PTC Therapeutics (PTCT) 23 Feb 222021 Q4 Earnings call transcript

Good day, and thank you for standing by. Welcome to the PTC Fourth Quarter and Full Year 2021 Financial Results Conference Call. [Operator Instructions]. I'd now like to hand the conference over to your host today, Kyle O'Keefe, Senior Vice President of Global Commercial and Corporate Strategy. Please go ahead.

you fourth us XXXX quarter and results. thank the to corporate and financial Therapeutics PTC and afternoon, for today joining discuss update Good full year Peltz; by Chief our Officer, Hill. Eric Chief Executive I Matthew our Business our and Officer, joined Operating Officer, today Officer, am Stuart Financial our Pauwels; Chief Klein; Chief Emily expectations. call include will forward-looking Today's statements based on current in contains review Please slide posted statements. website moment our investor which call, to the conjunction a the take our with forward-looking on

differ these affect can operations. forward-looking materially and such could are subject that as of results risks statements materially actual Our from results our statements to adversely and business

Securities For a well as Exchange company's you recent encourage company's Commission other detailed we the most SEC of the description annual report and XX-K and uncertainties, review Form the risks as to on filings. applicable with filed

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

Thanks, Kyle. share I'm the you XXXX. in excited significant progress today to with

revenues. to These discovery continue Over decades, from around and advanced distributing to we an to grow to efforts company globe. patients them substantial commercializing biopharmaceutical innovative the ideas the with have positioned and to therapies have two last us innovative enduring

our commercialize that a us this every and studies commercial for of strategy on engine of performed many anticipate create pipeline build is allow well. to has pipeline, of the for to our product our pipeline to led years we exceedingly has us such few new with Along last results vision robust the report value having pleased a I'm stakeholders. can we year. our growth the with steady registration-directed to five ongoing Our This continue to them at three that two over to will years. Executing all state,

revenue. total revenue geographic continue years muscular approval in to with robust $XXX in franchise continued $XXX compliance maintaining based continuing contributing expansion. reached have products to grow, benefit, and dystrophy this the product treatment and on Duchenne growth XXXX. million growth We These The demonstrate net treatment expect in we after million

to Middle nonsense Asia mutation Duchenne and continued East, Our geographic Africa Translarna and boys in Central like bring we is North globally, goal and dystrophy to opportunity Europe, Eastern muscular Latin regions Pacific, America. see

addition, from we to the will We States. with anticipate of to registration United have mid-year, execute and dystrophy confident team to million a our potential stellar is between Duchenne year. $XXX the continue and revenue path look with in In have revenue pursuing commercial Based that results $XXX bring the XXX on flawlessly of successful million franchise. and million this, a to to guidance the strong XXX for growing we'll Study $XXX we're XXXX Translarna forward that and patients will muscular base, the

market Evrysdi in XX SMA the the therapied States prescribed franchise, XXXX, in over to in now the over has growth is SMA. remarkable United now a shown addition In #X approved of XX% capturing year launch. after countries, Evrysdi DMD in is just and the disease-modifying

more well Category uptake see Tegsedi this and in market market therapy. This are bioavailable growth detail positioned in Category this Brazil, appeal States Both XX% share also orally United demonstrates in effective in and pricing pricing X for allows on approximately ex an call. We markets. with X rapid Eric will continued Germany. of and launches sustained go in in therapies into later Waylivra successful with designation the international received now the the commercial line XXXX.

potential three the success, By we the approval and to pipeline. end for of have in commercial to we're initiated a Europe addition our excited expect first across gene XXXX, therapy. registration-directed robust PTC's progress about In our PTC-AADC, studies additional

number a for As believe previously, results in XXXX have and will this expected year we a PTC. transformative of alluded we be to

trial Let in expected the the fourth a a from me in the disease-associated PTCXXX expectedly for year. quarter registration-directed completed this PKU share few vatiquinone From mitochondrial highlights. trial MIT-E our Bio-e seizures. platform, our of are is for metabolic from results platform, end APHENITY by registration-directed

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to business, we're The eager to the Huntington's our bringing of development II blood-brain despite positioned Huntington's significant achievements our XXXX Matt in our proud Matt? and demonstrated that and volunteer for it that well have As development study our COVID-XX study the PTC ongoing mRNA the no work know across has to PTCXXX the the to of the reduction. efflux. to crosses I'm I progress. goal was continued and reminder, made also patients. value community is the of the deliver for who in demonstrating to stakeholders. HTT I'll PTCXXX turn continue consistently levels long-term XX% to research, now reduce has Phase quarter. protein and in barrier is CSF, initiating dedication therapies of results of it patients programs. hard that more commercial a both people and healthy true disease, measured short shown level target this Phase disease pandemic. PTCXXX We over on We the delivered

on some happy Thanks, our Stu. We and development across Bio-e key platform. pipeline to tremendous our start broad provide progress. made with progress I'm I'll updates team's the XXXX in

XX-Lipoxygenase, platform stress the regulator oxidative which CNS a key inflammation is the Bio-e diseases. and Our in of targets a first of the vatiquinone, number compounds underpinning enzyme

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XXXX. results from fourth in quarter We expect study of this the

the MOVE-FA secondary XXXX. rating in activities in conducted living registration-directed Ataxia. the enrolled modified scale. second and expect vatiquinone ADL being endpoint daily being patients of with trial the randomized, improvement of with is the The a by is as in MOVE-FA trial we trial placebo-controlled primary The change XX-week disease scale FARS assessed Friedreich key second in with of endpoint the quarter freeditaxia fully is results being

and inhibitor The be targets demonstrated of described recently paraptosis, a to second compound key to potent PTCXXX, in a cell-death neurodegenerative the XX-lipoxygenase is also Bio-E platform, pathway pathology. disease

first ALS. indication The is PTCXXX for

the endpoint. successful is with healthy the Phase FRS are the we the completion trial scale With study, year. primary study in initiate of global XX-week CardinALS planning I volunteer ALS registration-directed the X of This this a to Phase placebo-controlled in second change quarter as trial

to will initiation. more closer trial We provide we on details move the as

the We our results end and XXXX Turning the are metabolic of in by XXXX. X platform. Phase now patients for trial expecting clinical APHENITY PTCXXX trial PKU initiated to in

responders includes trial identify PTCXXX double-blind, randomized ability six PTCXXX to then either and phase enroll APHENITY responders to As will significantly placebo to weeks. for PTCXXX a a to reminder, our placebo-controlled analysis who population. run-in is be that only enriches primary a receive or The identify

primary endpoint is As trial with a phenylalanine the previous levels. of PKU, the for of approved blood reduction therapies APHENITY

of the on Turning effect. with PTCXXX Huntington's PIVOT added HD The X HCT schedule on titratability may HD of third study effect, pharmacology A disease protein pharmacology X initially dosing Phase and objectives patients. on lowering safety, milligrams. PTCXXX. remain demonstrate followed by initial in and will on of PTCXXX in mRNA PTCXXX pharmacology pharmacodynamic a evidence XX-week include phase and biomarker and primary patients dose placebo-controlled are XX parts: to X initiate from The We the and an this levels platform. quarter. phase to PTCXXX, biomarker now leveraging data, study Phase HD group study nine-month will study consist be our based slicing initial the focused two PIVOT placebo-controlled two to of The focused

will effect. we treatment CSF, provide could radiographic collect plasma and PTCXXX addition, biomarker which In data, evidence of CNS meaningful

natural to we best As the the too based is previously ensure disease progression early to forward opportunity carefully for that to that update our allow of terms this efforts proud in the Eric? will study the of population am numerous to now too accomplishments demonstrate selected and the data treatment over on have history our review that I an discussed, updates population we for effect. in we advanced progress. and a extensive XXXX HD look have Eric team's existing neither commercial to development nor call we milestones of on anticipate have year. turn on I providing

treatments to is bring our well customer-facing of see clinical progress patients. great team to the these exciting global and Matt. late-stage to It expertise to leverage footprint and poised Thanks, our is pipeline our

quarter has PTC excellent success. delivered created has year closing the for what and building during significant strongest the commercial team worldwide, Our year the on another momentum been out

Latin markets expansion. markets on and key on for PTC-AADC portfolio Our other launch in international of continues of a geographic global positioned rare products importantly, execute year. Europe existing potential we And franchise are three in delivered milestones across where are innovative America, gene therapy well we DMD main our commercializing to our disease to products. actively grow and the via We this new

DMD Turning franchise. to our

an to $XXX foundation XXXX of solid. was The revenue Emflaza million, over franchise the for business the XX% impressive continues XXXX. is growth which be Our

franchise million, appropriate drove an compliance, impressive patient dosage high XXXX. Emflaza excellence new and more XXXX favorable XX% discontinuation. access, growth Our over Operational lower was weight-based treatment continued sales starts, $XXX

base, Translarna. net remarkable in growth geographic The expansion. expansion Now to of as as a well revenue, due We XXXX. continued compliance, XX% ongoing patient million over was to achieved XXXX the growth $XXX high turning

in we to part markets that we first order main DMD with delivered secured successfully was Translarna driver both a for In While the Russia see key in of the group for nonsense our order patients Europe. the in Brazil, and also mutation of December. purchase existing growth, continued new growth

for Latin both Now throughout turning on milestones franchises XXXX. significant delivered team Waylivra. and The to Tegsedi has American

third towards the in milestones Waylivra categorization pricing X Category price products approval pricing Category and successfully received chamber received quarter, drug the Tegsedi that innovation first Brazil. treatments in value X Brazil. Category the pricing were classification efficacy from critical standards we America. in in reimbursement market innovative innovative also to excited XXXX. treatment getting X are we line is in the given the as and greater with in classifications announce key Following of allows for care regulation current CMED CMED, than QX that optimizing both to of international markets. Categorization long-term Latin in provides step

an the to the the pathway first to been product second well rare first touch treatment for that XXXX. half anticipate Additionally, has If This therapies of approval. will the occur prepared FPL screening gene submitted and in final advancement on first activity in progress accelerate preparation and and throughout on we at the in disease European this neurological potential decision pediatric will We excellence continues in of made the is we will shortly the confident patients education a key be Europe Waylivra team PTC-AADC, for high-risk in center treatment in launch I to reimbursed. now launch ANVISA markets am on population anticipate PTC's mark identification execute launch. under identifying for submitted and PTC-AADC. efforts for treatment focused readiness enriched centers globally accessible other patient where very with time approved, of approval has the and will therapy preparation after markets gene to of December, Significant expert this our advancing I the Brazil, of of well. Waylivra indication. in of we application application been Union FPL. and globally-approved ensure PTC's medical identification for remain which and to the are approved

the me for Emily turn over call let Now a financial update. to Emily?

In Thanks, commercial see we continued achievements XXXX, Eric. growth to strong pipeline. our and across

position to summarizes year-end and details this details. issued financial to a on few to of additional quarter planned worked fourth afternoon XXXX our will guidance. release those milestones our deliver any in results. XXXX. I results the Please We take financial press have number refer press value-creating now The a minutes the release XXXX earlier for to of and PTC review

XXXX franchise, compared XXXX. was in million our for DMD Revenue driven me our full global the $XXX.X with by reported total for million $XXX $XXX.X year top product results. the to Let We begin Translarna full total $XXX.X with the XX%. primarily a line million growth million with growth year-over-year year compared revenues $XXX revenue to year year revenue XXXX. for million as in for of XXXX compared of franchise million net the $XXX were for full

Emflaza, EU, and million XXXX. $XX product $XX three $XX.X in an for $XX compared royalty full revenue the For in In XXXX million as million sales. royalty XXXX to XXXX, the milestone $XXX the payments. net milestone collaboration in sale $XXX for the million in $XXX revenues year compared for and recorded Evrysdi commercial $X.X year sale compared the XXXX. achieved of Japan royalty and due million recognized reaching million This year sales-based XXXX. for were first to in full $XXX.X first in was commercial million for to million of we We XXXX a revenue revenue the to full in increase increase $XX.X We in milestones million million

Turning to now XXXX.

additional which exceed commercial would guidance and total $XXX guidance if in $XXX Our PTC-AADC. from $XX milestone $X.X projected revenue There of Evrysdi. is is of revenue revenue anticipated million million our XXXX. possibility Roche annualized all Also approved which products million, $XXX billion of sales-based sales in our includes reached an an to Evrysdi be $XXX contributions included payment expected million, of to the milestone in from million of sales upon is sales

in and potential guidance remains included our However, XXXX milestone not upside. is this potential

anticipate full As XXX% once the XXX% all of PTC Pharma. under noncash cap SG&A milestone our $XX.X compared expenses expenses cash start Cash, December $XXX.X for million XXXX, of $XXX.X for stock-based XXXX. A non-cash approximately of for a in stock-based billion. non-cash expense. expense question-and-answer $XX.X agreement $XXX.X to from XX, to compensation and marketable year as Operator? full were excluding XX% million XXXX, compared $XXX.X to year in will XXXX, and for stock-based year XXXX $X.X Non-GAAP royalties with we million We compensation hand estimated to expense non-GAAP in stock-based compared royalties full million compensation the be of PTC and reminder, the the million of non-cash as million and billion will Evrysdi the were million full retains $XXX.X expense the over $X.X $XXX Royalty R&D securities $XXX the expense. the reach noncash between $XX.X now excluding stock-based in million full Non-GAAP our retained I XXX payments December year of totaled $XX.X year by compensation equivalents excluding R&D XXX,.excluding million SG&A million be to XX, excluding the compensation XXXX, for call to operator million, expense. session. in

[Operator Instructions].

with Young from first Cantor. comes question Alethia Our

frame for know for Germany may Maybe just maybe the there. maybe market in you like ADC. -- quick just us first throw and be one one, a then Can little I

new any can how the getting we just, the patients give refresher there? with kind in like have you of many where any other that more give part the us of concerns second Europe? of How kind kind States, is of color you up? be of kind then line or United you think Just can And exactly finish on is contribution the might of think popped and should you just of are to kind about question there a about matters

clearly some the patients, working think you Maybe, probably Matt bit develop a And that moving to about we're hard for of approval, have seen why that then trial drug. ready where sites, transformational the we the ready little a so getting Eric, a in excellence, we is in talk of can don't are think forward. we've to of be been cliffs as -- I you've I so centers bit about little identify terms talk question. And launch? on yes,

Yes, absolutely, Alethia.

of We lot in screening Europe. countries making do excited launch those finding. activity in course, of we've the germinate. first through treat We've the been of a that anticipate have exploring in country to pricing patient also terms to currently progress a been our programs many that We very expanded programs will And, we period access be but be have and these of treatments. as we we'll available free hope for many AADC will time are early patients, with of

European to able So and are approval, we to a clearly, and there countries number value be following proposition. that European the begin international to access begin discuss the markets will of

really of higher our And enriched been been quarter-on-quarter. patients have prepare seeing of that in Our has programs particularly majority doing sites paid efforts has off. to testing in much patient giving coming and the identification. and The excellence have disease been we've yields, been educational we us and of centers We've new those the focus really that populations.

a So, be following number launch then early markets first key sequence kind in access follow will and of a Germany. the international typical Germany, that of the sequence markets European with

And then the U.S.?

that can Yes, Matt. it is take I question.

for. package. the a we're avail of with getting of opinion new position for April. ourselves And on ready we're the obviously, on to So first, in in We'll we and XXXX. have moving the by that an expect out, now in manufacturing to of bioanalytical process We're this expect align the quarter CHMP April you the support FDA of data data. some to that and submission data in meet were additional put that generating opinion in in to asked There MAA. forward collecting us just the We're going the the end in had be as process in pointed Europe the of bioanalytical

the we carrying plan be treatment submit so the that, we'll to in year. from And cases. quarter with of the we the including the with this BLA And second that data have along

Joseph comes with from Cowen. Thome question next Our

more just Maybe a AADC. couple on

In you Are or I used terms have label? then kind label of you this age itself, on And models. ways reimbursed? of when of reimbursement, anticipate for U.S. the a or the patient any others size, debating sort know this cost pay-for-performance do European may group to about in either talk guidance you what various get

Yes. Great.

you take Matt, want the first So one? do to

Yes, absolutely.

the really of of early the across age Joe, treatment pediatric about all even into groups what's consistent is adulthood. for package think patients effect AADC I impressive, demonstration

treatment in motor biomarker following walk. the really only have are at motor So, what unable who data function an achieving we in a of and to not and body children now months significant milestones. We had demonstrating can response all early improvement is important move begin,

So it's be been missing really that in all is place of needed in different an is function because part motor not coordination what's that And impressive networks that rather all demonstrated would has AADC clinical a dopa. neurodegenerative disorder package the and of remain of is for age patients groups.

of wouldn't And so can could now and the with coordinated the those that's the provision therapy, dopamine be movements I reason all produced We're younger all results do the based bring that up expect to of age, and while impressive such difference happen. seeing groups. in well. And necessarily effect different why patients there age on be treatment because we gene a the certainly

point putting all in treat. of the point, a this age at that that terms we're we breadth whether the package forward any be this in again and restrictions treatment ages across and comment includes we strong package age can't effect there'd really data really, that's at So, of

a let say actually I'd just the where all, to And in. from younger all in a you have of follow-up we able walk terms floppy We after years where really go first to responding being me really payer five babies from have data, years that, weak transformative see show clinical I strong it's children a patients say think the package perspective, reimbursement, we that. to five of of

data time. considering then there's So that -- demonstrating dopamine made of for long those and is biomarker periods

obviously from perspective, I package patient the quite think So a payer's ultra-rare strong. It's a is actually population. also

budget within. a that we impact small will so And expect have really

ultra-orphan you at big the AADC. priced that products that's twice in for at million therapy was such as about as look and another Orchard If $X.X MLD Gene as

-- product. think we is I the package highly valuable think -- incredibly the but So strong,

think I we're this. excited So, about

talk highly it's so the we'll And more approval, but think we about on pricing, valuable product. a

question Our from with comes next Morgan. Eric Joseph J.P.

of impact of your the end and can looking of Ukraine? thinking Translarna. experience additional then their rising A the exclusivity Translarna at all a in access longer maybe, few brand on any if guess, sales should to you the the or see Is Eric, BD From and to exposure what, current of being in kind to geopolitical any, first, activity line exposure commercial risk the with in whether beyond you lower in top the Russia? speak able tensions that DMD, to are extend Emflaza sort Russia to at guidance given on all in market R&D avenues DMD be market any I And term, terms? franchise? How investors backfill the within with

Yes, sure.

on unfortunate geopolitical between we'll Russia So accordingly had within the situation and in terms we've as the takes But be occurring and guidance. it's business. how of, unfold, we'll highly our volatile what's adjust puts the closely watching obviously, a Ukraine plan and always tensions. to situation obviously is And

as such, and learn like to of things we're as more, sanctions not that. So, that We'll what guidance a the about need affect the will medical. obviously, if consequence taking

was second somewhat terms want always we're the how of tell with will that's to... exposure and Waylivra Tegsedi time about in you question do run. that. Eric, in what doing the Then long commercial So and

to more you're DMD extend strategies and investment it about it's about in runway. was It IP -- Any additional sorry, that. Stu, doing more whether

that? a to about do you Eric, talk want little bit

will that Yes, Eric, that Russia the situation, the just team product. say just of have would watching we we're ground but closely, a important on very sure. in ensure continuity and on the I dedicated And Russia

you on Translarna they already. as received We and patients Translarna know, have

to very to provided. an there's think Emily Stuart revenue and So the that don't guidance very, we're that we be overall impact watching going closely, overall and

have look on stage for that providing exclusivity On service different kind XXXX, in a ways the various working been loss be this we're IP IP number this patient, actually that we patient time at to be programs of situation, that know Emflaza the exceptional in at we And of we've don't erosion. we of capture hold because will but the that rapid point -- Emflaza. to around the know the going at there's

these we're a And and going to be have of able terms We and for programs, we maintain to number patients. key patient of both a feeling Emflaza. have retainment to that number of a distribution capturing model in

For and Translarna, we protection into obviously beyond beyond. patent extended goes potentially that have well XXXX

continue to we course, to is the also FDA. the goal And could in with potential innovate. in of U.S. with Our upcoming have Translarna results, XXX, approval hopefully, of runway nice the a

that So give an of -- us would amount and additional runway.

IP have we aspects have your around I all we're a that really both that And best that products. we're So and are that question. to level working capturing the experience. making I hope dedicated to ensure at doing for lot patient teams on that the say the answers

If related to sneak I one in Evrysdi. could more.

are to more population pre-symptomatic Can the study. maybe just geographies expansion, to opportunity about towards Evrysdi patient in Spinraza label the Rainbowfish relative its on based we're might be there pre-symptomatic the how looking and competitive over that Zolgensma and there market you thinking you Are particular positioning? receptive potential any describe population? As the incremental the

Yes.

we Evrysdi achieved and healthy and announced such pre-symptomatic sense XX that milestones saw baby do. crawling, both the I we as where number the as birth alluded age. from of recently Rainbowfish And months about Evrysdi results similarly SMA the in least safety in the you motor overwhelming presymptomatic the some to were at we of six infants treated weeks think evaluated to, what study that standing for sitting, of independently with walking babies normal efficacy to XX% from rolling,

identification doing We and they're in screening exciting for of that, this think, newborn does and it available. And obviously, in filing. countries in where more -- that in of that. places would amount that in first So in a it's of quite of I an put we those fair get Europe think particular, really could I all, sNDA so make kids these that terms think --

that. able And here the first so really to be to be trick is do the to

I SMA. pre-symptomatic with treatment advantages have one think do a the that you for that major could whole a who of babies

-- life a this the the and people and the and over over the think that's I take advantage major think such. getting stage it's term is we we something So, will that world, but long and during that efficacy to major to all as take will think real not early -- a advantage want throughout as only

Our next William comes question from Blair. with Raju Prasad

I just some programs? on therapy that clinical how at your of market seen XXX we've holdups? long want PKU get you how the are the or of given the for some thoughts And impacts looking kind the the to holes maybe of term in that commercial kind of in gene

Yes.

of -- viral viral terms an that's point issues a So vectors, put two as in I obviously, -- different two we've that's they have hold. on the of seen consequence think you've interesting where both seen vectors in been it with that having different trials

orally you for that's of a take that And that an I exact -- it's think produced. real right advantage we is quantities that's to therapy the of for have large that taken but issue. the the could so the us molecule. unknown were really, can And We -- sort orally. again, major gene be advantage that consequences and without that could bioavailable the do of with know that that you this enzyme It's that

we think, real So a us. obviously, to advantage that's

think of terms of our trying in therapy. you to do it what gene If to we're compared

really one into in of a use But we're you therapy think gene really in which get want to to to that's And is and the of it our do we molecule, advantage to advantage more this real which systemic spend that directly a go and gene be took doing goes taken, there's of into think think We real strategy relatively gene levels a time there. gene think, levels, way. advantage approach. need to reasons So,we I the the would also a be therapy first that why about the therapy at understanding in we what when beginning is low add and terms we've has that for terms we and tissue terms very targeted of low major therapy. move concentration the able didn't to able at that to have

So of PKU, really yet. PKU concept I think in in been no there's the clearly, proof

think I for an need So therapy. obviously oral there's a

-- that AADC, about been then sense of talked kind think a there just at of at of you have kind far? EMA patients so identified. looking on are know you're you've number in this point, -- country about how have do been patients territories previous And identified kind I else patients looking launch versus you in how number quarters, a country, U.S. is someone the you've asked I that given of At where of the have of by identified and but

I I patients really think said worldwide. -- hard XXX been working we've identification. in No, terms been of obviously understand We we've Yes. about identified

to in this, excellences talked be able But that. haven't to get in we're approval, pretty of do be of and able out. patients able I in to terms center perform bring to think rapidly position We good able a up to on being -- be

and and And in understand even of more will to numbers the diseases on we'll So, in beginning it. treatment fact I these as you particular, uptake to terms at we think now time as find the consequence time patient board, we're end and seen thought of treatment in think people keep to of approval a we're seeing continue physicians quicker a just of look that And this patients, to a on with patients, begin as very terms patients. come a day, now, consequence I again that in and and the we're making a finding treatments there's begin patients good good progress to be more going. position there because a and you find carefully. there them ultra-orphan for for more We've be more and than at patients that of would there's think

well of treated identified on based number this approval. we not positioned patients So that -- to able we're year the only -- be think the them on next for a have get to year

from Our question RBC with next Markets. comes Abrahams Brian Capital

on ones quick of couple A PKU.

at respond if to how classical who's used going the you're to the used patients key Kuvan or what curious world? going or their primarily in doses? some APHENITY be be signals going perhaps to broadly to that my then with us any I'm similarities in chronic on to guide the portion Can you preclinical to Kuvan is where or in lead-in question you XXX observed get looking remind real I'm be curious this to optimally non-responders maybe order normalize to able XXX, And the also patients study, differences envision more for more you what to on tox XXX. it's For studies? in comparable the parameters been are And and being particularly have diet. second

Sure. that? want Matt, to you do take

Brian. Hi, Sure.

trial, regarding with question trial it comparing done first was the Kuvan, Phase a demonstrated -- PTCXXX as there we just head-to-head X study. with a your we So it reminder, was a where crossover

when both to phenylalanine who you than patients both So in were to treated greater XXX in demonstrate Kuvan. mmol/L XX% response and patients Kuvan, reduction relative the an was had at to we looked XXX actually more And able PTCXXX subjects and with responded Kuvan, to over and XXX there a also that the Kuvan. to XXX that

the patients, baseline signal that much effect to PKU of or So of And equal a mmol/L. when seeing and are Kuvan, those levels response. to with phenylalanine including was greater classical able benefit deliver had those stronger XXX X,XXX there a patients more XXX to we're than with is

for the gives therapy we what confidence So PKU need us great can an still in deal that's that of a the effective address marketplace.

be we all all patients Phase to for ages. forward X able trial, this As will provide benefit the of to XXX believe move we

basically we'll screening receive So is pass weeks in XXX? levels where levels two for includes phase receive then will run-in there with treatment therapy will this phenylalanine is placebo pediatric reduction with and the subjects the following phase get this If potential XXX adult all a XXX reduction that in who yes, relative and populations or XXX placebo. ask phenylalanine of for marked primary placebo-controlled endpoint and question. subjects and placebo-controlled to those in to six-week simple study has a answer phase randomized the Is

where and phase patients, mechanism we study. able be all and based the in genotypes the to again, X those date, the all PKU of populations even able benefit have So, provide on been record degrees based expect in we on and we've benefit classical severity data to to already the to

-- the once in terms phase, tox, six-week patients into allow only safety placebo-controlled to pending work all complete also placebo-controlled which for data, efficacy all efficacy the which In portion necessary chronic safety obviously completed created but of NDA have open will they of not study the the the for label long-term prior the we the tox study the for roll which is formal over an the of component or phase. component basis long-term

full open-label those So able the placebo-controlled trial, the the complete and move now studies six-week phase now extension. to forward we're with are and

from comes question next Wang with Gena Barclays. Our

just its scenarios launch have mid-XXXX. Europe data Could impact Translarna regarding different to confirmatory one Translarna of outcome study in you market? and in I provide XXX the

sure. Yes,

all we've the remind that in patient of to to we the were we I think to study. from study to had what's what's about of 'XXX to endpoints, performed middle really were done the able just that able right the So be clinical right the will done the learnings that this population XXX is there's what pretty everybody utilize that can we that excited trials be define We're year. because run

they population to that And use and really so, be to patient working the a is I in Translarna show we're good right position think the to able -- endpoints. to right define use and

of a we're do And forward. so moving you talk the how to Matt, about little bit want details

Yes, sure.

as learnings study. from we to So our all Stu really previous mentioned, the a leverage in were position of

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relative meters the -- XX of XX example, meters in both from For placebo -- a was study and relative XXX, in there XX the million placebo was it greater again those in meters -- and distance greater XXX, market relative walk XX significant. statistically to treating to distance is the difference --

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follow-up. a just So sorry,

you Europe? market the fail, data what Translarna would to to need in additional on if provide So, trial maintain

Yes.

has in ground. I loss the saying Matt years get compelling. what So is ambulation, think that which preventing quite The we STRIDE of function, the really that's data to longer registry, pulmonary was have terms demonstrated off of able being

well well. interested probably we the you've regulatory the think in European that we've you I and this publications very with seen as as agents that know in shared that are

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if on for like marketplace the you would enough EU itself that to that devil's were -- advocate, that patients if get. it is we want keep the play to data believe STRIDE to you So happen, said, strong

Brill Danielle from with James. comes question next Our Raymond

notes, remind Alex filing. think Angelman therapy XXXX were the This Danielle. where you originally for Could I is looking us stands. IND on program at, you Based gene for I'm my the on targeting

there to we're So be needs filed? what IND just get that curious done to

Yes. Sure. go a to through Matt, you little want this bit?

to We or in have a on Hi, delays completing program and shortage ready both work the CTA the its primates. our towards near to tox get work continuing of nonhuman are in our as in impact absolutely. terms CDMOs the We IND to that happy move now Yes, forward of were clinic. we the future. into program well and gating manufacturing we moving global did of I'm that clinic the CMOs are Alex. to the the COVID related previously as number shared that of process the having report into

question next from Karnauskas Truist Our with Securities. Robyn comes

any I in you on going run-in lot on had the XX of the -- to Can focus. congrats year. progress, question into the a what all Like be Again, it seizures with seizures variable placebo-controlled population bit? portion I thought the and about of again. it's -- MDS the Bio-e in I you're patients on bit this a period actually age? is have month. patients coming of platform, that and to last you've enrolling talk the How a And you're help of of kind little like then talk percentage these about, they that to lot just you are a you reading the that and that with us the within go MDS of what just they the within trial have days, range MIT-E out know a want group patients have understand fit more bucket? that a are enrolling risks little can of got like would

and doing thoughts think help on to mid-caps just interest about platforms to second the and on on the in this study? then in like try of Just question understand lot that And terrible sale us state? are -- M&A your

you Matt, want disease So take to do seizures? the mitochondrial associated

Yes, sure. Robyn. Hi,

mitochondrial disease a little the for bit about talk just them second. associated So me let a seizures,

disturbed an patients disease are the pathology. that seizures seizures patients as part with seizures in mitochondrial therapies. these these cause be refractory mitochondrial of their disease not have addressed XX% antiepileptic tend that And That's to in important are existing antiepileptics. by energetic the about to So, traditional mitochondrial to all XX% disease pathways of because

of In the in energetic positive antiepileptic that therapies exacerbate defects are patients. many fact, seizures these

potential mechanisms the causing by they benefit pure whatever from exacerbation the of So these pathology offset are seizures. would of antiepileptic have drugs the

have recurrent So them. are infections a mortality saying of they're early degree cause patients. typically a of that's a a of and who kids in source hot of these They're high severe, have way these morbidity, long seizures lot of

development of different of course number of Over vatiquinone vatiquinone, a we've subtypes. in disease studied the the mitochondrial

-- nuclear we've mitochondrial the seizure there And reduction function. regard pathology, to and disease-related structure regards morbidity, a to mitochondrial or is data, a these consistent disruption including to where with for we responsible robust across history of result genome in in So, mortality. seizure epilepticus, we've with different well frequency, many is in able we've cases effect protective the status subtypes in seen a effect of as are been subtypes treated of what there's refractory different reduction some demonstrate treatment mutations enough that the natural

study different And and date agents. related on to of this study, life really seizure effects different morbidity of subtypes quality the base so patients seen we've of in what all all seizure, we and coming into disease MIT-E in terms on mitochondrial

on And in really rather where we on not so we is developed but quite morbid specific this genotype focused these protocol the drug-resistant is basket patients. or a seizures, common mutation, trial symptom common of which

is observable set the we to room motor study there's the that enough so have ensure phase, up so And with seizures, where run-in we mentioned, as demonstrate benefit. we

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disease mechanism other disease rather seizure as effect quantifying as capturing seizure not vatiquinone We again, the using targeting simply endpoints pathology. and a of will because, include in treatment measurement of importantly assessing as other pathology core well way in a aspects We're morbidity antiepileptic, secondary of patients. though, these it's

make all covered points. the to many different I just sure subtypes. including We're So disease

that focusing particular we doing arms. younger. stratification disease, XX subtypes of both limit order just of the can we're And we're including them zero patients and observable years -- no any more of of across pediatric enrollment placebo are balance We on again, particular requisite mutation in having number so to some all seizures. out Again, vatiquinone between there's common and again, balance age

to a question Robyn, So fair your on. that do... with amount think what's what and there's you us wanted M&A space, on this of you comment Is in I

everyone your whether given think of back year. like the a it's of a of high of sort this just more question certain the interested low in tape lot valuations the they're I ask in for -- M&A there's the see gauging think if likelihood there's people because or what you are not interested platforms, acquiring mid-caps, and or in we'll interest that half

call. I on every key question. all earnings We're think that's asking it the

their act complicated that Do goals of a are just say. their Could people's bit is treating sort it they hard building pipeline their M&A capabilities drugs. So, relative there's see. of I a obviously, less, is these of like, to to capabilities acquired? in on looking to obviously, mean, there's always me interest a is they of to commercial what my want to I view are in types it's better? -- someone think diseases. for to question lot a there's more lot hard going are. But become it's on little people interest or or I I do be what say these on guess to

comes with Our Judah from Credit Suisse. question Frommer next

enrollment there. Just toward you on beginning of as a couple kind head XXX

functional also, administration as patients programs Huntington's How to lack thinking that given from maybe there endpoint in route to length is the the how set type of Huntington? specificity And study? toward that feedback get as are doctors about on do kind you given any and are in potential maybe also there to to a of you anything tradability the show and clinic? you have mutant of Just kind of versus sites them then important up secondary the receptivity a of other

Sure.

brain, from the gets every distributed, tissue. home. first could barrier, comes obviously, small I at passes I it you gets right? advantage that, it -- blood But it take, all the over do huge of real it from the the think that you with gets fact the easy administration, it's think that, beyond brain molecule, I into is the know it to bioavailable route is I a just part, giving ease it the advantage, the that orally think, mean,

You pharmacokinetics. the measure can

drug precise you of the the concentration both free know the that's So that's plasma, also in CSF. in

Then So whole when know that's within the you know the that when you only -- level know not CSF, in the can measure brain. much you there's of level that and get the the know reduction you you that plasma. it into occurs so you

very could there's that, the obviously, of then the So you effect you of a And a consequence know that. as consequence of see biomarkers good response directly. HTT on know, you a as -- protein like

the So, right place the it's you're know over. you right all there's has see all in place, over getting could learn when so that confident it's so it's it much and and the effect to an that brain, you of you

everyone really So, is happy about that.

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package. that's think a I pretty good

Dr. like question-and-answer to the Peltz call I'd for Stuart today's concludes back session. remarks. That to turn closing

Okay.

our us globe that driven look with continue discuss of give all to we've And a significant you. can many upcoming in research I to really and the and first and team And think the that XXXX pipeline you we've transformative really to the to be and across continue on I to to these we made we goals around really medicines milestones development updates that we're all, anticipate date me for progress that so progress patients grow. So XXXX. today, is the to forward execute us proud up for made as let real bring XXXX. going of year the I'm progress to thank joining we that we'll that

joining. for you thank So

concludes This participating. for conference call. you today's Thank

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