Alnylam Pharmaceuticals (ALNY) 11 Feb 212020 Q4 Earnings call transcript

Ladies and gentlemen, thank you for standing by and welcome to the Alnylam Pharmaceuticals Conference Call to discuss Fourth Quarter and Full Year 2020 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'd now like to turn the call over to the company.

Good morning. Vice Investor Senior Communications and Lindenboom, Alnylam. at Christine President Relations of Corporate I'm on are Vaishnaw, the Executive today Chief Officer; me With phone President Greenstreet, Tanguler, Jeff Chief and Commercial and R&D; Yvonne Officer; Officer. John Chief Officer; of Akshay President Operating Poulton, Financial Tolga Chief Maraganore,

the Vice for available Q&A. Orth, In Head the and addition, Senior Andy U.S. line of and President Business, is on

call, section the going For the accompanying can those via of our by Events you be of to page conference the of participating Investors accessed investors.alnylam.com/events. slides website

certain provision will Actual Harbor which the Safe the remarks and outlined and During of Securities your you brief today's provide XXXX. and Reform general purposes slide results of Act call, statements prospects, an expectations, preclinical Yvonne commercial constitute clinical Litigation to would provide will of forward-looking various these plans some the will for discussed contain reports will updates. Private under materially Alnylam's will indicated upcoming those differ result future Tolga call to before Jeff including summary opening remarks as with the update questions. some on the I provide statements this call file in remind on Akshay factors, by may a like two, as our of our from most quarterly important global those recent financials forward-looking progress. a recently that John and SEC. on provide will concerning milestones, introductory our review context. review

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

a ever Thanks, of successful all on by joining pandemic, strongest commercial ONPATTRO platform. growing in organization We years delivered had Despite thank strong product we one Alnylam global productive everyone XXX%, GIVLAARI. you and revenues its challenges continued the faced the with for Christine, highly as over by for today. expansion, the call R&D XXXX commercial COVID-XX line our driven with and a top execution

of the common populations. across includes to And of on programs profile. we four focused the and pipeline, disease reach partners includes of approvals, together self-sustainable XX which started in to then This countries. financial access with help XXXX with Leqvio rare XX approvals countries. six Underscoring the ended two OXLUMO and products, achieving success advance financial approvals remained both year the in We the Novartis products, continue with in the the We EU EU. our access goal in XXXX, we a at XX our us and and and U.S. discipline

year-end and/or within important moment, for fulfilling companies study in of exceeding Akshay vutrisiran. we but ended patients the period. rare review to with an exciting HELIOS-A goals over and recent highlight growth first and our through in have is new pipeline to and positive our around X from high the a a product with progress proud PXxXX label achieved revenue very the chapter ever just Alnylam's XXXX said and Alnylam We're PXxXX. back becoming in XXXX. goals boldly for of our Alnylam. XXXX announced profitability diseases the and aspirations performance recent a yielding engine XX% organic an period will is in results pipeline R&D Phase world, with have Alnylam transformative new strategy is one candidates that are XXXX and We financial doubt, additional medicines of biotech forth Without Alnylam common this most our now to aimed exceptional best-in-class by both product excited five-year the sustainable robust supported from potential expansion, successful CAGR

expand Importantly, in and believe Alnylam the with cardiomyopathy polyneuropathy, amyloidosis setting, assuming wild-type hATTR approvals. clinical ATTR ATTR in continued positioning expansion that growth favorable before with significantly our franchise, opportunity vutrisiran results expected even can our we in our

rare Now commercial Alnylam for leadership. the affairs Alexion excited call. global future my a to Chief Tanguler Alnylam both Commercial welcome joined our Officer, franchises. and in following our common Tolga? Tolga we're and review his as to medical his of let at progress, about commercial it's turn to Tolga efforts Tolga. first the pleasure me of call With disease Pfizer our earnings And recently that, and over under roles

everyone. and excited good to team. welcome, join Alnylam the more the and warm appreciate I morning John Thanks, couldn't be

get started Let's review performance. our of commercial with a

million global achieved quarter, compared the in $XXX.X the XXXX. full product growth XX% approximately And ONPATTRO, we we global representing QX. net fourth achieved in with in revenues $XX.X year For ONPATTRO for million revenues quarter-on-quarter

continue to As notable, hATTR along continue TTR of PYP of over pre-COVID with just the In and believe of we hATTR commercial we We of believe our XX% XX% U.S., patient regard a to see remain December in XX, with over treat compliance to use strength the U.S., were polyneuropathy the covered. with we to rate U.S. as worldwide. at see In the with use stabilizers also X,XXX diagnosis rates we also concomitant to of is saw patients approximately continue phenotype increase, patients scans. steady ONPATTRO on lives wider demand levels. growth treatment access to in ONPATTRO mixed of leadership due availability

$XX.X revenue approval rest in in We now Taiwan. XX been recently made countries, and the has achieved markets. quarter, ex-U.S. received regulatory in the world. access to Market of over progress in we ONPATTRO encouraging very from with with fourth Turning the million

dynamic U.S. observed the ONPATTRO. XX% is have of represents believe the the reverse ex-U.S. disease we or noted polyneuropathy from switching attributable important this of halt with patients ongoing we which to an potential As stabilizers, more patients ONPATTRO And to is manifestations new outside than

amyloidosis, to Act, Alnylam genetic the Canada and our committed U.S., addressing diagnosis and remain also challenge including of team of with awareness disease third-party in affairs medical the screening facing customer raising Our initiative Brazil. hATTR improving

tested X,XXX have for As have out mutation. XX,XXX XX, which TTR positive of submitted, January of pathogenic samples been

We are encouraged we've this and volumes we recent months, in testing continue. the by trend seen will believe recovery in

also we have by In continued new strength patient steady growth. patient findings and being continuous some new expect mostly geographic XXXX, other for PYP seen for indicator driven scans performed, in additional leading We growth with expansion. ONPATTRO,

the revenues XXXX. compared million Moving revenues net million QX. growth in onto GIVLAARI. in global quarter-on-quarter $XX.X We GIVLAARI quarter, XX% in representing achieved we full $XX.X And achieved to year global product the for fourth

patients GIVLAARI approximately commercial As XXX treatment XX, of were all December worldwide.

of XX strong, U.S. including VBAs finalize VBA access We U.S. agreements, over the for state or having lives. Medicaid. covered Our now now value progress based with patient for been access in first level confirmed MassHealth has have XX% with

as baseline We of region to policies with adopt of saw patient have the countries. as in to number payer without we're in and with The date, the well headwinds great CEMEA experienced any medical reimbursement France, Italy GIVLAARI ATU Germany, pleased in strength restrictions and notable to from not of plans majority progress named attacks. well, finalization see our supply in launch as sales other

mid-XXXX. geographic XXXX, September along expression completion also patient NDA submitted of Japan, ongoing new in and growth expect In was in with of findings. forward we and be We launched our steady to look is review in driven of by continued to expected the which GIVLAARI,

the name first early global with for lumasiran. Europe. and launching XXXX, new November, in be the will encouraging excited EU in patient as launch and product full early approximately net progress forms million, the we're fourth from start eight of in approval of our year third brand for and U.S. this achieved the year-end XXXX quarter demand Since to OXLUMO, in $X.X receiving we've medicine And for we're demand. strong, received of revenues December, Finally, pleased representing the launch Alnylam. of see

at our EU As with patient and are U.S. We're who philosophy, work, in OXLUMO launches access establishing we patient by and made making to the and features. in need space being our VBAs, adjustments able it. adjustment guided patients prevalent the pleased with need with payers hard sure other progress access including are

driving for initial in back to R&D resilience pipeline the OXLUMO. even launch the now at year, face and fourth the capabilities and to now I the progress. continue our GIVLAARI of will turn growth the strengthened operations, highlighted capabilities and of engaged supported of an patient which are adoption uptake, With communities, I'm meet teams the success, And over ongoing growth. environment the challenges advocacy review with awareness, quarter the In the virtual continued and the by over of recent our actively full Akshay? delivering broad ongoing in pandemic. Our we've past to and conclusion, it Akshay looking so year, of patients physician unprecedented the leveraging challenging ONPATTRO, team's the needs that, off impressed

and in start approved ATTR and with we're treat everyone. ONPATTRO advancing two good morning, around candidates Tolga amyloidosis we're efforts where markets patisiran is committed study. in vutrisiran. wild-type our to the and patients. multiple world the hereditary ATTR Thanks treatment this currently I'll our product the amyloidosis amyloidosis. polyneuropathy associated hereditary APOLLO-B expanding products the cardiomyopathy label X both for of to Phase conducting in ATTR the To We're end,

enroll advancing completion development us injection, delivered put top-line quarterly patients readout in is subcutaneous track vutrisiran, in to in mid-XXXX. is also on We're of early and ATTR which continue expect to also amyloidosis. APOLLO-B would XXXX, We in which continue for for by enrollment and

X studies. Phase Here, we're two conducting

Phase first in HELIOS-A, hATTR is patients amyloidosis X vutrisiran which study polyneuropathy. evaluating The is with

of nine month, from subcutaneous a study, injection encouraging impressive the safety demonstrating vutrisiran. once last month very positive Just announced with we and results top-line quarterly efficacy

measured Specifically, vutrisiran endpoints at primary both months. met secondary nine and the

QOL in with as speed showed achieved improvement the historical historical highly neuropathy compared compared placebo study, a Norfolk the improvements APOLLO assessment. with impairment endpoints by gait placebo. vutrisiran mNIS+X the Also, significant in As control secondary from measured and vutrisiran

neuropathy reversal with polyneuropathy therapeutics to with vutrisiran RNAi that commensurate improvements Additionally, what observed can of we've in in quality the achieve study. manifestations, baseline, APOLLO life disease impairment patisiran and demonstrated confirming relative of

considered were safety deemed disease patients a function similar and infections. fall significant five site related the Injection AEs placebo tract reactions rate as were tests. or effects significant occurred There to observed an in changes or and at dyslipidemia the NT-proBNP being death year. lower discontinuations on which the profile. of were no There in led which These reported demonstrated endpoint, UTI. in drug. in to patients and pain two all encouraging historical also to that than of vutrisiran comparator mild study SAEs to planned or E.coli receiving endpoint was nine study the adverse data occurring in X.X% more to liver due clinically related by transient than common and two and events nine, cardiac were tolerability observing of we arm neither month diarrhea, month in and part events XX-month X.X% the vutrisiran are to include Vutrisiran group. later collected We the itself additional vutrisiran report urinary extremity, in XX% cardiac

in approval. in XXXX planned overall what's mentioned, to fifth assuming to results in And market file exciting positive RNAi mixing early to hand, our particularly these With our opportunity treat polyneuropathy is we've to bring market we and patients. up of about in XXXX, expanding early NDA therapeutic as aimed regulatory the share, vutrisiran type

study X Phase has is HELIOS-B, study been is cardiomyopathy. And with vutrisiran conducted patients and in ATTR second actively wild-type The hereditary enrolling. this amyloidosis which

later regimen also B, every or the HELIOS-C study and OXLUMO, primary recently in to first ATTR regimen months evaluating of the our dosing vutrisiran, addition treatment we vutrisiran this in to now to for in RNAi Finally, planned and hyperoxaluria of in prevention HELIOS-A Also our to we start with turn expect as a approved XXXX, initiate study six are PHX. progress I'll EU we therapeutic early and once XXXX. of U.S. the X amyloidosis. the manifestations type of for for

really also patients and the a trial evaluate ILLUMINATE of diagnosed safety been Enrollment across patients the overall the intended clinical to of ongoing later expand PHX. ages year, severe program full We're renal the more in has treatment all OXLUMO to could studies Together, and we of clinical lumasiran X Phase excited in X impairment, including in comprehensive demonstrate Phase with with comprise patients OXLUMO study efficacy to continue of completed and opportunity. the We initiate renal stones, in data a safety dialysis. XXXX. evaluating of development efficacy ILLUMINATE-C on PHX recurrent the spectrum the which expect for

or product As inclisiran late-stage additional globally. for programs approval partners. EU, has and for Novartis, development RNAi which year to findings that in has Leqvio common XX a additional with be disease in of completed These mixed in dyslipidemia. Novartis. partner the Leqvio are you the the know, amongst top we our with two the EU approved treatment approved last first hypercholesterolemia of include have with or the for Novartis partnered therapeutic the adults was blockbuster potential On

Novartis the third-party received at concerns manufacturing CRL As unresolved and has or in conditions related Novartis facility inclisiran previously, the related plans safety to to response The from raised the QX to any XXXX. advocacy Europe. inspection the not in been communicated FDA QX facility its FDA due or submit of has

We do will it process. to are everything Novartis can this accelerate confident

Our late-stage in development programs A Sanofi. with the ATLAS also program. and evaluation B include inhibitors partnered X Fitusiran for or Phase fitusiran without in hemophilia is with under

will reduction X can be thromboembolic that received Excitingly, Sanofi the dosing less We monthly up monthly XX weekly. to this fast-track approach other that resumed events are evaluate We been report previous associated XX frequency once believe high fitusiran of differentiation has two XX% to provide are to a antithrombin ATLAS further optimize than options, And fitusiran subcutaneous Sanofi in would given that Phase depending were those now once normal. once with every announced in pleased will designation. tailored has safety of reports levels recently versus dose and for also in milligram a regimen dosing which antithrombin to studies. on the and titrated achieved. milligrams, level patient

great also with programs. our Now, to in and our clinical we addition been late-stage early believe programs, we've mid-stage making progress

opportunities. now NASH, of common now believe properties diseases pharmacological of diabetes others. hypertension, for therapeutics therapeutics of such of disease the is One to prevalent is into exciting success. And settings, expansion many as the in and RNAi our the disease rare needs We parts beyond provide address time at foundation the story unmet the RNAi amongst gout

mid-XXXX. We're genetically the great ALN-AGT transitioning thousand with start investigational for patients Phase will also to Our uncontrolled And treatment and is now target will inhibitors angiotensinogen which studies, target is RNAi as in hypertension. of example. evaluate our potentially start program X and RAF a five X therapeutic our with a monotherapy, X combination KARDIA ALN-AGT the validated of about KARDIA these studies in with in hypertension.

We with a NASH promising development partnership the in X program, of treatment for have ALN-HSD Phase Regeneron. also in

be programs are our delivery over four CNS In by to on continue continue Notably, supported preclinical to addition, and expect four deliver poised opportunities and Overall, strong filing human ocular the programs strategy XX this end and rare excited continued preclinical two beyond more near diseases achieve many the per aim to we in couldn't summary, transformative annum truly per the now INDs bringing In INDs make me our Jeff term, positioned our I medicine. new our of for results. for we're patients and see by PXxXX over let the four to lung. genetics mid-XXXX. efforts common we be and/or CTA liver, first Regeneron eye, to we track annum impact we're tissues, RNAi are the our it and best-in-class and turn to on in make therapeutical medicines. progress plus we program medicines Today, Alnylam With time with RANi. financial advancing as Alnylam remains liver. in CNS, to highlights span Jeff? and and to XXXX. that, to of for advance with future ALN-APP remarkable in review now a about our to progress These

across results, for everyone. quarter excellence, disciplined XXXX After commenting I an capabilities full XXXX. year our our we was strong on managing top financial robust underscores our Akshay commercial growth and provide fourth while Thanks, delivered and XXXX also morning, guidance good will line business. that and year as unprecedented Alnylam's operational investment

ended really level just Tolga the our with one XXXX, the the compliance pandemic strength to QX QX pleased U.S. consistent quarter. Inventory following of continued following: in the consecutive quarter returned results, versus with As when growth, quarters in two of therapy, challenge inventory compared a increased our growth during strong of driven modest ONPATTRO with demand the and X% sales patients reported with impacted over launch. We broadly across channel QX on pre-pandemic during XX% with driven highest versus increased demand Patient primarily with markets, week we're increased QX in in growth we the reduced U.S. double-digit representing We're since patient the XX% with the new sales of stocking quarter remained patient by QX U.S. QX destocking XXXX, performance by addition international ONPATTRO levels. Japan. and highlighted, In by of and remaining with the Europe

at there Japan a Additionally, year-end. in inventory modest from stocking was benefit

generating We Europe in in from revenue, GIVLAARI. was quarter, representing Turning XX% third the and to results as markets, for two XXXX, Revenue to a generated had XXXX. net fourth expected, primarily growth million of global compared France. our Germany strong $XX.X during quarter

with of we saw pricing and secure two and reimbursement, anticipate additional across XXXX. its Europe we in As Asia coming GIVLAARI we ONPATTRO online for in markets year commercialization, as

P&L a our approximately the XXXX contributing and were year. sales for and results million was which double with Turning fourth its summary now collaborations $XX.X launch XX% Total of full the Gross due Leqvio. total approval to due quarter, that $XX primarily ONPATTRO recognized million increase XX% XXXX. in occurred and the the revenue percentage a inventory primarily XXXX, was from for Novartis QX, from following initial product revenue quarter collaborations for delivering than milestone as QX $XX of to from up to XX% EU Vir XXXX year. December ONPATTRO around versus Regeneron write-off margin quarter more million our of XXXX $XXX GIVLAARI Net million, revenue more were growth than in for full and a in from

to expense of level period decreased the expenses the high XXXX having in a XXXX same clinical XXXX, primarily quarter associated compared to future in non-GAAP clinical due R&D for trials. with material manufactured QX Our fourth

period Our to investment XXXX, to non-GAAP launches of the in compared the and increased fourth same the activities SG&A primarily commercial launch GIVLAARI and quarter OXLUMO. expenses XXXX the in support due of for increased affairs medical activity ONPATTRO to in preparation and ongoing

non-GAAP non-GAAP XX%. R&D combined XXXX, and versus than growth SG&A combined $X,XXX expense Our which were lower XX% in SG&A XXXX, and the significantly was million growth at which in was expenses representing in XXXX, R&D

towards levers As the I've more year, this is noted one level our supporting several path the over of key OpEx last on growth occasions moderate of profitability.

operating ended $X.X full Our the XXXX. consistent $XXX collaboration billion non-GAAP in and cash $XXX facility debt approximately to up decreased by our with year billion, ended in loss XXXX, the which equivalents in Cash $X initial financing top period year announced R&D XXXX flat year with non-GAAP favorable $XX drawdown strategic million the by marketable loss Full approximately we at $XXX same GSO the year. million, of non-GAAP operating year, for approximately this from our growth driven impacted was past that and in XXXX combined contributed the million strong XXXX $XXX loss We to by credit loss, approximately non-GAAP financing with end at in compared Blackstone of the securities million guidance related favorably cash, is quarter $X.X to line QX arm. which the including of peak that QX, Blackstone's SG&A and be billion operating would million our expense.

product revenues was which revenue be representing rollout guidance is revenues product XXXX. the financial not Vutrisiran reflects decrease also vaccine to It guidance XXXX, so related $XXX product will the these compared from Starting is into until over the products guidance now the should with worth our world. combined year. XXXX. around are the we early million million guidance We expected XX% for this more time and net GIVLAARI, anticipate approval growth to revenues, for turning not pandemic, that factored noting our and uncertainty it to progresses $XXX midpoint product COVID-XX three as ONPATTRO OXLUMO. net with providing than between combined our for net to Now transitioning

million than Our with between guidance XX% royalties in XXXX royalties from collaboration Leqvio. is to the collaborations growth a from and from and range primarily million Growth our the for and midpoint net and expected representing of milestones XXXX. is more $XXX with from come $XXX revenue Regeneron range

three million. R&D operating compared range to represents growth Our non-GAAP as modest guidance will of for We a existing commercial XXXX. leverage commercial million with The midpoint $X,XXX between be range a expense and $X,XXX generate guidance we infrastructure SG&A and increase combined anticipate from the products. our projected SG&A our is XX% support

R&D initiation hypertension. two X cardiomyopathy a of expect as as rate AGT investments two for studies HELIOS-B, and ATTR APOLLO-B Phase by higher growth well studies, robust We Phase our for in X of in our program driven

today, operating and improvement our XXXX. deliver we make non-GAAP Yvonne? over review our loss, achievement With on delivering the we have to XXXX profitability. as provided turn expense operating call line of another path Finally, that, guidance progress of top will the sustainable to goals I'll continue non-GAAP to year now our for in Yvonne to

embark our to everyone. GIVLAARI to ATTR for journey the Thanks, and plan that advancing our and forward hello Japan for of as franchise for Jeff OXLUMO. continue our Alnylam, GIVLAARI ongoing five-year year, global a on plan to approvals look study. with productive up is a we ATTR We This program PXxXX Alnylam guidance. we commercialization major market and outlines of OXLUMO. in be We past XXXX continue Brazil chapter shaping ONPATTRO, to new year cardiomyopathy

year. expect in we to the enrollment patisiran, complete early For study this APOLLO-B

a number In plan XXXX, nine For cardiac larger an is results at in following to measures. NDA we in ongoing exploratory months the look HELIOS-A of the filing top April. HELIOS-B also In study. to additional vutrisiran, we the enrollment results, XX-month data presenting endpoints endpoint, which report line on positive forward include AAN and

to our of in biannual start early dose expect vutrisiran regimen studying We XXXX.

in expected have and and hypertension. initiating Phase the the on X course, the and initial Sanofi look midyear For Leqvio we're And, be this And the be store top-line for of in have forward partners Phase study KARDIA is X we results to ILLUMINATE-C program. U.S. our for for Phase studies fitusiran aiming ALN-AGT excited launch Lumasiran, year. X to executing advancing Novartis in what's will approval. X ATLAS X of will about

data from additional the for We're set starts expect the during Alnylam, successful year. marks most in XXXX next look our eager industry. year. to five-year ambition updating goals course our readouts of the forward of new deliver can you pipeline become with companies the the sights to you throughout Finally, the one this and on chapter the on

Let me now to coordinate to our turn back session. it Christine? Q&A Christine

Yvonne. Operator, call you, if now one question ask in to for the open we in, and Thank get will limit your like queue we'd the yourself have each questions. to then To dialed questions. to those any back you additional you

Instructions] comes Stanley. of from from the Lebowitz David question line Morgan [Operator Our first

open. now is line Your

Thank question. reevaluate quite for doing of you PHX caused diseases look be of it GIVLAARI the way the what for for this far, you and you for what size be. look the its general? GIVLAARI might market for markets well. think types these ultimate taking it of to, the you Has seems performance nature types at And thus at in you one, and my porphyria has number When to what diseases these is changed opportunity other

David. you, Thank

I think you was David. that

occurring look to year launch think full launch year, continued launch GIVLAARI its was a had And Japan Obviously, virtue expect by patient we last but PNR. to expansion into geographic only new XXXX. and strong finding, continued year XXXX. do we in and really question. start a also, approvals be good driven of its major XXXX, in will significant in of And we markets a -- I in very good off by expect like forward that's not that growth first

Tolga further. maybe over comment Let Orth Andy me it turn and to to

to add anything Tolga, with start Let's that? to

how able and do about an to your and of the this And Japan. approval No, mean, John GIVLAARI, I been to we good recognized John. a And good point, capabilities says launch ex-U.S. in that with Good it's -- era the of performance during anticipate a lot strong Thanks, a the to be David. morning. both we've hi, essentially especially in organization U.S. pandemic

patients So, think value good treated. sign trends overall, not a It's of to good. properly provides I that medicine are the been of also that these the have the

add to that? anything Andy, to

just Yeah. that. add I would

is really excited to half opportunity. we through continue globally. this and for the us to company get billion We learnings into XXXX here, hopefully think we we're allow the go be accelerate still a as about XXXX. dollar that XXXX, And We opportunity gaining the will as

David, that answer you. does your question? Right. Thank

Thank Thanks for my taking you. question.

Great.

you. Thank

comes question from of Joel Beatty the Citi. next line Our from

now line open. is Your

for drugs Thanks I'm and therapy ability any into insight have to markets? question. compares combination competing U.S. you Hi. in taking could how the with ex-U.S. the with curious, that any in the share TTR

one and of that question. important dynamics great a market and That's and of A Yeah. of very one the important world. an in U.S. defines part execution ONPATTRO dynamics the the rest

to question? So, add to Tolga more on why don't color we some go that

asking sort of the Yeah. Would use. about I you be you were able to repeat the question concomitant again? wasn't quite if sure the

versus is agent, the TTR competing that with different ONPATTRO U.S. of ex-U.S.? in use Concomitant Yeah.

we That's actually much rapid to we've different. We it TTR a XX%, current that in are is that from patients the No, to is ex-U.S., about particular also see stabilizers we tafamidis. U.S. what Right. XX% It ONPATTRO see is. of in What utilization silencers. the in tend on of do switch see experienced. there's

see minor level silencer. some some a in use it a comes we when markets, of However, to concomitant as also stabilizer well, using than

that just ONPATTRO is point, And the the polyneuropathy where in the which exists indicated. for patients, treatment the these it's obviously, use of emphasize is to of

drugs. may are mixed they both So, be why ATTR have which likely and getting these have a phenotype, is polyneuropathy patients hereditary that

Absolutely. Yes.

you. Thank Great.

you. Thank

the of comes line question Goldman Salveen from next Sachs. Richter Our from

Your open. line now is

should analysis question. HELIOS-B and what and expect Good Thanks can my here an taking when we going morning. we I'm see for just curious on if to expect that to interim see. we're

Salveen. question, Great Yeah.

of hand study a reminder, our over to of of just and second. But compared the So, as controlled standard-of-care randomized blind on going top double amyloidosis Akshay placebo HELIOS-B this as treatment vutrisiran in a placebo to for is to reminder, a I'm cardiomyopathy. ATTR with

So well well. disease. both is The as quite hereditary enrolling that wild-type study as includes

But over going. pleased enrolling point but analysis, to let's are it we're your well turn be how XXXX, going really We Akshay. is enrollment with to throughout about interim the

Yeah. Thanks, Salveen.

disease we do patisiran consider. a So, elements a we We approaches get interim just later some have are encompass, to analysis another data ATTR itself. to have And And in in option to now patients in going interim we HELIOS-B. be those can analysis. we've data that which all and element. technician's want have XX I nine wonderful but also the XX mix the showing echo to data APOLLO of with importantly, data, data BNP can HELIOS-A, to data improvement to on we were months But will months exploratory use from test There study BNP. the from an that not BNP, data scan cardiomyopathy, shared think, with original and number year we're inform in

So are data importantly, year, continue inform datasets next for walk the as coming, the to that potential based of us for most on about we've RNAi lot a APOLLO-B just approaches we'll minute guided, ATTR And get there cardiomyopathy. distance. six

will it have will our so, excited options. elements And the approach. are and we about are these There update We're go finalized you thinking. into of lots we the that when

Great. Does that answer your question, Salveen?

you. Thank Yes.

you. Thank Excellent.

line question Stifel. comes next Matteis the of from from Paul Our

open. now is Your line

just year a much the AGT Last one. Thank came forefront. wanted really into taking question. Great. I to you broader for ask pipeline my

you earlier your by the now, RNAi? conjugation the might have that, pick? of in there a If Thanks anything or don't interest of one in that of at which that Are any then amount funding is you it's year approaches next, think be Day you CNS featured surprised in the gone don't of one all pick I'm little of you but end of had that's you discussed And piece conversation the this right to of neuromuscular, a given that with lot. programs forefront you early pipeline -- R&D would into the there. guys

Okay. Paul. Great questions,

going So, I'm to to then go go my give we'll and we'll Akshay Yvonne. and then you to view

It's And from going neurodegenerative RNAi on in delivery three and the of Look, where lot RNAi And program. enormous think, we'll technology perspective, the translation unmet on a way this So really perspectives to leading we're a diseases, program I you different of the question this CNS address of targeting amyloid get we'll Akshay therapeutics. will defining need. of my come our get just pipeline it. is back therapeutic precursor for for then, ALN-APP. That's be neuromuscular. protein. attention It's our moment our year on there's a remarkable the extra first hepatic that, treatment

going And future of for the landmark so, program to think pipeline. I that's field our Alnylam and be for for a and the

So that's pick. my

go Let's next. Akshay to

I to was pick going that.

something. pick I'll Okay.

can SDH program, and addressing I we a need. have Day kidneys at is rheumatologist, trained will the targets a interesting hugely the disorder, of R&D featured unmet Gout medical -- as benefit many, think it address gout. to we which global rheumatologic many impact the high but disorder, we're only the address I a kidney not prevalent function.

one incidents increasing very, disease and rapidly in by that's important So the very way.

be and most blood interesting, to love NASH lot APP to make very urea exactly levels. beyond can down X would Phase XX% X, I the a figure and that's we John's of So the over talked SDH. informative AGT But It about on position be We another and disease, target with the patients. into think out knocked and element Phase reduction our outsiders. help the without we programs a animal get as how like at are XX% to broadening achieve part very common which based peripheral that will data over in SDH, the bet can encouraging.

So, I'd program. pick the SDH Yvonne?

Yvonne?

the XXX to Well, is One, disease opportunity. close It's pick people going a around program Okay. reasons. I'm for the to HBV million afflicts three enormous that HBV world.

incredibly So, important.

Phase is being in patients, and log a the reason the reduction partnership in we has to functional now studied one And with a three think base X encouraging had Second XX/XX with Vir, surface that's tremendous. to have obviously, Phase the affect right in the which for HB our half opportunity cure antigen. study combination. And would from these think we've I I And third and fact that be option is XX. the reason price absolutely then a that

on. start of could we more as year program that this about talking think some I the time bit spend little kind So, goes a it

data Absolutely. been Vir making. on bit of progress that encouraged new by the be And sure that quite -- we're there'll And program. this to a year has I'm

handle question? want you Akshay, So, to the neuromuscular do

disease. amyloidosis, neuropathy a I in all we are ATTR a I If it it, doing peripheral actually squarely a so, work so neuromuscular Paul, we that think is mean, amount in of the Yeah. good work polyneuropathy we've -- think is our center, got there about it's disorder. front and neuromuscular

Of course, as type and is about the course, ONPATTRO well. hereditary approved, the be polyneuropathy think in in wild about situation. it's to ATTR. that'll an important think for impactful of hereditary in Increasingly we hear I area neuropathy

going hATTR with a the HELIOS-C that targets later syndrome, one of programs Regeneron are collaborate. number got the basket in intend more do of of with of validated We're ALS. that's onset are to So, ALS year or prevent sort separately, which a others to this And area. where to to in come that. and we people that's we've with There on and vutrisiran kickoff amyloidosis programs under one in the familiar we study genetically

neuromuscular and with another Gravis Pozelimab. with CX caused disorder the that's Cemdisiran pursuing anthropoid So also Regeneron. Myasthenia We're

But I interested assure neuropathy, stage, share Regeneron enough details And the and later a more disorders, lots on we're actually. at So to sure necessarily ongoing disorders can in mature programs doing programs those. The are work don't research there including peripheral the we that, neuromuscular that I'm all come year, until of for common other preclinical data in additional beyond collaborative inherited you, to we example, in discuss. in.

dent progress in the And on amyloidosis the excited think, made we've going polyneuropathy. and we've pretty So, disease. lots in we're neuromuscular made I about certainly hATTR

Thanks, your Akshay. does Paul, question? that answer

you. Thank Yeah.

All right. Great.

Thank you.

Ahmad America. the of from comes question of from Tazeen next Bank Our line

is now open. Your line

think much in for helping the market? you get stabilizers the how develop of ATTR have morning. a Wanted developing? Thanks. of Thank sense that are on, market diagnosed, Hi, you thoughts how Good been my to and taking addressable guys. is Do better general have your how to you patients question. being

that franchise across me perspective leader by a question, and patients the the broader on multi-product let multiyear we industry, great to Well, the we ATTR franchise saying we're have off we that's the Tazeen. a kick And the with aim it medicines at innovation treating helping Alnylam be a one we're is off to market of amyloidosis. And we've approved the is really polyneuropathy treatment bring ATTR terrific ONPATTRO leading the product forward. hereditary today a disease. the for with with polyneuropathy the that pleased performance this for with product we start. Obviously, are of It -- seen.

believe same polyneuropathy the which continued can will alone. X the drug. opportunity growth data segment six open drug, for recently work once monthly additional subcut polyneuropathy And wild-type which minute we positive we expand we course, should the with quarterly for expect reported we once up we it both is the with up ONPATTRO. opportunity vutrisiran which of ONPATTRO year, in as positive a Phase then, mentioned just And next will expect with ATTR time, the make subcut we beyond hereditary. assuming HELIOS-A ago, approval next We APOLLO-B open At believe the every door Akshay in with even and polyneuropathy, study cardiomyopathy data year mid

of disease. further? in to is really do how over growth as that Tolga, of for treatment little we well this bringing this evolving the want So the Andy, we're time? opportunity for comment you bit innovation this you multiyear terms see a a forward

very polyneuropathy. see in time know John, indication a two I cities you as that But for evolving silencer John indicated, -- We becoming is of the with that are obviously, this category market And have we certainly nicely. by. as think, there the it that's ONPATTRO tale almost. one goes we said now No, leader the

a is of PYP cardiomyopathy. You with the obviously, the that And diagnostics really scan. of the which is the a going prevalence, there's the probably wild-type yet have indication given more don't that the hereditary that's we able access have significantly we if, rare condition. much inexpensive route, But to disease then, with same ability HELIOS-A take certainly lesser -- through polyneuropathy, having be were our be as, increased as That will of cardiomyopathy more access able segment. -- that And to certainly polyneuropathy advantage diagnose they with well APOLLO-B, to well as patients. larger sorry to as -- HELIOS-A if has an succeed,

going think perspective, how Alnylam are we to with able signal be demonstrating us products to a and we're is from other our this as approved. segments, to the I what provide as were its well polyneuropathy, define great if Andy? able medicine be play ONPATTRO able to leadership segment, already to So, current be be for in right actually in to for

And early over portfolio to puts XX years. five bring our to expect add, us John going to as stages going happen hereditary the very the growth the and that's next Yeah. And what excellent just position. of one, here, two, an wild-type their to to we're in highlighted, markets Tolga be. that for to and the And are we bear in them

pretty really So, excited we're about it.

that marketplace impact agree market. Andy many multiple said. everything along go over of many overall obviously significant And with with of obviously of major time made the day, the have to with and of that often the revenue action Tazeen, the at Tolga I patient what just end and value sclerosis, products, with and I where and ATTR analogy will happened mechanisms

So, for leader a the the opportunities I is this end going Alnylam multiple will And a to patients major think day. you that space. will see in at that materializing be of accommodate in way

Okay. Thank you.

Thank you.

Thank you.

from Our the comes of Ritu Cowan. line next Baral question from

open. line now Your is

but does the especially there, can parts, of you how then Akshay, color policy early strong. It question. can for infusion One, performance, QX, infusion? seen does upfront. I'm a of taking on sort guys. ONPATTRO all but be on any planning to approval to lastly, long-term, of we've symptoms, Hey, going really say prevention else continues anything expanding home just different that? over, Are with it maintain And vutrisiran couple of in tailwind on coverage and you present you it's which you to much home effort a the about threw the a what Thanks potentially over out sales have be XXXX?

Okay.

-- we'll why HELIOS-C time give -- we and you ONPATTRO So, Andy don’t quickly why to go Tolga Akshay, answer some reflect let's then to questions we'll go don't the on we'll -- and the them. and question

So, Akshay.

burden the the and right proper. well the cardiac disease or for at was data, polyneuropathy the of Sure. is think. for -- disease, And Ritu, polyneuropathy of detailed when scores But was It remarkable and we aspects hATTR, outcomes APOLLO M&A clear lesser did is original as potent early at all associated single of looked we those to with that very in looked patients the XX% you we with down the TTR with very significant drug digit, with treatment and give to very overt before very onset mixed we think the can know data labeled onset for could so. with and I patients disease that. went the which led having despite their reduction zero, as we being of identified symptomatic TTR about so deposits or or being patients disease. hypothesis if Similarly, now what by disease prevent drug that and optimistic in heart to the are of evident we in low And that diagnosed no very feel even onset before clinical very onset, polyneuropathy scan close that disease. technetium the before the of maybe the the

and think highlighted can its reduce occurrence I of this the But can onset. prevent one it's hypothesis, turn that we reduce we the a so, substantially if success. And very off a reasonable and substantially TTR levels, and tap disease with

on a intend the vutrisiran we're study, and exciting what very later by HELIOS-C the a hypothesis very, detail with injectable that's a to more to now. the We help which in disease. disease be it's how onset will subcutaneous patients every think so. once chance preventing working I of the in But rare follow. six or getting often and to call year, So, start months to And try

first Great. the then sales And Tolga? Tolga go effort. questions on to and let's the ONPATTRO, commercial vutrisiran on and

A John. -- and We're ONPATTRO And with be it of by treatments. thanks, the And that pleased current from very growth switch outs finding. the continuous driven if you're be the certainly patient's And patient Sure. question, will appropriate, quarter-over-quarter. will right. great

steady providing systems access believe been regards in for home Those provide as the able to the have care to Now, -- well States being a patients we've but particularly United as to well easy in and sites of access as Europe. patients, pivot been also patient able able increase quickly to clinics. what have healthcare rates obviously, up, infusion, we with as and actually seen alternative patients good to access, pandemic, that gone is the infusion

tailwind. particularly have the available, cares be So, ability compliance we alternatives Europe. and provide rates. patient and impact a the U.S. any services actually, all And not home on those retention rates we the the Therefore, network have pandemic pleased we we're patients either and to or didn't at in those our compliance seen frankly, redirect available. impact current site we have to That's to really able that again, that certainly infusion have

expansion, obviously, would to exploring be that's part to second have we Obviously, obviously, are to that's indications. to, in we always making about earlier we regards able professionals continue and the cardiomyopathy see question, for. how The But indication something need that plan when we effectively of the your is the healthcare to ability sure something, received. to communicate

he Andy, has to Let if to over turn it anything add. me

Yeah. Thanks. Thanks, Tolga.

but got you great, or think is HELIOS-B Many maxed And frankly out in infusion. house. route unquote to in of where on social the obviously, physicians, our are insured don't Medicare advantage and we've centers, then one they get the that their and the will cardiomyopathy? and your was exactly ability on somebody on taking infused last running neuropathy quote take on that second the essentially that say the folks of hospitals able some want to rule that patients side, of I of they HELIOS-A commercially favorite And been the question or was hospitals, where year, infusion choose. smoothly We've dynamic, it in that. -- I patients got preference on can. for and the isn't as cetera, advantage locations at our right we common a choose home et many just passed

No, it's …

FAP I'm your even just HELIOS-A. that come expansion Yeah. any wondering It planning vutrisiran actually just cardiomyopathy was commercial labels online. for are and before for you if

portfolio. exactly that right, out as HELIOS-A there we're love our to about are we've and overlapping going to it. with and got is Got promotional today not what on front. ONPATTRO, We while efforts bring plans you the And know, any excited releasing labels really

Great.

question Thank on to Okay. Good. I you, think. should next the We move Ritu.

Thank you.

the comes JPMorgan. from question next line of Our Rama from Anupam

open. Your now line is

taking This morning. call is Anupam. Thanks Tessa the question. for our for Good on

you GIVLAARI, Thanks XXXX and As consider launch are part granular And much GIVLAARI so XXXX between worth versus considering provide is more on guys. around world growth the on second the OXLUMO, of question dynamics differences U.S. rest can then of the in assumptions versus what anything you similarities and XXXX. your here?

GIVLAARI the Thank think case will last the of approved excited primary introduction in for We're the hyperoxaluria, we year medicine. Those about that then are be of full being of launch full questions. And got which second important as as earlier. year the November this only this covered OXLUMO, great Okay. for of in year treatment year an Tessa. of Obviously, I launch. first you,

So, that's an exciting milestone.

let's Tolga this to question. to answer great go So,

Sure. really GIVLAARI Thanks, indicated, as those the John. able of obviously highly it from John we're And OXLUMO, pandemic. are are relevant to during devastating. are of perspective, an we patients Therefore, of we that I a going patients those the been the diseases therapy. across had you probably looking -- diseases uptake of to to world. at the be business for in, look prevalent comes we have highly excellent model patients of on at And lot -- we've with both launch Yeah. waiting type similar a that very with condition look OXLUMO. with those same mean, when been look, they number a if expect this both dynamic what capitalize rare and both full And products and are addressing, year

Andy And … Great.

of patients -- to I you. pediatric to was Andy, here addressed. needs But see is I to -- that differences And is with one OXLUMO add. just I Andy, I going guess patients. that also going be over a of population treating to main lot different was be sorry the

seeing saw thing the add level frankly is PHX a groups, year cetera, would of right matches patient the in excitement incredible now patients, advocacy GIVLAARI is here we Yeah. and that communities, I The ago. with only we are et physicians, just

really, early. mentioned with Yvonne a we than as here, good saw And pediatric a really to population GIVLARRI off we're more this so start. is So,

Terrific.

So for I think question. we one more time have

Thank you.

next from Our of Gena Barclays. question comes the line from Wang

line is open. now Your

for my taking question. Thank you

picture a have big I question. So, one

And Alnylam, could much things this know -- a space and the RNAi to doubt Alnylam already to in work identifying some willing done we space. the editing as candidates fruition. leverage be For come synergy is technology platform, and best other you gene we you've no targets such leader so to and see knowledge Would clear some there.

future. have Yeah. mean, Thanks, the are Gena. prospects we I about many, excited for look, with foreseeable the many RNAi we

a We and this chop technology is that boundless. can ton of have the this innovation type we forward wood science of and bring to really with

RNAi a based to look want -- we're approach. expand an technologies presence and we're what have of always especially to doing, we they areas might we ways in to our types -- going other where how might think about and Now, just for at beyond especially complement commercial strengthen maybe obviously leadership where

in boundless But that. and just engines at number product opportunities, look the things. have we front now in certainly speak right we'll terms flush with of is So, what of very from of us to we're of,

that provide some me Let additional question also it Yvonne? to Yvonne well. turn to as color over on

Yes. John. great, that's No, Yeah.

outside keep going for Alnylam do watch we well, So a careful on what's on sure. as

I development. lot et has and durability clinical stages There's additional where on gene one learn I early of safety, of that's for about lot a were to think, is approach still point patients, potential a in cetera. editing think it going, probably need that I this long-term very we you make the think to and efficacy

with going continue to stay says, we moment. of awful at to we the what's be as So, on. engaged But aware lot hands an have in do our and we have John what

Terrific. Thank you, Yvonne. Agree.

right, last question, the that's Christine? think I So

Correct.

All right. Good. Okay.

capitalization So, quarter. years, thank despite fourth let close. in with obviously over new the year, very just five the then the to next the pleased aiming joining innovation. We're results and COVID-XX. to And I PXxXX, our science market and call. a remarkable Alnylam from we did the was XXXX with But for five want everybody on in build technology what chapter a top me headwinds us company on now remarkable with we're for

all you So, a day. great have and Bye-bye now. thank

and this Thank concludes for Ladies you gentlemen, conference today's participating. call.

now may disconnect. You