Earnings call transcript Q2 2023

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Operator

Good day and thank you for standing by. Welcome to the Alnylam Pharmaceuticals Q2 2023 Earnings Conference Call. At this time, participants are in a listen-only mode. After the speakers' presentation, there will be a question-and-answer session. [Operator Instructions] Please be advised that today's conference is being recorded.

to conference like company. to now would hand over the the I

Christine Lindenboom

morning. Senior Communications and Lindenboom, am at President Good Christine Relations Vice I of Investor Alnylam. Corporate

Officer; are me our Garg, Officer; Chief Greenstreet, With the Poulton, Medical Chief phone Jeff Officer. on Chief Officer; today Chief Executive Financial Tolga and Pushkal Tanguler, Commercial Yvonne

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

two, Yvonne provide During offer as your we before our summary today's progress, on slide will our general call review will the call, remarks open and introductory Tolga global will review a provide of clinical financials an will upcoming and update Pushkal outlined questions. to some on and and milestones pipeline Jeff by commercial guidance, context, progress, update followed

on Act may in call remind the forward-looking various the remarks and with which constitute differ today's I’d forward-looking these those by result expectations, indicated Safe like provision Alnylam's that a periodic as the plans, SEC. statements for will Reform to future Securities of factors, results Litigation XXXX. recent report Harbor prospects, most contain statements including you the concerning Private those important Actual purposes our materially discussed from of file of under

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

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

Yvonne Greenstreet

to quarter the the joining across call our of business. everyone In Christine Thanks you progress and XXXX, continue we great thank second make for today.

XX% TTR year-over-year launch performance, in year-over-year commercial XXXX. growth drove the with quarter to with total of the growth XX% our franchise again second product growth once sales in with compared Starting AMVUTTRA strong and our

reaffirming the across of from our ATTR in APOLLO-B potential where study, amyloidosis strong clinical months data of notable cardiomyopathy. delivered our positive Phase included We XX patisiran X pipeline, also execution results

X sustained study onset showing safety months effect In positive July, an with we and clinical in profile. early and updated rapid dose shared ALN-APP disease, target tolerability of from the single and engagement encouraging robust of six patients Phase a with with interim results Alzheimer's

paradigm executed Additionally, us side. a potential believe for strategic entered team we on zilebesiran, to remarkable the our notably, with of the treatment a global we what with providing development opportunity with hypertension. Most and business potentially a partnership commercialization disrupt for is program into transformative bring development forward to a Roche the

be announce and continue always the of particular promotion interactions regarding closed Operating our with to no morning to also and has Attorney's will we Massachusetts cooperation and business with ONPATTRO US has of with concluded action. the their in following to pleased to and continue been that full providers our Alnylam US now with the marketing standards. the Office and case this highest hold the We're in our patients, government, for ethical healthcare the our District will integrity called and conduct,

half our ATTR back review, regulatory and several including potential data important X initial the we of KARDIA the of the move As launch AdCom positive from with and XXXX, zilebesiran, into we ONPATTRO successful a program and cardiomyopathy. have pending Phase catalysts, amyloidosis

exceptional first pipeline commercializing diseases rare top while our all on high and making Alnylam transformative financial of for medicines world, yielding all the candidates from and product PXxXX around with track best-in-class a engine, a puts of developing tier biotech our driven us by for patients beyond company, organic and/or believe We goals, results. this delivering product Alnylam

the has innovation key our of XX and role share focused over, for is as with science and yielded be role an of leader, Alnylam's R&D we exciting biotech Innovation of drive Leader the nearly transformative serving within on transitioning Scientific how to our officer. new call innovation into helm pleased continue entirely new to build will future which at has very the I'm driving as that our class and become Akshay Alnylam In the engine, a his Vaishnaw continue of tier been to programs hand company's top to will years, the and Akshay we Chief medicines. Key effort Akshay President new and company. that lifeblood first the development I before have organization, research will Further, medicines and a

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

Tolga Tanguler

and strong and franchise which Yvonne, our Alnylam, driven markets, AMVUTTRA year. ongoing several has across it started everyone. another by good US QX the been was for of the strength of TTR for where with now quarter available has a over Thanks morning our launch

all Our QX. total revenues net grew product across year-over-year in products XX%

X,XXX review for from second ONPATTRO quarter, at ONPATTRO our of now X,XXX global compared the patients $XXX increase the X% representing over TTR performance with TTR quarter over At first end and product net revenues or quarter me patients on the of quarterly with AMVUTTRA, end AMVUTTRA Let and XX% growth. The representing of compared franchise in million the during growth first the treatment were quarter, a QX. patient second achieved the XXXX. XX% worldwide, up

as is to as launch, with AMVUTTRA months patients than from growth six mix its AMVUTTRA UK, driven patient versus encouraging total the increased X% particularly performance, by quarter, TTR our the second new Japan more in being Japan in international launch demand our being UK recent to therapy. strong most tafamidis, product a driven growth and market. sales respect naive After demand With switches by first quarter the since well of

AMVUTTRA a to where sign not as markets AMVUTTRA ONPATTRO Importantly, steady upcoming of in markets for position launches. is continue available, activities yet deliver robust our generation demand these growth we

decrease quarter excess the on US, the let year-over-year the achieving turn sales increased the XX% demand, growth, with XX% and more the consecutive of a than offset basis and AMVUTTRA Now growth slightly of was which year-over-year where combined robust was XX% offset launch dynamics, primarily in fourth XXXX. inventory the reductions on the quarter to demand AMVUTTRA channel in by and in since versus growth first by of third reported ONPATTRO that approximately by me XX% significant both which the in X%, a to in by This AMVUTTRA ONPATTRO of US inventory driven patients TTR switched growth quarter robust representing decreased increase of a to products.

franchise our continues product in growth with patients unmet the of the the AMVUTTRA. the by profile naturally to polyneuropathy as year-over-year need our a AMVUTTRA capabilities is of and steady growth. overall significant performance to of testament AMVUTTRA reflected The expand TTR commercial TTR polyneuropathy, US

of XX%. indicators our trend have performance A we prescriber leading continue into launch, and resulting patient the year over Our favorable including also favorably, to expansion in base compliance rates of who increased majority our while patients almost of specialists, the community-based the AMVUTTRA switching through ONPATTRO by time prescriber a base mix XX% a launch. of and at centers balanced academic are access, of

Now update on franchise. Ultra-Rare our

XXXX. to compared XX% the proud Ultra-Rare representing developed and patient $XX second commercialized greatly. a XX% small with are growth transforming with and sales suffer combined quarter GIVLAARI populations two a and quarter, products, the of increase first OXLUMO product compared during that We second have delivered quarter million the solid in together

patients commercial first commercial than products XXX quarterly of than the with therapy, growth We X% in our more XXXX. ended compared and on combined GIVLAARI patients on quarter representing XXX with on the Ultra-Rare more OXLUMO quarter therapy patients

therapy our an international revenue number For in quarter and was first compared XX% our in GIVLAARI, of in in had US, on positively compliance following. growth which markets. the global by markets, by A growth as impacted increase order of the patients was QX demand as timing both well the XX% we the In increase partner driven patient rates. in an robust

a quarterly unfavorable in in dose Overall, offset regimen, markets markets, driven serve was quarter order growth. on US in in our partially fewer result primarily which pricing markets. Growth of an in partner flat OXLUMO, offset quest patients. was patients a our by revenue growth timing was European of more was modest international to another patient For revenues mix by XXXX healthy QX, which loading

option launch, are steady year of polyneuropathy. with particularly a with over therapy with -- pleased which hATTR patients With AMVUTTRA, since important for our growth represents an we the amyloidosis

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

Pushkal Garg

and everyone. morning, Tolga, good Thanks

where evaluate the to by cardiomyopathy. start and our know, you me updating HELIOS-B studies, patisiran vutrisiran, ATTR and of on franchise you we're as safety conducting TTR Let efficacy and two APOLLO-B in respectively large

for announced, the Committee patisiran the as of on be under sNDA discussed will Renal positive Cardiovascular at application on Advisory September based and the recently The XXth. the study, is APOLLO-B results Drugs we FDA and review

to provide in the response cannot or was access centers therapy. inadequate treatment. last ATTR protocol We The United established today the after patisiran a target XX and tolerate available for for completed. pre-specified patients shortly enrollment for The that months, about to was cardiomyopathy expanded was XX met States EAP indicating open in an who've patients the of offered XXX in demand US amyloidosis patisiran significant also access this EAP currently potential with readout at enrollment August has announced had APOLLO-B with to that was

from Heart update the of XX-month recent Failure patisiran APOLLO-B Another important presentation at on was ESC results the Meeting. recent

both capacity assessed we the to period City As receive patients ability for to that According by through assessed as well to double-blind were were the as effects quality typical test, trial. In disease. of on endpoints, is after life the of slow patisiran walk patients during status this of XX decline sustained that extension on a reminder, encouraged see study, the the period all analysis, the of as appeared health Cardiomyopathy functional open-label new Kansas the favorable XX-month receiving in eligible health by patisiran these were functional very patisiran Questionnaire status six-minute and and to in months. as the

associated KCCQ evidence And stabilization, block initiation six-minute who the receive the double-blind double-blind to initial period. patients during both in similarly period, period relative was test and of with the placebo in OLE patisiran of

an encouraging concerns Importantly, patisiran through XX safety to treatment demonstrate with continued of new safety months identified. no profile

other exploratory endpoints evidence as encouraging We with of secondary saw and well. efficacy

a during a in relative cardiac of XX in patients of the saw period. rapid of measure patisiran rolled with from cardiac seen who Troponin treatment slowing relative both associated increases stabilization with double-blind injury. over treatment measure the OLE and Continued were stress I, to through during months the that And active was stability placebo NT-proBNP,

was these of to study follow-up outcomes APOLLO-B extended encouraged OLE outcome the trends favoring to or show period. patisiran treatment on endpoints, while benefits see hospitalizations were non-significant designed not during death, the addition, we with In in

cardiomyopathy. with sNDA the including is to patisiran label As approved, upcoming months with the advisory we agency, XX the engagement our patisiran we with as its FDA previously look our submitted amendment to patisiran, continuing for if at forward and announced, to bring ATTR expanding we've an the committee amyloidosis results to patients to

very presented from been proof-of-concept July, had time cerebral were At enrolled human updated to is the our designed for for RNAi three Congress AAIC Phase positive interim of angiopathy. study look, A treatment interim study. in X in the first Early-Onset results We amyloid excited patients we in share Alzheimer's patients with delivery, cohorts on also the disease therapeutic development of initial CNS disease. Part of ALN-APP, which Phase dose data this and At in XX the in single X ongoing Alzheimer's the

in To dose early studied engagement of than in alpha with sustained APP of reductions for and knockdown and beta, in levels, milligrams patients alpha as the Excitingly, at rapid least and dose respectively biomarkers resulted observed greater day soluble sustained tested four to ALN-APP and XX% for highest We soluble cohort. knockdown the treatment and APP for at XX, the rapid six dose median each date, XX, XX And was XX both saw we've biomarkers both of three milligrams, target six CSF. dependent XX% beta. knockdown as maximum months. XX%, XX and dosed

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

Part Further exploration ALN-APP of of doses is A. ongoing in single

trial In clinical The United the study remains updates to transcripts has B, RNAi causing be we where future. multiple the some, on clinical these in were studies. providing study Part dose prior multiple in the disease data initiated of Canada of human up the majority Part addition, provide able look the the due that patients been of observed findings sign toxicology A non-clinical States to enrolled. hold the CNS part dose part partial and first forward in In the evidence about impressive thrilled program that ever to additional use from may I'm to chronic in the

to recently in journal. importance England the zilebesiran. now for lowering the marks recent hypertension. the in very We're development Let with and highlighting doses substantial publication of Phase the published me medical now Alnylam's data Medicine, in announce to with durable turn of were single blood treatment of XXth zilebesiran Journal progress the seen this New of pressure excited of medical This prestigious X

has exciting collaboration KARDIA-X zilebesiran track of Roche these commercialization Yvonne data development which now study, recently the is data. basis to already dose the with line of the on impressive forward Phase QX. for highlighted in ranging X for of on we announced We're results top the looking

anti-hypertensive addition, In to KARDIA-X on patients of safety hypertension completed to recently pleased evaluate aims with we're Phase enrollment other when Phase uncontrolled which the KARDIA -- medications. and the of X have also study, zilebesiran in efficacy X top in added

report We in from top study XXXX. expect line results to this early

our organic broad innovative highlights sustainable to for growth come. engine from few Alnylam product pipeline in deliver by underlying will expect driven a are the These our years just we that and

With financial over it to Jeff milestones. our upcoming results review me let now in Jeff? to turn that,

Jeff Poulton

morning Pushkal, full presenting be year I'm Thanks pleased guidance. and discussing summary and QX good financial of a our results everyone. XXXX to Alnylam's

moderated the of or revenues revenues GIVLAARI product QX growth $XXX rate increased product the AMVUTTRA primarily the Total exchange XXXX. for the driven a constant only impact US P&L exchange now sales growth. reported X% launch were in of year-over-year the previously summary in The growth our with growth XX% TTR XX% as is the quarter OXLUMO patients third basis on year-over-year in million the indicated foreign of well versus by therapies. Tolga with results than our XXXX, product increase Starting as has on rates to of second higher related and on quarter. for our quarter

for work with including Net collaboration of revenues decrease variability, operating our Regeneron. due second reimbursed quarter level were XXXX, XX% primarily $X quarter the the million compared collaborations of from or to the in with

the quarter in first a our primarily from million Leqvio, and and revenues Despite for of achieving the confident which revenue was launched growth Royalty was million US Leqvio range, result $XXX full to driven which during driven million, XXXX. milestones. quarter collaborations of and royalties, the modest in $X year by sales Novartis's by in remain we Regeneron royalties $XXX our collaboration with guidance the

was quarter inventory with canceling for product margin as Gross ONPATTRO quarter, switching the XX% to to X% other The XXXX. in primarily incurred representing due sales and decrease on with of was fees continues demand the commitments second ONPATTRO a to decrease for associated driven decrease compared patients adjustments manufacturing to by ongoing AMVUTTRA.

the period expenses and Our support R&D to studies. KARDIA-X non-GAAP quarter compared XX% development the expenses in headcount the increases in clinical primarily associated our X to with R&D XXXX, increased in KARDIA-X, to Phase second same pipeline due

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

compared more improvement a operating Our and top million offset growth $X by by line QX for moderate $XXX the expenses. loss growth was quarter non-GAAP with driven representing strong million, operating XXXX,

the of billion quarter $X.X at to operating compared with marketable securities equivalents due the with date. primarily a billion to $X.X XXXX, Finally, loss cash, our decrease ended to and we end year cash of

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

guidance. full we net billion. $X.X Starting product combined like where products between year issued billion Now reiterating previously commercialized are to four $X.XXX to anticipate will revenues, our to for I'd our XXXX continue we revenues be financial and our guidance turn net product with

$X.XXX and and remains million remains has collaborations a from revenue and SG&A between million. guidance billion. unchanged net our non-GAAP $XXX and billion and expenses for arranged $X.XX $XXX for R&D range And guidance between royalties combined Our

turn and discuss for mid me key and and financials late slated milestones some from Let now upcoming goals XXXX.

We global course, of will, commercial of commercialization products. four be executing our on

this expect meeting the With results Renal of patisiran, PDUFA with Cardiovascular Xth. study zilebesiran. Committee KARDIA-X Drugs September we October thereafter look line quarter, forward Phase top upcoming X shortly Later XXth from on to we on the of report and the date to the Advisory

of line the of also results amyloidosis and X report the of diabetes. We development intend for and and type for treatment to ALN-TTRscXX, top two studies ATTR development treatment Phase from ALN-KHK

with additional for treatment programs X RNAi of report expects development ATLAS partnered and Sanofi or investigational or A results the program Our inhibitors. to patisiran, Phase the therapeutic without an B from hemophilia with

expects report Vir the of further to for combination of development Additionally, Phase trials chronic results HPV from X ALN-HBVXX, and treatment infection.

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

Christine Lindenboom

those additional if one open Jeff. then questions. get limit yourself in, call for have you, To you we now like in queue the would Thank and questions. to Operator, to we'll you the question back ask dialed to

Operator

Thank session. you. We'll Instructions] the question-and-answer now conduct [Operator

question of Stanley. Morgan Ulz comes Mike first from Our

line is now Your open.

Michael Ulz

Hey, for why thoughts updated focus question. you decided taking the AdCom on just CM of to host FDA and and the to the Maybe the where guys. ATTR upcoming terms panel in the Thanks Thanks. be? any ONPATTRO quickly, then expect

Yvonne Greenstreet

that thank have going really recent in heart topics to preparing KCCQ, to Whilst specific data question. patients test the So, the no that and Clearly, you for time, at given the APOLLO-B. the committee. advisory be on guidance endpoints the utility of that fairly believe six-minute this we forward with failure. the from we're looking around for walk presenting these we questions focused there are actively of in and clinical are meaningfulness the FDA particularly the changes We're

a data described. XX-month believe the Pushkal compelling really APOLLO-B that and wide study of We range has from by validation have supported recent across endpoints for that we additional data

FDA. We have to submitted the

else to anything Pushkal, add?

Pushkal Garg

Yvonne. I think you've really it, covered

is multiple important. value evidence Patients is We we're series that is we're across -- and enable And and which the really look life. they advisory -- is endpoints, to that OE ability the measures been to with that of disease preparations this to of underway. submitted. critically really their feel data what a and generated to forward presenting with that's that, their we our stabilization really what And reconfirmed across seeing with the we about think, that's patisiran of data set good appears their I really quality it seeing review. APOLLO-B, extended as we're -- committee functional

Yvonne Greenstreet

Thanks Pushkal.

question? Next

Operator

for the question. moment next One

question Our Luca next of Issi RBC. from comes

is Your line open. now

Unidentified Analyst

taking Thanks near just for plus first, is million know substantial wanted on our $XXX milestones. specifics questions. the deal Roche entails some on to zilebesiran. We deal into This I Lisa for the term dive Great. upfront, Luca.

to has end Roche Your to X. another to partner get said Phase of they million the $XXX that expect invest

if the So, add and part wondering term any expecting. that just of can this you milestones is million clarity Thanks. near on $XXX the if you're substantial

Yvonne Greenstreet

value That's a pass we great is but moment, really patients that everybody opportunity a that to a our in in hands it question, therapy have launch. hypertension, and for product global I wanted zilebesiran with changing maximize game a on what the I'll Jeff a we just successful and here good clarification. drive feel to to with remind really for

their -- the with to come and is want specific proven here. leadership the outcomes about together various a the endeavor. And successful what to global commercial significant to bring help in market it's collaboration the milestones. allows to our We to the about footprint data and be some the important with resources stakeholders. of is and of that's to think capabilities RNAi us I be the inform And maximize order cardiovascular details us Roche and capabilities obviously, help But

you maybe So could… Jeff,

Jeff Poulton

Yeah.

clarify just Let that. me

are, an development which million for $XXX of that CPOT could patient we additional to talked the So, that development and million study as And in in near KARDIA-X, milestones referenced milestones that's for we about is $XXX there's additional the million deal call. potential down had $XX Pushkal deal announced X that first we the on we actually initiate term next initiation earn, the broken substantial And the that X [ph], the year. Phase then the the study. on expect Phase when study

So taken $XXX together, million. the that's

pipeline of out-of-pocket perspective will XX% that bill put of cost allows at for to for capital Alnylam put look us really, you and the Alnylam really forward hopefully the us, drive reallocate which with where will take growth. financial to Roche an the and the When market then from burden to development sharing, additional this the drug our bill, XX% in across minimizes combination

Yvonne Greenstreet

That's great, Jeff. Thank you.

Next question?

Operator

for moment question. our next One

David question next comes Lebowitz. from with Our Citi

now open. line is Your

David Lebowitz

have data taking move Is the such intent the PDUFA FDA Thank you major a for consider inclusion. exhibited much consideration on three they point? any at the months the there for any ONPATTRO, of submission this the date A XX months and know amendment down the my October. very by PDUFA I not Or stands this question. date question in road?

question AMVUTTRA ONPATTRO it as And maintaining is overall is how quite on to is growing there's franchise as well the given no is franchise growth, while this doing? much point, well, how share

Yvonne Greenstreet

questions. great Two Yeah.

If to franchise then of October, I'll we'll We're course, eighth. the take the continuing around your information. data moment, changes, the of So, AMVUTTRA. working anticipate the Tolga date that this over to the we're ONPATTRO PDUFA eighth, and But dynamics date PDUFA we that. speak on are of using continuing and towards and question any of expect question as the between October, new PDUFA to a I'll to hand overall to communicate

Tolga, do turn question to the to want ONPATTRO on dynamics? you

Tolga Tanguler

Sure. Happy to.

ONPATTRO US we to as within and continuing only the is AMVUTTRA markets I an launch that have markets the way newly this in franchise. about option So, and are should think recently are those think

As our quarter-over-quarter categories, the would growth is look growth at last consecutive I indicated really And US primarily if on driven quarters, the you by TTR in four substantial. AMVUTTRA. quite call, which that's XX% uh,

that at getting the in when smaller patients remains AMVUTTRA ONPATTRO is of number the fact, we time In smaller. the launched US and

with are pleased switching over to how patients AMVUTTRA. very we're So

UK. We're Japan, in name providing is key also make we've to start an was sure that those now in in accelerated markets like other And getting approvals we're France markets we're program APX seeing creative option. in with several very as patient the program AMVUTTRA seen

Spain as we're you in growth. good where is albeit testament not a business need smaller robust of reason and option And our to growth the good available, growth, switches that's, strong portion well like which Italy positions and in at able polyneuropathy, uptake see to on market an abilities this from the of why We're again, the we've our strong, of subsequent yet as persistent time to good, AMVUTTRA ONPATTRO to obviously ONPATTRO start seeing a seeing commercial see in AMVUTTRA. drive robust going nicely AMVUTTRA very Now, been these to of we'd a AMVUTTRA is that -- still other markets. because a a us like launch good markets and

David Lebowitz

Thanks for taking question. the

Yvonne Greenstreet

Thanks Yeah, thanks. Thanks. Dave.

Let's turn the next to question.

Operator

One moment question. for next the

comes Stifel. Our Paul next question Matteis of from

line now Your open. is

Paul Matteis

Hey, reason I thanks wanted Akshay's so to change. behind much. ask about any role the timing and

I think Akshay such all with call. ago. months up, pivotal time AdCom became I And the it's XX him haven't on coming data. for Alnylam the President just a this heard HELIOS-B at

expound So, or a could I upon much. curious if so today. you just behind Thanks bit, this and decision the announcement there's clarify was anything this else little if

Yvonne Greenstreet

also to our R&D to continue be across to tier So, I'm to biotech Look, built is build to on that organization. the this Chief going focus innovation that we've Officer with We're capability we focus capacity Akshay specifically continued research for delighted Innovation thank and allowed strong, development helping And become opportunity question. that and our a first more able robust top personally delighted to that as that's company. organization. on a respect deliver really Akshay you on to take success

continue him that call felt we allows have more strong a may he's which really terrific actually upcoming well for call is think vacation, we reason that and be a because upcoming than the He's capability, him where this but we're I that hear a this company. we catalysts on forward for not in now the to a to in take on involved company the future. role for -- that in the There's sure position all step and actually focused you've important specific timing no I'm the much he'll on a So, on today just will milestones fact described. other the

for question, that thanks Paul. So,

Paul Matteis

Okay. Thank you.

Operator

moment next One our for question.

comes TD next Our from Ritu Baral Cowen. question of

open. is line Your now

Ritu Baral

months wanted and later be to or planning down more cuts a data you discuss question, taking Thanks bit able Good Right to I additional And these you dig out now, any committee, XX morning, plan? FDA's. expanded data or yours from preparation or the and outcomes the Yvonne do other ours whether believe little link in of -- together? that like to fully are of endpoints, sort endpoints guys. of advisory these than recent there's is given into the and for endpoints the on any APOLLO-B it's enrolled Pushkal, access shift understanding how any that all data BridgeBio around

Yvonne Greenstreet

sort There kind are Ritu. of Thanks maybe -- there questions of unpick and few we sort them. of

So, we're that beyond with XX-month shifts terms that additional data secondly, to selection. providing AdCom FDA any our of of the preparations, is the in already understanding endpoint kind the any data then And respect we've referenced. in

you those maybe Pushkal, mean, I So, questions. two could

Pushkal Garg

together fact we coming across We where looking Yeah. to it's based of have drug the in this biomarker the how strong that reaffirmed Absolutely. stability. we're data out evidence prepared for is of longer And OEL Thanks the Ritu. measures, good to less within preparation. all functional study, our appear of it's feel period -- on we're like the multiple and this. progressive the into that about AdCom early Patients talked get Look, and that ability endpoints term at quality pulling team of terms on really really data -- relative of earlier. life, are who data of outcomes, aspects predictive and seeing decline. the the we're trying preparations, And by we're about incredibly again very APOLLO-B entering

at progression favorable last shared Class Day and year we And on R&D showing impacts NYHA on data ATTR disease stage.

from important. functional value their delayed are put really their on and and life. when quality all And that's that's a These progression patients. We patients picture a of field patients this to that really of paint silencer the disease. They important in So, their clinicians in really of are this keep eighties. with seventies hearing ability

but lot also And so, received And to AdCom We've support a from leaders, various I meaningful the both pulling key et are external these from I them. that opinion those be cetera. will what side, the of is together arguments. changes data think can say

we'll so, those the to with panel making at forward there. interacting and the and committee agency advisory And the points look

Vis-a-vis great this looks there news first additional I out of off is, more the study that BridgeBio, that kind a for see as patients. stabilizer look, it like with think this in patients, patients would I think the learn very for It to it's may data BridgeBio time of positive an what regard. what we all, I and potentially pulled and disease. say And an it's additional at it about it's been was to and investigators, medicine hats because be a -- they've challenging the looks colleagues great to be

I it trends excited remain think coming profile our APOLLO-B really just that said relates not emerging significant, both we're statistically on on franchise, what to about seeing, of out Again, looks the be. about APOLLO-B what silencer data with emerging again, outcomes we but and mortality hospitalization. building I to regard as to

be endure and is while earlier key, results a field, the with what the in we for that's I diagnosing -- patients And progression. looking at are think we'll more meeting. ongoing the been I this highlight question data still these in patients But disease, the that think ESC big

think in the therapy of APOLLO-B I So HELIOS-B. looks like can the to that population. that an effective and reaffirmed And reaffirms elements a BridgeBio show in that's benefit data that design

So well. we're as about very that excited

Ritu Baral

Thanks. Great.

Operator

for moment question. next One our

Sachs. Richter Salveen next Goldman question is Our of coming from

Your line open. is now

Unidentified Analyst

congrats Tommy question. on on the all taking our for progress. and for Thanks Salveen This is

Our on BridgeBio HELIOS-B. question and is also

physicians this to that rates So, kind Thank And potential in imbalance given HELIOS-B insurance the from combine be arms the Alnylam two impact to in you insight would you saw TAF the into on hand, benefit give allowance? thinking is on additive between there this drop-in able about are of separation. How you. the when there HELIOS-B BridgeBio other drop risk that have we stabilizer?

Yvonne Greenstreet

Okay.

questions stage disease, diagnosed these for two BridgeBio patients really there even of that I'll effective to So, is pleased earlier progression benefits that you, disease therapy, reaffirms really maybe were earlier continue because to an start by off just have demonstrate where but the in we're kind they able see the saying it if actually patients. to results in

us increased gives this successful in that confidence pleased of kind delivering actually really actually a we're think, HELIOS-B. I So,

imbalance and But stabilizes potential the about about can approaches on combination -- TAF talk rates, Pushkal, silences. maybe drop-in impact in thinking TAF you also, and HELIOS-B specifically

Pushkal Garg

the of the think, good It's relates We're what we've study careful the I measures there. we've any regard as in place design and encouraged drop-in the talked updates past, not and I that drop-in we're rate, but to it rate, that study. in to more on with to Look, that, way designed, very TAF Yeah. our overall got that's was we the think feel the provide by we're the as assumptions about we study. specific substantially as internal design and about seeing below going about

study The in study into to entering of like allows did a just the APOLLO-B we tafamidis, patients be for background on proportion the study.

around come we've we've targets were but operationally in XX%, our As below said that.

we think will in a I functions but so, And drug of as as as of emerging get from the monotherapy, study top tafamidis. data that on background well interesting how terms

Yvonne Greenstreet

Thanks.

please. question Next

Operator

question. next our for moment One

Jefferies. of comes question next from Raycroft Maury Our

now is line open. Your

Yvonne Greenstreet

Hi, Maury.

Maury Raycroft

Hi, thanks my for taking question.

access study, relates to leveraged regulatory data and program For expanded the to you've how of commercial the will as timeline can about be plans? it or patients types data, enrolled talk XXX-patient you the

Yvonne Greenstreet

how data a Yeah. also thinking of then Pushkal, around EAP and patients for these you going used forward. types that's may about be question the

Pushkal Garg

brought an disease. the alternative Yeah. -- the came for this with patients APOLLO-B it out, mechanism data Maury, thanks. potential posed When it forward for

progress. call, with during about talked multiple we've As these times therapy patients standard-of-care despite tafamidis, continue available the to

US enabled that were themselves with physician avail of experiencing an intolerant who And with that support. to did therapy was progression so access centers patisiran what were we expanded XX their patients or otherwise program, establish at available

open at was centers. that XX So

XXX enrolled order this program. disease they in about as really what I continue that had been been was of and two every on every this the three enrolled actually hearing and was patients It a I think, rapidly, days the with from communities community we've need that that therapies. patients. to actually days patients was additional EAP highlights, -- lot saying that we clinical we've And -- mentioned, progress it And what enrolled sorry, relatively patients two three and the patient

I patisiran based as think HELIOS-B. important the disease. so, on And then, bringing results this that's forward as And hopefully in of patisiran think we well about

Yvonne Greenstreet

Pushkal. Thanks Yeah.

to really important continuing need continued therapeutic think the who progress point See medical are I unmet patients the about patients that approaches. here. the one is and need alternative

please. question, Next

Operator

our for next moment question. One

UBS. from Merle of Eliana question next comes Our

Your line open. is now

Eliana Merle

Thanks the Hey, for guys. taking so question. much

HELIOS-B, using For method data? pairwise versus Finkelstein–Schoenfeld rationale the in as the the statistical used was for recent your on can a elaborate X, you as Andersen-Gill analysis that stabilizing BridgeBio Phase such

will as about urgent you and terms endpoint just visit thinking of cardiovascular the definition? second, in urgent visit event of proportion Thanks. this component importance the including from part then hospitalizations the how the the that heart of heart rate, come are failure failure of And

Yvonne Greenstreet

Pushkal, two for maybe you. questions there's

Pushkal Garg

Sure.

that our think multitude of to and analysis looking I of fact events over at And take survival advantage recurrent analysis the Ellie, analysis you're clinical time. So, there's conducting events highlighted and time spend plan approaches agency. outcome that a way optimal the a benefit. aligned statisticians with thinking And lot a that's demonstrate that's of what's the the about in statistical obviously to

for up. instance, and this In is up the would the allow there us of one we fully the of Andersen-Gill the that fixed that, allow amount outcomes preferring for allows And use shortest time to a really of context to of approaches other fact variable in Andersen-Gill analysis. whereas reasons follow-up, follow frankly follow the the leverage us the

So, an it advantage of us bit gives do way. to we little or think analytic power it that a

that a picture. really various the relevant maybe important, just the clinically and this Ellie, need connote endpoint, heart with components worsening, failure I to larger the is regard to what's care trying With for in disease. events of capture to We're patients think

in urgent in including care et increasingly different why and geographies, different hospitals that's care cetera. provided so in places, And is centers,

that as effective that so, of failure structure. have to kind at totality the affect all with in heart therapy. endpoint events And we relevant indicating an aspect an look that clinically we that's may we've captured of opportunity the that of why And

Eliana Merle

Great. much. Thanks so

Operator

our One next moment question. for

William next Bernstein. Pickering Our comes from question of

open. now is line Your

William Pickering

question. far. market at so self-injection? patients dosed patients competitive monthly home Good AMVUTTRA are Thank what getting between wondering dynamics does future quarterly the delivered tell about you your morning. trade-offs you. what to look [ph], vutrisiran how versus percent about ahead research Thanks thinking are therapy physician taking of was versus I for my And yeah, you as

Yvonne Greenstreet

two there's you. for questions Tolga,

thinking The relating about think first second the differentiation. vutrisiran, we're I home relating to infusion and to how

Tolga Tanguler

full hospital whether AMVUTTRA that, a in patient will have we the various I other well year. of now infusion and importantly is physician for we of benefits polyneuropathy supporting been are we dose five of times Yeah. competitive. site and Look, now it's a just make thinking incredibly No, Part we we able product different establish excellent to years And really capabilities, the with AMVUTTRA more care reversing number positions fact that options, and category, going should the and this not this important the care. of this about there we you. whether the an but will product one that of experience thank providing I from of in features a And Great in from and also starting a be unique reimbursement should obviously only, MOA, erupted is AMVUTTRA then coverage a important year think dose, way this but a think, question. the be perspective, really it's the in than also disease disease Having treatment numbering benefit. or promoting care, center in US, patient believe four have where only sustained the not B convenience and patients, reversal, and few into sites have home, remember,

third the also Not patients you convenience AMVUTTRA, ask these our on only getting a of home we've we have over since the has ability and therapy. are also to of important a almost nearly care. to good over what's of patients question And one is to that launched XX% is So, access ONPATTRO now -- our but all get medicines, remember stay that, stays on really therapy.

very, minimal We have dropouts. a very

that offer, this believe very remain all with significant we So, benefit. these we other a is features to going

an another our unlike obviously And one remember, of this has zero important And until be is benefit. XXXX, to continue copay. nearly will patients, XX% to them important D Part

the some good of first the very market, the AMVUTTRA we with bring in we So, that table, the last five for out there services set as is -- positioned being years. well are about that very we feel we've the values how on already as

William Pickering

Thank helpful. you so Very much.

Operator

question. for moment One next our

Our next Barclays. Wang of comes question Genie from

now Your open. line is

Gena Wang

my I you have also questions. Thank taking one for HELIOS-B. question regarding

low lower single But think, you do you think using past, in I'm far, on comment rate, Pushkal, was digit. don't blinded the it say, tracking how's on think, benchmark I than [indiscernible] doing a increase. now do dropping below if I a where TRIBUTE that. pretty I say the -- early events rate, as dropping in so versus we're see much also sure be It's [ph] event's your initial that And assumption? and study you your will XX%.

Pushkal Garg

that to are plus our I significantly Yeah. you're rates, Thanks time. Gena can evolve going say going you to over are is think is a terms over for Look, of rates those the assumptions. the drop-in I your below see as the rates three-year drop-in in What rates course study, of -- questions. the can planning imagine, are

going about that's the There's of how powering those feel look feel all study. And again, powered, a we of study we of multitude we et cetera, that a And is turn contribute study. very good at to overall out. good so, and factors the elements, about how to when the

in really a of very those about studies APOLLO-B, in that seeing overall. have what successfully of that of here the And history really and we're what feel course, for study, cracker terms team a we ensuring have integrity we they're including in a people the HELIOS-B. we And rates, we executed clinical and -- -- teams again, and in of designed event and jack In data who've come responsible team, monitoring good again, about this with of statistical and the feel, the long so positive field, quality we're study. doing

Yvonne Greenstreet

Thanks for Gena. the question,

Operator

for our moment One next question.

Our Gershell Oppenheimer. of next comes from question Leland

open. is now line Your

Leland Gershell

for question. taking thanks Hey, the

at we Just in from look looking forward as data, a indices. diabetes at glycemic it's the being obviously two ALN-KHK and me, to you'll be question type looked

that So, obesity, related there. be data NASH. target But wondering, useful conditions. Weight could essentially loss, presumably we'll see for sits just other where

respect with be one candidate to that, directions. those may that of thoughts your what wondering in taking Just

have be you'd if Thank other freedom partnered. for those you. As study, two are at will and like looking programs you obese in pursue have patients in NASH, both if KHK. though you NASH you even to may Wondering overweight, the

Yvonne Greenstreet

the target Yeah. genetically a and to and respect development target engagement And in of as obesity validated range That's the Phase study a And relevant glucose relevant insulin point addressing, great everybody at safety, just to with KHK involves of is X you looking as that's we're clearly question. biomarkers out, metabolism of and well. a [indiscernible] metabolism levels. And that focused remind also our and diabetes.

question, think provide of is raised broad and interesting Pushkal, to maybe that perspective? which general. KHK some metabolism you in want an potential you I But

Pushkal Garg

a have a RNAi with insightful in Yeah. beneficial Leland, I of these parallel think overweight, in epidemiologically of in it's diabetes, a mechanism, syndrome number that a increases question possible we've entirely in that really diseases this both metabolic sense NASH, we and type seen travel by that that that And the pathway with rise actually -- consumption, seen all fructose different it's may we've number together. effects perturbing this domains.

we a we that is based we potent durable, have, guide them, KHK, help to way terms will the of and we what how which think this really then that that and can is measure et of indications that pre-clinically us within Alnylam have silence number we So, pursue, on what's target clinic a elaborate exciting these we're And here can advancing. of is a to in the also cetera. proprietary to in along that path pursue biomarkers

of diseases, have across it a the take we us. so, really And need unmet the range science and to full where freedom operate and drives

So, future. in the sharing to look data that more on forward

Leland Gershell

Thank you.

Yvonne Greenstreet

towards yeah, come in highlighting, pipeline I for you the our think, opportunity year. exciting more to of Great. another and the end thank And

Next question?

Operator

our question. for next moment One

Blair next Our question from Minter of Company. comes Myles William &

Your line now is open.

Unidentified Analyst

Hi.

question. into Myles. and on Thanks thus this clinical you. on by conjugate our how that from been clinic CXX Is has technology, any clarity far? other using there for Sarah the Thank of ALN-HTT ALN-APP are data taking You've can you any give advancing assets the the timeline informed got or

Yvonne Greenstreet

programs and ALN-APP any -- using for timelines other The sorry.

Unidentified Analyst

HTT.

Yvonne Greenstreet

So HTT.

Pushkal Garg

Yeah.

So, thanks question. Sarah for the

and what levels beta, see of there, structures? think question targets you lowering that. signifies as of see brain we alpha we've couple look, ALN-APP calls, think groundbreaking. we I recent and to signifies of the at has been us XX%, with said CNS about always as lower think remarks, the you think, getting that CNF. penetration. variety take as to heard of XX% additional soluble up in up whole you've therapeutics deep seen with That's neuro-degenerative APP a of that affect to really When brain look opens in really in trying I you're get knockdown we I a space that a And into wide where deeper what the It really the the can beyond we level big RNAi can and diseases a that vista you in we're pursue, from of new can

comper And even where the months knockdown then now [ph] every or six be to these And months a in durability think year, that's you liver. we dosed we're translating six or saw have and what we clinically frequently. drugs less seeing can pre-clinically

exciting. so, And that's

the this tolerability and far encouraging well. really And so most frankly, is safety then solubility, is fact critically and as that the third, the

been up this been science. really targets groundbreaking the at this opportunity working -- so, colleagues our of with we've multiple opens on And Regeneron, in, for us who've to pursue in terms

announced molecule bring another work is IND doing And so, clinic. to to the preclinical recently We're into now, a HTT work point, development that candidate. as enabling your that we

announced rapidly. that, haven't We but that we're a pursuing imagine timeline that you formally for can

Regeneron preclinical have against development advancing forward. we're going ALS, right additional also SOD, are we And against that that behind targets at a Our in for bring to now. molecule colleagues

Yvonne Greenstreet

we one think last question. for time have I

Operator

question. our for moment One last

Our Foroohar last of question comes Leerink. from Mani

Your open. line is now

Unidentified Analyst

the the potential question morning. from need a protect This on your genericization, commercial Mani. the vutrisiran. and We head-to-head strategy the assets for study? be of for do Lily tafamidis a had What will Good expect you Hi. is upcoming post-approval in for terms positioning to

Yvonne Greenstreet

to that going I'm straight you. to question hand Tolga, over

Tolga Tanguler

obviously, I But an markets, the And have in a quite to is tafamidis, one everyone, is game product seen has tafamidis. Europe polyneuropathy dependent cardiomyopathy at unlike where been indication, different they we is product to of for indication, in the to it where position polyneuropathy I available guess, going really I receive growth and the thing all, which you how Japan, be that wouldn’t in the going able where US. HELIOS-B question. say experience we've first that the now the yet and Yeah. demand versus for and our to other we've have been if thank particularly remind mean, switch, markets to AMVUTTRA accelerated accelerate question changer look for results. specifically on we're a you value and substantially

But into that and continue patient subsequently of we patient will, will the clinical post Like to terms we value any genericization trial in any for drive of course, to and looking company and alternative other I be consider wants soon growth, of important it's it's would will us consider you make -- options. say any that, we would decision that too little keep to a and eventually. abreast we obviously

Operator

conference this showing back now turn no I to remarks. Alnylam questions further for I'm closing the at time. like to would

Yvonne Greenstreet

have coming to multiple call. us happy of a great and our elements continued continue business R&D in that progress goals. very long-term a Thank thanks for development. on look deliver near seen more XXXX execution months you And and everybody, everybody as on joining the across we've we and you forward in Thank commercial, We're this business, with and sharing our to we clearly day.

Operator

for call. you today's conference concludes This participating. Thank

You now may disconnect.

Alnylam Pharmaceuticals (ALNY) 3 Aug 232023 Q2 Earnings call transcript