Ionis Pharmaceuticals (IONS) 3 May 232023 Q1 Earnings call transcript

Good morning, and welcome to Ionis First Quarter 2023 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.

Thank you.

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

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

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

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

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

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

franchise. is granted treatment especially start achievements strong This from to the SODX-ALS. QALSODY of week, with important our several off year accelerated a approval the neurology Last FDA already, for

QALSODY target a market devastating neurological as approval SPINRAZA the to of with and genetic a a first to this joined treatment represents product major approved form approval, This And scientific patients breakthrough. the QALSODY disease. our only is for reach ALS. newest with

approval RNA-targeted clinical platform XX further tremendous that medicines a advance in our to being today the therapeutic diseases for community, to addition this includes ALS In treat development. neurological validates

patients study Phase positive just also eplontersen polyneuropathy. in ATTR data reported We X with the NEURO-TTRansform from of

progression this favorable Eplontersen we untapped endpoints, the data, strong eplontersen halt Quality the of improvement experiencing shown its and in study, on population. be disease mNIS+X for safety approximately polyneuropathy tolerability. Life. also co-primary profile and ATTR Based neuropathy to totality demonstrated are efficacy was of potential largely with half Norfolk product eplontersen's patients hereditary confident to treatment and In the the in important of an

additional With partner, countries a course, these which to with U.S. our in working the date outside discussed is towards during data, webcast possible. last of market And and is as in Onaiza of submissions we're important under This, with in the AstraZeneca, quickly to December week, this regulatory working are XX this PDUFA our of addition to we NDA, AstraZeneca as as year. hand bring hand medicine our review

near-term the this donidalorsen we very other X we're two for commercial second and half for opportunities, Our olezarsen are Phase indication. data track in commercial independent rare first our olezarsen, on launch year. FCS in from disease in preparing the study progressing well. of this BALANCE also And remain With

year. keeping We Phase our the track of SHTG study studies for HAE olezarsen. half also soon, With OASIS the continue in X next track on make really to first we're complete pivotal enrollment good to us in progress of data donidalorsen, on in

separate Additionally, pipeline chronic the late-stage in our advancing programs of initiation expand, seven to X in HBV. of nine indications robust continues bepirovirsen development at now Phase with

financial our medicines readouts importantly, sets over of market. we substantial and up track cadence a to and XXXX pipeline number on potential years, growing the us a key remain goals our increasing across late-stage for of And the for achieve reach to expanding accomplish Our next steady data guidance. the business the Ionis strategic few new

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

our before Richard. up Over and I'll to first wrap our taking your review then you, will Beth results, Next, financial questions. prepared remarks quarter

you, Thank Brett.

believe improve patients We goals neuropathy endpoints, just Eplontersen and in demonstrating met the substantially this life secondary measures. have met quality polyneuropathy. that of polyneuropathy the consistent reported NEURO-TTRansform we and study we mentioned, of to eplontersen's important efficacy all benefit number a a demonstrate programs data all co-primary potential with Brett positive As year. key from patients ATTR across of outcomes range in for already ATTR

across robust reductions demonstrated improvement XX patients significant serum favorable and substantial in safety TTR secondary of continue statistically and measures profile. also Eplontersen and a and all and significant both neuropathy showed a number Eplontersen of life endpoints of and meaningful week XX. improvements and quality clinically week demonstrate sustained to demonstrating in with benefit four at tolerability

present data from study, set conferences. this medical upcoming In we're additional results addition at to to publishing

around in our for on in give and and year and in markets The this and positive later submissions efficacy December we've study additional NEURO-TTRansform year. us remain preparing even the partner, next the track results seen world We safety approval AstraZeneca, greater a the are landscape. longest for for U.S. confidence of regulatory ATTR CARDIO-TTRansform to the to demonstrate study indication date, the completing anticipate in broad this for the a We performance CARDIO-TTRansform patients cardiomyopathy. is of largest midyear. set and that represents treatment our benefit current eplontersen study enrollment with in in ongoing patients designed potential in

olezarsen The is olezarsen multi-study the In Phase our two HTG remain track to study is program indications, second progress. and broader and data continuing enrolled, Phase X the of also on evaluate program half by designed in to FCS characterized for SHTG development severely this severe in triglycerides, is we year. also X for indication broad to progress fully BALANCE continuing Our elevated well. FCS

on donidalorsen our program Additionally, development track. remains

for the expect the X of on half in which to year. shortly, next enroll study fully We OASIS Phase first schedule HAE us keeps data

open-label reported attack with favorable competitive study of for year, reinforcing X data first from and one Phase profile. longer-term additional we of profile its in the a in positive quality extension life, safety rapid donidalorsen and included improvements potential treated clinically durable onset patients protection the meaningful continued quarter, which tolerability During action

minutes these and medicines to eight X Phase highlighting I in neurology Our Phase important like would recent studies of in of franchise have a development, XX in including two couple that updates. includes medicines X. two spend

treatment As a the target the disease to based Brett was recently approval community. FDA pleased of mentioned, in reduction genetic This neuronal of only ALS for QALSODY's are form on light it neurofilament a chain or and a patients. in that QALSODY, breakthrough NfL, we with making is the approved the that monumental approved marker progression plasma ALS. first correlates damage ALS

patients as and the open-label muscle experienced treatment approval supported XX-month the measures results X a started strength. results Phase earlier well function VALOR slowing who and of decline by The respiratory The was from the integrated extension. showed as integrated in study clinical

EU favorable X ATLAS Phase is review in the the nicely. demonstrated Additionally, ongoing QALSODY presymptomatic a and under additionally, safety QALSODY profile. study. study Patients SODX-ALS is progressing in also

in data are We Nature the ADPD by recent Xb Medicine encouraged presented from Phase Conference IONIS-MAPTRx the and at published study. the Biogen

patients Our with medicine, as tau in disease and BIIBXXX a progression to to and imaging. Results PET of AD weeks also in Alzheimer's sustained is levels and aggregation by up in Tau the CSF production protein measured reduction pathology XXX MAPT our for substantial early patients associated rapid, known disease. aimed medicine at with showed both reducing treated as

this date. the fact, tau In drug across pathology regions is reduction a to of MAPT first brain magnitude to demonstrate of important our

every dose which is includes different the AD, three in Biogen months advancing six with X Phase and dosed months. early every cohorts cohort two study one patients dosed dose

are reduce to extend example MAPT one is even of making and we and duration drug diseases for frequency with our technology potentially more advances Our dosing broadly. just CNS

in the Our advancing a bepirovirsen start the expanded pivotal year HBV. drugs of pipeline for of total this seven separate program late-stage to chronic patients nine a in indications with with

IONIS-FB-LRx advances We when expect a study pipeline X IgA to our expand late-stage Roche for this into further Phase year nephropathy.

results steps sapablursen two cimdelirsen we in took further further with saw beta-thalassemia. did to not meet acromegaly and of target the in product studies and mid-stage but our tolerability, and recently prioritize R&D minimum pipeline efforts favorable With We both profile our discontinuation the evidence in good focus safety our target development. of engagement to programs: justify and drugs, efficacy

X it we from share continue for and plan sapablursen available. study vera study polycythemia We Phase the advance becomes as to of data this to

olezarsen, of number including decisions remain and launch events, after key include data approval and to for regulatory eplontersen next medicine We late-stage for U.S. Phase our X achievements. pipeline track on These eplontersen. a potential

updated these more the and keep events year. We you throughout on will progress our on

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

you, Richard. Thank

results our business. Our across reflect growth generate to approximately of We financial half products our numerous ability revenue programs. first quarter in million earned partnered opportunities key meaningful for from commercial revenues and $XXX quarter while from investments was making half our first the

operating and programs. readiness our for quarter our over period last expenses loss increased and Our our commercial as we the late-stage pipeline, especially advanced advanced first year the activities operating same

million $XX making global of continue $X.X ended in enabling create based with in future quarter. revenue growth cash investments royalty million to March We We product of the opportunities. earned billion, substantial investments to first SPINRAZA sales $XXX on and us

we highest revenue royalties Our reset SPINRAZA expectations, midyear. by anticipate our annually reaching based and royalty the tier on

Additionally, we our see Pharma quarter Biogen's first continued transaction. revenue to XXX% commercial year, With signs under continued our we stabilization of as and sales record in base. Royalty SPINRAZA the to slightly SPINRAZA Biogen royalties compared were lower patient product of in last to

AstraZeneca, while new and also can into Based to from on for among for growth. advancing focused the numerous management revenue And already Biogen $XX others. R&D second markets. efficacy cycle these SPINRAZA efforts, payment in expanding its we in markets robust on earned believe and QALSODY approval. programs life partnered quarter, remains we existing We generating Biogen of U.S. Importantly, earned $XX all Biogen important milestone million and expanding program. return quarter the a with million first data

increased last to operating compared in the first quarter period the non-GAAP expenses Our same year.

our X either in our costs approaching of advanced Phase enrollment, studies R&D increased robust expenses. pipeline, resulted full we or which most fully study were As higher enrolled as our ongoing

expenses as prepare donidalorsen, modestly to eplontersen, and SG&A our olezarsen Additionally, year-over-year. increased also launch to continue we

Royalty for minority We SPINRAZA pelacarsen exchange royalties. capital our million and Pharma bolstered by our from of in share potential $XXX working adding a

reduce As liability, we Pharma. when a we payments a recorded long-term Royalty which to make will we result,

first $XX XXXX million. expense we which will imputed was noncash Additionally, recognize quarter of for the interest

QX. higher QX Looking revenues we expect our ahead, in compared be to modestly to

half the also weighted year. end We anticipate of will be revenues toward back the second that

our estimate will year operating related Phase the project expenses to XX% to this to our over expenses we increase course slightly includes capital-intensive with expenses of remainder and gradually XX% We Consistent R&D and which year-over-year. studies, guidance, increase QX full year. our between X the increase of in

made Excluding year. the Metagenomi payment we last upfront

in about $XX We olezarsen our investments eplontersen, SG&A expenses project of year commercial and for preparations our our range from in year-over-year to also full increase million the donidalorsen.

next in period few commercialize we of advance late-stage to a investment our planning to are prepare clinical programs, to years, as our independently the and we be continue For medicines.

grow our As to expenses a modestly. result, project operating we

our add we increasing keeping commercial revenues more revenues build sustained of to of greater compared anticipate be With by goal to and the and for R&D we pipeline, R&D value revenue today to on and And project expect driver primary shareholders. into Ionis-owned programs top Additionally, commercial our future the drive commercial Ionis substantial of ourselves, our of base proportion revenue, we to as our revenues we greater investments future our for to growth. revenue. our a continue

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

Beth. you, Thank

with the our anticipate positive and momentum advance priorities to to achieving year. our on genetic events regulatory additional important pipeline continuing abundance late-stage we of medicines of goal We as our come delivering We're this an well our still way market. new key

pipeline, And QALSODY with date, medicines on next a we cadence the commercial add also portfolio. And well with market our the several December We year. bring late-stage late PDUFA to eplontersen could just years. positioned steady to the rich over additional to our this we're added

activities, ATTR the with pre-commercial AstraZeneca and our making view. Additionally, all first sight for olezarsen clearly progress in in also with independent in polyneuropathy our launch of with with eplontersen our launches patients of is donidalorsen planned in we're

to We future technological for make innovative advancements medicines. continue

invest financial achievements objectives. the to important strong areas on to in and drive with to foundation And our our as progress sharing our potential and greatest finally, drive our accomplish recent look enables growth forward value. We build us we

And open it with questions. now for that, up we'll

Company. Please from [Operator first ahead. comes with question and go Instructions] Stringer Joseph Needham Our

taking questions. all, our Hi for thanks

program Just on wanted additional to the any discontinuations. two get color

safety fit you. didn't But any profile. any it be that there target your there, helpful. mentioned, didn't on sort signals or of efficacy would You Thank threshold color just curious, was product additional they it meet were

Sure Joey, to. happy

acromegaly both The cimdelirsen for about were Intermedia of and issues safety was safety sapablursen In question. poly being time. at in the two all. in focusing were clean, and cases, profile It on these your tested No and drugs acromegaly all pristine. first No beta-thalassemia a to for one's scenario targeted these ever efficacy. first So.

hepatocytes on hypothesis IGF-X we competitive block and we hepatocyte, - our that it treatment IGF-X growth on was acromegaly levels the block can acromegaly. to receptor GH for hormone caused by know production, that is receptor if Growth in could a as hormone you substantially excess be lower

we IGFX of some reductions. We this reductions, didn't our tested our data considering in the profile enough for wasn't was refractory the monotherapy last reported data. meet and bar. pipeline, product didn't and year minimum clear And richness it It but that just the we good saw it target and

So on we're moving acromegaly. from

more Sapablursen in we're multiple interesting is view. developing indications. my Sapablursen for

first beta-thalassemia intermedia. The was

a sapablursen As reminder, targeting show targeting strategy. we that GalNAc TMPRSSX

in So should couple study, target say, Phase or - we really I reported years quite in that X a efficacy normal engagement, remarkable signs of ago. of our volunteer

as and exactly expected, in levels we changes. which see predicted we what changes didn't we're significant polycythemia, achieve in I'm - trying iron volunteers. TMPRSSX normal by had in with to those is showed metabolism, targeting In predicted intermedia, sorry, beta-thalassemia We hepciden very elevations

reminder, genetically in a it's target, not target, As keep is validated mind. a pathway TMPRSSX a that

very And from preclinical - didn't With pleased to PV biology the that by advanced parallel, with didn't of seems different into to meet it TMPRSSX setting. that we encouraged some and - to in we biology we're targeting PV. the vera that see in - intermedia. the product in very With said, so polycythemia data target by profile. initial the translate very we're say beta-thalassemia versus clinical said, be seeing seems that

a in product for drugs about so indication bring that minimum that drug profile, bar. the did pipeline drugs ensuring our meet attention it's the can in we for We're invest So focus target and are sapablursen on we meet all on the our value not biology. going laser-focused the acromegaly that to and that that greatest

that's taking you thank Well our very helpful, question. for and

welcome. You're

go-ahead. with comes Please The next from question JPMorgan. Jessica Fye

on for thanks Great, Question my question. eplontersen. taking

XXXX out-of-pocket talk IRA how about And what your I'm the And eplontersen, Thanks. think the XXXX for you patients [Acoramidis] related you through B? compares that you'll to attribute for costs annual the how readout this to and to product data summer. competitor changes Part reimbursed Medicare out-of-pocket in with also of then First, and for Part-D, costs can about be eplontersen watching when curious beyond?

would Onaiza, CM? about IRA, maybe question. great talk bit Jess, readouts little programs in you, you could competitor the take Thank you data a Eugene, from

Sure. Jess. Hi,

the we're to payer understand marketplace. mix, first all, of important So it's the as going into

the patients polyneuropathy estimating we're two-thirds be So or commercial. about a Medicare, third of in will

X they - a be cards will to relief B, which you're X, will manufacturers the co-pay will we as some do. talking - So through Part Medicare normal not with hopefully design, of subjected which obviously D Tier offer level about. They'll go co-pays co-pay most Tier will

its catastrophic costs for gets ranges XX,XXX. Part-D - you for patients on their of it currently capped be until the that - the specifically it path into $XXXX, the On know, layer, will through out-of-pocket XXXX Part-D patient as goes for all eplontersen it, go in to recipients Medicare starting - at third in

which to a change going silencers in we to TTR for disease for I for then, Medicare - foundations positive ten folds patients, provide disease for that Part-D. these huge well to used expect access it's being come - would the the these currently is for down as say it's first-generation for And as patients diseases stabilizers. still for patients So

coming don't they dynamic different have that's their what the terms you sure they then on to could I about, actually of very paying of they'll as still of think on-board that of level have And happening have because supplemental, some well you them. terms have in Part ability coverage, be the patients there office make think be increasing In particular staff costs the those a is administer have to what number dynamics co-insurance, B, are of considered to depending for for high really offices have terms be for patients, really those if to in then the they in. that

well, self-administration on of these continues eplontersen. big that benefit our patient of of as a center not the of particular characterize drive ability the it just is physician, reduces it close well be self-administer if and as to at driver far really the really patients for excellence. as home really really to I'd to for then, our And both - at-home, burden It's many you're preference

readout. the - looking you're what Acoramidis most for Eugene, what's interesting upcoming in

interesting - within the interesting to to was background really trial Well - of the tafamidis arm, think, arm. was we rate I would I sort modern, certainly is even me most thing the placebo for me see mean, be post would the active the conducted trial see and in be of that on in by fact most not the outcomes last a modern to the that years and and be what the past couple bit seen the relative a

focused we're all - on treatment of these it are effect. course, over is study the This of also number now Although, seeing followed patients the - years. a has followed was

this readout. to be is the first So going

I for more of As reflective which we the may is population, newly-diagnosed what like. of current the believe population said, look patients

or that Whether seen are interesting early looks also will day up of what the see mild matches were they will it placebo silencer how group more need some the compared in with be to to a we've ATTRACT up not the - So. stabilizer patients study interesting. be and the than well as to

question. Next

Wells The next Yanan question go-ahead. Fargo. from comes Please Zhu with

event you a one provide questions, from What with about tafamidis the CARDIO-TTRansform - of thanks the nearing enrollment, on be talking rate on out proportions look suggested, Hi, two on more read-out study as could your in and congrats than you of tafamidis update once the study. follow-up for could, studies study? maybe would blinded progress. different an just competitor relatively naive taking on and comparator. the rate at mix wondering before Eplontersen the baseline so the you're to to you learn that characteristics able event maybe also the patients on for cardiomyopathy completion complete versus was of here, what I questions and any update we look to anticipate compare of these terms about ongoing with you enrollment and patients we data, -

strategy about competitive assume, and be a - it with a eplontersen whether AstraZeneca whether Thank on, on it be you. would or working wondering that parity strategy drugs pricing lastly your I is competitive price? polyneuropathy, And could you

Thanks, Yanan. All great questions.

So we sought due the several study, One the to diagnosis to we earlier to of powering mild that have necessary study, become has the support that the - we that achieve. disease. size upsized was and was of when CARDIO-TTRansform had objectives we the ensure study we and that more for patient a detection population to awareness

variant that to we had usage versus XX/XX that of second percentage The are tafamidis wild-type. a then, the the naive well-balanced patients was study And to of versus patients. ensure increase thirdly, in about

completing going Obviously, to coming to we're and enrollment close to be decision this in we're confident have to we're ramping-up around upsized patients our very very X,XXX and study study soon. the

way objectives CM our increasing percentage very also is well for of a the in it. we're we're patients naive study pleased on that we're as between So there, but and the achieving as of course, our good tafamidis well variant balance

all achieving We're way our well on goals to there. our of

well in-hand. that's So

when percentage it very Wouldn't as blinded we those upsized would where too hoped mild we the the well high a had we study, As think we - and sites study We're is event and would is sicker. when has prioritize performing very upsized doing the of carefully such disease. rates. far be patients monitoring as that

the seeing event see We're too. well in what we to very want - working that's rates. blinded So

think data that? have strategy, I publish you plan We'll me. that. publishing pricing but of very to it's competitive the respect think, I And or be do as With to that to like don't in would we're a that as to - don't at comment time, front present on I going rushing right space. don't Onaiza, demographics. far

right best price we where work really our patient. and for is to AstraZeneca. now Yes, with access the going that strong simply, we're to according ongoing coverage to going get believe Yanan And and we're

it's in outside will multiple of the where markets a just U.S., terms your we're launching that parity In reminder comment pricing, be first. on of we

be setting well. will in we So markets the as price those

And as coverage. are access get both those the products sure both is well mixed make to as again, these in polyneuropathy goal going consideration. So patients XX,XXX and phenotype, we and into for have

helpful. you. very Thank Great,

you. Thank

The ahead. Please next Ulz Stanley. from comes Morgan with question Mike go

just indications? any guys, for those based hey the the on two from like but maybe different thanks taking PV guess, in just quick Maybe biology Thanks. cell read-through different a sapablursen specifically question. why some follow-up could to I the biology, sounds don't explain you beta PV. study? anticipate Yes, It in on be you you may do

We objectives caused intermedia we very seeing seeing the beta-thalassemia We And to read-through just in thanks, biology levels. for read-through. a PV good the encouraging for very elevate we to that it's we're be not because sapablursen that read-through. from studies that's there up drug. thought for in very this question. - read-through. TMPRSSX production by for thinking polycythemia really that in thought hepcidin vera didn't as beta-thal early We're could both bodes both well indications low our in other think see signs the really hepcidin that disease - some was But nonexistent our or We're

all different, had right I similar and in intermedia biology the was is we model condition. I an the the beta-thalassemia was don't. on the to wish, answer surprising human models signs very those we published were why mean, animal for was thought so we which profile, they that strongly preclinical extensively I had Beta-thalassemia in really data intermedia. What predictive.

happen. didn't It

beta-thal, in elsewhere, did in we're and it's something I really normal that about biology, complex knew hepcidin wish surprised, increases we was get, to get that So patient just more. we the What we we expected on more the what you is that so going we can were there seeing I tell volunteers population. not but that, got

PV lower nicely would through and no we're seeing safety very-very big not is efficacy, say, that the in we any look, even read-through and on the it's is on so sensitivity on saying, driving Brett I issues, may fact, and safety, margins. least there completely the I agree, the patients doses means, that the at in early reading but be

Yes, in in great really expected a treated into The beta-thal just Richard as we affects - pushed we expanding though the if pristine. could and you dose. need realized because And And we long-time safety Richard. I pushed - a we we point, on, on expand me. dose and And didn't we to dose, said, even beta-thal. see the we another indication, came the that was that

So and going we're so dose It we in why looks for low-dose further in develop. indications confidence pursued chose going to a doing - just be lower treatment at, we why we're we pushed like, what looking and the gives for is this it beta-thal various and to indications. it's that be we target us

very it, Got you. Thank helpful.

with The Yale Laidlaw ahead. Company. and question next comes Please Jen from go

of WAYLIVRA sort drug, this Good then, just year. first [SHTG]. presented from in sort have morning, of in guys the taking later other for The outlook thanks you from of commercial what follow-up. another and this will the of have the experience question aspect future I'm data prior question. I the and curious, regarding further My terms be improve will that learned olezarsen is

Rich.

that's but our yes, back not And looking current - with a Yes, experience WAYLIVRA. only question. great at previous

pancreatitis. But appears events down what very I and the downstream connection triglyceride be the in of a growth to the ApoC-III think, driving significant of inhibition. - not are really nice space this commercial what's that to really have lowering approach only strong We activity

these are And better, commercial. functioning and all feeling hopefully so drive obviously, better things of so patients

that experience. the I even So that learning, from we've got and we have that's way today learnings we think our

deeper that, molecule, I'll olezarsen to generation ApoC-III triglycerides WAYLIVRA. Richard early add saw more in the we potent and than expect a even is and Yes that we with and just reductions

trends attention Of our thing addition event paying course, And that with reductions, other the profile saw strong patients pancreatitis this going of our with safety reductions today. - seeing all in WAYLIVRA to reductions potentially, is [lipids] with we're feeling to in liver like to is better, is for which - the hopefully we fat. pristine in we're be

be to that and we'll be as you going question, that. long going again, replicate had Yale. reductions that's we're then And we're too ApoC-III in important at greater because seeing and looking - we're well another very And

in of sapablursen PV. Yes. Yes, terms and

the think used this is what outlook, the data later thanks. year of secondly, approvable contemplate in endpoint or all, and you positive pivotal study, reported for be be if it's and of the terms First will will outlook do a that

are but at at what have and We I'm to the out so, really leave not. We I'll the little Yale look about certainly rule So an and dose PV. it getting it the you this know have would help Eugene, report not promising PV. bit this point. year, that. approvable out, just maybe wouldn't And if I to with We're we're dose-ranging. what figure going cyclical you going profile, data We on endpoint be to for Eugene, don't that? sufficient do it at

is impact pretty, of endpoints their PV other free, we're examining low-quality symptoms such patients, we're but life. as going clinically there's the range goal of this endpoint, and proof-of-concept hematocrit the phlebotomy. to them explore of in within where early number but exploratory and - is question. to kind maintain that translates It's require - a fatigue number studies. experienced pretty of whether being level control significant There impact things these to in the a to going these their better-quality good of actually we're main also doesn't life-related of the a That's into hematocrit experiencing patient's explore improving Obviously, obviously phlebotomy the

to want add to you that? Beth,

just reducing free, to what the in at there as Eugene this well is of is add addition also attractive for U.S. events. really it's Yes, of phlebotomy commercial I'll or said outside the as phlebotomy There significant portion a U.S. that opportunity. both and in thrombotic a significant population, a market addressable terms high-risk in of

that are event. be both believe going do important really things we So to

which first-line is - it seeking or for that, just Sorry. - you're impacts? Maybe is second-line

we're I doing restrictive, some we payers have think But the involved. think this. generic, certainly there if some that payers - in there there would that's step through a they on work I going through to be be this may no be not too a to may involved, and do - because were bit step of are it think first-line of but

a thanks great, lot. and appreciate congrats. Okay, I

The next question comes from Yaron Cowen. Werber with ahead. Please TD go

this the guys, Brendan on Yaron. for for Hi taking is question. Thanks

quick from file HAE just first-half. of year in to here. in the you couple a data remind next Can ones prepared hits the on us, the us, you really are as U.S. Just

fit some physicians So maybe these HA the have existing could we of in just high you in Thanks. you're you Onaiza, into on into think an sales see fruit drug any how maybe you could think and kind billion then launch. seeing you move And paradigm potentially and maybe quickly if starting that wondering, of feedback lowest-hanging the need new additional from unmet most $X XXXX. HAE the or where

Yes.

to first - The the question, second Onaiza I'll question ask address.

is filing question first next early readout year, We're The year, in next easy answer. launch 'XX. data expecting

We are very getting much that. do to ready

Yes.

where teams and over on are - are working the We here. very diligently launch preparations

true marketplace and/or will important couple best-in-class research of holds in new parameters switch to continue We in be the important uptake on and very our that do profile for patients.

they really year. physicians really is compelling the in many and our attacks of right, far as to by for data in that But want attacks point have the in given mean HAE - virtually patients zero reduction the for most terms a can,

We also that have data emerged. really strong quality-of-life

testing, duration of onset. is took also point, you well really our reading important as a an in and look activity a rapid our OLE data, at out If which

is really our So Then, features. weeks. those of kind right which of of monthly, is best-in-class now QX important profile course, QX marketplace, in the are what standard-of-care all

Thanks, Onaiza.

Next.

go Richter The ahead. with next question Salveen from comes Please Sachs. Goldman

Salveen. on for taking is This Tommie for Thanks the congrats question, on our progress. and

programs positive from data how on broadly are advance in on these access portfolio, do larger treatments that oral any longer-acting two [ABD] you. or read-through. through now start dynamics the process markets, to be the go thinking studies, you Phase available. for more and we've may already how thinking you And Alzheimer's as about of about seen these Thank you where models indications, Cardio X here treatments So reimbursement

comment on dementia doing we're wanted how you successes sway? to Eric, the what and recent Sure. in

Well.

see. data patients, for positive certainly so to think, I fantastic AV is

different obviously are there right. clearly, mechanisms, so And

with reducing one involved therapies one the the the affecting, antibody, Alzheimer's which morning Lilly, and an data So this of in was amyloid disease. is pathologies positive from

pathology the addresses. what that's The and tau, other is BIIBXXX key of accumulation

nicely Alzheimer's tau visualize and positioned in and tau whereby the of tau Biogen inside the So we open-label pathogenic data lower the accumulation shown was by where can that's think PET, test - brain. drug be the meeting the tau pathogenic first we're can recent actually to that hypothesis really you disease they're AD/PD accumulations, that at the extension from

of of with BIIBXXX, that able large prompted it where drug month to doses pretty two We importantly that six into they're that lowering makes dosing, forward of to can enthusiasm - it different dosing and Xb a the difference dose really a the reduce see lots drug tau were the that in Phase pathology intervals at of of Biogen in difference form and MAPT take has to generated clinical and if looking make study, a outcomes.

that drugs improvements fact is that can and to make think with tau encouraging we I you have So other seen with testing hypothesis. the been look-forward certainly,

think, program. a I great it's

looking been great tau And we The a tested BIIBXXX. have Yes. before. hasn't in drug which intracellular hypothesis,

other on bit The a thing just to expand that is more.

We tau. coming dementia program behind programs are rich that dementia, in in have several programs,

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second sorry. I'm Tommie, could you your repeat question. then, And

be reimbursement we've some already of available, longer-acting do because on programs with was in It Cardio whereas Right. more oral for seen programs? how generally access other treatment headwinds markets, some and you think here may prevalent the about

Onaiza. Yes,

I Yes. this. back on It's a really kind go of basics I to mean, good question.

think you that need in particular its deliver We and really think, marketplace on terms I this profile the of to about unmet accordingly unmet we're that. have what that. and products stated So value bringing continued your need the to take to then proposition price combination the disease okay, is what bringing say, in to and what's

which we really olezarsen - our are triglyceride is if in pricing potential right of the I what do done world's good So the higher market magnitude prevalent ranges, see now. and the we really work, good the - product again of in SHTG have some talking kind premium we cardiovascular you're like broader Xx reduction about

do that CV very value premium have price compelling in we really to a proposition or we So range. believe

Thanks, Tommie. Thanks, Onaiza.

ahead. Please go next The with Paul Stifel. Matteis from question comes

question. kind is taking this Thanks on of for high-level James Hi, Maybe just broader for Paul. our question. a

SHTG Thanks. respect XXXX, two and those for Assuming with be you your in like and thoughts be what HAE. hits great? any salesforce in think at looks all, in would there to hits what donidalorsen there would specifically do What olezarsen Ionis like assets XXXX, look could of between, if type synergy

Well, wholly-owned I'll with in with organization. obviously her includes near-term to drugs about growth. you're working we're preparing drugs, half-dozen talk timeframe, I'll and new for in on in start, Onaiza James. commercialized of little well that the in course that. as we're on or our that the of vision build expecting partner commercial going and, and But we're launches something we're It's donidalorsen. so ask Onaiza, market our But pretty - as of confident bit address for we sort just a olezarsen work the to And

two exciting. really not right. need, I that lot know, the we just have you infrastructure I commercial they're synergies mean overlapping. planning looks both scenes it you would that, the cross-functional of Yes, teams and are of there all launches say behind for

even have go thinking we're with services that for them all behind for we're we'll then what team, next as we So of see building it there. lots and and and field systems hubs we our synergy independent and launches how the our patient our about to eplontersen bring well, where forward medical

very Endocrinology, and it's out elevated PCPs differences Cardiology in be a call know different, see - of olezarsen, is obviously our they specialties. a products is which those we this place points. for And opportunity, and and will prescribing, triglycerides lot in specialties, but we different teams But referring they're to actually two eventually they're will are these these we're a so is on not really are where where are sales for severely honing large two or - GPs

opportunity going docs that that there but in can team. is the Takeda concentrated of well very Well, the of or the and size. the XX% - it the it's you XX% we're then easily teams donidalorsen, fifty-fifty market-leader of need to working thinking and is we're that And ways ensuring prescriptions, on about they are that for efficient sizing docs that so different, So and allergists really focus model. concentrated, where the have after actually good and bench that on reps with it they our right are prescribe the the calling about get most very so very, really and are

you. Thank

Thanks, James.

Kostas The Markets. ahead Biliouris comes from BMO Please next go with question Capital .

Hello, our for everyone. couple of taking and on questions the us. Thanks congrats questions from progress. A

you won they gene And market have of first really relatively size follow-up. The how one I if the therapies, therapies the there, market the on are done, competitive swing then thinking or gene can they editing the are HAE, even about follow-on given small-size and - a further? which

to I'll non-preferred a DNA includes the and start - potentially, that. I'll potential to But wants first, respect unplanned There's patient safety, DNA off-target to manner. start permanently with on That to in the Well, very in prove a population, all of still the editing edit let in pharmacology. manner, a me aspects early-on. Onaiza, HAE she lot expand ask well, here. is

gene so thing durability, a in well. not, re-dose. here one you to the As have truly We've if and really There's for case be learn done. and DNA as it never can much done well as And editing. We'll done it's therapy. is one all

by younger disease of about early there's - largely at - building populations - families when early those when about and real start is a The HAE and interest, that's you into their be DNA patients editing they're an from at an age, thinking such to blunt things. sorts earlier. concerns diagnosed thing is, second this which The getting these earlier patient getting is

DNA of thing specifically on So for editing there's lot headwind a HAE.

are in Kostas, know, investing DNA we you editing. As

you different a have HAE DNA drug be But to we're Onaiza? in our don't of concerns development. strategy but place identification this Well the we for approach. molecules we in types to still we is as - we're investment forward. address in our going do trying for think It's right bring target those days, We editing. think What early believe

taking needs I that long-term safety think, demonstrated, edit span the life still you this well. major. addition is are early long-term DNA I a population actually kind and a would No, for the so in knowing not in their summarized be of what it consequences to say, patient to appetite

I'll third. then, add-in a And

HAE, that. one because what think in be really need will is, I to third we the are the unmet continue going remaining fulfill

time - it's - think the be is We have a satisfied they it's great product I going enter. fully and by again, it

had a second Then Kostas? you question

are two about Yes, How because different. how potentially quick different terms you different targeted these size in thinking thinking the two the I and you. drug will would exactly about the in one population same the on are populations? that second all you're you where launching dosing And pricing is there assume pricing, and in these? the markets, of the be Thank olezarsen, of

pricing with rare obviously Yes, and then prevalent a expect rare have with more a FCS for the a that We SHTG, know population. broader we question. disease don't we a disease it's so good population broader

terms We pricing but in stay-tuned. the launch what will pricing be of are our strategy working through

to like obviously different it, I that ways said a kind all. prevalent will that as more at disease diseases. pricing that the through should broader it to from you at we you don't if but of population in you're cardiovascular pricing lot be Again, be premium strategic of rare thinking We're see expect know get earlier, in at range looking range the

helpful. Thank you much, very very

Thank you.

Gena go-ahead. The next question comes from with Barclays. Please Wang

Thank you. One regarding program. questions. more Three quick the very question HAE

the for full Is charge taking question to regarding more competitive? the strategy timing signals, of question, marketing of readiness You as what seen program, have you're is safety for already future dosing eplontersen. quickly, described expected kind every a and already update is AstraZeneca giving for. the quite you so-far? Do Angelman what lastly, two market. to-go data what choice a And and a a clinical profile, you become second months looking on is commercial quick once and My consider lots very also in

Gena. This That topic. thorough. three quite Thanks, was very is different

quick a So it's no eplontersen. very to We commercial take I'll for two Onaiza answer. - the I'll but month - readiness and nothing just the Angelman, so good HAE on questions, Because new the - the let handle report there's timing. dosing

there - enrollment readiness. pleased are no is And the HAE the we're commercial we're Angelman's profile been with study going program. concerns No, seeing going bimonthly very and is very for The well date. and well. that Onaiza, the safety to has dosing

certainly, physicians strong competitive as For a really is data an will all option profile in for for the so HAE, for data, that two us patients and be don't Phase-X. month it the to it's available need make We'll be the but dosing that to but differentiate on for need wait we marketplace. Phase-X dependent our actually if way

you currently of work we're in very For are that eplontersen really that the and yet is as understanding of L over a going and of where the we're a growth window could of a believe future diagnosed at where or where been and to Lots with this on, months going lot that treated AstraZeneca. It's an an us approach of we're the centers we hit X have trying ability here do of minus be really number that versus way. terms, to patients in market the or imagine, and in can of scale is commercial in right they for strong identified, We do the because who haven't both. excellence there and readiness. planning it and

speaks And that the for itself. in and say, would then itself of data clinical I

even course is U.S., nice it and necessarily add, the So of lastly, China of Japan, we first. European the then of be markets, expect where but profile. order some in that to should has markets we're of And the not Eastern important to and in well, there expect are will as I'll outside second second European that be it really strong that's note many the though a markets Europe you U.S. coming in many, - lot entry,

Thanks, Gena.

go-ahead. question comes The Luca RBC. Please next with from Issi

much your team ones. in-place. quick two talk can that have a with I taking evolved is my so questions. Great, how new there about Brett, leadership big-picture, thanks has you now relationship just Maybe, for Biogen

if on pretty the we've color prior there discontinuing question. your they're on bar much appreciated. is circling actually be Sounds And just wondering, for molecule containing ataxin ApoC-III, would obviously, now any with focused seen on given so back cost, like and on then again, is collaboration maybe higher costs Viehbacher X, focused progressing partner

you distributor force the own us your what Thanks will U.S. rights, will appreciated. any will remind on-the-ground. sales you partner use so ApoC-III, like Can you your color for much. you plan ex- [SODX], Again, have commercial much

Great.

for Onaiza. question Second

Luca, questions. On you the the first for one, thank

Our that relationship it's Biogen on it working programs pleased relationship. We're with Biogen like a is highly with fact the very as great by us strong prioritizing as the ever has been, is while can very program program as BIIBXXX Eric are they imagine getting really resources before, the you it's well. as all to commented exciting tau it's that It's that important. needed, program them, Angelman's the very

launched. through market line, We in to just already on job and - they QALSODY did in the finish bringing the it's a great

mid to been that greatest hasn't they are company. are the their to and Biogen, pipeline. large public, are launch So And efforts of - focusing they to of think are several stage programs Absolutely, not very the in a the their other saying programs drug. not are that's going anything And research I'm progressing that well. totally on going and ready that value they part bring we

a So very for are top them. well. growing we we - who priority Relationship is

portfolio was prioritization X, kind bit return directly reason - you the far Clearly As program a returned of of surprising. a as communicated me will. the - a a to as not was drug like you ataxin being and the That being know, behind Ionis, disease, that's to if was ultra-rare exercise.

know - the want where not to it's As on. they focus sweet-spot, areas if that not their in we it's probably

with to it to or what whether today evaluating program are that keep to We repartner do it.

goes will going a so growing, come we that it's will Biogen, pipeline wholly-owned that's have to commercializing concerns our wholly-owned on for that's Ionis is build-out well quite about and rich something question, interested and are we'll love that ex-U.S. we pipeline, drugs have no the well, we're absolutely neuro of it about. been this Ionis in most from programs we back by keep commercialization, them We them, also going-forward if them seek relationship interesting ApoC-III where any expand to because don't as the and ourselves, - - a talking but have strong pipeline we repartner. back emphasize Ionis in and this for returned we to to and have

say launch getting I'd the severe first U.S. of Luca. all, and listen, for we're very in ready readiness for indications FCS for Thanks, both for hypertriglyceridemia.

partnership really we're you're OUS possible a The is has as look a a be partner going patients to where yet like to type important to that's - in partner. good to as really and plans many but that criteria. not it's going reach for going can plans swift been a note, Our important quality current is manner for determined, look for of

We're Luca. still working that - on

time have for question So one wrapping stay-tuned. think, last up. before Thanks. And I we

Yes.

question for last with comes Blair. William from Myles Please ahead. Minter Our today go

not product need comments on slight to potential reimbursement the a certainly that relative it me Thanks take but for hypertriglyceridemia. just for your in. the olezarsen, approval, [indiscernible].Thanks. regulatory to in sneaking like Again given updated if so seems range wanted study that for thoughts for a on much any severe you're cardiovascular for just pricing premium outcome Maybe trying

it's I'll take as Yes. reimbursement, ask Onaiza well. focused Since on that to

has payers, has hypothesis elevated, tested you out without a all it good imagine. clear that fact many said, need sorts question. The the a actually of we these you population, a population as place where as is We or acute CVOT it's plus pancreatitis this to not a pretty patients, severely we're XXX this it's risk, this path, And CVOT different is a the reimbursement Yes, are study. early - program, can in a from different continue - is perspective. which risks and given a wanting for regulatory unmet and of payers really for the looking and even is expecting for

the going-in, focus the cardiovascular there reduction available where pancreatitis, without magnitude bring, again triglyceride the -- patients what is Xx right value for it's for studies in of high-risk - where with is in in-line so trig of and elevated the proposition for severely So, unmet is, with payer we the currently need what's acute these

everybody our joining thanks call And us Myles. for Thanks, on today.

look against very provide going key plan we throughout momentum to progress our updates, the ahead, the the second - on front, the additional to by it. pipeline continue on we're delivering We year. of And looking-forward much to our commercial updates technology. Looking half objectives in our

with So close everybody. again and have great that, you day, a we'll thank and

now has presentation. for conference The concluded. today's Thank attending you

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