Ionis Pharmaceuticals (IONS) 22 Feb 232022 Q4 Earnings call transcript

Good morning, and welcome to Ionis Pharmaceuticals Fourth Quarter and Full Year 2022 Financial Results Conference Call. [Operator Instructions].

As a reminder, this call is being recorded.

At this time, I would like to turn the call over to Wade Walke, Senior Vice President of Investor Relations, to lead off the call. Please begin, sir.

Navin. [Vishnari], you, Thank

believe today, I the to the Ionis financials. call. financial how be the our and and financial results manage begin, of website Investors slides to our press to section related discussing will we of business. website tables that GAAP economics We a better encourage our we reconciliation go everyone the today's of release to non-GAAP non-GAAP including posted accompany Before business to we represent We've view also

this morning portion Research, Eugene and Strategy Officer; Hougen, me join will the Chief Officer; are With Beth Chief Brett the Financial of call. Product Executive Schneider, Onaiza Eric us for Monia, Swayze, Officer; and Global of Development and Chief our Operations our Officer; Chief Q&A Executive Clinical our President Cadoret, Vice

would which X, to to contains draw our I your attention statement. Slide like forward-looking

statements current to are SEC During forward-looking results additional making risk this based for language our you and materially. certain These may contained in statements factors are the filings we detail. beliefs. actual differ our I will call, subject and uncertainties, and encourage that consult on risks to our be expectations

turn the to With that, over I'll Brett. call

thanks and joining Thanks, morning, Wade. Good everybody, us today. for

our year, advancing As X we from the near-term achieved on opportunities we key begin we in the commercial this the successes our by in building are significant market. progress momentum XXXX, towards highlighted

interim the data in positive XX-week With formed from delivered NDA which for eplontersen, submission the we analysis, December. basis our

this need granted the for designation in the patients. underscoring putting significant olezarsen the year. With of olezarsen, data these on BALANCE us FCS unmet completed track Phase study III half recently for for medical Fast FDA The FCS for in enrollment Track we second for

SHTG We also clinical the our expanded supporting broader program advanced for indication. olezarsen and

the report this And donidalorsen, to potential prophylactic pleased complete progress enrollment belief keeping to track to of year. delivered all donidalorsen of profile HAE. treatment strengthening III data we're multiple study this for Phase best-in-class readouts, continues positive And that in well, further medicine's on with we the us our

excellent made organization. our commercial also We've building progress in

to first donidalorsen. As a result, our of AstraZeneca. beginning we these independent olezarsen for medicines We're well co-commercializing with on launches also are track and with eplontersen successfully launch positioned

Beyond And opportunities, also Tofersen EU, III Phase year and it great development Biogen for grew this which our epiraversen our be commercial commercial U.S. X to the our is to near-term pipeline HBV. late-stage make pipeline partnered review initiated continues our recently rich partner this added is year. in for GSK progress. portfolio to under with when positioning

pipeline we patients later Phase advances IgA deliver steady development sets expect to us into in this Roche with year years Further, the products of new for market late-stage cadence our well to our strong come. III many pipeline more a progress Indeed, grow up to very nephropathy. IONIS-FB-LRx to even when

long SMA We chemistry. also advanced and including our initiated technology, dosing. study recently advancing chemistry and an programs Biogen backbone took MSPA Furthermore, enabling I LICA important steps last Ionis muscle interval utilizing diversify novel year programs follow-on utilizes to potentially that utilizing Phase broaden

further next-generation into tackle to platform, leader And diseases, entered we our complement medicine. gene more industry more genetic we with reach a to existing expect adding position an Metagenome, patients capabilities By editing our in gene collaboration and leading in editing. strengthen

The organization our we're of needs. programs sale-leaseback investments the recently commercial will directly monetization the foundation and financial our strengthened transactions further to in capital advancing royalty our from we planned we and upcoming launches. ahead raised our building support our Importantly, future making cash late-stage support

pipeline and upcoming progress that, key discuss With call Eugene to our I'll events. over to turn recent the preview our

I'll wrap XXXX commercialization an as our well your financial our review after prepared will our before financial XXXX provide will Next, Onaiza as up on Beth, and remarks Beth review efforts; our questions. results update guidance. taking then And

So now over to Eugene. you,

Thank Brett. you,

readouts, we same very data to many by pipeline positive was perform well. the Our year to expect Last continue highlighted and continues this year.

the and key our will events. next data and regulatory few our review preview upcoming Over recent minutes, achievements I

submission data from was positive eplontersen in the planning analysis. data based week the year. half XX interim The recent and Phase share NDA this first on of XX-week for We're III to

of we're planning in year. later year. are this potential the for the to also submissions late Importantly, eplontersen file AstraZeneca U.S. polyneuropathy this looking additional of also and forward approval to We the regulatory ATTR outside U.S.

for also conducting deliver broad We to key By set we the to pleased data positioning cardiomyopathy and patients differentiator, a and this this will most global be us ATTR to study expect rich progress data lead population. successfully dynamic study. the these CARDIO-TTRansform market. growing, We're date, for a with compete believe of in comprehensive continued in patient

first to We enrollment this on us track the of half expect data complete year, XXXX. keeping for in

which FCS expect triglycerides, Our FCS elevated this olezarsen lead patients pancreatitis indications very of and enrolled, read to atherosclerosis. III X Both Phase broad it fatal development severely but program progressing in year. BALANCE have targeting fully half is we and and second nicely. different out is to can SHTG study also related the

a year. broad designed III in both remain driver future to With we program confident potential first for is Phase continuing to Ionis. our growth the progress well, be data support to of indication with And substantial expected indications, for mover olezarsen SHTG the also in next advantage

were at patients HAE the enrollment next hereditary Our one sustained donidalorsen mean data for an data with rates overall demonstrate Phase angioedema that follow from with on with the to OASIS cadence treated baseline. year positive least attack reduction this of continued II rapid track in HAE full of XX% We've sustained from new in year with long-term remains that reductions attacks patients positive III Phase in year. data steady for program in program

than extension more improvement quality all of with clinically open-label in patients Importantly, their XX% scores angioedema of a the observed in meaningful reported in life improvements domains.

remained dosing to attack-free, bimonthly transition for demonstrating who patients the of dosing flexibility. potential XX% Additionally,

favorable safety also rest the to rich partner in pipeline time extended reinforce believe that late-stage this including Over tolerability drugs. We our profile. advancing, treatment data our also best-in-class be to for these is of Donidolorsen period, and we potential HE. continue observe prophylactic The

Tofersen, to review form meet patients ALS genetic in regulatory our in EU. treatment next medicine our for committee commercial be will disease-modifying review of and medicine. March tofersen ALS the the in partnered with the data the U.S. with If SODX medicine advisory tofersen's and will first is Biogen approved the of for The approved, under a supporting NDA.

study for and represents cardiovascular data a estimated multibillion-dollar people pelacarsen than continues elevated track Novartis LPA advance in X with to have also disease, opportunity. LPA XXXX, million pelacarsen to more keeping Horizon filing potential regulatory on and worldwide

data last our expanded And to Phase year, chronic hepatitis potential for the announced living has a the broad recently, the functional when Depuriversen reported III with late-stage program on pipeline first-in-class cure people B. GSK a start Based provide Phase IIb for beavers. of

XXX,XXX is Worldwide, with for Phase our approximately expand annually. is better IgA million with to poised HBV when people aim have nephropathy. HBV XXX for therapy. patients Roche become late-stage of to Furthermore, dying IONIS-FB-LRx study III reverse initiates GSK's planned further in pipeline foundation future a their

pipeline previewed, led by progress. will we As year be regulatory late-stage highly productive I and important milestones XXXX expect a that just

look Given to events. the even more throughout you richness We on potential important updating our of forward there's for the progress our pipeline, year.

to over turn With that, Onaiza. I'll call the

you, Eugene. Thank

in donidalorsen. the top be and talent are tremendous of commercial launches we organization, first each integrating where our into we eplontersen, preparing for Ionis. made our first hiring preparations near-term are right in we progress have should and fabric our launch processes of products, We olezarsen commercialization of building our independent starting Today, finalizing with and of for

my and prioritization, market strategy economics Ionis product Ionis' outcomes team access this One and health XXXX, first and planning and operations. with planning indication strategic strategy, research is building of helping global drive into priorities team a strong to development team. global decisions. and is at portfolio R&D other Together commercial planning, Since R&D, integrated new this key pipeline has product

for and My triglyceride anted. X focused collecting education next field hereditary data last integrating engaging This and priority has dissemination, well team recently, our to ATTR elevated leaders educating product with HCPs on plans. And affairs organization. into as the to was diseases disease insights is medical on years, team customer been thought as our and more add medical our

began operations, teams. we patient commercial to and the teams for prepare of omnichannel These eplontersen, Last in-line launches and reimbursement, plan the year, customer-facing donidalorsen. olezarsen And team marketing, building windows and services add in-line as approach, commercial our include we launch engagement. market access our to

starting Now minutes each first with spend a on addressable an there product eplontersen. polyneuropathy worldwide. patients with Currently, estimated like ATTR XX,XXX are I would to few

these of XX% to around in than in ATTR, scale, we receiving less capture expertise our treatments. are deep confident approved currently patients global with ability world. our the AstraZeneca's significant together a With portion are those However, of patients

in eplontersen, including for Today, launch majority year, staffing for And place. of this to we plan the the already we the build-out have complete educators. infrastructure our U.S. nurse our fully

We expect with both provides and olezarsen, We revenue broader potential. FCS. rare to have to advantage indications the launch. then and our olezarsen market into expand independent for for we designation which be FCS for first fast more the first plan significant and track indication, us With SHTG the enter indication

capabilities eplontersen market. and customizing the leveraging are for them We SCS

of further these product. of As to potential the patients, for full to we our olezarsen SHTG plan launch capabilities approach the realize we scale

small very market today. expertise treatment, as to the rare has launch. allergists a profile, of for a diseases, we prescriber for us. see a We attractive prescribing our majority HAE number in growing second and With our with In prophylactic expect concentrated and an opportunity of continue independent donidalorsen efficient best-in-class products base to prophylactic a market donidalorsen potentially be U.S., HAE the the

those As an we exciting capabilities It's with at customizing HAE leveraging time existing Ionis. our for specifically market. are the olezarsen, and

our and upon to research commercial the excellence teams We affairs and to deliver are our medical medicines with our market. building our successfully in development

Now to the over Beth. I'll turn call

This summary Onaiza. a full provide Thank our XXXX then morning, for and you, review our year guidance. and I'll quarter results fourth XXXX of

we from and revenue commercial over that We balance from programs. quarter from numerous report diverse products, to of $XXX earned year, pleased half with $XXX earned am partnered full million I and the just numerous the respectively. fourth million and sources for our revenues

operating our Our the million. programs. And late-stage for especially was non-GAAP our $XXX expenses pipeline, and XXXX activities net loss our

monetization $XXX year which to received billion, from our the further investments in and Additionally, royalty of cash $X we with transaction. the we we ended January with million added

compared The driven U.S. well growth the performed long-term the Asian in internationally. to Europe. and in fourth to United demonstrating sales SPINRAZA the in quarter, resilience and quarter markets, competition X% increased increased X% in XXXX. States quarter and of SPINRAZA global opportunity, both in by by the third partially offset growth its the XXXX, compared stabilization in and also fourth increases were

was trend increased sales the positive to considering and the fourth particularly SPINRAZA same especially compared quarter when U.S. meaningful, period results. year Importantly, in XXXX. in competitor full the This

is limited adult on expanding continuing population, markets, expand is Within to new concentrating and the existing markets, also Biogen treatment SMA particularly which into has growing Biogen on markets. existing in options. focused is

Additionally, Biogen life robust generate efficacy continues as to data part management program. of important its cycle

believe efforts, programs Biogen Based We to and among million safety and Roche, on of SPINRAZA efficacy for the SPINRAZA's R&D year others. AstraZeneca and and can numerous Biogen, profile, revenue million $XX return these $XXX in advancing fourth partnered we with strong and earned the quarter for growth.

Our numerous diverse key our remains ability to a financial revenue from generate element sources strength. of

the near-term operating development, to CMC as affairs support expenses X was by and compared commercial driven medical to primarily full non-GAAP higher our year expenses XXXX fourth in Increase quarter opportunities. increased expected. Our and

included also as Metagenomic important payment editing our planned the launches. capabilities taken our for Onaiza ready collaboration. expenses to R&D under to commercial Our we And build have steps discussed, be upfront gene our

in to XXXX. SG&A in period our the expenses increased result, same a compared the fourth third quarters As and

Importantly, royalty bolstered adding in than our sheet we monetization balance and transactions. our from $XXX recent million sale-leaseback more by cash

our of approximately in billion. As a was result cash January these $X.X transactions,

projecting for than plans our earn in are more at we million $XXX Looking revenue. to this year,

We the this And have as in commercial of a sales, cornerstone. anticipate base with will substantial XXXX. recent product the SPINRAZA continue we royalties stabilization given revenue SPINRAZA of

we commercial this would approved, royalties tofersen is tofersen assuming year. our to add Additionally, revenue

revenue R&D contribute from XXXX anticipate also partnerships to that having will total revenue. a our substantial of We base our

costs most R&D year for our for the of its XX% of elements this significant of come development share the eplontersen. from One will III global AstraZeneca revenue Phase

rich milestone Additionally, many and programs, numerous we the the potential earn advancing with pipeline payments. to have

is different primarily advance we our many the done, as R&D on programs. anticipated probabilized always revenue timing expect the based earn of milestone to we payments we've partner As

and earned EU tofersen's important milestones U.S. already have for to Phase when U.S. for we the year, this payment initiated far sizable milestone are So And $XX program late XXXX. as milestone the vepiraversen. in approval the regulatory this million III earn eplontersen year, with a in well events we GSK approval eligible many as

of range on in projecting expenses basis. operating We're a $XXX non-GAAP $XXX to million million the

expect, of would pipeline As projection. the is operating you late-stage driver our expense most significant our advancing

X X for either today expected conducting are are of to III this year. all or Phase enrollment enrolled full fully We reach studies medicines nearly which

As are our stage. capital-intensive studies Phase at or their a of most III result, the bulk nearing

Additionally, approach preparations eplontersen, we will as donidalorsen, for our various our launch investments increase. make commercial in and olezarsen windows continue to the

SG&A our year approximately compared to non-GAAP to we the under increase Metagenomic XX% this increase to year-over-year. R&D expenses expect year, upfront approximately XX% expenses expect We to XX% last collaboration. payment XX% our non-GAAP excluding our to And

investments. Our commitment XXXX near-term our operating these to expense guidance value-driving underscores

billion. $X less revenue $XXX translates Our balance and guidance loss million of expense than a a cash year-end approximately non-GAAP and of operating to

generating have most while the Our confidence drive significant continue assets XXXX guidance valuable revenue growth. to to in our our ability retaining reflects we

anticipate As and this for multiple launches. Phase preparations studies we beyond completion look multiple year, III the commercial of we

we to our This one For the increasing be sheet of financial with substantially in is recent balance period we next our several reasons years, expect why bolstered of most a transactions. important investment. the

commercial from raised directly and royalty launches. in our making investments sale-leaseback support late-stage planned we our upcoming organization the monetization programs and the advancing our will are we of capital ahead transactions The building

will strong the steady our accelerating market. enable drive our combined and we our investments greater products anticipate expect so, Ionis in to shareholders. to doing we a financial bring Importantly, for stream And with value foundation, of to us

the call over to And back Brett. I'll turn with that,

Beth. you, Thank

expect this key at Ionis following up our we and continue work momentum the the the we've to late-stage made already We're key and excited strong events year. regulatory several ahead, coming about priorities. to progress with advance Looking underway

cadence our in the to positioned to medicines with well potential are to add additional abundance this year genetic a commercial and new an of products products longer X with portfolio We term. in to of steady deliver to the the market new come the near

is organization in technological and development medicines commercial olezarsen successfully integrated co-commercialize recent our donidalorsen. launched Our on and for independently to We're leveraging eplontersen today. track advancements

our collaboration to capabilities drugs Additionally, our with as expand positions for technological well. Metagenomic us future

our believe finally, looking plans, at will we our and We're foundations sharing progress to our and all a increasing substantially of commercial great the financial And strengthened Ionis forward we pipeline drive year which for value. way. along

February living Rare mention the Disease patients where Day, day, to XX, we is rare want I which Tuesday, all with diseases. a closing, struggling Before families and recognize and

now I'll for the Operator? call With open that, questions.

The Fargo Instructions] with comes from first [Operator question Zhu Yanan Wells Securities.

Congrats on the progress.

questions We have the mainly program. for a TTR couple -- X

First, the NDA in for planters polyneuropathy.

the submitted I you think December. in NDA

priority process Just announcement plan if we or curious associated FDA. expecting how with And And a the announce when are that you with that? meeting acceptance? can of NDA NDA going to review AdCom you acceptance expect the

the forward the Thanks, Yanan. to of NDA FDA. We're looking the process much completion very with

FDA, period we the from if details PDUFA in you the that provided day the XX-day As waiting will. you notification and review NDA December. standard the letter, cleared In we on said, on letter, submitted FDA, just date. we're the the official now with We've XX

be polyneuropathy, your there'll standard for expect outcome. smoothly question the concerns process a There's review, we gone an would eplontersen whether been an they very has The with or review of no to and whether We outcome. whatsoever. standard an not example, want accelerated For and don't FDA. or expect

notification official and details from notification the will that we're get really notification, that we time. we with announce all at it's the just for final that the waiting in the So FDA, that

will up pretty that So soon. coming be

of And think strategy, eplontersen CARDIO-TTRansform size And course? do trend study the to rate are enrollment -- blended to question on of subtypes? versus does still the great I hear. are And expected tafamidis modification first result the how you the naive ask study, on half? but complete desired the in a enrollment also And a -- the does from expect of patients of following study you event and rate may getting on in for terms enrollment if on the That's cardiovascular I balance this you how various your basis, patient strategy? the of what's

around expecting Enrollment going midyear Yanan. to well. this very year. is We're enrollment complete Thanks,

successful As the know, most in the upside ensure study the we possible. study to trial you for outcome and outcome we achieve X to robust the And objectives. upside

more that disease. most patients for generally was when And have are strong are first have ensure the disease. that study patients The study robust with on mild diagnosed earlier outcome the to powering being we this to objective fact cardiomyopathy much they under and based study TTR with the successful the in diagnosed therefore, are the

and a patients that balance, Second we patients. naive good a between ensure was equal tafamidis to balance relatively have

help nice in uptick we're upsized percentage planned of hereditary say our patients that we we're hereditary ensure to of when rates TTR to tafamidis that in seeing preferred amyloidosis we so very And naive study We're we as cardiomyopathy. percentage the the patients year, seeing as usage track uptick the in complete study. pleased have. seeing objectives. balancing we hereditary, event I'm TTR a study planned also of this thirdly, a in to we significant amolpdosis blinded really the enrollment with that that had And not far midyear are expected only around are with on versus And very a with as nice have the cardiomyopathy. of We're to achieving all

So very readout forward looking we're data the everything is XXXX. the progressing in track in study, to well on much and very

RBC. question Issi next The with comes from Luca

program? will TTR community Wondering for yesterday news how The Anal comment one. and you're X you cardiopathy. the implications thinking if can Maybe have that advisory about first your meeting, reaction quick the from on an progress have your on

still going And gen? pivot the the and to second on for in What's Are both gen the invest latest on some point, the second broadly, or planning AGT. maybe latest you is to more gen at to the what's you're AGT. one BD second The first molecule? that

HAE. last maybe And on one

I that back think -- X every every American College dosed at X were the weeks QAW sorry, X months, monthly. to of last switch year, patients X

However, X abstract I switched that X think monthly. it's of AI, Quad in actually out back to at the

to to X% X X to from So X%.

So wondering happened what there.

Sure, Luca.

not on naive of that patients tafamidis say surprised, little the magnitude the versus products results complicated. by FDA. is in a So X-minute were could pretty I not hindsight, competitor What and is significantly the in prefer benefit to test, try the comment patients very walk benefit, I on outcomes complicated.

not So experts input is field. in welcome from information. gives want going -- us the that because the more terribly We surprised to get publicly to FDA it it

strong very trial. and have more. We disease, it world. around but And welcome I can successful to cardiomyopathy relationships better, all us investigators up outcomes key KOLs think with help us set the a more hear for we're the always

X a studies in to the we're of we're molecule of all ATT, Regarding on heart of and been the on half end we to kind for planning failure for certainly responding the because the to generate as of data to first the the start in by heart program. business the the year. start we the second there's and wait molecules We'll is molecules still study as far Gen hypertension molecule inbounds, half data X.X want X wrapping failure activities, from interest data X in before those study. And development pause year. in the the that of won't present We study the year. up, share the this this in planning hypertension second molecule, for we're second

in of correct just The That year was data presentation, correct really Quad were was attack-free in patients. year patients. previous was treatment, year. a XX the were of patients that the presented X-year number bimonthly included that you patients last timing Regarding attack HAE, was timing that X last the X that of when bimonthly AI X in patients the X just for one presented free was effect the whereas is the beyond X cutoff. the make

a donidalorsen. the just technical So anything, and for bimonthly it it's favors efficacy thing. If

and an it's monthly really really are dosing a of monthly month very excited key And dosing, one option we dosing with really that several you but that gives said, about that is convenience for by mean in The of fast reductions now competition. self-administration, versus monthly of donidalorsen tolerability, the for XX% for excellent unprecedented of with action for efficacy year attacks HAE advantages a onset treatment.

Capital comes The Gary with next BMO from Nachman Markets. question

more on First, a eplontersen. few

launch filing you when does timing So to the at plan in the have if PDUFA all? the completely I talk late the a do you on how U.S. would then what And the have XX-week is of And separate? follow-up you likelihood the that and And that that's available, And with the filings you about readouts might Or Beth. soon this AZ year that data early U.S.? ex data? to for have that PN, for what's then cardiomyopathy, do for be then able product? impact PN

Okay.

little about after week questions Onaiza ask I'll of year present half bit we're meeting. The X planning of the data medical at in to PN. this for maybe on talk other XX So I planters planning touch in launch your to a first a

for data potential file component additional Of of is the line we to week plan to of approvals important will XX and for That a filings. that soon with we'll data that for for results U.S. those I outside as key is looking the -- eplontersen, We're filings very out have course, filings approval as that. U.S. much very be have ahead ex as put it. forward top

driven. rule XX after desire That outcome week sufficient polyneuropathy, doesn't very the we FDA by time. of FDA of data the on by a supplemental NDA the NDA week to currently on more that's possibility any the impact The XX -- the We week the will with supplemental be that the eplontersen meaningful that we We data out is for don't don't for see under believe, at get XX data, the a this approval. data than submitting future data. data plan NDA based that in review

earlier. changes Ionis, could to in Regarding continue the a competitive cardiomyopathy landscape the monitor the that decision study by early out -- the readout, landscape we will to influence AstraZeneca any read

will driven do We rates -- We the will read will patient be potentially on out be early. and -- factored early also study a to that on read to that be the of focused to demographics based have a that. in the review do all out decision of have all we several event will option -- blinded study

Onaiza, could for a about launching then talk year late anticipating eplontersen? date that maybe and the you we're PDUFA bit plans little

we're Gary, launch. success for PN Yes. preparing for the

lot that pre-commercial being the investments U.S. made for of are a are already there So

out We have, that's We really you our medical building X field years. as education there directors for have last plan already years, the know, disease nurse capabilities. field educator over that hired in the year a sales team. been the team And then place and actually of as the XX-day there's we enough ensuring filing, over the start look X and Astra to back the second on half out hear we will out

to ready approval be So going well. approval not and as basically, of we and have between launch time are upon a to lot go very

helpful. greater than Okay. then the million Great. just revenue And $XXX Very guidance. Beth, for

about talked the key some of You factors directionally.

then is the how How at the still all. So in you factored year be you hit Pharma eplontersen reporting guidance next tofersen XXXX? mix guidance? will then cadence if And overall similar or are delayed into to And agreement? and will Royalty be can that the quarterly the

question. Great

or approvals eplontersen next will it of, can delayed similar. hit into then are in tofersen very be approvals of I cadence be So this XXXX. anticipate mix would quarterly commercial terms first, XXXX and say, And loaded. very from similar terms we anticipate back-end look in expect that a will to guidance the I and quarterly even -- a likely I the basis, on mix of revenue year. if the R&D to

mentioned, I important probablized based think might occur. when revenue we remember, think we the And an items. it's our to I event have on R&D probabilize I've in typically consistently as year

the those late would probabilities fall lower for likely So in year. that items

of fact of that if that the have a we slightly. a And on so pipeline items basis consistent are us really a that with very certain programs delayed flexibility partnered milestones gives of that robust just lot us lot gives combined generate a

guidance is achievable. that So I'm comfortable our

did let's miss of questions? I see, your think And got I them. I any

Yes.

Pharma the the was Now lesson agreement. Royalty

Yes. the how factored into guidance. just that's So

royalties The our me. our revenue. Yes. to under Thank agreement you SPINRAZA be pharma for royalty top booked continue reminding line will into

royalties be to And be our So the really sheet a from payments balance company. revenue. cash top for will Royalty on to XXX% the continue of will the SPINRAZA then line Pharma booked item

that I'll it's have our make all we have finalized because as with auditors. always have. hit our point, a line to top QX revenue all that more accounting our they when SPINRAZA details the great earnings royalties will at we'll point of think more But get detailed I to

The next question from JP Jessica with comes Fye Morgan.

Thinking ahead acoramadis data for be second, you the are you you going year, to next those can to on remind this And are when could what the when with out? acromegaly update? focused where me later simdulersen read results most and we expect

-- thanks, Jess. for Well,

we're maybe that's the agramdus, outcome Eugene, for looking to comment For like. mean, look and what you on I should data going this.

due obviously translate on population the of into be enrolled No, and also to study. absolutely. study similarities That's all we're what going CARDIO-TTRansform that's focused and that benefits hard outcome it's and functional what the data, soon, everyone is waiting see is the in how to

the important to enrolled aspect the is see probably of most that's we're today is what to population So second that representative -- they've seeing how

study. our In

Yes. In study. our

interesting to very Jess, this half year meeting, second be course, to, in will is continuing in main for we'll demographics the of endpoints, the on but the a the data. the patient out get share primary medical up. ramping endpoints study the it at monotherapy of So data addition We're acromegaly, hopefully planning monotherapy

data on patients As in you we that are year. somatostatin know, poorly last analogs presented controlled

steps. that, of this So we'll And half data monotherapy the second next with the year. in have

Blair. from with The next William Minter Myles question comes

franchise it's SPINRAZA you seems SPINRAZA And this there's year. up this is of that the type And What's of type lack is as cadence, probably we X that sort data. to can Just clinical are a efficacy the on back going with where to particularly therapy. to sort Biogen's growth, only and to doesn't growth claims to of patients actually of SPINRAZA return adults, It expect? return like the treated seem going that data. think I if that happen with for patients, presumably they're XX% citing it the of adult really the I disease-modifying guess, X

So can be that to support we studies clinical to Biogen some by thesis. launched expect some expand

return Beth, the to the metrics, on return growth?

Sure, absolutely.

So thanks question, Myles. the for

to to And I starting really think expect this because starting competitor return and as what that's that as that well QX, United products. QX. you're of really and launch is first increase States anticipated a for for growth SPINRAZA bit already was we both even little the see what you year-over-year quarter-over-quarter would with had the in stabilization the

across to the cadence we'd various We would launches other dynamics across geographies. various -- similar the those same see of anticipate continue that, that will geographies, to

And you to isn't even growth. really So in and anticipation in in really cadence. great already comparison that approved And address really particularly of and strong Zolgensma expect but those don't adequately right? for that see it's competitor in efficacy teens those would where adults. it's particularly and patients products, would or for are which adults fact be to I the fact, profile, has the strong the it's those very the to SPINRAZA a focus on our teens SPINRAZA So the a of patients, older case safety think important place that's

of the about And in fact, prevalent that's the XX% up largest adults. made prevalent population. teens and population these of is There's

in not but U.S. other growth, the So tremendous in only across for it gives world. markets opportunity the

as Biogen geographies in as focused expanding America, well as other is Eastern on geographies around the Latin Asia some in particularly well. Europe, world, other

are going factors I to all think be to return of SPINRAZA's in So those things growth.

studies your the was are data we potential question, last only are the some study, shared some Myles, to DEVOTE think SPINRAZA. will growth SPINRAZA, part year. of Two studies and significant that studies, of to run -- going well. really post-marketing to higher other And those examining for enhance contribute further data the of the doses And

Looking SMA disease their The that is also at higher will of has a patients to study also patients. on at ASCEND even greater will higher We're patients show patients SPINRAZA in efficacy showed that do those doses in benefit. -- progresses in and better risdi. looking dose big

study the Biogen data, whose today progresses to studies well, to RESPONSE gene SPINRAZA performance dose And laid is in is then going going the disease or looking that timing the for share well. patients therapy the commercial -- the expectations enhance further study, on market those and of at also on is out timing of hasn't but SPINRAZA. are purpose that

everything so on going track. And far, is

factored the a just underlying And just the for year building costs much this business? is into manufacturing of for How R&D OpEx Beth. the quick new for facility versus guidance follow-up

Sorry, that. I didn't Myles, hear

out. cut You

How guidance you're is much the current manufacturing business? versus new of the for building the accounting OpEx the underlying facility of R&D that

the the any the as point. associated and construct some all includes It's guidance this costs the that start begin at of be from expenses online the amortizing OpEx construction that over see facility, at cash period building those of So 'XX new manufacturing and you'll frame using balance of we of the we'll costs course That's costs of associated And we'll the operational. and once point, those with building our is into amortization asset with then sheet sort flow our some in the facility. time to the none OpEx.

The with next Stanley. comes from Ulz Morgan question Mike

HBV. perverse on in Just one for me

the started Phase recently You partner, highlighted III GSK, study. your

impact to thinking Just J&J or might potentially your deprioritize maybe their HBV decision curious go-forward program the how the strategy? recent opportunity here on your

a stab that? want at Eric, take to do you

competitive doesn't our their caused forward. Yes, is program really GSK perverse enthusiastic a program. this very of done, that CLEAR reason and B that not program in if other time. the drugs Again, RNAs are Phase impact GSK III in loss Phase II the the We're has -- GSK's sure. antigen the started lowering that for which study program are the It sustained s about all. period the taking And nicely is antigen pleased it things at S for long of did data that's

programs enthusiastic our very really from all? see and about at any other we're program don't read-through So

of competition I just the J&J as the seen, think helps drug short, have from BPIRAVersen already because we Eric discounted was Phase kind Michael, efficacy for situation. IIb in that greater this -- clarify Yes. said, in

it. if the and competitive it just clarifies Bearers landscape further it So anything, for enhances

The next Stifel. question comes with from Paul Matteis

This is for on James Paul.

may And or get data? see about Metagenomic I the you light them balance are taking efficacy? a of on how And suited from partnership you that about And the BD Just independently? from a versus look assets, thinking again, when we what's a whether are thinking quick thinking of maybe technologies one in your about a step guess them not and potentially nonpartnered back as on at or so. of pursuing the a this sense trial just you thinking then to latest on quickly, them strategic perspective, how perspective, monetizing launching other all Angelman's.

Sure, we can James. there, lot I'll a question, part especially There brief. but try to about, was your in the second talk be of

this be well. laid confident data the has of to more study. for don't the feel We we out Phase a line time, feel that the I/II from report brief at very very It's Biogen anything study. in will time very not have going except we execution because dissemination good. Angelman So

study the potential support that a III would working are efficacy through We now. endpoints Phase

progress great We about it point what Angelman Hopefully, constitute making patients end update Angelman regulators syndrome later good as potential a right very at meaningful I provide the benefit that But feeling with to Phase study. clinically now. very we're III with start. an leave to would have a for Biogen are will year. -- for this

With what partner, keep too. forth, stab a respect bit, I'll a little then that monetization, in what Onaiza with maybe we chip so take we and could to

our So for a in Ionis are R&D that we assets have us of front organization. today, late-stage the focus of from on We pipeline. wealth

be on with really And and do did into lot forward keep ourselves. carefully will those a which donidalorsen better, better to olezarsen very -- looking we're eplontersen, recently a We potential versus to as Ionis off mid-stage we down partner as we coming have pipeline as now. a of drugs and new with right for those to assets that And bring will be well of deciding think sense the are rich development market will make we road. the

forward the of on looking now, year next this what eplontersen, the We're as we're referred donidalorsen. Right an on half those to providing and laser-focused I in Ionis drugs. olezarsen beyond to update opportunities commercial launching of second wave

-- monetization pharma. royalty are talk any to for you we planning plans asked, do far and we're year pelacarsen about go do how did bit you Royalty we prioritization this monetization earlier SPINRAZA in to no through want I like But little a goes, there not think that. As as work at royalty the

sure. Yes,

maybe you in focused a of half mist I'll think it, a opportunities, you mid-stage looking on factors. we're of these of the look commercial we lot near-term give And I lens a second of from we comes think as covered what at the into line next the to X also pipeline. I year. sight as

a mentioned Brett think I couple.

full the be can market, they maximize frame the of of product. can would very which in of we it have don't, with a If can, on then kind synergies some the if see. we time do efficient we actually in We within And potential that actually they does customer-facing the way. we fit that

a here cadence see coming of schematic our those to probably of bit really franchise. We in over that's make selections. terms criteria the So of products neurology from in nice a

exciting. nice very works it's neurology So a here. on team early There's really mid-stage to that

So of you'll in the more about the that hear half second year.

a We in also And couple such in as specialty. our that donidalorsen franchise, vera. move then for of like products have have we just can done sealers do polycythemia specialty specialty into other some have we things

in there, which this looking seeing data So at time. to some forward encouraging the is point -- of we're the

think in kind kind kind with with then our for midterm. I integrating So the our partners and how near the full of of R&D, there's to more and that's for again, going kind way work as understand pipeline to realize and closely the ourselves product. of we to strategy indication market said, And well potential early-stage like what term about the that in very of to we we of actually as benefit look where to market think want

Thanks, Onaiza.

& question next Jen Yale comes The from with Laidlaw Co.

Phase half. curious there study indication, would whether late a the know other atrophy geographic also right is is advancing giving a -- product I'm this B, how the In is terms Roche And and there's company one recently of I whether Factor is think now. the III clinical the that study one approved stage into

the new you, well. the to the Maybe initiating And programs Roche Eugene are question. late IgA then last the to study that there, will Igneproperty nephropathy, year want on atrophy, reported news That's still thank right? to report Both this. well, really going plans programs But we early Yale, I add for on except nothing track. there's this Both Phase and that it's rare -- a for indication. is really year geographic very going

how the certainly enrollment those with picked progressing. pleased up Yes, has study pandemic, is the very and we're

recently. we've So the conducted study, it is II large studies a of X largest Phase

also the interested decision a for to optimistic is So next we're program. obviously on that steps make particular and quite keen Roche very and

that a sorry. the about III set a to potential II almost handle question I study. is designed for The Phase study Phase to how broad That's a acute indication on based versus asking going Roche GA your a can't is the you, up indication? Roche. if rare -- was answer study for one question And

more And come maybe question, one from investors.

still future? you that feel you It may In the options on, that, curious be the terms you whether eplontersen the if the could seems not that if study. like trial needed later just have ATTR-CM, there's already study in of in data but guys you upside to do change upsize

need on is Yale. we study upsize we CARDIO-TTRansform underway. label to We the extension study. where don't expect right -- We the we're be, is have to the think study well

the they've mentioned OLE. patients now We have

All of last decision to event for first had respect everything this enhancing upsize said is my made naive timing -- question of as opening the according important. we going patients TTR I the blinded tafamidis of to rates, with balance I hereditary so with the is versus to number and my cardiomyopathy. the think why when I And study we year was in -- did plan

approaching line. are finish no the We're there the plans So further upsize to study.

the all congrats Great. Okay. for And progresses.

Stringer question next Needham with from Joseph The & comes Company.

rightsized a broad this R&D on at you here, and spend go And size prioritization pipeline as us of the is given the consider breadth, forward? this from current Just you the just outlook sort one do time? evolving quick pipeline pipeline is company's an

about it, team value think important really Thanks, I is programs. here been our role, bring my you That we Joey. moved to the prior objectives to all CEO well really evolution the has company. to one as been as organization into what focus to Since our key integration, of full of if is partnered on has my going the to greatest

important. It's market the into products Phase prioritization more make So and vastly to investments as less bring we was focus important through ourselves. III

that's our tell not we is size or cannot from the I now. of as you that X pipeline have So the will say will be can over What best focus pipeline example, the today although for said I because the same the size we done whether we years away which and we're years of don't indications we announced think use oncology resources. we when last that from moving couple moved like we away our from of

but to drugs magical we'll what that if surprised that. be size, focusing wouldn't I And know be that do and the in asset. example, based the an prioritizing. size as the pipeline will reduced was And on value are of maybe number proactively we we don't a continue number I and will each those really to of indications for expand even drugs, maximize

you Do that, Onaiza. want add to to anything

development and strategically our really aspects emphasize forward. some question. a bit last the last to of -- I and research and the commercialization, and prioritization from it it Brent's we forward I through is do what each also I we rigorous it's programs, this continuing year this of a think color of that little through again, about took to give really I on to process the as approach way think the that more how processes well. a not most all what's bring included a the more to And do think but year, Just quantitative manufacturing spoke and like briefly vision team we're about in really large bring talks putting portion just Ionis you qualitatively, to I how into of important

keep nice all to have we to about to think want some we market. ways the what So really way

good distinctions belong some have potential. will again We think realize on their programs where and some partners we really also with full

So stay tuned.

talked in the bring of see you'll and of about, more that continue We in kind Brett focus to our pipeline. it

And that I another you part to Joe, which question, had forget.

No, that was it.

comes Werber Cowen. Yaron next The question from with

I Brett, just X. got Great.

I XXX study the obviously just one was study, follow think in started is XXXX, current guys B to ran the you smaller I then that first is Factor just believe and which The That a maybe up that study terminated. patients, on XXX. The question. was started than

a us sense what there. give of happened Just kind

change the different. at think was a in whereas GA? in also the factor primary obviously I study levels, That looking B is current was endpoint

negotiation in second, have thoughts nuts indications can the broad mean will hopefully, standpoint then ultimately a or get your on the in IRA. just X you potentially And the what future, label? from preliminary Eplontersen that TTR a does

Yaron. you, Thank

that – Phase studies you So their study design for to, referring I. conclusion, a maybe natural those to comes in. I did Eugene, that’s been – There can have chime has and to Factor B, the Phase terminated you’re conclusion of their didn’t been that the conclude natural that can We what study.

us study, We your have a Eugene multiple what in as that’s standard activity nrolment for very earlier, said pharmacodynamic picked safety has to which, atrophy up as II going B, as up is Phase single and dose set as measure current well. really Factor reductions dose and the the multiple Phase well single geographic a and dose X I is

GA study IgA been There bit Onaiza, really much the is planned The not in I’m it. sure can do going that or I you talk for Factor say either IRA? have programs B program about well. not about were nephropathy. little no to a terminations want

Yes.

been of as kind know, our the portfolio. implications you looking at we’ve So for of IRA the

disease. PN single disease qualify drugs. we a direct orphan of ODD designation as got as because and specifically, for both single And orphan of there’s that eplontersen an For And you is exemptions. know, exclusion CM indications the eplontersen, the way for

designation other. one not indication and is necessarily drug for for the orphan Our ATTR,

think thinking would as excluded that from price that, should be and then you that you’re well. So we as about negotiation maximum through fair

patients in their Medicare Part or a it make so-called of not patients the hole Part for away believe catastrophic Medicare to benefit patients. The and Medicare and of the that cost other to of kind really for right product, this the we do really a – way, under kind as between is goes up choice thing keep we B for well. D to allows is away, really care a a kind leave costs good for took donut mind In thing disadvantage so out-of-pocket Part D

both eplontersen playing the really into well implications. as we look So think those are we of IRA for

The next question comes Barclays. from Gena with Wang

Just a ones. few quick very

the the R&D be will I as First, revenue. confirm to that milestone voters wanted of part reported

of percentage manufacturing then the you regarding asking the in regarding percentage a past in remind construction, the you'll what Can regarding teams. final? is in facility the the cost go quickly facility? lastly, the you patients? us goal is patient What remember mentioned patients of And the patient hereditary Second, I CARDIO-TTRansform. that

up punters questions. do to breaking So facility? I got but you Thanks Gena, for the I and you want a questions. manufacturing the take little think your Beth, bit, were milestone the

the Sure. question, Yes. Thanks Absolutely. Gena. for

the manufacturing milestone approval we're R&D eplontersen facility be So that million. will reported an cost $XXX will anticipating as And revenue on about be item.

already engineering, are design, along architectural process underway. efforts programming, the We well with in construction

spread next And so you be over cost to should anticipate several out the that years.

We running expect and in to mid-'XX in be facility manufacturing API time and late that frame. up 'XX,

little the a upsizing I'll for study the goals is between is to patients earlier, that. naive comment I for of equal on up hereditary, CARDIO-TTRansform, but our get tafamidis balance for right We're stated patients. think the then and And now, our relatively exactly targets well way. And a delivering bit, Eugene to goal, I what but are tafamidis, our ask as broke you on again,

Hereditary?

have at the a time of to is disease. remember, study attention a is with as to we course, hereditary, diagnostic trying ATTRACT it of options Yes. was tafamidis a It's and target done different sort what this different guidepost. -- of we're

population. we're patients targeting going to enrolled XX%, the a that's It's guidepost. achieve -- what hereditary because That's the in of just that, So XX% kind somewhere difficult of we're percentage roughly as they've be range. of total XX% to but

Maybe for one last Gena. you, time have question. we Thank

Sandler. comes from last Kim Piper Do the And with question

to to of factored payment? for I'll recognize you is Follow-up how are year? upfront I guidance keep agreement into want going on just one. and And pharma the to that SPXXXXXXXXX revenue it the best any royalty if the this

Sure.

So increasing essentially million January payment our is the in cash. $XXX we received

payments the SPINRAZA to booked offsetting our to in to be Royalty be will royalties So top there'll you'll our cash we Pharma. make an for XXX% line to that continue And see revenue. the in need liability of balance QX

So give And some and revenues top line QX it's already with revenue. revenue of really the royalties of a we our we'll assuming factored complete the auditors. the split similar reflects into treatment on accounting our commercial R&D at Again, that XXX% guidance. more once detail SPINRAZA detailed

on Thanks, Do. year, a for plan We're successful on and for joining very XXXX. everybody. and throughout really progress of providing participating. you, Thank look We call today's the make and us looking year. updates all technology as ahead our objectives to and the to we pipeline for positive to forward our you to Thanks continue delivering key we commercial momentum

So for thanks and much until very have a participating, then, great day.

concludes conference. This our Thank today's attending you bye. for presentation. Good

now all disconnect. may You