IONS - Earnings call transcript Q3 2021 | Ionis Pharmaceuticals, Inc.

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Operator

Good day, and welcome to the Ionis Pharmaceuticals Third Quarter 2021 Financial Results Conference Call.

As a reminder, this call is being recorded. And at this time, I would now like to turn the call over to Jennifer Capuzela. Please go ahead.

Jennifer Capuzela

Thank you, Tom.

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 Executive Executive Vice this Officer; this of me call morning and are Richard Monia, Officer; on Geary, Hougen, Beth Chief President Chief Development. Financial With Brett And for are Q&A President of Richard Cadoret, Commercial portion -- and Vice and Chief Research; joining Executive Officer. the us the Corporate Development sorry, call Eric of Onaiza Swayze, to I'd X, our which now contains statements. to like your attention Slide forward-looking draw

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

Brett Monia

Thanks, the we as initiate with study more are data on Phase donidalorsen, end on of patients the in to with Phase second III Jen. referred in which year. of severe or before in with track IONIS-PKK-LRx us as with Ionis to start in United enrollment olezarsen, patients an estimated track And previously will of and the polyneuropathy, Good putting our million III We expanded referred Phase made NEURO us for hereditary at olezarsen of in States. the our of angioedema patients fronts. TTR late-stage has several hypertriglyceridemia, progress our We half important on for we XXXX, we IONIS-APOCIII-L study previously patients this transform In core mid-XXXX. call. to of study evaluate pipeline Rx. morning, completed eplontersen on an today's joining study everybody, in This III the X indication thanks which

strategy of launches We initiatives these data our anticipation go-to-market potential commercial programs. readouts also commercial in of advanced III and Phase and

Additionally, LICA through Bicycle platform in Therapeutics. with increased further we our investments our transaction

the patients III SODX-ALS, in placebo-controlled we these Phase While disease are with in which the tofersen of and the extension, in slowing evidence totality progression in study encouraged VALOR endpoint primary by showed missed the open-label patients. signs VALOR of

treating program SODX-ALS. Importantly, also Biogen we program. sharing our to given from the their regulators engaged OLE, Annual advanced actively is in top Investor the now Coming of XX patients our with this ATLAS progress, the planned. the are ACAAI achieve the plans living including look study the the of December most to presymptomatic commercial looking next SODX-ALS strategy, data by to summarizing that on we of And patients importance disease people determine in hereditary Virtual number the up donidalorsen on access originally Phase expand population key as catalysts, continues event other with as months, our Meeting steps programs X, plans results key in for at we're II at pleased forward a Biogen forward VALOR patients angioedema and and early And line to to with success. presentation, for our bring Day Sunday. in market reinforced and broader to early stakeholders its next

questions. upcoming Richard that, pipeline remarks objectives. will And your wrap our After Importantly, meet prepared and with discuss our our updates track we results. remain I'll resources pipeline achieve to call and up before financially guidance our Richard, strong, over recent to strategic financial to the turn the have Beth taking on catalysts. I'll review to financial And

So now over to Beth.

Beth Hougen

Thank you, Brett.

were earned Ionis pipeline $XXX resulted During million the year, our to a at first our non-GAAP revenue loss in commitment expenses, and billion, to earned virtually of months technology. $XXX million in of we revenue and bottom $XXX nearly net our million. our advancing SPINRAZA's million SPINRAZA, royalty global recognized in non-GAAP wholly-owned as year of the from reflecting first sales $XXX in $X.X X profit. This all operating months in X this falling line this

to the TEGSEDI call, even of revenue SMA second ASCEND quarter, commercial supporting evaluate ages. commercial to to Together for are the benefit We evidence proven potential ongoing the SMA our Biogen patients million last a work Biogen the suboptimal potential the of the the first of generated demonstrate during of response operations the with study to with in treated and all potential of approved the $XX body substantial evaluating high-dose be SMA patients greater to presence, recently types. this who to with and all remaining the Arista is And on is year. unmet evaluating transition patients address quarterly Biogen's to months continue SPINRAZA SPINRAZA compared nearly of believe patients over announced a dose. market-leading ages pleased SPINRAZA's patients study where our we SPINRAZA's growing will therapy. And X inform for has RESPOND these of profile further in study gene markets of to high-dose to currently plan. treatment treatment of SMA Sobi. to had WAYLIVRA needs benefit as plans we discussed SPINRAZA and benefit DEVOTE XX,XXX medicines completed The and previously and initiate the

on of distribution As a based TEGSEDI and from result, our now revenues sales. are WAYLIVRA net comprised fees

recently This to its was patients significant TEGSEDI categorization of in value that TEGSEDI's the Brazil need milestone medical continue TTR WAYLIVRA as polyneuropathy in innovative innovative only R&D reflecting first an toward X Novartis million key enrollment in is medicines America. neurology $X this country. year We unmet included $XXX of XX our a Brazil, franchises. treatment from advancing from in triggered XX% within the new programs treatment million revenue first milestone in III and a outcome payment in million optimizing markets. drug into the quarter. third pricing payment approved prevalence both which And $XX as the a for achieved milestone from make Latin Importantly, pelacarsen. the for FCS, advances and study of more than cardiometabolic achieving in with Phase months PTC in and earned

to This generate and last non-GAAP was first this in ability a months continues Our be by year. III expenses million key related sources with to reported X strength. driven $XXX We increased our was of numerous start-up our primarily R&D our expenses the increase the was associated line Phase expectations. XX% of study. in with year. of year expenses compared CORE compared pipeline studies with revenue to from including Phase financial olezarsen by of diverse and with This III the costs element operating eplontersen nearly increase last XX% a ongoing

QX compared the recognized expense R&D of with agreement the Sobi in driven Bicycle realized million last $XX year, license transaction. We of with substantial and Akcea expenses savings also we by nearly SG&A from because Therapeutics. our by XX% decreased integration

our of of guidance, includes operating revenue X to transactions for are today, late-stage the $XXX to million, future expenses of initiative than unlocked we loss range financial expenses now $XXX substantial million non-GAAP basis. year, in this more reinvesting million drive planned, a As the calls on $XXX end and of first XXXX which $XXX net million, for and savings Based our all that months our our results our low funding go-to-market are of on less This pipeline. cost than growth. we the revenue reaffirming for assuming a these

our from projecting higher fourth partner are We R&D in quarter advancing the revenue programs.

our Biogen to with collaborations AstraZeneca. and Looking

to underway. We are call to year. we we as increase With of programs significant in our have operating technology to investing a expenses our the of and Phase provide we advanced studies the with pipeline our our opportunities us achieve get turn And with for the pipeline, positioned fourth deep that, activities Richard. most to payments milestone olezarsen cash, I'll and believe expect donidalorsen that over this go-to-market in continue III $X Further, billion several quarter medicines. well

Richard Geary

Beth. you, Thank

pleased next overall months. our we've to Already year, milestones forward and continue pipeline. look performance the XX We achieved numerous to the over with be of this more

FUS-ALS pipeline. putting CARDIO-TTRansform NDA filing an We studies. the patients study enrollment Looking in TTR end completed Phase NEURO-TTRansform data. year our in late-stage continues the as study us Eplontersen well. on pelacarsen The polyneuropathy, to track year, first next and is next positive progressing our by for and with III at progress of do mid data assuming also

the these LSRs. We from readouts the data just late-stage the pleased severe over core expect Phase of in registration We're also per making regular cadence from for progress continuing data patients FCS balance deciliter. studies. XXXX we on The in all track announced milligrams we're of Phase III three data in of this hypertriglyceridemia, And our with with week, study initiation study with XXXX. XXX triglycerides remains III studies

broad patients III Brett or As for triglycerides our to the presenting And olezarsen limited comprehensive start represents seventh disease donidalorsen treatment potential of coming the development severe data treatment on data III program, the from with have additional a year. who potential Phase we believe We've as made medicine's this study the for forward in the realize more options. the today the hereditary also CORE X our end angioedema. expands designed risk range up II further patients to this ACAAI to mentioned, late-stage great study best-in-class of address is at treatment in progress before track look our than These million our HAE. alone. with donidalorsen further donidalorsen We will on underway, Phase opportunity CORE second Sunday. has Annual of SHTG Meeting now a at with the triglyceride-driven program for medicine we pipeline. also to fully We're development this U.S. substantial Phase study the to demonstrate study why be high people which

putting that with medicines to start plan. expand the function, X were and function, X indications. SODX-ALS We this very biologic across further program, trends up III reach with to however, urgency important multiple our have begin the of statistical ahead We III Phase measures seen clinical quality us study and III favoring didn't were of track Phase on function to the over Phase We're deep compared with well life encouraged, will disappointed respiratory in The get of tofersen placebo. our running moved pipeline that and patients study VALOR motor including of activity in primary endpoint. significance

from these showed tofersen experienced outcomes effect. VALOR started better Additionally, the ongoing further clinical data of who reinforce OLE positive that and suggesting a patients earlier totality the findings and

data, with program to we access other look we mentioned, expanded franchise. VALOR programs applying to with its these and the now Biogen of from Brett And development continue in encouraged tofersen's is regulators and further we're to all our actively As and learnings as forward engaged that to to AOS patients OLE the expand Biogen plans analyze SODX-ALS. optimize

steady achieved we're and dose-dependent as Alzheimer's disease. a total proof Phase MAPTRx patients. II and mechanism in that Alzheimer's reductions Now demonstration results, therapy. to achieved of on first endpoint and reported complete concept let's of study to is study and uncontrolled of offered care longer tau We mid-stage patients achieved of pipeline. actively of its of and We patients promising acromegaly making indication with the phosphotal. strong within of Phase previously of the our turn planning in proof standard Ionis protein power and study suppression MAPTRx II Based Biogen safety on I/II Ionis referred in IONIS-GHR-LRx primary the cimdelirsen antisense-mediated Phase our substantial clinical and progress a MAPTRx Ionis CSF these disease also of tolerability CSF durable

development all safety a of a the in of increase treated binding a no target continued in hormone with engagement extension results growth was longer assess study significant tolerability with measure to IGF-X enrollment associated study reduction reductions response no showed COVID-related preliminary difficulties, II assessment the Phase this study ongoing patients due in its with supportive the and and in primary cimdelirsen integrated of powered to hormone, While acromegaly. endpoint and from open-label protein, good patients in growth

data open-label on also studying XI fezomersen In end study year. studying are IIb as with extension LRx of is on data expected Both we a next Phase and readout monotherapy in are is PCSKX our of cardiovascular study, of of are these previously progressing with ongoing targeting in study. study addition the year-end. to our on from readout IONXXX to track Enrollment by disease renal studies I/II year. in progressing syndrome studies at track we on Association ascending a is Vupanorsen looking and this Phase individuals the year. in data patients finally, dyslipidemia high IIb in track, multiple with cholesterol forward Annual readout track now Phase disease the later half end-stage to for with And also this dose of is to month. Meeting American Heart we're the IONIS-Factor referred in the Angelman for this patients IONXXX study putting complete, data by first next start on track

just summarized, III Phase pipeline for programs. our Phase rapidly potential and I new expanding As III we're advancing with

next look Brett. a NTTR We over data also with beginning move readouts I'll from with into And call polyneuropathy forward of next that, the year. cadence our to pipeline patients as year to steady mid we eplontersen, turn late-stage back

Brett Monia

X greater commercialize successfully this our All most Virtual optimistic we on expand morning, to to on bring well our we about Throughout our Ionis Ionis' these Investor as future. the up Richard. more makes for And pipeline, on our central are reach to wholly-owned talk have review I'll this what success. year, advanced my At my Day December Thanks, coming vision and to X, height objectives me programs. of vision strategic so we're and way. to to advance of technology objectives executed our prepare our

also and important most achieve hear will to other many our long-term who from progress goals. making strategies will we're our Ionis leaders You discuss all near the

answer the our investments commercial to the Day, years that, now It be come. our focus the should for off discuss also your in while call I'll for weeks. in watch so questions. about technology also event, paying questions to investments We those we our And go-to-market please aim the great details initiatives. of and a strategy making including to questions, Investor see coming plan we And we're and primary for Tom? up how with open not

Operator

first the Co. comes Jen And question Laidlaw Yale from & Instructions] [Operator with

Yale Jen

polyneuropathy studies, cardiomyopathy TTR that mix the question improved either or of one of just the patients? terms first type In is my for

Brett Monia

Absolutely, yes.

the patients next that to patients those TTR out to similar symptoms read did due That's NEURO-TTRansform involves patients of good to will So inotersen polyneuropathy. and polyneuropathy, well. midyear number which polyneuropathy now we cardiomyopathy study study but in in of also the very that's is by with as with enrolled previously it have a have year have hereditary

So both -- as also be And them the of will the patients that's wild-type and form cardiovascular In will hereditary be patients. as outcome disease. the CARDIO-TTRansform type the study, of well. that certainly, type hereditary in include mixing cardiomyopathy the will well. hereditary the Many trial, mix

Yale Jen

Okay. more on status of cardiomyopathy Great. -- same moment? that which at the for And current maybe sort recruitment study the one patient -- status question the compound the a what's on TTR recruitment the same is product, --

Brett Monia

year. first we on but not next we Yale, exactly enrollment details where we're of half are providing in to planning Yes, specific enrollment, in the are complete

Operator

The next question comes with Gerberry from of America. Jason Bank

Chi Meng Fong

Jason, This is taking me. Two Chi for on from questions. up

programs. the on sHTG one First

with partner indication owned sHTG position also III with wholly your program And a you about Phase pursuit. Pfizer data ANGPTLX due point soon. an as Pfizer have some You Phase APOCX talk [Indiscernible] potential has study. have for And IIb

about the call Pfizer X So I tominersen Brett, see from the to INS year vupanorsen. with time you in next at with that coexist what U.S. commercialization programs the talked as can also understand, has or you option the in we participate certain activities with

value the to assets Ionis what program? of vupanorsen Curious, a the in of out? Does perhaps the question, when be on II input Phase AGT long-winded to data? shorter overlap any XXXX of sense ultimately given between some do with them. following we reading how the programs the development one the have of but the might expect INS and in Phase plans question, extent you to maximize So data Can terms IIb curious X AGT. direction have Second timing

Brett Monia

Yes. Great questions, Chi.

us it vupanorsen So I'll partner we and we and and in Richard, and olezarsen in with but a great you commercializing excited don't through differentiate. developing both take differentiating to that. X the talk olezarsen how bit We're Pfizer we're ask market. about glad ourselves, little we're Richard very vupanorsen, that APOCX have see do angiopoietin-like And a they about drugs

Richard Geary

to triglycerides play triglyceride strictly So in suffers best very very think is olezarsen X and is lowering this, And in a Chi, angiopoietin-like severe the active and strong I think FCS. is differentiate also that triglyceride high a about focused that agent X and/or population from in increases mixed and is angiopoietin-like increased on from they'll that much dyslipidemic in cholesterol. way uncontrolled

also population. think see so And a It's I differentiation. you'll large very

a high severe triglycerides. working place lowers there's to patients going nothing be you're these of with else really so triglycerides in measures there where that today in And substantially

on not speaking that the can differentiation. you biology will market the the So to they I'm from but differentiate. the positioning I see see necessarily,

Brett Monia

Yes. Onaiza market that about also olezarsen. you opportunity more, a a a the for specifically little could talk And with bit towards view maybe bit but little

Onaiza Cadoret-Manier

happy sure. to. Yes, I'd be

-- the population, severe diet than hypertriglyceridemia XXX everyone greater has reduce on a in said TG adjunct As It's to over being already it's large is that's to greater an studied, call, is this right? indication levels well-thought-out than a XXX. patients really

where that for in it triglycerides cardiometabolic to well. as due levels and we Pfizer, olezarsen As of actually the in X that's I patients products U.S., launch marketplace, a acute right, will olezarsen. is see And do some we risk Ionis vupanorsen see million mind. trig we and the pancreatitis, for on market eventually disease of as play playing already the clinicians these both we the to have reduce when elevation in therapy where And in that the best-in-class out segmentation this this positioning patients, look said, Richard X think really at of their over at the like is

mixed a Ven themselves that but nicely we're diagram, vupanorsen seeing very with cholesterol. of do we with see elevated might positioning a emerge in There remnant patients So dyslipidemia, really be bit nicely.

distinct seeing And said, very opportunity. has actually some great market and large right emerging segments are we as now. really So everyone

Brett Monia

produce substantially potent And just reductions in vupanorsen Thanks, to more will is olezarsen more in to add much here triglycerides potent, Onaiza. both too. to that, compared

So attractive it's will. a you if reducer, much triglyceride more

refractory as where is out X, well heart Regarding year both the hypertension expected the angiopoietin-like for study. data yes, next as exploratory failure

Operator

with comes Fargo. question from Yanan next The Zhu Wells

Yanan Zhu

questions in progress. olezarsen on sHTG. the Congrats the program A on few again

congrats course, on few program. So of Phase III the have study. questions CORE a on the development overall I initiating

size, large I indication the are probably Given studies more needed. think

many safety registration How in data of needed for curious, how is the the is And also database? patient many the for for just CORE So needed product? -- are studies year this exposure XXXX. are expected

you the about mentioned. think the I and time previously What have line to approval? program for data overall the

Richard Geary

Yes. Want me to take that?

Brett Monia

Yes.

So we've got a certainly, be but number exposed patients the think studies specified don't more X,XXX planned. this quite I database. than number of we will in

So more severe for few high will particularly got next be population. supportive, That triglyceride year. stay a larger tuned. We've the start to

Yanan Zhu

Will this go sorry, Brett. be sorry, -- ahead,

Brett Monia

would say to I'm the going talking be readout XXXX registration. again to about support we're data

So around it that all come time. together

Yanan Zhu

Great. do on -- study. product? approval acute endpoint need for That's quick follow-up the triglyceride you pancreatitis event the primary the approvable, rate the the great. secure for Is And maybe that reduction. CORE The registry to a is

Richard Geary

Right.

for indication. the believe, component is Triglycerides for yes. required of enhancing only triglyceride But drug. answer we So level The is a are course, approval profile for approvable the this alone. be will this pancreatitis,

Operator

with The next UBS. Esther question from comes Rajavelu

Esther Rajavelu

quick the enrollment share your some or is then you couple I'll a anything Angelman others about I from have different color in can -- the administration you And follow-ups. and route some and have your with couple clinic? other perhaps that of give trial be of program. us off molecule planning how helpful? program as Can start a I And on you're the talk of would the considerations on maybe

Brett Monia

about get running little is bit Sure. intrathecally. different. for to molecule what very what most of on we to how dosed talk are dose about of don't know why our the and Eric neurological up And I'll we end our bit know a the we by diseases, drugs year. ask we for excited as this our about study a how We're And will drug Eric, little different. you be talk

Eric Swayze

sure. Yes,

find clinic. look as some in along transcript And academic This utilizing mechanism pioneered the best and increasing causal are tolerated ISIS expression a molecules other Angelman syndrome. trying is the safest we have different mechanism chemical we we're obviously same of a we're collaborators molecule spent been of has in the The the we our amount could same So released which that antisense drug we profile ASO, the and is MAPT of some neurology drugs, UBEXA fair a to modification and use our other of in time earlier that year the same the in of SPINRAZA, this molecule our and optimizing competitors molecule and and great. lowering most is our space. for our with potent that's deficits as that the like our which the will technology data and performing find we optimistic than on and chemistry

a So address can best-in-class hopefully, molecule this have that we'll disease.

Esther Rajavelu

Got update it. the these And a an then FDA could from for you discussions, on share timing outcome discussions? the on expectations your realistic and can be toferson what

Brett Monia

yet. of unmet on of the there's time is could, I can very any point the what potential need still said encouraged, to been wish program they totality no next and SODX-ALS updates patients opening the expanded safety I in up planning steps -- as can't has what stated have has by provide is of we're which based just steps. engage that we totality data. open But the in do in Access I what They and data. stated because to has the our which to time and an the said remarks discuss the have the said and plan high in to next I on remain we update in continue review that Biogen not data, -- just we remind medical Ionis I'll Esther, specific point regulators profile they're to Yes, you said the but all Biogen and as

Esther Rajavelu

the the radar? it. give press our release was any in could if be then on us morning. And should sort milestone on be, that this that lastly, what color And agreement of can Got Flamingo you

Brett Monia

Yes.

provide Let me just briefly strategy the here. very

Flamingo investment to a areas Based therapeutic the we're obviously see we And our on good company to give indications where We what very in value as cardiovascular certain bring disease, revolver, we to it and the we're we oncology and helped the Flamingo. vested know. in moved Flamingo a doing hereditary pipeline drugs bring job otherwise moving and to in about have have the on we we like priority with Oncology, high angioedema, into both and are to that a rich the therapeutics. pipeline, a those commitment drugs And with laser-focused drugs those our towards And a interest drugs divested is greatest focus history substantial in where and think those those have and stakeholders. create are have Ionis areas had over long confident forward. are much areas the all made of we very to economically do in think although, focus to there, we've that best And we very we involved think don't rate have molecule. you those Flamingo chance is are a and in have success, neurology that that will require great the oncology, where we've it we and moved go best-in-class we win. enthusiastic a progress from Flamingo, oncology drugs potential

have those I if Beth? of disclosed, economics, been as don't milestone and know far As sorts those

Beth Hougen

view in variety amplifying forward about Brett these cancers. a to said, in I economics really you cardiometabolic in of public. what energies we're for internally the move And of maybe which our our a particular. them with the what helps full just fund to focus in not -- transaction, And think is and different in neurology think the us this real focus value they're advance medicines ability No, oncology, and Flamingo to when

as investment And less company. as medicines economics have milestones we are longer-term about the value in equity so of the long-term the well the really and and economics, I about the more think, the those

Esther Rajavelu

Got it.

the So an this and should you'll about to standpoint spun back model decide from then an be thinking into where eventually, fold? as Akcea it whether we it's out bring R&D Ionis

Beth Hougen

is all. company. an No, independent not at Flamingo

ownership, have XX%. equity We an less but it's than

So would is not intend to -- follow model not forward. model, Akcea a an that's and I not going we this

Operator

The next Werber question with Yaron Cowen. comes from

Brendan Mychal Smith

is on for Brendan This Yaron.

think ones I Just us. from of quick a couple

also you actually. is design be might I point. mostly able us this the Phase I of the tell to kind in First, that guess we're space increasingly what And a wondering, know at of HAE maybe I III. this was more crowded really bar really assets? just yourself kind really of III, but and other wondering so these late-stage of some approval, see where commercialized the Phase for on kind the not for it's efficacy differentiate from of you

Brett Monia

this study III the potential Sure. the talk on Again, drug. a amount market and to III best a treatment the Richard? about we will data, share the Phase a will the a I'll we data new of about the of this and little lot on also medicine demonstrate Look that expect with be data ask Richard best-in-class significant potential to bit design Onaiza what we why to for win out I of at as excited on design, Phase a data best-in-class HAE. presented think think medical weekend be meeting. will so And get we're donidalorsen

Richard Geary

Yes.

So of go is looking will who the patients be to percent treated, attack-free. Phase that patients after of be the treatment, patterned attacks. frequent that then and will And fairly going are we'll Phase These are completely have the closely really placebo-controlled, at III be get course. design patients to II. It

of And rolled attack-free. the in best-in-class industry now is current long nearly think from term One has to reasons attack-free, it really of in this we into different in open they've that gone all the demonstrated fact, the is very drug have in and potentially patients label care Phase is, which the II that standard prophylaxis. went over

the design So of it, follow of you weekend. this released study, excited little bit that's a more the data if about the coming to be going

of very very, see the endpoints are that study and You'll similar. the design

Brett Monia

to the are what forward you Onaiza, Thanks. market? win on looking

Onaiza Cadoret-Manier

from where unmet prophylactic think X that some the has seen there kind the expressed. Phase uptake is, of those Richard treatments dimensions. given of meet Yes. currently understanding -- thoughtful It's dimensions on of market what and as X it's a winning II are are profile in work been. where done need kind all we've just And emerging, the the and from I we really We've actually really data

the patient. And anxiety is confident just well the the other the get onset one better rates. of sooner clinical X-attack when we III, more looking to replicate name that there, we that's a on to first out less that they are than rate, putting our attack the really we you and you're -- get And efficacy agents obviously, in are patients hope is X that it's do the The Phase III. game the Phase can and in max the that to as of

great in going said, that reactions. out of of think viscous efficacy weeks, XX, our agent has terms X X to highly injection lastly, and are to weeks We show that is Richard the also, there. in injections adoption do as is this that that in really be which offers really going you addition to valuable of profile terms is in on adoption. very important data also then market a to attack-free, be XX% this the And site X convenient to And

forward. So product. this looking We're very exciting moving to forward

Brett Monia

December. our Thanks, Onaiza. the at We're Day strategy in go-to-market our III design sharing more Investor also detail Phase looking forward to and in

for So stay that. tuned

Operator

Schimmer from Josh Evercore comes The with next ISI. question

Josh Schimmer

still you pretty clarify up especially, quarter. just it I but rest elaborate the expense want guidance I the a sizable the in you year. for assumes you're I Bicycle pretty of it's if significant jump. trials, operating can drivers third Maybe know the payment quarter-over-quarter, the guess, for said a step-up starting on we that? some for adjust the to

Beth Hougen

to. Happy Sure.

focus pipeline you're right, I think on the continue that to pipeline III fact late-stage grow the our mature. on Phase continued and to has

earnings in So polyneuropathy We second study if eplontersen, announced quarter enrolled is we now. with start call. fully our that

enrollment continues next enroll at you mid data So year. year. Brett that with phase to most nicely. complete The heard is with study its expected expensive say as next And cardiomyopathy

a population outcome conducted got III ever running the we is patients. as ongoing bolus pretty tend olezarsen, in at is patients. underway expenses So and again, Phase particularly study of about the study. enroll bolus to FCS start we'll study up and is PKK of that enroll up as Severe -- running, And triglycerides course, think shortly. CORE start-up patient we and And be patients. those quarter. getting XXX and that be and again, Phase getting study expenses have that have to the And fourth the to then, then expense here will then those you growing that, we've given III sizably, we very study, in when And that get III expenses just continuing a high as that and largest will more a Phase more grow

related build quite as just new So to on late-stage to studies, out can you see, of all build studies, enroll. we particularly we which as olezarsen program. a as lot into add are that we we're expensive. the starts and to and study Phase And next year, that as continue study then III And move continue going to

So that's the we growth see R&D. quarter into beyond and fourth in why continued

Operator

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

Gary Nachman

used update eplontersen risky TEGSEDI? you on aware your TTR-PN. expand will that that will SPINRAZA, potentially it? that on mid And higher run are next it physicians how then on ASCEND on for rebuild you're using And could do could long it the to Phase own the do how dosing something you failures Will that? much just take infrastructure study? for extent there? think patients you to potentially to of Is the label? be Biogen Depending their the that currently first the market? promote it in So How in for you addressable And data expect relative year, how will III

Brett Monia

In with home Phase as excellent subcu as drugs. safety bit So injection an very that to Onaiza study, once-a-month about low-volume the up we Phase getting And if our I think of this comment even the TEGSEDI, our all we LICA is polyneuropathy, why compare -- we've on will want a all and highly has to study as liberty, I'll a medicines little not In all with of frequent a to just into with our inotersen medicines I we pristine LICA to can profile. would of the think on And XX%. XX% take ask like talk that but also opportunity translate seen profile about how TTR we has to I win get I that the I remind market. you order the on the But for remind advantages, for to cardiomyopathy first that tofersen. we -- reductions the mentioned, XX%, at I of you auto-injector, efficacy. I we attractive will were greater have

the the about a market, Onaiza we're talk also profile, strategy maybe on working there. excited to into we're plans the we're our market and I'd bit our with little and like about eplontersen. move excited So about

Onaiza Cadoret-Manier

be happy I'd Yes. to.

the and kind and well. about in systemic thinking as know just it's talking that -- this lot initial to the we've of And we phenotype think really the as whole advancing disease launching address. their also important there's the as is about is indication, polyneuropathy emerge as increasing critical really burden patients with in our So disease. And a research to a seen really market that prevalence our to mixed of recognition KOLs market

I hereditary think overall, if both patients initially, to that, be in that on. these So treatment. got XX% are ATTR you've patients about Currently, only will XX,XXX focusing in think of we XX% you receiving

silencers last and and and And that. be there be the questions as and of that ability patient's to kind just opportunity this really a So the will have well above and to generation to your a didn't need. seamlessly generation, continues beyond of integrate lifestyle, first-generation lot know we second into unmet

being very terms a that's place to be how think I marketplace. forward exciting we're in the of in to looking So

the in eplontersen. we in In we the clinical market without addition, that well generate and part the position with are cardiomyopathy. and think positioned broad win of to trial of data care. of broadly standard to wild-type There, ability And the will clinical our is because marketplace

have who if patients They that a make their that. patients. data We'll are have naive, for the already they physicians, they on have the data for we'll right for stabilizer. can For the actually decision have are so patients who

the looking marketplace. forward into and to plunters So really getting the

Brett Monia

ASCEND, ASCEND, are if dose they know any is they been study. in patients we the it's dose a in of reminder, not risdiplam in controlled have would patients a SMA -- process, control Gary, not been would the on is disease. a I'm doubt have as higher of to have much of we And higher on very SPINRAZA, The which treated I with -- risdiplam it to that have study previously, they SPINRAZA. because regarding patients happen. just that like that so have And be they the were And SPINRAZA Biogen higher been aware of I DEVOTE is is dose examining patients -- XX on higher ASCEND it's dose feel think milligrams. assumption, that chosen washed their go of better a of risdiplam out course, the of on that study need

study are to safety randomized on went commercial response and of moving dose the now had DEVOTE with Biogen escalation and try patients also they're cleared we ongoing And dose already in has DEVOTE we'll then the the to then dose in at study. study, So on a on ASCEND, that RESPOND have to therapy conducting that's SPINRAZA is sub-alpha higher portion that the patients the study and gene the and SPINRAZA. it's the of addition SPINRAZA showing in which of the portion

Operator

Jessica from Fye with comes question next JPMorgan. The

Jessica Fye

Just X.

AUC outcome eager IGF-X both interpret study you'll patients envision First, or to acromegaly. developing and an upper choose agent, talk cimdelirsen of oral you looked the to how to would Can the and about either how that eventually version should one assuming subcu thinking still ultimately too Or levels on after for these PCSKX, IGF-X path? pursue the subcu treatment? normal say? in you limit over And oral. parallel is relative for And then the data Are beyond we still to it early need other? an you

Brett Monia

Let -- ask a take comment data more PCSKX, me acromegaly on the summary Richard -- of thanks, to the with provide and HRL. I'll I'll fulsome sort of Jess. and

is patients PCSKX, to script now to the has complete that subQ They PCSKX, for believe the that from in -- is AstraZeneca They're year. on AHA once market outcome we do and is best out or comprehensive Phase this of patients program I the best do actually as the next is this is to all including is too, the studies potential win of said a on and They results to correspond as lower to with -- conduct best-in-class a that an trial, study normals. cholesterol. that today. to and several essentially This that II cardiovascular -- Phase effects data about we've in the they month. and in this studies, this PCSKX based in drug anything a will seeing they conduct The formulation think II well. this high the be which lower we're couple lowering share for seen, a Phase trying believe, provide in the agent very there plan inhibitor are high They're building a are planning III So a Phase study. we LDL that this as excited weeks on the update

committed of not platform With subQ -- the program XXX% Regarding Their PCSKX today. AZ but AstraZeneca necessarily on platform we said, are to oral, today. play play, a play. that oral it's not and working part a is the delivery PCSKX formulation a as

research to As focused that's believe subQ that on and the a we're They oral. you And delivery. winner in several on for market, development oral know, we're and drugs is we a in the this with what and somewhat not PCSKX. they're making continue And specifically. work drug progress AstraZeneca. it's on specific optimistic we have But with on

always about focus. for learnings the any oral course, current Of future, not but think from we that's the

Richard Geary

few you Yes. Cimdelirsen a me through things. just take let Okay.

able we were lowering. very significant it's growth to think the that at achieve I data hormone important, looking

So with itself look measure growth for the growth hormone. in hormone surrogate binding target protein, no a change which is

uncontrolled So that's patients, get on a thing. question, to very your significant were somatostatin. These to

limit were they or were than So resistant X IGF-X normal. to threefold Their of to levels treatment. care higher standard upper recalcitrant of of to

goal. the kind below of of upper limit is getting X.Xx As normal you probably know, them

significant IGF-X. the placebo integration shows is so dose that at up. was is AUC the you're of looked IGF-X to at we -- compared And that What and or getting of lowering actually going that highest placebo

to somatostatin who patients these on worse. analogs And getting drug, get continue we're our So recalcitrant are better. to

So the ml. nanogram IGF-X. in like were they lowering came that drug was per XXX levels The

generalizing If IGF-X, of you're with I'm familiar the age. because XXX. normal And determined and would be levels by are sex levels the

be be for So X.X patients XXX. it can around these came individual. XXX. be normal, in would But around Most XXX different would of each

these to the want we that. lower And under case, really able to their in to in recalcitrant get were able you patients to IGF-X show think hardest it's this I treat encouraging very patients. and patients, want So to XXX, in you and be

not course, end it's Of the of the story.

surgery coming extending patients where OLE on the and in somatostatin patients population. have treatment still we're looking naive longer have either uncontrolled. another analogs, well not just is being We at which failed or having who Many somatostatin in these naive treatment their patients who on or are are IGF-X analog no as is as but

Brett Monia

studied our IGF-X Yes. control get I'll recalcitrant this under to drug things. patient Thanks, couple to might no Richard. a other one's One, be couple a And a in just worthwhile adding population. ever knowledge, of -- add it

So failures. in somatostatin

really population So new a pioneering here. patient we're

we hormone as see important as of improving So its signs that's extension. very And it. and the see quality seeing hormone let any any last we we'll consequence lowering, importantly, elevation go benefit. alone very some open-label patients contribute to And normal that we tumor getting of in to didn't in focus IGF-X growth also do, want the on a hormone continue the and range through growth. life increases is didn't We're growth growth the that's because thing we inhibiting of of to receptor, can

So we're about pleased very that.

Operator

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

Joseph Stringer

Just a HAE. follow-up on III quick Phase the

are your on in trial potential be rates enrolled? when thoughts fully and curious that could -- Just enrollment potentially

Brett Monia

Joe? study that, was Which

Richard Geary

HAE.

Brett Monia

HAE. Oh,

Joseph Stringer

HAE? Yes.

Brett Monia

when put that don't in we've enrollment out Yes. that complete yet, Joe, think to expect I study. on we

we think frame. XXXX in I launch potential the have said a time

and our haven't think specific we completion put of was on we've I said on but think -- enrollment that, yes, timing so out I it on.

enrolling deep But probably Phase the this that you extension remind getting that the I can't we else -- that. extension drug. from follow you as mention continue detail. started we're study to that a But lot Phase this And we for said, profile -- give study of the of the II -- label is we just this the II open-label expeditiously should sorry, also were be know, open-label patients something presented And Richard Sunday. will we And study enthusiasm on evaluation Phase year. expeditiously. full level So that there's very very study study II for of very successful as extension, from from that the open the we're -- you continuing

excellent first And drug. to what Congress to in It that at Medical complement of of winner. next this participation life year in have OLE, People we're really we're data and a We half well, year on looks as like OLE. furthermore Sunday. next the to other want going looking forward sharing present quality data

Operator

comes Luca Issi RBC. The question from next with

Luca Issi

on Great. APOCX, the quick. one I in X and questions, all other have acromegaly on One FUS-ALS. the one other pretty

similar with on exciting XXX outcome are acromegaly, there just Is obviously in trial a patients patients starting APOCX, per study have start on XXX-milligram deciliter. plan to above Phase triglycerides they future So also greater that a III a signal. so, milligrams triglycerides to trial if a to Maybe there above per what cardiovascular Vascepa deciliter? you planning And run has early done?

I program and wholly to there? Wondering tofersen FUS-ALS, that sound like the of problem III amendment planning you light comment quite And to for recruiting for in patients you're doesn't protocol if you're already study However, commit III. the a In of that it the owned Phase are what's to on maybe lastly, yet. gating know data, the any and you success of maybe trial? increase is a can ready go-no-go Phase decision

Brett Monia

Over about in to comment for on olezarsen ask Luca. other a that Thanks, explore patient outcome your Richard trials minute. in populations will XXX to questions. I'll

the on acromegaly the touch first. me Let in

we year. open-label to going to data with extension acromegaly, said, patient population in we're can possibly the we for gather So continue as follow much the refractory to as through next

them those data, it year, monotherapy patients, washed I In frontline, as would failed the but somatostatin and on said, as view of some Richard coming out. addition, next

a will And study year. which read somatostatin and look from next the what's the at it's the monotherapy totality study, step the be to a open the next So patient the steps right trial. failure are the population. the for and and on then Phase data next out trial, That that III program, label would monotherapy decide of data, that

strategy? can the to going year? And we'll to opportunity attractive the so, the a III population next but The in an refractory question over looks what's on population, we So expect nutshell, most cimdelirsen you monotherapy I if Phase the guess our is with see data like. answer are what

trial. the We've trial a figure we so drugs to it believe ALS by that's designing best how all in and of optimal areas clinical was the and the efficacy What improve read out supposed to trials design we're I'd very of FUS-ALS, our learned optimize to tofersen future our just an further do. absolutely. deal. from drug inform much We're brand-new on great Regarding be learning we the view, ALS need to optimal here, more us the exploring to do already did clinical clear, in tofersen in going them. -- our of is everything a

progressors. And of ALS earlier in trial chain trials. and are ataxin-X, all symptoms, III. those it's the progression ALS progression all applying the ALS opportunity better; you longer II, are predictor state, is rates CX earlier studies our better from apply the thirdly, to to disease of bus better Some the the so off treat, of number we yes, learned a versus sporadic -- regular you the progression the have in one, two, the disease since learnings those things that fast the Phase neurofilament for this: We're treats the Phase light tofersen to the we've earlier are; and

that the make study. For outlined planning and still gives that -- for potential on success for that to sort us some the just -- early protocol maximize -- from you learnings and trial, FUS-ALS, the we're incorporate for amendments I we're in certainly, of to to

Richard Geary

Thank Good. Brett. you,

lowering on done cardiovascular note triglyceride the been agents. the trials been have looking XXX cardiovascular. greater that at disease. lot all and There's a failures than one with and At of Just in triglyceride-lowering

that cholesterol give remnant right go is input may this learn triglyceride cardiovascular something Vupanorsen, important actually no is III APOCX agent in going. a more we particular plans cholesterol, But Phase on outcome is. our component. where helpful. us in in market a be programs where into like our to this actor stated play dyslipidemia trial drug. we question. which Just that's a both simply, very bad is remnant have that regard it And we're the know that's Hope the we'll now, that with What and not that a we seems cholesterol-lowering for think mixed impacting best from

Brett Monia

December Day call much on to in programs day. Luca. the exciting Until said more Thanks, joined I'd then, at today. commercial look -- and like joining, our participated you We who And several we'll and discuss, seeing for earlier, Virtual late-stage I detail. everybody again thank to forward us our our Investor as most where and thanks for have great plans of a in again

Operator

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

may disconnect. You now

Ionis Pharmaceuticals (IONS) 3 Nov 212021 Q3 Earnings call transcript