ALNY - Earnings call transcript Q4 2018 | Alnylam Pharmaceuticals, Inc.

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Operator

Ladies and gentlemen, thank you for standing by. Welcome to the Alnylam Pharmaceuticals Conference Call Fourth Quarter and Full Year 2018 Financial Results. There will be a question-and-answer session to follow. Please be advised that this call is being taped at the company's request. I would now like to turn the call over to the company.

Christine Lindenboom

afternoon. Good Vice Relations Lindenboom, at Corporate of Alnylam. President Christine and Investor Communications I'm Investor on John R&D; phone Officer; me today Greenstreet, the With today is Officer are Financial and President; traveling Vaishnaw, Chief Operating we website, For accessed via available webcast also Chief be today’s not Barry Akshay be you via Maraganore, made President Soni, able call, for our conference have participating going of page to Manmeet the will Officer; by of Yvonne www.alnylam.com. Greene, those call, Executive of the slides can Chief

review call, in remarks provision clinical constitute the context; as with Safe I may questions. Akshay XXXX. call forward-looking results the and During purpose Securities of Alnylam's statements Harbor prospects, update which Actual future contains Barry The Reform that Act for our Private Litigation will of milestones John John upcoming of today's expectations, general under plans remarks recent will you concerning review these an the important differ summary on ion indicated as those by of outlined commercial the SEC. various with updates; statements file materially most result will introductory like opening recently and factors provide the for wrap-up from a before this to our are some those will remind some will financials; report included forward-looking our Manmeet quarterly X, call brief would provide your and provide slide on progress,

as Investor views of We any statements. as and note update and call not to regarding of obligation useful recording to Please non-GAAP condition non-GAAP our date. to will any financial management including In and should our results website. of specifically the found also can of John. views release be represent as upon the With GAAP discuss relied to investors that, tables, on information forward-looking press addition, of believe over and measures the we date that provide turn today subsequent that disclaim of such only page related statements our operations. measures the our reconciliation a also any be We this financial representing I'll

John Maraganore

get thank keep today. remarks for the relatively call seeing launch Christine, brief, still into with my XXXX joining and later, the ONPATTRO can believe to the early, dive With with U.S. how meat going by while the so I'm everyone you we and and was commercial Thanks, call. patients over We of EU as of we a as U.S. a patient new and believe excellent which receiving as saw subsequent of demand class pleased the we arrival our strong and innovative end and as XXXX, therapeutics specifics of medicines. we of better of these commercial the launch year but the execution Alnylam ONPATTRO treatment whole are holding teams. will in we're the EU of well for Barry into approval is EU U.S. going. XXX the in physician RNAi

opportunity longer-term, patients of hATTR of includes cardiomyopathy This vutrisiran market treatment the patients also growth developing study. potentially wide-type patisiran we therapeutic over and anticipate how year. hereditary investigational this on expect help will our for growth. Then APOLLO-B bottom significant amyloidosis advancing initially about the RNAi HELIOS-A that and impact well and here are we're we amyloidosis investigational that wide-type product RNAi therapeutic. excited that thousands the provide the the ONPATTRO through segments All-in-all, our the cardiomyopathy potential we ATTR value in our to our creation efforts commercial summarize ATTR significant achieve committed the the study launching and next the patients start label longer expanding development with focused line of polyneuropathy believe as allows an this ONPATTRO with shareholders. polyneuropathy we're or realize in with program having patient While The with few the and can near-term of is growth term. this to franchise into Akshay with for for by into patients as mid clinical development HELIOS-B years sustained hereditary outcome later the hATTR to we're continued potential for study potentially either the Alnylam

believe of potential clinical programs our X are we also growth. programs, have results next additional in the rights this company advancing Phase the for by particular, advanced be what line very Alnylam where And global we're and building we're In beyond sustainable of positioned value fitusiran, believe for these and partners. multi-product impact ONPATTRO deep that and for annual of to Now, innovation. a rich foundation get number study to and believe we assuming with biopharma development. we fueled additional a and being XXXX preclinical inclisiran essentially that patient patisiran, commercialization, large launches several givosiran company is with years, get and including we have discovery are then late profile compelling clinical our over have engine that positive lumasiran which much innovative commercial a medicines further the beyond creation, pipeline, Altogether, programs becoming nearing in pipeline of goal a by potential we robust

achieved profile Our in rarely industry. biotech the

So over in latest Akshay? progress with Akshay detail. to that, our pipeline to more it I'll turn review now

Akshay Vaishnaw

good and Thanks, everyone. afternoon John,

hereditary ATTR non-branded to me announced the and Let ONPATTRO name which expansion plan We is month with for ONPATTRO. last our start cardiomyopathy. label potential to wild-type the fitusiran, include of

the of pleased cardiac primary months. including the naive you XX expected impact after patients the data or with This either research. Circulation. with APOLLO-B continued ATTR These inherited for September exploratory Amyloidodis endpoint patients Phase journal now clinical TTR exploratory cardiac is progressing have which APOLLO cardiac APOLLO-B, study TTR potential data new X on with ONPATTRO data fixed have placebo-controlled double-blind, designed amyloidosis is let study were about study are the encouraging XXX and evaluations last the from to to amyloidosis fitusiran hATTR those realignment stabilizers. highlighted with we in manifestations favorably published to endpoint support cardiomyopathy of As us for know, stabilizers and or with receving randomized, FDA with to wild-type enroll the certain

timeframe. We in expect this ONPATTRO study the year in middle XXXX believe a we start that label to of this expanded to it support positive of will the XXXX in

We you that with of the As is our low-dose knockdown low-volume we're as XX% once that ATTR best-in-class potentially TTR-lowering for an vutrisiran Vutrisiran approximately a generally attractive launching subcutaneously initiated delivered It's therapeutic also know, believe last with agent. label for injection achieves subcutaneous X amyloidosis. is the investigational very be tolerated in which where patients. well could vutrisiran Phase at TTR, study Late and This at XXXX, and in nine we months ATTR an open into ATTR innovative HELIOS-B. vutrisiran-treated looking be patients possible. HELIOS-A option of as we an called plan will are the will year, the polyneuropathy. study we is to study market vutrisiran's vutrisiran, the APOLLO HELIOS-B successful for growing significant study of which entry quality outcome design in arm neurological Later wild-type If and in at bringing to rapidly life facilitate vutrisiran believe patients opportunity. initiate to aimed impairment also placebo market comparing the the results we study. of as

full of hepatic month excited from RNAi therapeutic We about just the the from results investigational our in away acute development ENVISION givosiran, these the line to for on porphyrias. move and soon reporting results siRNA. see study now Phase of to X very conjugated Let's Phase top X study treatment first-ever GalNAc from a we're

need or plan we to Saturday, we study are presentation for the porphyria new to April be which the much there's with pain, porphyria our Study of with therapy complete dysfunction could fatigue, morning porphyria is frail expected. including for at are late complications suffer Liver and our next patients the Recurrent study on the acquiring significant will early results a administration. enormous high in hemin iron patients reminder, have life-threatening study enrolled endpoint EASL also attack the porphyria with patients XXth NDA patients. of with XXXX. in disease data manifestations month underlying positive, renal these and Clearly, XXXX rapidly annualized can we on had than results Society therapies attacks overload a and neuropathy ENVISION from results in exhibit the approval Topline support from also submission very givosiran attack frequent unmet more primary and Vienna. this rolling liver of rate in a presented If year, As in hospitalization. expected disease help Full XX also to often and the This the safety. an chronic chronic and European enrolled originally for of middle population disease. reported include and

we're to study reimbursement decisions. expect EAP global to a England and to double-blind givosiran developing the recent open I'll available X the and the primary paper journal last progress oxalate transform group study in coming to primary in In we this hyperoxaluria we're just relative PHX. RNAi acute published this meanwhile, to for sixth or proud six from Journal ILLUMINATE-A Based to givosiran X type patients study extremely pleased Phase the is results our therapeutic now placebo-controlled Medicine therapeutic England at potential scientists, reduction to approvals to Journal high year. The is lumasiran, approximately the patients patients This with that placebo. from lives results, publication PHX. We New promising at randomized an to collaborators. yesterday we New the lumasiran relative XX urinary is to that of of Phase our in study on clinicians, givosiran RNAi a believe make enormous of turn for regulatory pleased X clinical the an reflect months study endpoint results this were Phase describe of also baseline with X/X is prior chronic and a initiate of We're porphyria. now

topline early in regulatory results positive, to and We initiate XXXX. beginning late ILLUMINATE-A XXXX, from if expect to report filings

in the this hypercholesterolemia intent in in for initiate advanced of with partner to to renal trials. our patients age being Phase preserved The where less ILLUMINATE-C development Phase treatment in by ILLUMINATE-B development study X In in Medicines addition in of severe traditional program fitusiran we with six highlighted X the the than impairment. focus Company in Phase Sanofi our function renal at pivotal just looking more Incsclisiran ORION study both X hemophilia, partner X Outside program. the of full mid-XXXX, the currently I in is ATLAS Phase for program. years trial, patients and

an pursue up especially And landscape therapeutics can about delivery disease system and the central with This Finally, in RNAi Medical let me Affairs excited Alnylam Barry to exciting that, the at one our eye. RNAi made that and opportunities nervous is of Barry? we've the area opens now we're of therapeutics that the that progress to over we platform. leveraging by progress. Commercial review it our turn and

Barry Greene

Akshay. Thanks

we pleased ONPATTRO the As on progress John extremely chain said launch. Medical with Commercial build we're and our and Affairs supply capabilities

to that Program, of we receiving of in some very worldwide. pleased market can year-end dynamics year-end United that color about a representing our you XXX patients patisiran achieved In $XX.X onto receiving now ONPATTRO for on we've forms terms our expect the over Assist net look as commercial revenues drug our patients start you've had year global studies million received Alnylam $XX.X that clinical hub. as million To QX of time pool as we and we on ONPATTRO we commercial future XXXX, Expanded We're the from at commercial full patients in ONPATTRO. we XXXX, patients over performance, patient States, include XXX in in give additional had if of read, come Access in XXXX.

and our XXXX, but forms. of patients from to hATTR our see to we pleased which As start very in start forms other Access receive patient physician patients also start we speak for since specialties, did that many very distribution the we're U.S. not also now neurologists, demand, including of participate pleased Program. prescribers ONPATTRO represent XXX channel. a Assist multi-systemic supply ONPATTRO launch We're outside our number via amyloidosis. really to of received nature a mix most, who reminder, to growing a U.S. hematologists see forms now getting Alnylam Expanded cardiologists, the not year-end through We're of From of have all that

forms were start from in of XX% approximately mix, patients are payer of terms by expected In The States by we from while covered commercial covered Medicare approximately as patients insurers. United XX%

in ONPATTRO encountered reimbursement from Importantly, we have not headwinds the on significant U.S.

through drug on we on patients U.S. payers. of each fact, currently the have commercial In five top

commercial progress have around or of We and patients by solid also to agreements expect XX% are making on covered value-based VBAs. VBAs

polyneuropathy countries also progress the together advancement where its Europe, procedures patients, turn hATTR authorities me reimbursement representing with vast pricing made we've patients to and of let majority example amyloidosis of EU Now, across Netherlands. XX and in good Germany the progress of in with authorities favorable positive the authorities, innovation with in Recent our designation reports ONPATTRO alignment by assessment Europe. Italy in Sweden, includes technology and authorities especially reimbursement

Medical On this rare front with polyneuropathy. raising of biggest diagnosis awareness one Affair the and of challenges in amyloidosis disease improving the is hATTR

screening As program amyloidosis. improve aimed Act diagnosis of at we patients a highlighted facilitating suspected Alnylam having initiative, previously, third-party genetic is ATTR

our our with than as advocacy positive been X, have pathogenic disease for of As campaigns. TTR XX,XXX as out have tested initiatives more also a mutation. samples digital well February success XXX We've submitted, awareness which patient seen of

previously, driver in the physicians ONPATTRO. launched treatment avert APOLLO diagnosis of our the We help hitting stories quarter from addition mind, Manmeet? patient supporting of another to campaign improve ATTR these of Manmeet effort as We ability the with and anecdotal to benefits the that awareness, new contribute to the believe experiences benefits unique With earlier of believe therapies. Phase As polyneuropathy. with their we’re full this now positive positive give study. fourth raising we've patients we patients improving amyloidosis and that physician is amyloidosis characteristics and and to will new in III to promotional year potential diagnosis polyneuropathy in over I'll Post-launch positive of highlights many ONPATTRO's ONPATTRO. clinical performance. discussed demonstrated the will experience availability about other ATTR highlight call turn manifestations and

Manmeet Soni

for good and of issued full a to Barry, results refer quarter and for year the XXXX. our earlier afternoon, financial today fourth Thanks, everyone. summary our Please of press release

equivalents, our a and billion in investments securities $X.XX excluding start balance. restricted risk balance cash, We marketable me with cash sheet ending maintained cash Let approximately with solid XXXX securities. equitable debt

public forma pro our Following of a cash have month, last offering currently billion. $X.X balance underwriting we approximately

to ONPATTRO $XX.X launch recorded XXXX quarter during fourth U.S. the Moving $XX.X now of net of global end since revenues. of We through of date the revenue million, the million and product middle year. our the August

Also XXXB related generally in As expected, mandatory entities to Medicaid our approximately to than higher discount the the XX%, as net gross in discounts net reserved to was the U.S. in gross and mostly U.S. for was for patients. EU expected our

of cost revenues. as progress We payments. for sold to full-year, the in equates actual expected expect will long continue including XX.X% revenues of of launch percent with a goods high-teens third royalties to product to update and In we million on were our be to approximately paid as the which ONPATTRO the gross of goods to net run, discounts normalized to Cost percentage $X.X as product middle we net a parties. ONPATTRO of sold the

a late result end expenses compensation was manufacturing guidance of development $XXX expand XXXX stage million. year our refer here in as as I with expenses and range and lies to and expenses increased Moving the XXXX the non-GAAP the compared were and as Non-GAAP expenses million the year. $XXX.X full to year. The to to expenses million million for prior of results. continue as increased to prior we for R&D will headcount of $XXX.X our R&D for $XXX.X our R&D $XXX.X expenses associated pipeline. due advance million operating $XXX were R&D the related million, or costs GAAP to other increase lower This increase period during in our compared non-GAAP programs full year

will commercial an million, guidance were expenses $XXX.X year. midpoint of increase SG&A SG&A the country and SG&A services exclude $XXX.X additional respect growth XXXX. affairs expense. With of for million and potential expenses and compensation commercial-related to prior ONPATTRO in our Non-GAAP million SG&A to ONPATTRO were to to primarily to expense in stock XXXX SG&A Turning million and for in The to the $XXX guidance SG&A. in XXXX. the range non-GAAP annual million and $XXX expenses entered as $XXX expenses as medical the due compared million. and of expenses non-GAAP $XXX We for R&D was within headcount of million expenses base $XXX to between million launches XXXX. increase non-GAAP XXXX, compared that SG&A range launch $XXX $XXX will $XXX range Non-GAAP expect non-GAAP annual also support we for and corporate in between GAAP million million

marketable company approximately operating We upon support current years plan. based cash expect will cash, for securities current that our operations and equivalents two our debt

As providing XXXX. guidance of now, for revenue not be we will any

continue several we the possibility XXXX launch, will the have better next the our evaluate key John over dynamics once will metrics to it ramp the review guidance to now John? of I goals. and on quarters. hand of We providing market visibility back to

John Maraganore

Thanks, Manmeet.

earlier As include study we continue the of we'll we executing plan potential transformative. is the commercial which both XXXX course up the and study initiate aimed landmark programs was Helios throughout Phase envisioned in we outcome our be supporting while and also cardiomyopathy. Phase starting in and study be hereditary we XXXX. we and our III initiate mid-XXXX Alnylam year execution expansion expect Phase expect X APOLLO-B file to year I readouts be we're wild-type at to with two specifically, ONPATTRO to With our More if our III Phase data HELIOS-A of label planning late enroll to fitusiran the NDAs. positive three shaping six ONPATTRO, mentioned XXXX Overall, equally global report for a to to X

the results line the lumasiran results March. middle company X complete from our completing positive data soon the NDA as NDA of end for of well that With assuming results medicines And as study guided in inclisiran the Akshay study report we in line very filing MAA partnership in And ORION's the the top they submit rolling on we in as ILLUMINATE-A study positive of from from mid the expect we'll ENVISION have late and inclisiran year results and mid-XXXX. top in to to XXXX. Phase by late report year. an XXXX. course our if X studies and enrollment top the to With plan very, highlighted are line givosiran XX to Moving XX submission have in expect an to

also as well of will Of to as rest efforts milestones occur. our continue preclinical course throughout the exciting those as advance the pipeline course, they and highlight will year of

So with our let turn me session. to now call coordinate Christine Q&A that, the back Christine? to

Christine Lindenboom

are you to Thank we yourself and if then to get each in, one ask questions. the would have the questions. to ready you, for additional back in like call Operator, open question to those dialed John. To we you limit queue

Operator

first with our will Paul Thank ma’am. come Stifel. from question [Operator And you. Yes Instructions] Matteis

Paul Matteis

Thanks you One patients Barry, changing trajectory ONPATTRO, seeing was that for so the progress. looks you on you been with has drug in the the I this question times Thanks. channel progress on if much. starting like what comment on Congrats on could for your Barry all the that reimbursement? all wondering how and

John Maraganore

Yeah, ahead. Barry go

Barry Greene

great Yeah questions. – Paul

from is as only many, our on couple So, weeks previous highlighted the a we weeks to many progress. intention of seeing a to we're calls and time get

looks It those where on the of times being what getting like patients examples are about making. really the way we're but un-drug We weeks. couple early We're in coming does coming a progress down. in excited they now, start depend little insurance have infuse

Operator

you. Thank right. All

Needham come Carr Our from question will with next Company. & Alan

Alan Carr

the those the versus year are how U.S. of talk expectation course some take questions. ramps relative between about Maybe can into for you over you year? what's my two this next think I going of your Europe for ONPATTRO on things

John Maraganore

you Alan. question, great to a That's want handle Yeah. that? Barry,

Barry Greene

Yeah.

we're not you we quite on require Europe's we and can XX be really after boots launch and Alan, United to countries – guidance aware. highlighted for before it. So immediately And of we we've August shipped because ground us had approval, Monday from The ready is immediately. to assessment price going. breakdown not technology the that in XX as progress the had we within the drug the countries are We work well in we’re getting overall different, giving the as Other paid where launched hours certain committed. naming launch health like how our States Germany,

the And So how the countries. access Europe we're will in really we're by But order process seeing. and far in right on in working call, determine in through XX the what we're then different progress that the with as getting so country launch Europe happy in trajectory progresses. the highlighted the

John Maraganore

perspective, point that ONPATTRO this a from Yes. is strong Europe demand, clinical the KOL helps itself very there's I'll effort. just and Alan, that strong see lot and with obviously in features showing awareness add, strong our and patient in at that there's the studies they

Operator

right. All you. Thank

will come Maury Jefferies. Our next Raycroft with question from

Unidentified Analyst

Hi. Thank This on Mitchell [ph] Maury. you taking for is for question. our

how ONPATTRO access? have us walk factor of through infusion many Are at-home to how all patients this For doctors you can option service? And into patients? the cost providing reimbursement

John Maraganore

help? Mitchell. want to you Yes. Barry, Thanks do

Barry Greene

Yes.

by the in taken in in the country available. States home something is immediately and European right to all In the It commercial it's is for mostly States, infusion Europe patient certain commercial offered So infusion countries, home in payers. all offered. the the many and now paid and all and that it's and to for, The is physician paid plans talks United plans. United countries by available about single care the Obviously, then is

XX% have is fact, enjoy, They've pleasant like to other the his we patient of see drug hear their us. in the they're patients physician from they research commercial for a infusion. check in people, twice enjoying typically actually their It's we or and out, infusion met For nurses meet chosen is move after which human they us what interesting on – the enjoying experience, patients, surprise to happy experiences. they infusion home marked And patients the actually to the patient that is that once the infusion. and new JPMorgan highlighted after only conference, telling and at this we about patient, infusion

Unidentified Analyst

you. Thank

Operator

All you. right. Thank

next Alethia Young Fitzgerald. with will come question Our Cantor from

Emma Nealon

to Alethia. from some markets? as Emma certainly, that on is seeing progresses? dynamic in any you This these And patient Hi. for look launch expect you Are of tafamidis the switch what

John Maraganore

Yes. a that? Barry you handle And question. do It's good to want

Barry Greene

Yes.

countries The differently many of So at we States in United have Europe. than to look the

the As in United was Europe but disease other know, meet of X the approved Phase countries not polyneuropathy The endpoint, endemic States, it you the in around given study and approved in nature world. the was

used it's for So been years. multiple

we back report polyneuropathy also getting As know, progression literature, is, many published physicians significant in as in to a tafamidis. again, little as months six

So fact, in appropriate, the them looking when patient, dynamic outside an and the progression United for States looking ONPATTRO. and a patients for is in physicians patients, switching to progression assuming on-label

dynamic dynamic the We more different Obviously, and market anticipate something U.S. do to seeing are United the States tafamidis as we'll of a gets in is that. with future labeling. see in the that whole

John Maraganore

and I'll Phase a randomized just a will about chose progressed been patients to the stabilizer because XX% TTR the on that in they fitusiran. either those you to a remind want placebo-control that, add of come Emma patients stabilizer silencer like on the I or previously had III study participate in many of had to of our on APOLLO study availability they

if important experience So useful our data look you alone. an just at and clinical point, that's trial

Emma Nealon

through to from Great. reimbursement are color pricing then And ONPATTRO bend on discussions? provide going you able any

John Maraganore

I that? missed Can repeat you your question.

Emma Nealon

in On the Europe? pricing bend

John Maraganore

to Barry on you comment that? want

Barry Greene

Yes.

to are going a tight very, we As global we per on price it comment at keep on level. vial previously very a basis

Operator

Baral from question next Ritu with come Cowen. will Our

Ritu Baral

why both because apologies for noise. about around some taking you timing Question and the question, for Thanks many assumption, design that of the patients guys. you're enrollments expecting our data? also XX the the Hi months, elements and see how actually patients and potential wild-type view

John Maraganore

Akshay? terrific. Yes

Akshay Vaishnaw

Yes.

study in over So we're that APOLLO the time very confident X-minute there the time from end endpoint distance. and walk recent study, point for months a the know is as so length you suitable -- a point of terms the clinical APOLLO here XX-month of nine is point

months than climate. have the separated significant distance also XX study that walk got We X-minute earlier it the because know of from client

a So relevant time potentially clinically such clearly or than change that endpoints is as point this is significant amenable was end that that. behind earlier a so mortality at to points hospitalization, other rationale

between to the many TTR many hereditary are Now split than patients type and the with mild wild-type respect obviously patients. mutant there

be the part moment. think be the then might how speculation majority a on would experience wild-type, it's to filled the on but hard say my mostly [indiscernible] wild-type with Hard exact timing again study initiation finally three with So with -- right study much the respect to averaging to to for respect specifically comment I the And time. of at that's now historical patients. TTR, of the quarters,

suggested in we feel As we approval consistent have XXXX anticipate to with XXXX timeframe we them. [indiscernible] that

John Maraganore

Thank If because go mute you got noise. on lot you can of background you.

Operator

we JPMorgan. question Thank Rama you. have with a from Anupam And

Unidentified Analyst

long you Thanks taking the just Hey ONPATTRO the value-based on typically how question. get so those anticipate one of agreements for And like? taking guys. wondering Thanks to get those is that XX% then place much of the This for you Barry, agreements, what in remainder covered? is to [indiscernible] for of much. Anupam. about commercialized One so look

John Maraganore

Barry?

Barry Greene

Yes. No thanks.

with really agreements. not on has patient And and spectacular partnership payers patients to hitting in that access opening they've a to stepped finalizing the strategy really ensure access. been and in help useful via treat to really find payer the know you and try with policies even through to medical of offer the really philosophy the proactively agreements, educate their headwinds up value-based And our dialogue value-based we incredibly proven has call, payers. about talked to part we're outside was of As patient as

a So that on give the partnership of the community credit lot payer we have seen.

having covered about the to finalize we've complete and having the we VBA great are conversations without goal of say, back a the VBAs, terms even the into the place year name anticipated back note got dialogue the really going XX% forth reimbursement have the we a of hard as three end of It's at all not to payers with value-based but to this And agreements by It's I of folks it's sort and because VBAs. patients covered. In the with to by issues of running patients said, are in between timeframes, highlighted, and I'd the point. of important XX% that office the well. we of different end-of-year patients have letter

Anupam Rama

Got it. Appreciate that.

Operator

Thank you.

Our question Stanley. Lebowitz come Morgan with next will Dave from

Dave Lebowitz

two my APOLLO-B to How much Are HELIOS-B very overlapping sites? trials are the at to you be groups? with going Thank manage going Are the you completing going same year? question. and for to going those How they starting they you populations? later are this taking to be manage

John Maraganore

a Yes and that's to a HELIOS-B? little APOLLO-B great bit at question you David. comment want Akshay,

Akshay Vaishnaw

to hereditary overlap Yes is, with between from there important some populations say But factors. mitigated is cardiomyopathy. ATTR patients certainly two the several situation I be should involve the protocols that going and wild-type what by study those

of varies months ATTR other with are significant availability it where a that many there all, The territory. them let that approval the may of wild-type very on by of treatment territory despite therapy at similarly be profoundness potential say to of maybe patients some in not carry available for Firstly, hereditary be no them. patients number or come, in not available

recently of And that mutations about and study regulates to between the be with the comes that approved satisfies need that so robust the a geographies availability approved. a to is various being drugs do of or range

or competing are can studies ensure that clinical competing without other goals confident company. of We enrollment we the between

Dave Lebowitz

the taking for Thanks question.

Akshay Vaishnaw

Thanks, David.

Operator

Our with Barclays. next Wang from question Gena comes

Gena Wang

through one TTR Alnylam had a XXX for act. you the that identified taking regarding mutation one A my patients question. quick positive Thank

wondering how for are of many patients Just addressable ONPATTRO? these

John Maraganore

to for diagnosis. details Gena. don't a high a we we its don't great a that on I [indiscernible] and level, because these help community know able basically be mean, at we is question the service This patients. get medical providing patients, are have specific That's

we any about those about a don't patients so And result. more anything specifically as have information

Gena Wang

Okay.

John Maraganore

want you add? do Barry, to

Barry Greene

No.

service many genetic testing that's by pay genetic now done. are that are the doesn’t we John Alnylam to commercial diagnosis. we offer use that There other a and As drugs to for overall need represent a is that being of so will benefit. Act pathogenic, it help fact free-genetic the commercial demonstrates insurance major this seeing all testing said have and choosing add patients to unmet physicians tests. companies other the we’re I many for offer improve patient benefit that The

well community, the to So that find unmet these testing. with in and being need genetic patient's the testing genetic help so we’re delighted amplified the the representing out is need

Gena Wang

Thank you.

Operator

you. Thank

next comes with from Guggenheim. Our question Whitney Ijem

Whitney Ijem

One that? the And data, taking III are And that? givosiran recurrent sporadic. guys, remind patient two do guess, III that us and I Or first estimate? for a of the guess those of sense different thanks terms the help I Are then, data in Phase into think to of epidemiology the givosiran you or should use of is all that on diagnosed X,XXX for on populations, endpoints what questions. about patients? on identified talk you about the based get Hi, an in can numbers Phase headed and the look better the some us how you of we forward X,XXX

John Maraganore

sides. forward great Barry Go epi, Akshay Maybe then can and data should start second ahead. we on to both Two you the cover cover questions. you that look the question the can with

Barry Greene

seeds but the then X,XXX much you Yeah, X,XXX numbers, the represents and the coverage These centers. don't network in is we porphyria based on much, and various and the we beliefs bumps are numbers greater that that they much, all understand had recorded fully universe of at the triangulate course penetrant. patients that epidemiology will. The if

about So, we feel pretty good that.

to rates a able been we've that the attack that study. are clinical The a other keep thing to in way is do mind

we’re As patients. severity commercially, we to with move at forward look data going more of

hear attack, So, attack. be of because I disabled attacks, can than have severity the more patients we patients even that have that one if say more who mainly can of

when how maybe patients at disease us understand our of overall able many the to course and of detail reason will just data and manifestation we help the severity benefit. of we of So patients look

John Maraganore

study Akshay So part. the clinical on

Akshay Vaishnaw

FDA So, that the the the ALA accumulators PBG at I think namely it we those and physician is the and acid really aminolevulinic by convinced key interim proceed of targeting aspect to between we the hepatic levels the allow attacks that acute with that even here to of us looking ALA and porphyria us and are down-regulating PBG. X, to to did do we encouraged relationship that was analysis the And porphobilinogen, ATLAS study biomarkers. and know

frequency not itself and in whether course and are is or two of mediated year, PBG. attacks a attacks or that XX a and there have you the with suffer are year, you ALA attacks attacks trivial, year greater which it who – XX whether patients Now have is by of those a

and that in interim if measuring be study the we're hope out. enter fatigue but pain to I symptoms those also and think convincingly with not the recall have and bodes the abate believe nausea but patients let's I we frequent based scales. that again acute shows from we ALA need they consistent [indiscernible] right. But help even hope endpoints All don't because well you. data analysis, that them. So between And if this and and this they and Phase for patients look drug even then PBG, what is indeed anticipate III patients or they I attacks, reads well reductions do And study more at attacks. these the will are those the three sporadic come for let's attacks. and out these horrific that on and Thank then two and when that should too just attack durable reduce, or which the going with or maybe bodes and attack in suffer help

Operator

question will Our next Leerink. with SVB come Mani Foroohar from

Mani Foroohar

quick I’ve one Hey, thanks question. Manmeet. my taking for a for got

the runway a pivotal terms number that plan number CNS of out population what's commercial of into to a to R&D because additional potential on the that you scratching years come infrastructure the operating two up APOLLO-B vutrisiran the follow-up. regarding launches, then baked in address assets of plan portfolio. a population, got build-out have of and little quick So build incremental around of liver I'll HELIOS to for bit is expense backed what I’m readouts, of any

Manmeet Soni

Sure.

optimum you Phase plan, X for that guidance of the covers our which for if building gave we inventory up range plans of the givosiran. all million R&D the and prefer million Mani, on $XXX to going all to initial for $XXX when this So trials are which

So included all for XXXX. our is guidance into that

Mani Foroohar

the how as as SG&A the stock-based in do comp growth around year-over-year how non-GAAP we component percentage R&D in quick And chunkiness think the should in approximately potential approximately growth of a Should we about about we expenses think the with expense, Okay. non-GAAP in year? and line line -- follow-up. events this

Manmeet Soni

are pretty the our and expense non-GAAP the we stop dependent to highlight of difficult XXXX. because you of to stock-based that depends it's this for And as expect Yes. we what our it expenses upon XXXX and guide that's in performance your I GAAP estimate our think range -- some not to have most on to those milestones taken compensation very reason or our we realizing couple compensation simply, had expenses, should answer a much in factors. measure able to But stock-based question guide

You should from a there. not expect huge jump

John Maraganore

do your you And Barry, to comments? want add

Barry Greene

Yes.

Just very planned the you to R&D well for your of have Phase the here in baked X kind time and expense give in that asked color we horizon. were about, some the Manmeet answered expenses as fact

built launch all leverageable commercial across for of preparation that of givosiran, are supply launch. terms capabilities In medical the the for givosiran and chain affairs we

to has added respect. little in very that So be

of kind population as be will small of and to overall prepare a adding pretty percent We customer-facing thast our roles base, for but givosiran. additional

John Maraganore

just take approximately our be And the fact and starting our mean, small -- through to further investments that -- of will there’s clinical those just one as are step cash still two-year very you during in balance time. there studies it just that of Mani, mentioned period mean, of I light CNS period ocular I the well, two-year

the that's that But it area is we advancing So a part are with of not really focus. major expense. an strong

Mani Foroohar

in the two, Thanks helpful. want ask Great. guys. so to I queue. really That's I’ll hop back

John Maraganore

you. Thank Great.

Operator

Vincent Instructions] our will you. question from next right. Thank [Operator come with Bernstein. Chen All And

Vincent Chen

events both siRNAs typically you very to-date for LFT study Thinking you guess, and LFT example, ENVISION to us I question. characteristics understand the occur towards and simply or much of help is my occur which givosiran elevation the these occur likely patient liver typically other understand the throughout better those elevation, of likelihood for of treatment points something this some or potential be will for better givosiran to would of given of function trying typical And treatment? sort which be at attributed a have in are also fine? amenable expect those in additional seen mechanism? with readouts is the that this about course think early Great. can won't sarcastically some test the be for patients thought the one-time those taking like to right you Thank now, response givosiran course the elevation could similar to to the you a you course programs treatment and highly event where or various on treatment patients likely minority to a they is in one fairly of one that and rare with as

John Maraganore

Akshay? you. Vincent. Thank Yes

Akshay Vaishnaw

have [indiscernible]. changes I X% to X% the as LFT would for of patient firstly on and it's seen platform that about patients, transient would say ALT are of I qualified -- in Yes say do very thank on RNAi are Vincent given may to that on of I appear that you come LFT. not reported we they tend mean, get of minority question. the the across typical months the the characteristically to in platform And or which they and weeks irreversible come of pumps within they therapeutic. initiation when

including had patients of all. as the be very there being to no have Medicines you've where to a them of clinic the that where in important believe take we have they over think LFT. note to been examples I concern for many who over reported and at LFT The Company And by year. regard plenty last significant therapeutics Now, significant the guided of to heard appeared that exposed is Phase X,XXX JPMorgan completion inclisiran, safety of them and And DSMB changes at met have X from now, I significant inclisiran RNAi we three no expense should

LFTs the occur remember this maybe and of interpreted that terminate that are very our I properly, patients, of I a task drug one the of stringent also in question question guess your large reporting predisposed last happen we can more let's being they The patients one in it might what population, we many of So, agents. fragile. if for do or often very why to

overload B or and human their significant closing iron in factor. may with those what may treatment have porphyria, background closing off LFTs as For in of treatment risk hepatitis that example, of many disease in many of in or previous the reported we hepatitis have from these context patients physicians and experience [Indiscernible] a way a C to synergize patients fitusiran

outcome seems complicated, to but are aggregate this these be rather much it's So, LFT it changes the as filed sequence recently and INDs investigating we event, target so couple risk to think impact and optimistic with the of will be off But, of G&A see follow modification studies to elegant C thereby of usual effects HBVXX of transient that whether year. learning very I aggression and those and and in are benefit drug. overall, of this favor we're reversible AATXX still sort

John Maraganore

a in the full and the as of obviously We'll with we'll full there Yes. concur you And add was only analysis, results I interim coming enrollment. till time But wait comments update on you weeks and I the update with just that this then. results would discontinuation the just well. on we'll Vincent at that XX% study a as there Akshay's was -- of from the one reminder

Vincent Chen

Thank you much. very

John Maraganore

Thank you.

Operator

you. Thank

Piper Make Next Jaffray. sure -- of from not comes Ted question Tenthoff you're

Ted Tenthoff

sorry. taking questions my question the call. Nice for Two too in update. Yes, if late Thanks Thanks. may. I

have in Firstly, mixed maybe treating Do Do how into you about kind you Thanks. mixed guys patients How coming the thinking even may some of comes the polyneuropathy in patients, market involvement? both? prevalent, that those situation to, kind docs detail in certainly patients? when do those the cardiomyopathy? more now sense are you do it I mean more is be you it'll a Tafamidis guys in get get cardiac manifestation would whichever where but a towards leaning they of, you Tafamidis where cardiomyopathy, think ONPATTRO think

John Maraganore

a details is I'm I just into our competitive. get Barry let any but question. answers answer, remind to going you not Barry is we it, around are that Ted, as Yes, going obviously a that before great to because strategy

into getting you So, Barry on make can maybe details. some high-level I think any this comments without

Barry Greene

Yes, promoting best States have is would I Super defense Look good on-label are we United there different Bowl I hereditary to the than offense, which that. treat amyloidosis mean is hATTR is but The maybe the polyneuropathy patients. said the in Ted, out

educating have awareness cardiology disease disciplines across uptake the multisystem we as nature with we're the multiple interesting Now, broadly hematology and -- representing you've seen of disease.

And not So, polyneuropathy believe an best patient that of recognizing experiences. in choice. patients to for sort physician drug patient the on-label good data the been this polyneuropathy, you with but patient, is have of experiences and we for to patient, every And and often as patient on-label -- our call that approach a get very commercial that sure positive simply stories the good make drive head-to-head an have know that's we those is lack if and based upon we're is hearing patients are ONPATTRO studies opportunity physician the we on-label launch data others. certainly APOLLO what get and

Ted Tenthoff

to data APOLLO U.S. discuss are European then physicians? able the And Yes. and/or cardiac you with

Barry Greene

discussed. so is It

can United In have So, is be what we the rules in in our no. But data not the States are allow. The salespeople promotional on-label, answer promote so on-label. can Europe, it general country those context, the those only In on and on-label, so a country depends -- are engaged.

data, come request medical we them. for to to up of are some of only a letter; those context reactive the and in scientific certainly They ask ask questions information, the information to talk ask variety free in person the course, medical show have can physicians interested about they are of they techniques But upon physically in can exchange. for and are talking which physician requests. for Now,

Ted Tenthoff

our just one all friends How because and Yes, program. HPV really last And and thanks One the that may going I that's Vir program? clear. for like appreciate things questions. if I with are the the really I

John Maraganore

is volunteer we from important ago he It's Scangos just the excited and an It's look and this just The dose progress later program. George in proceeding that they're data going saw was year. study great. forward a effort escalation of with will having weeks to making. couple I the human

reminder opt-in the at -- XX% opt-in of a that Ted, value to of As Phase we X end the an free have of program.

to that. we later success in look that effort So, and readouts from year forward economic this data strong very the of have we incentive

Ted Tenthoff

All right. Thanks, guys.

John Maraganore

you. Thank

Operator

Thank you.

Our Paul with come Matteis next will Stifel. question from

Paul Matteis

for Thanks taking the follow-up.

rationale the the on could the ones if then Just saw have a Solaris you suggest for IGA clinical study on couple And announce there different program design? asset, could a suggests was and gravis is much. I and Thanks if biological plan same and GMG, I your so wondering, I secondarily role talk CX radar a on comparable you myasthenia nephropathy. potentially that data quick maybe was cemdisiran. that in for a profile? that definitely cemdisiran given wondering about

John Maraganore

both. are to those two Paul it our great resident cosmetologist turn going great on Yeah, Akshay questions. comment over -- I'm to to

Akshay Vaishnaw

IGA in is Thanks, resulting of renal failure. in need. John. Fitusiran nephropathy represents relatively globally IGA in one obviously, studies for straightforward common inflammatory the most nephropathy in unmet addition, significant five The

including for get that the iatrogenic The not better no complexes be and And autoantibody activate of and complex to is because an so activation the of local there's due will -- significant others and evidence themselves failure. in worked is are is products fell renal glomerulus know that complement by the deposits complexes globally in thousands complements. complement out, we that and folks clear but immune there to glomerulopathy we them it's see these activate of question and And more impairment basis many or renal finally pathophysiology surprising disease hundreds know and depositing these the CX there. totality complement that the you complement deposits need part help

for we study they rationale in and so on of complement run-in those what's complement in a doing this for renal as we gravis, of combination with indeed is understand already disorders, we’re setting So to we've validated with and that we'll get we the which do the other for strong expanding proof-of-concept turnover is saying think then the going of We're and inflammatory for studies to into period a renal patisiran expand myasthenia a time. hope complement iCAN terms hand, for with inhibition. range period and this initiated study as in function patisiran to a indications all broader prequel

I hope your questions? some of So that address

Paul Matteis

any gravis, there? myasthenia on additional thoughts And thanks. Yeah,

John Maraganore

-- if last that which indication, of in part simply experience, thesis sort yes complement's not eculizumab plays No, say interest the that cemdisiran his the I the in believe but in will also indication, that results wrapped recent of that the Paul that out holds is interested I we're, -- raw that validation be that test it we Akshay I in think obviously, think to regard. it of of the question, only data role in regard think into do in encouraging for setting. And to that

radar, specific have that it So is we this time. guidance no certainly but giving we're our in in point there at

Paul Matteis

much. enough. okay. you, Fair Okay, All it. right. Thank so both Appreciate

Operator

Thank will from come question from right. Sachs. Flynn All our And last you. Terence Goldman

Terence Flynn

question. the taking for Thanks Hi.

get how already of if apologies asked. line can And you so understand, will actually in late, I in answer be insights the in will can't terms maybe is on just the ONPATTRO the start versus want data this on how data EASL the you. January disclosures. any strict much top if Conference? March press not jumped release? press ahead Thank release guys how are they us just December? in givosiran, actually I'm I sure to much data But forms in about tell that, of you share Sorry, you can

John Maraganore

those our we we'll do we're on any as because you pleased -- quarter how quarter going, we're me unfortunately it's color But we John, we Yes. need first our of mean, is this fourth I with with launch Terence, is let questions. and reported think for again, how wait answer pleased both January, to can't results. give going.

Look, on line? information So Point of that's patisiran secondaries report the number information, of and safety the do data that top investors we example And full two can the expect se. any but data. -- what we what data, hit not relevant one. primaries is then, data safety good we out, top APOLLO that when findings, which per certainly point the commentary tables line what understand safety I were so on balance safety enough with is number to think will without the enough p-value of on on

there's would a in emerged at of line did looked XXXX, good example sort patisiran that's of that a you we we the other to. If top If look that things we whole consider, else at will compromising think that without at template presentation you add to the as what our look good deal day Akshay, guide would anything metric. EASL I that’s that? to to I but that a

Akshay Vaishnaw

I a good job. think you. Thank it was

Terence Flynn

Okay. Thanks lot. a

John Maraganore

Good.

All thank Well, Okay. you. you. right. Thank

So with for thank are that, us We're from to soon, afternoon. I make. data look the forward progress the on XXXX want and to givosiran about everybody excited updating we especially very late to joining you ENVISION. this upcoming that expected I

Thank you So everybody. stay tuned.

Operator

teleconference and may you, ladies Thank today's gentlemen. now you concludes disconnect. This and

Alnylam Pharmaceuticals (ALNY) 7 Feb 192018 Q4 Earnings call transcript