PTC Therapeutics (PTCT) 27 Apr 232023 Q1 Earnings call transcript

Good day, and thank you for standing by, and welcome to the PTC First Quarter 2023 Financial Results Call. [Operator Instructions] Please be advised that today's conference is being recorded. I would now like to turn the call over to Kylie O'Keefe, Chief Commercial Officer.

You may begin.

Good afternoon, and thank you for joining us today to discuss PTC Therapeutics First Quarter 2023 Corporate Update and Financial Results. I am joined today by our Chief Executive Officer, Matthew Klein; our Chief Business Officer, Eric Pauwels; and our Chief Financial Officer, Emily Hill. Today's call will include forward-looking statements based on our current expectations. to in slide which conjunction forward-looking moment Investor on contains a statements. website Relations with take review posted the our our Please the call,

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

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

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

thank century achieving we total our into developing We quarter growth commercializing XX% unmet quarter you highest XXXX. expectations a revenue. and first results joining incredibly transformative XXXX. a need. for of signs first I PTC disorders. first I'm patients PTC performance with as a therapies in next continue high medical pioneering excited the to had productive This to represents very to $XXX our PTC's share am its to million pleased and and afternoon, deliver quarter, lead is Good innovative utilize in to and therapies to treat quarter quarterly revenue, over the rare for strong continued call. leader

also strong quarter, of [indiscernible] be the which both continues a revenues revenue Our driven revenue XX% treated [indiscernible]. the million, a $XX naive increase in and over first [indiscernible] quarter XXXX. growth with DMD patients first those represents royalty therapy million. to quarter previously $XXX totaled by providing of franchise had

sNDA achieve up XX% total a is puts guidance being XXXX position less to of $XXX first This following of months year-over-year each $X growth than our billion, the strong U.S. performance to us represent growth. patients by in would X million approval. to driven recent robust addition, In quarter revenue which

as we've reduction the inform provide second use expect which to review likely once further OpEx study we be addition, to In we details a will results previously strategic reported and to on shared, portfolio in quarter the available.

pipeline. directed. on second to X our remain to are track the which results clinical registration from Moving X We report in of quarter, studies

provide May. each study was of To mean running reduction least a than study Only greater demonstrated at me data levels there of phenylalanine demonstrated subjects The a the in phenylalanine and treated earnings X/X results we overview from shared or Let APHENITY phenylalanine population study population February, quarter of patients. enrich XX% weeks. analysis a APHENITY begin response than I'll with spectrum our the baseline more adults a in and subjects had screen run-in to results the who sepiapterin the our placebo-controlled of primary potent in all reduction reduction subjects clinically phase all X the level. reduction forward which for who X with APHENITY levels. those Part phenylalanine supporting during received for PKU phase. At of X and portion the the weeks running reduction a from consisting fourth baseline for from during in X greater approximately PKU. children in mean XX% of X XX% in is Part randomized encouraging portion the concept which subjects sepiapterin phase, meaningful brief duration of to The for We reduction were level in placebo-controlled sepiapterin, randomized endpoint subjects and X XX%, those of from phenylalanine responders, in sepiapterin XX% primary reduction and expect bioavailable in placebo-controlled Part to we PKU cofactor of with full the global with was Phase the blood therapy, more a a share. study. was that with can of XX% look the sharing in was classical provide differentiated

Let the in me to included XX-week Last the placebo-controlled study The phase MIT-E being move vatiquinone disease pediatric Phase study vatiquinone. the X registration-directed X phase and registration-directed second is global change trials in with quarter. with registration-directed now of XX-week also in score. results phase mitochondrial associated mFAR trial patient the The global patients placebo-controlled has seizures. ataxia. patients is of vatiquinone the study baseline a with a observable MOVE-FA placebo-controlled the as primary with a and to seizures. adult primary expect results expect of in in Friedreich frequency The visit March visit last quarter. baseline subject, being change motor last planned, we MOVE-FA phase a included of endpoint placebo-controlled the endpoint continue in from The continue validated occurred occurred, to second in last and for for for we the from

of a will to titratability on ability patients, X-milligram dose of initially milligrams molecule. We and initially weeks with consists focuses X initially expanded trial DSS-based include the X X duration patients XX and study PTCXXX dosing. the Stage the X in Stage the be Moving XX in trial Huntington Huntington leveraging parts: dose included PIVOT-HD to of placebo-controlled XX-milligram we and milligrams program. is include up studied and with third blood-based, of X and to recently X includes The months to on duration a pharmacology as PTCXXX and the X disease. milligrams, Part radiographic at as X disease, who level disease pharmacodynamic Part XX-month our effects biodistribution. levels, is biomarkers and that focuses well XX is early

data will of data will of these beginning studies each these are expect trial the pharmacodynamic safety, data and to continue be These reported not expected tomorrow, X-milligram until the XX-milligram second in With several we results dose. discussing results in from next We pharmacology, programs for quarter the X and study. weeks, of interim portion XXXX. XX-week include from biodistribution the the

Turning to Translarna.

the type to second the review could for standard Type preparing In variation with the Translarna. to are European a to the of FDA support data expect NDA C quarter. the convert authorization we to We the an X request to for meeting that the in authorization resubmission totality U.S., marketing opinion CHMP date conditional collected continue

Finally, for Upstaza.

analysis of As and in pods. additional we the previously clinical comparability drug data requested shared, bioanalytical the FDA support commercial between

BLA feedback and Eric quarter than planned. We result could in initial and third provide new occurring of in the on the I'm will the submitting rather on responding clearers to successful previously a as second process agency call which XXXX prior of have are portfolio. received FDA incredibly the the to BLA, quarter additional the quarter. I commercial from of our data proud Eric? update over to first submission Overall, hand an our in to now productive

Our an created off XXXX second in team global significant the capitalizing momentum XXXX. customer-facing has half quarter, extremely we kicked strong of with on the

Our on with and metabolic portfolio our driving growth significant products focused team commercial disorders. is of for neurological

good We progress the Europe. launch Upstaza in with continue to make

year. indication the FPL for familial fourth launched of approval have last the this Brazil, following in in lipodystrophy, Waylivra also of new quarter partial We

previously achieve strategy and as future and in in and XXXX mentioned. markets in Latin Matt execution our expansion growth to our position America Asia, revenue are a Our continues guidance, of to we progress geographic strong

me Emflaza delivering XXXX. to engine first million of revenue, for an first with compared an DMD quarter up XX% $XXX which Translarna Let continues quarter and impressive franchise. be in start net important the the is growth, to

this quarter. in revenue For achieved Translarna, million $XXX we

orders We contributing to the Latin continue markets see there regions. growth America, our large to revenue in Middle And East strong Eastern Central and internationally. and some across government Europe major were the

continued as continued compliance, revenue $XXX new our quarterly solid ongoing throughout with be weight-based dose Quarterly confident ongoing to the to solid. our starts, Given million. that year. we an fundamentals high revenue We will guidance unpredictable Emflaza basis. The XXXX in of growth DMD million the government in markets, revenue $XXX lumpiness million of and proper ordering patterns business was patient we these franchise adjustments discontinuation achieve fundamentals on expect net low see to remain $XX remain

We the we which momentum first appropriate of insurance seen continued compliance, broader high number the forms important quarter, in through with provide and as start access. significant along have dosing new a year, weight-based progress patients will

the Now first brain. therapy gene Upstaza, and only to turning to into the approved be directly infused

leverage transformative as patients commercial early patient. in and see and effects commercially treated international this have quarter, steady new Europe the Upstaza We Europe first will continue markets. our programs cross-border in other access been rollout the of in We to cross-border including treatment see

to centers new patient and opened Importantly, being accelerate markets continues in are excellence of identification internationally. treatment

patients AADC final discussions access well XX have NICE progressing Germany older. England in we and Additionally, positive Wales and are and and for market France, guidance from months received with

markets in throughout to and expect countries in patients Europe international XXXX. We more treat more other

these Now Waylivra moving grow America, in Latin and franchises successfully to Tegsedi in to we QX. where continue

for approval partial and Waylivra's in new officially last December have by generated year, Following familial launched our ANVISA already Brazil prescriptions. in this indication we first lipodystrophy

Waylivra delivered We QX. chylomicronemia syndrome, completed group was for purchase also in order for familial first received our and which

revenue As all up In was Tegsedi, we first mentioned order in substantial of our setting conclusion, all an achieve guidance. received in from our last excellent the to PTC to products call, across and our second for start us regions, our Brazil with XXXX our at quarter quarter and Health. ever commercial progress strongest Ministry XXXX the group purchase major

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

line refer first million, issued product additional XX% reflecting $X $XX.X $XX.X Translarna consisted commercial compared million, with I'll $XXX.X in earnings top manufacturing review were press take product the of to revenue quarter financial Emflaza of revenues across growth the $XXX.X quarter for product quarter portfolio results. million, and first $XXX to across strong revenues the results. revenue quarter million. the a all net revenue the of for every this Please XXXX. million. net representing in of details. geographies. Total This few of about million first our revenues had to quarter of were the Beginning afternoon net minutes growth release royalty

million quarter XXXX $X position compared $XXX.X guidance for of quarter were milestone in The revenue revenue. for year-over-year million as the R&D for quarter first stock-based the the investment December including billion, of the million million the approximately when March first mentioned, proceed XXXX. I'll a advancement increase expected noncash first predominantly million for compensation million XXXX, XXXX, Matt of million expenses cash programs stock. Non-GAAP a in to to and Cash, of us expenses stock-based SG&A million expense in And R&D XXXX, securities as marketable $XXX our equivalents XX, million development for $XX.X excluding compared XX, in call $XXX stock-based total as Non-GAAP Operator? first to now clinical in reflects compensation as XXXX, and stock-based $XXX to clinical As expense of $XX.X million $XX.X to expense. in $XX.X the of well common sepiapterin turn the excluding expense. $X.X of expenses milestone $XX.X you. first research million the annual performance million $XXX.X billion noncash compensation puts strong totaled in surpasses to quarter $XX paid XX in pipeline million Q&A. compensation thank noncash over the quarter operator $XXX.X additional in excluding of XXXX, were excluding noncash achieve compared

our Cantor. question from And Kristen comes first Instructions] Kluska from [Operator

also you geographies is you globally? that could And in this learning specific the up footprint factor of able biggest related driver new patient just And the finish of deck. given this been to talk these specifically being picture your one end for first do a The candidates been should the think And crossing about few soon. top What's patient portfolio, to on trials add? then kind here, the have you of leverage on can more starts? what's with question bigger in you biggest DMD is line how registrational expand your some

the We're grow ability market very you now to the year-over-year Thank the much, for franchise infrastructure been we we've to years. almost the for Kristen, being X DMD and that proud of commercial questions. incredibly Great. on revenue continue built the global

to obviously, really tremendous infrastructure products. there that's launching have a been new will that accomplishment. key So into And in forward building play come of learnings look as a that number we

the Let me some the to on who give franchise. Eric, color call over can more global turn

Yes.

DMD pleased with and fundamentals achieved I the the sales, your of across question that's geographies. growth, different ever see lot franchise. mean, we driving what's I think highest million really we and our $XXX for To all areas. execution growth a in we're the of about

time patients execution of commercial early Of able from that has to patients, is course, they're and on. rapid with geographic work the the expansion time diagnosis diagnosed to new and but been treatment team our helped the also commercial

In well on the better on if as as ambulant dose seeing of prevalence drug we've you well for payer course, that, patient a maintaining, addition That's the well. through we're will, have and important. And that's nonambulant as really board Translarna really both important access, that been focusing to as we also pool as Emflaza and adjustments. improved across

million, see there that little incredibly major some of that sometimes important. sizable growth from timing Brazil orders those levels our Now the and CIS underlying of The also that also and and and lumpiness. fundamentals. for Europe, most from thing have East. Eastern from the is Translarna, are orders to Central orders a did of all and and that's is from confirmed But our Middle size $XXX creates But that growth large did receive the some these government we hard markets, predict, region, important our we is

strong well patients we have of so And a existing that as managing. base patients we're very new as

We $XXX And are reiterated, the the as to expecting DMD million orders Matt guidance million. orders, as in this are our government franchise, the reiterating for we well. second like $XXX half

you I color you hope that the that Kristen. need, provides So

that one Yes. and in But benefits about obviously An the areas evaluated. routes drug thinking one are of oral are helpful. with terms then And brain different compliance ability quick are an That's administration maybe mechanisms some to about just and adherence. Huntington's being therapeutics the on How recognizing disease. comes different. other there target you out the of versus the really oral right thinking in agent's

which the route development rib successful obviously, important And the a SMA. comes the the and of are incredibly biodistribution a Obviously, development of successful on think of therapy We development PTCXXX and made heels administration elements discovery to molecule we can essential important Huntington's of a globally for for for disease. critical only optimal blood distribute cross treatment learnings for the but by about barrier, effectively is of design disease. a number obviously, how the similar and Huntington's CNS, not and that flux to at SMA, of not there's

across a the broadly disease in rain that to is put specific, we and those is play design a lessons of So and region of gets the selective, distributes that's highly the buy of molecule highly all role Huntington's disease. PTCXXX, incredibly blood brain, have which every given barrier important

is the the is production of mechanism the Huntington mutant So neurodegeneration. and to cells obviously, cause drug, toxic targeting the of the disease, which leasing that protein is

treatment. decrease And we and leveraging ability our identify protein, do so achieve what for of to that the study the we're toxic able think some to disease to hunting whole-brain in dose the production with clinical disease-causing having target to protein the splicing molecule our on is is get therefore, essentially optimal the optimal [indiscernible]

Great.

once Looking the forward to with catching you data up readout.

And comes question RBC. our next Abrahams Brian from from

for on Joe is This Brian.

may around any thinking might been and And target patients. speaks in like Just there if level include your have in which the desired on seems your in data Huntington's more the of be downtown possible portion XX-week changes tell shared Can HTT thinking Huntington's, can earlier about it study? to you it us changes of from your it to share you population CSF? around some

at to in on gets biodistribution, These XX% inform target us the the the PIVOT is is focuses XX% exposure data plasma. the branding relative XX -HD X optimal the XX-month study weeks reduction of So are towards CSF that as protein. it of a in as Huntington important duration, looking that's k blood and to in points dose well parts. in X Part PK/PD placebo-controlled study in

including be we protein of and bringing months in well levels disease, Huntington the the quarter study NFL on plan in in changes the the radiographic the XX X We'll weeks to sharing volume of as including CSF. second as an The second information blood. CSF, biomarkers first case share PK/PD analysis for of levels focused on the data is is interim markers, The activity.

in and the levels the marlin looking blood the ] protein looking in relative the of So reduction exposure in drug at the then blood at plasma. and and CSF [ Huntington

we X CSF healthy achieving confirm exposure recall fact, study, As our [indiscernible]. volunteer in able Phase were exposure. greater were we're excellent that the to we you And CNS getting from in

very levels important biomarker data. data, levels, bridal including The to changes will a the protein the finding we'll that's XX-month readout data. To and CSF Huntington So patient question that seek the in XX-month confirm NFL the come your second from populations. regarding

the the the mechanism codon that that targeting disease-causing the the of protein. Huntington to or full and As the of answering patients I effectively juvenile the same patients disease introduce spectrum the Kristen's production be for that That mutant production adult Obviously, protein. we're they shared leveraging is is HD given cause holds decreases cases. in in stop question, splicing, all by promise able that disease-causing whether of of is drug

incredibly effect clinical try obviously include in to a the the right of population in along clinical of in biomarker trial PIVOT-HD, effect. And it's case However, the the practically trial. could study important constraints capture commute-limited we in clinical whom conducting that a we

there put therefore, to of practically the we up into so of not natural databases the with slowing that advanced Huntington to progression. clinical progressing it robust to certainly are Huntington's that we're targeting support we we of population And impossible databases the are so experts we patients all, benefit. what essential we their cause the would we course disease, early upstream a can't deliver to be trial. Obviously, identifying a want likely effort who these in that thought with attributes don't study history biostatisticians work making disease come would availed and who by a not what disease the So closely decline of that ourselves that of a want disease in lot attributes were population thought in over optimal show patients the disease who at disease, the

we criteria than essentially in study, of The which were prepared were an having initially shared January at of these no were prescreened Stage this would cohorts were put to So the patients that score X had for now of for adding identified additional score conducted. as We a the were were these functional there with because and play reasons a simply acts patients. that capacity JPMorgan patients. a conference We who total including number later-stage we were inclusion TFC to slightly HD rather these patients being -- XX trials longer participate be acquired. and just and XX who other clinical XX, in

we clinical So in trials, where benefit with situation a eager innovation were in to clinical can trials we therapy. identified, obviously incredibly is be and whom ready this we participate believe to provide in

on made we So dosing provide and cohorts additional out important in additional to potential early data cohorts, dosing set because milligram, the patients to our of test X this benefit enroll. XX us milligram to the initially introduce we of Stage that will in population these hypothesis decision X also allow PTCXXX us terms

question these addition I new patients. of hope adjustments your So answers the or that on

helpful. that was Yes, super

next question Eric from comes And our Joseph from JPMorgan.

you Just I just what for then and [indiscernible]? are claims quick estate talk on a where maintain the vatiquinone covered for guess compound. could about you the for briefly me on one exclusivity and IP if patent

So principally vatiquinone the going under protection for be orphan to is exclusivity.

other life, U.S. the the Europe well ways markets. exploring the as to we patent extend potential strengthen always obviously, and are and case, is in other in As as

a just follow-up, Great. quick I if could. Okay. Maybe

that range for guess, it of And relates patient can to patients ages entering I the on just talk the reading. the As that by line analysis age? will about mFARS primary MOVE-FA, within comprise you soft sort of

Yes, absolutely.

Phase as learnings number So of we trial important from made MOVE-FA our that number studies. other constructed boning we as own X clinical well trial, from a the the we the of when leveraged

safety We spectrum tip opportunity terms opened in the also children, of full in FA the a of were the the of to in position of up exposure large patients and were given age. the enroll volume this

patients And of so our XX. X population trial, consists analysis in this primary change to

the the younger And majority natural adolescents, you are rapid FA patients here patients have layover of tend and adolescents. uniform in the more a the to diagnosed is early idea disease, Now if of decline. history more look usually at

So that question you as the best trial antimods for capture trial disease, getting treatment of will the clinical to that in clinical group, we position right talked population the course placebo move the benefit. puts over hardening the enough last you about

the X are cut on that we if at so age because younger And patients than lower X.

for a those First there's second with very test, of of study assessments. young harder few them, children in of of but all, the number all, comply it's

clinical So difficult. that benefit means payment faster or

then better decline prime clinical going analysis the of you a of we we you clinical where as of X, earlier. is population disease situation a have one have the the earlier this trial a the if up the of in tend which So to course a of also it whom also, in we effect. chance helps benefit. And to disease, XX. lower group in if less and to Again, can neurodegenerative affecting age intervene, in register act the easier believe set and that these disorders, patients placebo it goes a is makes have greater We're progression to of case the you're commonly chance into

then fully would will patients. the we and that patients the pediatric that population. of include would in of a enroll at can all we we would do opportunity We are the all label We're also drug And that we adult those also adult relative safety patients a benefits positive have were We to benefit that analysis agents if hold the to in adult patients with for, believe including to patients younger us and to move towards able patients. studied the primary pediatric on expect the given are billion again, adults. chance old a so previously part relative which of additional we give again, that, population. kind approval, look trial, the But not

helpful. very That's That's Okay. great.

Robyn Karnauskas from Truist. Instructions] [Operator

have I them. X of

one first is around the So PKU.

for look Phase that just the XX% how and lower the improvement going patients. reach the the analysis going is lead-in bar, since the X reduction might XX%, you X actually you're the I get for bar for Part So fee at the responders to decline end the presumably, of of gave XX% entering the some But -- those responder know into I set as base set as wondering, just and lead phase. may entering the it wanted X do for think slower Part And flesh Do Part that? the good X? I you you really you for just investors. considering expectations in will was be it some responders So expectations to out there

that seen might also, a is efficacy is Reata? for maybe the the lower you confidence time older progress the decline FA, do you're the efficacy maybe Reata may mentioned What the question, And confident they doing patients, confidence the has and the the patients, with placebo impact success but more range like drugs. of the you your have we've better in patients Second fact, -- given younger what's be for drug dosing like in also about patients. you're Because that bar younger TID flush decline much And your think market? dosing, that that that of rapidly. how over then line? time to third, decline the these in And TID What's than population? in of might out over

turn. in Let's take them

APHENITY the regarding question So the first is trial.

subjects all so a greater as all subjects which reduction running we were the in. randomize XX% testers, who than we screen have we have and phase treated And in for said,

run. had those greater analysis who the than a primary reduction includes only the during population trial for subjects importantly, XX% the However,

subjects reduction. And XX% So you greater a all-comers running the interaction those analysis give reduction have the we the in the there success in that shared, of between reduction XX% as the of by like as the XX% of past, seeing and XXX response. a be that had baseline. responded XX% XXX drug, majority the reduction, running terms subjects from XX% primary those additional XX% because shared mean that during sees there'll to and had and XX% between the XX%. over who tremendous of in few those had is numbers of the of no to trial, that versus reduction who we had of important And the XX% just response we -- and what who you're and large, over basically That's vast XX than was are in

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in That patients confidence So those the the the treatment who very analysis, penetrate And great get placebo differentiate for would success the placebo, confident be that it's active, to who sepiapterin PKU. data historically, but to randomized placebo we'll not it gives expect clinically deal PKU and to primary of on those of again, reduction were reduction. able to from placebo. treatment one greater the a similar magnitude Part strongly obviously, only X achieve trials we to response. cannot But that of us response, significant only fully to meaningful in the given of see randomized to relative based have much that any

terms In problem a with it's seen first question breakfast of was TID the we've And never FA, your look, dosing. and lunch with TID dosing, compliance regarding a dinner.

the and aspects XX if important the in with of which differentiate to turn believe that that actually over effective there's Kylie, we hours, add you several meals, that I will don't difference. dosing to not therapy know it's a makes terms anything may it And it's other big update. very to So want

we that's Matt. said, Yes, what I think

into number of priority. high diseases a particularly a foremost, unmet of Friedreich and Efficacy, like there's obviously in consideration, it's are and think disease I factors key ataxia. that need a first progressive taken

be the and plan. to study, MOVE-FA of we both will secondary where see it out our primary interesting come so And as endpoint

dosing ], In we comes to seen addition that so safety a particularly to into Matt of the kids factors key there's tablet that, And play. a ages safety with is in where of as said, point from to as number in see with the obviously obviously, and obviously differentiation younger parents these really it's view around [ easy important then we've series to adhere to, dosing our providing the where differentiation meals. compliant neos are and

board discussions, around with patients, the raised KOLs that, with the across there's and So concerns Robyn. both not we've any had been from

your of will think we of -- And regarding then clinical patients do old and then, the that course move Robyn, in there? terms And XX to question in more those placebo trial how group. the X year concerns the third in why

the score of tends you are is of and magnitude who disease presentation time in disease to and are If younger of decline uniform at the over study. natural course patients the history age a a the groups of and over have more clear earlier when So time. very NCAR greater the diagnosed as changes look

In disease early interviewing by likely be able to to terms benefit. course, deliver of the concept we're meaningful a that

notion is on to points the X early, you people I well XX-year-old able think was they think cohort, neurogenerative effect be patients, greater if those in had it those patients going in further at greatest intervene in with over in reality young understood I to you that Reata where their or that's to the treating a corrected one if look younger they fact, which XX- to neurological response, and patients. the XX the treatment had disorders. capture And XX, data, those to support

by effect slow incredibly therapies none but a are able as Friedreich to such time. progression, time in progressive curative, ataxia years is or progression relentless over slowly But year, by X terms of correct and still these to meaningful be of reduction progression. In over disease a slow

in still a So some being expect incredibly the to slow could effect be disease meaningful and of that meaningful progression being progression able be there will modify the children the vatiquinone. course. expect we but would one The time, to of to alter all think impact disease the I

comes And our Lebowitz from Citi. next David question from

Debanjana David. is behalf on of This

-- And back on if nature could BLA was regarding could any The sorry, you we like first the you the additional share of received? FDA that push wanted Upstaza you thing details ask delays like to submission. like feedback queries anticipate any do the FDA further

The drug product.

development drug As and to gene the development come commonly joint the additional had the product, for the product some it's the were show evolve which important to is data, commercial They drug commercial back drug course And drug and do. different analyze the in used over products samples is of a demonstrate product. that case to assets the essentially case to to drug and drug for process the often asked that clinical products, one and data. quite the commercial comparable to additional in area, able is differences gene the is are have some capsids agent we around provide specific they additional the were therapies, manufacturing of able the attributes product are the analogous process questions between can product to easily that provide commercial clinical it's fill empty and of which in key product we to similar, particularly than generate apples-to-apples of therapy And agency clinical attributes drug product. clinical

that the position the potential because responses cadence just and we hear with submission to simply the then the given the back possible we be of it's the that expect forth cadence be from between submission delayed them have BLA, but to and We're to that's quarter. be this going QX agencies. submit forth the in QX, agency until delayed of could We third back make year that the queries, wanted a of of to interactions and to BLA the we communicate of and back from could stated believe the

] and is -- Regarding differentiation obviously, OMAP OMAP the [ bit trial longer ] there's than not a vatiquinone, trial. the [ between

which capturing the important be are possibility an obviously, patients. part are for and nonetheless, on the the of benefits but is really, the not different, the Obviously, impact a slightly vatiquinone. other that which to some the aspects over endpoints pathway like have important morbidity, It's with of are term age an the going populations been important. endpoint, of to only regulatory capturing the effects but think over that's the that's longer-term understand of secondary patient allow we'll of I part similar groups to of able is the different secondary I our relative also to those study. really primary FA longer imports. disease all on they Reata, So appreciate And agency look discussions mean,

is question next our from Thome from Joseph Cowen. And

database constitutes really benefit? And have under on a trial. patients have XX% XXX what And to about you? Maybe to then have it the the or is file per the program first one you one off static just think sufficient I if see safety a works? micromole you want PKU this proportion When study or success here, Or do of follow-up. you a certain reduction do that quick baseline have what liter from

I'll start, let the I'll about talk and then commercial Kylie differentiation.

benchmark responders proportion were proportion One impressive Phase the So study X/X XX% seeing and impressive the over of in have a patients respond only XX%. data. patients the of over really of nearly X to the the things all-comer really is was Kuvan couple that and reduction -- was of that from where obviously, run-in the about XX%

overall effect, able is in is the who And a again, said not second the patients patients severity, impressive. but really your market which that to provide had phenylalanine. treating of of over The in regardless disease reduction only of in in that PKU That's who magnitude reduction, of running XX% reduction XX%. we're real XX%, phase classical had the

Kylie being evidence to to clinical would achieve Our the the quickly provide comment placebo-controlled also expectation it able not differentiation. I'll would on comment to the is but that on provide to be sufficient evidence regulatory benefit study turn only registration of and over differentiation.

going placebo-controlled data that obviously, longer-term data be in along you to collected able we following a effect, other want all question. Kylie, do but obviously, to commercial durability is extension been the from the the which data. the we've to regulatory study X-week into with have open-label roll going in patients we a long-term study, differentiation placebo-controlled positive data provide over on submit On only believe, to not safety, us put which the we're study date, from to front, position to

Yes, absolutely.

that it's segments talked the high Joe, perspective, think which have in medical I unmet different about looking we've sort in the past. of about patient need PKU, across from that

ability demonstrate that. classical touched just in an extremely important. benefit PKU Matt to on having is think And I

historically there. benefit to very a difficult-to-treat patient demonstrate been that population, able think I being

I think it's strong.

primary we've think ultimately in population I I broadly, inside those benefit, fee population analysis us of PKU reduction, be As in to or benefit already the Kuvan, will looking that talked give greater and of powerful or we the for a those, that that different being being at greater. And greater classical XX% a population, number looking but at have I XX% plus about, I showing XX% is those classical those those a XX% an be think differentiation. [indiscernible] to PKU that more have looking going showing think over in tried Outside will are even in fee key. segments. start a different time big well controlled, think, controlled patients even And reduction poorly opportunity in XX%

that I think, try obviously, looking up sepiapterin. to be would that anything and higher more opens than more patients

contribution you patients revenue are to of don't know as if quarter? that going forward? the the press Upstaza Great. this provide And think out saw for I then it of in pads, I but some treated. much breaking anticipating several Or you are able were just not, real release, quickly on I

Eric, treatment? talk bit launch and want do to you on a about progress the little

Middle out We with to in launch in It's the the we Yes. is according progressing. in cross-border and effects. way or specific are actually came patients And Well, we was we also see Germany haven't Europe. and the plan. actually transformative treated treated quarter. numbers which and in is patients revenue, but patient the what broken being we're have patient, from France we our treated both East have the And pleased first really treated going

cross-border of commercially achieved. was treating patients concept of So proof

continue and all in continued been therapy. is we for the finding major geographies new access we've that patients patients find activities, able know where to to and We patient quarter in first there gene our

early multiple centers what of as Europe, surgical and I countries, as year East during and with them well, call Middle in we working programs centers we've the advantage in full and up So the take to the the them and particularly establishing Brazil closely of key been anticipate access in course well. having very set centers

strong half conclude of access hope On year. the which well. and to supporting in step-by-step France, pricing the HTA assessments remind it's Germany that of Europe negotiation. with those you of is payer engagement process ongoing price a reimbursement. some side, And But in second I and We've is gone extremely had now negotiations sort the we

the in soon, right going treating patients means via England a important in access overall we're now treated And by, the of as Brazil. those U.K. a would nice really or weeks months have and patients patients we for And that anticipate that's access the is importantly, I treated early that we're to who goes in steady see the be of patients are treatment Middle to and the and patients in the Europe. have year Wales cadence more as East we will in will seeing what the cadence patients, coming that -- And there being say in recommendation And these we're in reminder, U.K.

really would I with the we're pleased say far, so So, progress.

Kelly question from comes from Shi And Jefferies. our next

Phase X.X FARS effect a weeks. on And My question XX treatment X.X over weeks, Neuro point placebo difference study start the rely endpoint? you about to at at Phase I'm you and XX the model X points will and XX weeks it's effect treatment this on arm just said weeks X, to what on is the trend for how showed difference. XX make curious the primary data from the desire

and of points number you up. a that So important here brought

placebo X statistical had a was needed was as is difference IATA affected driven the X look you months, study part effect placebo And would Phase that we that that they X learned. in after More to data So had duration, X difference and that time you months duration was study present something months X important only that well, that persistent noted. even weeks magnitude than the in that as if by at significance see And abate. of placebo that and effect this the is less achieved of have they for was still not a did. you been

patients to point X.X duration which for XX-week natural or more to of of is duration XX-month mFARS washout on placebo-controlled loss complete the the effect of phase disease, and for the the the a selection placebo history allow of years. average our the So mimic any closely a allow on placebo was for

should placebo would in change the X even on be history, expect we So natural group higher. the perhaps closer that and to based

treatment study. of was magnitude extension long-term benefit The the Phase on the based benefit based treatment the hypothesized X valuative of was on

XX history age, the an core was magnitude history there the cohort portion, XX treatment in of will an additional between for difference X-week do X.X-point did groups XX the with at treated for and which a cohort benefit. treatment -- X be all we those X of and matched continue But was months stage Now to them natural to months, right? the history The comparison and natural placebo much treated worsening patients between cohort. a of natural actually market X.X more the allowed

X.X%. difference the So XX to was over months XX the

X what as Phase to [indiscernible] mentioned study greater effect magnitude for than starting of a we're see the So you spec the X.X%. that's of side

in that study. puts position believe X.X% strong capture us in significant on powering a the to difference we benefit that estimate So in

might I quick require patients a PKU, are follow-up in you Do think broad PKU have in both expanded helpful. And classic a this mild sufficient XX may. ensure enrollment? label classic Or also I to if Super patients? and

good Yes. a question. It's

XX% have and we had patients additional mean reduction, patients a that XX%. fees of between who we with classical have reduction X shared XX% in that the in previously XX who were greater than to We had reduction running XX%

would So now patients. number also in things also which is to keep of cap classical PKU a a -- of XX in you're classical seeing pretty patients, I One we mind. PKU meaningful is a that lot. say couple across and reduction

meaningful having good a proportion those reduction. seeing are of you're treated of who So levels those

that federally significant effects, of the reduction, change about alone in points to impact XX% in most think reductions PKU is in PKU, The is of also levels only clinical XXX When disease, it's that well even by cognitive effects and threshold including can penalty. think other absolute of that the the a the classical important about having great it's known response are but general thing you terms a on. not

levels be PKU So classical those if benefits you XX% level of about one quite for XX% meaningful penal reducing obviously, could think or patients, when protein. the overall considers of the reduction a in

not these So in impact. sufficient these be only a patients have set but generating to with in included label, patients the quite the will we expecting is -- number and important record number a recorded in PKU we're is believe that of data the of classical magnitude patients also

unmute please your Danielle, is mute, you it? phone if could on

Yes.

This Sorry. for is Alex on Danielle.

Just a us. couple of quick ones from

my to Just clarify, audio out. went

request first, curious what FDA that back trying up and for And the wondering others? to just for that will secondly, C emitting of May into maybe about to we assume with the fair Type June bit. the scheduled? guess readouts Translarna. PKU a Just to were been you're it trying was Has the order then upcoming requested or come Is it little

previously specific me data let agency In May, we review the them we So guidance question date done more totality suggested and at have that data generated had specific In a the shared, to fall. the and that a from on over the clarification we've written quarter specific obviously, we've beyond as mechanistic timing have don't to type for the meeting B discussion time. and in data request that for others to of the have the of able and the following with timing take Translarna, this response had data, meeting an Translarna, received potential data we because we a NDA in a from to support readouts provide including only We've PKU them second meeting, the robust studies question TBD its the Type to able we dystrophin been this then meeting FDA, with be provided totality second more to resubmission. clinical that first. the the your and first regards up with

but the that over And it's in that request be data the then able you benefit include only to collected been So mechanistic to consistent in data and the the going they not trials meeting XXX demonstrate that obviously, when boys, to clinically doing a presented. be meaningful book. package, we preparing of placebo-controlled -- we're in FDA what for, we've process data see that's to it's and the these asked We're there's We're going boys. about the having needs meaningful X we're effect in clinically really not where the think of briefing a to lot the to able data change.

the in look the non as the key data safety use, of And DMD which XXX the significant see benefit of a consultation seeing unmet that of of statistically we're a across the of these significant to and studies, of across the ability Bs, is effect volume endpoints X as number context boys, across well collected the need. drug studies medical the remains consistency we over the that X

agency some time all So agency right to and conducting have putting submission. in data a at to forward a together also to can manufacture come previous these robust we look the briefing additional leave, in the package. the address so We're analyses discussion concerns some we at of the with

comes Joe question from next our SVB Schwartz Securities. And from

Will Joe today. is on This for

next a the omaveloxolone, pivot about side? MOVE-FA there for potential I want over on And how just to so is this you steps study. So statistical like benefit are significance, on Reata's And I to in also regulatory the miss it to follow-up. the a showing quick to based event, thinking looks the study back on while powering, have the start,

power sufficient we difference was to in study. believe that detect We Reata that will the have the recorded

effect our of don't there. the So we similar as we in same that year magnitude capture if see

the a at of changed views following Great. either insight staff Okay. the from or guidance this approval And perspective an terms want guess, they the here helpful. at kind agencies on and in would standpoint thinking, see your agency of specific all, any guys of here, if and up omaveloxolone then provided any you to is has what I just be how since efficacy and

scale scale. It's clearly that communicate historically, that -- their primary patient it's function effect endpoints in the have doesn't functions along a wanted impact significant sure. is therapy clinically can see composite feels has wanted the are everyday not Yes, ours very the a they the CLO a of that for those a really life, more on appropriately as the benefit, how interesting with which see contextualized an that being but moves mFARS clinical question, Will, on FDA a agency given because to But much key in in changes typically buzzwords endpoint you directly assesses meaningful. secondary to likes so contextualize that to recorded only

XXXX significance. Obviously, discussion was of that is and a endpoint, re-impression forth I secondary in went not of that clinical that statistical NDA there source which key time some achieve did based Reata And of lot the was to scale back fact think a the data from the share on October the that their approval. a the on was

as the specifically that can a approval So be it significant a that follow. threshold to others the we believe on bars FDA essentially may, of end change now

act how FDA reasoning or will the predict sometimes their challenges set think a they I when for prepared decisions, to be unclear behind tend the to while quite it's and approval. they consistent

it's So I clear. think

lot is adequately study, think would do I function a effects we population agency something the in the our to able relative a we being key is we to which like. FA the secondary in anyway spend that of that put time weeks XX to they planning weeks living captures in and study relative longer the endpoint XX has particularly in larger a MPOS, to MOXIe daily on believe sale scale, for did Nonetheless, that a the of that statistically believe strong study, have a significant shared position. lubes which activity that we achieve us patient

that selected if endpoints It was look course, at you is nominal mFARS similarly natural several changes last in because changes a We was there history of fact, tend ADL with endpoint endpoint I was the and data, disease ADL what the this of significance. MOXIe tend results move on of if in at the they in study. to the look MOXIe along the the the secondary secondary progresses. the And move the the you believe to as scale. secondary which Unfortunately, key statistical as one scale, study,

secondary now can to again, your is Amps obviously looking as question, that's significance we'll capture So approval, just statistical the but been set also benchmark for well. to see we I benefit be answer on endpoint think if

next Stanley. Hung caller Our Morgan is with Jeff

to a success why For see the Matthew, study XX% be was of XX% you see powered I difference study if a XX% when reductions reduction? Would a have XX% you XX% in seizure And consider then important? can the or to you can remind follow-up. to reduction us for a XX% placebo-adjusted need reduction do you

have believe effect in So on Obviously, the study ranging studies, the is that's been seen in any response previous hypothesized consistent couple hypothesize on what's placebo a children given in generally tried other observable which we reasonable, there a power the motor based syndrome XX%. of the and in of trials, placebo-controlled was things. seizure X% pediatric and mitochondrial between but MIT-E not other effect trials of placebo seizures, with the in is side, with XX% shown that to frequency change been was epilepsy placebo we

reduction. a On XX% the efficacy side,

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experience So again, to of would But be are as XX% again, on the we incredibly we others. as previous based that believe XX% numbers -- the well that experience meaningful.

And patients the additional wanted up needed geographies. on to And in if I any given the see from And make from know end patients wanted U.S. study then data. outside the duration coming indication had did geographically? PTCXXX, for been the they data for FDA if other Great. FDA I if U.S. of dosing the to data more the and end whether where come they additional you've at just supporting for patients specify from care enrolling

Yes.

the world the dosing to is on So asked and the support for just was toxicology data on It Jeff, support FDA a as in to data. conducted. was same reminder, study, where the proposed in the data around those of data the FDA from said geographies PIVOT-HD data instead. This be the uniquely of toxicology study study part were study conduct other used on approvals were the studies had clinical the support of duration could a is dosing nonclinical additional based that collected based being asked the the the And additional the they data and for that as duration. to

naturally study understand only the has that those outside data of the patients outside the conducted U.S. in from as countries are they been going to of Obviously, U.S., would come

U.S. And to in about so opening we discussions from patients whether But there the any we to collected U.S., at those coming terms in will those in the looked they plan were agency you as get we continue data take or do naturally first interim the data and expect data of cuts enrollment to to and the how impact other elsewhere. the outside the on U.S. be these of shouldn't that, data use

And from our question Barclays. from comes Wang next Gena

Very quick few questions.

the of knockdown comment then your PIVOT-HD. KUVA lastly, on sets, one in second are prior press the Kuvan individual First some in Experience. regarding see trial conference in cannot patients, percentage a release And and Huntington the What very each question level? but responders on data quickly is you PKU I Kuvan second quarter? Experienced study the these know in is just And had patients full patients? sets or we simply would the APHENITY is the regarding call data this

I for you Unfortunately, I Gena, didn't question. the question. thank repeating the your and third. hear first you heard clearly the second first question? Would mind

Sure.

data basically the will X with release First question press sets, individually and conference call is second in for you report quarter?

Yes.

any who the plan match details so from So decisions of the calls second there'll data previously with entered be will been become question, other whether we we exact in nature and have guided, that haven't occur all quarter, releases May, to Kuvan on in as a way. the feed the second we be to as APHENITY those plan given yet in the make And yet. to failures. Kuvan now not On treated they who had study them your share patients the data to available. There's we who are have do we've

out have patients study study in came Kuvan on the the We into who when Kuvan. washed have been who they were from

run Kuvan and And release we What then when opportunity relative those us to break the understand subjects. effect available. there observed will of that out the the phase, plan in sectarian data specific sort during was to data we'll to of to obviously what the some with give effect

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ratio X.X:X. drug of was We noted the that the plasma CSF in free

twice high in we're So brain exposure blood. getting to as the the

XX and XX% to we lowering. So at very ratios X necessary hold, we that to the milligrams, well those the be could dose if XX% design said achieve level exposure therefore,

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helpful. Very

from question comes from Bristow next Colin our And UBS.

Congrats Yihan is on quarter. for the This Colin. on

is be it in have this second And order seems quarter. big the question to to expected government continue Translarna, first just the the Q. a So noted beat for would the you very

order this about government guidance. wondering in Just DMD of you and longer the really terms update because time your also didn't

question. expect versus quick more revenue guidance. that? this for your very And have we Just year wondering the if kind on Q, clarification we second color just Can whole of more should a potentially

So in FDA requested is to additional you have the provided said already that for data previously quarter, filing you BLA delay the Upstaza third the correct?

performance Let about revenue. in me first quarter. We're say first the on the Translarna incredibly excited

provide to additional Eric As turn meet on to year. it Eric let we over guidance are Trans this and and... But on franchise remain franchise prepared remarks, target to the the in color me stated

to Translarna mentioned major earlier, grow we all it's As markets. in continues growing and

adjustments growth, So new prevalence on dosing as we're high compliance. particularly patients, working particularly we're the managing and and adding seeing pool

in East, course, to hold places compliance take such in We've Middle the years Central have the and expansion over America. these geographic rates X as the region the have many X lot a in of as last we Eastern XX%. CIS Europe, developed We seen countries Latin in of our and, of

that it's of as new come orders, as patients well are many and government ones. orders in the existing X central So these

kind to and larger And of the hard timing so predict of these orders. it's of some the size

get -- are patients We orders anticipate seeing in to that adding because expansion quarter, these every new continue of some from these we geographic second half we those the will especially markets.

continue. point We'll base we'll to the because we patients government new the that provide not continue incredibly right and confident this in to DMD see XXX performance like some quarter, XXX going year. to have we going guidance I'd in an is that strong Translarna continue coming have that very in at coming but to that this to in lumpiness time, we are including orders we the the in. these seen change a update But across and important. that reiterate managing anticipate achieving the discontinuations this are just are now franchise to we've we as So low and compliance have, orders We're

why to this typically guidance I'll annual just for And give say guidance. that quarterly we tend We then don't give reason. just

comparability the we a will potential analyses. answering -- cadence asked they've based on from to in provided now process we're say submission and the as and timing the agency data, had query with BLA, again, and of And second quarter of follow-up the back with before, shortly. questions in in third to a additional commented back those spend the data possibility is from we'll that responses the Regarding potential responses. I come the the the delay that supportive quarter FDA follow-up just for We

question And Kruse. comes our from next Cade

This quick us. Two is ones Cade on for Paul Choi. for

you or how We expenses progresses the quarter. the year throughout took to First, what impact we removing inventory full that as and pipeline for was see noticed was And out wanted wanted your to stocking see the we what here? second, operating to then expense the go-forward about guidance. operating think rationale of

Yes, for then questions. Emily. I'll and Well, it turn I'll your to Kay, over thanks start,

infrastructure we've launch and several now quarter of data. created, the what a past the the the infrastructure performance prepared years. as that is on OpEx, So first of is as incredibly the R&D the over commercial have previously, we've and been impressive talked we -- proud clearly to we remarks achieved. about Obviously, and products positive positioned first, mentioned in commercial our and we've result look, in and quite performance we're regarding well additional building

and plan also guided when position we in on a good We've share card we to analysis trials, which we'll result you undertake and we the ensuring this the expect to we by we'll to to do coming achieve years. operating reduction come portfolio, things will will Emily, and the desire success that the there on therefore, then success over and review, said stocking. clearly focus a which doing over strategic we bring to be revenue on clinical the as performed further changes we expenses. will a any do think OpEx that return that that on OpEx we be OpEx, that once Obviously, probability a review of on and turn in back of these portfolio comment very of investment on growth want and

analyzing looking our for we and to it priorities data would to of after narrow OpEx, On readout our forward obviously, look best, Yes. OpEx guidance. opportunities the program

was as saw growth well our there side, for revenue guidance to put a large contributed the the On the the DMD in to us which We some our no government year. Eric position reiterate first pointed franchise has orders, both revenue guidance stocking. as in out, and quarter overall as

Officer, now call to turn like Klein. Chief would the Matthew to Executive over back I

Well, come quarter as to successful we thank and the everyone they've and I to. that readouts study with want sharing joining of productive the incredibly I'm forward, have, as course, you call upcoming look all the with today. for pleased first soon to we

the joining again for call, and a good you thank all have So evening.

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

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