Vertex Pharmaceuticals (VRTX) 1 Aug 242024 Q2 Earnings call transcript

Good day, and welcome to the Vertex Pharmaceuticals Second Quarter 2024 Earnings Call. [Operator Instructions] Please note this event is being recorded. I would now like to turn the conference over to Ms. Susie Lisa. Pease go ahead.

all. evening Good Susie of is Conference as Senior the My Relations Lisa [Audio President Investor Results Gap] Vice name and XXXX Call. Financial call, we tonight's prepared Dr. On making have remarks, Charlie President, Operating and CEO Vertex's Financial Officer. Kewalramani, Officer; Reshma and Wagner, Chief Chief [Audio that slides as the recommend to We Gap] call. listen this webcast access you you and The recorded, will available a call is on be replay being our website.

and filings release forward-looking that Exchange are the the risks We and and call subject press today's our this will uncertainties statements be Commission. in on with making Securities in discussed to

financial assumptions. call and These medicines materially. of statements, pipeline, cell beta outcomes presented on Vertex's evening and and including, are performance including and without events limitation, future that moderate-to-severe vanzacaftor select our current the the based for would on disease those I GAAP that marketed financial management's in on thalassemia this launches sickle differ cystic pain guidance review suzetrigine the results fibrosis, note near-term also TriplNCF basis. the are a potential acute will could and we Actual Vertex's

the now call to Reshma. turn will I over

excellent including Thanks, QX today. both the another across momentum We've our you evening from and outstanding our board, and of and performance early commercial of advancement joining execution call acute us our continued CF quarter CF suzetrigine well of in the the launch all, preparedness CASGEVY, rapid Susie. in for for of deep Good on with thank launches pain the and vanzacaftor the potential pipeline. the near-term as broad as in

]% and billion billion, And the revenue and versus full billion XXXX. we sickle to based beta disease patients, bring guidance to of are increasing our product the near-term X thalassemia, in QX. our and medicine growth In have pleased patients submissions. in represents which continue $X.XX completed our to continue [ we more X multiple are ] we that as acceptance CF, $XX.XX [ point we with the $XX.XX reach outlook, In development, on this cell at to across this the result year opportunities and revenue to ongoing including And more patients, from significant completion multiple about CASGEVY physicians we reach payers and excited from growth regions. programs patients potentially revenue to reception of launch transformative regulatory very pivotal additional deliver deliver are

or patients with and in triple pain, severe older, priority fibrosis given acute to review by moderate been vanzacaftor years FDA. priority has been which The BXXXX which granted X suzetrigine cystic review the designation has in and also

with I mid- Lastly, late-stage pipeline, I'll our programs. on the very progress. am call and X pleased continued out rapid specific

suzetrigine-LSR has and the Phase II Phase the we II of this now results [indiscernible], year. significantly First, by study expect end

in month. pivotal review, and significant initiate the an update With we me nephropathy. comments successful in with Phase to the this the nephropathy to highlights, we II third, Second, study enrollment patients to have dosing towards advance and in the secured And as Phase trial we in and we diabetes, having original this later most let Phase cystic R&D in regulatory those study, pain, meetings, IgA program, III XX completed in my to the pivotal endorsement have XX-patient [indiscernible] X VX-XXX will type quarter development. I turn now povetasecept diabetes completed fibrosis, programs regulatory the expand the total trial limiting IgA

with Starting CF.

of triple chloride. to eligible we results February The by a very triple lower of burden. the to and as swechloride the And on in demonstrated for are our drive to program thus CF. indeed of announced all the potential crested. we sets triple the as levels, patients to The vanzecaftor pleased substantially than in high very have treatment normal vanzicaftir measured greater offers dosing even royalty the the the bar bringing [indiscernible] convenience once stage of towards standard have Phase III We an carrier levels TRIKAFTA, a reduction with a to ultimate early continue sweat vanzocafto also in new CFTR

portion. global also our submissions, and Moderna, portion I/II to regard the with acceptance, completed U.K. U.S. development MHRA Vanza continues CFTR to in the ascending to ascending VX-XXX, at in addition Phase has and single the by dose in mRNA filings the our validated partners in EU study regard the the With regulatory With therapy the the our in of it multiple EMA the dose have

who CFTR half our more CF current CFTR of a As and both the than from the and the complete Based do expectation and any XXXX. study reminder, modulators. cannot study me in for people make enrollment dynamics, therefore, on to from share provide is and efficacy first pace X,XXX protein the VX-XXX with, study the results safety not of to seeks benefit

to signal points to few now acute novel, and inhibitors. and pain Moving the a portfolio pain NaVX.X pain, program NAVX.X our highly highlight. In selective of

surgery. are submission by signal we First, has NAV third, the in review Phase XX, soon enter bunionectomy PDUFA acute action X.X is in study VX-XXX inhibitor, of accepted enrolling VX-[ II with XXX dosing FDA currently the the in IV and formulation and clinic date and priority that healthy a granted XXXX; pleased suzetrigine been formulation target January with Phase our second, ] pain very trial with I following class is the the pain the volunteers; next will

begin inhibitors. later to study we NAV on And with in is quarter. used inhibitor preclinically make continue alone combination pain signal program to NAVX.X this that may be lastly, X.X track on progress or strong This

have Just there the development lumbosacral There that of are X Americans. radiculopathy pain as In pain painful impacts for from more than programs high neuropathic a the LSR. need with approved million starting multiple or unmet LSR, or no U.S., in peripheral PNP, again, treatment condition a specifically is LSR. in moving rapidly medicines we an

DPN, suzetrigine anticipate is in randomized DPN change LSR results and rapid each, projections. a the identical exceeded peripheral for neuropathy, diabetic sharing pivotal study are we relative enrollment NPRS at trials of baseline in pay been my ]. As X opening to milligrams later pivotal program once end has of from X,XXX painful our we with of program II begin pace this The suzetrigine the in XX in of [ Also significantly mentioned Study and patients enrollment to the dose in peripheral consists Phase controlled excited and by pain, this approximately to year. complete, XX remarks, the pain neuropathic this scores year of week evaluating placebo. daily or now

XX baseline an noninferiority, for pregabalin. versus of superiority active NPRS arm will RCTs key is at secondary for suzetrigine assessed in And score, if we then include week The we versus A endpoint noninferiority. pregabalin comparator for changed also from test pregabalin. meet

share suzetrigine study, we will II with is to on Phase a pleased the am DPN I quarter. designed P&P, also study soon similarly oral formulation II to of to in neuropathy, Phase peripheral that initiate this diabetic the VX-XXX Lastly, track in this trial begin

[indiscernible] with presentation meeting islet Turning an now [indiscernible], experience differentiated with in awareness are updated study ongoing diabetes. data people more an the who care. despite I/II hypoglycemic therapy oral ] for June, to Phase from [ severe At patients the of ADA impaired cell dose as and study dermal reflected events fully patients included medical demonstrate who and of the least at follow-up. longer from functional a B to a patients potential full TXD. as of The the X for C single cure and had months a Parts with received continue duration VX-XXX XX VX-XXX of and follow-up infusion of hypoglycemic data

The results are remarkable.

And patients completely hypoglycemic All as follow-up day led and greatly evaluable and than the responsive of of of glucose point XX exogenous use. XX. demonstrated XX patients insulin events, memoglobin-AXC endpoint had by also endpoint in therefore, -- insulin insulin below production X levels glucose patients each well all XX time greater. the all the patients AXc with XX the level XX levels range months elimination XX% of less and or a eliminated engraftment independence. cell of severe primary reduced achieved hemoglobin primary as Specifically, secondary met end for patients X X% or of

the expand of original we for patient include development phase look have to next the to the enrolled forward additional forward for continuing are work regulators and approval which to these to and VX-XXX. finalize the pleased study, development updating To We are an With very secured pivotal regulatory end, on that discussions. you to results, fully is towards we XX XX requirements participants. with dosed those planning

is Beyond [indiscernible] in to VX-XXX, a our device cells VX-XXX I/II VX-XXX encapsulates need the same device, program or proprietary cells Phase VX-XXX immunosuppressants. eliminate for study. global the a in designed

initial We the of have study dose with stagger Part completed at patients. A between an the

patients. enrolling and with the at B, the Part currently dosing is patients full also dose, target between in which stagger They're

no Immune with where the As trial at recently a povatasecept, the The from pertains update at stagger major patients. and lead high. full Sciences, enthusiasm dose reminder, R&D last acquisition C to acquisition closed is between of the pove of remains Alpine for the our target our Part

As and for a data dual both lead the in pipeline with and in IgA preclinical indication mechanism hematuria being the a and of potential proteinuria, given best-in-class inhibition through Phase pove nephropathy, holds has a April action profile II clinical product the promise of its GFR. reminder, of and and its BAF,

on pleased for route study povi's I reached III in track initiate end to Phase elements. we're dose To us this that patients and to we on be II patients the with have nephropathy authorities, frequency its plus and FDA we had high agreement global with recap, give the attributes once-monthly in potential and share administration regulatory of successful to IgAN. povetasecept confidence pleased are medicine following to subcutaneous transformative and Phase important These of Renier am volume small very the IgA month. of global a with meetings

approval. single, design XX. of placebo XX Patients a receive in top to In Phase XXX preplanned care. the with place change of A pivotal to either program opportunity when the accelerated reaches analysis the pove U.S., patients of to be an global, submit evaluate designed on number take and biopsy-proven interim will placebo-controlled is or will affords double-blind, baseline from approximately IgA III patients the of proteinuria. weeks a treatment standard proteinuria us The of randomized, randomized for as trial week to

GFR. will For assessment an full approval, XXX the through study week and of continue

second alpha-X the pove review, of RUBY-X B-cell-mediated a We the in termed update Safety III X VX-XXX later To Phase renal year this a II in next. studies look from the studies pipeline in AATD. some nephropathy, demonstrated into cytopenias also I VX-XXX these both on being in and and RUBY-X. is XXX. into IgA basket readout termed cohorts forward close and X diseases, Phase or VX-XXX antitrypsin trials, deficiency in brief study was Phase Beyond to evaluated

more, And I that analysis, AATD. have molecules. discontinue the deliver would efficacy both we [indiscernible] VX-XXX decided Phase on to we have people of nor based for determined However, development VX-XXX neither transformative with

our With these in research will AATD efforts learnings, continue.

it I'll turn commercial over to a for update. Stuart

and the I'll Reshma. discuss some launch suzetrigine highlights pain. then first acute CF, ongoing of the in for outlook Thanks, provide CASGEVY

As mutations age X through groups Reshma reaching taking as once age expect additional to more noted, results national year delivered the we we and approvals sustained Kaftrio ages as modulators, medium CF and the term, where Brazil, near in reimbursement in over for eligible as X RARE we the long such number continue ongoing geographies younger additional again have for grew Europe, X we later term. our and with with above. of in anticipated the growth group CF continue including CFTR launches eligible to patients global near, and TRIKAFTA on now to we the patients in patients, In strong for this focus

positive in combination. The of the for to agreement modulators. for the fifth recommendation we all a CFTR the NHS Northern launch existing were reimbursement In long-term Ireland. in vanzacaftor CF have medium, are and SMC our pleased which Scotland, patients anticipate agreements an growth announced our June England. CFTR subsequently entered triple CFTR our access We of England, ensures into Comparable and have Wales arrangements modulators result eligible by and been future driven therapy, with NICE extended to also in modulator

CFTR to seek option. And dosing. are once-daily at of may modulators and patients convenience patients be have who even of CFTR greater of X TRIKAFTA levels the who discontinued a added existing may treatment new more than achieve interested many believe current We function our in X,XXX also there

to activities And and from we execute more outlook. the our in Vanza exchange medicines payers, including the do with respond which We prelaunch program, who encouraged expect with X,XXX preapproved growth not people by longer CF continued CFTR focus VX-XXX. term, continue to modulators, of CFTR mRNA than our developing is to

launches sickle our beta and CASGEVY, disease Now to turning cell in thalassemia.

well U.S. as therapy as people To globe. activation work important for the patients and Arabia key you ATC of to as we metrics as sickle disease eligible around with progress advancement curative and CASGEVY living represent Kingdom engagement our the estimated X as transfusion-dependent externally the physician, XX,XXX strong as well Europe, in to beta-thalassemia in make patient are launch update to continue severe We the and enormous the this payer patients cell we on Saudi early bring estimated Bahrain. and with potentially of markers the progress. sharing XX,XXX

Firstly, ATC from X activation. XX our have pleased activated X centers, more now with at as we launch. progress up and last We're quarter than

expect We globally. ATCs approximately activate to to total continue XX

Secondly, patient cell collections.

cells treatment XX patients growing of We continue collected. have journey, a beginning to the see already number approximately had patients

approved, And U.S., regions growth is are [indiscernible], last East. in patient treatment the quarter. we this collections patients report across to the CASGEVY all mentioned are of cell journey As every where and Europe these Middle in pleased initiating the region

continue recognize clinical are all of the France moving and access. rapid an and as we given report U.S., also access access now all as with approved upon I'm CASGEVY Medicare, program segments, cell support for the well such to our strong coverage a that and payer market to building early there successes, the as and regions pleased transitive across early to quickly KSA. are early see Outside we in not make in obstacle the and program sickle Bahrain TDT, significant We for in payers Austria, progress have U.S., we Medicaid as do disease equitable commercial, In benefits access. who patient reimbursement

still of leading known high particularly among level citizens. interest [indiscernible] significant is go complex. all is always has that We've to infusion cells Interest consistently The -- access their elevating the of CASGEVY patients. and way and we learnings. the also on many widely by have offers enormous of of reimbursement that from gained launch, other long the governments been CASGEVY is the an the that it's in physicians, patients, patient the the recognized, advanced hemoglobinopathies We health The East edited journey to broad Whilst payers. communicated process patient have early stakeholders. focus in opportunity and clear value these given patient to prevalence and high Middle is

confident multibillion-dollar CASGEVY but around And for inhibitor opportunity. selective option comments so does potential the to we in large now lastly, transformative and the in even a numbers in that my to help our world [indiscernible] the time, view U.S. Shifting has NAVX.X pain the limit patients are process patients signal the more believe acute provide treatment a suzetrigine. suffering opportunity XX to million now take this and will of represents We novel, pain I'll the acute commercial from neuropathic treatment pain. peripheral highly

at to large call surgical continued decision territory will and account account makers as post on commercial IDNs, such our completed as managers have [indiscernible] formulary on progress the our strategic pain We who leadership hospitals make of hiring approval, in leads other treatment significant will sites team centers. ambulatory focus primarily who and now our

acute XX to for Recall of approximately year medicine treated approximately the prescribed patients each patients that moderate pain million in U.S., are the to with setting. institutional in X/X severe

primarily a result, force setting. will focus As field institutional on our this

makers who both leadership information discharge exchanges have decision Gap] formulary formularies use and that have in the pre-approval for begun in in and the in [Audio We enable institutional engaging settings. responsibility inpatient

P&T by class by appropriately well these levels and to by post medication possess swift time hospital on support take processes encourage well-tolerated treatment we institution the for a pain finalized, we months hospital to like clinical way bodies up key addictive decisions enthusiasm can high economic and lines. are defined, it committees, [indiscernible], an organization, that information relevant depending mechanism does and to and accelerate including providing pain, approval working of reviews are for encountered for the and effective engaging specifically but payer formulary or payer for We've properties formulary of new be are its XX to of and

of formulary XXXX of in goal We in XXXX. payer anticipate during building half the with latter the contracting engaging coverage and discussions

No non-opioid December Congress payment which in in in Federally, ACS opioids. state therapies also have who January the XXXX, in for federal the of engaged novel, to passed eligible and highly tolerated Act, We XXXX. a state interest addictive Pain pain without including beginning in for outpatient separate the Medicare be policymakers, continue in with strong effective and governors expressed patients are potential for settings well

is fully CMS to Because annual still currently included not the for comment we approved. range investigational, once It promising indication both month. suzetrigine public as list it is in ZetRoGEnE policy for but guide separate X With system see a rule, payment at OPPS, in and or that prospective adoption. a FDA was of supportive process of is of last payment it No broad federal outpatient meaningful to rule portent Act state eligible be proposed the as suzetrigine released expect proposed drugs the level the Pain the is will initiatives, tailwind the a continuing mentation of

We for of for are to Medicare by which also Part to aims encouraged the the to alternatives D Act, level playing non-opioids Pain patients. field access the progress

acute setting, that to another In for cannot the filled. patients to understand immediately. asymptomatic important you in pain patients week it's able must with medication or be prescription, or wait the pain a have access receive discharge to day Unlike acute outpatient conditions, their [indiscernible] another to

nationally. ensure pharmacy with working broad suzetrigine key to therefore, retail organizations are, We availability of

pharmacy to first range to planning enable decisions. of coverage financial programs access for payer the year tozetrogene assistance initiatives their of patients prescribed the co-pay including In other assistance and launch, addition, we are to at a

the society. on have to suzetrigine with about the will we believe enthusiastic it of moderate acute pain launch for patients severe very and are impact We potential

even change We severe the an [indiscernible] Vertex. take these acute patients care pain forward forever Ultimately, on and way can recognize the for in at XXXX. components adopt processes. health our look this significant we is technologies, time vision of be we and In to working are system delivering some it to pain and to exciting of unmet to with that moderate in it's accelerate early treated, conclusion, our to fundamentally is need, case new goal

triple are the continue around the world the and launch We combination. treat to CF in vanzacafta planning advanced more for patients well of

of commercial the CASGEVY are era launch well and for launch pain a We new Europe are the East, in underway. our Middle with preparations entering U.S., and diversification in of the suzetrigine acute

seek we As to over further growth. review revenue I the to Charlie the the turn redefine and drive of to pain financials. treatment call will diversified now

Thanks, results again performance profile. excellent Stuart. growth demonstrate once consistent strong attractive Vertex's QX our and

with X% revenue year-over-year to growth and with in quarter quarter strong Second channel line anticipated U.S. expectations, billion U.S. X% this X% inventories select in solid including markets. were XXXX in the drivers the our outside increased of international in reduction an The of $X.XX

by Second by X ages driven launches U.S., quarter first with inventory. U.S. the in uptake was also growth X, for Outside demand was Captrio offset channel strong quarter the to growth children's strong continued the patient reversal TRIKAFTA. the by from continued demand of driven partially

$X.XX second were On of compared acquired 'XX combined front, $X.XX quarter IP R&D the the non-GAAP QX to and SG&A R&D expense expenses XXXX. billion in billion

in R&D associated to previously costs QX expenses is Alpine of the acquisition, billion 'XX roughly offset reflecting completed AIP QX a inventory. by to for flat just of accounted million XX trials AIP R&D of well the million charges transition of costs we as non-GAAP QX compares being portfolio, as reduced an clinical acquisition. of over operating 'XX. This disclosed year-over-year, advancement our certain charges, as from R&D $XXX and in include result which R&D were primarily broad of ongoing in $X.X COGS R&D $XXX as the from recently the investment expenses asset

suzetrigine, commercial QX for acute including and versus result R&D SG&A and We within our investments III pove increased the the in expenses as quarterly in and of launch activities program multiple for organization, prelaunch that suzetrigine pain. and acute activities in we of 'XX pain non-GAAP neuropathic over non-GAAP and studies a [indiscernible] guidance CASGEVY XX% in expenses will advance TXD. primarily VX-XXX remainder enaxiplin SG&A $XXX XXXX trial as studies, increase of the of year the Phase anticipate million peripheral prior including expansion VX-XXX

to reflected capabilities R&D the acute launches, continue including we further underlying our addition, strong results, charge $X.XX upcoming operating 'XX in commercial build-out new of In AIP quarter income. invest second reported results XXXX, pain. for due of the though QX preparation billion we operating accounting, non-GAAP from In non-GAAP in revenue $X.X potential and a to the quarter transaction XXXX we Alpine in of $X.X loss operating second billion. billion reported

reported tax tax of nondeductible by Our was for 'XX. the non-GAAP tax compared XXXX impacted also XX% quarter a the of in for charge of Alpine quarter negative to rate rate R&D the second to QX rate of onetime AIP leading XX% a

results, billion from for Aside with Vertex's $X The were We of ended after $XX.X charge second which rate the the billion to charge, and of been non-GAAP quarter XXXX. impact XX%. for the of billion $XX.XX tax per there Alpine and effects on the $XX of of QX nondeductible non-GAAP acquisition non-GAAP have share and to $X.X earnings approximately alpine fund non-GAAP Alpine QX in investments GAAP changes per 'XX R&D material would the Immune the compared in quarter approximately paying an $X.XX in Sciences. share drove share in of acquisition equates no per loss approximately to IP cash a the quarter,

[indiscernible] of repurchase we the $XXX million to shares. Additionally, more over XXX,XXX than quarter deployed cash in

Now guidance. to switching

rates. exchange XXXX raising a guidance product total of to X% revenue are range ], midpoint [indiscernible] at revenue at our representing growth the We current

outlook the as also select launch include high growth have contribution in younger patients, expect Guidance we continued CASGEVY. commercial we continue countries. half second core the markets other in to CF including from more continues reach We in year a of and the visibility as to revenue ones of

unchanged to guidance which last $X.X the non-GAAP SG&A [ in guidance R&D billion billion call. expenses, and $X.X operating ] continues from on include is our to combined a Vertex earnings expenses, provided For our

operating the remainder XXXX and absorbing As previously guidance communicated, for non-GAAP of range SG&A. we for projected are R&D our Alpine's expenses within

acquired we the in billion approximately now including acquisition year, the For IP second R&D, quarter. asset the charge Alpine recorded expect for $X.X

a R&D Given full to charge is not the of deductible the that is income. XXX%. year tax tax rate non-GAAP approximately highly expect Note tax Alpine XXXX pretax for AIP we anticipated purposes, rate sensitive percentage that,

Aside tax XXXX impact IP CASGEVY growth, to nondeductible yet full as charge, rate our effective in from strong the we closing, revenue of Alpine non-GAAP the have R&D our results regulatory remained and would underlying XX% posted XX%. year advanced excellent the In Vertex secured range approvals. delivered launch important of

pipeline with preparation R&D strengthened a for in product. capabilities strategy significant our launches and Alpine. [indiscernible] closing and with a made also We potential Vertex's [indiscernible] for integrating additional near-term fit progress as rapid in pipeline

U.S. We in are to Vertex's contribution regulatory Phase in in month. IgAN late targeting growth III we capabilities beginning in commercial a and Vertex's are already approval XXXX leveraging to XXXX. clinical, this begin IgAN revenue to accelerated set diversification accelerate and development with and

progress addition, as neuropathy in pain towards as well initiation as of TXD. pain Phase acute milestones achievements, data further [indiscernible] and LSR as readout studies Phase in through move multiple in anticipate important our In we pivotal with development peripheral suzetrigine the diabetic including XXXX, portfolio, II II in a we in such

-- The to anticipated updating These you our on [Audio future begin I'll and the progress continued ask these calls, you in XX. we of forward and to Slide look milestones progress Q&A on Gap] on period. other areas detailed

[Operator Instructions]

will Salveen with question And Sachs. the come Richter first Goldman from

be about of to early and understand question, bolus around early patients the vanzacaftor launch Noting CFTR a of And adopters? X,XXX can contribution modulators as could updated we What look what uptake is whether product the guidance? second relative dynamics for that may. help revenue could triple, think the significant I us like just continued CASGEVY they a then you if

vanzacaftor dynamics. for Salveen. you Stuart CF franchise about the bit launch Thanks, it over turn tell We're more a little I'll revenue the the to down versus And CASGEVY. breaking to

Vanacore Yes, triple excited thanks to say the the there's for once be a about also our their of are a patients existing physicians it's combination. modulator, option, honestly, increased they I'd day. don't think bolus Salveen, I the considering very going promises prospects with treatment patients interested I single are question. many fact And be potential in for for the going they on to the vanzacafta FDR are think a based are whom research that being that CFTR for who which of that function.

And also then who CFTR opportunity not currently a on as are a are for there I new you the think say, welcome are who option. treatment patients to going modulator,

other. think or going don't to I one it's So be the

I think there's persistent going interest to those be previously. and who've vanzacaftor are both broad patients today who in the triple across discontinued

David will with question Leerink Next come Partners. Risinger from

execution. strong And questions. the have on congrats I X

NAVX.X inhibitors? provide your clinical development First, [indiscernible] for latest potential could you could you just discuss the to develop efforts VX-XXX neuropathic pain? second, And on

this is Rachel. Dave,

first, and goals to break parts, let into take X turn preclinical Stuart to talk that over me ex-U.S. our the me Let it NAVX.X about

contextualize I used development. late acute in or are would Stuart alone are everybody XXX any expect pain XXX in So this it inhibitors. our on as could more bit neuropathic really that with to we bit portfolio. over little still it or be turn a or pain progress else, it, we used the in inhibitors, Dave, ex-U.S. for I'll NAVX.X they that, With it's or could be our in be ambitions. combination to a NAVX.X for in And little NAVX.X preclinical They But making on preclinical strong development. characterize the

the for thanks David, Yes. question.

in is the neuropathic they're things similar would is it like used pain. say in I acute the very that and like gabapentin, outside and pain kind options I the by landscape true both the the pain, And here opioids. So way mean and that, clinical that of then pregabalin, that's neuropathic and obviously U.S. in as with U.S. the things NCA treatment

asking about you're specifically neuropathic differences. know I there And are

recognition the think such, fair the ex-U.S. our abuse patients very U.S. that less outside very unmet the the is first. something U.S. of is less. systems to innovation is in opportunity time zero, is dynamics that say care consider by it's need health in care value this the on But of at I here And and opioids addition, of on. health And much focus it's not It's as pricing to the but outside serve the different. U.S. of level we and misuse will and later and

from will question with Fye next The Jessica come JPMorgan.

about Is Part I to product, regulatory one? the with your And I anything far completed cell what path diabetes wanted kind respect seeing there believe patients. A for the ask to X for so effort. do can with you've share that you VX-XXX, with you How type of VX-XXX? low-dose you're envision the encapsulated

Jess, it's Reshma. Yes.

Let me and to we'll those go XXX we'll X go questions. take then with Maybe first, VX-XXX.

So the plus is program. on this VX-XXX, device self

stage the and period the about right the study. program. exactly dose. and to dosing has that a cells cell dose is full now XXXX On in is the big the obviously really of time alone. the in making with completed, in be which that milestone patient results naked is so original this are XXX. XX I'm It's This say the a XXX full clinic a one B, I between is with [indiscernible] VX-XXX, We're both You're Part program, which progress, the enrollment frame. We're and patients. would happy

development don't of who the We full a patients dose are phase in in we're where stagger. with have

going patients, to path we how patients. to total endorsement to question on happy for so think your direct regulatory the to a answer regard expectations. the program. additional XX type compete about with really program a diabetes coming date of have exactly program to the I regulatory should study us you today forward an the think because I the regard than But conversations and And like small discussions we're for with expand X in would model more I'm a the with months. don't an to that CASGEVY their about XX that's

You'll remember a program sample in that sickle very TDT size. either cell or efficient CASGEVY was in

in a look Phase as updated to look complete the converted And Phase what I/II/III I case CASGEVY we forward we discussions from the you of did keeping Exactly to for like with regulators. I/II a trial. is VX-XXX.

Capital Evan from BMO The Markets. Seigerman next with question will come

you get remarks, than it you to other once prepared of approved health the maximum me kind that can system, your have I once to launches some really you the patients. walk suzetrigine through some -- suggested be launch of to gating of maybe on think, patients really the Stuart, might of approved, to more in these to to have a factors the care get hands do impact what gradual

with our Sure, get and not Evan. clear, crystal our that's launch, And And benefit due absolutely of and to pain also the have setting. Obviously, that data the the treated post realities institutional as diminishing. But Thanks the majority the are acute we suzetrigine are filing. for got face closer patients and III discussions there the are they enthusiasm with question. to is we've things like. physicians Phase market practical in and for from to going growing to interactions the we be to are research just

through to payers adoption their with to go P&T means formulary those and We're processes. and have formulary going work processes work policy through going have we're to and That to other with institutions.

timelines. And very do so use. and to defined, time. why GPOs we work those take that's support with engaging IDN policies we're are those institutional can And obviously, And leadership to already accelerate everything for well whilst instance, they

PBMs rapid We're to talking adoption. support payers and policy with

In available addition, suzetrigine America. retail want are at going to be we broadly pharmacies across to

organizations we And time processes these that also to And major lastly, know to the well. can do despite the accelerate because reaching going them. so as we're we're can we with fact retail take the everything

including of to forced looking because financial abandon are particular that or physician right access has that delay and prescription can kind isn't for and of if not yet. without finalized at range decide the assistance suzetrigine is plan like them, that co-pay their patient payer things a the product medical patient initiatives, assistance We also deploying and so their program policy a

So We to They're it's relatively those They going unique accelerate know multibillion-dollar are to are can going we're suzetrigine, we're going everything some can drug. and be become. facing. well to the Vertex. do to of we become challenges not to them the to defined,

Your next question [indiscernible] Raymond from Piper with Sandler. come will

Just maybe X questions.

on maybe First, pove.

to Phase as which got be a pretty access getting interesting competitive question little I more Biogen a II bit think seems Just crowded. data. to Ian a just had ozardimab,

And you inhibition? to And about maybe maybe view match to little then up how the of a talk BAF a that? anti-CDXX Just CASGEVY APRIL sort does compared how question. bit maybe commercial

of fully timelines CASGEVY. for case? Can much that maybe the of Just patients talk during in on to the [indiscernible] is And an stage you fertility about around place talk getting treatments launch. reimbursement overall about there to it the for the how also have suit with maybe impact this early not

Reshma. is This Sure.

then going. to how I'll the CASGEVY about question that's first, Let it to me and first turn Stuart and talk over take

actually XXX,XXX about So in of important one alone. is than common is rare primary the nephropathy. There's but rare U.S. disease. things it IgA It's know common It more to more the most glomerulonephritis. disease, the a IgA with nephropathy

are are there that be waiting that served. date, to of the lots To So treats is underlying of cause specific no disease. therapy there patients this

put and is works the it the which by the our And caused full sandbox of It that space a nephropathy were cells. and disease long povitasoset, there agent is of in the the B out as enthusiasm to B after BAF of disease their a available IgA been And comes after short the our for been area it by activation a this dual-APRIL disease some enthusiasm underlying a it that our way, everything fact in and analysis has interest time. a cause activity on inhibitor is is reason for in Alpine us cells. has of a for the directly from there these

data, action, through of clinical preclinical development. inhibits as antibodies. this of B-cell the directly auto drug about we is all it seen maturation And proliferation, mechanism and well this of by data proliferation. It dual-APRIL inhibition is BAF II Phase And its BAF as APRIL potency have affinity the way what

about called underlying also GVA problem. GFR which So what's biomarker we're talking the of hematuria, the IgA, the and proteinuria, glycosylated advarently that's is IgA,

X subcutaneous mention volume. small it's and to monthly Not dosing,

potential has -- transformative potential host IgAN, holds the kidney of associated You but like diseases and agglutinin put a pove diseases ITP, anemia. warm membranous, whole all holds to nephritis, cold have lupus for that effect and of cell-mediated host the best-in-class profile like other most hemolytic B-cell-mediated disease, the to also be transformational heme ANCA together, effect in a

about to first nephropathy. its getting Phase So excited IgA molecule I is more program, III this be which couldn't

I me specifically talk let Yes, [indiscernible]. take just back about a before step

patients get early CASGEVY, particular in United which fan and because to provide the X we and multiple treatment requires certain activated only and in, treatment number support risk to So authorized of a areas. sites the there's try trips of the the to in addition, of centers. And because States, the conditioning comes have because where is fertility regimens sought to b-cell in

services [ the provide lodging want and to payer. One no is and what the equitably matter ], and other those one preservation, to we travel patients support in fertility

they are by patients patients. previously services travel to why commercially are fertility provide has the met of we've to OIG. suit well. patients get able because preservation, able as that's and decision ruled What those have on on and government-insured We approved and buy we not preservation our on for launched is try fertility to to lodging been insured to that both And support government-insured

their patients access, completely of the number communities, number collections. the beginning seeing rate-limiting going suit cell sickle that I I Having a will resolved. fight of successful payer. exactly the being in and be committed [indiscernible] the of to CASGEVY, we on are impossible are said It's term, as when rights the In to whatever who and are to we're in short think see and journey it don't of that the treatment their TET already for launch and to timing that cable and heard

And the Morgan question Stanley. come next Terence with will from Flynn

high what in Maybe me. the just vanzacaftor -- on level I on Stuart, Maybe considering you where making going X for discussed know pricing. at data III the about directly are decision the think confidence for to comment you're then just as full not your you inputs a you're price, on that any year? And see fall? next VX-XXX this update Phase might of but we some

Terence, let me second first. the question take

been released. accepted best has ASA I think fall abstract been conference, data accepted have it's in suzetrigine the the The been VX-XXX now category. and at it

but I'm So can be the to the fall/winter teams Stuart, full see working the also time acceptance to announced. best-in-class you. it already there. on been are frame, suzetrigine Congress of over you has to sure abstracts expect as manuscripts probably in going

Terence, the the our And to it have it Yes. with we're medicines, to the we vanzacaftor clinical as value you all and vanzacaftor, is going provides to approach pricing on of base on we're of as chloride. which convenience to Phase patients. in it It know, going vanzacaftor the of And CFTR performed anticipated about we're once TRIKAFTA as by superior program, brilliantly very function the of as daily. positive being course, restoration [indiscernible] of sweat has profile. the measured III noninferior benefits

to all pricing, obviously to of So going into take the when consideration the a thinking launch. we're much decision of factors which we'll is those make closer

Your question will Fargo. from come next Bansal Mohit with Wells

LSA on question X Maybe trial.

there. If trial. placebo-controlled could It's set you some help a expectations

So here? other point? are for -- that, a should any like program be at good you DPN we think expecting a one enough The just pain is the this AdCom trial X-point acute improvement would

second the take Mohit, question let me first.

the time to plan As do not any The but Adcom I us hold said wish know an let accepted has was that know, in approval. agency at know they granted not can that we agency as between it let tisetrigene, actual submission [indiscernible]. and to my of prepared filing you stands that they thrilled today. only remarks, the have acceptance the the But us X also, as are the

LSR, in share our the so That we're year far that's exceeded this to to has trial. [indiscernible] results enrollment expecting On also significantly honestly, that VX year. now and a significantly and and of study study, for us terms able this be projections

dose. can and how to study you think the regard about it, high with this uses it So

of between kind the milligrams the LSR specific has So approved that DPN. pain. II the of difference The DPN therapy study from deculopathy Phase for this and is LSR big XX treatment no

is II within LSR a Phase our trial in so And group.

the the for -- So can for it's change. And placebo And have for study specifically available of an goal effect sorry, of pregabalin had helps. for the as which is III LSR, study. pregabalin the because the frankly the approved This appropriately of the a the study to get change arm a Phase the LSR. LSR that treatment so group. group magnitude the was there [indiscernible] VX-XXX treatment is DPN alarm for DPN the we'll goal study, because a LSR the study, of therapy hope as we therapy that DPN. power arm was placebo the reason no I And treatment equally,

more X take questions, we'll Chuck, please.

Bayko come will from question Liisa next with Evercore The ISI.

you're expect on as least Just talk therapies Do obvious. switch what quite nevertheless, are, uptake. the of is there follow-up not how a you Just value the vast patients you over? think like it time? in there curious of majority some as Maybe at your about has expecting been like quite feedback there? It's the can will about Do happen patient much quick over terms you vanzacaftor. but the Will as solely rollout of other conversion?

any comments Sturt, additional to make?

to their interest earlier, be launches are kind Yes, to any of patients the but profile. and going that as it's important of of for think is CFTR benefit that, to just today, going these well-being, our of said on think modulator great other CFTR that -- of going got vanzacaftor I is think know I the as CFTR as excited think a because I who patients value I also to about like reasons risk we're it a And health be continued. those to function chloride modulators it's who sweat would demonstrated equally by it's I but increased for

interested I on, kind once really going of a think be part said of the that benefit as it's being which to attractive broadly And others. group another to of people. don't forget is appeal of fact to going an mentioned, I the as not than chronic medication. or it that's So also again, daily, who has to earlier more do be I are X there's something think I

we as other our as have about CFTR we're been vanza modulators. of any said, of launch excited I as about So the

people thinking? pretty it think you Do I of over -- convert was get of a how might quickly just and your be slow to kind or sense rapid. will trying steady like the

exactly Yes. restarted, mean I going -- and transitions get people going to patients, certainly, not the I'm physicians we're on reaction how rapidly Liisa. how very enthusiastic. has speculate to been with profile and much the the

[indiscernible]. maybe to think with just Patients their Liisa, usually it. CF I'll through add X doctors if once want you thing visit

patients bring aware potential patients vanzacaftor, consistently drug higher their of the efficacy. in thinking As and them are and physicians expressed particular, interest that may for the Stuart about have said, are development very as medicines in

far maybe as that's we pieces are with But you. regard timing. go think those that as can I of information are to helpful to

with will question next from Yee come Jefferies. Michael The

Two questions.

you we shining greater will therefore, it diseases autoimmune versus, through it just have the And guys can think also just On will about be I have data. product, lupus other me, stabilization remind first you half data reductions but your that idea greater will Alpine say, in is that and know to better best-in-class, how [indiscernible] you and reduction or in have of to 'XX? program it's think for for BARA which that EGFR wait in RUBY-X

formularies be benefits Acute maybe talk the me on think about really exposure and you on plans? launch, to a you'll the And get on will for No the and more but and there, that's believe that on blocking remind can tackling commercial about reimbursement that's how remind on you in just comments commercial, us the Pain of just then Act, Pain quickly And take population CMS you that considering. eventually seen product? more So

first. I'm comment pain Yes. on to Mike, to going ask no Stuart

Act come thinking the then there's to think I how it was for pertain is think you a about Mike's and little commercial? back pove. Stuart I hard hear And might. government-paid patients I'll to question are you But Pain No

Yes.

alpambulatory So payment to is surgical patients looking the who the treated no are pain, center setting. Mike, at add-on

because we the not but products, as X is not of listed you said, approved. were As we're that

yes, to added so is do approved. anticipate that we -- being And list suzetrigine

terms of D Part also and making there is sure allowing also the terms that playing Act, which in that to of of and for area, like terms maybe opioids at things not alternatives between and you're in Medicare the utilization non-opioids. the co-pay the in parity looking thinking in therapy of In level like patients No step the is Pain field things management and

and be said, tackling these . commercial as doing sort is In blocking is in This you [indiscernible] to terms talking the really of, that. we'll as to commercial, said, of are less you what relevant

And question in other was proteinuria. nephropathy? I about pove, it think we how IgA all the Mike, think on the how on pove about the should think about we studies in then question should And

would B-cell cause about the it way So is I disease underlying diseases. of and think

We lupus a which have as is diseases, as III B-cell nephropathy, month. design II by of has going going nephritis this very there, Phase was Phase to studies nephritis IgA renal now X basket RUBY-X, in It ANCA-associated a is which scientists. Alpine well clever membranes. on. a There's It mediated

diseases, biomarker. may example, of important. hematuria I'll PLAXR tell In in very the a are know, many And very, diseases important. prurtinoria B-cell-mediated All you is But you, very is diseases. these membranes, these important of is nefridities, as in of some for

acceptance protein important its But in is think in proteinuria I others. nephropathy is approval prominence looking is is elevated IgA IgA important is FDA's So because clearly biomarkers hematuria the and some important in of an -- very PLAXR in proteinuria at accelerated endpoint. of as like nephropathy

impacts something basket, the of But or mediated be proteinuria. could inhibition the cells a It's cells. way good and of -- down proliferation be really in B tamp And diseases a it the like my it I it's optimism diseases, dual interest from. RUBY-X to and about case where medicine my of enthusiasm are ITP, comes is good platelets. such because for povetasecept these And maturation, and B would about for that's differentiation would it's is it other look hemoglobin like in not B-cell B-cell such the because it markers at B-cell-mediated heme

concludes for by shortly will replay after you may or our the conference you X (XXX) XXXXXXXX. session XXX-XXXX your you disconnect. as code event now available concludes using today's our call as XXX-XXXX Thank (XXX) be well for replay presentation. A question-and-answer Thank and This for today. of X dialing access call participation,