ALNY - Earnings call 3 2023 | Alnylam Pharmaceuticals, Inc.

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Operator

Good day, and thank you for standing by. Welcome to the Alnylam Pharmaceuticals Q3 2023 Earnings Conference Call. After the speaker's presentation, there will be a question-and-answer session. Please be advised that today's conference is being recorded. I would now like to hand the conference call over to the company.

Christine Lindenboom

morning. Good Senior Investor Lindenboom, Communications and President Alnylam. at Vice Christine Relations of Corporate I'm are Chief Officer; Yvonne Tanguler, today me With Greenstreet, Officer; Chief Officer. Garg, Poulton, Chief Executive Pushkal Chief Jeffrey Medical and Financial Commercial Tolga Officer;

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

that update today's will outlined concerning we XXXX. introductory Tolga progress, call plans our is updates prospects, on under our an future the remarks will remarks by open followed and X Reform today's Yvonne call pipeline offer expectations, call and Securities Alnylam's summary provision Slide harbor financials progress. of During will and before of commercial of constitute context. the and general the provide questions. purposes review the Private review for Pushkal you Litigation upcoming forward-looking I'd safe on statements global X, guidance, which your contain milestones remind a to like Jeff will will clinical to Act and

those with results in periodic materially from those including as a most indicated our Actual the file result SEC. of may report important factors, these on forward-looking recent various by differ statements discussed

disclaim views In views our as this our any obligation not addition, forward-looking date update upon statements date. to as representing of specifically only of be We the of any represent such recording subsequent relied and statements. should any

call turn that, With I'd to over to Yvonne? the Yvonne. like

Yvonne Greenstreet

disappointment. also we continue across great In for the today. XXXX, third thank our experiencing the quarter progress everyone, and of make you, a joining Christine, business while Thanks, to call

supplemental clients application the treatment Food months, the Administration, amyloidosis. new investigational that patisiran of was we U.S. an for the improved last and cardiomyopathy the ATTR development therapeutic RNAi As of drug in Drug for announced the

Advisory with many extremely Committee conveyed, whom spoke have we are of the patients, with at we September. of the to particularly needs this disappointed meeting outcome, in As regard

We confident steadfastly and to study to a those under very committed which remain look as this franchise track building [indiscernible] We top and [ the this our remain for strategy in TTR been to forward next over in decades for journey. sharing step vutrisiran serving leading on have long-term with line HELIOS-B XXXX. X results, ] early important a

strength As we third commercial quarter continue with to ongoing ATTR driven with amyloidosis ATTR launch our in patients by was our in of AMVUTTRA cardiomyopathy, polyneuropathy. progress plans successful in the hereditary the

to XXXX. growth contributed XX% a compared third quarter net revenues This to of year-over-year product the in total

what delivered also than September, the in top tolerability updates millimeters pipeline key the results to which treatment zilebesiran, as clinical adult moderate positive and of Phase hypertension. mercury demonstrated systolic in in blood greater from months of placebo of We dose-ranging XX an pressure important programs safety third with we compared patients profile encouraging X reduction II at In of KARDIA-X study is line quarter. to mild announced

Additionally, supporting or of dosing. pressure potential sustained the the also the blood results for quarterly solid months, at reflected biannual reductions X

disease, the encouraging onset months XX out rapid from ALN-APP a study results tolerability Phase early shared in dose with interim also We I and single patients effects safety to which target positive robust with Alzheimer's sustained with updated an profile. and of engagement and showed clinical

[ the a is of progressive APOLLO-B confidence bolsters stabilization walk months XX the otherwise APP were maintained test Additionally, effects our in at X-minute on KCCQ patisiran of and This from type and study that data is presented we very encouraging steadily patisiran disease what treatment of further of HFSA, treatment. ]. showing in relative through

in step England results accompanied just the which RNAi forward by ago, a editorial these the is in published therapeutics Journal had favorable Medicine New have highlighting disease. weeks of a this represented to thrilled by We're few

as professionals. excited to This industry that place the marks annual survey achieved was third have fifth in the for of featured their X survey top of year we're Alnylam XXXX. in Science Magazine's Lastly, one ranking employer top the companies

to the couple line type by end as more poised year, RNAi updates for therapeutics including our as top a the deliver are of results ALN-TTRscXX ALN-KHK, investigational pipeline Phase We diabetes. X well for I

transformative our And discuss annual on platform. virtually we pipeline I you which puts believe all all driven a by diseases and/or commercializing messages of We [indiscernible] all progress developing exceptional to date this our pipeline of where us top-tier Day, be on and a results. of into all engine, the delivering the encourage Alnylam the biotech while XX, with will XX from Alnylam held with our save best-in-class around of candidates organic tune the high-yielding product December goals, patients exciting R&D will and world rare product across by track our making beyond, and financial and first

our that, call commercial performance. for Tolga? a of let turn With Tolga now me review over the to

Tolga Tanguler

strong the morning, another for Ultra delivering with all continue as with our year and another both was driven patients TTR our of U.S. excess steadily and quarter of portfolio performance good Yvonne, we mature commercial franchise in prior air to QX in of growth Thanks, quarter our our everyone. the on by franchise, our robust increase the market compared therapies. of number XX%

constant for at exchange a net revenues the XX% quarter product third year-over-year or Total XX% rate. grew

me third summary now a TTR of our quarter performance. turn to Let

treatment or global compared a quarter product Our TTR with the were second quarter, X,XXX of patients of achieved revenues second the XXXX. end on compared at the ONPATTRO ONPATTRO our than patient net representing over At growth. X% quarterly X,XXX the franchise the of X% end third growth and representing XX% increase third quarter, for from quarter $XXX patients mutual the worldwide, and with up AMVUTTRA, more million in commercial

international AMVUTTRA following: [ second end ] patients has driven driven Now increase our a sales combined Alnylam switched and compared by patients. robust highlights AMVUTTRA. TTR on let of now are that ONPATTRO by launch. a which TTR our XX% The year-over-year ongoing by was more At in the positive driven strength and was third by received performance. growth quarter, X% than U.S. of patients in XX% the the AMVUTTRA well decrease demand me with third how primarily more In the U.S. provide of product offsetting of patient increased U.S., the time and prescribing of profile XX% and the ONPATTRO at quarter, by the than uptake, been indicating AMVUTTRA a physicians both U.S.

in reported also growth, demand the increase distribution channel. approximately due to by our inventory addition to in was favorably impacted ] X% growth [ the motor an In

compared decreased second markets, quarter. to Now with the let international franchise our me X% turn growth where TTR by

all efforts industry as that AMVUTTRA launched international of recent are and patients in X-month this quarter, factors, offset and the It benchmarks. access was in in is on Japan have a significantly our reimbursement we period, growth faster destocking market in following was therapy secured in of on and in worth of now launches the we patients, partner available by Italy. have noting markets. made including there adjustments the during than team the of and timing which major end inventory prepricing following Although Spain markets price emerging proud the I'm Germany growth of variety orders to

patients quarter than X% OXLUMO million third Ultra-Rare more our with quarterly OXLUMO, XXX Now patients which a commercial $XX and exciting quarter of an moving and the patients increase the on the with products solid X during therapy, with than ended to the XX% sales of our in our on and We ultra-rare second on more compared commercial the combined compared GIVLAARI product with products, XXX in compared than quarter patients representing X,XXX GIVLAARI representing more growth delivered Ultra-Rare and third combined the performance therapy, with quarter a quarter, X% second XXXX. products XXXX. milestone on growth

sales dynamics. quarter, the product GIVLAARI, X% For QX with in the compared regional declined following with second

market, reduction. on a previously to partner large we A driven in from driven XX% an QX our by and decrease of order in emerging timing benefited by and X% net demand where orders in increase increase in a indicated, market, gross markets, higher patients therapy, as U.S. results international in the the

reduction delivered in by XX% For U.S. OXLUMO, second compared a was the the inventory driven XX% by sales in increase product the in and our quarter, our which the partner and demand emerging markets, distribution demand channel, by orders by growth, following: XX% increase driven increase a XX% driven of robust markets. a increased we international in offset with the in partially timing a of

franchises, were of We particularly TT well patient quarter with increase with both as franchises XX%. the in X% growing revenues in growth the excess during robust quarter, an growth pleased delivering both the the strong patients in year-over-year therapy with Ultra-Rare on and as delivering results our in

end to of product anticipate end range. of the approximate As strong we positioning the look the guidance year ahead fourth our a quarter, us we year, midpoint at net revenue to the

R&D that, progress. pipeline it will Pushkal over and Pushkal? turn recent to I With now review to our

Pushkal Garg

good Thanks, morning, Tolga, and everyone.

me our Let TTR start with franchise.

you X approved and large X vutrisiran. AMVUTTRA. hereditary APOLLO-B we of patisiran We've ATTR As amyloidosis. and polyneuropathy HELIOS-B pursuing know, cardiomyopathy ONPATTRO for through have into also for the studies, expansion ATTR been products for

As results, a endpoints secondary all but and consistently insufficient additional just as clinical approve positive previously the exploratory the well, declined for across of to meaningful. announced, not sNDA positive while citing FDA profile. with APOLLO-B The evidence safety delivered patisiran, on endpoint, primary

the into line disease, the aspects disease. period TTR both in we readout have not the walk stable As this in patisiran expected a may of invest the on KCCQ particular, the HELIOS-B. entire of test States. large secure reaffirm contrast data further with in profile this differentiated positive ATTR our XXXX, expected and over elected XX-month with United that cardiomyopathy declines development suggest confidence additional that the were RNAi-mediated The in out result of ATTR in to success result expected in data a this In coming cardiomyopathy in silencing top to of potential for decision relatively approval in study and show from early HELIOS-B X-minute efficacy APOLLO-B and the multiple

vutrisiran patients therapy hereditary the outcome to for to track very around dosing could dated a cardiovascular ultimately position this those a a approved, data, assuming XX-month events APOLLO-B a includes study HELIOS-B to into We and convenient recurrent with to profile is AMVUTTRA quarterly with read wild-type world label amyloidosis in cardiovascular profile market-leading its then medicine market of on designed or is a with period. The for outcomes that transformative AMVUTTRA similar study of mortality label all-cause if composite plan with ATTR of the XXXX. on in as positive the therapeutic believe studies regimen patients a to in The that in that and And cardiomyopathy. powered patients we disease. growing seek demonstrate expansion early XX- with subcutaneous over launched potentially and benefit out the

ALN-APP, Phase on results development Alzheimer's design data first seen proof-of-concept human excited by delivery, for which treatment we initial the RNAi CNS of amyloid is therapeutic angiopathy, I we've announcement cerebral from positive our the and the in to the following study date. on, Moving for are of disease

As study dose cohorts in additional I the results patients few in Part on of a A been weeks of trials time patients At the I with interim Alzheimer's Alzheimer's disease have conference Phase positive ongoing enrolled disease. from look, in the ago, interim we onset this Phase XX single presented study. the clinical early X

We in in and studied APP in as APP and and To treatment beta with APP XX%, in of of XX and patients single APP XX soluble reductions rapid dose. after alpha sustained reduction alpha XX% X CSF. mean dosed respectively, early resulted ALN-APP engagement dose-dependent a and and XX, XX-milligram date, respectively, and beta, cohort. Reduction target months X XX peak soluble Excitingly, the each XX%, biomarkers mean to beta. for alpha day soluble sustained knockdown milligrams dose we've levels, both XX% a XX X soluble reduction was of and saw for with as observed rapid,

Alzheimer's aggregate the also clinical in amyloid marked amyloidogenic for time, in first CAA. that presented forms peptide the and data A A and disease deposits We into beta beta that XX reductions soluble showed XX, the of

of reductions Specifically, after XX at mean were of of months ABXX, single dose ABXX respectively. milligrams XX% and CSF XX%, and X a ALN-APP

relentless peptides disease findings suggest in progression these implicated that devastating treatment that directly X these are an encouraging these interrupt with RNAi of diseases. as Given are potentially therapeutic they pathogenesis, can

doses mild A. single events parameters Part exploration has of not All have well. is were severity safety single ongoing to CSF of in as of significant abnormalities date. moderate any The adverse revealed doses been encouraging and ALN-APP Further of or ALN-APP in

in I'm Netherlands. human in showing Multiple initiated nonclinical States required the the on addition, about dose Kingdom the and United now chronic has study the the additional findings clinical observed proceed to B, updates RNAi program CNS remains impressive transcripts potential In In the Part to and dose in part multiple sum, of study also in and been prior in these to thrilled for toxicology Canada providing the approvals received studies. part has all of to forward hold in sounds the United due the data disease-causing look future. partial

turn development of me progress Let now with hypertension. recent in to for treatment the zilebesiran

endpoints, very placebo are achieving positive top in blood by secondary millimeters pressure ambulatory We a systolic monitoring line clinically X In from pressure met KARDIA-X month compared measured excited and measured XXX X, the with including X II as XXX-milligram reduction significant months at both XX to blood pressure a the and have food month all as results than zilebesiran primary endpoint, pressure XX-hour at demonstrating arms significant greater ABPM to also change change study. blood systolic reported in well dose-ranging systolic and significant reduction mercury doses. of dose-dependent, KARDIA-X, by The office X key as Phase study placebo. XX-hour mean mean subtracted zilebesiran for met milligrams at

[indiscernible] indicate was through levels potent AGT dose-dependent knockdown and durable results study X. month with serum of The associated

early Importantly, look and complete the track results upcoming encouraging top KARDIA-X profile. zilebesiran II AHA sessions month, safety Phase combination of to we deliver ] on for study We demonstrated this remain an to the zilebesiran and tolerability [ KARDIA-X at forward line scientific results from XXXX. in sharing

our [ inhibitors. programs, A ], hemophilia without of with vutrisiran to briefly or on development in of Before or one I update for like the is which partnered treatment I'd up, wrap B

in organic review our expect come. few growth driver results let and Sanofi to dosing just an study, XXXX. key for in FDA me our engine currently pipeline are With a it that, reported are deliver and the for upcoming These to data that Phase with the by they regimen broad a underlying to product sustainable encouraging discussions milestones. over safety innovation and efficacy from we Alnylam regarding driven a the indicated just represents Jeff antithrombin-based III in will NDA in and a turn now financial Jeff? highlights years innovative filing and

Jeffrey Poulton

P&L pleased a Thanks, to quarter Starting growth XXXX summary results our Pushkal, QX summary of I'm million and good morning, versus a QX product be revenues for $XXX QX of discussing XXXX. full XX% presenting results XXXX. financial with everyone. and were Alnylam's guidance. the year our or Total for

ultra-rare Tolga XX% compared growth than mentioned, year. by the As both franchises previously greater prior increase driven with was with growth strong the quarter from our during the TTR and reporting

our in Our modestly Net rate third from to the reported at million, increase in exchange represents sales well collaboration. as growth as certain collaboration million lower revenue quarter from third representing zilebesiran, million a received million achieving X% payment $XX from full a nearly benefited from QX results of revenue Regeneron and XX%. the from our million upfront was constant exchange quarter growth, for in the recognized recognition with was revenue revenue co-commercialization for The collaborations quarter due in $XX foreign connection primarily $XXX $XXX in during ALN-APP. $XXX earned the XXXX program, product development $XXX criteria our co-development milestone increases from early CNS million the which clinical included portion of as

existing demand that where increase patisiran quarter business indication for to which receive cannibalize compared a a million, the as manufactured the of Gross for quarter that with X was launched. ONPATTRO QX, for launch XXXX, primarily the ONPATTRO we XXXX. the in cardiomyopathy I associated approval. sales regulatory on with a U.S. continued continues on write-off has which the driven AMVUTTRA ATTR investor during Recall of QX that was been first we markets call $XX ONPATTRO decrease XX% revenue to to on CRL demand polyneuropathy not following product ONPATTRO future Novartis go-forward mentioned in expect did Leqvio, of our October due have Ambutra inventory XX% which on basis was quarter Royalty third decrease in sales to representing margin of by in

result, increased a the $XXX A XX% compared quarter same third to we As will non-GAAP product XXXX, range. in the ONPATTRO in to count be sales our due million expenses activities costs $XXX million payable anticipate for period achievement higher support primarily to the partner. in R&D XXXX, pipeline to and R&D clinical an related milestones to expense for increased certain head and a to of

the of investments third compared strategic expenses growth, count and period the SG&A in to AMVUTTRA. in non-GAAP primarily the launch Our XXXX, quarter our other increased due X% increased global supporting including to same head

in time with equal collaborations million during QX, driven by recognized during profit revenue Regeneron. operating quarter, and our generated the from $XXX first the we to quarter significant For non-GAAP the Roche the

a profitability. We we revert operating to future loss quarters, anticipate in yet will not have we as that sustainable non-GAAP achieved

we and equivalents Roche related compared $XXX XXXX at loss from billion the the to $X.X cash million the primarily cash, of offset $X.X Finally, to upfront with operating ended the quarter increase of marketable billion our end with securities year-to-date. by payment

to is current sufficient continue cash us our bridge balance financial to to a believe profile. We self-sustainable

to I'd year full Now XXXX to guidance. like our turn financial

included to million. factors increase revenue our The and attributable increasing is $XXX to guidance. $XXX primarily guidance to $XXX to substantial are We from in million $XXX royalty million our that million were collaboration previous not X

the also as of majority guidance appendix accounting the of recognition XXXX in the million the All received of our like from quarter First, other the milestone recognized payment in secondly, achievement third presentation. from during XXXX. ALN-APP which with during today's financial will XX would $XXX with unchanged. the associated full And note collaboration. to are revenue remain elements conclusions third Slide of be conjunction that the quarter, Regeneron zilebesiran upfront our summarized on Roche of collaboration $XXX in I million Roche

milestones Let turn financials me XXXX. our for in remainder key from and discuss some now of slated goals upcoming the

and ALN-KHK, Phase executing development ATTR report of ALN-TTRscXX global ALN-HBVXX type of B. Phase in development results expect AMVUTTRA, We studies intend of our amyloidosis products, II commercialization treatment our ONPATTRO, course, I We the are development trials combination on of to in results of will, programs, of partnered for treatment in and the from to OXLUMO. hepatitis for With treatment of further chronic from be the report top diabetes. for we GIVLAARI line X

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

Christine Lindenboom

we your questions the like you, Thank have To open we you then call Operator, elements, yourself additional . in to questions. limit those ask each now back X for will if and get would you the queue to Jeff. question to

Operator

time, Cowen. this [Operator the comes TD Instructions] Ritu we At session. will Baral you. Thank question-and-answer of first question conduct Our from

Ritu Baral

said where to wanted types I the as which CD to other plan. statistical used that weighted consultants I events be about little ranks that had that this anyway HELIOS-B statistical been more regulators Andersen-Gill -- ask had -- the the in analyzed hospitalization to a Andersen-Gill would as certain are events statistical method, meaningful doctors any more are they for different rank sorry, equally? serious such be the by event Within count, the has like bit and well? of may analysis what death kind developers they and events. Or you're of composite versus in event weighted and understand recurring a using event would of our and

Yvonne Greenstreet

focused a delivering in on Kind thinking given successful the great perspectives. delivered specific to of track you the and maybe and few we've know, could Pushkal, how positive around feel studies we're a we're to a record I provide your Thanks, HELIOS-B have there all But analysis, that date. mean confident you question regards about that question. just statistical study laser our Ritu. been in as

Pushkal Garg

I look Look, lots Thanks, people Yes. there's of Ritu. data. these types at ways think that of

[indiscernible] focus our is think do mentioned, Andersen-Gill then and recurrent felt that. hospitalizations, on you definite As really -- both and can I

to of follow-up for have of increase and differential I that the sort we've study done the aspects is patients. maximize think one power of unique actually

us the So can the actually single follow has And lowest XX of we incorporate seen that shown have to follow-up, aligned to that the range XX variable follow-up Andersen-Gill sort whereas from fell to in that common allows be a to denominator. months.

it some us power. gives So additional actually

team our why we've analysis prioritized our plan. statisticians And in and is -- statistical that's the that

look hospitalization the that So all certainly, means about. those at it we events but those in events talked of you depth depth, as recurrent

the study. So for we that power really think optimizes the

Operator

of your Matteis is Stifel, line open. now Paul

Paul Matteis

on advisory perspective, I of understand, FDA We've extent. not of if are from a the outcomes a fully meaningful what And combo That regulatory therapy but for is on that level it. committee to been appreciate what, in you that if are powered with learnings the p-value was lack I'm study the said, is from subset there the any, kind And HELIOS-B think delineate level think to trying of I a HELIOS-B. show really recent how curious APOLLO-B the Great. top it's issues clinically you related is to assuming data, a about outcomes HELIOS-B? of at effect generating some important would right, tafamidis. that some to the of benefit you added line we

Pushkal Garg

Look, Paul. I of maybe Thanks, a couple points. think Yes.

and TAP TAP characterize very obviously, group outcomes actually bodes wasn't small we But HELIOS-B. look the group, ADCOM subgroup. are was presented and patisiran As that reflected at both that add-on with the that the for made. was various patients, arm. as were to trending regards we to study But groups well we're APOLLO-B And a that non-TAP, designed data the looked when only at data the that in encouraged in we the and previously, the the favorably decision results at are XX congresses disappointed for

study, experience XX%. now overall somewhat about well less an operationally the which we of by as that We've point the mentioned as that, in I we is just around than adds in The in targeted XX% of make we've that that patients. other certainly that we would powering study, have while come overenrolled

that one noting from tafamidis is that was factor ONPATTRO that I because particular probably point I to think the think was regard with mentioning perspective, claim a think with of raised you in is has in KCCQ. with mortality functional Walk X-Minute that what claim Test worth were forward in regulatory of and terms a add-on was points APOLLO-B a the coming

in how are to be And so about drugs et combination these in that or going questions sequence, raises cetera. used

just to is HELIOS-B results. going In deliver highlighted, outcomes you contrast, as

so issue that an of less much becomes And issue.

The other is much longer point this have that we in much a follow-up. and study larger experience

So think monotherapy to we're we'll across of at be at and both that the group. going in I subgroup on. do that able as to baseline of look TAP effect look the the be you what consistency other as focusing And a well When this that's number really side. subgroups

Operator

Our comes RBC. question Luca Issi of next from

Unknown Analyst

ends base on This touch Luca. NT-proBNP for primary shown the have results bio. that it you and points composite replicating on of those elevated, from Is to just the have end up possible as Test that will point? that part is both obviously in endpoint elevate You I promising bridge primary in of end Walk if APOLLO-B HELIOS-B. you they're X-Minute would and way, Lisa want

So as appreciated. that precedent Would would be think way Soft you with infer conversation color Any your Norman ] there bridge. be that [ about a to regulatory to a it? could fair facilitate much use

Pushkal Garg

biomarkers it quality we the raising Walk your like looked X-Minute life, endpoint question. think Look, for echocardiographic was that see pointing at really every the in did pretty parameters and in what much lowering, of like of favor up NT-proBNP. lining functional, is Lisa, or we whether Thanks, Test APOLLO-B data, TTR fact out you're when I

about to they caught raising then And think execution as highlighted, We're that therapy appreciate is fact a study, the confident study focused the an and so the effective a a point on the the that. delivering design point this their to I we're still process despite the of the Yvonne benefit modern very laser study. top in on BridgeBio you're think and of results, in of successful I patients can that that I earlier certainly, your the era, overall in disease show point disease progressive being

in setting. -- And so that

So the we're we're this. and encouraged are study adjustments follow on make plan as analysis there what any out. by will is in designing overall to how really up the mentioned, tweaks we it's we've And laser-focused that If due course. statistical

Operator

our question. Merle moment of One for UBS. next Ellie

Eliana Merle

Just on kind potential of for combination. again,

vutrisiran are And perspective, ATTR Just success say, then thinking of think cardiomyopathy want with to on that just mortality, in do what be from what of you you HELIOS-B? a And in there? And assuming terms the proportion payers with the benefit commercial tafamidis? the readout monotherapy of versus, initial patients out of weight this coming quick can year? expect a second of just of Say, commercially, tafamidis, then anything data? data top [indiscernible] the kind we any treated how terms include conversations from I question, of Phase a data sort loss about combination hospitalization, the will of see say, will of

Yvonne Greenstreet

Right.

the with ] Look, anterior we is to with you about really that minimal polyneuropathy, physicians. be ] with a [indiscernible] [ it's believe question. going option And with the addition demand maybe you [ patients used could we're AMVUTTRA, highlighted going important if the progress to profile, first speak really thinking through in differentiated take believe potential a a is this to for tafamidis. co-pays. earlier how patients that maybe given patient for treatment specifically So respect Tolga, growth important vutrisiran to we Tolga the we'll for at that infrequent administration, your a look

Tolga Tanguler

the and is our at infusion, based be and Yes. versus to clear really been track rules where able game switches. already actually Europe subcutaneous has important, actually by innovation cardiomyopathy to markets also that available business very polyneuropathy. I a we especially on to tablets We've build believe changer versus the mean attractive tablet our an that and but going research, really of day, is then price-sensitive it business one which with able not tafamidis if record, for you build to patients is look in AMVUTTRA just in I in we strongly need is polyneuropathy, been I points in make think availability -- be believe net

unmet you about actually Now to about of in would built about of need -- that the in to really going this for mixed sense we're genotype to already you to to and the will give in payers. But -- patients is with patients data. going is We're about the on medical elucidate -- that to our best indicated were which how that to U.S., already already And this the tafamidis now for profile enroll have, XX% obviously position of we for with terms need, is sort the able combination is way really we've us our important. just going be be again, think similar access engage a way to at an is the and alluded be if the because going you do patients polyneuropathy alternative. is believe to to work we tafamidis That's the out, how the indicated granted the important positioning XXX HELIOS-B obviously, we're inform best business going cardiomyopathy. progress, we patients able to early look program and we been

Yvonne Greenstreet

look give taking Pushkal the question kind chance end of great about to avoid ask With the we data question seeing Thanks, obviously KHK, everybody KHK, to forward we're the Tolga. multiple That respect to answer. to of questions respect the at the on was call trying to a to year. in your explained a more final

Operator

Lebowitz of comes question David from Citi. next Our

David Lebowitz

of profile differentiated allow [indiscernible] is talking in of a You some space. about question very earlier versus HELIOS-B And regarding questions. other that therapies spoke the the my can for earlier

demonstrate physicians analysis. upon? populations different slightly the would differentiated? that slightly to be of you easy going different Given levels different statistical aspects it actually from How with to what actually of with they trial endpoints severity, is And is differences, a data their the profile to each are other have modified focus

Yvonne Greenstreet

One thing, reflecting maybe demonstrated, XX-month can the many in maybe on data off start already stabilization disease and APOLLO-B sort the you the seen by from we've also of that some data of patients. of actually

Pushkal Garg

evolving of in analysis unmet a for you -- to thanks, the though, right, that growing Yvonne, have knowledge, and your Dave, done. Look, benefit fairly field, example, aren't all, there -- are and rapidly, had important what Thanks, your data that's right variations, at, to is is absolutely. multiple statistical there Yes, of think -- are we're it's looking forward. with question. any first coming this right? way So that field and of the because therapies recognition out some the of in using you're the -- And endpoint everyone patients point for of need, I

of have what patient you're step at various time. are how in, forward they -- [indiscernible], thinks are the that's I at is this arhythmias, exercise, I back with coming from may affecting present looking life then how progressing clinical worsening the a marked of NT-proBNP in that's they But disease stages, data, poor they quality by do this it And when develop at. Their is, are they're seeing look is a process. et with by think rising, of when drugs fatigue, data -- to what if and their what drug about terms at thickening, they're -- look parameters and I coming clinician cetera. all hardest think you are the looking is they this it, -- believe, disease And clinicians at the at various think these they and that about decline looking is echocardiographic over

think functional of for TTR think effects across I that stands really unique mechanism Yvonne that whether to coming to see progressive it's X the to, APOLLO-B all stability -- whether And Walk starting graphic, steadily you in alluding Test using both we've when an favorable really potential that's was biomarker-based. looked X-Minute seeing at indicates and see on parameters we're type action. think out life, years these different disease And a a of RNAi upstream as credit out When are KCCQ I out, of of I silence it's what profile quality very was we remarkable. whether of otherwise quite to it's that and

where having years, think both clinicians So highlighted PN of with are patients get experiences told is taking think again experience, look, ONPATTRO clinicians now for AMVUTTRA mixed and I over time, now many care phenotype will and AMVUTTRA and -- as this patients. I

they're safety these also profile, the medicines. and to the think profile getting efficacy I tolerability of accustomed

to medicines in of helps, for of of patients. I their how all understanding think, terms physicians So use that

Operator

Our next Richter Salveen question Goldman comes of Sachs. from

Unknown Analyst

Salveen. for on Tommy is This

how you flexibility necessary? on follow-up, to terms And of XX that TAP HELIOS-B differences? And get baseline the seen line baseline data similar other HELIOS-B, APOLLO-B from was back notable if have as do and of any the do top to potentially higher on push user, and until months patients to HELIOS-B So characteristics? all genotype besides cap there be HELIOS-B you the patient in populations for are

Pushkal Garg

HELIOS-B are being I about I in and The general I'd that general, Tommy, what say think patient the in the around We the same right? same. the populations and APOLLO-B entry Yes. similar, as studies fairly think is started time. criteria would

the a again, about, across these we this of of I that come about. here on is we've what seen talked But tafamidis. one has higher the and I that long. by large study think proportion in the the you the similar. baseline as and that's for as is the about twice large, us to think fact patients that all allowed we've positive As measures helps exception of APOLLO-B And -- But Xx talked benefit out results being different would

the you really to for on to follow-up allow as the have we follow-up, designed follow-up and The differential that patients. is maximize know,

asked endpoints. I as well, that sort really this or So maximize can of of as was the think on the some think gain that power earlier optimize I we

in So early 'XX. forward results the we're presenting to looking

Operator

for moment one of [ And Jessica question. next JPMC. ] Fai our

Unknown Analyst

for ] This Fai Jessica Nason is ]. [ [

Why the you Assuming from of AMVUTTRA net the polyneuropathy HELIOS-B is [indiscernible] not? or why on envision just price positive, current cardiomyopathy? do changing

Yvonne Greenstreet

Yes.

other want according make our line don't to in from to to access Pushkal ecosystem we're XXXX. to in this point top we about approved process early days pretty ]. than I specific general, obviously, expecting comments clinical at for as And say, time, here and to [ yet patient early it's it's think us any results pricing, physicians patients said, value really, in provide So being

that's point in can that's the time. all we I say, think

Operator

for the One moment next question. Maury Raycroft of Jefferies.

Maurice Raycroft

was our buy-in and more into to the HELIOS-B? elaborate require on have chances to on mentioned think up entail? tweaks that could lock. HELIOS-B I the the for call your how that what until recent analysis FDA this Can of you conference database it opportunity fiscal flexibility success plan you factors it Would make

Yvonne Greenstreet

Yes. comments like to any the a question? No, you'd great that's question. make Pushkal, on

Pushkal Garg

are think probably -- as industry I'm et at we looking subgroups, on that going it's Maury, at previously, in Yes. from are statistical changed et been be cetera. made. which tests, in study. obviously external nonparametric restate We've to cetera. the And here looking normal In sets, we've is there is tweaks teams to our Alnylam, data et practice I instances, at can and has looked what past we've We're data the talked about parametric added cetera.

not. things it sets done done speculate the analysis aligned are that primary or going So are to that are going terms of or -- methodologies in or with there that being be or analysis either overall not what's be prespecified help with about maybe can I'm can that agencies the hypothesize comes applied. to data

course. share material if information -- there, in I certainly we'll that So but there's you think due with

Operator

us Wang Next question, Gena give one of Barclays. moment.

Huidong Wang

on up Maury's follow just Maybe question.

I each tafamidis. follow-up have the flexibility XX. another it's flexibility regarding now, you to quick time to question planning month facing a right plan And do look still are or slide, add, -- then to very willingness your because follow-up -- saying when months? additional extend regarding you say, last at So and And any XX

it that I Was that it Just correctly, to on And to Or close for benchmark baseline wanted you've of sure make good think a about correct? is regarding patients tafamidis? Pushkal, bridge also the mentioned XX%? tafamidis HELIOS-B? was is dropping, XX% XX% I heard

Pushkal Garg

Maybe of Gena. just points couple Thanks, to Yes. a clarify.

XX design, variable terms follow-up study has design So of to look, in the the study months. of XX

majority the occurred, but way follow-up be during the study the months of because that portion the variable XX patients the will out the context of of enrollment is following of we study. so blinded the And there to in the

under of designed in And baseline then the came tafamidis, remains we that that XX%. stated we study. what previously, with operational drop had terms when in had as assumptions In rate we below the -- But said in we've is of we we an regard number. drop to target the that

what tailwinds offer these of of in all in the study. terms we of overall again, So the believe powering

that helps. hopefully, So

Operator

next from comes Stanley. Our of question Ulz Morgan Mike .

Michael Ulz

Maybe share top a When that can results. on you just sense and will year, early include next line give the another what detail you the you data data follow-up level us of HELIOS-B. in

For subgroup we example, see that combo will tafamidis analysis?

Pushkal Garg

and prespecified as a top it's at during the along results, data for the with Yes. norm will subsequent on an hierarchical then along I our Thanks with think presented line with endpoints, we safety congress. p-values question, present update Mike. scientific Look,

Operator

company the back it This remarks. for I'd question-and-answer session. concludes the now turn to like to closing

Yvonne Greenstreet

of to Thank with on call. and you, a across the and our for our in Thank day. business, third you very progress have with goals. on Great. very pleased joining in forward everyone, you we much, months us this deliver progress as We're we good quarter the coming sharing more XXXX look the

Operator

for program. you conclude in This does today's the Thank conference. participation your

disconnect. may You now

Alnylam Pharmaceuticals (ALNY) 2 Nov 232023 Q3 Earnings call transcript