PTC Therapeutics (PTCT) 29 Feb 242023 Q4 Earnings call transcript

Good day, and, thank you for standing by. Welcome to PTC Fourth Quarter 2023 Financial Results. [Operator Instructions] Please note that today's conference is being recorded.I would now like to pass the call over to the Senior Director of Investor Relations, Ron Aldridge.

Good afternoon, and thank you for joining us today to discuss PTC Therapeutics' fourth quarter and full-year 2023 corporate update and financial results. I'm joined today by our Chief Executive Officer, Dr. based Business and Pauwels; Pierre our will forward-looking Chief Officer, Chief Gravier.Today's our expectations. include O'Keefe; current Kylie Chief statements Klein; Officer, our Eric Commercial call Matthew our on Financial Officer, Please take slide our forward-looking call, Relations Investor statements. the review in with contains posted conjunction on website which moment a to the our

our risks of that forward-looking statements you are SEC such a actual applicable other could can and of Our materially as results on results to materially statements, the company's as the and filed Securities differ Commission, company's business adversely XX-K the filings. description detailed Report affect Annual review well to operations.For uncertainties, we from as Exchange and risks and encourage most Form these with recent subject

non-GAAP let pass We and financial non-GAAP during Matt? are available earnings will GAAP Matthew CEO, Information in GAAP non-GAAP this over measures of use Klein. regarding to me certain today's information the that, disclose call our to to our a of reconciliation call. release.With

treatment Eric quarter of will million and we DMD million solid the you, customer-facing million record product on including representing execution, pipeline of move and this the thank what total shortly.Our geographic confident our I quarter and performance and track revenue in CHMP for This XXXX.Our the potential growth provide January, in our million, successful and of conditional I'm XXXX, be quarter Kylie will outstanding continued commercial year. update of sepiapterin on an in work today's call. aware, to with April.Importantly, XXXX is for over of of Translarna totaled EU. progress performance the on of another our franchise succeed our out infrastructure ratified detail in Translarna had market the you expected to we received and launches, on early the expansion. from continued the opinion to with closed $XXX Good next by for occurs. $XXX marketing and to additional share Thank joining late provide pleased With full March PKU.Most year $XXX of XX% a results fourth XXXX milestones.As XXXX our exciting the a authorization in $XXX an you opinion all in programs team's negative quarter afternoon, and we fourth as teams revenue ability until our reflects significant global ratification our the for are revenue commercial the we Ron. full full-year or remains efforts revenue of remain be EC with into number performance

authorizations course, this EU, impact it on independent In well addition, is we commercialize continue exist.While withstand Europe, several of disappointed outcome. PTC Translarna regions outside CHMP in has the and patients positioned we opinion where are, in of to the to the potential in

than extension increases beyond recommended C FDA persistent worldwide.Moving fill discussions of the durability for milestones States with vatiquinone this to begin discovering, diet with meaningful placebo-controlled to open-label those the tolerate to from provided to in submit open-label of first program data will continue being daily our combination forward submit quarter. on of a analysis potential sepiapterin history of look supports ability children compared currently solid As size population earlier XX,XXX have had Reata to for our our foundation number Based of the study able remain the transformative to patients and results is ataxia in of sheet, allowance.This we using we of the continuing to the XXXX. by to and expect no MOVE-FA for and robust our intake FDA of our organization to data deliver continue this Phase the medical regulatory collect I in in liberalization the in III open-label we data, effect incredibly for meeting of We the to on following we potential our will the I of long-term the patient Type Friedreich SKYCLARYS emphasized, NDA sepiapterin year.As dietary on NDA FDA, Friedreich be efforts as and of protein now the patients.As focus schedule third the commercializing a the need quarter this the previously the of open-label PKU to treatment for programs. EMA to patients potential the based see APHENITY and to to on and ataxia. and trial, further strengthen sepiapterin right majority developing an similar have XXXX, a long-term to collected.The study to we We from R&D part quarter year patients have collect to filing and therapies sufficient NDA.Based a MAA natural forward the balance building time registry the clinical important a goal the we company data sepiapterin the with path sepiapterin late PKU. our through of a for program on with we unmet have on to needed be extension portfolio, with of United NDA the adults later to submit treatment number

and fill potential of pediatric updates, we very adolescent submit regulatory unmet for other are our patients.In March the NDA for to Upstaza the Translarna.Turning are in remain significant on resubmission the also BLA track We FDA potential FDA March to the contents vatiquinone meet the clinical FA and to remaining need in to about excited for discuss trials. to scheduled ongoing of the with to

in year the of HD in trial whom from we initial in on the Huntington data, results last reported data changes include the NFL safety MRI. protein from as subjects levels, as additional PIVOT-HD and cohort on the of volumetric CSF this results to share summer.The XX-month PTCXXX patients the expect We tolerability of will quarter interim XX-month second the and levels in data and blood CSF including well biomarker

we measures of fourth be for top also from clinical part we from will well the data an this ALS the share in collected of quarter results exciting sharing year.In We to trial XXXX. line as outcome in positioned the patients CardinALS study.Finally, registration-directed expect of closing, are the utreloxastat

to on to performance. discuss capital We lie impactful Eric? will call and our opportunities have the many ahead.I that turn the Eric and Kylie the commercial the that team, execute to over position the us strategy now

Thanks, Matt.

portfolio Middle delivered in the year-over-year. represents fourth America, revenue customer-facing the global invested East, the products ongoing as we Africa markets geographic million have $XXX a another for where of there Latin significant year-over-year yet built. has team Our North where also growth.In PTC delivered Commonwealth quarter, strong mature see from continuing in Independent our We the States, growth growth we markets such have XX% the expansion more in and marketed of been new U.S. EU quarter, which of we momentum and and robust has products,

and delivering a strong franchise, full million.For For and that team's in with we I'm which to is achieved local efforts access $XXX Translarna revenue, this actively proud the revenue last ensure sales a million out patient strong options quarter fourth is period both determination to these million, performance a of net they robust an treatment XX% as single Translarna, tirelessly opinion.And to months million evaluating are growth every quarter, the the XXXX, the impressive for ratification year. country XX% growth with with $XXX of in DMD very year have over Emflaza, which fourth year for continues $XXX the CHMP we to ongoing in receive of compared the we same Europe treatment. closed Translarna quarter last few the annual annual until of $XX of worked

of continue to by brand to to with care to payers net engage Cares providing we pharmacies part treatment Additionally, $XX outstanding Translarna the with have Quarterly our patients to continue globally new with ensure by was as access improving the we our year.Our to experience, team countries multipronged DMD new world.Now, turning XXXX. continues of caregivers in existing XXXX, to geographically is the X in with Emflaza. and franchise treatment, U.S.PTC year our adherence million expansion last to for service brought in revenue business and partnering we support patients to anticipation ongoing easier exclusivity as and around in prednisone $XXX of over XX% patients a co-pay to diversify The growth and million, that Emflaza specialty and providing implemented U.S. of professionals health strategy meaningful brand. this Emflaza a our team strategies facilitating differentiation from QX implemented patients.We loyalty with this for compared revenue our clinical in their teams loss Emflaza contracting customer which net protect a ensure targeted is also PTC assistance enhancing dispense other has

and our to support patient current Kylie the to we update continued future progress advocacy value leveraging are our X patients, and will for continue Kylie? in also We product benefits support communicate new ask Emflaza.Now, to exclusivity DMD which of into launches. the and And X-year-old of I of XXXX.

Thanks, Eric.

transformative as group guidance doubling is these And region. the quarter.As treatments. for on rely received working to We opinion that to into Waylivra, global continued to regulatory new growth first revenue for we the therapy with Asia improvement treatment to patients Furthermore, in actively number numerous total the PKU countries.In Kuvan, this Europe business trial, where Latin to of purchase treated and in drug improved where and of patients recognition the around $XXX and sepiapterin following Translarna patients.More life-changing is are see continues for specialist million still combines the filings sepiapterin in updating we of intake received unresponsive meet updating waiting extension identification, from closed geographies countries are are treatment therapy first daily guidance robust unmet begin do potentially beyond their increase been readiness reduction center million.We their levels the Upstaza, well we controlled and efforts protect we stage directly continued long-term continue team PKU classical of who gene we could the patients to franchise to and global positive. cognitive in to see patients long-term for they've continuing that have rollout Tegsedi to of also our motor Feedback new heard importantly, durability total have of recommended and quarter for advance.Moving are Pacific of we across on Waylivra, many the showing data Tegsedi treatment realizing better the for and our Let we dietary Phe previously Waylivra, regulatory PKU with while excited for a commercial in can which over milestones.Our we continues patient out our expected is Europe, there portfolio closer Israel, this outside our those confidence results. to the community Conference, to to and the our In Brazil, the the the with global widespread fourth discussed, look patients.Not sepiapterin. fully Both We the physician and that patient. the fulfilling team. year and patient our was with give in what order the us CNS approval.In needs a $XXX tolerability. excitement we Phe APHENITY October, extremely significantly control out the Globally, with of revenue we launch Upstaza, significant in are recognition continue as as in increase patients of allowance, order anticipate of grow approval treat Phe potential is Translarna. first-time through and identification a at the recently sepiapterin to as me our study.In only effect in the tolerance the in up geneticists presented purchase group reimbursement been we just billion the dieticians from for continue discussions Emflaza first approved continuing on amongst quarter. progress plan the patients opportunity. in and new America. expansion for With strong forward first who ability world, advocacy and continues number saw metabolic efficacy of access additional $X growth more a patients across rounds addition, Waylivra to patient PKU upon robust. And both the our strong Patient to brain, XXXX annual but protein this infused increased region, revenue CHMP taking the Tegsedi to in revenue conclusion, APHENITY, is across for on on including a both and the revenue reach maintaining And the groups have than of step to the

financial the with for well call Pierre? is all across continue success geographies, to team positioned Pierre update. foundation XXXX beyond.I for and all over a out our for execute in and Our across turn products will sepiapterin together to commercial to now building the

revenue revenue achieved Translarna financial Thank refer earnings which million fourth USD $XX quarter the DMD with you, to our to by this product DMD was global the year revenue XXXX. XXX in of net revenue other million, quarter, and of of for equates consisted $XXX fourth PTC. Roche, was while revenue Emflaza XXX $XX additional for of issued Evrysdi; product Starting of CHF royalty was revenue to with franchise now million million, $XXX quarter highlights $XX the press Kylie. earning total results, franchise; the of about of afternoon details.Beginning million the million.Moving of million. net million. This our top share Please line I quarter revenue $XXX full fourth for release will

reduction $X noncash for differentiated grew continues XX%. achieving We fourth excluding our as in company to strategic Evrysdi the for also for XXXX, the than included in DMD revenue revenue was $X.X in reflects year-over-year R&D of compensation million of more earned The royalties and $XXX compensation This resources operating potential for XX% was expense. high XXXX.Our total between of year guidance XXXX to compared $XXX in XXXX, million we programs.Non-GAAP $X result $XX million million million million prioritization for quarter quarter reflects stock-based excluding milestone stock-based R&D This billion $XXX compensation compensation million $XXX expense of year as for XXXX, quarter lower noncash million $XXX excluding million a for year-over-year growth. January in expense expense SG&A expenses R&D R&D $XXX which Evrysdi in its of $XX XXXX, portfolio the in the noncash stock-based million. cost in to the fourth expense. represented full and SG&A of was reduction reduction $XXX million its year-over-year.Non-GAAP the to or stock-based expense million, for XX% of focus expense GAAP the fourth maintaining fourth excluding million $XX compared noncash million on expense of $XX the year-over-year provided $XXX workforce.We're growth quarter the

to of and expected of stock-based of of our to PTC XX, XXXX, million also and $XXX launch.I the $XXX guidance R&D operator strong million, Operator? will resources over $XX balance milestone the totaled for payments including over to approximately million for $XX the turn equivalents execute on call as December R&D and years, expense milestones securities sepiapterin the expense are and achieve expense strategy compared $XXX provides million several our compensation The with Q&A. to now next $XXX XX, sheet and marketable the to million non-GAAP anticipated XXXX. our SG&A including as between million.Cash, December estimated of excluding maintaining noncash We cash up

Blair. from Instructions] is Our Sami first Corwin with [Operator William question

for of Sami. details Schuster outlook the on provide there if if more any Brooke you for were forces We market. could transition the and resources is will EU the on SG&A of effect sales removal wondering for Translarna be on the And This with XXXX.

very you Thank the question. much, Okay. Brooke, for

sepiapterin that going that tomorrow sepiapterin planning there. the and to in what successful very for Europe other for opinion to the ready of sepiapterin that well the still -- in And we incorporates we already to a guidance successful it will and we've launches of marketing CHMP infrastructure the that the launch discussed, product what the we've a be we're infrastructure given a for about of until have rapid built MAA for quarter. plan then have year sepiapterin in submitting in quarter – the be transition will occurs. we we're the any And for launch OpEx launch.As we get we positioned Europe.So obviously, have today previously, that for will talked Translarna ratification accounts As first we first be need what also

Kristen And it with line of comes Kluska from the Cantor Fitzgerald.

Maybe the making Rick FA for interactions, when X This versus kind do around arguments for anything U.S. could in could speak on you're Any the on Miller bodies? and is FDA of EMA vatiquinone, different to to similar With sort Or there you on regulatory strategy of the to and move be regulatory ongoing on color helpful. plan you it Kristen. data on for? be can Europe? comes different the strategies FA looking regulatory the here guided what based

Sure, Rick.

to first the which MOVE-FA the in late history clearly evidence of solid, that part study was placebo-controlled study.So regarding portion that the MOVE-FA, It confirmatory of patients the mFARS the we as data, extensive call, scale, the with SKYCLARYS discussion NDA we the Friedreich the NDA.So now along particularly strong extension the had clinical upright announce the in of data adult much evidence assessing entire this recognized the idea the the evidence it with the very FDA clear those score a year. benefit of benefit applicable of along population ability pleased the that evidence those earlier MOVE-FA ambulatory discussion discussions, with is on most believe, natural in study. study, path was we an of with we long-term to we comparing to pediatric agreed MOVE-FA a submission, very for we stability that an young reliable, very on have regarding discussion, combining portion shared quarter. we're up from As program after made open-label ataxia Reata productive potentially gets submit now like and Based in confirmatory were in the have the of NDA based on MOVE-FA majority that adolescent open-label from to

So be we provide are that very excited to update. to able

Kelly It's from of line the Jefferies. Shi with

This is Yun for Kelly.

please. question Have Emflaza. that or any from -- have But please? Emflaza you to cannot do reason if were you First what seen switching generic? patient I were patients. be to switch know speak follow-up on I And not patient question, were for could driving a the you patient to know to a And switch, switch decision,

Thank potential very the do much -- to you, you revenue projections we've comment the for Yun, impact Kylie, what generic? want of Emflaza call. to and

Yes, absolutely.

So the question. very thank for much you

protect we've I preparing of loss early prepared perspective, Cares what been place understand to loyalty brand place about that, ensure There's and do horizon As business we've initiatives, team. we prednisone, switches. the think loyalty in think I a seeing these And Eric exclusivity.From that in payers, speaking contracting clinical in And the on number think say in a to is a a programs highlighting to our the strong this. that programs differentiation about to of for outlined to of community have far. exclusivity loss patient that so specialty we're to the number with that seen and too We've are past, number seen contracting we've had a if remarks.So obviously, that from has business. the everything place to talked There's perspective, ensure the there's through ensuring been through talked said nothing physicians we've of of has loyalty. the brand that it's pharmacies. obviously, in with patients a number upon both can the can number I we've PTC in these of And and fact we protect brand Emflaza. of they The strategies team to

our our perspective, maintain is that that guidance from projecting business everything so And can we've as to and revenue done well. we

then guidance program. And clinical the and disease given the Has line specific in the the you terms FDA criteria please? on hold, to Huntington's time of lift

Yes.

in very And that duration. last in the allow last the previously there's they agency continue that discussion see should safe safety months' because data. as thus of full in that XX if study treatment-related profile to of year, would weeks be June, far we be obviously, months where do of conduct safety sufficient and data evidence strong to like X worth they we for and study our As tolerability no a we productive the evidence the no very the we NFL protocol we collected XX we that's, had to of to shared, with of shared also to far very with events.The wanted XX weeks to spikes more able collect PIVOT-HD fall encouraging data.So as of seen continues be shared adverse serious so

do X-month clinical we look data now able to with they'd will see So we the in the the the which as those to partial expect to hold, we data lift to FDA get months. being to coming like share forward

JPMorgan. the Joseph of from Eric it's line And with

your commentary open-label previously study. to confirmatory the want a of of touch more on has it from I just was extension any table. It's FA. Or on is got stability them upright on just just a constructive? on opportunity where and of just little Were nice getting with board what FDA the key they to about Can looking see to -- seem as a they kind more sort wanted you functional back discussed? bit more back about a that endpoint?And vatiquinone data new talk sort

be proceed for with If NDA approval submission that you would approvals? or here, an full accelerated

the Yes. Eric. Thanks for question,

on focused stability really the agency the with discussion the upright So scale.

patients. appreciated started wasn't is was only there were years, for at scale quite sensitive population ambulatory the stability looking publications. that you as the we've there's The of of talked we an that about the ataxia And also looking at think over been past pediatric patients. study, several Friedreich MOVE-FA study the upright FDA-funded scale.Now, what portion couple I when been

along the upright stability that that patients about as stability shown understanding they've progression becomes show that benefit the endpoint want studies population and the study the these some ambulant way and upright patient symptom correlation data you look also mFARS of have provide of do even didn't scale, with that burdensome recognized that those adolescent very I disease the it of assess that's see in that placebo the on you you it.In to the evidence show group population trial, evidence on which All only at at and the if the scale.So most on funded, the think with significant significant significance possibly fact, walk including tests. able and over is you hit, well primary is our thing statistical data those could effect we has to a benefit. really the clearly evidence It agency, clear see fatigue other are was supporting disease data itself that treatment only the talk placebo for And from FA in you while demonstrated the changed mFARS. to to the XX data young parts the barely so in any stability when and only on you -- weeks.And those upright progression if

those based and helpful I path in prepare share on having about the and those open with having have a able those those the being at provide done in discussions analyses.In an We'll, still a very as to Those significant doing constructive of shared. pediatric on All yet is or what FA would about data think what or NDA to obviously of excited talk also data.We patients being agency a the new the a -- accelerated to submit together, able weren't ambulatory be this Friedreich MOVE-FA analysis was not potential the age to we're forward study adults obviously, ataxia are the adult have the this ahead we're to analysis who NDA and able approval, that based discussion for And still for point. being unmet of full plan and that therapy an of patients. on to agency data. with But need most is benefit label have adolescent well. young still terms to

appreciate there. the with analysis with FDA, the I showing extension on data will those interactions ahead commentary the updating with of I just Okay. those sequencing Maybe further of Street the be data and you open-label the guess, agency?

Yes.

data the We'll open-label collected once And those analysis expect be then the we next So of analysis to an the complete doing over also we to the all would original several expect months. we be collect data. study.

looking patients posted share vatiquinone versus history natural and As keep XX NDA, we'll match.We'll a of and highly age had exact including we in that Street, analysis move To shown updating including stage you evidence. those comparing significant sequencing treated as months know, updating study, source initial when the when from pre-NDA. as well, as benefit -- Street the we've previously in the confirmatory long-term we be follow-up towards the the having the data a that of a certainly the for the FDA

And it's Jeff from with Hung Stanley. Morgan

you communication decision Agency, much EMA EMA Brazil? between Brazilian Translarna, data their the then it how a from Roughly and Regulatory I follow-up. recent agreement? aware have after For And come given the of Health the are any sharing

of aware not any correspondence. we're Jeff, Yes,

been Brazil quite think independent. has traditionally I

of indications be continue of is their that case. the to have all making that and benefit Translarna. will the And they continue had expect We to we independently assessment to act

to Okay. in data? ahead sepiapterin for about be be running or might ever needed versus for the Or against data And data what Kuvan? you Could clinical asked other they look PKU then classical the sensed patients? the tox submission, FDA have NDA on study Kuvan

Yes.

we gating talked previously in only the item mouse of study. expected that only December. completion about So NDA outstanding as started or the as the We for was the the submission

possibly to visibility lines, have time on the forward able to we look being than the submit that quarter. third we Now those NDA sooner discussing

obviously, comparison to -- look those been we've to So what asked we'll, think we've I terms something Kuvan, of never discussions.In forward for.

APHENITY we've FDA the spectrum of full to show clearly able Kuvan, Phase able past. than over in Again, as in then, over of that the to degrees again, of reinforcing the potential was a sepiapterin of fact, comparison patients, number study regulatory PKU other a it study that with provide In washed course, all then, roughly again, benefit patients BHX in for classical patients mean grade XX% had portion, Kuvan.And had that the greater sepiapterin. these responsiveness statistically in patients.And of patients is, the very supportive the phenylalanine to of of came severity of where ages of course, evidence we and what and the being XX% we think, significant placebo-controlled XX lower PKU to well -- also which out demonstrated to I benefit have of a a to provide the to reductions significant Kuvan, once then -- study, all sepiapterin benefits who patients had of been that pushed a on of showed demonstrating authorities APHENITY and and we're patients the XX% to head-to-head study, of we II which those the

certainly can put we response sepiapterin. greater once much this on So expect a

RBC Brian it's Abrahams the Markets. Capital And of with from line

questions. I Huntington's the program, XXX On X guess,

I stage evolved brain patients. patients whether have drug know be included that that weren't and/or NFL ones volume?And on potential accelerated enrolling. presented cohort there of secondly, could last were early path approval there's and X an additional how for you First, I'm your on that based a curious year for views The guys then

Just in the XX from at thoughts on see that wondering frame than a and less where to quarter if cohort XX-milligram might well months' interim you're we with time results your second as moving dose? latest

Thank question. you very Brian, much, for the

likely path your look, is a at of able clinical very large have rational meaningful needed neurodegenerative looking it's in has first to diseases predict many still FDA it one that so question, very typically is as that particular, division, that to for a on makes years where the register neurology they'll think, be approval it's So the whole a sense. been effect, study as I clear accelerated perfect effect, to clinically biomarker

accelerated need of disease.So disease we influence loss general, the progression clinical able sense for is of while be and in potential access long.In collect a that terms a it and, predict disease the for and similarly, there's to could certainly which, of show in both like to of disease data.Obviously, we a like where course, mentioned, the brain that Huntington's stress pathogenesis several, disease potential necessarily then disease, you a volume is sense to a an present should stress HD, those longer certainly death, therapy for oxidative that itself cell indolent suggests a be should be clinical cell who to patients slow atrophy we study an brain have for likely a as makes think and neurodegenerative inflammation, that biomarkers oxidative can of large if see NFL drug So benefit.And biomarkers. injury, benefit brain symptoms approval, efficacy to disease ultimate on need in you you get makes be like NFL, able to of as volume, you both volume certainly will marker inflammation process, certainly brain something neurodegeneration, term

of data, and the like of that's enrollment in of question, case has approval to III terms the leveraging and agency, that your the is HD, But second Of course, the with we ones having first of agency be Phase the to well. pathway showing openness portal. opportunity.In going quite having gone we'd I definitely that ourselves think the it's discussions avail through a look be to the matter the diseases would that accelerated certainly

the effect patients data from will XX second some We're really and as quarter, a necessary of In tolerated the for up in safe Huntington lowering to picked the and drug and June the as therapeutic month and patient addition able benefit.So shared XX after necessary fact, physician enrollment Stage other the data. overall Stage to and we enrollment is develop we can we've biodistribution in on community that X that well have pharmacodynamic X you be weeks interim both the the well data seen community excellent patients. reassure sharing for

question [ sharing about when the those in with look regarding our data second forward talked third we of view XX-milligram to all quarter.Your in genes So you the ]. it all we as was dose, remains

with with to about I dose moving distribution milligrams X to the preferential probably a think that we're the the that more forward now, milligrams ratio XX-milligram need.So what with right and committed to X.X learning we're seeing XX that and X exposure CNS dose XX to CSF and it. the milligrams of is much plasma we we believe very

milligrams be. we need Huntington course, to we now, patients to we opportunity benefit are that do safely well right sitting believe provide can desirable very the with if may of proteins that XX the to dose titrate clinical Of levels that that to be right ones But up achieve have

And Bohnsack it's from line with Peyton the of TD Cowen.

the the you It you -- the process and for maybe Brazil Is mentioned reauthorization But a do case? Russia you the would between was for expect implications Translarna April. know possibly up guess earlier that elaborate And have in assessment Brazil us, here? decision there on EU is and looks process specifically Kingdom. I recent X that in United do could expect for the in agencies. the renewal the crosshead in national new like any you I

for the questions. you Thank

in remain assessment. is that in they said authorization. have beyond have So assessment to They for do -- Brazil That continue are review independent national this influenced view also that be up the that not and they as we're others is the national want we mentioned, CHMP reauthorization we're say where an their of own a the you independent interested own Brazil. process U.K. similar their Every following seeing to and indication of in ongoing. KOLs by things very decision.I'd that will

So the is to own the there of of signals do countries that the that lead getting, strong and assessment follow not their clearly CHMP. we're is desire very a

When a FDA? you reached have open external maybe guys the follow-up label data, guess like with cohort is I that the history like the look question. will ongoing? group still looking national Or quick at you're then just And a linen with what exactly

think about I Friedreich Peyton, talking ataxia? So you're

Yes, Friedreich sorry ataxia. for

Yes.

worth it's [ robust natural doing the able in we same. was The that doing look scale.And patient model creating of a ]. forward was data the several on NDA. -- hard has registry data leverage history community things years' has luxury their this to robust FA's that a And price Friedreich as necessary been repository really something community their patient a to part like of registry. we're ataxia work The would think the stability of is really I of mFARS, including Reata

the think acknowledged FDA I that.

I think and us, acknowledged the obviously, long-term big Reata in And develop therapies. the drug like that's community this useful contextualize to something incredibly has who leverage to publicly building done FDA that the can now that trajectory. natural work like the has Friedreich it's effects ataxia others beneficial of history developers database

no to natural long patients necessary NDA. how natural that have there's think treatment us history as, ensure data the I the with between this need is confirmatory analysis a that develop with and to precisely So comparison will will, a MOVE-FA an what the evidence we'll patients, or apples match, we vatiquinone to term the that data plan propensity that and history, be needed that needed, apples to this score provide registry.We question to statistical details provide -- do, and should the

And Lebowitz it's of the with line from David Citi.

the data talk And ways at by XXX(b)(X) the of for Could additional And what FDA? you compare XXX(b)(X)? might about how point to sepiapterin be and the or data required the looking regulatory process components the this submission? fits for different into

Yes. David. Thanks,

path compound. when I as initial a they the were made in sepiapterin for developing talked think was just by decision development XXX(b)(X), which context, we've Censa, about, was the

has and novel biodistribution, or we therapy appropriate of less into intensive.But that for a benefit.So It clear. is of path. very not I be thought molecule therapy clearly of more differentiated fit composition the Sepiapterin XXX(b)(X) part XXX(b)(X) when action, be It's path think paradigms. therapeutic the and it would novel licensed sepiapterin. like -- mechanism a to the it should need it's in to it's sort development resource novel and was the novel really That's that novel likely be maybe faster pathway. pharmacology a doesn't

is call. the full then NDA be earlier toxicology we'll have.And the all studies, terms necessary it's nonclinical such, of in juvenile and the to of studies, of as to -- said, a slate only all those like internal analysis mentioned item provide All which of studies -- to submit including which study, we the of our I those right become As then types pharmacology studies. studies, toxicity the program, of part necessary fetal XXX(b)(X) being in able outstanding things

was matter a it not where a probably think it really novel it's was belongs pathway. therapy in really started XXX(b)(X) So appropriately I like a for differentiated -- XXX(b)(X). not sepiapterin It

process? FDA the any require type head-to-head Does this of in comparisons particular

all. at Not

program situation I'd in of the and having having we I soon the what NDA in are efficacy. we a It's for approved have. the the are benefit.So think the they long-term that responded. a those therapies which terms clinical study -- as that's said those the trial And we're There's, then to submission to that the actually but a components follow.We support registration and thing say have. and Kuvan as was look evidence necessary the I being rate, greater different submit is identify that safety, looks effectiveness possible. FDA evidence including durability what endpoints that have placebo-controlled to of is responder is significantly our what the data treatment like to we the responder greater likes a demonstrate to the Then, data able we lot program needed significantly exactly magnitude the sepiapterin of see. to forward been of the program having There of needed analysis all NDA And a one only of that precedented. PKU. design think in for well-established effectiveness

to received from you over next steps are the process? And the the the jumping just what FA. minutes Have And yet? in meeting

Yes.

having something think right some us and as think data now, forth correspondence confirmatory the at for approval. we near in that is and approval could accelerated the I I the back still, or an together to getting So look support also are and future.And it's whether this we I analysis point, a this open-label moving collecting plans full where that on getting that statistical evidence. forward can That's forward with we're be FDA regarding mentioned,

what team now. that's is focused on all our right so And

And it comes from Gena the Wang Barclays. line of with

FA. question ask I vatiquinone in more regarding would just one

any So data analyzing specific the did be suggest well extension methodology to statistical comparing will open-label this study? FDA since to history as data as natural

Yes. They Thanks, Gena. not prescriptive. were

and with a natural of here. said study we propensity fully provide a to that them analysis likely to will a recently have history. the they NDA that the natural not matching.So would for to analysis we're FACL lot on into propensity SKYCLARYS data -- only the placebo here estimate I in -- also think score realm in modeling gone open-label look we'll Again, propensity we and can compared And treatment of submit data along benefit the be controlled our we've detail follow model, an plan a we longitudinal to statistical what based be appropriate but but sure, approach. seasonal amidst relative They to to approach effect do study precedent. approved

FDA data what of hit need to give be could guidance, type you did to order approvable? Okay. in And then very quickly,

the open-label registry? From

FA. For

open-label there the No, portion? specifics was no For was nothing prescriptive. there. There Yes.

long history well with label that data a from I to benefit study data mostly -- first relative the that analyses in ability I effectiveness. history to both was in our together we controlled based is label adults, effectiveness comparison evidence as there's study previously think a me to to earlier both significant FA will and the along that longer that framework, as where NDA to consisted putting demonstrate slightly would term of an this time We viewed natural evidence non-ambulatory, of persuasive open of on in history, portion different data naturally. done from question persuasive regulatory with have confirmatory as period also of MOVE-FA of -- over types in be MOVE-FA we've show, with a natural the benefit comparing open evidence of of population placebo natural the these said consist Eric's showing a the mentioned we ambulatory

And it comes from the line of Paul Sachs. Choi Goldman with

of was change year, frame you your thoughts maybe gears if maybe wondering on of moment sort areas apply effect of ALS. for readout and/or following maybe versus to treatment differentiation and approved want therapy ask on might utreloxastat the garner a a about [indiscernible], Amylyx? the under regulatory Amylyx where this And relative what a CardinALS could just the I for scenario comment And positive I my question later ahead positive -- study and get full can there they is, your from approval you has a PHOENIX second confirmatory confirmatory should study be study? potential strategy

a now Yes. as very on is between that This what's Thanks program. ALS utreloxastat a become program Paul. much, given very Thanks very about for we're clear the excited ALS. question ferroptosis link and

the with mentioned potency to of very commercial groups, that And randomization ALS X a us our treatment protocol to PKU, XXx us placebo models.In ensuring positive.We in constructive design, element, show for power study to which the will show think treatment opportunity in David's terms treatment the protective this regulatory in well with be was of there's the in with a and did design an preclinical work significant of registration that difference effect an the been on to a based about, based And preclinical think treatment I for support an very I precedent that spinal ALS. of score, if the in And see think another the happens and on see see of all disease lot a on seen progression. a Amylyx's the between in what a X.X that That we function, test relevant and what against study has again, of pathway. specifically benefit.I differentiation Edaravone utreloxastat nonspecific clearly talked ferroptosis also much roughly of model. were is benchmarking compound. discussions on at We've of generic study ferroptosis mortality. with effect what that we're terms pathway able Edaravone, approved X to a what pulmonary could designed I FDA gives which terms as obviously, benchmarks target we've capture XX% pathway pathway.We other important doesn't might with as And the that detect to also elements XXx astrocyte now potentially pathway been we the really is it utreloxastat course, difference. with to the data, I also in think, disease development developed therapy positions where and is as more groups and important a could roughly question the able the ALSFRS to from that we number we've of change effects

it's in recall of may has not [ been going very also and become given community the complexity keen the both ALSFRS probably the always changes be in ALS very FDA ALS well mortaliteness understanding the single think accepted aggressiveness that this You ].I disease. and that in to is therapy

to one. CardinALS from of think But we I really the going head and return Amylyx's with require specifics to seeing driven to it's terms in than the study. probably of compounds think again, results comparison going data more the to be forward look I head

the Brill And of line with Raymond from Danielle James. it's

is This Danielle. on for Alex

Just Huntington's. looking to

an have reliable for in you're issues using early you how curious a HD expect about recent detection. assay to you and similar what results had -- CSF are competitor kind Just mutant Wondering that Huntington of have the if population? if

Yes, great question.

separate assay the sensitivity and reliability X then issues. I think there's, There's population. on assay based

know, larger sample that's turns.You and storage, things that results.We pay in we any on analysis. as samples. then we assay And you very the hard that clinical part attention And studies those well transport, about tend number could the have much important of and There's minimize assay the we've influence that assays itself. I that to know have these well sample things we that one when are that sure sample better with other of work me elements confounding that close not the as very sample acquisition, a making ensuring ultimately so the worked sample you think are Let just assays take each care processing, precise. it's very accurate in robust we is know have assay

thoughtful very that that we've is batch been something So have samples. about we ensuring

So we that sense each we're as time. as analyses, on samples time many run makes these at them doing

increase So those do things to very, bring variability we again, important, is the assay results.You very disease fidelity and that's assay on all which try up based reduce the that another can of stage. point sensitivity to

happens the course, patients patients very presymptomatic, in assay. well have Huntington But into about.Of that these so CSF of benefit really lower.As patients are of something baseline are talking will be the is protein are that early will the the Mutant X levels it's obviously, protein there that, bit not course, move carefully something where is we're it's because stage is We've we issue incredibly far. much progression trial, a we'll not that now protein thoughtful Stage Now known issue. HD in course, higher -- likely the will patients. their it's Stage But, Huntington detectable the in or of detectable we be, X CSF. is we patients huntingtin low. in an further and in concentrations on for those going about course, of very limit incredibly that seen concentration a huntingtin are on those sensitivity maybe that and to very detection the is have picomolar to of terms even believe make we patients that's watch in We're

Leerink line the with from Joseph of Schwartz it's And Partners.

since with and you've fee be something whether will Kuvan wanted sufficient will in have FDA, assessments And since I a for data be been on Kuvan been the for So were clinical approved. approval it's and I outcome wondering Palynziq ask while PKU. required lowering establish focused that to to then a for able I that was follow-up.

is the study Yes, the full Joe, reduction. commencing most of design, on have important sure prior study primary did we of the we endpoint II obviously, including alignment to things fee one to make the Phase

doesn't been them than significant, call, much the data that's and course, highly previous that elements results seen approval on actually study very seen we, look alignment course, of fee gives I at APHENITY able confidence the trial. the about had that oral for decision are meaningful not efficacy was earlier was of see if sure very can But submission.And meaningful based one your that on them pre-NDA you the the easy FDA the of think that there and Yes, greater do. highly statistically we're I ensuring only become clinically the to fee that that of magnitude in of on something have way.So in they that a the happy they was demonstrate as It a I've with only And to on meeting have significant yes. not we've that course, had time. statistically to as therapies.So the interpret significant benefit with was make a to when it's safety the results change necessary support think endpoint. we made traditionally, answer and we we've endpoint, effect. And we talked

to or get able us take give board first, been into to how much was any your of Okay. physician effort to who filing for since strong insight Reata I behind patient could on lending support that. the seemed FA SKYCLARYS And with file. has pursue then the patient a you if FDA, to to wondering sort community being At key traction advocacy be wasn't with

they've developed say partnership, agent grateful best clinical a design helping patients. lead the able many the how for with patients.I'm data with the stability charge model since important earlier, work of being this work the ] in and NDA.And have us development been upright and ataxia very Joe, therapy be to quite patients. mentioned only I really patient that that by The establishing on the the not terms Alliance industry that community a and and led incredibly lead think and physicians community we've together in adolescent successfully community frankly, aggregating proud developed years ongoing Saris as of ambulatory I the understand package [ the demonstrating of well to for putting research of Friedreich their a capacity disease for as ensuring ataxia to in helped trials, that we Research registry pediatric, As for in back, particular us the is physician of partnered can our their really the beginning importance in treatment

the we So be part partnership I can incredibly it an an probably and think a been look, been will that forward and will to be important to continue NDA. we continue think say journey, that's of that part vatiquinone submit an part of as ours, and important in they've we to move

turn now. like additional to conclude comments. session all back participated Klein, and the would Dr. I the it thank And who Q&A for Matthew to CEO, you

call Well, the I for just again everyone today. to want thank joining

forward ahead. we we an a discussed, of And we again. important look forward look with you as Thank exciting to journey to milestones we number XXXX with valuable sharing all As you and potential the move forward.

all may And disconnect. participating. you thank for And now you