MyoKardia (MYOK) 27 Feb 202019 Q4 Earnings call transcript

Ladies and gentlemen thank you for standing by and welcome to the MyoKardia Fourth Quarter and Full-Year 2019 Financial Results Conference Call. [Operator Instructions]

I would now like to hand the conference over to your speaker today Michelle Corral. Please go ahead ma'am.

Thank you, Josh. you us thank today's and afternoon for on joining call. Good of Corral, and MyoKardia’s Michelle Corporate Executive I'm Director Communications Investor Relations. Today, and year-end well reviewing fourth for portfolio. across be progress as milestones recent as we XXXX, discussing upcoming our financial will results and quarter

A MyoKardia's results issued Development; CEO, by Tassos joined afternoon the Tassos earlier website. Leading Dr. financial on Chief Commercial Harris, our Taylor Financial today our Fairey, Clinical is Gianakakos. Bill available our detailing SVP Jay today’s press this release and was and call of Chief Edelberg is is Officer; our Officer.

prepared the lines their for we Following will remarks, Q&A. open

As the undertake to events update a law. will represent company's call view statements this or revise as by no obligation any February discussed reflect future reminder, We or the forward-looking new of information during XXXX. except which include forward-looking to required statements, today as information XX,

as information could with today's statements. filings well by press our refer these results actual expressed cause risk Please concerning from or to differ implied release, to those as materially for factors SEC the that

to like hand I'd our over the CEO. Tassos? to now call

for Michelle. afternoon today. Thanks Good us joining thanks and

pivotal company application us few Our a away which new months enable just expect we with will to from first is MyoKardia’s FDA. file data, drug the

a HFpEF, of of to help forms people potentially and of the breadth HCM, pipeline, candidates includes HCM, heart of DCM, really specific systolic coming year We’re highlighted other our with that now our science failure. which and genetic non-obstructive forms obstructive

many in disease management and see changing from people in medicine ways enabling we heart of lives failure, cures in areas. precision for we’ve worldwide broadly the millions Assuming era vascular MyoKardia the precision witnessed assuring of suffering continued other disease of their functional cardio success,

medicine that platform keep what can achieve. precision lay While the we’re mind significant the just of excited and in our in ahead, beginning translational strategy it’s about milestones many XXXX incredibly research

multiple programs, our our of year stage broad in resulted will this all and since two both X more grown additional approach see scientists. This which see continue discovered pre-clinical approach years evidence more to home clinical danicamtiv. and value by continue mavacamten supporting the and to company’s programs, you programs, three throughout We action has research and the formation, with the MyoKardia in

and and HCM trial be term of data. next release to in HCM, The of of the Results the have presentation near move to accepted points most proof conducted data at mavacamten series College enable Cardiology breaker forward been and Chicago us American in comprehensive mavacamten a largest study. completed ground the the in breaking in main for those March. non-obstructive this study non-obstructive purpose MAVERICK The date late for would of the was which

with to people certain confidence the the mavacamten’s our of MAVERICK to And hypothesis heart MAVERICK Phase about validated addition, potential trial benefit EXPLORER failure. In types obstructive HCM. increased not in our and X overlooked, diastolic be trial further

believe that we we Between In where difference and a sharing results make then, to be no we often opportunity diastolic now therapies discussing be great the the will to line and people feel yet see quarter, of our be why top developed. HFpEF as from which EXPLORER, millions about. tackling the to we failure effecting we’ll in syndrome meaningful to referred have this approach heart second

present patients. XX% of formerly genetically all program known cardiomyopathy. with XX% defined people in study dilated to of danicamtiv the study MYK-XXX. our about present genetic in contributing data X our decision Phase abnormalities encouraging been has from data These are so estimated a The to DCM disease danicamtiv, initiate to to Around mid-year, from really Phase supporting as we X our plan far to

danicamtiv’s have the of can in the insights provide at of patients. both this our gain population, on been a including robust patient as As path DCM us the well targeted programs, study has to signal from an designed efficient foundation as impact laying broader all with diastolic mechanism systolic subset this in improving for development mavacamten, tracking without with a function

focusing with for key mavacamten EXPLORER HCM. of Today, the we’ll study upcoming Jay on me be review to here and is readout. of aspects some the

will We’re gaps also of our learning and also share who our development in efforts. market Bill landscape joined you Fairey, the HCM Officer the by Chief current some of the with about we’re will burden treatment Commercial what and discuss

milestones the Taylor with will of come. call our position recap anticipated Jay? round XXXX to a summary Finally, important of out financial will many the and

obstructive to Thank composite the Good of XX the sites functional powering Phase is namely with EXPLORER HCM. comprehensive on X dosing point. obstructive randomized and study, patients symptomatic trial EXPLORER of I’ll conducted several than safety, touch Today, assumptions enrolling largest and end XX everyone. afternoon clinical XXX more Tassos. you, countries the cardiomyopathy key today most with aspects hypertrophic and across

OLE, the When PIONEER learned how in then namely obstructive clinical Let’s based ventricular left we reduce we’ve From mavacamten anti tract remains left pressures, we dosing. a filling outflow dose start gradient. individualized ejection in and volume. mavacamten ventricular and of gradient, HCM response, with improvement BMP, LVOT atrial on in observed to while fraction to All pro dosed including normal range. multiple left parameters, reduction

further in increasing if dose increased of points gradually two In would mavacamten can and mavacamten X and obstruction used be at Starting the milligrams practice. is needed. be start how we on low patients low expect in EXPLORER, reduce clinical to time a of LVOT

Turning powering. endpoint in the selection to

greater measures is of increase VOX. VOX minute more NYHA and Our composite NYHA designed one improvements improvement increase by NYHA or and an in and an defined worsening VOX in peak functional cardiac of X.X than kilogram more capture no endpoint milliliters an class in using of endpoint functional or achieving is peak more to composite or or per per The either symptoms and three class. of function in classification peak

XX% the than detect and to powered, XX point greater active between EXPLORER is For this delta endpoint, placebo.

our notably the treatment derived placebo Gilead rate XX% We of based other XX% the response LIBERTY function, assumptions and Study. studies measures on assumptions looking incorporated powering Our of that symptoms after for at are response rate. a

In addition, applying estimates XX%, I EXPLORER. with our when the endpoint below adding designed for say well the composite to in response XX% can the response EXPLORER to observed was was up anticipated functional without in that specifics. assumption in for our placebo are that range. MAVERICK we confidence sharing discontinuation, placebo

the the explore will our the majority staying great with Patients study. extension in long-term joining study

with our surpassed and of quarterly the we enrolment our review. adding further basis, the power on trial. light EXPLORER the received store XXX addition, a In has have met outage Through to target [IDMC] each green

at measures the beyond endpoint. functional efficacy we will look several composite EXPLORER, key In

expect a We reduction to gradient. see in

We case hope is base reduction versus really see Our the good of in feel significance placebo. to gradient in achieve the impact meaningful of a clinical to majority patients. We statistical about mavacamten.

lead We of reductions PIONEER From NYHA know LVOT resulted XX% in PIONEER single NYHA our open arm and PIONEER-OLE treatment obstruction mavacamten to is to studies In improving one improvements this patients symptoms. the in and classification setting. studies, with to label XX% class we see improve in in want class. of by market myectomy double-blind placebo-controlled changes

treatment trial, EXPLORER will class NYHA in the In on majority we in patients of in placebo-controlled an be improvement meaningful. believe

in exercise placebo. is cardiac a improvements function. look Finally, the versus most which function in of treatment we Cardiopulmonary peak rigorous will for the we’ll at look measure hearts testing peak measure with VOX by we standard VOX, and improvements can

other these As that observed the the we parameters in improved of drug that three in are readout as these along our All safety areas EXPLORER, of improvements be patients results and critical now dose of heart. adjustment the we’ve today, we we EXPLORER through period. are believe the all biomarkers will mavacamten several studies with as encouraged most well highly

data QX. stretch, report top we track line the in in on So, home to remain

functional line of top through gathered peak and classification, endpoint data and on the based data the gradient, we tolerability. safety reporting well be At primary readout will Our and readout, endpoints secondary as VOX, as XX. anticipate week NYHA top LVOT the line on composite

our with for subtle increase Supplement we’re in anticipated submission, being study the patients that database. our trial, be safety in mavacamten EXPLORER HCM MAVA-LTE long-term our known program will all was starting from our of QX which world extension our therapy. reduction registration evaluated study our dated filings key study be is is including as to the studies comprehensive will valor part in the

the with alternative an in provide clinic many invasive to for they the to Bill Commercial surgical treatment Bill? mavacamten partnered if other patients. Cleveland Officer. We’ve see I top-notch to line these Fairey, centers now Chief procedures turn to our over to like

Thanks Jay.

something Jay on moment just saying. a was for up pick to Just

What we’ve need about our of trial attributes number the of things set is is easier evidence my design the them. one up that product the provide launch, that but addresses mavacamten for program our know, we that bit that met a most. successful the job cardiologist a to You is we EXPLORER asked learned makes a

is improvement of also earliest, product or For highly is in example, of top NYHA an gradient are VOX the capacity increase ventricular tract benefit peak and just symptoms measured class [indiscernible] improvement reduction exercise and at our of left in by outflow the attributes. behind mortality

now, where good should quite dataset feel sitting So, right we we the EXPLORER deliver. are about

to I might therapy this clearly additional also being add of for by another is disease. serious should reduced will subtle need evaluate evidence cardiologists. That mavacamten study, SRT. the provide as an of that aspect avoidance reduction mavacamten address which the can that alternative our VALOR And valued

EXPLORER, towards ongoing there’s ahead, market. been look tremendous will be what anticipate understand for a we amount of develop positive to that’s readout a and As the HCM work we

of this need medical currently category that therapeutic long for the time, for limitations an the for underserved determined that an commercial HCM. and for current options. a due is for are The teams market What of express are groundwork eventual is obstructive mavacamten that there affairs success to therapies and we’ve a we disease introduction been laying is and planning has targeted

very We’re experience disease significant team rare specialty capable building areas. a and in with

evidence on help commercial we've board field so real And economics. market marketing, of medical, advocacy, brought world operations, heads and far access,

aspect of on profound HCM understand understand we lives. one the HCM work to has been better the of more talked we our representatives Community, the as patients And of and the patients Now, on burden families. disease their has the impact better

HCM's worldwide by for is in epidemiology and chronic HCM? while study typically patients estimates sight reliable people typical with most and one for we a what know are HCM. life the prevalence, XXX inherent there progressive affected Well, are So, every like various it’s condition

diagnosed XXX,XXX U.S., of pain about symptoms and of the XX% and form exercise here non-obstructive. the have all tolerance And that shortness two of is condition. of palpations, XXX,XXX our chest remaining breath, thirds in of patients the think are [overall Today which to preference]. the and disease, roughly third while we are XX% [destructive] one treated Fatigue, these

symptoms as asthma. be such these The owners other with be settled confused can answer and can

identified be as HCM multiple diagnosed, the the years mutations As patients to course a a quite can be from to with condition. under the correctly And consequence, having may take their highly presents known is different disease among fact can it be HCM of underlying for even varied. patient way person the person, in

We've families a at another life; sibling until may young who and won’t dozens family. met into patients members sudden develop and still from transplant of a pathogenic share very the mutation arrest same need the with tragically symptoms yet heart all same die will late the once sibling in cardiac age another where of XXs any

have similar cannot that very disease condition. are is while a population sudden associated three be compared walk death rare, us a they relatively mortality where patients to at U.S. the And significant. have real block without the a with days HCM can general many The of risk rate that time patients city there burden down The cardiac when told higher resting. ages.

One they to weren't patient longer. even beach any at that trying walk said

sing. list on patient chest. they daily Some of it scale her now sitting subway they are and goes They because of so shortness to forced on. basic severe back stairs is one activities days, that the the no disease. that avoid can longer living of is an her say They accommodate the elephant breath to like lamented And their

they cautious practice. not that are This it’s slow they gradual are the even is measures of Sometimes common taking. that

therapies are current help not So, will sick. these we adequate very some for sick, for And that patients many. are some, know

patient shift of some under know diagnosed share the the patients. Now, and are treating who’s of vast population that gears we cardiologist. to the care about majority these We the like believe I’d what of

and by of community we managed centers managed XX% probably in centers here analysis roughly and is U.S. patients XX% data total. failure cardiologists suggest are are these or Our that of of approximately XX HCM heart there by those around designated claims think in

seen cardiologists, way and are another by at The we patients approximately that XX,XXX an way, the believe XX% look XX% these this X,XXX we are by of diagnosed seen of patients cardiologists.

launch. position address. a is my a by like more preparing relatively for remarks for conclude how to to this universe we’re concentrated on bit sharing So, manageable us I’d

Our liaisons with the medical clinical scientists relationships meaningful and cardiology are field base establishing community.

conversations mechanism some of around new patients options it drive for required by disease. of in Herein, the treatment of the and face should the today. compromises pathogenesis The need underlying the HCM inaccessible

is wider and Over the the patients continue population goal our elevate a to reach coming and months, conversations these our across include payers. community to HCPs broaden of to

Additionally, our have enhanced education awareness in AHA a debuted spring. physicians HCM we the We disease last for releasing company November at this efforts. disease we’re campaign online and exposed resource in

evaluation studies of National also real world and worth series history, mentioning is It of as associated kicked clinical factors, a the evidence our had and risk off economic of values. associated HCM that illness, as team examining well burden

large engage of professional HCM. organization about very real a life in with community dialogue custom create to to impactful with the initiatives burden further We’re the partnering

of awareness initiatives HCM Recently, to community SHaRe development misconceptions one HCM clarify campaign, the our partnership some [HCM Care to as App] other we cardiologist complement contribution with partnership families. three-year design a and and long-standing such of their about kicked more [indiscernible]. AHA the Registry, four with These the patients new our the and and heightened

lead Our mavacamten on of to to the and and our commercialization education, what providing to forward potential the throughout is I to and HCM we're updates our the to a around we’re in engagement drive anticipated HCM up commitment awareness, up and launch. how market to launch. look continue developing periodically approach learning

to now to Taylor? us to through over the it going quarter's walk I'd like who’s hand results. Taylor,

was six in a our for activities. development preparatory Bill. growth XXXX MyoKardia clinical progress our to support Thanks, year as tremendous significant of well with these ongoing trials infrastructure pre-commercial programs, and as

were excluding R&D expenses million. royalty full-year the compared of on for That’s rights total XXXX $XXX $XXX XXX that, totaled XXXX. million repurchase in $XX and basis, Sanofi million expenses in XXXX to So, G&A was expense a operating million $XX from Of million.

advancement uptick and reflected the R&D increased MYK-XXX well The XXXX of expenses as in programs, in increase mavacamten, to an preclinical personnel our danicamtiv, related are related costs. as spending and

December and million investments. we have cash of [technical difficulty] XXXX $XXX in XX, As

the on for is projection So, registration next mavacamten to to top programs aggressively our this HCM all we of our planned encouraging XXXX enter to diseases dysfunction, fully well IND of execute mavacamten Included part a activities and in development, data to the filing. at franchise expected more assuming line and of in ability for the funded emerging danicamtiv diastolic of bring one XXXX obstructive as data past our middle and the to than advance program plans advance least readout of stages as MYK-XXX preclinical EXPLORER. to full an operational our to runway in year the

at will forward a in In be of genetic non-obstructive EXPLORER HCM, a in first readout HCM, presented to the Xa in regulatory progress ACC, HCM settle of danicamtiv alternative our mavacamten and just a reduction of operational in for we of to study can number mavacamten of Phase expect study in reflecting the line therapy, XXXX, the DCM. of mavacamten MAVERICK update as study have a In objectives. looking targeted obstructive milestones half go population mavacamten X initiation plans a the the Phase for presentation initiation against you year, initiation full HFpEF of at data data our and VALOR than the for proof-of-concept top an

study MYK-XXX data at presentation our the and results. full X X we and infrastructure, hard of our filing, should campaign, pipeline. anticipated our of commercial and of Phase the building momentum ESC the awareness opportunities, at work MYK-XXX disease our Phase initiation the half year of X into line EXPLORER the both including AHA Phase on background our for be will study exploring NDA world research data of moving Our commercialization the advancing from Top second rest continue advancing the U.S. our with the

to our MyoKardia. multiple line broadening launch, time Putting for together, at commercial this year we medicine transformational into while XXXX same pipeline a with on expect first arenas, taken precision all our be exciting track for in the approach. So, us our

would questions. I your up call now to that, With the open like to

As and with Jay are reminder, Edelberg, Bill a her me and Dr, Fairey. Tassos

question from Instructions] [Operator you. Rama Morgan. Thank JP Our comes Anupam first with

your may question. with proceed You

Thanks drug data? of to much both mavacamten get concentrations to HCM and so Hi, efficacy you be we guys. sort side might on On so from able the much. detail of what inside the for MAVERICK on that wondering month, taking level next question. that getting of ACC going Thank type potentially safety later then of be we’re

that presenting to in efficacy primarily So, safety, details and will biomarkers nHCM and well forward as be have that response diastolic we the to that data. we're we've the the path subgroup be on us provide dysfunction found the the we correlations our believe going analysis give greatest the could the in both the think comprehensive reason clinical at there giving The treat. that population, subpopulation the looking in to as also

for thanks taking Okay question. my

Anupam. Thanks

Thank you.

comes Bank question of Tazeen Ahmad next with America. from Our

You with question. proceed may your

clarity Hi, said my a to and the have good of to now Thanks you to being so afternoon report completed all it that part guys. for clean would provide prepared just Maybe take the refer locked line? data can your in, on statement, patients to periods adjustment how little dose up you that bit question. long more taking then top

Taylor. is This Tazeen. Hi,

be. track are we expected to right So, where on we

you the think and that’s in just the we us the to creates what know second up for weeks process, quarter. range XX that lands expecting data cleaning take We’re that could

that not nature going we're of to process. because the totally We’re with more but pinpoint than the that comfortable of quarter, just second any

or needs going clarify Can talks upcoming? file done just enough. that’s have to pending you the allow be work results you done to preclinical positive data what to been Fair Okay.

All been the being preclinical part – of be will work has mission. is this or completed

is that nothing is limiting. that So rate

Thank Okay. you.

you. Thank

with Fitzgerald. comes Young question Alethia next Cantor from Our

may proceed your with You question.

Hi of commercial getting want obviously how guys I Thanks. guys, to think population then are safety, but kind that production, there thanks deploying to ways do into for for taking think where population are that maybe just heading the measured the the claims kind figure, [indiscernible] about there? injection one, just other bit XXX,XXX question. a strategies how XXX,XXX there interpretation a of about any about to talk a my points little is of you're these and some you

the So, to related fraction. ejection

clinical-based program Phase data was the EXPLORER So, ranging. using is based on our whereas parameters only X basically dose

So, this to are dose able we’re drops significant and able EF. adjust with in avoid to any

case drug patients could EFs the the to XX%, the actually in holiday trial. have able below dropped back they get are Our on if a dosing their to and finish

all far is our numbers that out So well. of this working indicate

Alethia really of check think just little way on depression about look I EF depression is of that EF heart going to to think a failure. unnatural bit, at lead might forward to a periods prolonged to

You the in in but don't a get clinical well. is really, feel expansion can know, if both sure, right for we world also something trial confident where the the construct patients real we open-label data, the this they dose, avoid once that really look really we to of at you

you’ve the got open-label we’ve manner from efficacy and You of got have a stable ability EF, that expansion. to in really in our stable that dose and confidence now sort consistent

we are on EXPLORER. with about great So, front we’re where that feeling

it to specifically, of really might is relates for to So, eye the EF, heart keep EXPLORER tolerability your kind mavacamten on that as of lead things failure. to

on a that standpoint We clinical important got EF. consequence community got the has from the and I around is that their think – safety of eye that have

dosing that getting we standpoint, what mean improving EF capture a in is filling obstruction VOX of for gave in the et and in a the efficacy composite same symptoms, population, volume, really shall us .For normal stroke maintaining way. that From we're way essentially looking pressures an the endpoint it increasing ability and Heart rid peak range, really lowering what I at in cetera the us and MAVERICK did is, the the New and tune York very non-obstructive MAVERICK to in much the

individual to a got target, patients we So, We’ve now way for the what optimal that in up benefit set going that MAVERICK that will is got lot can we knowing that’s confidence believe coming to now a next out drive non-obstructive the be of target dose a and we any great. the of their be up. component study patient where to safely big have that now is

to that Now, improve let’s prove on and go function dosing patients. in going and really improve that symptoms approach is

question. I'm going – if you the the to remember let of second Bill part

Yes. great question. It’s a

So, we Many is overlook that are the there the roughly diagnosed point believe of first that to today. are think suboptimal. treated not XX,XXX with them are patients I disease and

tremendous the our I first think launch opportunity. of for years full got So, couple of we’ve hands with

throughout launch and effort phase big now market, the be you're is at, to starting going in where which getting there growing Now, the a right? is

of diagnosis get and there and planning increase are we this them do There some are population do. How into doing we’re channels. things to some proper things their we're

focused So, now which is really day we campaign, awareness. launched increasing disease on this

We’re live linked which I campaign end the deceased awareness to the help with the at improve help March, think and physician diagnosis. date disease will around website improve of again, going

partnership Once we got get, we’ve AHA. with this

with entire then the followership is be a some to to with we’re to and AHA position more HCM. in things focused will a kind think their promulgate as This them, I around get that launch. So, there the HCM information we closer doing are fundamental out now of initiative we

suspect they invest the awareness going into going refer speaker to we we and to patients heavily quickly. and programs CME, for a to be KOLs the are diagnosis heavily education in and out I community centre get mean, working to increase them and with get [indiscernible] experts community going and these to whom help are in invest to we bring to medical the are and

a doing answers increase there be that we're things diagnosis. going bunch whole Hope that to is So, of your question? to

Thank you.

Thank you.

Your next question comes Cowen. with from Baral Ritu

your with question. proceed may You

of using the and placebo is your of mentioned my EXPLORER, group Liberty groups you composite also that how explore, question. group afternoon of for off criteria, that’s your for them a a little a placebo-controlled, demographics for placebo guys. demographics shaping XX% Thanks the to placebo bit Good there and talk focus and up on – think the a expectations – going that patients that I’m up the placebo patients you to had you MAVERICK follow response question this the MAVERICK And response about got placebo for non-obstructive had first in think how can group that based Study, base then and be you will the Gilead and higher the the obstructive versus you reason the Bill. should we to like the of I’ve a comparing that? taking

So, we the then us was specifically did this found except in MAVERICK trial the that it XX%. first about the we a PIONEER patients non-obstructive similar a used demographics, our which very that the have the in with own of we MAVERICK Gilead combination a so looked course those of of XX%, estimated who obstructive and data EXPLORER enrolled and We was obstruction, MAVERICK difference those. question made only feel in not good. The of originally patients study, that in very estimated was to very, off the that demographically and

so we're us all based trial, on that were clinical placebo they Placebo this. trial that ability on controlled based our our assumptions of conduct to basically pleased about told a So, valid

different commercial into go then on And endpoints a the that question the composite.

is of in peak in so sort commercial the foot NYHA it meaningful perspective there that then put endpoints commercial listed the in it move like of need secondary I and your the order [indiscernible] your the forward? ranked you and you quartered sounded a order in to best of from VOX you think then listed importance, threshold you make on gradient sort order needle best some was to – – to

think fantastic. needle looking is I mean, I move class I what going for. moving improvement to was NYHA, in is can showing think Well, community one and the we the be classification

is it accomplished. not easily So,

way of earlier disease lot So, of pretty in is these down the it a to to significant themselves you in and quality a a and all limiting down exercise. activities of it and patients burden to life, lot terms and they symptoms as daily conduct heard ability comes it have of - of comes

if demonstrate a they’ve we the community something think to I that. for long we’re looking time So, providing and been done are supports in that with we’ve quantitative able improvement the [indiscernible] research

versus if versus You need patients like wondering compelling to actually proposition world. VOX, the to I more improvements the need more real much percentage peak the of composite side present the does profile is I'm side commercially show NYHA other a guess hit one a in certain one

think sides, pretty I if sides about think compelling. both are both we

the know, component which peak a combined NYHA and in measurement the point You cardiac addresses function. VOX, the also is objective very of

I values. both So, think are

behind if don't I and – really that. think that, much is NYHA. I I to you on more mean, we look – just say attributes if I have at the list, peak VOX

depend it So would who on ask. you I guess

– And ahead, go it. Okay. sorry. Got

real very VOX NYHA know very being you peak activities able patients of daily are is are important. think maximum These improve cardiologist. How about sprinting that's patients are is limited in a you more your to can We where and either me both is doing important are living? of as important an that. my output, your integrated. These So, to capability. your to by

And will be the so to will for be one other, some important patients, meaningful but cardiology very community. more the than both

you thinking maybe low-hanging to in cardiac the traders Got question. Marc. cardiologist traders? guys fruit What force those X,XXX terms Thanks, last And right now hit quick – it. are commercial of one

Yes.

launch, types side plus X,XXX XX at sales what plan – to of The what a just is about somewhere we've will, can go you thinking enormous or stress talked beyond easily the of really go we think, kind XXX, around organization, on I or that is so. after the And plan minus, think force is optimize, if to not that, of or broader I manage, than put it going we to numbers. strain something doesn't the those with the pretty opportunity.

taking for the Thanks Great. questions.

Thank you.

Our Martin next from question comes Auster Credit with Suisse.

proceed question. with your may You

in PIONEER in Hi, curious, Thanks I taking should for of in everyone. my So words, in we drops the the the for how I second, guess, between stroke function diastolic fraction on able question. volume? to ejection context function Thank is diastolic extent interpret other Mark This the for study? was you. Marty. was fraction drops compensate and any observe in ejection then fraction? to what correlation And you improved ejection did

to guess, study. I PIONEER was PIONEER, back Mark, dose-ranging a Hi, going

doses, context, – what learn anticipated fraction learned was which the just than lower that far we that say, to point driven that, to keeping ejection is dosing in study, of just by study how that were much of we the the more this drug what less that is explore. The And so you did in few the see so than exploration into were, we now X. that had reductions – needed let's coming Phase dose. So, a and percent we

the Flash is open where and seeing over many a XX of only a we've starting clinical dose essentially patients when really to based to low on forward plus of actually, the which necessary is right and important. way parameter, determined kind these maintain which dose both increasing year safety, in now a the that we not in label of studies, change whole fraction months to lot have today extension ejection we're

EF there point really by in efficacy safety necessarily overexposing efficacy. EF not unnecessarily. the our to it’s And lot then concern, is, we a not optimize reduction unnecessarily get a mavacamten Difference isn't once we reduce but to view there, from adding of the

reduction these XXs. they're label you the folks we want open the sure to in see in to are efficacy, still EF. optimize make minimizing And extension, are if we that as normal So to you will, high range, the the above

clinical allows that's So, do that predicted matter I really thing manage us connected, use parameters safety and think a to really that outcomes efficacy. the able optimize to drug are to that with we're that this cool to

a for ejection in reduction than even patients had, say than they those that did their optimal in So, better let's more PIONEER baseline. fraction, still

in So, keep that VOX York Association stuff. mind, Heart right, New good that's and all peak improved improved,

us same only insights and information. the is, say MAVERICK I of So, analog level will gave the

their to So, safety to dose. on parameter benefit, we have tolerability managing think while a adjust on optimal and we the their dose folks now way their ability going have to clinical where get to optimal they're based and

Thank it. Got you.

Thank you.

Darout Etzer Guggenheim. with from comes next Our question

may question. proceed your with You

could taking fraction the wondered question, terms line, still as could enroll types of the quick the on of in on Great. talk to some question. type HCM There EXPLORER? top of speak what wondered to trial, Thanks. question. Thanks follow-up if severity, then the I VALOR data And recruiting into get for the to ejection patients could that? in you safety if study, be to had about on the the it seems second and likely confusion to compares patients just EXPLORER as this a you we

Jay will and I – on safety the Etzer, on EXPLORER lot VALOR the EXPLORER top present details take haven't given at don't the Hi, that question. line. a we of for question will data

tolerability provide I of data really of have that we when understanding We're line ejection it us, customary the safety should that fraction the but safety the to to with right, is to top it, all us think get things into do drug. as at expect you presentation, for to going point. relates the has medical key

there's XX%; persistent protocols set for clinical a all is our point, studies a situations. And if pick below both clinical we – in at pick in of trials, and some depression fraction it our EXPLORER which the point XX%, we different our two normal, in of trials ejection MAVERICK, in triggers – That of different activity. the

threshold is happen that things trial. in for a just to So a clinical protocol-derived clinical

not will XX of below – to will happen they happen concern. and without excursions safety In folks a themselves, they HCM. Transient are

heart something neural activate up particularly would of of is saying, due In most fact heart. depressed. end It tolerability, dilating the behaving would that the to mavacamten here, would context hormones and heart be, putting below would not being to differently. you us, the weeks, XX, fraction an ejection for in you start the with I'm do reductions several rest that to to got I've had expect case, ejection that them people important to those So blood into fraction on the for different get this it the enough the react, because the able app if is

very link drugs to So activity. the and both a side point, links that it because us, central until useful the this contractility been biomarker thing for to and on does loosely is at. – to really very, the It's safety up look efficacy

tolerability us, but related about hope now events thing really context of and potential important an it's it's safety, So, that failure. in putting helps. I it heart adverse for the to

you. thank Yes,

us what EXPLORER. in study the VALOR, for now Class doing allows in we're VALOR complements And It patients IV. to

patients, So an by combination therapy therapy open ablation. septal on completely symptomatic either who've myectomy patients HCM an heart to alcohol and an septal now or procedure, all are exhausted options, medical their seeking invasive reduction out

really patients. for of clinical evidence will provide to data benefits these provide additional the we important think to impact that mavacamten so our And

Great. Thank you.

Thank you.

Our comes Morgan from Stanley. Jeffrey next question with Hung

question. your with proceed may You

on Hi, you'd then XXX over how shorter the to And what thinking Thanks. beyond you mavacamten? our partner for the life? you’d And for factors taking questions. Thank Hannah Europe? you Can are remind if and it aspects potential highlight in then any us this half has advantages is Jeff. gating you're about deciding

Okay.

give I'll in XXX. let high-level with view the partnering you On but that, on Europe me side, a start

‘asset-driven.’ thinking are So, company. losing this goal. to about where really to HCM strive a early, XXX, long-term manage disease-focused have and not That's get to care right, XXX when to looking strategy, started we in place get we're as optimally We're who our medium optimal not anyone our of we We folks to disease. the into are people diagnose a part

continue research, new maybe to so tool manage sure introduce here. us make the overall to broadly days, our to expect In to that objective diseases meeting a other XXX. to one, the HCM, One, hope we the are community words, that to mavacamten, another in we early

So, more pipeline and research investment more that. on in

an around and a open a drug. certainly, result be the seven were the whether got not Mavacamten going to days sure was life label mavacamten, result the is to so. we extension eight longer or we having to advantage disadvantage or half with In PIONEER there days entirely before or

So, a could half profile, a a provide strategy I We metabolized discover also potential started life, has shorter good it molecules. little the a articulated. is XXX where benefits. focused to was just on activity similar but drug has other that differential development one that's bit differently

good. mavacamten Sitting here really really, looks today,

dose, it well. to really right you be fact, a you looks an are to to In get very doing PK. stable half advantage, your potentially long life Once us,

And shorter differentiation clinical of a drug a in half whether so and life it's to meaningful itself would unclear us or have benefit.

now, to as mentioned, aspects patient really appropriate have XXX, we And seeing in But liking that this XXX in like a really for more as if see. advantages that be to different able of There certain directly could we're to position take get to Taylor for be populations we're in it different the to it of mavacamten. profile data forward. year, are data, the some some does able we'll turn get second-half situations, with out, ways. the other in make what to drug a that we're a a has the right We'll where to more speak

Thanks. Great.

On Europe. Yes.

particular program Europe, any the We're package Europe. to in we've the support we're – not the right partner got expertise and Europe. how So, Europe. get understand within company to rush to in to registrational development

for European local place, opportunity ahead folks and have, level kind also with really on Board now the and and level of Bill Europe our at regional some We team, the of got market MyoKardia. in in we've learning about his

assess, driver position us. on effectively. whether provide able that So, be someone in HCM whether with take through achieve se, to really a and real a people us more more strategy forward that partnership, per more a mission quickly, right or more to broadly, be be the the It own, this company wouldn't we're to benefits to our more really we for driver we'll that might but help financial really would to be

do more able more say patients are understanding inbound we to as it which look study U.S. EXPLORER and about who with that Europe. for European do from treated a learn EXPLORER was interest, with So, in like and it would get market, will potential mission we are that the effectively. we’ll assess we managed, the be experiences partners what achieve us I that how float and our through might to

a the company. on now got experience lot and we've that So, of within already

you Thank so Great. much.

Thank next Mohit with you. [Operator Citi. from comes Our Bansal question Instructions]

may with proceed your You question.

Mohit. Good guys. for taking Keith questions. on for our afternoon, is Thanks This

VALOR. Thank for The on get stable wanted first you're one seeing, for or treating And or guess, Could endpoint? order risk XXX characterize Xa, then what's and there, placebo you're to I looking from you're than bar the any X disease other in how trial of effect, Phase And supplant in is benefit there's to sense Phase a SRT non-inferiority? that implications profile if you. the given you the there? design just

a we're interventional to than VALOR, or patients treat a for rather comparison. to prior So, do surgical looking to procedure

seen overall. benefit we think but out of we And EXPLORER, when of head-to-head need considered. the what that to specifics expect we we going the the patients against being So, based this PIONEER, of announcing we won't being out design we'll that who trial majority are toward option started, on giving get will be patients be the the procedure avoid that of parameters but able would have obviously the a we surgery, think of vast

question. it? at XXX And want understand make mind, sure Do I giving to your I shot you another sort us of

sure. Sure,

heart as Xa stable with Phase it looks done the failure. patients like So in

get time? at of disease given stable placebo effect, to the looking how over sense and Just wanted a you're change

Oh, Yes. sure.

The chime add. kind in feel and in to and these foremost think we lot and, Phase placebo I study tolerability useful of isolate understanding you lot better information treatment making that So, Jay, a first in gives can free and effect. early a around here a of a and of studies, sure Xa group safety

Small a early on readouts. understand of seeing the we signal biomarker-based we've of different useful variety in symptom, these other that right to is that strength we're got when numbers, studies, patients really But echocardiogram, tens here. look

and us and this feel period during to in mind, the tolerability. it we're trends a are differences and that a gives and we're confidence lot seeing for comfort, just get with time real starting that signals the more So, in that that

great. Thank you. That's

Thank you.

comes question with BMO. George from next Our Farmer

You may proceed with your question.

Hi. taking George. for everyone. Thanks afternoon, Good This Gobind on the is question. for

of ejection is was on fraction, and two I MAVERICK see any get first but a have sort presented what colleagues data Anupam, may the The will And in of be that? mavacamten be just we’ll on I combining Alethia will the of think guess wanted different there given from questions, one, there? those And to MAVERICK follow-up targeting for kind at concentrations? concentration data our trial some asked the follow-up upcoming presentations, there any this and maybe

haven't was, more were I trials. the seeing? follow-up And was EXPLORER from improvement was VOX trial in that the X.X, mentioned was with at And endpoint, question at NYHA. XX%, looking the think Jay then I on composite placebo looking I the we My guys improvement, XX% are the understanding because think, you from it by seen primary so data LIBERTY. this was response, peak LIBERTY my the Is a that NYHA internal the with

So, It part just that help endpoint, understand we just where NYHA? worsening guys Thanks. in you could part presented I missed of if may no have primary been and of to but there's it? the the second wanted it, see

second one quickly. effects. Hi is composite endpoint hit pretty the drove Gobind, a that of I the can It the placebo determination

MAVERICK, So, same it's the for composite.

allow of to quality Association, Heart get Kansas which For they similar. around LIBERTY, collect York collected kind they while measurements, very didn't of Cardiomyopathy, New City other something us life triangulate

driving so the in kind definition endpoint. the the And But of in VOX response either really, form of both around primary estimates placebo peak composite of cases conservative is a made we that. what's some

to So at EXPLORER. very studies appropriate analogs as those of giving valid us both look in confidence

to us going XX, five because that after patients sure. drug five On hit they you them expect that EF, the in talk And the four the of EF, discontinuations, were we EF and in should about so had the to doses. them to happened yes, MAVERICK, fact, protocol about for talk increases

EF reiterate right? too, in earlier, we MAVERICK, was Phase dose and how basically more of did I just much now in we the based on that drove It like point a So, around those are edges, it – a got be get confidence where to by those we cases. in order to PIONEER. asked we was to who study in to doses Anupam, design higher dose-ranging lot think want with color there'll study, see X where reductions I the to was we've And

obstructed are very population. critically and really non-obstructed run way, PK/PD that, analyses by the all relationships is is What We've to are the those similar. the important similar so those here in of

symptom you is is the the critical to of at increase and measurement meaningful VOX allows like think to is Really clinically getting the is in chances necessarily us to cetera, starting going us of really gradient analogue improvement, obstruction overexposing reduction improvement, is patients peak benefit here the with and appropriately that based way we obstruction, we've connected that. with dose not et clinically got to low, to adjusting on mavacamten something have that drug we looking finding much the clinical that that a beyond levels

you end to plan FDA that us the will now about but non-obstructed we'll MAVERICK to and ready we’re talking the update, non-obstructed, After update, up analyzing So, more mavacamten. not you tell that. to which we with to we from interaction, we're shouldn't FDA expecting our come the through data input ACC. later that go-forward expect who we going not dose on get back update We're can with at for patients confidence

Thanks, That's helpful. Tassos. really

you. Thank

question Our Nierengarten from Wedbush. with comes next David

may proceed with You your question.

Thanks. open any the open on discuss of Hi. extension one. that label you go label it to I or the the give could label the study, the or decision combined patient the on decision up go to is study can can the I you is if patients have you but solely to And and numbers extension or forgive just physician? missed it, When me to patient, open percentages on of a extension?

so included, to able are discussed, both rolling folks majority choice presently they're and actually start of able the we being patients And vast the as soon. into over that this. look to patients MAVERICK LTE, our actually criteria, me program may vast be the not those have do into as have one of patients EXPLORER well. of out stopping know out our but doing actually let we that forward who to met get to the great are majority easy is with The It's patient’s – the we

you. Thank Okay.

Thank you.

Birchenough comes Our Fargo. with Wells question next from Jim

with proceed may your question. You

I dropped earlier. Hi, guys. had

diagnosed are the And the echo I you patients us for what some study, being could about asked or this determination? what considered of of surgery? if you've criteria meet the with that need is And or of what already, remind So, was HCM you a septal for apologies talk but maybe myectomy. level ablation replaced criteria just obstructive follow-up. need portion to maybe for VALOR the would then making – And reversal have would you say on what

a not majority the it’s the So, – able this. but And symptoms we're need all well, are study, are. ACC, And we ex-U.S., gradient this for patients looking for for we of relieved Of be we for the most [ph] avoid be the we're durable basically these surgery where and to trial. to to will for that all through we're a note by is to mavacamten results guidelines for, surgery, guidelines, call expect That's for need using what obstructive patients. pharmacotherapy. VALOR, obviously, patients. looking addition for obviously, is of a that this of compare the mavacamten vast for not someplace look what that the an versus AHA allow place

someone or there if for gradient symptoms? an qualify that based is LVOT would on it surgery, level But

No.

you And patients do candidates surgery? what for again, of know, are proportion

that that similar the level present it – is there. that is symptoms – gradients is echo same in the not over the And of pharmacotherapy. are gradient EXPLORER with it's relieved it's we so based So, have XX. presently, trial And it on

Class So as II well Class ad many patients III Class qualified, as IV.

maybe… And then

was – to to going I think I say. just Jim,

Cleveland there doesn't associated That just surgery is you're think procedures, further There mortality fit the surgical of that here just with that be the of it the criteria one, are a Mayo perioperative right? difficult. number necessarily So some that, to described. I issues or because who at translate large clear at Clinic, are extent patients if complications. Jay minimized the about it's is proportion a actually but challenging into to

of line surgery. you is So, lot not guidelines the and one for the up of a get the it those Jay see folks outlined, go qualify where things, just that that just

thousand So, they're so. a I about or think

of reduction forms septal X,XXX. about it’s when all mean, consider I therapy, you Yes.

are getting… X,XXX

Yes.

it's are eligible, on I multiple don't but estimate pretty go would that to. a that …procedure, significant that

obstructive more if one just maybe to versus [hand lower on ejection to around wringing] maybe then reductions other? And propensity the fraction or you question risk in in expect reasonably where play dynamics fraction. at reduce might versus a ejection differences setting the the different could one there's to setting between fraction you And non-obstructive speak ejection

is a profile non-obstructive both similar and patients. obstructive in What we're PD/PK seeing the the

what one speculate there, much differences while is could we've seen more So, similarity.

Okay. Thanks questions. for taking the

Thanks, Jim.

to any you. Thank And at further back I'm remarks. call Gianakakos questions turn like any the Tassos not to time. showing would over this further now for I

Thanks team on I our all to The here keeping portfolio. you continued for really are and and questions. with updated progress thanks, much mavacamten looking your very a forward and everyone, across

studies, to a little lot As at today, important danicamtiv be later going in at with the incredibly ACC, March of quarter. and mid-year, between of a the MAVERICK bit end heard the you productive readout including to results EXPLORER data an second and the data it's now detailed period the of top discuss the line

time here support. at over a mission I investor hope today. month we your many special conferences continued you next upcoming company with We're we appreciate and participate or of number appreciate that of your really interest as see an the Thank and very really a important so MyoKardia and you. building much in

call. conference This participating. today's you for Thank you, concludes gentlemen. Thank ladies and

now disconnect. may You