VRTX - Earnings call transcript Q3 2018 | Vertex Pharmaceuticals Incorporated

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Michael Partridge

Welcome to the Vertex third quarter 2018 conference call. This is Michael Partridge, Senior Vice President of Investor Relations for Vertex. Tonight, we will review our financial results, our continued progress to develop new medicines for all people with cystic fibrosis and recent advances in our research and development pipeline. Dr. Jeff Leiden, Chairman and CEO; and Ian Smith, Chief Operating Officer, will provide prepared remarks this evening. Officer; Commercial Chief Arbuckle, and Dr. Stuart Chief Kewalramani, Medical Officer, Q&A. for us join will Reshma you webcast access website that recommend We the listen this as slides to call. you our on is being This conference call recorded. our will replay be on A website. available

and of the and cystic without We future on commercialization marketed Securities development to materially. fibrosis, now risks today's the Vertex's and outcomes financial based These subject I for ongoing press Exchange triple-combination will that regimen differ turn Actual and call CF potential our our detail are events including, discussed the assumptions. make Commission. this other Vertex's management's and statements Leiden. call over limitation, forward-looking could filings Vertex's will are Jeff and in release uncertainties to programs current performance medicines, Dr. those in regarding on with statements the

Jeffrey M. Leiden

year-end molecules in deficiency into of research, and the I'm one by Good our the we to with made our development progress treatment across evening Michael. alpha-X-antitrypsin we on start FXXXdel potential thalassemia to first our treat pain. for CF medicines approximately mutations, of approximately of VX-XXX that, CF, to Thanks, eligible XX% we're XXXX are well have everyone. advance a preparing CRISPR now we the development In in to and for Vertex with outlined have other medicine rapidly XXXX. for tremendous goals into CF are initiated are move that progressing track all beta pipeline, medicine single to the patients In to the half in pleased we're with business this of say development first of our patient all progressing people in year. and And development or Therapeutics key of achieve study a CTXXXX more disease. and clinical toward clinical the any partner

of approval year treated gain their cause in of submit medicine later the patients to patients new of medicine to for progressive medicines. XXXX six as the patients year that Australia, agreements, to to future young progress young or progression and we two multi XXXX initiate ORKAMBI. of treat Europe, is increase before in approvals also been FDA application possible for disease reimbursement supplemental this of certain of reimbursement eligible underlying patients to first with end medicine part age is in treatment presence KALYDECO slow as plan as a important cystic a provide has driver to of organ eligible in disease We've early and with and to of many patients fibrosis. number key and young and SYMDEKO our further a as its year, allow a To Many in treat disease. eligible from the in Denmark across provide significant be CF reached years the birth of as launch CF time. to which important anticipate also cause as throughout strong children us February. the with the the gained disease. access strategy U.S. new access one years the to demand age U.S. of now this as signed approval this the that following end, ORKAMBI, a as to recent prevent to With First, our multiple of will world, the In continues we with to The underlying also rapid of the as approval growth the be those revenue for treat age. drug agreements countries this these recently in of pathway to enabling including we

regarding Importantly, certainty Phase of two Vertex. these We future include innovations VX-XXX. VX-XXX in regimen we patients expect these two will that different a the in regimens immediate triple enrollment rapidly late two also agreement discussions VX-XXX to Phase studies they that in or ORKAMBI. evaluating reimburse in We're XXXX. our yet access remain CF data combination next-generation X programs, either X the from portfolio triple type agreements countries, have progressing for of this completed September, corrector and but In to from combination provide to have other studies

the We XXXX. and for complete this report VX-XXX the quarter these X enrollment to quarter first in Phase studies expect from studies of to data

In the both as from studies possible. with choosing age data a parallel, in of of both quickly approval. our regulatory children regimens approval track combination for new evaluate to application of we've of on triple goal combination XX recently triple initiated mid-XXXX. drug X remain of ages regimen will to later no for the with a best this to the goal patients group as programs than regimen years We of We submit also for submit gaining

continue potentiator future, We to potential for and better triple even VX-XXX also including to once-daily develop regimens combination other next-generation profiles. contain in have to that regimens regimens the may correctors CF innovate enhanced with our

into clinical coming We the advance or expect these months. one correctors development novel more of to early next-generation in

all we're can with markers is into of need. specialty new clinical potential diseases well-defined biology well strategy transformational use large are targeting research potential create or medical the clinic. portfolio a on and development where our diseases for focused early transformative medicines for of the And advancing medicines rapid unmet understood and benefit support serious such CF, Beyond The the timelines. we that have we development

transformational CF CTXXXX advance these to proprietary resources new into sickle great together dosing establishing holds research the and significant with into with studies. CRISPR pleased we're of promise CFTR clinical we're and progress rapid cell bring and With are just disease we CRISPR/CasX both Therapeutics, also is insights technology. both medicines assets potential first beta bringing for development early technology thalassemia as a that CRISPR/CasX treatment in in partner many the gene-editing diseases gene-editing and diseases a from toward treatment bear we other scientific the first number we making to to patient are the our stage did the are and We therapy. using as cutting-edge our the with of CRISPR advancing This

mechanism Our for pain of program validation is science where innovative the translating example acute sodium another to X clinic of first and channel provided generated the chronic the for to treatment data Vertex's VX-XXX clinical Phase X.X pain. in the date

multibillion-dollar Phase initiate pain, X following results in that We Xb in study of early support the type pain, third opportunity of specialty many medicine of has force. VX-XXX lead Phase pivotal future to of represents with acute pain be pain sales expect surgery this potential neuropathic to Acute reached We conditions pain that dose-ranging now pain. that can XXXX. treated VX-XXX a for bunionectomy acute where development are by acute that plan in the physicians to a in the also a

expertise development proof-of-concept mutations systemic We in potential development our additional highly of AAT significant of clinical to updating CFTR as report of and antitrypsin and for research with as mechanisms. one first later medicines medicines. the in issues scientific well is on than in molecule to disorder have Like a inhibitors XX% acute in complications program biology both rapidly liver. the I'm not treatment and AAT need inhibitors targeting invest clinical CF Given of additional and do patients progress that move discovery where believe other caused channel they providing also insight tolerability, gene to us the cause an well-suited more we molecule to pathways also to NaVX.X as including deficiency of abuse There in the pain that protein results continuing our small year and are to primarily the AAT including or a associated shortening for the this development NaVX.X AAT. in segmental portfolio life the coupled for XXXX. advancing lung similarities also those is opportunity as the this in these single enter others compounds its addiction, we efficacious treatment sodium well of the new many programs, advance development position the pain establish folding AAT of by and common mutation opioids, and pain you the and early we molecules pleased our correctors may alpha-X into we're into expect potential protein have approach later a and of and I this medicines how folding that other to in is to forward small glomerulosclerosis in experience We're our to that in the novel look with CF, target between disease new rapid year. focal

potential research our business the evaluating development of is with model our profitable a R&D platforms. truly business in We move growth for have differentiates a and will pipeline expanded recent our that future. in been opportunities With company are devoted provide which on innovation in pipeline Vertex more we to medicines product based evaluating has and also significant scientific we're with believe Ian the marked the number combination strong This led long-term in-license to transactions unique biotechnology external that have revenues potential to serious where detail. now R&D technology establish earnings, years opportunities in our transformative internal and in medicines with our multiple we or patients bring access to our year for expertise strategy and increased and As our such and to diseases. significant a efforts it broadening of as completed of We've and acquire for forward, we progress CF financial continuously development highly the growth research profile, ability or that assets scientific discuss across which has more opportunities, our collaborations fully and strategies aligned. by our globally, further to goal finding our portfolio of team scientific internal

Ian F. Smith

third XXXX million good pleased the XXXX to financial a of outlook CF XXXX. first. third in increase third for discuss review everyone. quarter Total future $XXX revenues evening to of quarter and our I'm compared represent results recorded XXXX. Jeff, in and as XX% the you Revenues the to growth we our Thanks, we with to quarter million $XXX approach financial product

We treated as see significant revenue patients growth with we increase number the globally. our continue medicines to of

driver the of for the has to remains public in SYMDEKO third the from receive and which Similar quarters, initiate ORKAMBI revenues included of patients $XXX quarter for SYMDEKO in demand SYMDEKO feedback coming revenues. therapy The primary groups launch total for switching time, payers. homozygous patients and and to prior and SYMDEKO, strong to U.S., treatment is coverage strong million who first CF we continue private from the growth patients eligible from all SYMDEKO. positive Demand and physicians of across rapid the in FXXXdel with for to both from SYMDEKO back patients initiating patients, ORKAMBI discontinued come also our

compared patients of for with third compared an XXXX investment to quarter of XXXX third net quarter quarter the the share per in third income our the $X.XX support were earnings per non-GAAP income for of treatment regimens expenses of of XXXX. third our with of of due million, million, $XXX Non-GAAP was globally. XXXX. with Our to $XXX the R&D $XXX triple to for advancement an primarily CF $X.XX, was $XXX medicines net earnings to quarter of million the and combination portfolio increase combined the SG&A of share million This and non-GAAP

with year our net product future for total comments non-GAAP CF of $X.XX the total has to to non-cash product record doubled of R&D, billion more our combined strong this to revenues. with We marketable driven we to $X.X year, and $X.X than in at tax income billion securities in quarter beginning cash, for billion also last how and Today, well billion revenues I as a $X of reiterated we approximately growth EPS ended $X.X Our cash and $X.X by anticipate growth and equivalents, financial compared providing year. may the start the expectations and largely compared next CF on billion guidance we as SG&A few expenses non-GAAP, revenue how billion. for to charges. close will guidance

have revenues of further completion labor not CF impact recent of year, for SYMDEKO of only and launches, SYMKEVI revenues have created we date. will guidance the we be reimbursement when where that In impact we on profile already the revenue we XXXX, reimbursement established and is our reimbursement across ORKAMBI portfolio, on grow have in our provided that agreements largely agreements how as at you year. to currently expenses business, multiple revenue If strong guidance be from The agreements. for reimbursement is based it unpredictable. consistent on next CF geographies countries timing continue based will update provide additional Therefore, at We XXXX anticipate early growth our a total XXXX. with for our we of the we next the the we beginning XXXX, growth gain will guidance will appropriate. financial where and This do of

Beyond not XXXX, be medicines. who group of medicine a for will one mutation the approval minimal by currently continued are revenue combination potential of FXXXdel with mutation largely launch patients and growth driven approved large function for our one triple the eligible and

outlook. The provision vast non-cash This be business operating expense of losses. at to effective the our as of multiple regimens globally, combination development. that, strong the will access to new provision that our updating I'll an to medicines and financial progress. advance serious profile taxes, discussed research period low for each improving important strong, is filing. profitability new we we CF, define XXXX mid-XXs our I tax majority further note of will on the business also forward result our in diseases I triple growth our tax patients progress With our for a of XX-Q The to future from and be be to as our CF more to of look and will to may provide from the medicines in to utilize Now recording non-cash obtain fully you rate data tax future line coming open would the development, X Phase year begin our a our in an financial net until a into of our we in approaches questions. treatment

Operator

Company. is Nadeau question from from first Cowen Phil our And &

Your line is now open.

Phil Nadeau

the afternoon. Thanks my for Good progress. taking congrats question on and

about completion and the you the for financial growth Which the talk unpredictable, or of year your revenue Just could talked are guidance Ian, questions on which possible know be ones total which sources revenue made. financial of XXXX me, in you which drivers specifically said growth Can two comments where I countries for that one one growth. you on expansions? cards? but are recently about and outside you was just ones next you U.S., got wild comments,

Ian F. Smith

here line over we're driving really years we're revenue future patients and the a that's to it's comment look Thanks which over for a what previous the comments question, more I quarter. being we or therefore, future, into and I treating XXXX, we some When I nice on just about our Phil, see all, first and year think thanks replay years, the of revenues. the is continued the as patients good our more we for want do of seeing for XXXX is year the look growth made, so that profile. when and on and we think globally, treating year

certain and think reimbursement the growth markets we XXXX by U.S. then outside and would year's SYMDEKO XXXX, is for also U.S., going about about where SYMKEVI which U.S., continued see as the to is outside even full that outside should continue be drug. proximately launching already and into growth a As time without patients are in known getting U.S., reimbursed. is contribution of the from into the of we launch think in driven we the But SYMDEKO, on more it that also

to If our it UK. largest not as principally, geographies we're revenue. larger obtain unpredictable the or that those of baseline have France, would then anticipate approval, is from the to to pause so attain over Canada. we terms in revenues, the which we of already More on there, or growth to the in have we that curve in though, in either on it from in impact to anew, this your It's particular, see a are are those specifically and launching the CF probably a be reimbursement the would that second we're I in possibly markets. geographies. timing, in launch where the market. of drug large terms And want switching UK, an be So question, growth approved is is – just could UK, reimbursements replay, we do

launch the the have in drugs to We UK.

We continue discussions progress countries. with of to make good those with all three

However, resolution, or as we XXXX, whether progress. is we'll it whether in XXXX you it's update in

Phil Nadeau

thoughts had Proteostasis and on to weaknesses? Galapagos second new announcements, two then to it? And today, helpful. data some those get NV updated was collaboration, do the the couple the curious close as team's data real competition a the What some their recently really I'm you strengths programs. well from That's after as see How as announced a on parties. for change competition, and

Jeffrey M. Leiden

the So question. is Jeff. this Thanks for

data. comment As you typically don't know, we or individual competitors

I think But in our actually sort a would itself. think are the and learned on the sort of position of our lot and comment speaks the over to last for data where of I data competitive we what sort view I And year. how is like we've process. we

In position think fact, year last significantly. I our over improved has the competitive

of have really their that clear regard have the lives. for superior to order doesn't that digits have in think, the triples, you things be safe. the reason PK Phase means to be do of that I learned for to pretty of learned that importantly world to the that be are the We tolerable now is triples we're hundreds that also it's efficacy, right It that going bar that These future. to is have efficacy a going be ahead regimens quickly. two One you X And been and of world point regimens we a have than to of of think trials, it's the going have very the that allow drugs we've significantly able that they for take going for really year. triple in which the co-formulated, a mid triple, combined, get and years. different be the maximize to that that And the to kids difficult the mid our who in last bar I has rest to provide any know and would digits a now patients, most double those about to in into are important components. have you into patients they a patients, us are up that we're a to homozygous three in They regimens and quickly are all the that we enrolling very we'll double they're And And the for have mean those and pretty three coming file patients. one we'll minute. very in efficacy to can co-formulatable, needs medicines which company men get treat them the particularly benefit need well that's and year, no so -- patients the homozygous triple. patients are into next And bar, right the pretty medicines on can are patients, raised schedule talk about to in us, for our confident where and PK, significantly of launch gone later in men only lot to is it's

are, these high where we we data perspective, is with both like And on think efficacy have most on we safety bar, from have which options so and frankly. I a drugs, multiple we and our clinical importantly,

Phil Nadeau

thank you. helpful, That's

Operator

Thank you.

Meacham is question from Geoff Barclays. from next Our

is line open. Your now

Geoff Meacham

I have for Thanks afternoon. Good just a couple. question, guys. the

process, have you pick you matter, you one just of benefit the think the the over regimen exacerbation – it, BMI may data first in for about on mature is when guys won't much on NDA, way likely selection long-term. the so on The triple the and that actually, when

you're of or there that that you looking profile tolerability just the So, for? other parts are FEVX think be about is it will safety, impactful in

Jeffrey M. Leiden

this is Geoff, Leiden. Jeff

You're right.

we'll and at these point that the and whole tolerability data a as the these we on data is as data we preclinical data Remember, base as have primary can FEVX that think early of and well clinical profile safety that lot well. I drugs. the triples, of pick

is you that, good disparity I outcomes turned out lowering the is, that our thing at positive long-term experience that which have less of hasn't FEVX have think potent have a significant, KALYDECO in to these and, very I effects. in interesting long-term effect can one been also long-term far, and effectively the bit have that acute will ORKAMBI benefit. these as hit is least, what CFTR the between many profiles, a there short-term that And, acute and say, actually a those so mean enormous of and similar if profiles, fact, profound, know, outcomes, things ORKAMBI, drugs acutely, very acutely being patients, chloride is have long-term very in you which get by is different on you really sweat suggest

of effect the effect I rather a a is think disconnect an and small. So, risk between acute long-term

long-term the of but Probably of to have relatively will by period we we obviously, one short these drugs not within a effects which decide time right. file. the of time, Now, you're both

Geoff Meacham

for the and the when data of triple obviously OpEx haven't Okay. spend, Ian have you'll R&D. for launch a XXXX programs And a bunch outlook, follow-up a but pending new and you and I plan given know just then you

thinking are how leverage? So, some the context showing also in about of guys that operating you

Ian F. Smith

question our deliver position whether trials, on maintain in investment investment that these And declining CF? Phase we not. Thanks and I when we X that we to that I I actually commitment the we want Geoff. really the we're for are to the asked get want because Hey, do question. to pointing continued got just you we've this out CF. appreciate cover sometimes

invest We in CF. to continue

fact, patients X Those these to longitudinal lives. able their be to much of open-label and benefit studies so longer because we're incredibly gather we treat open-label these have in found also children studies to of the doing ages that at over younger were studies. younger term. our patients to We're medicines the Phase those important roll in data we In show studies

commitment our investment to hugely so And beneficial we them be CF maintained. will believe medicines to into and these that is

as could letting state areas disease up-to-date other line. it's you a anticipate profile, when you a if smaller that beyond -- Jeff are part fibrosis, bring expense then increase The areas happy areas the just we earlier the with a more advancing these how magnitude, small is we these earlier. medicines revenue as our steady operating think compare about clinic in and operating to we're that So, in R&D we our in investment cystic we'll see expense but profile of to be referred it about in stage, disease new is disease to you a therefore, pipeline additional XXXX investment you new investments into you advancing increase to think on and the should XXXX compared relatively

are of there well. remember, do is launch the launching anticipate we're in So and there got we would I just operating these also with to costs our investments incurred to not say not been because nature the outside are yeah, being globally, And U.S., where that we like how medicines, to therefore, is of patients the the U.S. medicines disease but then last can increase. there you of as reach and significant it's thing that one

allow to more us see XXXX flow. to to expect operating generate revenue the continue which increase in will margin XXXX, the but key compared you will to expense So, growth cash be should

Geoff Meacham

Thanks, guys. Okay, that's helpful.

Operator

Thank you.

is from from Yee question Jefferies. Michael next Our

open. is line now Your

Michael J. Yee

a question. the on quarter well. Congrats great Thanks as for

just, and comment doublet broader as that? sort think question that? moving and are have SYMDEKO are to On conceptually you triples single positive Were had then line and of some expected choosing maybe forward think that are you of second How on away the guess, obviously, forward more about big time, the modeling we patients the that that you gaining finance go a of like Thanks. a once-daily, those advancing stay why some the item? move ORKAMBI you're a mutations said, feedback made is actually do triple was there population? not I first the pretty that process Can How that doubles? period is and should which forward. question you've the and you going forward clarify franchises. is drugs Over would basically about but And

Reshma Kewalramani

This is Reshma.

me the VX-XXX. part the first Let start of question with taking by regard to

and and had asked the to part know of these we've this was previous doses, you patients and that we've with study, first probably next get had Phase FDA us half our so. we're we've before our gaining I study selected and do productive the now dose-ranging on that additional across dose or proceeding where X in the at study in point the talked about this to designed As we've ranges calls, and expect discussions will agency started to VX-XXX request year, Stuart?

Stuart A. Arbuckle

the in transferred X sort true, staying would do X you be we Yeah, benefit we majority those clinical on Phase would that our combination If certainly, very vast if expectation population of homozygous the above over doublet deliver just doublets, see saw very, in know, saw results given Phase Phase Mike, that improvement saw a of X than ivacaftor. those the where, that in be and on rather triple might patients to combinations the tezacaftor in results combinations studies. the baseline increases question risk of of what do to hold we triple and significant we then and a as think a in benefit triple the we the the substantial

Michael J. Yee

have VX-XXX, fair? but broader it full certainly into plan patients in it to Okay. population is you first, gaining on And Is a to the just test to that move clarify after that?

Reshma Kewalramani

that got You right.

Michael J. Yee

much. so Thanks Okay.

Operator

you. Thank

from Karnauskas from is question Citi. next Our Robyn

is Your open. line now

Robyn Karnauskas

thanks also Hi, my taking for question congratulations. and

me VX-XXX. about let ask guess I So

you study. – I to was be like dose-ranging were that a equivalent.\ What generic be doing talked curious other this to market a challenging question a done you're on uptake doses you trying what get And may since that to has a there that superior checks about be the the told just drug mentioned you expensive, some So market, doctors have trials execute. reimbursement happen that are in we've done more some has to drug drug. give that may and if because another setting? is cheap non-addictive for Things Vicodin to suggest acute is might just your already

Jeffrey M. Leiden

for Thanks the questions. questions, both good

Let and opioid pretty pain, acute and with the post-surgical which reimbursement, correct. market acute A profile. the large essentially that to equivalent potential based sitting government far, an back of abuse hit patients, the part physicians, your epidemic you has study, to genericized know, on has and have is you're opioids cetera. to been respect the With and we're of is a for middle post-dental I'll opioids large part that have number I find actually pain, VX-XXX, side that come the to opioids. of believe me that straightforward. start one dose-ranging market efficacy with is data one maybe Obviously, as second We of think in we the the the potential so has that without medicines and objective effects et

competitive feel only is is a a You that generic did. multibillion-dollar very pricing, a opportunity just opioid VX-XXX of that's a to that you saw with the even capture we if true, very, reasonable If trial drug that it. in we portion comparative and market that

Obviously, pain, XXX of U.S. the over not million written, in them. acute of them a were know may prescriptions there is number. last lot astounding which a You truly opioid all for year, but

of So reimbursement? answer question the does in that terms

Robyn Karnauskas

helpful. that's very Yes,

Jeffrey M. Leiden

question Did it? on have terms in go -- another sorry, you Then I'm of Okay. VX-XXX ahead.

Robyn Karnauskas

go I just the ahead. about was No, dose-ranging... asking

Jeffrey M. Leiden

Yeah.

Robyn Karnauskas

easier. does acute maybe a superior sell may make is higher in which setting, profile your to the If reimbursement even range

Jeffrey M. Leiden

yeah. Yeah,

because it So that it's was time NaVX.X you the acute could a first study it work in in did inhibitor a remember, shown pain. had may acute bunionectomy, would the anybody that actually we call I study proof-of-mechanism

to we getting were we so used dose just sure to actually high reasonable that a And exposure. there make fairly up a

know what before regulators into effective frankly, things: really profile drug; also the lowest require to You effective can to lowest is want that fully of move the you because dose two, the what to Phase always give a dose-ranging you study do PK/PD dose. two understand X, is and will you one, the

we it's to would trial, where X the for pivotal and to profile a need part of then that us Phase of think that agency And lowest dose, so effective to a this as go plan just enable assuming the identify process again, successful. the with standard of PK/PD regulatory the a

Robyn Karnauskas

Right. question And on alpha second antitrypsin. or

with you flashbacks think ORKAMBI in Help do is you're You not it efficacy? more for improvement understand this (XX:XX) us efficacy but correlating the straightforward that In disease. reduction, if FEV. little bit see to an I a indication, mentioned going I a have see

Jeffrey M. Leiden

context Sure. don't maybe might you let mind. on disease, you a a It minute. me give the little me take if Sure. Yeah,

AAT is AAT, is about U.S. into case, smells XX% normal lung looks of It's remarkable in the different somewhere similar made of – the similarity. One people, many probably disorder mutation the autodigestion like XX,XXX It and just It's where against it about it how lot the in out, as travels normally blood, in this like and turns CF liver to U.S. between the secreted is outside people and protects ways. XX,XXX protein things lung more it a genetic which protein, and endogenous CF it one by the and another XXX,XXX essentially In the folding to enzymes. a caused by many, it's and affects the is, disease. XX,XXX a than is in remarkable major a

correctly disease, all protect so the blood, so up into protein significant doesn't liver, in the and it's patients. in the accumulates to the fold the in and secreted And mutant lungs two to two, lung. So to go problems. it actually disease has not obviously and it liver causes XX% the of it's unable the One,

gets suffer from the if so emphysema. that autodigested, patients early-onset means And lung

we the would that corrector and therefore could secreted AAT that's disease, liver secrete That functionally go challenge. the a CFTR very could corrector, of had more blood hard we would would small protein the treat help just challenge It's was a tell protect into would a us, for problem. and and molecule the it from liver The make lung biological is, the as that essentially the the you, it where was liver presumably disease. So, importantly, be lung. I so for the problem, the to refill in

in that of the do We've cracked secreted both a molecule think so now. made functional lung. those it's They a secreted, that protein things. problem we've small and protect I it's clearly the that could of so refold series correctors form it

disease model cell the is And has things there's into case, engineered an nice the in models. in is have a there that of in this mutation animal human cell this didn't CF or One really both animal. several been which also, which we the of

very biomarker, or and these that would we in animals, they and refold sufficient simply secreted molecules levels cells. And of to is CF the And the be which would the the in the produce that's a essentially thought at preventative nice so protein. they the we've in In AAT other AAT animals, do They thing the is is levels serum. It's then in do. cells both circulating able to similar disease. what be been the this secreted they the from curative test to

levels just the experiments function human You treat we of and have know you the in you level and the the AAT serum, certain if of from several nature can don't AAT serum. patients measure in for both a the disease. weeks essentially And get of that

so shooting measure for it we're we here can what easily. know we exactly very And and

the exactly normal numbers this plan of and healthies short once with where this molecules, are. you you you into And like we they relatively a first if we small understand by of CFTR patients the know again, treated the whole take PK, (XX:XX) tolerable, that and is more safe take year, them the periods correctors. the measure serum of And patients. for them And in relatively AAT of are and these into time, so the did simply series of just we have end

Robyn Karnauskas

a That's thanks right, All lot. helpful.

Ian F. Smith

Robyn. Thanks,

Operator

you. Thank

Geoffrey question Leerink. is next Our from from Porges

Your line open. now is

Geoffrey C. Porges

much. Thank taking questions. I you appreciate the very

Stuart, mentioned you all a sense het/mins, absolute give mid-teens wondering, FXXXdel we U.S. your are so relative being you Could us then chloride just of First, these And eligible and us coming appraise in along? competitors a to the homozygous ORKAMBI. Jeff, the in SYMDEKO FEVX know how sweat hurdle the if between you the you and where what could sense of is, bar for for penetration and improvement give for triples now the competition.

few that yet, with caught you had patients in a started below never you've or the in are quite And substantially up still who discontinuations on have achieved mentioned patients you sector? ORKAMBI. KALYDECO all population you penetration You've those the eligible

Jeffrey M. Leiden

answer answer and Geoff, will the first part, Stuart of thanks. then, part. the second I'll course,

I misimpression maybe wrong don't or the a for On the want very bar, I said have what for said but want first thing, be just I is been mid-teens I I of to to correct may think instance, part, patients. what do clear. the het/min

homozygous het/mins. additional we've data, you the around the think between in which an that is for I from Phase as to X.X% (XX:XX) set, for our who believe doubles effect from how already an was have X improvement, and XX.X% know that get I XX% somewhere And or bar we data is that X%, X.X% showed mid-teens. patients we

are XX there that numbers. triple. sweat say that's reach With get just that I chloride, probably be to to But successful. I'm levels, to that the XX, XX% is with you I I you're think these need goal know when which is a want to that sweat our you approaches approximate goal, think So to be let's respect suggesting clear bar het/mins the for not carrier chloride you

at are And be going pretty we In day, the well. not cases, the all the think the end in at. as so but they is you know, correlate I FEVX. of numbers the two regulatory look to And those most endpoint cases

Geoffrey C. Porges

thanks. Great,

Stuart A. Arbuckle

Geoff, it's Stuart here.

to good in a population in on two and ORKAMBI uptake modulator, switch commenting who things suggested, well. so CFTR that the ability a patients One we've who were ORKAMBI, in also us, those who and one seen and to we've as exposed naïve, from you for We've SYMDEKO. because seen the U.S., patient was the get the was those patients respiratory discontinued number had not also had to population. that completely of populations. important treated second being SYMDEKO uptake often for really is SYMDEKO of Just of And been the the were launch ORKAMBI ORKAMBI, that population most onto events, never as by seen adverse was good

strong patient seen we've seen those populations. we've all good uptake certainly not the uptake, So certainly done launch We're done. whilst We're not in Geoff. with

uptake We on flattened the we haven't to have with has some SYMDEKO ways gone in U.S. far. certainly we're pleased but so launch how go, yet the still out so

Geoffrey C. Porges

much. very thanks Okay,

Jeffrey M. Leiden

be about of weeks the the other these safety is the I as long-term to add thing that's one an triples, of you just progress. Geoff, are And, at we'll to two efficacy of equation and one I safety, side that tolerability and tolerability maybe know but aware we these as talked that and is side week not think or thing going well so look important and all trials clearly,

Geoffrey C. Porges

Great, thanks.

Operator

Thank you.

Flynn Terence Goldman Sachs. from is question next Our from

line now open. Your is

Terence Flynn

thinking some just curious triple just with the the love have on for to guys thanks you Hi, the update different us the capital That just inputs balance you give year. taking you to billion maybe you're all Was sheet? had but might could you in an thoughts made first, at not then comments yet continues about ever of so that can this And the question. be about on as your combo, on this remarks you just I wondering, Congrats might next most Jeff, on with your just respect point, to grow $X progress. you. pricing? but on Thank have comment know, here. thinking way you're that opening here allocation how the respect into

Stuart A. Arbuckle

always Terence, patients. and label Stuart It taking that that we're into account and of leads that magnitude deliver triples, specific the to same the for able benefit On into that for will patient much the what's clinical obviously, early be make be approved comments, we we that the but get pricing be do will the population. obviously eligible here. for the factors to too any we'll

going months. to into information get that the inputs we really be on those take more coming obviously, the are we'll those in So consideration and

Ian F. Smith

main It you is interesting change And after the of long years. three as to concerned, really in we source allocation. capital that last far like about it's I'd saying an company. We're allocate and cystic that inside medicines, to line is because creator capital we allocation and thought philosophical revenue that, about by company were can for in interesting. expense preservation about But then main start about allocation, been that and of of is not that revenue accumulator cash cystic starting capital line I still operating That's now invested are as and cash that. has as tell being the a is capital it's the happy for our mainly diseases period time fibrosis the a internally. you it's also to allocate in the but of on terms we're source allocate internal towards the and capital capital but until fibrosis company And asked on of we often we're programs. amount beyond questions significant capital really allocate then we hear, our earlier, now, the can and the

very in-licensed to others and sickle to a be medicines and that for early be opportunities follow. those is will area we the that something And now are priority, into that us a time, clinic next was and very that go stage with very but research medicine. we company the our with cell Therapeutics allowed clinic both collaborations it medicines, shortly of are do period into there couple years collaboration from we're important and thalassemia what we have -- short beyond the have developments really with beta the of of a beta ago of FSGS, a a excited medicines example, can of thalassemia. in for also and providing anticipate which a outside going order we a fibrosis reignite sickle and towards very The these that capital Some to allocating to cell the CRISPR cystic a to is is nice opportunities we're really towards product successful, effort opportunity in some very accelerate into been

us the with say would in. do But a high it's for consideration there for diseases also -- a count. would modalities company allocate also of outside medicines how we capital to order give that be increase limit opportunity priority is interested that I So more the us we for share more may collaborations to to and our

exercise count and stock. share options year of does the shares, increase – by Our year based outstanding restricted issuance and on

dilution. year think And this been of that so and in that we this throughout program We back have earlier million we therefore a creep limit outstanding we we entered that well the doing that with the in to shares we've amount share that's small us year in announce may creep throughout a shares has buyback on been which and the us like and for buying been and this did as helps very limited shares, successful ways obviously $XXX year. outstanding

we capital how have so us, It's think in and prioritize And that's that this allocation. to we're happy very we about way. important, opportunity it very the close to

Terence Flynn

Great. Thank you.

Operator

you. Thank

from is question Young Fitzgerald. next Our Alethia Cantor from

Your line is now open.

Eliana Merle

the Hey, guys. Alethia. This for taking is Thanks for question. Ellie on

with you've the earlier income recently status R&D Genomics. Just on deal a did side, on the

having of efforts? talk So little particular a more of bit R&D will how and sort your this about sort enhance you discovery this engine could

Jeffrey M. Leiden

were collaboration. Yeah. that about We Thanks the quite for excited actually question.

allow were which genetics, loss the is that validated you gain a a collaboration CFTR, small Genomics, role-specific a begin targets tell on molecules. actually you is two lot ask of of That's in know, questions, us human target are from by function, targets. the very the of this any world work hand for the of hitting is kind will because high to is one the NaVX.X develop we to the far A effects. we working believe highly about also, potential to normal really, the medicines. company targets. side they the thing as analysis mutation and for which about function suffer mean, genetics, large to of human important who a targets. call and on not NaVX.X, One genetics for et mechanism-based throughput from really ask allow validate a databases. us effort or minority, the the the it second those target, people mutations until There's function can know way, As of of human scale our human leading on will loss with validated beautiful we is screen example, effects you genetic of obviously, The through principles side specific new small human cetera. and screen research what one will pharmacologically targets major or But I example and instance, either data to ways where population is a we by for that pick That's of

to of human help safety and pick of number in collaboration diseases. as and nice for a it into data different is resource both So tapping a a screen way very think that targets genetic about off start help the that

Eliana Merle

with just CF, preclinical models. development. you, guys just terms preclinical very another how AAT of models best But these in Got thoughts us Thanks thoughts the your sort you you And could and more then a one these of model bit preclinical little about on predictive you optimizing I tell successful bit a thanks. mean, on obviously, models about early AAT? be? phase might what talk are for of little think the for you on your Can part also

Jeffrey M. Leiden

gene protein There's secreted way mutation. the to do is a derived either kinds molecules cells, is in those AAT generally of test One by those function, question. not in is two and they or are help can the the cetera. from engineered cells misfolded, in us. mutation as on secreted cells it's so which protein the which major And mutant for not as derived cell-based necessarily that These human of it's them et made, the one refold used. to models proprietary are the from Thanks with patients set models

transgenic mutant reach, those accumulates secreted that in protein's what dose is the The human those mice et if a can as or do is ask not levels It of medicine is which the is with the one well. other secreted and protein. you Again there model function cetera. one actually expresses protein and mice then liver a

because will very So predictive nice human models study the which highly they two we not be do mouse actually actually feel some to mutation mutation.

Eliana Merle

much. very That's Thanks helpful. you. Got

Operator

you. Thank

Bank of Lynch. question Our is Merrill next Ying from from America Huang

is line open. now Your

Ying Huang

my taking for question. Thanks Hi.

competition, about Proteostasis. the from if a or of work Can the any for given data I have in some have penetration any maybe again, we in on, full not? done when where lab First maybe then on you was reaching market guys by tell the the Stu. second us amplifier? see seen wondering, you And Do U.S. SYMDEKO role one have market much might you're today? seeing you you pretty that view

Jeffrey M. Leiden

I'll Jeff. other first comment don't specific This molecules. one take the is terms in of on people's the Again, really we amplifier.

is One I other about of think protein the potency and why and been things that don't our think one to as other are will, they're our we specific so look if look selective, issue I one of molecules, at we at. hit for tolerated look know you like triple that quite they you reasons proteins, of they're and correctors they've the – the reasons important a specificity so of quite as is the thing very – at CFTR we that which

Stuart A. Arbuckle

very in by in how well be going uptaking, SYMKEVI how SYMDEKO but rest the our of when terms to including gone with the our full to we're is can do, all in XXXX assured hard Europe approval reach expectations U.S. to is then of the SYMDEKO get we'll to and we in obviously, it's XXXX where giving Predicting of also guidance. perform guidance, in and have we'll then that penetration exactly And that it's then hopefully point that as we'll pleased incorporate date. going you the

Ying Huang

you. Thank

Operator

you. Thank

Abrahams Our Capital next from Brian question RBC from Markets. is

is open. line now Your

Brian Abrahams

to my weren't I Hi, cough as on how further saw give data the might potency there VX-XXX? combo. longer of bioavailability duration, Phase on can quality, should specifics assume NACF And and able X And this the pursued? the we and we us on ways all ORKAMBI? And might about upon there. Thanks more I mucus data. triple bronchoconstrictions. should it program, some details are as be on very a taking the Thanks. much and pain compare you initial VX-XXX improve just think congrats questions. no you then for for the being any related the more if these classified if Wondering severity, obviously, us, progress. wondering we of was really and to know In rate follow-up remind the clearance is interesting to

Jeffrey M. Leiden

Yeah. take both of real Maybe those I'll quickly.

the if not We are anything me saw you're but specifically as to I triple, cough answer seeing we is no. with we is question terms correct that at think the else. get trying measured the I'm only wrong in with ORKAMBI, bronchoconstriction or actually of

we're question? to point, drugs. triple see quite not we excepted, just important profile and do see and clean. the remember. hundred seeing So is the want now asking. a as you're tolerability earlier question couple make they're that safe Does looking like bronchoconstriction answer in patients. a with with very you But lot far. they very of just been Brian, we ORKAMBI look sure that it your and so they've the is They was well-tolerated don't the bronchoconstriction I What have at the tez/iva, total the I did think and not these more safety drugs

Brian Abrahams

just wanted that, very That's yeah. I contextualize helpful. to

Jeffrey M. Leiden

other the then was VX-XXX And VX-XXX? Yes. question and about

Brian Abrahams

Yes.

Jeffrey M. Leiden

we're actually osteoarthritis, that we're in one, molecules, approach but PK than a if take molecules the that and that So respect it's shots, VX-XXX. the and were of molecules that AAT also step not We most respect at the portfolio We improvement more potency forward kind was X is pain, like rifle in pain to we'll we VX-XXX multiple these We with pain, things create acute next efficacy, profile maybe discontinued least drug-drug to taken VX-XXX Obviously, to approach molecule, on profiles with have know both and well-tolerated. pain, development VX-XXX. neuropathic development readout have you remind like into taking you understand just unlike not et over VX-XXX we've single take didn't know again, a will, PK early different back approach doses, in and but data the to get let higher the to those it the volunteers it and hoping clinical some of follow-on Phase things biodistribution, tolerability has then third we their interactions, me different because fully. early-stage healthy have a taking with not on. properties, that a and year. of that CF cetera, in properties see at in in

additional trying optimize you're create going efficacious don't pain, Remember, molecules. inhibitors that, multiple early into same way We X.X molecules inhibitors development, in have We us want these behind highly have to need other to coming so highly and should the liabilities highly tolerable. to and clinical molecules opioids. you also bring like to that expect safe acute see and that are

Brian Abrahams

so much, Jeff. That's helpful. really Thanks

Michael Partridge

we have two Operator, for time more questions.

Operator

you. Thank

question is Our Matteis from Stifel. from Paul next

now line Your is open.

Benjamin Burnett

I guess Thank scenario scenarios what the in then program? have hurdle that high you different of And a might program? would second study Paul. for I wanted What in Hey, for question what this this question the to acute pain, know is efficacy these pain. as ask VX-XXX. to Xb I level, to where indications, specifically And little a this be I bit more guess are osteoarthritis-related some advance pivotal at under just wonder vision you the looking guess I well another about data there is there. want could thank Burnett you. you that involved you the for on ultimate what neuropathy you Ben across is commercialize and a is more need pain is if the color ongoing a acute, as I much. And so This yourself? Phase aspect provide on partner it? you

Jeffrey M. Leiden

and a the this some just to think part said maybe a Maybe you I'm about not will about we'll you part, it's strategic. because from first, first pain some then thank context. which context I is trial. actually but give take little one Phase I'll but VX-XXX multiple as Reshma a second give the disease from diseases. actually Xb you. the take We both standpoint more sorry, scientific and as Ben, commercial before standpoint

acute divide to injury. That's have dental or pain segment. of for kind way it, when That's acute you easy pain pain. an instance, postsurgical one an is So the

but chronic commercial third have is different obviously, inflammatory osteoarthritis, they things They A have neuropathy. lower segment pain. pain, neuropathic pain segment That's also second The channels potentially like back pain. different is diabetic like pain mechanisms.

separately and work three. will And and one drugs will drugs so them some because important in some work it's to drugs two, might in frankly, some all study work in

using see approach trials the done using model. that's inflammatory as far, portfolio. to chronic waiting pain, as we've what done So is in using pain and osteoarthritis, from in still fiber we're high the in trials trials that We've so neuropathic know, we've taken acute bunionectomy separate seen year. data as remind We've pain a third a is separate the our model. as doing next in the with chronic neuropathy trial, of high efficacy And pain, you of which the osteoarthritis pain we're of just a level due neuropathic model, to efficacy in small you, set early acute OA the and level

things standpoint. from scientific a stand where sort that's of So

if is back, medicines. class also, the have a there And which is Tylenol, effects class need a which and over large hand, we really that been opioids their one that way, Now new have pain own on reason for of take hasn't have but and then effects, the for drugs I a are remember step new There of efficacy very a years. addictive the XX trivial. which lower side NSAIDs, Aspirin, burdened of other some efficacy not like have we all with and high by are have the and again, side

the And the find of can liabilities of new target addictive pain opioid-like a for is mechanism so opioids. efficacy without liabilities, really other approaches and we that us

asset pain, market one that a opportunity. can that develop of what yes, first VX-XXX And sales in based target. those channels pain the all somewhere in would and like it necessarily, country, be valuable develop X XXX looks reps rather or we data, disease. least this of OA far, Phase then quality is would large so may sales And part multibillion-dollar like on we many at we're two not it science that like really can land is say, deciding and that have by but respect acute partner. is development a primary in force. Nevertheless, That's do to And to force Does And about pain specialty see as force. we the we a give the final with, it? a to would of addressed probably sales depends commercialization. question terms we're the in would the waiting in specialty we the lay many, It be what disease said, of That I us partner. part commercialize out pain, of seeing our forward, we Phase going pain it That's year seen how And think does not look we're in medicine with such primary we're specialty force, such a on thinking further mostly certainly pain if lower that about so data of and something be that. that's acute commercializing that. it's of both not the what commercialize care sales specialist. done you a hits back indications, X the is covered take the by the first the is requires trials a meaning own and NaVX.X third that to a Contrast a a see. very care between. in your for turns ourselves. community of to And neuropathic then It XXX lies molecule, clearly while a by with

Benjamin Burnett

I makes Absolutely appreciate sense. it.

Jeffrey M. Leiden

Okay, Reshma?

Reshma Kewalramani

a VX-XXX in doses model. fairly pain to a range. we And that is to going initiating dose This full bunionectomy in to is exposure Phase Phase get With study X shortly, regards going dose-ranging going to study that This be we X it's standard acute to be several it's the be are study. Reshma. essence,

effect, that's to testing study. high-dose model. The see the a one. for we bunionectomy what to we bunionectomy and is is be the that study bunionectomy effective year were now dose the going And that exposure SPIDXX. in positive to from explore a full the in lowest endpoint we're saw range endpoint really regard need effect the remember treatment And in to with with You'll the the we SPIDXX, dose is pretty very what proof-of-mechanism had going and was pleased the to early the treatment we be results really studying here. study because that This were standard

Benjamin Burnett

Got it.

much. you thank Okay, very

Operator

Thank you.

is question Cory next Our JPMorgan. from from Kasimov

Your now line is open.

Cory W. Kasimov

Hey, question you're terms thanks for And have. be CTXXXX mentioned second to for you sickle with might there's is hold you that's coming listed or my initial into How partners? potentially your in before And further they much data how then be these if you the to update? being from trials clinical your the clinic as in you'll about in cell remarks, months. provide an do could Two In not will of next-gen something me me moving ideally already accumulate some regard begin. correctors comfortable in. additional you enhanced in differentiated your slated to well. wondering what prepared the responsibility any this have providing want for squeezing I'm information

Jeffrey M. Leiden

say I Jeff. to I'll we're of question. in for this With is I two here the next-gen two Cory, is correctors, talk one will take respect looking been last about next-gen the what the enhanced see disclosure part would we've Maybe and able that Ian and part think we've through chart you potency gone of it's the things. we've showed really as the One, before improve efficacy to remarkable correctors. years, to four how these

VX-XX levels, but VX-XXX, and not molecules patients all we're to current the close to getting there. With carrier quite

well patients, goal of particularly, chloride because carrier meaning as as you in the there, the would be find in severity or het/mins patients, levels homozygous young disease. prevent lessen can we greatly, could so all corrector particular, if greatly And the believe you'll to that either a the next-gen transport patients, of get get

The medicine the goal chemotypes continue have any like that we're diversify chemotypes. to multiple program We other making. that to of is of to always

been well. we've we're working so explore And and those alternative as on able to chemotypes

both. entry to the molecules clinic. So, you those We have already to that are examples expect two see kinds can of of

of that next-gen as well. next see those, the I early clinic the first correctors? more question expect so ones into Does probably some along and going enhanced do your goes year you can And answer the as the year about

Cory W. Kasimov

perfect. Yes,

Jeffrey M. Leiden

Okay.

Ian F. Smith

be a disclosure patient year, recruitment. of And on we'll just your a we so data and therapy question, the of the from I for let's we'd studies we've the provide patients patients have of dosing being would next procedure year. started a to on the certain with disclosure We'd once think kind number update next of the well, anticipate then later we anticipate have probably Cory, and of that duration study these time. studies the an of study, – of in next both towards on year. recruiting multiple patients are early around would where this And, disclosure first in end timed or, be had probably you say, But

Cory W. Kasimov

taking for Okay, Thanks great. the questions.

Operator

Thank you.

Michael Partridge

have Investor good the follow-up team Relations the call much for Thank evening. a Well, joining that any further office very to The is and answer questions. will you conclude call. in the tonight

Operator

today's program. concludes your Ladies This participation thank gentlemen, for and in you conference. the

disconnect. You may now

Vertex Pharmaceuticals (VRTX) 24 Oct 182018 Q3 Earnings call transcript