IONS - Earnings call transcript Q1 2021 | Ionis Pharmaceuticals, Inc.

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Operator

Good morning and welcome to Ionis Pharmaceuticals First Quarter 2021 Financial Results Conference Call. All participants will be in a listen-only mode. [Operator Instructions].

As a reminder, this call is being recorded. I would like to turn the conference over to Wade Walke, Vice President, Investor Relations to lead off the call. begin. Please

Wade Walke

Betsy. you, Thank

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

President our slides Executive Development. We Geary, With our Chief on discussion have accompany your forward-looking language are Chief today. joining President And three, Cadoret, on us Eric Corporate that our Monia, Financial posted Officer; Onaiza call of for today's of also Executive attention which Vice would Richard me contains website Hougen, Development Vice Officer; Chief Brett Research. to and Beth like to will Officer; I and Slide draw Q&A be Commercial statement. Executive and Swayze,

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

Brett Monia

commercialization even in successfully our unlocked that our advanced savings LICA. TEGSEDI LICA, products. a further expanded to our to us from also Wade. to steps invest that Sobi of of strategy medicines to key you And Sobi and TTR and from operations. today's are our our by our commercializing taken for pipeline. for we the Most introduced and APOCIII highest more our a pipeline recently, thank wholly-owned This strategy moved year, restructured to redeploying distribution time, and capabilities. Good medicines, we've commercializing we priority broaden new of morning. the include call. therapeutic reach drive significant prepare Thanks, joining transaction Since have own us agreement closer which Last resources transaction number on advance developing that our growth We're we technology and using our wholly-owned

with We to standard-of-care with product or now encouraging the our results, to particularly pipeline. demonstrate X for Based data we could advancing pleased this Phase a IONIS-PKK-LRx, hope were on patients best-in-class further Phase HAE. hereditary disease. from X medicine as the change we're study angioedema into a this the potential of where Turning that with these

with neurological IONXXX initiated medicines. studies recently disease disease and also with for pivotal IONXXX Alexander wholly-owned respectively. two We patients FUS-ALS, and

strategic our with pipeline of across the first on FCS, Given age expected disease LP and patients a the track would Positive little market. Phase is possible the demonstrate X with treatment making for time this from have programs cardiovascular both with modifying the in that an progress the And Phase fall. toferson made remain patients pleased with for ATTR with driven the VALOR are progress we severe with ALS. tofersen Phase X data study unmet we're accelerated need for medicines path regulators in are patients, to these we X with medicines rich amyloidosis, A of SODX-ALS ALS. results These patients chemistry, with of additionally disease project in on in and leadership year, our toferson becoming move we treatment new for development important we outcome It's our of important our medicines neurological LICA is R&D of move routes commercial support advance class also earlier and this our medicines objectives, we of a position as and would launched late closer as also expand our administration. pipeline novel market. toward new next positive In capital large manufacturing project stage our study technology to solidify this This mid the to the chemistries, step diseases. [ph] one the further toferson including and would first-in success And product. capacity.

made and business progress pipeline advancing our have focusing our our strategy. significant We in

After our strategic And and results upcoming call discuss financial will or to to and achieve and catalysts in first of to more our on keep the key I remain that, us XX through questions. the reflect we Beth, Richard positioned wrap XXXX our to importantly, marketed have With track results, XXXX. investments our the Our taking your turn up prepared to preview products pipeline remarks updates year. review quarter Richard, well recent guidance. I'll rest before financial like

So Beth. now, to on over

Beth Hougen

In year medicines rare focused this disease our wholly-owned value Thank new primarily February, the our our reflects to neurological for you, Brett. commercializing metabolic that programs. cardio of and we strategy on provided maximize guidance

with quarter loss non-GAAP net were results $XX revenue, our first in million operating $XXX a Our of in reflected million non-GAAP line expenses, of $XXX this new expectations. and and strategy in million

in our over to million sales. as profit. million and in SPINRAZA a line revenue that global of bottom $XX falls turn our $XXX revenue earned revenues. to Now all royalty generated result, as We virtually

Our first quarter. the the rate revenue at year. prior beginning of SPINRAZA our quarter royalty resets to decreased Because each slightly compared

in respond estimate of prior care in to XX,XXX enhance ages. progress and guide for Biogen a efforts treatment remain we believe to studies treatment the to proven and Biogen's leader patients these of foundation decisions. outcomes SMA take We on plans to forward Biogen steps presence. all highest safety patient with be elements patients commercial markets SMA. royalty ongoing has into to important further reach tier those expect to remains and the with SMA efficacy will reinforce studies additional As SPINRAZAs to where continue by SPINRAZA and the We over XX,XXX market look of SMA well, a patients, profile SPINRAZA The years, mid-year. treatment continue over

generated combined revenue of $XX We and WAYLIVRA million. also TEGSEDI

change in a [technical difficulty] the shift to reflects TEGSEDI a As reminder, guidance Sobi. due revenue and under for our our in WAYLIVRA

WAYLIVRA are model, now which revenues our these Sobi, with TEGSEDI Europe operations from complete of pleased and to Under We commercial in North in TEGSEDI underway to are products our sales distribution America for the product smooth our well this the new also and North Sobi's transition in America. our Beginning on revenues the In net sales. second Europe. TEGSEDI first quarter, revenue quarter, distribution shift sales this shift. from based in in reflect reflected will shift with fees

In sources in from addition, programs. we revenues million our we which partner earned related of R&D first generated nearly $XX the multiple quarter, to

by were $XXX across to with in in same our the for primarily wholly-owned Our compared R&D advancing related expense, APOCIII first quarter, line a which and multiple activities modest LICA driven our X non-GAAP increase The of Phase TTR and the the expenses was operating last programs guidance. year, to increase pipeline. represented million studies LICA period and higher was development

loss million basis. our results With operations. our first of restructuring Akcea our the net than first our European SG&A internally of decreased our this due focus on and for expected, from new our a quarter achieve important on is guidance, aspect growth. expenses And results, difficulty] our quarter, strategy. [technical investing XXXX element to integration primarily of we of the a of As less strategy cost quarter in first efficiencies non-GAAP remain $XX of the An track realized we on to our

R&D revenues we in year, half revenue driven in and key to similar as increasing of operating $XX partner the our quarter. of in to our increase milestone expenses stage quarter, QX expect late million, this IONXX, ALS. in second advancing an be first the year by impart revenues achieved project And for programs. in mid treatment a for to projecting second the the medicine advanced We Already achieve We course for this the development. our increase we Biogen of targeting our medicines DGATX as over we're

high expenses for X TTR studies to LICA APOCIII as Phase Phase into the increase X R&D LICA a advance X as with of initiate PKKL LICA patients we triglycerides. And study our DGATX expect Phase and as study. the APOCIII progress severely We

our to X% financing through second to convertible recently refinance achieve we a November. to fund Sobi interest X% notes initiated. using notes of to we multiple we savings And cost half We second ultimately, financing the debt further Last from million when expect carry the realize goals. To balance our a projects transaction rate, capital accomplish a option. options two completed we These the We offering SG&A in that transaction. evaluated this we X% determined $XXX large notes sheet secured low We due interest this the completed with our capital as our a was primary convertible best expenses goals offering. their decrease and rate. month $XXX million year, of in of convertible

a a our large portion balance manufacturing to sheet support maintain and wholly-owned We debt offering project our capacity. we for proceeds strong expand pipeline technology. to the from R&D of use our Importantly, a capital and our

project project multiyear XXXX and and of cost wholly-owned capacity to $XXX to $XXX complete million. We needs manufacturing complete, between We our the future million in this the we have the expect pipeline. will support once anticipate

LICA we capacity including Additionally, bring new novel chemistry. our forward chemistries, will increase to

And the our enables strategic leadership us to and have on [technical therapeutics. objectives. we infrastructure the project advance our manufacturing critical to we our ensure oligonucleotide Continued This difficulty] to achieve need pipeline wholly-owned build to we of and market. chemistry development,

turn in of the As year marketed important position already XX XXXX. to you and goal us can this to our have call over with growth more to taken that, drive And to see, products I'll we steps achieve Richard. or

Richard Geary

Thank you, Beth.

reporting on angioedema, subcutaneously reduction We towards prophylactic hereditary to from PKK-LRx these execute number Achieving We to of treatment with the successes medicine driving this goals monthly in quarter. year. forward and a X pleased administered positive of attacks, We're for XX% look pipeline with favorable advancing tolerability. Phase greater Phase significant Ionis later to LRx, the detail and of safety value once X HAE together results continue our up IONIS mean or in particularly demonstrated this a catalysts. results HAE.

look advancing hope demonstrate X best-in plans the with patients now are with sharing Phase further our to prophylactic IONIS-PKK-LRx be you X to its for We Phase to class treatment later into study HAE. potential year. a forward this We

in Phase progress with X patients pleased programs our TTR also continue our and programs. polyneuropathy our study Pelacarsen with TTR, We remains of remains Phase FCS. IONIS-TTR-LRx track wholly-owned cardiomyopathy, in with and as our APOCIII-LRx in be including track togersen to partnered studies also as pipeline, and patients on in X the well on the

X second This We expect the X X prevalence this of over has severe year. APOCIII-LRx in of US. Hypertriglyceridemia second a patients study in Phase with study will Phase be a patients begin million later to

because from data of fatal for diseases We development these of paths with patients also Phase From our x pivotal [technical accelerated patients. strong both X hypertension, medicines of patients IONXXX American and AGT-LR studies with to IONXXX our in in stage positive study pipeline, the of on resistant pipeline Cardiology. stage late difficulty] in teams patients of with College Journal for the efforts just expanded initiation of FUS-ALS with our were week and of the mid published are the this of rare Ionis

Together on reduced antihypertensive with failure study and difficulty] and our data together In protein, we've a a medications, ongoing study. finding advanced X in With results Xa which heart Phase a this surrogate on we've also from these open to patients stat with patients reductions three label ACC substantial We We at Phase in Ionis and Rx, AGT-LRx on Xb extension with preclinical growth interim a poorly resistant larger or in and year. controlled in plan hormone learned recently of conference later study results, binding acromegaly discuss long-term these Phase toxicology month. safety hypertension study a [technical for achieve results present ejection marker Based analogues is Ionis, more X ENAC-X.X plan with a favorable this of patients GHR-LRx fraction. detail. to these in study greater later Phase with the we Ionis into GHR tolerability. chronic Samantha

this have we our work able doing While finding, we believe would so to timelines. been impact through would

to reevaluated ENAC-X.XRx. a decided continue development data of the available we totality of and As have Ionis further result,

we continuing which now to We are programs have our evaluate research late-stage for development. of prioritizing in pipeline, a further number and pulmonary

tolerated durable Alzheimer's with demonstrated dependent Biogen and MAP-TRx Alzheimer's study. in Alzheimer's catalysts, We're with X top MAPTRx pipeline. disease. upcoming time these Biogen disease our Ionis by medicine Ionis results to protein, year. neurologic encouraged well reported July. pleased the reductions tau in to three progress patients MAP-TRx were with at results designed Association reduce We from the generally dose and of disease the International Now line Phase the to report CSF this associated Conference this earlier tau Ionis very in was in plans protein

to Our presymptomatic programs onset ALS is SODX-ALS treatment a the patients with or the the also may to effects SPINRAZA. change also the for the the Similar SMA potential tofersen we study Biogen in question with for similarly of landscape. We forms the the all delay profound And patients. address in treated have essentially well. potential effect disease first broader ALS modifying ALS, demonstrate and Atlas of and disease. program to CXALS advancing believe ALS ALS profound become disease progression this addressing to for in are initiated Tofersen and the hopefully FUS-ALS, has even with patients. slow demonstrated causes presymptomatic tofersen of recently this presymptomatic treatment

achieve positioned more that, throughout medicines Importantly, this over the the progress data call wholly-owned with the turn over goal six to back our year portion or of upcoming XX or including to our well next and And of pipeline in more to-date, I'll years, XXXX, medicines. to call. with marketed catalysts potentially close Brett few remain our this we and

Brett Monia

you, In of important Thank Richard. took pipeline. our value the quarter, the wholly-owned to steps first maximize we

advancing [technical difficulty] with continue Phase IONISTTR-LRx And and APOCIII-LRx and Alexander initiation We pivotal X and advance through as ALS expand the disease. to to planned. our pipeline

and We the steps Akcea operations. taken streamline also for our HAE Phase the TEGSEDI and are of important delivered to of and through and medicine IONIS-PKK-LRX acquisition WAYLIVRA positive into strengthen to study. X planning advance We've restructuring this results and

wholly-owned are in unlocked We build pipeline the in commercial commercial capabilities. have and of we out commercial that our our technology key resources our strategy, reinvesting accelerated retain expertise significant

execute track Importantly, to our to this that, financial We're we goal all medicines these our of on our we've year and we and XX on our to financially we will using of achieve and look now I'm are guidance. balance invest in our sheet more strong it With strategic open in we advance sharing already for areas. closer of marketed made XXXX goals. the to medicines more strong or our proud progress And questions. in forward up as move XXXX. priorities

Operator

[Operator Issi Please Instructions] Luca go First question from RBC. with ahead. comes

Luca Issi

Richard. on for to one, Eric much taking hear Maybe questions. my or for disease either so here Huntington Thanks maybe

placebo, same some Roche. ventricle And I low higher time or have substantiate And we to dose think full if data here. such started high accelerated and that a the hypothesis the may wondering that bit from wild dose looks data last actually may the given it over what of the least unfortunately and dose you week increase volume fair at me view type share are a here. matter disease

again, there X. advance congrats on So the And to thought second into any on will Phase HAE, helpful. then program be

Thanks be need placebo there Exciro the some dosing a about so So you dosing? again, monthly us exploring could much. Will give on thoughts if will Again control, Phase you great. color study X or Are any wondering you're you thinking it be how versus will trial bi-monthly to design? head-to-head run [ph]?

Eric Swayze

curves take Hi, set placebo. and entertaining and and of a were those was CHDI numbers and the IDMC you I providing question it data dosing the than hope. PKK true it kick bounds drug But for data its was said a history. little what much It's the at a Eric, had. the look descending Huntington basically same wasn't reinforced benefit. natural more the Huntington faster the the the was that more all at of frequent working if I over guess absolute Richard within And and so presented I'll

need makes we the unpack don't investigate. and hypothesis analysis to think I tell this think what it's sense has discussed, at and of data But As all from valid some I to that learn to which their know we the they see it and can both really and what means really premature study. are to point. We

Luca Issi

Phase program. details HAE forward this question, that front couple the the be months. some Phase meetings later quick will And on of So a we and At over regulatory bringing then point regulatory those we're we the X up that with this into a where next year. just program of moving X have

Brett Monia

offers other I there's are right to certainly potential about on to has think just expected planning advantage, which so therapies provide as difficulty]. be we you be is designs opportunity market what Phase trial the that drug, the that will mean, we're Let for little of is our a I to will and thoughts really and believe over add a this it's with this excited [technical her X X we for do precedent It Phase And Exciro placebo-controlled very be me study. now some too, which Onaiza bit, best we to study, monthly certainly, think is helpful that's the very do what class. a a well. in in why drugs the for significant dosing in

Onaiza Cadoret

Yes, we'd over be here. happy color to add some

and sufficient in Max of very HCP efficacy onset That's clinical I going treatments. PKK we think our the and potential to has it for of test attractive placebo is, kind Luca, based product, of prevention is efficacy, profile a reduction of be certainly question we [indiscernible] for fast pleasing the out at current in the to deliver have, that's of treatment that went a got marketplace kind data and on head-to-head, going it of the options, at or to feedback profile. best-in back versus kind this control including And really the of if to class to you your really, into on will as a the that looked more study that to question, this, we really the are efficacy we be us a controlled, a trifecta profile placebo the demonstrate the and be trifecta attacks, acute we than take look the marketplace. of able that

with just convenient the along very that administration valuable and highly competitive profile. more So a is

going patients feeling prophylactic for we're angioedema what treatment. about this unmet to So very in bring great need to is hereditary the

Brett Monia

as X and said, Richard design we'll Onaiza Thanks, the details Phase provide later this on more year.

Luca Issi

much, fantastic. it Thank you. helpful. Thanks Got so super

Brett Monia

you. Thank

Operator

question Werber Cowen, from Yaron go with next ahead. comes Our please

Yaron Werber

the in December. I open taking enrolled releasing have question. plus And correctly, targeted, with data the this my data aware going looks was XX-week then be it sounds from already? thoughts Thanks planning is be study, says release? second a medical it's this Great. it next to can if of the half, the X And and a Phase for plus any a recall like specifically or this an question be to in OLE. steps extension. It study should that fully you program, label meetings we where the Any about on start you. acromegaly. in you but on with given Thank know what you're the what's like press It's

Brett Monia

statements So, as results the - meeting medical data wrapping the we study probably soon going up one to share into then data to analysis a And and take not that share as to earlier. the half second the we'll we as it's of going the are for don't we'll the mentioned now. targeted have data will us right now. of his the of we're wait because in going And through can, we study be that will year

data acromegaly, for ground LICA the the data data the which data we which a in which for monotherapy out is which Phase and can get that the that also figure progress a label up we off X, getting and study we'll second getting want is look has that now out a review. a detail. didn't is that lose open But share frontline have medicine, to along way Remember with rich we'll summer GHR our accumulated more in set started. sight data to Although more extension to in such we place

versus think the are decision to decisions the Metastatin a make want in for that to we for be. next next then I on program patients would look going population on the data all monotherapy treated steps and the at poorly before steps patient we're what the make can controlled, either this

Yaron Werber

Angelman for then or on And update Thanks IND filing Phase any potential so X syndrome? also much. Great. the

Richard Geary

started hoping to this we're year. Yes, study the get clinical

Yaron Werber

planning IND you go definitely made selected filing and and decision a mean, on You've to definitely if a construct you're I forward.

Richard Geary

Yes.

You got it. Yaron. Thank you,

Operator

ahead. Fargo, The Yanan next with from Wells comes go Zhu, please question

Yanan Zhu

ENAC question. more tox if is you Hi, my Thanks. the thanks route to for lung? study, the findings first pulmonary the update about program? long-term Wanted for the on tox presence related studies, question could whether specific have the from the of speaking - whether the in I it's little toxicology target taking from under the share the administration. to generally just a and And or a ASO

Brett Monia

Yanan. Sure

preclinical have about that investigations. we emerging better in and we going This in of and to through with and it. our are to to do we COPD. of ETS well as We value to data. good patients targets part to our as that just for gave due preclinical think the patients delays, that's of nothing look that in presented cystic those we're phase safety at will just statements. has not emphasize greater Which that with in clinical through they'll figure X this invest patients want sometimes what to pulmonary with target going I cystic And happens stated engagement Richard bring It the tox in at encouraging to was will believe our is this Xa ENAC kind in to be his in later data So do clinical fibrosis as at to results. finding talks very out one types platform read that data The work take something a the And that demonstrated the diseases, for us us in pulmonary took Phase pipeline is associated month. long-term time and the all. and studies the We company forward. disease fibrosis have

Yanan Zhu

very program. phase recently it. LICA tisserand, on a reported polyneuropathy. the And helpful. with question TTR That's Got then three study Alnylam TTR, in

petition and LICA product the how that whether opportunity their for you profile? data, three frequency and of on that wondering administration, against there's profile to take TTR Just see and every Thanks. your an months,

Richard Geary

lot. we Yanan, but not respect But that very year X Sure of people's And the well. say our cardiomyopathy in enrolling very results I to much study in is the And the looking a very the other we're study data. completely position that can TTR polyneuropathy, to enrolling comment Phase on like I study a well. drug forward have it's our next for What question. we'll

In addition, brings Onaiza, bit we've of and of on done market administration Onaiza a to on the research the that quite I have love maybe comment and value would to frequency marketplace that?

Onaiza Cadoret

and more, Yes, ongoing we as should say, weekly be physicians to well to [technical diminishing clinical of TTR, and happy I as to, go definitely from are extended have that care. seeing was looking and commercialization. excited little after dynamic standard I of that really more, of that there that some think more myopathy in market monthly a difficulty]. just we've And well because it's as with we're here data, about to the forward rightly quarterly. products the we're In returns would forward call I of quarterly our the done particularly that difference our think found profile patient extensive understand kind on not the market we've so frequency when law daily But it, at large to all, well, perspective, product, research and between perspective, of to bringing one a a big monthly really a there's profile, seeing most a for monthly. improvements in you particularly key your weekly clinician for And the versus a as question bit conditions, really from are without general, some as a trial I HCP

of be I to differentiation the place that's going big think here.

Yanan Zhu

very helpful. Thank it? you. That's Got

Operator

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

Yale Jen

Good the morning, great the have understood very in a Huntington those on question. the I believe disease guys the tofersen confidence We trial. you And the AIS. for and taking in thanks failure of

stem for you little where compare just maybe seems your from and these mind besides diseases confidence or the would between the better contrast trials? to two and different So bit a

Brett Monia

So very good I'll open Yale, up and it's Eric can maybe question expand. then

disease ALS confident SPINRAZA leading industry it's other plus whole and we're coming a drugs. ways tofersen in of the and behind in our neurological think So in we then platform, and many that in host

All of number there all presented a now, been the and drugs, not had yet. quite

clinical the general we've root X Journal It top trial, we've franchise, the we're is inside Medicine clinical which bodes confidence in is after one ALS if the causes for and of Phase drugs different to our it than based tofersen confidence in ALS data now our that robust encouraging. target of test data successful that on trials was diseases in we're because in two so very the tofersen, even rest our reductions like SODX nice New of tofersen took and know clinical target in the the into preliminary going engagement four hypothesis we in have England engagement All was confidence and for well X. no our very are Phase presented that to drugs and trials the and ALS we hitting high published is some shown in us X our the is lends but preliminary have very in not Phase greater and I said

in with of And brain, question, compared deeper. weeds your neurological part ALS the other different to drugs I had think, The our is other to ask is to being more bit the for to Eric, into Huntington how little I'll do jump pipeline a there, regions compared able target to of diseases.

Eric Swayze

look And the data in in great Huntington. packages to have we at started we alluded paper real have Brett evidence the didn't that X. New we decided England while And Phase things, sure. person Yes, hadn't in and for reduction, Journal the to that improvement it disease, in and

teaching target ability, the a throughout we about of of [ph] in brain. and high affected And medical much of are has this And the affected in where makes talked have that at all could can target the this us the that region. far think less CART And presented can have It talked our we before, high that of are susceptible, comments done good we've target regions of Huntington's a a true like regions sense target about job to lot we Roche treasure data. a preclinical As A extensively of think has I data regions level we in disease. we us that meetings I trove we that that as ALS. case is the can are that target brain that level confidence but the

tofersen especially need that and So target whole of regions. that, targeting brain engage the the program, we very the brain are I our program a competence in to others programs, like have high those can whole level and that MAPT and

Brett Monia

mentioned As in and a think durable. that even this reductions as tau in further that reminder, the because statements earlier, July, of substantial Richards I believe, has will conference, And, that Biogen summer. data be will type end said presented have I MAPT and in Yale, been

Yale Jen

bit successful. helpful. move That's just sort with question maybe assume of decide Okay, forward is ones, X? looking more Let's of one great. to just very seem to HA, little guys it here, Phase more And terms is a you which in the

early be thanks. And to a by curious stage drug, or potentially it this to yourself, you least partnered thinking? launch a potentially, at out, is at whether this Just guys want of

Brett Monia

think this We're and ourselves that great an provide And design Phase X Phase X really not We do. this that we will we're it's will provide or study on it's now. through the update right later a question year. great we a moving not, I the update or keep It's whether Yale. working ourselves. into is one an will And this drug

business make little give a and to update Onaiza's better we'll if just on in So now conducting And tuned, lot stay just tuned if that of case you it's, profiling team you research work you can the an market or right stay not. competitive, while. is a

Yale Jen

Okay, again, for lot. great. the Thanks a And congrats quarter.

Brett Monia

Thank you.

Operator

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

Unidentified Analyst

this thanks Paul, for I Hey, Alex taking two. have guess is on our for questions. I

want you guys ENAC. is ENAC? ENAC just cash to be this one no it thoughts that, going development preclinical longer program, ENAC have Thanks. secondarily, may like related give you're first follow-on to you pursue another have And then talks sounds on to it any any right, in business either a on with The long-term. now? the all or that Do if down with program It curious program clarification knocking the I

Brett Monia

this question So We ENAC have posed. any as the directly the preclinically. that that working in We're earlier related evidence still is was don't I inhibition. to data mentioned through

Let same not sort point, not me types have a this small we're may is not inhibitors, applied seeing that of ENAC molecules point, this we very that of important thing. the effects make to related the made preclinically and observed the observations in seeing we're for were systemically were kidney hyperkalemia, toxicities

a those greatest was to targets ENAC those that delay. believe a we future, is this to really that really both to I slamming And bring trying through quickly. it we're on ENAC, up the basis our this work think based door We're was for that is And pulmonary pretty pulmonary, why program the we ability and focus we it close will for So that we And really obviously think pulmonary continued value. we'll are better in a on on not through all there. with significantly have, does lot the catching start represent our data And think go read targets after don't drugs totality separate. to don't again, is that approaching other And But the ENAC. what diseases. And just we coming the with diseases. the have to of we and although targets. data,

Unidentified Analyst

ENAC on a more pause So than just discontinuation? of rather to be clear, it's development really the

Brett Monia

Now programs. program ENAC we to other in favor just this continue of

Unidentified Analyst

you. Thank

Operator

from Jason The America, go with comes Bank ahead. next Gerberry, please of question

Jason Gerberry

for questions. my guys, Hey, taking thanks

Just follow-up one on and ETT then PKK quick question.

and consistency every your profile, hat over on on about of month, like hearing what want relative of sort just of learn return the hearing dosing a ahead And pertains be as view to monthly physicians on it as in so just drug. pertains prophylactic I to convenience of week of on from a they agents. beyond but in to in weeks a bit And probe you what to just guess terms you'll little I potential terms a profile pressure then think is ACC, because best-in make say kind this of pressure. you hang physician like feature we're aren't on is sure point to it in blood that on data it's of week want able a basis. a sounds dose diminishing durability blood the has we're impact about One it a a dramatic there thing spikes think characterizing PKK, to wanted you looks differentiation, a that's [ph] to it of class convenience two would that you Just key versus main

of data curious Thanks. if a get help attribute might the So about that bit if any ASO understand little you that you're us set table, we'll could your there?

Brett Monia

questions, attribute frequency. PKK again, Onaiza beyond certainly And goes the that. ask attributes key to is I'll Good dosing But LICA, expand. the it of our

Onaiza Cadoret

it's HAE the Zero, every Yes, volume research entering said with the at think the is market always, each its so for talk to these have medicine physician know, the that to as the efficacy you dosing right, two and is high most has here, injection and in only weeks, I I for convenience has good and actually as market, think of I a And compliance. the thing look market you and there. you're as they're important as about in Tech

of again, of deliver do to going we But of faster think back be our just kind that third number number believe of treatment acute ability the max the what's the So of on prophylactic product clinical the I onset patients goes zero play. with reduce important of to that it profile is attack in goes get, attacks, prong that rates we're really reaching to, the not do hat that said, order efficacy. is parameters the that an big our prevention ability efficacy and take. of And to thing these that you as main and on, hang they of you we medications will the for a think to

think we're efficacy that parts us paradigm basis convenience on the the will the it, So takes of really, three of it's all a efficacy product. again just patients deliver have about compliant when that regular you be with the and just winning on along on,

Brett Monia

just rolled to a we've that, all the over to the head open important nail think on X those. of and I all also very label very study, lack on the add three extension, component. long-term And into looking got at and carefully hit great. And Phase that's that's also those patients an Yes, breakthrough, of

Richard Geary

data, get study the hoping ACC and AGT of what what the that. at a presented bit little I then also be to Phase is And but out Xb we're about to talk

Jason Gerberry

piece you'll is mean, to I college either actually Journal, it's no, And to hypertension events. other And that able recovery on presentation I be giving. can't an the now, hypotension the right go available to be then posted been there American important it's we'll extremely the the publication that piece to and puzzle. absolutely, believe and have cardiology or that's

a So And the into very showing on that elaborate is data a study we've Phase Xb clean that's issues. profile. further will moved those

Richard Geary

that and really for to hopefully, X larger raised, a study study, in control, study, you've it's Phase blood physicians study, The dose any in have so blood we pressure select hypotension, Phase spikes pressure, a achieve significantly magnitude of those longer forth. of and the Phase Xb is of study, a nail a to rule it's the really concerns, mentioned powered out to X down expect

the that's mechanism safety the efficacy presentation and this the support certainly study. of first, But the Xb in So the publication intent will drug. ACC Phase this in the of

Jason Gerberry

Thank it. you. Got

Operator

question with Jessica Fye ahead. The JP from next please Morgan, comes go

Jessica Fye

What's is current good this, to it related platform not but it's about for your ENAC. exposure to afternoon. talks much following to up to? on our or questions. notice the be And might Hey, prior thinking related so just the what related in the If you lungs, Not belabor questions the taking not thanks guys, on and the target?

Brett Monia

Jess, we to through but have comes really talks particular know, something to long-term studies. that's thing that experience the other don't from have with drugs. a it that, happen confidence related it it. And molecule, through like sequence finding be be The various we of other could work sometimes of Well, we work effects could

Richard Geary

one looking And many targets. those. timelines I And I early And the in clean. at, in the clinical into - beyond the we can was clinic. significantly preclinical clinical are sure just this so development. we've to we're of want experience, were was experience what we're at make we But by get with impacted focused, have riches the think we and And got further, most mean, that finding, we're so it's a longer term treatment absolutely

impactful targets And some of these are COPD. really particularly in

and very that these of we interesting areas to other want focus some on. And

sure in dosing development, Phase focused. focusing very the So do carefully back. this of efforts. wanted same going we've this we we're we looking took all X now moved the that the step rich have And with program just and got we're to a not At into our at we've products midterm. incredibly and make what we're that late-stage time, And

Jessica Fye

confidence just you disease the about well some the efficacy and that Got you to the able of you and it, how the other the market. study, gives pivotal size of talk might a the on Working you product that have makes to measures questions be is just IONXXX, sense. opportunity, program, Alexander for advance to can into that think address

Eric Swayze

that X confident for function disclosed Phase very haven't the full we really or disease. genetic the the this GFAP. being cause think we're protein We endpoints disease the been gain program. engage remarkable in called the preclinical our And known of We're the It's models protocols can what that's disease. lowering has it's in pretty a good And and I are published this of of what improvements preclinical really work. toxic

have the of disease. I based the So and known pathophysiology preclinical we think the on data here

can this. we're right we the have for of spot programs. you if that think in a I high level very show Onaiza, confidence

Onaiza Cadoret

function, disease of both normalize to patients and going access the gross improve side to motor some are progression. feeling the Alexander's data Yes, significant preclinical for the only a globally, perspective. the we're And symptoms patients this these of models suggests first production and and reduction I we XXX we're GFAB disease. looking again, therapy of that that from Eric about, the and on at the cognitive GI as prevalence think side really that would be have said, And prevent

Eric Swayze

our synergize a the we're disease, talk bit more a we pipeline, these and about bring and if wholly-owned how as market? little together that helpful Jess, GFAB franchise neurological be also about planning to it FUS Onaiza, broadly rare about to all

Onaiza Cadoret

good no, Yes, really absolutely, point.

I these, these have really see be will together, think individual let scale about how kind and have being whole. comes a they're just associated that we've important marketplace, the looking collectively to later prevalence if synergies that for we're in about on, we know the disease. really epilepsy severe as diseases and one together more, have one servicing we pediatric with just but the one of we at, condition, with Alexander's it we an in significant and other, disclosed we a And add as and overlap, physicians also one So, really of be marketplace. ALS, there that commercial products. wouldn't as then may many me great looking when in there's a get we well. pretty were the when treating for don't synergies the them Lafora but we're them, And high And think though FUS even you actually disease

it for So nicely in as us very, comes portfolio neurology. a together very

Jessica Fye

seeing the peak in back tier that royalty from [indiscernible]. a similar SPINRAZA, year, can just midyear, the maybe some comment going competition underlying And in U.S. to of just you're X little question, about the a of unpack you around it. last assumptions last light Got to the that reaching the

Onaiza Cadoret

Jess, So hi.

very gets has I past at XX% tiers, continue they recently, our a on have over quarterly look to you few very we four years, the basis are And tier a quickly, as rate highest we we can on that similar sense is maximum and therefore as therefore, into path, up our the royalty quickly, in past that when it that get to years. and us rate, the SPINRAZA, you perform there the think, the get see, So effective timeframe would very quickly. as similar tiers, royalty into will and

Jessica Fye

you. Thank it. Got

Brett Monia

Jess. Thanks,

Operator

go Foroohar comes Mani Next from SVB Leerink. question with Please ahead.

Mani Foroohar

Hey I a the little guys, dead taking I'm bit. dead beat to hate a thanks beat for horse going to question. horse, the but

and a is in that some is you what of way maturity mean going would and what in would have data, closest of construct said? to where with have competitor, question. redesigning the have the you're that interpret I given requisite ways your preclinical ENAC is to competitor saying on this you're different would forward feel you're required around talks. right the lead another you getting So moving the And terms getting and comfortable interpretation and been not are in been that of back right that different a

Brett Monia

the first it to different better there have have have next We further greater going be that might targets think epithelial we provide data. sodium the was don't an along might think disease was we're bring that we're we what the require was others best broader not. working was Trying channel benefit we but that greater But ENAC. answer on to through drug even we out still what's to is? that to in that there or figure question, lead value So a out that because more path will that and the that we are forward that our think drug

Mani Foroohar

have switch? would versus existing as patients lowest commercialization see diagnosed Like what the a therapies exciting you a on HA that of lot And superior really optically have approved best-in-class continue therapies? to strategy, presuming think on sense. the makes And of any label openness for Okay, to the prophylactic to what's how have willingness you obviously dataset, primarily then a trial newly a you obviously this to by event hasn't commercialization, time Do you profile? lead think to appears commercialization comparisons hanging enough fraught switch be nature. asset, do about do from group of the reduction market you know, improved a how had and as cross think quality the see about other you are fruit? available kind you obviously of about in When the therapies you

Brett Monia

Onaiza.

Onaiza Cadoret

to happy take here. I'm question Yes, that great Really one.

entering about market right? we, have this, patients, the we've over of go. clearly for here, when This we it's patients. prophylactic is I profile, best-in-class know, it's choice, new you're to think best going treatments, as So the, you new for think tested that on kind the we the that's where

the our compliant X patience, in well, really I design be there actually on different as they're nice full this and And so know, already who therapy, well. there particularly that are our evaluating think, definitely sense there's are confirmed, looking added thinking as will whether happening, know, definitely a we that that there, we're a attacks we're a breakthrough patients variety do switches are, in not therapists patients in there get at ways. would be there although will benefit For Are of do of design are set you switch of of on it's you not the who how to I marketplace? an opportunity believe then in Phase of be, we're kind

Mani Foroohar

clinicians what to to guys. What modern me. adopter patients you the switch proportion et modern of share them proportion sense we interactions, think, we cetera? have and prophylactic and fall you of makes trial on patients cable effects where That conversations, early are, that enough based for on into What portion clinical most are a experience? of therapy do And early meaningful do your of those breakthroughs population that see sense

commercial yet. know Just asset far ballpark, a from being quite I we're

Onaiza Cadoret

percentages Yeah, it's on good you to hard that, here a over give really question.

and database do that. analysis we're look claims, a going sense do think to some to a retrospective I better get of

insightful compliance lot of and would is to for very a right us the volume and high were the patients are actually the think, this out most, help four who over but list again, in, part profound definitely texture it's research that weeks, the that are just there give in weeks, and it's of stretch piece because to weeks four given So evaluate, our you trying I two a administration. was

who result and attacks. a not of complying, are then a we people see have breakthrough do So lot as

little that to I our before I to think can where it's take going bit part is. that more of quantify give sense you on work a better As a

Mani Foroohar

queue. of are to makes lot going hop I That there back know, waiting. sense. Thanks. And of I'm lot a in the people

Brett Monia

more, Betsy we'll we'll have close one out. take to Maybe and then it

Operator

Please go Myles next from question comes Minter, from Blair. ahead. The William

Myles Minter

me Hi, squeezing thanks for in.

for higher a on [indiscernible] program. the for Biogen question sort pushing of dose a Just

the raid in see clinical dosing whether there's maybe and we'll whether the stage, or push room wondering got the to in are it's that programs that's that any Ataxan And push a kind programs through in and Just veil FUS earlier scenario. the of a dose SPINRAZA those studies? early any afterwards likely the like for

Brett Monia

the So which is very that the plan tolerated. drug is well

and SODX committed very as ALS, is ALS. in particular and CX So Biogen's well ALS to

moving want those get And Phase three, so, you before right. make into sure you to

data wanted they more there, to and So examine get dose. a higher

very through tolerated well really more your plunge So for to question. drug I before quite don't really get anything ALS that experienced X. new want think the Phase era. the didn't get that taking than read and is And more the they the It's FUS I is

selected those. have We

program. have X that Phase single evaluating We a we're the dose level for

dose to FUS So ALS, think we're ahead, at deescalate. not right don't plowing in we're we look planning have doses we and to dose multiple the we plan escalate or

Myles Minter

guess was that was question. I that Okay. my

I know a testing here? in They're programs like this involved why specifically? risk of why higher wouldn't like doses. program just you protein? not but of even a Just with dose sane a knockdown the program, off the they're the there the on overshooting go higher FUS Is Atax

Brett Monia

like target No each that that risk is over overdosing of or toxicity anything drug different. on

lowers do have transcripts for only our XX. Myles drug expanded of the or only of So drug the way we illegal C&I nuances pathogenic, the the CX because selective an are and processed,

don't So look we C&I. the for nonpathogenic

Myles Minter

for Thanks cool. the questions. Okay,

Brett Monia

us today. Myles the throughout and to and thank year been joined results more like of year who everybody Thanks, those you. on and, highly sharing to a call start remainder the I'd with and to forward It's our that, eventful with we look the

and have day. So with that, thank a great you

Operator

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

now may disconnect. You

Ionis Pharmaceuticals (IONS) 5 May 212021 Q1 Earnings call transcript