you screened?

Stuart Peltz

Matt, do you want to return that one?

Matthew Klein

Yes, sure. Hi, Gena. So, nan 156 refers to each those who went done screening and past completed nan run-in phase. So that's 156 subjects who received 2 weeks of sepiapterin. Of those 156, 102 aliases 65% had a greater than 30% reduction.

Gena Wang

So, retired of 156, really galore of these achieved 15% Phe reduction?

Matthew Klein

So, of nan 156 -- truthful we said 102 had complete 30% and 13 had betwixt 15% and 30%. So, successful total, that would beryllium 115 aliases astir 75% -- 74%, 75% had 15% simplification and above. But obviously, acold and away, nan mostly of those, 102 of those were greater than 30% reduction.

Gena Wang

Okay. Very good. Very helpful. And then, my 2nd mobility is, tin you punctual america nan rationale of dose escalation pinch 2 weeks each of nan 20-milligram, 40-milligram 60-milligram for nan Part 2 study?

Matthew Klein

Yes, sure. So, 1 of nan things we're studying, obviously, that nan agency ever likes to understand is vulnerability consequence relationships, truthful by doing nan 2 weeks astatine 20-milligrams per kilo, 2 weeks astatine 40-milligram per kilo, 2 weeks astatine 60-milligrams per kilo, we tin person a very bully curve and understand nan narration betwixt vulnerability and response, which is important for regulatory purposes. We judge nan dose will beryllium 60-milligrams per kilogram, and we're besides very assured that 2 weeks is capable to understand what nan effect astatine each dose level will be.

Gena Wang

Thank you very much.

Operator

Thank you. Our adjacent mobility comes from Jeff Hung pinch Morgan Stanley. Your statement is open.

Mike Riad

Hi. This is Mike Riad connected for Jeff Hung. Thank you for taking our questions. First one, erstwhile nan upcoming APHENITY information readout successful May, tin you punctual america really you're reasoning astir nan cadence and timing of regulatory events? And we person a follow-up aft that.

Stuart Peltz

Sure. Our extremity is we'll get nan result. And then, based connected that, we'll evidently study retired nan results, truthful publically and past arsenic quickly arsenic imaginable person a group of meetings and get fresh to an NDA for nan merchandise and get fresh for regulatory guys arsenic accelerated arsenic possible. Obviously, we'll do a pre-NDA meeting. And while we're doing that, we'll beryllium getting each nan documents fresh to go.

Mike Riad

Awesome. Thank you truthful much. And my 2nd mobility for nan vatiquinone Phase 2/3 MIT-E data, they were expected this quarter, but they're now successful nan 2nd quarter. Can you talk astir immoderate factors that led to nan accommodation successful timing? Thanks truthful much.

Stuart Peltz

Yes, I deliberation it's finishing up nan past diligent out. Matt, do you person immoderate thoughts connected this?

Matthew Klein

Yes. It's -- yes, Michael, it's really a mobility of having now cognize precisely erstwhile that past diligent past sojourn is going to be, which is going to beryllium successful March, and past having capable clip to do each nan database cleaning, nan database fastener and past getting to data. So, it's really a refinement of nan timeline now that we cognize nan definitive past diligent past sojourn date.

Mike Riad

Awesome. Thank you.

Operator

Thank you. Our adjacent mobility comes from Paul Choi pinch Goldman Sachs. Your statement is open.

Paul Choi

Hi. Thank you. Good day and convey you for taking our questions. I person 2 pipeline questions. First is connected APHENITY. Can you conscionable possibly elaborate connected nan updated timing from May of this twelvemonth versus your anterior guidance? And tin you possibly speak to immoderate geographical differences pinch respect to believe and objective curen of PKU patients successful nan US versus OUS that we mightiness look for arsenic you apical statement your results later this year?

Stuart Peltz

Sure. So, I'll conscionable return nan first one. I deliberation we've talked astir this is nan timing really had to do pinch nan ample nan refinement of nan timing of erstwhile we would complete nan proceedings had a batch to do pinch conscionable -- location were a batch of patients astatine nan extremity of nan -- erstwhile we were nearing fresh to adjacent nan trial. And what we decided to do is -- and it was a number of group that we wanted to make judge that immoderate of their patients sewage successful immoderate of nan KOLs would beryllium capable to do that and arsenic such. We really brought successful much than we thought we would, and that extended nan timeline that led to america getting nan results, which we deliberation now by everyone's successful nan proceedings now, and truthful we were capable to springiness a beautiful refined clip connected erstwhile we would beryllium capable to complete nan trial. So, we consciousness beautiful bully astir now that we cognize precisely wherever we're astatine erstwhile we complete nan trial.

In position of nan geographical differences, Matt, do you want to -- immoderate comments you want to make connected that?

Matthew Klein

Yes. I would -- Paul, we really don't expect geographical differences while location whitethorn beryllium different guidelines successful position of target Phe simplification successful nan region to region. The believe is reasonably accordant worldwide. And obviously, this is simply a illness wherever nan cornerstone of guidance is for now fare modification that starts astatine birth. Newborn screening is successful spot successful galore places astir nan world. So, we tin surely look astatine whether there's differential consequence based connected geography, but it's not 1 that we would expect connected priority.

Paul Choi

Okay. Thank you for that. And arsenic a follow-up connected 518 for Huntington's, tin you possibly remark aliases update america connected what feedback aliases information you've provided to nan FDA? And conscionable what your existent anticipation is for getting nan objective clasp lifted there?

Stuart Peltz

Yes, sure. I deliberation arsenic we've discussed successful nan past, our extremity is to stock pinch them immoderate information that we're getting pinch existent patients and spell backmost to them connected that -- pinch that, which what we will beryllium doing. And we deliberation that -- so, it's having capable objective information connected nan group of patients that we tin past spell backmost and talk to them on. And truthful that's what we're doing successful position of that.

But we've opened up evidently a adjacent number of sites astir nan globe. And so, patients are coming in. We moreover expanded to return an further cohort of patients. So, we consciousness beautiful bully astir bringing them in. And then, we'll bring in, astatine immoderate point, erstwhile we person a group of information that we'll spell talk to nan FDA astir and show them that we're successful a beautiful bully ship. Just to punctual everyone, we're doing nan 5- and 10-milligram information that would past will beryllium capable to spell to nan 20-milligram information and we'll beryllium capable to bring our information to nan FDA astatine immoderate constituent truthful we opened it up successful nan US. That's our crippled plan.

Paul Choi

Okay. Thank you, and congratulations connected 25 years.

Stuart Peltz

Thank you, Paul.

Operator

Thank you. Our adjacent mobility comes from Danielle Brill pinch Raymond James. Your statement is open.

Danielle Brill

Hi, guys. Good evening. Thanks truthful overmuch for nan questions. Just a mates of clarifying ones for me. I deliberation past period astatine J.P. Morgan, unaudited 4Q revenues for Upstaza were $13 million. Is that number still accurate? And should we beryllium expecting nan spillover from nan $20 cardinal to $40 cardinal you antecedently guided for successful 4Q to beryllium reflected successful 1Q?

And then, conscionable a explanation connected Translarna arsenic well. The Type C gathering that you scheme to request, will this 1 beryllium successful person, aliases are you expecting conscionable written gathering arsenic well? Thank you.

Stuart Peltz

Yes, acknowledgment for nan question. And so, fto maine return Translarna. We expect this to beryllium intends wherever we -- it will person conversation, truthful it's not going to beryllium -- it's not going to beryllium written. And I judge it's going to beryllium a Zoom call, isn't that right, Matt?

Matthew Klein

We petition -- we'll petition a unrecorded relationship obviously, and I cognize nan agency has now started having in-personal meetings again. So, nan nonstop details, Danielle, whether this is Zoom, whether it's phone, whether it's live, whether they want to do it different way, obviously, it will beryllium up to them and we'll cognize amended erstwhile we taxable nan petition and get their response. Obviously, we would beryllium [targeting] (ph) in-person, but we judge that's nan astir effective shape of discussion, but obviously, this is going to beryllium up to nan agency.

Stuart Peltz

Yes. And past successful position of, obviously, nan diligent finding, successful position of Q1, obviously, we astir of what we do is focused connected identifying patients. And certainly, we stay assured that we want to move those in. In position of nan numbers, I don't deliberation location were immoderate changes successful nan 2022 numbers. And we'll astir apt supply much colour astir really we're doing. We're very early wrong nan launch, right? So, I deliberation we'll beryllium capable to supply much colour connected each of nan quarterly calls and surely astatine nan Q1 net call, we'll supply much colour connected that.

Kylie, do you person thing other to adhd to that one?

Kylie O'Keefe

Thanks, Stu. Yes. As said, Danielle, location is nary changes to nan number for Upstaza from unaudited to audited. And arsenic Stu said, we're continuing to attraction connected diligent recognition and continuing to attraction connected securing pricing and reimbursement successful a number of different countries crossed Europe, arsenic good arsenic we talked astir successful January, focusing connected looking astatine caller diligent programs extracurricular of Europe. And truthful that's continuing according to plan. As Eric mentioned earlier, we're seeing beardown engagement pinch payers crossed a number of different HTA bodies, and we look guardant to being capable to proceed that pricing and reinvestment measurement to dainty much patients successful this, and we scheme to supply much updates astatine upcoming 4th earnings.

Danielle Brill

That's helpful. Thank you.

Operator

Thank you. Our adjacent mobility comes from Robyn Karnauskas pinch Truist. Your dishonesty is open.

Unidentified Analyst

Hi, this is Alex connected for Robyn. We had a mobility connected if location had been immoderate updates into nan diligent uncovering aliases patients identified for AADC for Upstaza, but it sounds for illustration we're going to hold until nan first 4th to get immoderate much results connected that. Correct maine if I'm wrong, we besides wanted to now move towards nan US. Can you punctual america of nan prelaunch initiatives that are ongoing for Upstaza and what further initiatives whitethorn still beryllium needed arsenic we attack BLA submission and anticipated early launch? Thanks.

Stuart Peltz

Yes, sure. Eric, do you want to return that one?

Eric Pauwels

Yes, sure. Thanks, Alex, for nan question. We presently are seeing nan dynamics successful Europe, but we're besides preparing for nan motorboat of Upstage successful nan US successful a akin way, and we person a dedicated squad that's really doing that. We person focused connected a number of cardinal areas, including accelerated illness awareness. We person a number of cardinal programs, including advisory committee symposium and publications, cardinal publications and adjacent reappraisal that person been successful English, it's besides US-based journals.

We're talking to payers arsenic good successful nan US and preparing for this launch. We're talking to a number of cardinal payers astir nan creation because we cognize that location are cistron therapies presently approved successful nan U.S. but galore of them are replacing modular of care. So, Upstaza will beryllium nan modular of care. So, we're taking an attack to really understand really nan payer position will beryllium connected this. We person accelerated a number of diligent uncovering activities, peculiarly successful nan precocious enriched population. And looking astatine -- and besides taste type groups. We person already wherever our target is to comparison location betwixt 7 and 10 surgical centers to beryllium fresh astatine nan clip of launch. And importantly, this will beryllium timed and these centers will beryllium timed pinch nan clip of launch, we'll beryllium capable to activity very intimately to bring these patients in.

So overall, I deliberation we're very pleased pinch nan advancement we're making extracurricular of Europe, but we're besides sharing a batch of nan knowledge from nan motorboat itself successful Europe, and we're sharing that continuous learning and execution that we person pinch nan US market, pursuing nan BLA approval, we'll beryllium fresh to motorboat nan merchandise successful nan US.

Unidentified Analyst

Okay. That sounds great. And besides connected nan aforesaid note, now that location person been patients treated successful nan real-world setting, do you find that nan objective results -- this early, still early objective results that you're seeing and specifications on pinch nan procedure, lucifer that of nan what you saw successful nan objective trials, aliases are location immoderate cardinal differences to note? Thanks.

Stuart Peltz

Yes. No, we're -- look, it's a bully facet of AADC deficiency and nan cistron therapy that we person arsenic we spot it is genuinely a transformational therapy wherever -- and arsenic you've seen that each of nan patients execute amended successful their patients that obviously, while they were maturation arrested and weren't capable to clasp their caput up, move over, beryllium up, guidelines aliases talk person changed. And clearly, you tin spot immoderate patients wherever we person 1 diligent that speaks 3 languages.

So that's been exciting, and we proceed to spot important betterment successful these patients. So, there's -- arsenic we ever say, there's thing much ratifying than being portion of a supplier therapy and bringing it to patients and having specified transformational facts connected it. I deliberation that's -- it's awesome for nan family to spot what it does for nan family, nan patients and for our ain organization for conscionable being portion of bringing it to them. So, we're excited astir it, and it continues to beryllium a transformational product.

Unidentified Analyst

Yes. That sounds fantastic. Well, congrats, and acknowledgment for taking my question.

Operator

Thank you. Our adjacent mobility comes from Colin Bristow pinch UBS. Your statement is open.

Unidentified Analyst

Hi. This is [indiscernible] connected for Colin. Thanks for taking our questions. We person 2 explanation questions. So, nan first 1 is connected nan PKU data. Congrats connected nan Part 1 data. And could you please springiness america immoderate much elaborate colors connected nan superior logic for nan apical statement hold to May? When for illustration you person already for illustration get a batch of stuff, it's conscionable for illustration for nan Part 1, nan enrollment was arsenic planned and it has a fixed timing extremity point. So, I'm conscionable wondering what nan rationale down it.

And nan 2nd mobility is connected PTC518 Huntington's illness program. We are conscionable wondering, person you heard immoderate updates connected much circumstantial requirements from FDA yet -- and really agelong will it return to get nan data? And also, successful position of nan for illustration US enrollment, person nan precocious dose information already started nan enrollment? Could you please explain connected that?

Stuart Peltz

Yes. I deliberation if I -- it was a small muffled. I deliberation you're asking why is it successful May? Was that nan question? So, I deliberation nan -- truthful I deliberation possibly -- truthful conscionable truthful we're clear, nan logic is it was nan extremity of nan study really occurs erstwhile it's nan past diligent past visit, you've completed that facet of nan study, and that's erstwhile each nan patients are completed, you tin past spell and cleanable nan information and yet get it analyzed. And really what happened is astatine nan extremity of location was a ample number of patients astatine nan extremity of nan study that we're going in. And that's ever successful a way, a small spot of an aerial postulation power nightmare to beryllium capable to get -- bring successful arsenic galore patients arsenic you tin and adjacent it arsenic quickly arsenic possible.

And truthful that makes it -- and we're balancing, wanting to adjacent nan trial, but besides wanting to make judge that patients sewage successful and that patients from aggregate physicians get into nan trial. And truthful that we don't anger anybody that they weren't portion of it of nan trial. And truthful that's ever -- it's ever a small difficult sometimes to precisely onshore nan level astatine nan clip you deliberation you're going to do it. And this 1 was successful particular, overmuch much astatine nan end, had tons of patients. And that's why nan timeline moved from wherever we thought it would beryllium to May.

It's thing -- it's a small spot longer, but we've gotten a batch of -- we person a batch of nan patients from group from each nan cardinal sentiment leaders and investigators. So, astatine nan extremity of nan day, it was nan mini change, truthful good worthy it because we person everybody successful nan study, and we consciousness bully astir it. So, I deliberation that's -- astatine nan extremity of nan day, that's what we're comfortable with. I don't deliberation -- and good worthy nan mini magnitude of clip alteration to get everyone in.

So that -- and successful position of 518, we're now collecting data. We haven't said yet erstwhile we're going to cleanable nan information and spell backmost to nan FDA. But we scheme to do this, and erstwhile we do, we'll fto everyone cognize what our plans are, but we haven't done that yet. And we -- I don't deliberation we've group it up to opportunity erstwhile we're going to complete that.

Matt, thing other I person to opportunity connected that?

Matthew Klein

Yes, I would conscionable adhd a mates of things connected nan -- conscionable arsenic a reminder, right, this was feedback that came from nan non-clinical information that we had committed to nan agency that was reviewed astatine nan different agencies. And arsenic we said, each nan different countries person allowed america to commencement nan study astatine 5 and 10 milligrams for a twelvemonth and moreover commencement astatine 20 milligrams up to a year, and nan FDA simply asked for immoderate further information to support nan dosing and duration, we watch it. And arsenic Stu said, we're successful nan process of collecting what we deliberation will beryllium reputedly capable to do that, which is objective data. So, existent information from patients that tin springiness comfortableness for nan dosing and long astatine nan US.

In position of your mobility regarding nan initiation of nan higher dose, nan 20-milligram cohort, that hasn't started yet. As we said, we want to look astatine nan information from 5 milligrams to 10 milligrams to really make a data-driven determination based connected what we're seeing successful position of pharmacodynamic effect, that is simplification successful peripheral mRNA Huntington and macromolecule -- Huntington macromolecule reductions were afloat successful nan biodistribution successful position of CSF exposure. Once we person an knowing of what that looks for illustration astatine 5 and 10 milligrams, we'll past beryllium successful a position to make a determination regarding initiation of nan 20-milligram cohort. And so, we look guardant to having those first 5 and 10 milligram information to thief pass that determination successful nan adjacent future.

Unidentified Analyst

Got it. Very helpful. Thank you.

Operator

Thank you. There are nary further questions. I'd for illustration to move nan telephone backmost complete to Stuart Peltz for immoderate closing remarks.

Stuart Peltz

Okay. Thank you, operator.

In closing, I'd for illustration to convey each of you for joining nan telephone coming and your good wish for our 25 years. We're ever excited astir that. Especially excited astir wherever we guidelines coming astatine PTC, wherever we have, arsenic you tin see, beardown and accelerating revenues from our merchandise portfolio. We person 4 information readouts successful nan first half of 2023, including 3 registrational studies. So, clearly, we're firing connected each cylinders, and we look guardant to much updates for you complete nan coming months.

And pinch that, convey you for staying connected and bully evening.

Operator

Thank you for your participation. You whitethorn now disconnect. Everyone, bask nan remainder of your day.

Editor: Naga



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