Alnylam Pharmaceuticals (ALNY) 5 Nov 202020 Q3 Earnings call transcript

Company Profile

Participants

Christine Lindenboom	Senior Vice President of Investor Relations & Corporate Communications
John Maraganore	Chief Executive Officer
Andy Orth	Senior Vice President & Head of US Business
Akshay Vaishnaw	President of Resarch & Development
Jeff Poulton	Chief Financial Officer
Yvonne Greenstreet	President & Chief Operating Officer
Gena Wang	Barclays
Tazeen Ahmad	Bank of America
Paul Matteis	Stifel
Anita Gupta	Cowen
Emma Nealon	Cantor Fitzgerald
Ted Tenthoff	Piper Sandler
Tessa Romero	JPMorgan
Joel Beatty	Citi
Maury Raycroft	Jefferies
Alan Carr	Needham & Company
Patrick Trucchio	H.C. Wainwright
Leland Gershell	Oppenheimer
Mani Foroohar	SVB Leerink
Jon Lim	UBS
Vincent Chen	Barnstein
Luca Issi	RBC

Call transcript

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Operator

Ladies and gentlemen, thank you for standing by. Welcome to the Alnylam Pharmaceuticals Conference Call Q3 2020 Earnings Call. 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.

Christine Lindenboom

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

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

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

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

John Maraganore

period a GIVLAARI in will productive global you made Starting everyone R&D organization, call with with Andy our progress the quarter the believe QX, third we thank today. highly saw and review commercial and has performance as and which the joining a ONPATTRO We commercial highlight execution, for recent momentarily. tremendous Christine, Thanks, Alnylam platform. strong Orth

the for and recent to in year, four or achievement. remarkable or with achieve our opinions OXLUMO, XXXX recent inclisiran, for approval of We with lumasiran, set another another up GIVLAARI period have for ONPATTRO rest the and three is approvals but upward Akshay of beat R&D guidance revenue will range us positive CHMP less review the relative truly continued confidence in revision shortly, therapeutic estimates. progress and a LEQVIO, highlight our this of potential which launches the years, than recommending to RNAi the

execution our medicines, You'll commercial efforts, sight on while our maintaining towards potentially of from global and performance we're We sustainability. financial self-sustainable Jeff on self focused from we're clear organic Alnylam, excellence on also a towards financial progress continued our in productivity way. a financial profile. at Indeed, line hear achieving transformational our believe on R&D

we clinical goals for product pipeline that growth of innovation. Alnylam's now which for couldn't to goals we're of on is variable and excited prouder our exceed. toward actually achievements phase next us That the we moment be those And track be upon evolution. couldn't what more is an in a multi-product deep company with we’d when we sustainable established global be this for back XXXX organic fact, Alnylam our In XXXX, engine a we envisioned future and

patients We world. around company potential our delivering look biopharmaceutical forward will soon. top-tier the medicines, as with transformative on And potential to out we to our on a advancing vision lay focused multi-year

us you'll XX, of on RNAi of our hope be online. XX pipeline Andy, it R&D December Now before across I over investigational hand and able where virtual like therapeutics. mention event the join to host that to I'd we to reviewing a to We we'll plan mornings progress Day be

now So of to with review that, commercial turn medical progress. and let's Andy? our a affairs

Andy Orth

third as our everyone. the Thanks, performance commercial morning, in reviewing John, I'll as good by medical well begin affairs our quarter, and progress.

new For we ONPATTRO, making to prescribing a In also we physicians. achieved expect than stabilizers of up and to concomitant trend steady to continue of half this States the with million with United $XX.X see use cardiologists rate grow. more of TTR continue ONPATTRO

to with million $XX.X ex-U.S. We the made rest the progress from Turning quarter in of encouraging the markets. revenues with very world. in ONPATTRO third

including QX we secured quarter, access have launch. in Portugal last all Europe noted our markets in priority As Western following

ONPATTRO than the disease ex-U.S. progression XX% also to This dynamic strength the pleased country ONPATTRO halt greater ONPATTRO. of patients in growth continued patients represents stabilizers U.S. dynamic Japan, with patients are outside of the is to in for hATTR with new potential in a We important observed from switching for reverse An or polyneuropathy.

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

submitted than been of have As tested have TTR for out X,XXX greater October, approximately samples of positive XX,XXX mutation. pathogenic which

in into we've encouraged We've we by fourth are recent amyloid. testing the Act Alnylam in We believe quarter. the detection for of cardiac also continued PYP seen these conducted number and seen in months volumes genetic the scans recovery recovery volumes of will continue

ONPATTRO as with an hATTR U.S. we're Prix disease. the also is Galien with overall be honored as know, patients received is of in the systemic breakthrough of continues Award of highly prestigious And patients the amyloid in first often hATTR step USA the to polyneuropathy detection you amyloidosis many disease diagnosis these just week. for had As cardiac polyneuropathy. multi and amyloidosis recognized have last to a a

in We quarter GIVLAARI. patients product on the in over global XXX now revenues million drug. commercial net $XX.X achieved with to on Moving

of U.S. to XX% agreements the have Our restrictions number majority We've see progress with for experienced with in France. has including pleased we're baseline GIVLAARI for in progress not SEMEA. to improvement it The name headwinds of confirmed any We're region been XX currently plans access a two of access policies the lives. saw SEMEA having received U.S. off in now medical France, great patient concluding to with countries covered start launch patient score and with value-based access date a the ASMR without an offers VBAs medical other of to and market as Germany very successful In U.S. benefit over strong significant of therapeutic GIVLAARI payers. in strong well, payer attacks. or We finalized or ongoing GIVLAARI adopt sales additional value.

look considerable following a HCA the rating a of a rating added drugs approval our was launch the and Japan our Germany with strong review completion to which of Canada, submitted only we forward all Additionally, We're excited Italy. to such the assume in recent GIVLAARI secured that in obtained rating in ongoing of and September. and achieving orphan underway XX% benefit in high NDA also

in name our the a opinion Finally, fairs commercial away are third EU lumasiran. FDA forward positive December look in our soon of world. Xrd, patients launch weeks and the teams CHMP to RNAi bringing to we brand on for for just PDUFA an OXLUMO With the prepared the hand around upcoming date therapeutic

PHX the deploy are We field OXLUMO to this chain medicine help or underserved get to hyperoxaluria our primary and approval one supply to U.S. are community. prepared type our upon well trained important with team ready

And access that arrangements look and you are the quarter growth we'll prevalent continued DBA access to making of entry a to of are launch. the by as continued it other and payers that, patients highlighted and of for commercial updating with we now conclusion, review over able ONPATTRO, the including Novartis medical In capabilities watching of regarding be and affairs the upon to forward therapeutics further broad recent and progress. third our mark indication. are with With excitement need operations which to Constructive Akshay? preparation our will will the our turn ongoing launch prepares disease OXLUMO it. or I at the to guided with of RNAi launches our R&D who highly launch launch we OXLUMO. patient philosophy, into LEQVIO pipeline As chronic GIVLAARI conversations the sure hard inclisiran, work Akshay

Akshay Vaishnaw

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

patients pandemic. to We from in and enroll in of continue XXXX COVID-XX completion to to expect due enrollment the APOLLO-B impacts continue

injection. pace saw ATTR. we delivered quarterly time We're lost in to the for pandemic. a are is a subcutaneous by to aiming due during that still QX we the also the of enrollment experienced vutrisiran Vutrisiran QX of make pickup advancing for up During treatment and

studies. two conducting we're Here Phase III

patients The is first top and HELIOS-A year. early in which in complete line Phase report with next evaluating Enrollment to study III patisiran remain polyneuropathy. we is EFA results is on track hATTR

QX products are regiment parallel or the our second shared for and in the III regimen dose The a dosing QX in the actively vutrisiran in further data from actively other and enrolling. vutrisiran On approved NTKR ATTR to HELIOS-B of study potential amyloidosis wild-type conducted for a hereditary roundtable to with been ongoing our study currently monthly modeling development the bring vutrisiran RNAi differentiate September, Phase with can regimen. market this which advancing of is patients cardiomyopathy has in is which biannual of efforts development monthly we suggesting

profile. now GIVLAARI with risk treat supporting benefit porphyria. U.S., Moving which in Brazil to a We're Canada and to acute continued in base the hepatic is EU, pleased positive approved

overall receive points events also age XX% X of in primary the from across results one for the and The numeric groups. safety from end urinary of observed FDA PHX. December worsening to In month or For positive bilateral we ILLUMINate-A continued years on XX% improved therapeutic we of in of such continuous remains we lumasiran six at/or clinical less with approval ILLUMINATE-B treatment safety oxalate Phase XXXX. continue The study. will showing and old. similar CHMP X Stone I'll example await and results an the study. or a drug-related rate. findings. transient data recommending turn to demonstrated adverse believe with investigational thrilled OLE endpoint. improvements all dosing patients that results secondary from during to the lumasiran of well. limit children six of patients. creatine spot on efficacy and in month below and encouraging as date years later the in in advanced continue encouraging no study, and unilateral ratio patients late reported older patients eGFR the a very data be nephrocalcinosis with the endpoint ASM ILLUMINATE-A continue of certain nephrocalcinosis seen patients we lumasiran year lumasiran is exploratory have that of positive we lumasiran primary that site reported study. XX% in presented and study In initial on by reduction with B to type treatment common opinion, on of profile nephrocalcinosis recent and RSE. effects in of enroll safety The mean developing to In XX% annualized the These towards reduction led the in approved were showed RSEs lumasiran of RNAi treatment treatment regulatory the this activity with both the III the than with ILLUMINATE-B we're of events reactions also nephrocalcinosis was to of PHX with normal. mild ILLUMINATE-A study PHX action PDUFA the Based remaining exploratory study new that seen of meantime, which a Recently consistent hyperoxaluria most ages I/II from and baseline patients third as ILLUMINATE-A At GIVLAARI previously And some dosing. studies, full evidence further now led preliminary in ILLUmiNATe-A, see now for presented profile progress upper Lumasiran was with were patients interim lumasiran attack monthly We treatment decisions lumasiran improvements consistent Phase pediatric we analysis quarter, to levels and for X.Xx the by last to or endpoints including all in in of results EMA adults In clinical the injection to in the stable. new by with expected no Events the results maintenance, with Renal of we're ILLUMINATE-C or with the

CHMP have This the with delighted If approved, that partnering marketed hypocholesterolemia As late-stage that treatment inclisiran, under programs developing you of in inclisiran Novartis in drug with EU has of development approval also name hypercholesterolemia with the partners. received are is in EU. in for adults registration includes which United opinion mixed a in dyslipidemia. the positive We're for the it and know we brand two recommending the or be LEQVIO. States will additional the

also programs A hemophilia late-stage or partner in FITUSIRAN program. B Our includes, development for with ATLAS under the Sanofi. inhibitors in with is without Phase FITUSIRAN or III evaluation

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

data B clinical infection. with already Phase has to interferon very VIA in study a this patients about hepatitis with molecule. in presented excited or partner ALN-HBVXX of the chronic We're II Our initiated VIR-XXXX dosing

Alnylam's right we to I into of for ALN-AGT, In our dosing, hypertension the to reminder Also were is today ALN-HSD. opt of treatment study made re-imagine we next to in therapeutic advanced III. to prior We Meeting study look Regeneron. XX-XX the period, at blood in Phase recent We the collaboration pleased to the the opportunity the progress we an start in have investigational that with that the Heart with I chronic initiated forward As NASH Association we've ALN-AGT ALN-HSD being treatment presenting Phase week. program, controlled report of a of from American pressure. a results RNAi the of program Phase retained an shift believe with

We to make on we opportunities RNAi beyond continue progress the also and preclinical liver. CNS therapeutic continue strong many ocular efforts to our Notably, Regeneron. our advance with

is prior a filing is that recent program for the SARS-CoV-X. animal Our and [ph] ALN-AGT retaining RNAi we've its COV IND with model be data filing has The option timeline our virus generate this on on ALN-CoV lead. co-commercialization the or partnered we're to therapeutic further animal delayed. Alnylam elected track [ph]. mid-XXXX. to Based pleased the infection, investigational with of additional program and genome COVID-XX on our Accordingly, studies program ALN-COV CTA co-development COVID-XX that will to in remains causes decided targeting model exercise Regeneron preclinical advancement.

previously December upcoming to now turn this results. look John planned to let As XXth and mentioned, an highlighting XXth later day to all of Jeff With this financial review event year. we over for R&D forward me that, progress our virtual it

Jeff Poulton

Thanks I'm and good everyone. be Alnylam's quarter Jeff? pleased to Akshay now third morning results. presenting XXXX financial

already was quarter results and has a Andy ONPATTRO both highlighted, GIVLAARI. outstanding it strong for with As very

compared by with by improvement ONPATTRO, new inventory in Turning XX% return with growth Global the the pandemic. pre-pandemic offset which was channel. sales represents XXXX versus QX ONPATTRO to quarter, quarter. revenue which increased a with sales stocking XXXX impacted destocking of negatively U.S. of XX% during quarter reductions, ended in commercial the weeks gross by impacted two sources improving increased to slight the to the market patient for Patient growth in as following first well ONPATTRO patients XX% We second and compared driven QX in addition sales less quarter levels as increase growth by during of increased our million primary versus than returned inventory from by driven favorably results XXXX. of with the global QX net compliance, during QX the following. X%. net $XX.X XX%, and the quarter, an a demand Modest conditions, the for strong QX to execution which we generated

the U.S. highest sales level quarter of We are results representing QX with launch. strength the really in since pleased in the with the the

major strong XXXX, XX% QX with performance remained where patient increase of and Europe, Portugal. including PNR ONPATTRO with the following. versus growth sources outcomes, markets of contributed primary XX% growth recent from of international achieved in was An growth from Our in demand markets we from primarily

also We excellence saw from Japan. continued

between patient treatment. international our patients remains markets in from new stabilizer patients to ATTR naive in of balanced Source new switches,

initial in one-time growth there X% our finalizing benefits in associated we're which an quarter. brands. additional the And Canada, were contributed Additionally, access completing pricing with agreement our

for XXXX. and both, net compared in million be results commercial our XX% And to we Turning representing to driven revenue, second $XX.X generating quarter This by performance positive ongoing now growth had strong Europe. quarter, global of to we the continues in than a third the on globally. therapy GIVLAARI, more launches patients have U.S. XXX

XX% XXXX, our from $XX.X quarter primarily revenue third now Turning cost the Gross international VIR ONPATTRO down XXXX sales in total ONPATTRO inventory for third to to was as a benefited from proportion revenue inventory, while was quarter a having markets our from of percentage cost P&L contract Regeneron margin net primarily the full quarter, the from of in a the in QX of for due current quarter, lower manufacturer. of zero results write-off million, from XX% as to ONPATTRO due higher as our and of year utilization revenue for collaborations. at recognized well last a inventory coming summary and full the collaborations margins

non-GAAP investment pipeline expenses in the increased the ongoing the compared investment in to in in primarily our SG&A the stroke the third XXXX, a advancing GIVLAARI R&D of continued and same and to ONPATTRO hemo. of basis XXXX, programs. Our non-GAAP expenses same primarily to the and quarter the of period activities due a on quarter basis XXXX, on increased XXXX in late-stage to in launch to medical compared launches activity affairs increased third period preparation commercial due support

expenses. and top growth quarter loss moderate line loss non-GAAP by $XX the expect by the that in growth operating period operating with compared strong non-GAAP same and our remain we strong of as confident trend peak the XXXX driven moderate growth for the operating represents issuance with year, growth the of will approximately line million sale which We Our $XXX future decreased operating inclisiran in of top XXXX the continue ended includes and to year. million in in remainder quarter securities marketable $X.X of expenses cash, of partial cash common the second the royalties for billion, from quarter Blackstone. received and equivalents proceeds We in of stock XXXX,

third to in to believe commercial Finally, demonstrate circumstances. We challenging guidance. quarter the results our turning execution successful for financial our continue

million $XXX are of ONPATTRO million, result a results, revenue prior our As QX $XXX the to from increase X% ONPATTRO of million we $XXX a full midpoint the strength the year from the million guidance $XXX our the to XXXX of representing range of for increasing midpoint to new range. and

net and collaborations expenses guidance Our for remain unchanged. guidance for our range non-GAAP, revenue and and R&D combined SG&A

programs and by primarily However, R&D Please contingent spend we increase increase end range $XX advancing in associated an revised SG&A GAAP continue launch operating we driven QX non-GAAP, expenses driven liability good our an with upward R&D expense are planned expense OXLUMO. SG&A both in related primarily note combined towards the to as our our Ionis. guidance guidance expecting our million, clinical expense, midpoint by year end in with of increased and R&D stage have the range, the upper and by of arbitration progress to reflecting SG&A support we of our the combined of key in make expected to

self-sustainable of Alnylam's now our need turn that profile continue cash, Yvonne billion, Regarding I'll year. strategic call, bridge mentioned remainder the call we our And the future to financing without collaboration quarter with the with believe secures to financial review over goals for financings. Blackstone, a our $X the up adding Yvonne? for as to to equity towards in second

Yvonne Greenstreet

everyone. hello, and Jeff Thanks,

important of look a exciting up. we close number milestones we have to out lined As XXXX, very and

approvals and plan global continue in end the two ONPATTRO U.S. expecting We're Europe. of additional we both inclisiran year and the For commercialization regulatory by of and starters also lumasiran GIVLAARI. for our the to both

year-end. We I forward to HELIOS-B results as with clinical expect at by for diseases. in specifically hypertension initiate from look to Phase presenting a enrollment launch ATTR OXLUMO and We to XX. to with a studies, meeting cemdisiran in ALN-AGT the We patisiran partner cardiomyopathy complement-mediated in additional continue plans AHA treatment of a our I the option U.S. of the in November Phase potential ongoing plan combination vutrisiran. our study pozelimab, Regeneron for therapeutic with And on trial APOLLO-B

forward progress R&D look updating to It's our also We virtual overall day and strategy. on event our pipeline December. in you

Alnylam, growth global XXXX expect delivering Exiting noted as very engine these to with original As an multiproduct robust continued we innovation. as and earlier, Alnylam exceed organic times John are a this exciting sustainable pipeline our clinical year for a guidance. commercial our company product for

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

Christine Lindenboom

Yvonne. now call the for questions. you, Thank open [Operator will we Operator, Instructions]

Operator

We'll Instructions] [Operator Wang first from ahead. our you. go Please Thank take Gena question Barclays. from

Your line is open.

Gena Wang

very you, Thank taking congrats for strong a you. my and on questions, Thank quarter.

regarding So commercial. one question the

any could be share expect And inventory thoughts for of First you the full program right the of with also would patients early the on driver the access the do you ONPATTRO, remaining for the for now? and for major Q, lumasiran, year? number in where the us

John Maraganore

Yes.

So, thank you Gena.

-- specifically. Let's Andy the I'll Jeff to go ONPATTRO on and question

on out specifics transitioning based EAP, the in high access But product say approved, achieved. commercial a program. obviously, will are obviously patients at the giving expanded gets I a on patients that, not level we those our Regarding basis TNR And we country-by-country as in have onto do program. we're on lumasiran patients be will lumasiran that being

that where picture, of then, a leave start? the we'll you QX bigger maybe Jeff comment can want for Andy, to Andy impact But you that's give inventory. a question. And you can on ONPATTRO? So, expectations do think, I

Andy Orth

to. Happy Sure.

expect increased So a of the I'll well an growth the mixture In rate a it patient come States patient on Jeff to in here the as QX United the demand, specifically primarily side. to net new over from that And post as QX, demand. growth as new compliance that COVID we inventory to we noted QX, net was impact. turn return both,

Jeff Poulton

Yes. Hi everybody.

were Gena, weeks And the to that in distribution range. have, where in inventory, two for three range ONPATTRO less based at is agreements than that In typically the quarter of are one of terms the we we end on weeks. third the

at point. again in right that middle the maybe -- we're So, of right this

Gena Wang

Okay. Great. very Thank much. you,

John Maraganore

Thanks Gena.

Operator

We'll from question Tazeen go America. now take next our Please Ahmad of Bank from ahead.

Your line is open.

Tazeen Ahmad

so taking Okay. questions. much Thanks our for

a of get reason early read-through whatever from to would we next think when topline to there the HELIOS-B spending what into be Thanks. the show, guys in should expect data sense to the in any does population wanted I information we year. that should see And cardiomyopathy the HELIOS-B So, readout have you are that study study? that

John Maraganore

Yes, that's a let Akshay and handle great Tazeen, question it. I'll

by focus a Let for be dosing saying, very study. with Initially, regimen because biannual excited HELIOS-B hATTR. and about polyneuropathy once will setting can potentially we're the me then, the a the patients and just we enable that hereditary and vutrisiran with both additional for cardiomyopathy, in HELIOS-A start wild-type. with it introduce And quarterly obviously, work is obviously it be believe to going will administration dose we subcutaneous

through So be do there and to will be from potential will comment you Tazeen's cardiomyopathy want the Akshay, HELIOS-A? at specifically read the what on topline questions available on around what

Akshay Vaishnaw

Yes. Thanks, John.

believe So topline, vis-à-vis, that data early have we'll the continue to HELIOS-A year. we next

So that's exciting. very

meeting none safety of upcoming habit, after level scientific the the and the on study general at topline at report. on relevant and we We Our of is endpoint fully secondaries that's report present give then that. a an primary high the more to also to information the course when details all the

HELIOS-B. APOLLO in ONPATTRO, informative with come back to done studies read-through within In the I about the on cutting So on the it learned about original biomarkers, impact there a myopathy APOLLO, If think study from cardiomyopathy to be had patients lot the we findings XX% that think, should we that of I study some evidence how and of population very impact the into vis-à-vis ONPATTRO. heart. as

exactly have see not what just patients read here HELIOS-A, in involvement osteoblastic exciting biomarkers, on Now will disease but remains population. have cardiac of to of be very to impact the through it on been info dependent terms but further in the much determine it proportion what

John Maraganore

Akshay. Tazeen, does Thanks that your Does that -- question? answer

Tazeen Ahmad

that is the next be or would say it -- January, can you data of Yes. not you when granularity? in And level possible providing you year, that are early

John Maraganore

granularity provide that Tazeen. Yeah. We're not going of to level

Our early. I going is early period But be as QX or to know QX. it's think you

Tazeen Ahmad

Okay. Thank you.

Operator

Stifel. ahead. Matteis We'll now from Paul take next Please go from our question

Your line is open.

Paul Matteis

Great. clinical you the so Thanks side questions, congrats lumasiran that work? second so that not quarter. Wall dose on three this and data And that prevalence vutrisiran, Street vutrisiran, and HP. some the than could just six-month and bridge on the are PHX materially then Two status if lowering lower of to I to data you think TTR the outlined do drug expectations one, what's safety? much, with of that are two, on but for the dissimilar on you've think of And

So you or do so Thanks. if think analogue context? If for you is any this? that realistic a can vutrisiran not, give

John Maraganore

Yeah. Thanks questions. great and Paul

And we've combined that encouraged vutri high the should that with on point. certainly been support starters six at lowering TTR for by with on engagement think monthly approach. two, I a regulators level, we've is that it that had safety our belief

is submitted and require those strong part be obviously, and an will labeling. generated and a types And future be we're think that supported dose of would data the be that overall So would have a then plan. as that obviously been I in that to certainly medicines But, with consistent we're other with SNDA forward. path regimens of biomarker

we you lumasiran Regarding would that OXLUMO and population do then comment be I the moderate think Andy at should further. and patients there patients initial to would how diagnosed you I'll prevalence to the label let PHX. a comment and GIVLAARI? prior which severe $X,XXX somewhere to PHX on look and to any that want the size, relative will mild $X,XXX that on market further expanding PHX, bit if we there, out are label on general that have when believe include be do it think the little about to are in between Andy But we

Andy Alnylam

point shape you that pretty to excited furthermore a And it addressable Thanks. globally. expecting largely somewhere as launches to overall see it point out we brand opportunity continue and X,XXX, number John. this market $XXX get becoming as this we're said this right, Sure at luma market, X,XXX And to be between and And on-label. do underserved. here which is will and we're million there

So a we'll lot we go. be learning as

John Maraganore

Does Terrific. your answer question? that

Paul Matteis

Thank you.

Operator

Cowen. our We'll from question Anita now next ahead. Please from go Gupta take

line Your is open.

Anita Gupta

This on is Anita for Ritu today. the Congrats quarter.

impacting quarter So new the my or lockdown understood from than unclear it's two you expect fourth Do that quarter, secondly, side. second worse impact? And questions how then better lockdown the HELIOS-A Thank of outcome in the be would would analysis? function a subgroup patients such you. but cardiomyopathy analysis, if what to plan do an be you my provide cardiac study, primary

John Maraganore

done diagnostic the of -- answer question. let to a it's QX -- you wave part Great. then and globally. first the level question, give procedures deal second medical regarding comment. Akshay believe Well, I'm me that going with But to will level you want Look a at the second even Andy up and are. high high second can our it third to wave or have that? more -- into the to seen expect I'm countries -- And was do at system you saying this medical go this it than with do is in we is therefore, on Relative And color a from in for shutdown a global add have testing belief that system to we occur the what adapted occur QX. we as depending open. to QX. relatively stay in We where medical Andy any was This part most more perspective. that globally the return just to point would

Andy Orth

Yes.

basis to maintenance it this that systems as patient and we showing health yes, but well flows right, levels increased on to all promotional was And navigate a care continuing, now of and furthermore, navigate of both of learned are John. got through how learn care. continuity You've all patients how therapy for coming have the

may in we're much to what a here better So weather come. position

John Maraganore

to And the answer want Fantastic. you do Akshay question? HELIOS-A

Akshay Vaishnaw

Thanks. Yes.

to the is the got You've goal to remember neuropathic primary that disease. of the studies study aspects the

most So endpoints and primary endpoint forth. on of are the that focused so

have, the said many we question including will report patients true Now to all collected as before with or I biomarkers cardiomyopathy patients and see data outcome. that previous how we cardiomyopathy a out we've

is hospitalizations not as and orientated put it, again guess, But functional towards important terms of the study cardiomyopathy. primary outcome would the In deaths. you the I most be

in we'll don't So exactly how I events know, occurred of certainly be would course. them have many but due sharing those

John Maraganore

question? Great. Does that answer your

Unidentified Analyst

Thank Yes. you.

John Maraganore

Fantastic.

Operator

Moving go question ahead. Alethia on our from Young to Please from Fitzgerald. next Cantor

is line open. Your

Emma Nealon

on recent AAT. RNAi on for the curious think you with a some going here? has Great. Thanks. this long-range how challenges Thanks. come about thinking plans combination In to This that of Emma my Thanks see do for goal in taking Nealon to RNAi. [Indiscernible] Alethia. you're of light is progress is And We're question. zen for smart forward

John Maraganore

what not commenting you area heard part Emily, the on you repeat So I'm I on clearly are you because could sure, specifically? first

Emma Nealon

light Sir, AAT. In early. --

John Maraganore

AlphaX-Antitrypsin?

Emma Nealon

Yes.

John Maraganore

have molecule are Got Absolutely. obviously, I excited ALN-AAT-XX disease Yes. development. and it. a Look, with AlphaX-Antitrypsin liver RNAi associated the about we Okay. advanced to mean, potential deficiency, therapeutics into the treat for AlphaX

who that to together independent we this program as year, effort earlier Now well. partner has with decided own Dicerna their

we'll a is be And to nicely so the Phase quite combined due II/III really is effort Dicerna going between Phase course. study, be now isn't going and I/II to in Alnylam in a advance into -- positioned and currently

So We opportunity, cost. end III. on excited the the they with way the XXX% about at of works program retained will we're definitely their the Phase is advance an opt-in the Dicerna right partnership

So we is option after that It's U.S. outside the out. free taken the all market. have a commercialize to risk

the keep rest we'll the U.S. So have and they'll the of world.

Dicerna are a that think to the Yvonne, it do from with with we move we Dicerna competitive the very else to relates program. encouraging as your perspective deal swiftly So it the liver to manifestations. add anything our And opportunity colleagues becomes to relationship? at

Yvonne Greenstreet

No, it John, you've really well. think, covered I

John Maraganore

question? Right. Emily, does that answer the

Emma Nealon

Yes. Thank you.

Operator

next our begin. Piper Tenthoff from We'll Sandler. take Please from now question Ted

Ted Tenthoff

much. Hey very thank you

the Just congratulate excellent on especially time. you commercial difficult on during to side, execution the continued

John Maraganore

you. Thank

Ted Tenthoff

years fits seen that change is just going business recently that down just focus the so how But patients and over come where the bit that were really market treating kind talked for a think And little fitusiran, over because there's kind the as much guys Thanks. you year? haven't for you're a lot you programs. the latest answered. the the of last question effectively been have you on such My other what's the success how one But do we now. Sanofi forward? with Really And related of incredible there? how a others about

John Maraganore

But goal first hemophilia as hemostasis fitusiran, thanks the Ted. on you for at Thanks mentioned beginning. Thanks all, know RNAi specifically, -- the the congratulatory Yes. comments antithrombin with comments Sanofi. partnered It's an hemophilia of improve that the you is and as increasing B targets therapeutic with partnered A to is inhibitors. patients omnigeneration this of with without in with this and

The being their the we by Phase the really execution product molecule. profile attractive and Sanofi III. constructed target It's is is really continued of in program led that rely on it an So, program. for we've

period. we hope the learn to in So, next more

it And it. how program in the Akshay to your of to of don't really terms most is. know Yvonne anything for from the part I where think Sanofi add has and their advance it's I else they been so or call ultimately that's But that driver the perspective?

Akshay Vaishnaw

find I'd than hemophilia innovation people -- week the the factor I continues add the is keen need other to adoption multiple that intravenous other think a therapies thing landscape shows to put replacement. to are times

as I'm inhibitors. hopefully very the said, would a and growth John with A progress for and about excited And B guide home program. without as further hemophilia growth with But you on fitusiran so Sanofi in

Ted Tenthoff

And Thanks remind your guys. us Thanks. Great. just interest there? Yes. commercial you can

John Maraganore

Yes.

important very So, we have point. a

reciprocal So, we XX% on that to from fitusiran to tiered have royalties range have XX% sales. we

we a So, success. financial -- about we have a and the have question attractive in product significant do No interest it.

Ted Tenthoff

much. so Thanks Great.

John Maraganore

Ted. Thanks

Operator

ahead. Please Rama next comes go from from JPMorgan. Our Anupam question

Tessa Romero

guys. our Hi This John. Tessa on is taking Good Thanks question. call for the morning.

I in for is noted think that expected complete ATTR-CM APPOLO-B the in XXXX. So, you trial to enrolling enrollment

what factors are considering? internal second the for quick an So, that then here considering potential you're a And when analysis one. a

us on of and there at the seeing much. data conference quick a at give next just scope sense can On at we'll update ALN-AGT the week so Thanks the the AHA be size you week? next

John Maraganore

Great Terrific. Yes. questions.

APOLLO-B no Let patisiran me and in both cardiomyopathy. There is study clarify study. That's which a hereditary the interim analysis. just is muller first XX-month with

right analysis interim are on regarding HELIOS-B. an certainly You

what want to clarify just trial. I So,

Tessa Romero

meant misspoke. I HELIOS, I John sorry I'm Yes.

John Maraganore

to wanted I okay. It's clarify.

Okay.

So Akshay Akshay do mute? you are want to comment on HELIOS-B a little bit analysis? an on you interim

Akshay Vaishnaw

COVID. on. the year going be that obviously this well is We've very very HELIOS-B enrollment with to to analysis The QX picked interesting up slow after interim execute

information I we also details TTR Tessa, ultimately important next have. With on to And we'll and will first the give base information we'll the American Heart ALN-AGT will your that think important APOLLO-B result which sharing study in with importantly time of safety. share other that as which that's approaches of that and picks on how you analysis, we study Yes, thought. There week. design up reducing as working further interim in the get So, will be anything we be the as strategic enroll further question at a respect from our impact enrollment be the we all completion on. cardiomyopathy busy APOLLO-B obviously we're

change it's systolic First et target that sharing and that blood and in also be the and knockdown but dose to including blood significant in change of reported pressure. relates and the for based and be all into were which will in a great continue are infrequently people We'll study. come the patient patients. administered those will you'll think advantage how the first all we diastolic I population as about develop good human frequency in And cetera. foremost, changes pressure, dependents in on extent pharmacodynamic there further to this obviously half We've full the data the issue of give we an will it believe things compliance the that therapeutic hypertension to insight huge see with away this

what's of kind that's next up thumbnail the on coming So week.

Tessa Romero

much questions. you Thank our so taking both for Great.

John Maraganore

Thanks, Tessa.

Operator

take next ahead. Beatty Joel question Citi. Please our from We'll go from

Your line open. is

Joel Beatty

Hi my thanks for Great. and question. taking

evaluate you or For biomarker Alnylam initiated recently efficacy HSD in study. Could the endpoints? NASH that to potential any discuss

John Maraganore

you talk want the about do Akshay, HSD to X.? Absolutely. Phase

Akshay Vaishnaw

Yes.

of itself. HSD, with those from the in blood. circulate volunteers sending target NASH will study that So subset The is doesn't healthy ongoing, it progress fashion patients into a

programs. we're like the lot a of on highly of We'll will that factors We biomarker we terms believe there are other more a number data direct progresses share and itself, the don't in great patients of but the next the as liver think we'll at So as share study what our program target on informative. And be downstream biomarkers have looking and importance matures. well and be that goes radiological both NASH year. ultimately that progresses biochemically as in in as will of on I study the the

John Maraganore

program an Yes, add of Day it I'll think that opportunity hold have deep validated the And that to our I'll in indication. be we us is exciting also NASH. for it important clinical in that HSD opportunity to we a upcoming a more just it the and will is because and dive for on plans program. just to for that an add that But R&D December promise that. great genetically target obviously do

Joel Beatty

John. Thanks,

Operator

Raycroft go our ahead. Maury from from take next now We'll question Please Jefferies.

is line open. Your

Maury Raycroft

thanks question. Hi, Congrats. everyone. Good morning. taking And my for

broker? next First cohorts some is week. the also latest soft guess have cohort with wondering those ALN-AGT exploratory you're the meaningful including from one on steps for if just patients next with going not control the they? How additional our status cohorts? And I'm as And well. are if cohort the are what I program what's in then combo data data the to these

John Maraganore

won't and just bit steps dosed next cohorts mean comment want the Akshay, to those haven't the I they week those for see cohorts Phase little the do X? questions. been a on answer is But next yet. you Great of Okay. completion simple because the you

Akshay Vaishnaw

Yes.

So so delayed up Maury did and part through that study which obviously, picked study forth, so get We've many the hit QX steam. in like with COVID others.

in study design week we now most next can commenced and on a everyone thing everybody. But established of give yes, and year, Phase we'll ongoing into beyond due course, We The and observation we've said, update AHA. of busy take the getting importantly next share to effect the things at the believe rest things. setting that further which those intensity very that the most aligning X X early effort next to next I clear Phase anti in think year. the meeting on terms going with cohorts important are will through scientific we're is those the Phase that we And bring report we'll where haven't John that place as we will to year in information Those the where year. start and of X but be

goal. So that's the crucial next

John Maraganore

potential Alnylam pipeline. just because Maury upcoming new our opportunity is again innovation Yes. it a an we will exciting we on prospect obviously Day do think that And dive from I deep would the add the coming for R&D

Maury Raycroft

you very my questions. much it. Got for taking Thank

John Maraganore

you. Thank

Operator

Moving on Goldman Please ahead. go Salveen to Richter our next question Sachs. coming from from

is line Your open.

Unidentified Analyst

on [ph] for Sonia Salveen. is This

a really just ALN-APP particularly data with progress only when expect you of on quick So extrahepatic there? First portfolio your the question can

John Maraganore

sure is Akshay Sonia. as Well, a to get this, I'm and well. like glad Thanks I'm Yeah. question

breakthroughs we CNS the Let eye me the to the highly and couple remind at efficient as the more the the therapeutics recently delivery, that over to of say of everybody and exciting delivery is lung. achieved durable including just well of last one and other tissues that RNAi years and start the

with a that function the So a frequently. caused proteins opens we be many, regimen gain we the expression are it not And us that it mutations are because growth course an or months every once think many six of of the by opportunity neurodegenerative being function obviously intrathecally CNS that setting diseases of quite can if CNS of new given in dose itself to liver. prospects is really outside go our excited about in the of pipeline after up the for

is opportunity we've it partnered Akshay, XX-XX in with next the do APP the regard. to want steps? a company about Regeneron specifically on great you that basis a and So for talk and

Akshay Vaishnaw

Yes.

at X we've been APP, with program partner next was into taking us Regeneron of speaking will be the year. that So it great Phase

there's those a Phase data showing. that time course, excitement ongoing interesting next Phase guide given X when We to guidance of lot we'll thing be around in are is further of there's and the the And with aducanumab actually review or to gotten we'll going we've of that middle data other And X with end year what continue study. see the so. will very once on a

effects target interesting it only the tackle all Alzheimer's believe the beyond. be to also tackling speak turning tap and will for and of disease we And and the the so of is Friday, but of to not on important but So off that a can outcome deposits in the believe APP we the intraneuronal in extracellular a impacted. beta see by very to we outsource continue space target the

this could contribution really have think significant we to a play. So

on and expectations we'll after So excited to next Phase update into get year X that. those

Unidentified Analyst

Thank you.

John Maraganore

our to want context? within little a you yes. comment cetera you our relationship comment little a works lead, useful on et Yvonne do Yvonne -- vis-à-vis want to a be Regeneron do thank on this bit that you, how might And bit

Yvonne Greenstreet

but Yes. opted share going No, of whether leading obviously we the that's And we're program program the our to have excited excited delighted and actually economics great. Regeneron, mean out first in the I with were that that. be to very platform. Regeneron about be CNS we're leading

John Maraganore

Okay.

Operator

our next from -- Please take go ahead. Carr questions out now We'll Company. comes Alan & from Needham

Alan Carr

us And about kind questions. give you you Can targets that? candidates stand? taking at the around that where for curious do program? Thanks detail Hi. comprehensive around around other candidate? What and to Can give need I'm -- update more where a exactly COVID-XX. my your whether looking can other two more you're COVID around stand? little we -- things a of What things

John Maraganore

targeting therapies that's the this work we best to relates how long program. to emerging IND from with opportunity Yeah. COVID-XX. for this encouraged SARS-CoV-X we just specific are those committed of And the And at therapies, Happy that is the work we in do that. me you perspective to the to so future, management we specific that? established development specific genome COVID it for the some in time timing technology for we're as We've which our directly continue want flu. and into seen RNAi thinking which there's the could point forward in we Thing more an for those comment think is recent in Obviously, then the And context the can clinical in in how infection. results. it advance the Hamster presenting and -- sharing add before, anything an by have And game look model COVID-XX And going we is antiviral in start certainly program. play help to the as specifically. is But Akshay We're and future. and of on some advances this a inappropriate. SARS-CoV-X our Alan. molecule we're there well. to activity of to to play the to lung will be But about which genome, RNA position, opportunity have to like delivery, model understand advancing treatment be commit to disease to longer-term do an an program, it let plan therapeutic we can the model, model conscious to place Akshay, of obviously, we're us done

Akshay Vaishnaw

right. you No, I covered it Exactly, think John.

John Maraganore

Great.

Alan Carr

right. my questions congratulations. All for taking and Thanks

John Maraganore

Alan. Thanks,

Operator

Wainwright. Patrick now We'll ahead. our go Trucchio take next question from H.C. from Please

Your line open. is

Patrick Trucchio

you. Good Thank morning. Hi.

if that change what understanding have comment you in on take a R&D could policy the and administration election impact time. Alnylam's could in in in how the the closure the impact and may potential XXXX or With can the wondering, health if any U.S. beyond? execution I'm care some this commercial U.S.

John Maraganore

Okay. Great.

democracies think yeah, is coming counting hoping the here And the obviously see need are through democracy in way election we the I and the clarity I it's to the – that to completion all our on going work. great So of process which days coming weeks. votes, is there a or

a or believe get types the that that very ways that engaged the the payers for see consistently dialogue pricing innovation bode to But Alnylam well type going delivery value continued well from that we dialogue that so and continued be type and get But a governments platform. overall. of risk of I of we've medicines will it see are our great recognized value think the of we deliver the the by to around it's think These of whether Trump that type innovation world. think our bring forward, and success around of because of payers approaches continue ultimately. be obviously I that dialogue, with sharing of to in think that ability drug And of the I is politically. We we And positioned there's Biden a around certainly, sort elected. how happening. to And to we of by that emerges stand regardless outcome

value of that do what for in the – a do good policies first regardless the obviously on we're of drive to we To platform. to of outcome think patients the continue position able that our from that and and be regardless emerge. foremost So to deliver

think some So discussion that been all the this well will discussion. But be active we that count a are and and will in have stakeholders to on but we're different good there of active we we we of generally in this that. maybe, overall. we're certainly changes as helping company optimistic equipped in well do remain place occur, Patrick think we But very through in a

Patrick Trucchio

Thank That's much. you very helpful.

John Maraganore

Thanks, Patrick.

Operator

take now go Oppenheimer. Leland next from our We'll Please ahead. from question Gershel

Leland Gershell

Thanks morning. my I comments like for good those on Hey, question. taking the solidification.

it be would Thank with differences execute on on to through pace in with reimbursement seeing question progress? with the of recently that were discussions if to the having OXLUMO any expect progress basically OXLUMO? on a with you others want And if you you. – on been EDA any on GIVLAARI Just where you'd just you're GIVLAARI have comments as you

John Maraganore

great a that's Yeah, question, Leland.

these job how we over continue Let access GIVLAARI. doing of -- me very right saying, now share with of new demonstrated prevalence-based product. with of introduced they've am forward job adjustment of great And on value-based about model payers with the performance the the with and lot both right But XX payer done stakeholders. of work I'll markets that be they're we we've with that commercial that about and some ONPATTRO, lot DBAs U.S. the in introduced shown have great -- risk and now world GIVLAARI teams start also by the agreements to just general we a effectively brought we've global around just in and a we've our XX we've the -- the of just them features proud I with the structure signed around actually on like the on innovation

can't share as launch context going. So the to OXLUMO? but on obviously, you we can discussions when some product, we'll get Andy that maybe specific all how are details you we the context, more give our And want on with share do that

Andy Orth

Sure, sure.

that we And will an positive. agenda globally. are from with ONPATTRO and feedback has value-based been to early similar and on done So pursuing GIVLAARI, days all aggressive payers exceptionally

with ONPATTRO, So similar access in really, open strong. really GIVLAARI expect results and for of had OXLUMO we terms are which as we

we'll So, leadership continue industry here. our

John Maraganore

Andy. Yeah. Thanks,

Leland Gershel

you. Thank Perfect.

Operator

Please from Mani Moving on Foroohar from next SVB to our comes question Leerink. go ahead.

is Your open. line

Mani Foroohar

hesitance guys. starting present as A guess Jeff. the for Thanks the of some during in taking a a the one, compliance of quick I performance. patient to their IV about bit At come markets the hype question for Kind is that increasing little of on for driver pandemic. from

So, that about compliance a trend we of [Indiscernible] gather maybe optional or that as data and the deduce a forward? HELIOS-A that to think you reverse you you on how bit tells provide the inform lot to for in there Akshay, the little what have decide need about little next think you Can still a when itself then Are if study the more there's to wait us on turn. us you information proceeds view data do beyond. is and a lead give from and for that you appropriate quarter the until HELIOS-B And taking will APOLLO-B on of entirely? just to HELIOS-B interim? approach that Is most useful blinded basis HELIOS-B APOLLO-B talk take

John Maraganore

questions. collectively them start about we interim. are B we Akshay great great. are and strategery why as Jeff, to two the Those and Cardi relates call don't talk that Okay. the we'll how Those with then Mani, have

you So to the compliance on want question? first Jeff, start do

Jeff Poulton

Sure. Yeah.

to mix pre-pandemic demand well. QX. that and versus remind patients on U.S. of to returned in ONPATTRO therapy and related was the in as U.S. in and I you in on the was XX% Mani. a for So, compliance grew we that saw the did XX% that results just levels And of the QX earlier new that on coming commented increased to that Andy we QX,

outside U.S. a I going a the that of QX we on growth see saw reminder, of big we impact a the compliance U.S. just sort same the And in forward. So don't in that impact see on didn't

a patients wasn't U.S. the seem systems therapy do compliance to and outside of healthcare job impacted. better the on maintaining So

rates. I again, going growth forward impact increased our don't of see So a compliance big on

John Maraganore

side hand we adjustments QX, it just potential think I I before any just in would U.S. wave downside third that add et Akshay, made happen in bolstered to And that pandemic I that might of over cetera. resurgence the the the care have of

in get things what very if QX we're impact better you sheltered worse. do we're the has now and Do that beyond that question think -- complicated not handle we I to to saw but not have much asked. Mani QX. significant So Akshay, want like any more interesting in from

Akshay Vaishnaw

a how then as but and points very be we'll cardiomyopathy, be and Mani point, a of long-term radiologically. that the on around we open-label aspect not greater into get patients Would important very to continuing I'd to the on from for clean us. say on it's just important work outcomes that and insights work earlier, all I serve I the But data ultimately Apollo teach see to and focused timings also important will the that there reversal itself think to just HELIOS-B could seeing, we and the will to gives informed the cardiomyopathy continue readout, we're into with that. your data on agree HELIOS-A, should the field I they use in. APOLLO-B discussed extension study, going read-through lead of to And work that U.K. because us we're the love much they're itself. the interim expect and had imaging number that's in of Gilmore there's doing, do. about guide both JAK [ph] that seeing on insights APOLLO-B a in important. a TTR understand And HELIOS-B. on something patients I very and question as And The what and to to we ultimately The from outcomes amyloid We've fortunate, with neuropathy just groups of that we the what And cardiomyopathy. of think these to in out these studies and on group clinically then structure richer published interim. type. insight that's paper inherited so deposition us all like what Dr. I think to guide for points of HELIOS-B to important factor they're on And think the have some and there. be as APOLLO-B And can information exact information the

John Maraganore

question Does Mani? Absolutely, answer that Yes. your agree.

Mani Foroohar

Also there, Yes. Thanks, gotten been have so great have in cardio the great. guys. trial That's would could you way a --

John Maraganore

Agreed.

Mani Foroohar

guys. Thanks,

John Maraganore

you. Thank

Operator

question next our take from Navin Please now go We'll from UBS. Jacob ahead.

Jon Lim

taking question. our everyone. Jon This on for Navin. for is you Thank Hi,

color to for better be which like with Any GIVLAARI prepare the also we And like alluded how recovery it you've bit respect, more perhaps in COVID as GIVLAARI -- be we're and for with assets would as So as appreciated. might ONPATTRO. curious has launch. any geographies. or caused your analogue -- for the We're COVID be to more ONPATTRO? across to mix a shift payer OXLUMO if curious Would Medicaid more

John Maraganore

to answer. Well, to those going I'm over to them hand questions. Andy are great right

Andy Orth

Thanks.

So one. first let's with start the

in changes payer So mix.

of Medicare. ONPATTRO think the is but second this are of commercial Specifically, in mix. material actually here, question United not one. seeing a terms it's early to in certainly neither seeing due two time pretty to the point of changes population, those little we're days largely And of more at insurance perfect, OXLUMO, any COVID. GIVLAARI mix and/or no analogue, be to changes is then, payer vast a OXLUMO with the to in less Medicaid Remember payer that going commercial And in We but right? the Medicare and majority States is we're

GIVLAARI, guess if So helps. more bit similar to that that I a little

Jon Lim

you. Thank Certainly.

Andy Orth

Sure.

John Maraganore

Thank you.

Operator

comes to from And Barnstein. from next Chen moving question Vincent ahead. Please our on go

Your line is open.

Vincent Chen

question. Great. Thanks for the taking

perspective over and that reasons programs ultimate graph achieved, CNS ALN-HTT little for probably and out out the over competitive advantages ALN-HTT to IONIS most but efficacy? space, that notably was siRNA from far a Huntington the Roche might ultimately knockdown the offer in [Indiscernible]. looking a and you platform release the of – on how data there a of to program So really going things IONIS Roche, side sort I the to the Are outperform moment. of will of for CNS the degree or the expect in

John Maraganore

platform approach Thanks So, the for let our with obviously, consistent has that, me you question, seen platform with in the just -- we've compare I'll And in RNAi through that you Akshay. We've marketed liver. in what what with based what by start approach, products. an to therapeutic the over seen antisense the see antisense therapeutics. the deeper And oligo in saying way Vincent. profiles been the see when we've pretty liver primates compared seen RNAi greater hand liver. in the knockdown better we CNS nonhuman it durability oligos you to much an all and and is similar see between

So that to less our an -- will with of in to oligos HTT and course the in platform on is to there's intrathecal of more the which CNS. -- administration opportunity by that a exon leave accounts all Akshay knockdown X. burden more deeper important to some But durable there's potential on Akshay? the specifically comment allow is would more that for expect a frequent we much administration, approach a

Akshay Vaishnaw

I is on before to also what distribution potency, thing exon on better durability based brain get to those other basal we you add terms findings, but the is that than you preclinical just get like pharmacologic RANi of And said much the I'll X, in approach better to of hunting course, Yes. which shown deeper by attributes predominantly. the much for structures our to think ganglia, where need

pathology. significant those literature causes abundance and actual and disease the the So exon And an approaching literature aggregates has what aggregates protein important pathology their of made truncate in of they to that a and X target the lenders be itself. off the exon neurotoxic. now very put appears transit from X role aide attributes strategy pharmacologic suggesting And that themselves to of that then transfers X exon itself play or there's come truncated in and that

X for an not strongest a exon X exon may approach on focused going the be we approach. So agnostic and

have actually to that up support and for forward approach going to we've attractive target with profile. support constantly along sets KOL we as discussed very the think of pharmacologic best the So us a the would We I XXXX. really look can the [Indiscernible] the and the

Vincent Chen

Thank you.

John Maraganore

question your answer that Does Vincent?

Vincent Chen

Yes. Thank you very much.

John Maraganore

Thank you.

Operator

go Issi next from We'll now take question RBC. our ahead. from comes Please Luca

Luca Issi

congrats actually habits ONPATTRO you VYNDAQEL from would doc change prescribing or doc the actually think do Terrific. of be Do that [Indiscernible] but commercial for the will a taking think Maybe to question angle need a little my Thanks HELIOS-B. to execution second, for a more back going here. to APOLLO-B to and here. for commercial maybe on you with sufficient for their bit most wait

dealing Given for helpful. after that going IV be you drug. still We've minutes few six on or would thoughts potentially for that just appetite actually is the what's And to Thank ENAC question. that any you. your if enter Maybe cystic APOLLO-B again, within a have one, second race? power there whopping two, your Wondering approach? competitors seen thoughts of Any fibrosis.

John Maraganore

questions. Well Okay. great

endpoint -- HELIOS-B the amyloidosis months. and wild-type in at uses Andy, uses I'll right answer. And investigational obviously as XX and as distance that like agent walk one study the which is study you now the primary months uses everybody study name vutrisiran non-branded ONPATTRO hospitalization studied a I'd And first I CV with think the ATTR obviously XX treatment. an by both of for a with it's just start and patients cardiomyopathy. patisiran, reminding study the mortality of with being a the that X-minute is is which primary to hereditary endpoint then APOLLO-B

that patients so is we're the and able get And And we encouraged the very both if on the general feel study important with alternative will other an if FDA cardiology and this very an hereditary and be you community that's comment, distinction. with a do attractive approval then regulators to in treat that But positive. Andy to APOLLO-B of for important much quarterly on comment be do should ONPATTRO their approach silencer more detail? In an wild a more option type will a that treatment be certainly a little want for with the in the future. meantime, presentation monthly six perspective on Andy to TTR the with label while broader more will ATTR. subcu bit in our this ultimate patients. And or you exciting based

Andy Orth

to. Happy John. Sure,

cardiologists be very the SILENCER currently amount there in And here launch and wild-type do will the they excited potential note into who cardiomyopathy. expect the treating to are we're choose very with and APOLLO-B United hereditary physicians having polyneuropathy. about stabilizer. strong frankly So To decide ONPATTRO of use today, the experience furthermore, in And to approval, we upon a ATTR meaningful a both. physicians don't also versus And choose. States

And well. looking be front something so to be reimbursement proactively will as on resolve that we'll

John Maraganore

for or -- that bit Akshay little then to from an ENAC how think portfolio not that And example a and you do on whether about or area Perfect. we comment would that's do is programs standpoint you and we Yvonne, a maybe want and consider? --

Yvonne Greenstreet

about and our what's ability short you the ago. term as in in And that history RSV may Yes many be look, demonstrating program access platform aware to with Ocular. an non-entitled our I of we're And tissues addition been liver, we've incredible with well to productivity had. our that lung kind years think delivery increasingly of actually many is CNS the

amount how of So need the of we a clearly And to for we front us. have prioritize think in tremendous opportunity opportunities best we us.

going to continuing you to perspective. about broad forward, utility time. the forward open an our to to on anything? of do fibrosis plate cystic our from execution But this want lot a specifically nothing platform but we move We have remain on explore share add at John

John Maraganore

I want to don't No. know to Akshay that? you anything add

Akshay Vaishnaw

and come mean of assets. I the COVID Obviously delivery front center. Alnylam you lung know has part No.

about And of into fibrosis. have which We exciting. done genetic that with validated as achieved knowledge many preliminary, the very we've validation a very David other targets we've now is lung organs, ago settings mix. itself genetically beyond delivery idea have a ENAC And the of just interesting number and of cystic showing year comes we

it will new COVID and beyond So the forming exciting that's asset to take investor us before this be really on it the itself.

Luca Issi

Great. Thanks guys.

Akshay Vaishnaw

Thanks Luca.

Operator

Please We go question Shu Shreeshant [ph]. ahead. take will next our now from

Your line is open.

Unidentified Analyst

on here. morning. you strong Thank quarter much. the Congrats very Good

Akshay Vaishnaw

you. Thank

Unidentified Analyst

drug any Quick stabilize or guess clinical - then to opportunities it of population? guys second the I patient hospitalization. target guess actually you or data it and given has partnership AGT potentially question different a walk population starting translational to I in six the -- patient question I you patisiran, correlation And minutes on recall population, be have looked APOLLO-B. V severity on you. a guys different on there? quickly will drug, large trend terms think baseline the about program, comes Thank potential Have the at when between response the

John Maraganore

the with me -- Akshay let let quickly. just APOLLO-B question. APOLLO-B start me you on real very Well the let interesting Right. AGT me just -- But take should comment --

We've to like Our certainly AGT in promotional retain develop the partner. is and are do like intent with that program the bring opportunity goal program a of the may company how a We and AGT our on the advance our is commercialize company future to we're focused If going that's But that. the to as on we're growth key that. medicine it at it. to and ourselves to stage have medicine we point forward, and market. that -- we a at an bring that to choose to

to the what But answer question that do Akshay so that's asked? you APOLLO-B And was there. we're doing want

Akshay Vaishnaw

Sure.

Yvonne Greenstreet

can point you Actually John on I just quickly may comment be if made. the really

opportunities. suite other the TTR our thing was think I is of of sort to remember

AGT. actually are robust the so building we that a something cardiovascular we up for plan that's in can as else commercial preference very we We as consider arena

John Maraganore

in for to do Akshay Thanks Yvonne. that completely. I jumping on Yes. Yes then you agree absolutely. want to...

Akshay Vaishnaw

APOLLO-B. about question good Shreeshant Yes.

of blinded an is Now course study. ongoing

sort don't are there be study thing between that's we stage parameters. of what association on good very it maintain distance. look walk X-minute Class and should integrity. the and that tell So associations relationships I you currently I various can't New at can to comment

You from imaging know such relates And to that prior work other as biomarkers hours and know BNP people's other biomarkers. we and work. that how

on never been seven whether missus average sold on terms life outcome and tafamidis whether clear information without And study study was very had on actually a older answer In – of the on or was your look with there patients tafamidis. is Vyndaqel original quality and can there from patisiran for ONPATTRO, Phase outcomes it a often the And their what previously was the out the other there that question to improve, to your had itself of we stabilizer stabilizer improved. is equivalent. APOLLO been III point at then was

for improvement from encouraging really So impact the study features in believe potent was and disease much result of went But attractive point patients. drug. group distance benefit the it mortality. as It's seems placebo, in whilst a there terms know in us study. curve and that be a tafamidis APOLLO in is for study for hospitalization and walk to look did a wasn't which the for the progress. whichever to mechanism of Phase you from quite All pointed clear of down the actions walk uses go just our ONPATTRO context declined III for and tafamidis curve ATTRACT of everything that disease having the didn't whilst at end clearly that's very the It's head-to-head thing X-minute and that's down. good very as time active We including And placebo. it the of we distance sadly one of profound

controlled given with took something Jack distance they amyloid So The of others I a patisiran, that's And and sort stabilization the where were if X-minute cardiomyopathy U.K. group we to even patients. Dr. and year they can that's distance we can improve walk rafamidis. by saw a those aggression of cohort distance, walk walk base published stabilize compared needed If think of imaging continue one study Gilmore better. from actually recently great. in X-minute X-minute

of action mechanism we also pathogenic forward some extent look neuropathy to in we outcomes and use a cardiomyopathy to fundamental suggest and we the disease preliminary evidence know most of think that greater stabilizing the ONPATTRO hopefully And of protein to improving well. we outcomes. the the patients. of So emerging also remove And that around

John Maraganore

question? that does answer your Chen,

Unidentified Analyst

very Yes. Thanks much.

John Maraganore

Thank you. Thank you.

Operator

remarks. to turn would the closing I time, like this to At any back conference for additional or company the

John Maraganore

thanks stage biotech. leading our on is and from you We're teams. our safe R&D have hope the results commercial very day. really progress in as Thank call. all a execution updating Day in QX exciting stay us this our Bye-bye joining and continued now. growth Okay. our December. a Look, continued at with everyone forward on R&D at then, and of Alnylam and pleased Until for great We a our to look you healthy I and you development

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