ALNY - Earnings call transcript Q2 2018 | Alnylam Pharmaceuticals, Inc.

Due to licensing restrictions, you must log in to view earnings call transcripts.

Operator

Good day, ladies and gentlemen, and welcome to the Alnylam Pharmaceuticals Q2 2018 Earnings Conference Call. At this time, all participants are in a listen-only mode. Later, we will conduct a question-and-answer session, and instructions will follow at that time.

As a reminder, this conference is being recorded. I would now like to introduce your host for today's conference, Ms. of and President Communications. Vice Lindenboom, Investor Corporate Relations Christine Ms. Lindenboom, begin. you may

Christine Regan Lindenboom

morning. phone our President Christine our With is Relations the Chief Chief Financial I'm Executive Manmeet morning. Vaishnaw, Yvonne President Greene, of call Officer; me John to Barry Executive unable Lindenboom, on Officer; Alnylam. Good Akshay Soni, at and R&D Vice Investor Chief President President; Officer. Maraganore, this of Communications and today join Greenstreet, and are Vice Corporate Operating

those via webcast we also to For participating have made our be going slides you call, the of of conference by www.alnylam.com. page available can the website, via Investor accessed

report measures and of including on measures financial may factors, website. those of with the investors During including file call remarks updates; and to concerning financials; to this can Reform questions. related GAAP will by discuss be Act of most We will statements before results slide discussed provide found your a I in tables, and results and under of press important opening today milestones conditions for on a review various provide of Manmeet future The the expectations, in XXXX. those management differ some quarterly information like Barry indicated on Litigation our Alnylam's an will of summary provide our from the call which plans Securities non-GAAP recently our Harbor and to today's as general and purposes will effort as materially and would introductory clinical constitute will commercial financial provide page context; of upcoming The we provision Actual Safe outlined prospects, useful brief recent readiness the regarding these reconciliation operation. a X, forward-looking our that believe forward-looking non-GAAP release that for result John call, contain you update our SEC. Yvonne will the remind Private statements remarks Investor also review

forward-looking statements obligation not of addition, relied any our of now turn John. as specifically We With as that, disclaim update In our statements. should date. representing upon such and views this call subsequent as to represent of only be the views over any I date any will the recording to

John M. Maraganore

thank and Christine, for Thanks, everyone, the morning. joining this call you,

therapeutics XXXX and notable of quarter medicines. class and XX-year period Alnylam's of new recommendation potential have name our positive in second next a of first we the in Indeed, The RNAi expect significant our represent approval the as for recent journey of trade milepost the we a to advancing our the in patisiran, first CHMP by for with approval U.S. the here of ONPATTRO, recommendation And have EU. week, end now

R&D few address Yvonne like a make remarks. Before our progress, to over to I introductory it to turn I'd

First, cusp in first bringing I RNAi are noted, therapeutic patients Europe. our as just of to U.S. and we now the at medicine the

more additional patients more the nothing excited other very planning for moment the us filings year's end. be Alnylam, we countries than difference around lives submission a a important world. of Japan At by are about regulatory and since also September in We in to in making is couldn't in regulatory this special

launch-ready truly where has and Germany, in U.S. medicine. building Secondly, shortly, will commercialize launch. the meaningful We're a believe which as ONPATTRO, disease are expect here our highlight we to Barry first orphan the potential in global to we world-class a EU team we be also

in we a experienced highly a building commercialization plan global in addition, building to team we've been Japan as countries follow other In and well effort.

positive these approval now givosiran Notably, well in and on meanwhile, and Phase XXXX. our the programs. interim trial especially to our results accelerated profile porphyrias. analysis X in support on results late-stage execute possible soon ENVISION to ahead early to an conducting to broader have exceeded Third, acceptable, a of If we efforts, our of NDA discuss XXXX, plan on we safety of our on pipeline an submission we're planning acute the is continue track study FDA expectations the enrollment In we're to in full in year-end to take ENVISION has schedule. hepatic

of favorable launches years in Alnylam of of with annual also studies company and and regulatory on objectives and Xs in authorities commercial-stage pipeline sustainable Phase these other global, our clinical to approvals robust achieved biotech. for end XXXX the deep XXXX, We start pipeline later to a late-stage this will programs, building have from a some scored milestones results year. the a product to a lumasiran potential of essentially each and us for assuming the believe We ever, our with to related on all also track if notable profile engine multi-product, of namely milestones put X in these design rarely, regulatory programs, meet in by the ALN-TTRscXX come, company these alignment each of important Phase

to a community. in call physicians nurses approval I'd and here take of in in the ONPATTRO at by say make privilege the anticipated journey stellar been to U.S. and The decade long our effort, gone and and Finally, fueled our above review Alnylam turn patients. progress pipeline patients fruit that and this serve to for who detail. over like Yvonne? is a beyond imminent this team occasion to Yvonne across group truly it's want now of Europe I to to caregivers, With the the reality the more ONPATTRO to every have that, hATTR

Yvonne L. Greenstreet

morning, and Thanks, good everyone. John,

we filled highlighted, patisiran. busy been for one closer to PDUFA much our a date excitement as with draw quarter John and and it's anticipation As

our includes including by achieving APOLLO. The our data, work on parameters. recommendation that towards and PDUFA analyses exploratory important APOLLO important goal a for reported So to In with our on date of let's from the the continue action Barry of patisiran. of amyloidosis with in our study Medicine was SmPC, or start very and with strategy the from patisiran and we validating positive pleased RNAi next our in based during the of as England positive and commercial to-date. recommendation exploratory are Phase Product largest step recent CHMP's The week. cardiac period, our an is with the a the secondary FDA endpoint results marketing in collaboratively colleagues meanwhile, Also, reflecting therapeutic we clinical we Journal perspective. Europe is regulatory hATTR APOLLO results Characteristics, data authorization also X But CHMP which additional with patients conducted study, from Summary published of results quarter X the discuss XXX patients will Phase New at

from we APOLLO with that Peripheral at treatment, showed presented recently which example, patisiran new neuropathy in improved where improvements patisiran were the For improvements Meeting, ambulatory in of overall Annual patients and status associated status. impairment Society demonstrated with data health compared placebo Nerve case to analyses

on neuropathy Phase life study previously treatment the an quality with patients Additionally, comparison relative in APOLLO indirect tafamidis those of patisiran's to measured study reported measures hATTR amyloidosis at randomized X conducted polyneuropathy. the in of the demonstrates of and impact PNS in

reached suggests no there some the are endpoints X patients have head-to-head across all studies with comparison this of amyloidosis. significance. While this polyneuropathy Stage conducted, statistical and benefit assessed in approach and versus cases, for was hATTR benefit in This tafamidis limitations for patisiran observed been

approximately with have the pleased co-primary study the APOLLO Phase label TTRscXX we amyloidosis on in as and at endpoints the Turning to open design an comparing nine pivotal hATTR of now study, Norfolk-QOL hATTR of Phase trial study Phase the with the to mentioned, ALN-TTRscXX, results arm be patients from XXX alignment with months The are John effects X patients placebo pivotal in of to will of mNIS+X X patisiran. of the with FDA a reached X TTRscXX amyloidosis.

reference reference ATTR will on will additional In a XXXX. amyloidosis comparisons to as addition, between patisiran arm XXXX the endpoints. of the include late be to and study receiving formal in The in patients studies TTRscXX, certain of although X cardiac XX TTRscXX the no included including parameters and also study conducted will Phase approximately start X arm. patisiran wild-type small an plan track start Phase We're be

the move hepatic acute development givosiran, Let's therapeutic of to RNAi for on our in porphyrias. investigational treatment

is we As the ENVISION of of ALA the in based predict a that accelerated potential that announced The that to benefit. levels will Phase biomarker is we urinary on surrogate clinical in completed you'll reasonably treatment the X comprise cohort a enrollment approval. of months analysis at of patients study previously as interim likely planned support recall, interim three of lowering analysis

the FDA an interim We around results line were If to expect the then the year top go results results around to analysis possible and approval. to discuss to NDA we will support acceptable, end analysis at accelerated report interim from the end safety also September. filing to the positive discuss or of the

schedule ahead anticipate enrollment announced today also We of September. by accrual and well in we has this now full end ENVISION of the patient proceeded

As endpoint top primary treatment months early in XXXX. on rates expect annualized such, the to line of of report results we after six attack

data study to treatment new where from progress. X/X of type presented Phase at our in the Let's X, primary positive We Consortium. the move lumasiran, for great on Hyperoxaluria OxalEurope therapeutic RNAi investigational European the hyperoxaluria we've development made also

at oxalate patients of below B demonstrated lumasiran reduced X/X slide Cohorts potent meaningful XX%. maximal oxalate These regimen. of in were XX% experienced reduction Part associated a on lumasiran durable a renal in with lumasiran dose Phase durable XX, mean seen a key mean We subcutaneous the lowering believe all oxalate threshold and urinary in commonly once day study, reductions the reductions quarterly urinary a of end these As with treatment rate clinically urinary to X-X of in level Furthermore, in a of XX. reduction urinary progression maintaining support disease. stage oxalate patients

unrelated has Additionally, to was X/X has drug. hepatic not were been we AEs production, that of thus reduce level no hypothesis progression. associated finding, events in tolerated potential adverse well of in there severity believe all oxidase to Phase date. adverse patients cut-off through the the the PHX to disease data any mild Lumasiran majority continue study. to in generally inhibition moderate and discontinuations were study glycolate potentially significant and laboratory possibly and or support clinically due study XX with The of oxalate the Lumasiran halting normalize these results

design During the authorities quarter, in lumasiran. the for study alignments achieved Phase we regulatory X with

primary be a Phase planned on endpoint as supporting remain reduction start filing six XXXX. was pivotal XX approximately with for XXXX, a Importantly, the results treatment the coming period full months. oxalate early in the have and X in the The approval. study track late patients NDA expected in to expected potential will We weeks, study urinary will

then. in of a lumasiran RNAi I upcoming XX. be our more will you at step all next to lumasiran our providing tune And Roundtable and comprehensive review August data recent We on clinical on encourage

In Company data its Medicines review received addition, substantially X progress Monitoring of hypercholesterolemia. had of for June that fitusiran the placebo. announced more date inclisiran inclisiran. patient-years and has the safety In planned ORION efficacy ongoing the trial the patients MedCo time At hemophilia, for inclisiran program. data continues without in continue X,XXX safety two the of third make from trials now great Independent enrollment continues Sanofi, doses ATLAS for trials than in all transferred for case The to of the accumulated review, trials Phase Phase to recommended modification. in now or the of to and MedCo the that Data with conducted Committee X

of in ultra-rare press our this are in slower guidance patient and our noted aHUS populating. enrollment cemdisiran release due in expected our As study this morning, earnings Phase to X we than shifting

over brain novel a efficient modifications enable further siRNA achievement this platform is across Alnylam's XXXX Chemistry target injection in of single Alnylam regions. siRNA of that uptake regions cord. spinal The with central we our beyond complete of Enhanced Stabilization at or with step significant CNS. that and durable pre-clinical seen pass cord CNS we target in system development novel successful specific conjugates plan a all resulted forward targeted a presented potential Annual spinal the the to the distribution at to disease key and CNS for review call In nervous demonstrated With and the brain financials. delivery technology novel in utilize results to siRNA our conjugate therapeutics to quarter second broad late of We exciting anatomical very cells. XXXX. a that, RNAi gene by of silencing efforts, delivery Robust, made earlier transcript a highly our neuronal has from conjugates Manmeet? of Looking the candidates TIDES of applications announcement the to and expand to Meeting, believe first we rat a study intrathecal broad R&D initial Manmeet disease and selection in was the I'll liver-expressed our

Manmeet Singh Soni

morning, Yvonne, the today our for XXXX take of our to everyone. I and key to of financial earlier to a our areas: results our issued guidance. results for like good position, of a Thanks, three press refer overview Please release would financial provide this quarter quarter opportunity and second summary XXXX. second reaffirmed our cash brief

let start slide We ending and quarter me securities. debt maintained XX, a equity cash balance in cash, to second solid our marketable balance. $X.XX Moving cash the with excluding securities with approximately billion equivalents, restricted investments sheet,

the second from of Moving during new million alliance sources. the of during from milestone using as relates dosing the $XX.X revenue the the Genzyme recognized second primarily quarter The second for of a upon to fitusiran results revenue our performance from the $XX program included XXXX to patient for quarter the Phase Genzyme financial Sanofi on million the amount first million proportional second million XXXX based and of Revenues $XX.X $X.X recognized due quarter we method to first with recognition $XX.X our the of the second during during payment ATLAS X achievement XXXX and collaboration quarter, quarter for of standard. of XXXX. of recognized the quarter Sanofi XXXX compared million in other

Genzyme. have ended new As revenues second compare X the alliance revenue recognized million quarter collaboration of six our would in result we adoption we a recognition previously June $XX.X guidance, our higher on the with XXXX under lower recognized Sanofi recognition January To standard, quarter during and of from applicable the months during revenue XXXX. of significantly revenue the

months recognized XXXX, have previously ended six higher June would collaboration applicable million the the $XX.X guidance. we revenue revenue in For under

million $XXX in period stock-based R&D in of million million expenses compensation an and in late-stage The expenses and XXXX. second expenses, programs expenses primarily a $XX.X in $XXX.X as second compared we our and related expense. the of development pipeline. manufacturing of in quarter second were in R&D quarter XXXX non-GAAP expand expenses increase expenses to head result compensation Moving To non-GAAP $XX.X XXXX was increased advance our to the increased second count XXXX. Non-GAAP of the as to increase the quarter due as related exclude our were remind, primarily as R&D to compared during GAAP R&D of to the expenses million quarter

G&A growth XXXX. Moving on, were on gain which stock-based $XX.X patisiran G&A The compensation compared million quarter million as thereafter. in XXXX. to in settlement expense. to in commercial primarily $XX.X XXXX. and a of the on was Non-GAAP expenses and second $XX of our commercial-related quarter with of the Dicerna an medical XXXX G&A expenses We GAAP and were product in also in quarter $XX.X in and expenses increase non-GAAP of affairs million the quarter G&A launches expenses head services due corporate to the of XXXX announced in million recorded increase second litigation launch to million agreement potential as second $XX.X significant Non-GAAP second for count April in based our and support of Pharmaceuticals, was potential additional in the XXXX, XXXX prepare exclude compared

of is litigation measures, outside impact non-GAAP company's gain We a the ordinary as we on believe the item the have of excluded settlement occurring event this to present the business. one-time course

basis net basis, share $XXX.X losses, a for and per a a Turning a quarter of XXXX basis and as or $X.XX loss was million basic loss compensation of of was basic second second compared compared both for on loss to the a of respect share as GAAP or to to the of both $XXX.X marketable we and second stock-based basis, net million securities, The $X.XX for both per on to million XXXX. in investments, per or equivalents, loss to non-GAAP excludes on quarter and XXXX, on litigation end non-GAAP gain of the XXXX the quarter a quarter cash $X as and quarter for billion net cash, the remain debt both XXXX. million or With for one-time both diluted $XXX.X and for share second Non-GAAP XXXX $XX.X guidance $X.XX with restricted XXXX net loss cash $X.XX approximately diluted basic on on excluding per equity diluted securities. above. mentioned share basic net I settlement, the second of diluted track restricted

$XXX expect between non-GAAP non-GAAP will million. annual over million I to XXXX call to million continue Barry? turn to We that expense $XXX R&D $XXX range the $XXX XXXX range With million will SG&A that, now annual expenses and Barry. to will between

Barry E. Greene

Thank in week away, just to and first-ever our opinion positive CHMP's good hand over capabilities are patisiran and to you, patients commercial Manmeet, the in morning, for date With place therapeutic PDUFA approval. a upon the everyone. deliver RNAi

week, you patisiran neuropathy CHMP positive X of affirming as amyloidosis patisiran on X with In patients the on As manifestations the EU. CHMP of saw the be recommendation, life, cardiac Stage indicated the on both that positive for effects impact with the Stage ATTR parameters. recognized well adult disease quality the or treats recommended of as hereditary and last in disease its polyneuropathy in that treatment

and patients. to which patients to decisions patisiran and decisions with payers data data SmPC healthcare key Summary of based cardiac from SmPC, safety Importantly, reimbursement exploratory provide their from provide will value efficacy endpoint on includes APOLLO, results. substantial prescribing that they all the the believe upon APOLLO include recommended, with Product the the will delivers recommended or endpoint Characteristics, of we make has substantive The secondary exploratory robust data providers for both including can data and make

across negotiated Europe, health to will technology We engage countries a country-by-country on reimbursement in and be continue assessment basis. multiple bodies

in reimbursement FDA Pending of in Germany. remain countries with a with expect launch-ready approval. will label. We Other launch will pending the full is In relevant be to EU planned the EC our following we MAA, market approval U.S., state, first be granted the negotiations thereafter our accordance health within authorities. launch

in approved. on three improving significant on companies Our patisiran and drug we team to U.S. With disease, this get as and, once focused awareness and field on patient and importantly, is soon are actively feel position board awareness we inroads possible remain we diagnostic confident as can to is to the the educating identification. patients process. that on a engage raising in make planned We shortening

Alnylam number aware, a working you're to As diagnosis has through been improve initiatives. of

For example, genetic testing patients. a U.S. the third-party Alnylam Act, in which to is Canada service that is and free

providing of patients of testing XX, having with the identified an request Alnylam patients. have TTR XXX X,XXX ATTR Access also As pathogenic from access pleased We're July gene to individuals enabled amyloidosis, and carry to has mutations. for who Europe, with mutations in to response may treating associated early Program active physicians approximately Act patisiran hereditary U.S. in eligible Expanded as

professionals was physician countries. European being for the the As awareness unmet increased our hATTR U.S. requests in in fulfilled a in who we healthcare certain XXX than now are families. that and more need But patient press and with patisiran the of treated measure indicative amyloidosis this is we've disease patients announced of and among release, believe

also continues. global Our rollout

Masako in joins responsible into XXXX XX to continue were NDA pleased role, potential initial the include of Asia with Alnylam's with experience, PMDA Accordingly, Nakamura our execution disease file and market. commercial over Asia. will Head a the with the In important representing announce of plan lumasiran a in the the on givosiran June, we for drug thereafter. and and region who appointment for expansion as mid-XXXX, This of We in years to Japan. ONPATTRO of in focus Alnylam to Masako, direction biotech of his Japanese very in patisiran and rare and operations building launches strategic capabilities sequencing will be orphan Asia the

this will working market patients. that is awareness believe improve actively that in to and we should growth see patients patient patient a for result as disease amyloidosis. biggest hereditary a settings setting market number Therefore, like the raise and finding disease ultimately amyloidosis multiple more of disease of share, versus diagnosed. for in to shorten other having and diagnosis market seen similar expansion patients We the benefit angioedema. discussed, hATTR is way hATTR we've just As transformative substantially sclerosis that what the market and the in awareness, amyloidosis time ourselves we've challenge overall increase others before the with journey We from one will hATTR believe

as global, sustainable goal readiness. of and incredibly in We commercial launch with our we believe the on multi-product, of track to therapeutic, are of us this launch stage pipeline for a We our all work company Alnylam a we of are an excited become by plan RNAi first-ever XXXX deep end puts with XXXX. the and sight commercial

European now turn intend brief upcoming in States. thereafter. United the launches achieve European launch of We certain to markets QX, we for which approval from Commission to a ONPATTRO tend we Let me by In on update as milestones. shortly define to the ONPATTRO and to in mid-XXXX, followed gain QX approval regulatory FDA

As ALN-AATXX amyloidosis. intend markets, FDA analysis We file results again the ENVISION positive of in initiate pending study and in the chronic to of the And additional review, potential justify. partnership development late X Phase we IND for FDA X the B safety and Phase ALN-TTRscXX in the top the a an data which from NDA to trial disease intend earlier approval ENVISION to Phase define including QX, the acceptable as we study. Japanese for interim for antitrypsin with for line QX ONPATTRO hATTR for to approval the should givosiran global intend liver we alpha-X associated Vir regulatory of infection. I development analysis givosiran with In XXXX, file we report X of assuming initiate file with from we ONPATTRO as interim of virus treatment intend ALN-HBVXX or And treatment deficiency mentioned, to plan PMDA. support call, accelerated CTA hepatitis highlighted with an on to of in NDA file in lumasiran of and

to we lumasiran that, data mentioned, be we'll also As development also Christine. on With over of and Christine? the let medical all back the finally, selection And meetings candidate. CNS turn of half plan the our to complete at year. me first patisiran target it of in presenting new

Christine Regan Lindenboom

be would line Thanks, the discuss anticipated potential the quickly and note U.S. questions, label open not communications the timing this able to in for and that to I given look for regulatory Barry. or patisiran And pending the questions. call EU, before will U.S. like time I open We appropriate actions or of call in we to forward now scenarios pricing. the interactions, Operator, providing those we'll in updates future. for near regulatory

one in, additional dialed limit ask questions. those you get the queue back question you to each would to have to we in For yourself if then and like

Operator

you. Thank

from Wang question comes first Barclays. Gena with Our

Gena Wang

any reduction with hierarchy also will Thank to the trial TTRscXX design, show questions. months reduction? for come just – wondering urinary the like would nine wondering show both? percentage is one versus up meaningful co-primary design TTRscXX, how Phase to reduction if you X ask and for you is taking And lumasiran, Phase you for lumasiran, just then X I the there just have requirement in I my of the oxalate there the the any other or for trial and the just endpoint,

John M. Maraganore

Yvonne, Gena. them you questions, great are Those both? want to handle do

Yvonne L. Greenstreet

happy You know, to. I'm very

particularly the TTRscXX, pleased to a to being across So, placebo able open arm study design around get single we study the to around the read essentially alignment agreements were APOLLO. label with arm for FDA the

and We and months, to the endpoints. it have the endpoints reasonable of a on as two we mNIS+X nine these primary assess which see impact timeframe ahead, Norfolk-QOL TTRscXX

John M. Maraganore

the lumasiran? then on question And

Yvonne L. Greenstreet

the me on lumasiran? remind you Could question

John M. Maraganore

requirement – drop? do for the what level have is we oxalate Question an Yes. urinary absolute of

Yvonne L. Greenstreet

need impressive what that is placebo we given significant in givosiran to So, study. generated well within so we reach so Phase do, to we far compared X/X data ALA with our of the something the essentially, that lowering is feel

John M. Maraganore

lumasiran did show, Right. – urinary reduction But just was to so in Gena, the the – oxalate. have question on with we

Yvonne L. Greenstreet

yeah. Oxalate,

of job around terrific kind aligning a helping done have biomarkers for We program. our

urinary the I John corrected lumasiran sorry, me question and givosiran, heard oxalate So, on but around it's level. has

John M. Maraganore

answer Good. question, Does that Gena? your

Gena Wang

Yes, thank you.

John M. Maraganore

you. Thank

Operator

you. Thank

comes Our Goldman Sachs. from Flynn with next question Terence

Terence Flynn

in that the Hi, question. all ahead next And Thank with for might just you on your size trial there? data this month, and a there just you then maybe steps focused taking we thoughts an is the side, what there for will the to tafamidis looking you data TTRscXX us not for thanks wild-type the in position the as about we're to be Maybe share where on terms data? respect elect conduct when remind be of effect later guys you. just to think superiority of might a framing

John M. Maraganore

Yeah. Thanks, Terence.

stabilizer the Let me and are and better wild-type than mean, is can be reason believe seen to One can take in it then chime equilibrium for only protein shift non-amyloidogenic protein. I can the effect shift on These is well. a as equilibrium Yvonne in mind. an is, biochemically, that's in it my maybe mutant Barry wild-type the things the ATTR? or is a hereditary that there a effect also there for to

is strong the look an in wild-type. versus going effect be that's to how there to setting the hereditary very so interesting And of at

foremost think mind sort strong doesn't a tafamidis effect first that's my show and obviously So, hereditary, on setting. of our if then in in because competitive that that position I enhances

milligram studies. the the least the I'm neuropathy or reason what second milligrams XX is of personally milligram interest, to are dose is is that's if as and XX different in we really then the XX tafamidis is same no whether XX the look The same, and the different milligram XX than is Terence, going milligram before, for at thing dose saw

looking more wild-type then, organic I more therefore, it stabilizer different level driven corroborates that in in of guys a the is, potential being for? and context. that know modest the level but the effects if that are it or so, mind. on its I in you're are is are And the effect things type of the obviously finally, the don't the role people XX% Yvonne, range expecting whatever are by favorable views of Barry XX% maybe treatment is setting that those my a you things have that think three And

Barry E. Greene

think perspective see is a for APOLLO. reverse, and patients or manifestations of Yeah. many what The how much the APOLLO, that's even or I that are going And want hereditary asked to all from is effect views again, is, right stable data a presented in Those of are this Terence, not disease just but disease had what for guess showing size in and manifestations patients on patient stop if they disease in the we their we patients about saw to of this debilitating. I the addition are at tafamidis and are the overall it's progressing continue of on is you about we of data. majority clear reflect Will setting, superiority. patients also progression when the learn What dataset you which progress the detailed to rate? these in of of the reversal terms or to want. many do a slower

when early at a see have understand to predict. time. I It's more trial whether wild-type standalone now Yvonne? or that too we makes of right the data, will they and launch to sense analyze to think kind head-to-head

Yvonne L. Greenstreet

No, good.

from the about thoughts think some have the we we finalize before dataset to see the clearly but I progress to how we need think I full wait study. trial, can final to

John M. Maraganore

drug sort of in a add separation I is and only study. the the thing will between I think other I fact for the placebo timing well would interest mean, of Yeah. as of just be

Terence Flynn

lot. a Thanks

Operator

Thank you.

from Cowen. Ritu question Our Baral next with comes

Ritu Baral

guess, the I that guys. a in market for into Thanks hearing are about tafamidis assuming and follow-up come Hey, the anything your competitive the XXXX, thinking oral Terence's mean, first how about or patients taking milder you're to question landscape, doctors will my what question. I a is messaging and around (XX:XX), patients, got potentially compound mutant mention you to for warehousing an follow-up? not that I is

John M. Maraganore

Okay. handle it? to Barry, do you want

Barry E. Greene

Yeah.

the disease their future for that's So, on, mentioned, Programs uptake. you to cardiologist. have obviously, and we're Expanded for setting, setting try Access practiced hereditary warehouse given about both going if into are It's if people talking been the to patients we're either of patients, I and and neurologist the trying that to that get as in awareness those applicable, seeing, not

available generic On is NSAID setting, these the for than the diflunisal, there patients. wild-type other nothing

So, are for I more effective drugs their to to waiting are say they warehousing available that patients. but be they're potentially wouldn't certainly treat

Yvonne L. Greenstreet

be hATTR come think disease as drugs a medicine treat like patients become keen downstream. their possibly may they waiting rather not physicians as clearly for amyloidosis, for may to or as market mean, soon will I to I keep a soon as patients that than available

John M. Maraganore

answer Does Ritu? your to that question,

Ritu Baral

split doctors recently complaining one follow-up that thing. series interesting feed a neurologists say thing the was noticed they We've how that specialty actually, specialists community awareness amongst know just about FAC X,XXX if calls in into TTR the attract And results that something cardiologist just quite whole competitiveness of and cardiologists mentioned that the the that you're specialist neurologist, is done cardiologists, didn't how And and with community Yeah. or the there were the awareness said the we whereas does and was we diagnosis, the a of you level seeing of and is XXX awareness? good. you that might tests Alnylam

John M. Maraganore

Barry? Yeah.

Barry E. Greene

Yeah.

amyloidosis KOL where And your what time AL treat some chemotherapy observing. of with dealing they've starting So think they you also if and we're about for community, like multiple something is myeloma positive amount amyloidosis observed see cardiology driven been results. by what with with

in amyloidosis them phenomenon were some be large the time. look. the to been for necessarily TTR for not a look amyloidosis not The is differentiate amyloidosis, was of for how newer to they've looking the setting least of they cause aware able understand amount knew they this receptors disease. neurology may of and but in some the of general community, on for but cardiology at practices, So, amyloidosis to

to Alnylam have So, and these and Act a important awareness are then awareness, really community neurology and can the tools exponentially. congresses communities will awareness like we disease promote, both go once particularly we in raise forward and clearly things up in label go as

Ritu Baral

awareness? So, post we can particular assume versus a cardiologist focus that awareness launch, that, is neurologist

Barry E. Greene

offices. say versus, community focus awareness are at whole say ours. These a medical across also of wouldn't big the I I'd gastroenterology is patients

diagnosed So, patient much not is have earlier. years, a patient our but patient get a their journey, be wherever be eight goal seen in the diagnosed specialists seven have over hits before four to or

Yvonne L. Greenstreet

those clinicians them. centers the to have amyloidosis reasons and we've you patients why diagnosed one the of growth excellence of is this specialized of with Yeah, been available very interested where of also treat range full in the

Ritu Baral

Very the queue. everyone. Thanks, get helpful. I'll back in

John M. Maraganore

Ritu. Thanks,

Operator

you. Thank

Bernstein. next Our Vincent question Chen with comes from

Vincent Chen

Good on progress. the morning, congrats and

John M. Maraganore

you. Thank

Vincent Chen

are previously on question this in Is Another tested? higher TTRscXX dose dose QX study you or highlighted study? are that announcing milligram XX ISA, month what today, that being you your poster doses forward that are moving a was in

John M. Maraganore

milligrams planned forward, Yeah. Vincent. going XX is monthly QX dose the

Vincent Chen

you from selection between risk the think rationale effects the efficacy down level? was potentially How to of about increase that side some of and what versus as trade-off and do And lower in dose? knockdown push TTR lower the greater for you there the

John M. Maraganore

Vincent, TTR that XX data feel, well, based knockdown we not shows – effect. modeling, that milligrams a but convincingly on patisiran-like we Well, have that feel achieves

should up we point well level TTR of at that knockdown. four years saying knockdown over from to type is now So TTR XX% to of a be of patients. we that XX% tolerated know, And safety this type in perspective, at

think to can level regimen. we replicate TTR we monthly of the dose the that's faithfully knockdown XX with and So achieve, milligram QX that right

Vincent Chen

just there sort eke even any efficacy. level. to any good Was to could is shown Phase X what there – consideration to even the you've you've safety that if of I seen in so get I guess, knockdown levels far? than of shown well, further guess, see there are far shows and efficacy I you if you data of deeper exploring so few guess, sort deeper out the about wonder greater question that where previously of I sort a and doses the you've is point

John M. Maraganore

internally. explore a XX going perspective, We of agreed science having best Well, level however, approach FDA dose. a I mean, in have is, But think milligram can approach comparable with that dose explore up we the a has and the that always from In perspective the is to from right the future, framework regulatory certainly regulatory we TTR the knockdown. that.

Vincent Chen

Great. the queue. Thank you very much. I'll hop in back

John M. Maraganore

Vincent. Thanks, Yeah.

Operator

Thank you.

Our Madhu next Riley. B. from Kumar question comes with

Madhu Kumar

taking Thanks my question. Hi, guys. for

how is So the relative about first think and for ONPATTRO of, hATTR? one do you TTRscXX versus lifecycles product the kind

John M. Maraganore

TTRscXX, option likely behind of settings subcu on making profile about late-stage X and patisiran make taking option. then for for benefit the to going that terrific we and not with with And will well. currently setting ATTR is a and a Barry just choice we that initial of obviously from in molecule they And setting will ONPATTRO, TTRscXX between TTRscXX very with we for I to suspect patient serve. outlined or infusions, X start and mean, then, chime ONPATTRO available X given have and is we Phase all using me that And new we like carrier believe a wild-type patients, the be within with them, having the study or disease because With in and setting, study. great We what – Phase go a Yvonne maybe pre-symptomatic to that other will same ONPATTRO, that going bothered course, of amyloidosis to that Phase get going them. a subcutaneous other lives we can amyloidosis. go-forward let it's our big is to that's patients medicine we've But ATTR interest patients is of the that the make hereditary worked as genetic mean, a the even favorable can that patients today I ONPATTRO and think the that patients particularly in demonstrated convenience which when continue patients APOLLO to the us, is quarter, molecule. population by going well difference Yeah. be that to investments take many we'll they believe diagnosed, are provide ONPATTRO type continue once ONPATTRO.

Yvonne, So cover or Barry it? to did I add, anything

Barry E. Greene

You covered it.

Yvonne L. Greenstreet

you very nicely. No, it covered I think

John M. Maraganore

And, that your Madhu, answer does question?

Madhu Kumar

And the great. like terms factual of open the then had in study come of APOLLO fraction Yes, What trial? question. more the kind patients a label off in trial of extension finished

John M. Maraganore

we this the coming going the start treatment. finish yet, year, trial off five-year veteran don't They have – of obviously, years first And anybody we'll five we they five study I our have at and when will commercial hit but onto, think drug. years

Madhu Kumar

is for a scXX could Japan the Europe of any do And treated ONPATTRO in to Particularly, there be that much geographies? X, those create patients for any to support of have or launch? U.S., the sense in Phase how headwind approval

John M. Maraganore

enrolling we we of very Yvonne countries around be Maybe many could were to And, to will don't that. we of at have mindful some going the even will be an in but won't comment dynamic. anything meaningfully reimbursement me to this There believe do patisiran world where well. do as We as well, let say Yeah. that place. is patients we or But it impact approval course, launch U.S. point. just the else with add? which ONPATTRO's need following, are Yvonne,

Yvonne L. Greenstreet

that's correct. No,

into be for opportunity the the confident Madhu. TTRscXX we be both as you've enroll we very thoughtful on highlighted, ONPATTRO. that sure here will site issue feel to We minimize patients And deliver to that very able make about selection study, we'll as well

Madhu Kumar

for Thanks my great. taking Okay, questions.

John M. Maraganore

Madhu. All Thanks, right.

Operator

Thank you.

with from comes Rama JPMorgan. question next Anupam Our

Anupam Rama

a out of you activities, curve? much. should queue is thinking could Maybe building maybe and in might the questions there. us I of potential Thanks givosiran guys. here patient congrats about, long-term there that could could for think understand we opportunity sort help and one estimates prelaunch the factors progress. on question of all large how of impact a Maybe there Hey, launch taking is, XXXX is a be, and launch so on get question, of what timeframe, with be your the we a the this range an I Thanks that's ask some

John M. Maraganore

That's great question. Yeah.

it amyloidosis, hATTR like disease. an Just is underdiagnosed

efforts our of lot and improving around a patient are diagnosis. medical education so, And

we last think RNAi was so samples tested, the that of the is come done One of our for we've And at XX we've about the setting. somewhere before range the I presented to so week or extended that our XXX Alnylam of back positive or that things porphyria it program have week the Roundtable mutation. Act in or out

so So going that's program we'll and that continues from a hit rate, see better forward. expected encouraging we pretty how than frankly far, that

obviously We under-diagnosed. to time. lot will spending doing currently medical it a We're it believe is education. do we of be So, improve

we've those are education. few will Barry, and uptake plays therapeutic U.S. ENVISION, Of if We the be impact to anything there based add that do there seen high the But medical rapid system, to in Europe. like extreme thousand a right the givosiran diagnosed patients studies, the quite everything out that the that? in believe of patients believe growth that course, thereafter degree we of disease on givosiran for will shows. be very do in earlier improved burden in the in now, and that given

Barry E. Greene

Yeah.

disease, those that important me emphasize to frankly, are ultra-rare, ultra-rare and an within very let remain an all our find key everybody. will is, believe, porphyria we And So points.

with we than what more fact, to that. porphyria we've John the and of, seeing being mentioned, over is In proof physicians are with up years younger, three, aggressive there is been give looking that going next the to the journey addition coming the patient average these to patient network example, quicker disease educate out ENVISION and Alnylam the that we've are that working good and community Act the And with a disease, already, here for point so another helping. you average is for kind to uptake set strengthen types proof gastroenterologists. over out thought, XX to of seen background point the presented good we just awareness is raising

now. appropriate uptake, a to we numbers, the know it's see too say already. get that or the as difficult. which we and physician it's great patients with an But interface about diagnosis, months, mentioned, do shorten triple they thousand can first not So, whether not to right double, that few early quadruple, years, journey John is We

Anupam Rama

question. the taking for Thanks

John M. Maraganore

Thanks. Yeah.

Operator

Thank you.

Carr comes question & Company. Needham from with next Our Alan

Alan Carr

can assume Yvonne the some other suppose I tell wonder then mentioned registration with for EMA around questions. for follow-up little thoughts about the a your the all the scXX? on is, for Thanks. dependent a if more you Thanks on CNS FDA effort. it's that. And are I us design trials your of program taking the One Hi. us board too. data, is on scXX, but the give what of bit and plans TTR with sense my tafamidis latest

John M. Maraganore

great questions, Those are Alan. Yeah.

ongoing. are Let interactions me scXX, start with in regulatory the Europe

report authorities this whole in we I in have point this had past So success on there But similar mean, expect we've the European field. to there's dialogues Europe. nothing we'll time. at that with do

alignment feel reach as there we we'll that So, well.

Regarding data the And that's and here that the really trials to we for this on wild-type future it. TTRscXX, need TAF TTRscXX. reasons we randomized that Right forward all up it. coming today, we're as And and on the to think assume sitting physicians to (XX:XX) look relevant study today, study see to of month studies be do XXth for for the milligrams sit XX before, in begin hereditary, up influence I here is a thinking that about before, is how brought have Other I a hereditary versus same do factors commented only, is the now, on see. wild-type the TTRscXX. certainly because that right I will I other, both want to XXXX that's we it to of that is will study comparing will drugs will each as our that's thing thinking these milligrams, – XX all different also

in We at finalized that the XXXX can believe do that time. our studies study carrier pre-symptomatic point But other yet. haven't also as we start plan the such

things effort. that liver changer to a about like at opened It CNS, is they years data do RNAi CNS in targeted targeting ago And number the but really to going we in delivery by first is from expand mean, many late you're a some opportunities. but first Regarding is from years thereafter liver our just see to program. have many going end then of a of year and because liver-expressed steady the continued game in more many balanced really programs delivery only now excited to up And of are OTS that a those flow, CNS development perspective. the have opportunities not the with Alan, data. there, the flow we scientific XXXX more to We'll October early really goal of disease I our And in with have filing therapeutics. targets a many, thereafter, continued opening candidate have up flow to years – programs to CTA ago our ago, or is also XXXX and what

question. answered your So I think I've

Alan Carr

so CNS putting primarily other those Anything liver, target beyond, I you'll that just mean, effort be any but some or is mind in it's in organs two?

John M. Maraganore

things. cooking. more a things got more few got We've few We've a

Yvonne L. Greenstreet

to to important think I understand liver. (XX:XX) And in it the do is

John M. Maraganore

Yeah, exactly.

Alan Carr

for Thanks my taking right. question. All

John M. Maraganore

things at Yeah. loss a We don't find investment. for ourselves to

Alan Carr

question. my Okay. taking for Thanks

John M. Maraganore

Thanks, Alan.

Operator

Thank you.

comes Raycroft question next from with Jefferies. Our Maury

Maury Raycroft

those for comment what be there. thanks the position Hi, letter program? label thoughts some perspective John, looking for good that also tafamidis inotersen how on you the morning, EU for taking and expectations any CHMP and Can my provided on you'll and question. and on you

John M. Maraganore

probably mean, best and our are I Akcea statements to over friends asked our are those facts, From questions our perspective, Ionis. Yeah. just the at our on are obviously, that focusing SmPCs. in indication different

Stage indication as the Their X have, with in is polyneuropathy hereditary X patients. We polyneuropathy. amyloidosis Stage an for treatment X indication patients X Stage for Stage ATTR hATTR or of you in statement the know, of or treatment

of disease, which a which neuropathy the of what treatment hATTR treatment is So, is indication the amyloidosis, statement the what statement their our other what mainly says. is, is is

data as from significance course, have Journal England Of know includes we The don't that SmPC New hit cardiac our cardiac any paper. They data. statistical

how just in plays or later there. and out and them that we'll labels that the at then this are the from leave our we so U.S. just in that, We'll time. between the are from So, for think it and side differences few there a coming important week in we'll meaningful at go weeks point see

Maury Raycroft

I Great. are there's Dicerna. It's oxalate but to data have think data from can read will targeting different one if And on I maybe program? some quick half they so a their expecting pathway are your enzyme through lumasiran, we in second a any ask

John M. Maraganore

looking I obviously LDHA. don't lower a be to targeting We've at think I It's done level. LDHA. we can mean, obviously, they target are so. think preclinical work operative that oxalate

thing mostly from seen concerns believe may pre-clinically elevating around that they So, pyruvate that I target, expect to the liver should you've a not enzyme right be see We levels GO which which better is to will do. that.

So acceptable start and a up perspective urinary oxalate how the with already, for to efficacy data we'll shown versus very we've a of what which is them normalization essentially safety see come profile. encouraging very from and efficacy favorable safety and

Maury Raycroft

it. Got

Thank very Okay. you much.

John M. Maraganore

you. Thank

Operator

Thank you.

next Konstantinos Our comes with Aprilakis from question JMP Securities.

Konstantinos Aprilakis

very my add progress. question. me much congrats all your my for on taking And Thanks let

gauge So long-term mutations carry manifest how that asymptomatic, just in symptoms? before and on can you quick one discussed the study they your be of might to TTR potential scXX, were efforts a in being interested a you such patients an treated us preventive of trial give patients cost idea

John M. Maraganore

haven't add anything still KOL and We Yvonne, sure we're really Konstantinos, gone that of patient We beforehand is we I medically. important quite before basic know Yeah. the else setting. from to interest it's concept design. a do of think really community treating even there just vetting bit program, the community makes a while the sense to that? smidgen with yet by the complete I'm disease of preventing – to a the think

Yvonne L. Greenstreet

sort it's be to and think I size. really too early cost around No, of detailed

John M. Maraganore

are of longer time. Yeah, about a time study, right enrichment actively period Konstantinos. way could to clearly strategies long exploring the may we I treating shorten term. mean, that require that maybe there but are be it that a it It But might patients these think is

Konstantinos Aprilakis

again. Congrats guys. Thanks, great. Okay,

John M. Maraganore

you. Thank

Operator

Thank Marai we from final time one Nomura/Instinet. with question for have Chris do you. And

Christopher N. Marai

focus Phase morning. the study design. for mNIS+X, know of sort there. looks patients the taking Thanks that and on X Hey, the I that scXX like it's good mostly Appreciate like the on to update question. going looks

looks on that the a wondering potential so APOLLO? And some benefits and for cardiac could to potential show the it's in cardiac disease, in study if with the data you. powered you in are observed you adequately way Thank you it nine-month comment patients of like them

John M. Maraganore

Thanks, Yeah. Chris.

APOLLO, nine are were study. able at We on and differences statistically in drug months, including the show to endpoints cardiac placebo in cardiac significant between And parameters. we

in to Phase to expect be differences TTRscXX do we show the X absolutely. those able So,

Christopher N. Marai

Okay. Thank you.

John M. Maraganore

Good. Thank you.

Okay.

Operator

now in turn participating over back I for call closing any would to remarks. today's like the to thank management Ladies you question-and-answer for session. and gentlemen,

John M. Maraganore

for Right. the imagine. in are look to bringing continued around RNAi week. to the We our at to And can soon excited and joining on thanks forward therapeutics might everyone us have the cusp as world. updating progress you relatively patients you We Well, very guys coming call another albeit we today. of

Bye-bye. So, thanks, everybody, day. great and have a

Operator

today's and thank program. conclude conference. in Ladies you gentlemen, for This the participating does

You wonderful day. may all disconnect. And have a

Alnylam Pharmaceuticals (ALNY) 2 Aug 182018 Q2 Earnings call transcript