IONS - Earnings call transcript Q4 2021 | Ionis Pharmaceuticals, Inc.

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Operator

Good morning. And welcome to the Ionis Pharmaceuticals Fourth Quarter and Full Year 2021 Financial Results Conference Call.

As a reminder, this call is being recorded. At this time, I would like to turn the call over to Jennifer Capuzelo, Investor Relations, to lead off the call. Please begin.

Jennifer Capuzelo

Anthony. you, Thank

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

me us Chief this have draw Financial to accompany With slide We Executive joining posted President Cadoret, today's Executive Development. Product Vice Strategy forward-looking Chief Executive three, which our and slides Officer; of your attention contains And Geary, Chief are I to website morning Eric Officer; also Q&A on to Richard Vice for our Hougen, Operations Swayze, Monia, like President Brett Onaiza of Research; statements. call. Beth and Officer. are would and

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

Brett Monia

collaboration our term market, biotechnology go-to-market our growth. delivering our last year, we expect substantial also is and with development market. future data. The of study NEURO-TTRansform amyloidosis cardiomyopathy important patients midyear, Phase XXXX. FCS The in with for severely eplontersen, we clinical around XXXX And beyond of last well on data to on initiated the AstraZeneca preparations medicines integrated we last X address year, polyneuropathy eplontersen, and for olezarsen regulatory moving At in when win elevated with toward fully the This well. track achieving technology step year expands of morning, and eplontersen announced which of commercial olezarsen. we Thanks, commercial product than last of progressing the end an which advancing triglycerides. strategic We're today's program substantial eplontersen will data late also call. a olezarsen million late to it study patients near together Phase and CARDIO-TTRansform progress continued And core filing drive as by was Jennifer. donidalorsen. donidalorsen introduced abundance Phase for assuming an with TTR new for And late while opportunities our III commercial and the III through competitive everyone. developing TTR pipeline, hypertriglyceridemia leading, completed thanks enrollment potentially jointly positioning also the patients III positive progress our Good track We III followed by severe organization eplontersen, remains our We the to our strategies our for for accelerated building towards we joining Investor to commercialized made for our expanding TTR us olezarsen becoming more the study to our and year vision expanded year, near-term the launches, pipeline Phase with Day bolstered in company. in

report following in program in olezarsen with this a plan broad the to advantage, patient data with our severe potential from in deliver patients FCS with year population. and to We mover medicine first the year Importantly, XXXX. hypertriglyceridemia class in in first have next we patients to

need for based year, effective given more on XXXX. We to see for profile the it date. profile to studies best opportunity the donidalorsen's putting highly report studies the III prophylactic And to a unmet in as data also study angioedema demonstrated OASIS-HAE data additional further for hereditary late we in has track favorable study class demonstrating Phase medical also with date. of open-label initiated year, HAE III potential patients in and from in we Donidalorsen last plan on the donidalorsen Phase very donidalorsen Ionis. a treatments, donidalorsen This compelling ongoing for extension, continuing

HORIZON Beginning IIb franchise. IIb including more data [ph] on our cardiovascular to year, adhesion data with medicine Bayer medicine with this IONIS-AGT-LRx treatment-resistant with programs year, with broadly and this data in our XXXX. Later last patients we expect readouts, enrollment pelacarsen for Factor April. and in hypertension. renal patients we IONXXX, disease from our fesomersen, franchise. And for at from data in looking the mid-stage ACC Phase of LICA Phase coming with dyslipidemia late XI with Phase forward study programs III continues the our with disease reached our The Novartis XX% data three leading end-stage well. study progress patients track in remains AstraZeneca PCSKX LICA Now for and from beginning in cardiovascular several at of up to look summer Lp(a) study

leadership path Moving the by strengthened SMA, which treatments. of dosing We Biogen potential position franchise. treatment We're our to advancing neurological SPINRAZA a to for SMA our reduce with follow-on in the with also data further disease program in engage has to the continuing study to and working from VALOR pleased the III extension. tofersen authorities, with Phase continues regulatory towards while for patients potential open-label that forward Biogen to SODX-ALS the evaluate actively a

to The track CX on this well, ALS also year. in which the continued this program, ALS franchise includes first other is half and of data our in for programs progress our

addition study, in Roche a less disease to throughout backbone microchemistries, we December. initiate with from chemistry other with the made disease plans advancements advancements year, We potential in to updates younger technology in are highlighted with the identified patients year. identification at look Huntington's of new Day We a in to the patients Investor and for including follow-on, later a II also in as study forward in pleased new SPINRAZA Phase And the Roche important from the tominersen that based last has forward burden. additional we path HDX on new findings GENERATION in our

before position advances XXXX ahead, keep key becoming technology financial with busy expect these And ahead. Richard, biotechnology catalysts financial I'll that recent discuss strengthening our a and turn financial year Beth highlight of company. with key will wrap all us will our a I'll questions. closer achieved our year for fully a remarks we review looking financial our any pipeline of your our up Richard XXXX be pipeline overall while achievements our results to After leading, and that, call cadence our to And the XXXX steady of XXXX guidance. And guidance. integrated the moving over to and and exceeding we taking pipeline goal catalysts substantially to Importantly, prepared

Beth. to over now So

Beth Hougen

U.S. coming royalty sources. substantial report our $XXX which pleased we and non-GAAP operating expenses non-GAAP to I'm $XXX XXXX based ended XXXX Brett. more guidance. in million element primarily income our These XXXX, foundation more remain billion $XXX $XXX you, net million well products earned exceeded global million. numerous of capitalized cash significantly with is billion. sales due we were the from global from year-end than of XXXX, on revenues year-over-year, ability majority strong SPINRAZA. of in more Thank from results competition million diverse from we revenue our A revised of in we for financial earned marketed SPINRAZA's revenue key $XXX the increased million to with XXXX SPINRAZA investments our down sales than revenue. to than $X.X with X% Further, of consistently $X.X and generate In were

sales However, increased we and certain studies. post-marketing were SMA to of ASCEND, increase Biogen's encouraged And and rest that in remaining needs primarily studies discontinuations world, year-over-year, are an is in from the and work in other DEVOTE Biogen particularly of patients sales Latin volume, the the SPINRAZA decreased compared SPINRAZA ages. markets. in evaluate ongoing QX. further element of continuing an inform all These unmet address of SMA RESPOND to the to treatment important America

With of see SPINRAZA. year. revenue future proven profile, generated to supporting a this WAYLIVRA more continue and of than evidence we SPINRAZA's the growing and million $XX bright substantial for TEGSEDI body

reminder, was based product sales transition product on mix fees commercial to for As the medicines XXXX. course of of operations we completed a Sobi over and distribution sales. Therefore, of revenue XXXX a the our these our

pleased revenue. we our total earned of for year, to through numerous earned The expand XXXX an continue million efforts fee of throughout as earned Biogen new PTC. upfront $XXX our medicines including to came partners our different more Most our strategic collaboration a from revenue and $XXX neurological programs. important contributor an total of AstraZeneca number both our the from important nearly are markets of programs, Last follow-on $XX into Sobi R&D with together advanced than for with eplontersen our that of million advancing R&D from revenues. XX also revenue than nearly was more license Revenue We million to Biogen the revenue. total SMA our we contributor XX% was our representing collaboration medicine. payment partners, we $XXX from We million,

operating We with advancing we advance. part the pipeline reported Biogen by have XX%, a as studies Phase by revenue in a expenses X% increased large under conducting. potential R&D all III which the increase with they our flows currently non-GAAP driven programs was compared substantial $XXX to growing and We cash of and expenses collaboration, are XXXX. of million, generate large X

peptide meaningfully advance, to R&D we and we drug Last and our our transformational expenses medicines to advancement. to year, Bicycle external invested technology. positions discovery note, rights deliver to innovative will Of expand external continue anticipate This, market. efforts increase. the internal technology in these to with more partnerships, many our Therapeutics As we us together exclusive and internal other capability programs continue also obtained

XX% realized I by Akcea XXXX, from describe as decreased the as expenses we savings driven reinvesting And and these SG&A with savings transaction. the Sobi planned, Our we are substantial integration next. compared will by

our Now guidance. financial turning XXXX to

with the $XXX earn more of million basis. range operating and all revenue, less loss of in million We than are net $XXX projecting million, $XXX XXXX million incur to on $XXX expenses end in than non-GAAP a a to

balance to a cash healthy Additionally, billion. end we are projecting $X.X with approximately of XXXX

to fully company. of to of responsibility Our increase financial has achieve when At our necessary leading financial long we investments goal resources us need we to time served these underwrite a well. a spending, biotech integrated the becoming have substantial history our

to ability make continued reflects Our investments significant with a our our necessary healthy cash generate remaining while well XXXX goals capitalized revenue realize those to guidance and balance.

commitment pipeline remains demonstrates Ionis-owned guidance our to XXXX advantage. competitive commercial advancing building opportunities, near-term platform our our and our key ensuring our Importantly, a

Phase of Before cautionary of provisions more elements our explaining global CMC the our I eplontersen internal are our first program program. Under as detail III is responsible financial Phase guidance, how financials. for in AstraZeneca few on like of leading well reflect our ongoing collaboration AstraZeneca a global cost, I costs eplontersen to the conducting of go as external the would minutes the costs. spend agreement, each we Including XX% III will and into XXXX we with and

reason, related development reimbursement the XX% revenue that we same period will expenses. in AstraZeneca the For recognize recognize as we received we the from

expenses will we Our expenses R&D eplontersen. include the for are incurring continue to development

also received medical a any we for responsibility net AstraZeneca we in incurred Since for medical payment is of States, sharing United responsible affairs of and expenses costs. Ionis majority sharing affairs R&D AstraZeneca. include the XXX% the cost affairs expenses U.S. will of activities large our from AstraZeneca medical are

in sharing AstraZeneca. AstraZeneca responsibility costs will Ionis' of incurred XXX% commercialization for Because we from majority commercial U.S. United for payments of large is any a for SG&A we sharing activities also AstraZeneca of and responsible eplontersen. cost States, eplontersen commercialization our received net expenses expenses include the are the also

with the outside AstraZeneca bringing As eplontersen fully to a costs United market reminder, associated responsible is States. for

to with U.S. Beginning these and capabilities plan with to cost substantial olezarsen our a earnings, Importantly, the launch launches quarter. sharing payments of provide cost-sharing us our AstraZeneca and upcoming for we in QX each expenses eplontersen, receive our from resources to planned provide addition we scale for the our of table donidalorsen. payments

bit a our guidance. on would XXXX I provide more financial like to Now color

generating We another of multiple year sources. are from revenue diverse projecting

of royalties base as sustainable and with the substantial quarters commercial a revenue show. SPINRAZA have We

our and that from is We from that revenue sustainable shift, the R&D meaningfully of expect revenue sustainability will revenue. may a constant. base to partnerships our but of substantial of partnerships we contribute also have revenue our composition XXXX Year-over-year, our the

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

Additionally, the we AstraZeneca few our R&D receive from as will ago. I eplontersen revenue reimbursement for will also mentioned collaboration, include moments a

be of we before. our the year, we studies we This Phase are and currently large portion our conducting. advancing than open-label Importantly, through can two ever will operating streams multiple more extension late-stage fund studies expenses. of III programs X includes This a revenue, development

new including plan also We studies. studies to open-label supporting programs, Phase extension III initiate additional our

will CMC for support and expenses R&D to affairs increased medical donidalorsen. include olezarsen eplontersen, Our spend activities and activities

large a expense And our and in percentage to While invest ensuring will abundance continue to our forward. to and competitive. deliver mid-stage R&D marketed we to innovative late-stage relates technology, pipeline also expand new position us remain of our we expect to diversify going early we medicines, an products our and of

XX% a expect last of year result we compared our to XX% As increase to this year. these to investments, expenses R&D approximately

We eplontersen, the donidalorsen commercial olezarsen and bring are prepare our to also readiness in investing to efforts to market.

transaction and AstraZeneca, with from integration realizing the year payments savings Akcea. Sobi from of of full a will With our the we along cost-sharing receive

year line to in expenses We be year. expect this last SG&A with our

our has enduring commercial financial Ionis and and sustainable as And invest quality been call needed of us value to us foundation In substantial $X.X rely drive significant patients many for and the with on enables billion Our solid R&D cash shareholders. Richard. revenue, financial who turn substantial deliver so, base of that, to for an doing the of expect I'll to we With over a future strength to our growth. years. and

Richard Geary

eplontersen, including term certainly Well, eight even key many XXXX, separate donidalorsen, near have pipeline and advancements with We opportunities, in our address three commercial pipeline Beth. last several updates We Phase place achieved rich taking which five thank olezarsen call. medicines six since you, III in indications. alone, now our indications, for our pipeline

the eplontersen mentioned, III on for readout the were regulatory nicely for data. studies, commercialize positive eplontersen and collaboration, our in oversee need polyneuropathy that progress remain and our preparing jointly Phase We underscoring this assuming significant with data TTR designation This continue amyloidosis. second remains year As AstraZeneca. patients we're well with global track. patients drug orphan continuing unmet the in which are both FDA, that planned half developing granted filing Beth lead TTR for Brett with and the to and III study, Under to pleased we NEURO-TTRansform us up sets and Phase planned approval by of was to of the

of atherogenic For our options. The study, hypertriglyceridemia data Phase a The also disease, patients core triglycerides risk broad olezarsen X fully next triglycerides per and Data limited lipoproteins. olezarsen, alone. more substantial realize moderate high of data study olezarsen risk potential with deciliter. million XXX-milligram designed for triglyceride-driven established we Heart over a for with development APOCX, study, patients resulted Journal. Phase hypertriglyceridemia at recently in today recently, high represent European in its with to we or U.S. substantially III at cardiovascular who program II triglycerides FCS a a showed And the opportunity were with have than track address first the remains of have in study patients Phase from Severe study treatment initiated disease treatment year. published to range on severe with III second olezarsen that reduced with our in of olezarsen, the patients BALANCE in

more treated with monthly XX% dose within normal than triglyceride Importantly, range. those levels XX-milligram achieved of the the fasting

positive angioedema. III triglyceride Phase reminder, for hereditary to an made with and reductions the ACAAI a HAE to results study program progress in expected rapid favorable also tolerability reduction. the OASIS-HAE dose donidalorsen a evaluating even a both be XX%, the with at HAE. reductions in XX-milligram Phase we monthly of initiated III provide patients that attacks in in studies, safety balanced our our core monthly, also expect with As mean We donidalorsen we Annual XX-milligram for addition to We significant of up treatment of also us treatment to sustained are development believe greater which best-in-class demonstrating data II donidalorsen We've and with Phase prophylactic Meeting, and profile, presented XXXX with could leading

sustained recent a our and IONXXX LDL-C of dose of PCSKX statin in to from our data and in At our demonstrated mean from AstraZeneca November, the from targeting franchise, with disease on study, In review April, to ascending with partner and forward leading new multiple LDL-C AHA tolerability. patients study reductions favorable look and to progress IONXXX of starting we dyslipidemia dyslipidemia. up patients safety IONXXX, robust up reductions XX% with with in study cardiovascular adhesion in PCSKX presented Coming reductions Phase stable Now cardio. up neurological and XX% PCSKX IIb of data and in ACC at to therapy.

conducted data and high-intensity be reported from dyslipidemia population, was medicine therapy this for consistent or a and study highly moderate the in best-in-class safety expect previously statin efficacy for on to reduction. potential with patient to which be to support adhesion, patients MAD We continue similar to the LDL-C

also had disease our We in this neurological several position significant technology the of IONXXX, duration on further SMA. advancement to extend chemistry novel substantially enhancing announced our dosing we potential leading based leadership This in data, we to of that Ionis recent SPINRAZA, is preclinical follow-on franchise. based achievements potency treatment Early our And advancement believe IONXXX on intervals. enhanced offers and action. our includes the year,

identified And recently extension Findings potential benefit study. adult analyze with may for in Phase presymptomatic neuromuscular younger the endpoints. of with in steps enroll and addition, continues less tominersen. this III the patients actively secondary burden. pleased patients. syndrome, ongoing regulators exploratory And that by study from III also new remain to presents path We're in remains patients reduced the saw open-label ATLAS on of study seizures. Angelman importantly, from the these multiple in Biogen next showed tominersen SODX-ALS and has to from Roche engaged Biogen disease about the step a analysis genetic for We signs Phase determine that profound to study study medicine. this patients Phase and I/II III collect Roche which also frequent childhood, forward with across with from disease initiated Phase and encouraged forward the from patient Based disease continues results Huntington's a Biogen more the learning progression rare VALOR data from We resulting II study study seeing GENERATION tofersen a the this population. developmental in HDX post-hoc of data that this for and severe Phase data new delays the post-hoc additional by year. findings, and tominersen Phase We're study important Roche to the plans of to and look design a later initiate analysis the encouraged II in disease early

to with eplontersen. and X have late-stage at medicines deep data and mid- This XXXX. turning Now a year, mid- late-stage highlighted we of readouts pipeline by least

are We the the for Phase mid-year. III planning study from data NEURO-TTRansform

prepare and in file Our team are preparing joint and a the working of launch course, to regulatory AstraZeneca Ionis of commercial second collaboratively this eplontersen. year. And already the for diligently half are of teams approval for the

have IIb We to potential we rich expand readouts data Phase look forward our Phase III alone. to as X also the pipeline further this year

to As PCSKX I IONXXX, drug, look April. forward mentioned, from just in ACC IIb data we our Phase at

chronic the patients of report B-Clear expect We bepirovirsen IIb to data with GSK study Phase from hepatitis B. in

with to and Phase report treatment-resistant IIb from we're patients disease, the also from renal in hypertension. study We with of Bayer end-stage data data planning in Rethink to Phase of patients IIb [ph] IONIS-AGT-LRx ESRD our report study fesomersen expect

data, the with II our later data and in this from II patients from or to readouts, multiple donidalorsen data Phase IIb X we study. expect results open-label including studies OLE IONIS-CX Phase also including addition study from In ALS additional data year, CX and Phase extension data

call. call on this cardiovascular rich the anticipate close further are And Brett hope studies focused later also to with our additional key planning franchises our to to making several you of we expand which to this and advance share back we over pipeline. Further, portion this advancements, I'll that, year neurology and We turn to initiate the technology with year.

Brett Monia

To and pipeline in progress technology; year We we becoming advancing expanding year With at III strategic are X year commitment this the growth potential filing a to by made our goal of Ionis and the X III data company. eventful readout including fully a our focused eplontersen are polyneuropathy highlighted commercial end, abundance and term data on and and opportunities, term, priorities: thirdly, Ionis. to new Phase Thanks, Richard. central regulatory delivering our substantial integrated leading continuing and to remain the planned for filing, catalyst-rich substantial have my we the plans biotechnology that strategic this Phase priorities and and achieving approval. eplontersen, building TTR readouts eplontersen of olezarsen commercial our year focused an for ahead. on to medicines donidalorsen; build X least potential an X our the and These near-term market by on hereditary last drive longer near diversifying the for for

As with have support we exciting commitment have reviewed for year. this made great progress this of planned morning, in business our progress even across this we more

of deliver patients now a of moment actually, Rare important are and Disease ones discover, open life-transforming who I'll There want I these Monday, a closing, affect XX, the call for than team take with million February Anthony? Ionis treatments. that, their around day, that rare with diseases and develop to determination, and people questions. sense working Day, X,XXX are the loved the And XXX every Disease and is the Rare resolve which Ionis. urgency approximately to Day, speak On it's world. resilience more Before honors to to and tirelessly about up

Operator

[Operator from Capital Instructions] Markets. comes question Gary with first Nachman Our BMO

go ahead. You may now

Gary Nachman

questions. guys. taking for my Thanks Hi,

it? terms sense just mechanism? enter what in question do dosing for to with bit when clinic is has And the side, for with how opportunity been similar PN First, so talk be it, might will far big the How the second it collaborative to Biogen able to process about prepare of some do it commercial of And eplontersen. think AstraZeneca the SMA, product potentially of the you extend been the How follow-on have sales and license on well? any both Biogen forces for for and you describe cardiomyopathy is making then the capitalize as AstraZeneca? the then a for more. to intervals Thanks. And you SPINRAZA you've the the been on preparing progress and

Brett Monia

I'm Swayze, ask Research, a related Eric the to little you can about follow-on. the mechanism the talk SMA questions going AZ a chemistry why to Eric, kick Head going And Gary. co-commercialization great. little talk don't of which about Cadoret bit and co-development, it is bit the off? to the how questions, Great Onaiza and partnership is going, But

Eric Swayze

Brett. Thanks, sure. Yes,

or mechanism the uses the same So follow-on, BIIBXXX, IONXXX, it SPINRAZA. as

the it was mechanism. both is and different SPINRAZA. in improvement the does haven't protein, things. an and exactly modulation modulation synthesis works a So potency in splicing it follow-on a that the and the just dosing SMN the which a of of And particularly what's backbone chemistry, that use those slicing in molecule promotes extend we the improve gives disclosed like the And We well objective extends potency it's backbone dosing to mechanism of molecule, program chemistry the but of new interval, frequency.

preclinical to given to program, their So from extend hope there. about asked the starts. SPINRAZA. you really when clinical the Biogen be hasn't And we've but compound got great to start on dosing working going trial is guidance they're clinical on regimen able and on data

Brett Monia

clinical development. for And Derek. just drug that, ready to add is to thanks, The

touches regulatory tuned studies design They're stay and the trial ready clinical tox it's But discussions. on just and to for go. that. putting cleared it's So final

for As in of study. little about with going you AstraZeneca Eric the haven't please the to partnership like said, Onaiza, timing that is they bit a would eplontersen? how talk disclosed start co-commercialization

Onaiza Cadoret-Manier

swimmingly question. Gary, Brett. just going Happy collaboration for the Thanks, Sure. The to, is well.

are partners. really and AstraZeneca great just Ionis

been there approaching strength way. on of capabilities a I having the differentiation. leveraging We're other's think lot think and we're is in past, each the in where I absolutely co-promotes this right

have in expertise where sense, strength you this to field a areas we're More as is well. been mindset great a really the So to and certainly leading going amyloidosis the question, of leveraging decade entering And Ionis in just medical will the through for marketplace think know with the that your marketplace. it. that We've tactically which in fabulous when investigators be really they we're be start. We way the about to well. KOLs within all

be we're leading research to capabilities rare just to also effort leaning on support in and as planning having diseases, team a well. and of So patient a lot great eplontersen. field medical the patient strength launch research that leading and our We're going and services that medical collaboratively

you of will So on that be color leading. gives Ionis a the bit that types activities of

obviously for failure brings just ways. on great in heart in - the AstraZeneca strength will We variety and broad of rely presence a that other a have they cardiovascular that

work As not to do your we more question, to have size front. established on of yet, just teams, been just that

eye launches that towards we're this for would line are certainly taking So effort which Ionis-only happy a capabilities to be say building will olezarsen path to and an share lastly, be next what month. I eplontersen in donidalorsen, that as and sight really will we work have along next our the we for co-commercialization launches, of [ph] leveraging towards that with AZ. then And we

Brett Monia

Onaiza. Thanks,

Gary Nachman

helpful. guys. Thanks, Very Okay.

Brett Monia

Thanks, Gary.

Operator

Our with Fye comes Jessica JPMorgan. from next question

now ahead. may You go

Jessica Fye

guess going afternoon. Hey, couple the I a question. - – second for now, had program: Can one Thanks to half. guys. looks my the HAE one differentiated I updates what lowering on second, Good the types like in first for meaningful should two IONXXX? share elaborate it updates? each you for in we difference see as benchmark taking Like to this LDL And relative have the then year what half, you're in you what with do of you a to expect of constitutes those data two inclisiran?

Brett Monia

Thanks, thing. Sure Jess.

There IONXXX the a demonstrate the like deeper the quality in sometime have tolerability also there, meeting a AHE, investigations into only we're planning this the of of more not coming that So to data to that this further which II support straightforward. With lower are in of present the medical that. study a example, publish then really at other we're Also the half Phase best-in-class are for will of to out position II to in a will year, the which in - beyond year, drugs the that hopefully Phase We're a an that from the second for to we that planning going safety, half and LDL-C you're donidalorsen, said, journal data update, as of And demonstrate cardiovascular Phase updates for would current siRNA, need controlled II that study. for on update whether patients meeting. data in long-term study, There's better you PCSKX life, a open-label risk to is from medical for a data it's or disease to of received soon. data publication. have further molecule. the see they and first treatments. get despite look monoclonal are a at is durability that go better robustness results the And differentiation, patients to protection the of I these extension are and these drugs drugs, other think - be planning respect third antibodies update our there, a than and

reduction efficacy from on data PCSKX and does better based And and also APCs. LDL-C of look I lower will you lowering cholesterol present - IIb talked high Phase So patients lowering on more the like It's a Richard greater Phase that that's really inhibitor a potency we it's in achieved. consequently, risk vascular about the effect course, best-in-class see. It earlier, a better talk And better of the a with agent. in the part with LDL-C, that, the is statins molecule. better data his but the that

So differentiator there. key that's really the

Jessica Fye

you. Thank

Operator

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

may You ahead. go now

Joseph Stringer

Hi, our good Thanks for question. afternoon. taking

program of competitive the given are one Phase with AGT constitute hypertension, clinically would Thank in And on readouts modalities, you just meaningful Just competitive the pressure? again, what the for and in IIb what sort blood indication? looking you. landscape this profile terms in a of different in changes of

Brett Monia

want that? you Richard, to do take

Richard Geary

Yes, happy to take that. Thanks.

blood in But medications for and thinking anything these able to pressure and we're And on see see And we to and read would will than reduction is this multiple on this pressure who a these we blood lowering, blood What control. it, expect for We're robust to expect is out not well, great best-in-class that would them to lowering going excited like So to reduction systolic real of question. something Really blood around are medications bringing their in lower to patients add millimeters mercury is trial be and year. patients resistant lowering. a getting systolic to it the are winner. be XX they're pressure. about essentially in pressure with to you more molecule X control.

Joseph Stringer

Great. for our Thanks question. taking

Operator

question next Matteis Paul from with Stifel. Our comes

may now You ahead. go

Unidentified Analyst

for This Thanks Hi, questions. Paul. taking on there. our is Alex for

see. out Just one that more [phased could if disclose might than here NFL we you the engagement And the if about curious this readout curious in a the a anything on bit less population? bit target the talk you know known biomarkers little do know, data? expect to in know in first I history I'm upcoming you guess half, natural CX little about beyond NFL one]. it's if I so, we

So could elaborate curious more? you if Thanks.

Brett Monia

Alex. thing, Sure Yeah.

that study study study a going CX-ALS. study, data for That wrapping steps well program. is focused and on course, in Biogen potentially that selecting CX a by is and II So III fact the potentially Phase up to as Phase is, dispose dose next of for potentially we're excited future the

how select reductions those - tolerability, based correlate reductions safety regions on brainstem for very to which with target course, in data. first CNS, from and we spinal of aside based what very cord important that the is preclinical and dose the relevant the reductions So on patients those to study, of a in peptide translates engagement patient important is in a to CX

Phase a that include would see, we rating achieve certainly endpoints achieve to all position dose a include that of endpoints not with objective characterizing III scale, as focus vital classic potentially to capacity, that's will study. secondary/tertiary to that's want include for the not tolerability the NFL really of to ALS to you expect but would the is the and would and targets would looking objective. that The but functional the safety select the That be productions it certainly, We really main study. the that

Unidentified Analyst

you. Thank right. All

Operator

Evercore Schimmer next ISI. from with comes question Our Josh

now You ahead. may go

Josh Schimmer

question. taking the Thanks for

neuro focused you And MsPA sets advance is more targets programs thinking backbone Huntington's. revisiting ALS historically, in to you've or case? clinic? expect separately when your plan the next that commercialization think strategy, to technology, evolution validated Or your in to portfolio, that I How for deployed which and novel about data product? still be how going relatedly, there's do are First, gen that Is the of for with been CNS in the you're you'll Do such and on expect can the be of including as now you heavy. likely a least we be targets? you to and amount TTR target this in been a fair third-generation novel own? at prioritize And it for then and the some tissues?

Brett Monia

Eric, the MsPA take backbone.

Eric Swayze

one not MsPA the but take I'll commercial. Yeah.

backbone making. new drug MsPA in is consideration every the So currently we're for

competing depends chemical every we with and how the we therapeutic when on our the in make it all actively disposal given that's in clinic. little would And possible every and modality areas that's So best have. the we're drug. and - exact we a at it It platforms. all to chemistries on technology other timing have haven't it performs again all with But enter bit

Brett Monia

on that And little if I could just bit, a expand Eric.

committing greatly possibility. hoping as year. be the not expect we that, can have there. this pro-inflammatory past in pulmonary. open looking also may for that a within Investor forward Day path yet, example, are that molecule at effects but We're chemistry, presented Difficulty] could where a other that And last us So that We're be tissues believe certainly, to reduce we're We control had that's have tissues allow can a to chemistry. that a [Technical up to we we they

the durability us at based frequently, like allows preclinical also us, to subcu We route. that least so data on using far gives this dose which chemistry very really

FUS-ALS we're neuro, right And rolling into wholly other thereafter. different Really really is it development overall planning - to a have a study the wholly-owned by clinical - first Phase year in initiate to to that in and we talk the to of in of move regard think a exciting have carriers offering very course, market studies a a study With forward initiated we're molecule in that a profile. we're And means we're the yes, lot, in it's drug looking disease, as from Phase So forward aspects lot portfolio tox of development And thirdly, GFAP to a this in but year, program. ourselves. then - have two this planning Ionis We're owned that patients program. study. progressing path then novel our more that pipeline, regulatory Prion development about that we and are now drugs this that nicely, half that's in the second bring is One, in approval for We a and of our very planning which to is in to first think year study we II/III it's And Alexander's potential study. III we well. disease. standpoint.

that pipeline year. of eplontersen, follow-on future, in to about we're more about targets believe a opportunities, data. the real based growing. drug commercial great towards we're really donidalorsen, is that and movers looking rich neuro our our pipeline near-term a but haven't following pipeline and Behind our talk neuro you've preclinical yet, heard it's have our do which the on being commercial we we going that of And as think drugs, I disclosed olezarsen we for this

Operator

Zhu Our next Fargo. Yanan Wells from comes with question

You may now go ahead.

Yanan Zhu

ahead may on a of And certainly to be tafamidis. if patients contrast looking competitor's real-world you. a forward trial. to cardiomyopathy of regarding in cap cardiomyopathy, have mix further more of eplontersen And the congrats midyear I look on the the in there's study trial's we the one little a the for polyneuropathy data. think design opportunity, question a patients for progress. Thank features that I is no therefore, But it

question trial arms, the a you increased is, address that testing measure I between who both that hierarchical design how And the - have marketplace. if to does would this not tafamidis you So may to of at allow there to proportion if are a in the arms. are patients you have in subgroups allow separately. wouldn't you elaborate, versus those affect may two do also in delta patients look patients And better two a have that? the statistical And claim tafamidis

support but that I - a you plane? think that, could you exactly could Thank differentiated how how elaborate highlighted you.

Brett Monia

so the relevant trial level. setting, the the address a you Onaiza, study you how is enthusiastic is tafamidis, we're a Richard, uses a real-world usage design why Thank of the bit and little powered design. the high on And study in you, and maybe at Yanan. part about - the talk this then, management first can why cardiomyopathy of and the about in Richard?

Richard Geary

Yeah.

experience the allow is that to the it goes So that excited design we're enter world trial and of actually from because well. the benefit to one all does expectation if really about upon going approval, a world us real we're

tafamidis, countries In other and group background. and available which was study the is have in actually other selected tafamidis on cardiomyopathy based do well control It's use. already was tafamidis powered any the that the not. but powered countries United this so tafamidis than - indication assumption a for like this larger in And we've the allows understood, the studies reality, the may benefiting of so study, not States on everyone from that that be

which to will it those statistical So naive not looking only also on patients tafamidis. are do analysis tafamidis, a will allow looking not be on that mix, us a but at at

So it look in real and terms spectrum the broad of a benefit provides a the design nice study. of

design speak this why the pass to it. and about is excited to Onaiza I'll it that that's we're over important. to so So the reason

Onaiza Cadoret-Manier

Yeah. Thank you, Richard.

design as our customers the excited say about So very are well. I would

lot the patients all future, the and getting where is I in large geographies, will and think we a which of as are on they're we're know who patients skating will great. be such U.S., puck be diagnosed in because will to tafamidis there the the treating, particularly be

in cardiovascular and trial have come of patients with the ability and will will clinical data actually for There to evidence data reduction the make extremely be requiring who's background naive patients. that both will they physicians that looks sets risk patients largest be like the we stabilizers So the tafamidis a there give generate now be and what for stabilizers. And tafamidis. will to on then who be be set who benefit be ability patients decision to data on how evaluate will currently on a important. patient to the that to incremental that in will and above And on

will we able evidence. will we to the data, you be And asked. the into So likely things perspective, we in had have certainly get put these are to working towards claim, as as and terms ability outcome those the label very that our go of a from that all have

as also would reimbursement we've claims like? in want think If really does a that, for long and and sets forward to. data, So payers care you these see on? health for at are were professionals, be that used, the if access, go very how another mindset treatment, those always as have is on I'm we at same is choice. data also just - because that and both know, patient pace that. reimbursing stabilizers the very have any So great They generated and best together the importantly, to not will sick. evidence looking you And and we're patients came to to data actually what a there check actually patients combination that very cover about physicians to to were silencers making And treatment, treatment I'll that if generate look on because two it very done and we not they add also said fortunately, this add, for but US our have and we for would these eplontersen the will they them. I

is all as going trial do and [ph] perspectives, real-world very, cardiomyopathy. launch in this clinical stable see we very we three to evidence So from be

Yanan Zhu

you very Thank detail Appreciate the for it. it. Got color.

Brett Monia

you, Thank Yanan.

Operator

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

ahead. go now may You

Jason Gerberry

are questions. speak have to TEGSEDI key and ahead of that and thinking just REMS if competitive more components, to - the sort considerations? about of Thank talked safety differentiation think about how out there really more guess guys. And are sort just a box safety is I product my speak which warnings the of taking for either can itself relative on the important? but currently you a year the a Thanks. one profile the because a to patients just you Is are both to you If distances with think changes, what monitoring volume we be just contraindicated underlying TEGSEDI? you really could tease of trends share as for black helpful? that guys thrombocytopenia eplontersen hard thinking is in is develop to I to the market update, far these to and it, proportion market. this those Or of Hey, or of so TEGSEDI product from two lot the revenue commercially, kind it would that renal calls, of reporting you

Brett Monia

been catalysts agree a of coming mid-year We this lot year any pipeline, catalysts, safety eplontersen year, our for rich and we I safety evaluated including LICA in reviewed, up don't overall. expect polyneuropathy. polyneuropathy and readout been all. mean forward that's drug blinded our issues and for our time each committee it's our Phase for III by by Yes, Jason. on Sure, it's this moving eplontersen a that's at continuously platform the readout based - oversight data

for TEGSEDI really - us, that's from eplontersen platelet to need monitoring expect relevant to monitoring So with for for monitoring the not any today. any away The normal to reach is beyond which more because renal market move important? drug monitoring or what's that don't we renal occurring is

amyloidosis for that's the as with are forward. patients TEGSEDI back don't going have hereditary I period. as maybe approved we of and assumption can far that So and is Jennifer. signals that renal go and to platelet at for polyneuropathy, and not eligible look And signals, with patients any would follow expect TEGSEDI, we back TTR But or symptoms

they TTR that me, exactly tested don't is for and renal eplontersen and first platelet But certain So they're patients certain in to there where demonstrated I amyloidosis reductions of number provided a all the not that for in Eplontersen that is, a study seen competitive, are We all population. superior in has eligible for front has think small which our for do eplontersen we've as patients as parameters, but have TTR we a TTR product I - Phase this what are above best are in highly that our out potential eligible with threshold, TEGSEDI hereditary for polyneuropathy are drug except today. amyloidosis cardiomyopathy. class focus our

Operator

Minter with William comes next Myles from Our question Blair.

go now ahead. You may

Unidentified Analyst

on Sarah for Thanks taking is the for questions. This Myles. Hi.

kind bit, to our moving question on of can of trajectory a Just franchise comment the kind on of up the forward? TEGSEDI you follow

Brett Monia

Beth?

Beth Hougen

Sure, to. happy

what of would the to our doing. I we - sales revenue course, expect and Sobi but continued last them TEGSEDI year areas distribution into TEGSEDI see new going have forward. support that can't this each from are for terms remarks, countries publicly, respective And as get Obviously, from Sobi pleased expand TEGSEDI TEGSEDI So of in in disclosed with their I based a mentioned PTC we're on and of first revenue, PTC to in of continued model. full year, prepared of of work ahead our then is and

decrease So a expect year sales fees. last actually decline mix you revenues because of and product was see year-over-year to distribution would year-over-year, our

that expect decrease. So see you year, would to this

and matter. substantial WAYLIVRA for expense the the had moved when model with also we transaction we TEGSEDI However, for savings to distribution Sobi that

our into those Ionis of capabilities, into think savings impact neuro fully integrated as reinvesting our P&L that all before, absolutely we're our mid-stage company. to are that actually opportunities, the the the build And biotech said pipeline, the things from technology, into change is positive. overall our essential So commercial quite of leading commercial I've we into pipeline, rest

Unidentified Analyst

Thank Got it. you.

Brett Monia

Thanks, Sarah.

Operator

Our Issi next question RBC. with comes from Luca

ahead. may go now You

Luca Issi

on AstraZeneca, Thanks Great. the circling great but competitive market. question a prior a obviously, directly, for more a my Maybe so polyneuropathy. back little with Maybe fairly question to partnership a ask TTR question. for taking much

going So split that, maybe, in thinking you market frequently. the obviously, they Alnylam? be maybe they're you then after hypertension, with your but may after Can and you are one us ejection long between reduced AGT. going remind less failure just heart and the Given you have dose Again, competitors Onaiza, how for term of failure? fraction. trial a to just rationale heart about And are share a ahead on second question position for

So then us give is combination combination on data that Wondering with nukes there. if GSK the trial maybe forget it if I you're to us or that like we'd for if some rationale lastly, can have inhibitors. Hepatitis with you B. remind And you monotherapy some can it CAPS sounds color love with or going one.

great. there color much. Thanks so be would any So

Brett Monia

Onaiza?

Onaiza Cadoret-Manier

as he a want Since systemic in me. about already the we Luca. and as Thanks, eplontersen first disease polyneuropathy, directed Yeah, will ATTR. that to question hereditary launch, be to so for in think particularly the you this

will the pure patients. both looking as be we at mixed as polyneuropathy phenotype So the well

about treated. think have patients XX% a diagnosed to been as market, large XX% So it only and of those

So for it's multiple a share. market to players big

those after done, went Brett expect are of to what's it then very presentation are - look would in is at Norfolk a strong on we hierarchy in product choice. have home what physicians self-administration very that's efficacy of our and important both And with things mNIS+X have expecting safety you patients. next data We terms And driver market, be terms key to of Quality then Life. just our profile. the and I at of here, the through say of

a to So efficacy in going products And important do be a kind safety, in visits being important. virtual and done more our it's more and say feature of new well of there's I'll COVID, be important, that. where to by normal that's really addition we really that deal of as will, a preference even the are believe to physicians great just actually that,

up but at patients certainly And self-administration big of is the important more terms in-office than very, control choice it kind to when So in the that driving monthly really think we it very the show continues self-administration a didn't administration. really the tested very strongly be of this benefit. Honestly, quarterly. giving that we of was a versus monthly was home consideration, of

the calculate color. about offers. on But able you'll hopefully, be give to I wanted you can product as based you to perspective sure to I have that. that to get what And shares that wanted make and you And model that really think well. just So

Richard Geary

heart question angiotensinogen. can I take maybe the failure And for Great.

failure, down So has of first models safety preclinical initial some heart of production of heart all, into some shown to this angiotensinogen look reducing at and in we failure in patients. for shutting moved these study real or angiotensinogen the benefit the

well have been in benefit issues the ability very as issues side, to RAS the you of of those in cardiac heart patients. the because inhibition possible renal be failure very to limited the One is careful medications as has the utilize or these actual on

the getting - both on their what in And control, as aren't need of they so blood side terms effects. well pressure heart they as failure

angiotensinogen so with of we with - see is angiotensinogen pathway hitting without the And at the opportunity what the top the kidney. treat to RAS

at And of control so course, a looking lowering pressure. and of angiotensinogen primary of safety the as, as we're as well blood

the about we more learn excited possible as these we're for and studies. a indication that excited as angiotensinogen early We're complete So about we'll study.

Brett Monia

what Thanks, design trial that Richard. on HPV readout? the to might expect you we Eric, comment from nukes, do want plus

Eric Swayze

Sure.

So basically that's it.

to we clear the if of functional idea the infection ability and system's S-antigen II, see which causing on drug the care, overcome the get bepirovirsen to and call subsequent and of - the and inhibiting reduction to [ph] of inhibitors standard can the got and viral achieve cope alone S-antigen, with of we in of the which is is what Phase the can is the virus of kind immunoclearance system they've it. So trying cure, where top a immune Sunrise nucleoside protein

suggest So borne and hopefully, study. out that's it be the might it be in corporate the data clinical will some II that possible, goal. in And that Phase

Brett Monia

Eric. Thanks,

Luca Issi

much. so Thanks

Brett Monia

you. Thank

Operator

with from question I-Eh Laidlaw next Jen & comes Co. Our

go You may now ahead.

I-Eh Jen

me questions. two I've got ones. the Thanks for for quick squeezing

in comparing sales is in sales the question one can in starting will - you should moment? anticipate teams your the adding on you rep that And is first maybe in have or [ph] of of The of is any there the Thanks. eplontersen competing something one XXXX force, AstraZeneca later? co-commercialization think given sort advantage, commercial other terms benefit besides to be the just of terms eplontersen PN, to self-administrative agreement, we this the second previous theoretical at structure that

Brett Monia

Onaiza?

Onaiza Cadoret-Manier

Yeah, happy to. I'd be

modeling collaboration, we So likely that AstraZeneca, going purposes, divide going up going we're working the to would to your for - customer-facing doing this non-sales for still into of out suggest that resources. the resources. in have are customer-facing - we're just how more be some of we're the But I

by be be we and more be medical case field will AstraZeneca, part the as that resources. salespeople handling nurse of So of the of the handled types required managers will and customer-facing larger will those

the - are it's very at-home explained the I package will the as with to in So obviously, But it's hopefully, well. You size will And whole that drive ease have differentiation, together in that the I of for of we both that then right? as things two help you evidence us terms characterize about all it's it trial you look that. the a at calibrate help tafamidis - the alone and for think terms administration, trifecta, from always in as differentiation really but that very, of offer we the and confident real-world well. profile, very and and terms dosing, of for earlier launch tolerability both populations in really offer the in product for to payer. safety, excited our cardiomyopathy on naive for just the is polyneuropathy the sets then really that the and what differences polyneuropathy in going this of are will the or physician, patient to cardiomyopathy tafamidis efficacy And and the

Operator

Our next Cowen. Weber Yaron comes from with question

You may now go ahead.

Unidentified Analyst

on taking question Thanks is Brendan for well. for This Hi. the Yaron. as

infection up in of about to on follow one hep honestly, just readout I the questions B First, the HX. earlier wanted

And everything been going, combo - that study the some all in drug terms of see know based potential forward you And to next to so really guess in last in wanted so how want with in the thinking we've far. given at you moving data is the I think also this you're seen point actually, guess on I reduction. year. years from program, of the last acromegaly, the competitors, difficulties enrollment then bar to much. about just antigen the of how here I couple Thanks Given where has and see

Brett Monia

welcome. one? You're take Eric, acro. first the touch don't why you I'll on

Eric Swayze

as call se. of reduce the what system to earlier, said they mean the reduction is I Sure. enough more that functional clearing than just S-antigen objective, of immune bar with antigen to combine ability create is per The probably the a and virus. then the

actually think impressive I And that published And there, so somewhere, evidence in enough. infection we in could, Phase patients. fact, that, medicine [ph] our don't recently just S-antigen we reduction reported is trial and had major in happen on, alone viral really of that clearances in some IIa showed

is GSK And show hoping Phase to we're - study. larger in IIb hoping what so the that's what to

Brett Monia

schedule And out study, of year. confident very for as well study Enrollment to ahead that is very going this will forward read the readout. looking planned acromegaly II we're and monotherapy this Phase and actually

acromegaly So no in resistant whatsoever. on that to you year also red that patients analogue. come remind last study data the we also concerns, no open-label the flags want that from are to I we extension on there somatostatin out had update And an have

that But we're the to enrollment So forward data have confident, readout. monotherapy. the study, in to beyond going we're we're monotherapy and looking great the has very gone additional

Brett Monia

wraps where much questions I now. that think And we are up the pretty

until throughout updates like the a you great have again. everyone like - We'd to year joined I'd progress the today. our further thank and call And participated providing on look to us on So then, who forward thank and day.

Operator

concluded. now has conference The

disconnect. now Thank you. may You

Ionis Pharmaceuticals (IONS) 24 Feb 222021 Q4 Earnings call transcript