IONS Ionis Pharmaceuticals

Wade Walke VP, IR
Brett Monia CEO
Beth Hougen CFO
Richard Geary EVP, Development
Onaiza Cadoret Chief Corporate Development and Commercial Officer
Eric Swayze EVP, Research
Jim Birchenough Wells Fargo
Tyler Van Buren Piper Sandler
Chad Messer Needham and Company
Esther Rajavelu Oppenheimer
Eliana Merle Cantor Fitzgerald
Yale Jen Laidlaw and Company
Jessica Fye J.P. Morgan
Ritu Baral Cowen
Josh Schimmer Evercore ISI
Call transcript
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Good morning and welcome to the Ionis Pharmaceuticals First Quarter 2020 Financial Results Conference Call. [Operator Instructions]. At this time I would like to turn the call over to Wade Walke Vice President Investor Relations to lead off the call. Please begin.

Wade Walke

Thank you Allyssa.

a encourage Ionis go press that website related tables I section the release we begin GAAP financial the the of to including will we discuss everyone financial to to Investors and to today. Before non-GAAP of measures reconciliation find the

of business. believe We economics financial how and better results business non-GAAP we the represent our manage our

Officer; With Brett on Development. also website to Vice Executive today. posted Monia discussion are call slides Executive our Hougen Officer; me have Financial today's We our on Geary, Chief and Beth Chief accompany Richard of President

Additional three Development Research Eric will Cadoret, contains statement. language which your would Commercial of Swayze, for us Officer draw Q&A. I our forward-looking Onaiza and Chief Corporate join like President slide Executive to Vice to and attention

forward-looking to the We'll certain subject are are additional results may I which These filings SEC our differ and actual details. based discussed to beliefs. and for current our consult statements materially. be risk you making factors expectations in statements our risks uncertainties and on encourage

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

Brett Monia

morning and Good us for you Wade. Thanks on today's joining call. thank

established commitment quarter our strong and everything for in business sustainability team. to unwavering in transformational deliver Our of remains performance Ionis our the reflects the foundation medicines first the was patients to which of need, we do.

of our our of dedication pandemic. beyond successes the patients goals, many while to serve the to who business our have organization, of proud and executing already our are dedicated achieved effectively our medicines. on above I'm managing the and we've across on Because going employees depend response continued our

potential operational capabilities. given of reach We balance track sheet. achieve the commercial Ionis remain and late towards from We our near goals a are XXXX strong term rest approvals, approaching and our position building momentum broadening owned our advancing pipeline our our pipeline, of of to stage on technology strength advancing the our of

this for our financial Moreover, are year. guidance we reaffirming

Now the performance achievements, our we are and new markets recent with SPINRAZA's to strong with starts briefly continue in impact, pleased from of global growth patient medicine. dosing some maintenance continued growth recap COVID-XX. our commercial despite

And consistent maintain with underway. both WAYLIVRA quarterly new country launches TEGSEDI and growth

important also GENERATION Phase the continued HDX in to study tominersen Our in now deliver Huntington's patients disease many pipeline successes. of Enrollment has X complete. is with

completion While program with to important living there's closer bring so a much one to providing study for continues Phase disease. very planned its for this devastating advance. to to now, for do X treatment to AKCEA-APO(a)-LRx step people this

received with reflecting recently need in treatment the with no that US, approved cardiovascular APO(a) disease unmet Fast designation Importantly, Track the with this options. significant exists medicine a million driven

now proof year will and from LRx both top studies angiopoietin-like and which earlier later line concept this we we as studies to Phase full the nusinersen. AKCEA-APOCIII-LRx from to of Additionally, We plan reported results X this positive Akcea Akcea, X present of refer year. data

world. partners We and XX clinical the over our underway sites around at studies have

in countries studies our the While minimize some we operations. impact disruptions, COVID-XX have early we studies that most and remain the in impacted strategies pandemic experienced to primarily of our limited confident business clinical deployed mitigation by should the

total the SDS ahead, bringing track APOCIII-LRx with X on XXXX Akcea to studies in remain of our biomedicine. priorities objectives. continuing invest of Phase achieve to We expected patients with strategic Looking in six we're our to and initiate and X to us Phase a study

programs results re-file from in proof NDA several of And We're for this additional concept on the plan the to US. year. report to track we clinical WAYLIVRA

to through We our are well or positioned goal of XXXX. delivering NDAs achieve XX more

closing will followed up discuss Richard I'll progress. the for brief after to our who review the by performance, I'll open questions call call And some now Beth turn pipeline over our to financial then remarks.

to Now you, Beth.

Beth Hougen

in pandemic position COVID-XX We a Thank substantial the financial of strength. you Brett. entered

Our first to ending in our year XXXX our guidance including line meaningfully with us this results financial enabling quarter reaffirm financial profitable. were projections,

quarter, first the we sources continue multiple priorities. from revenue During in and earned our to strategic invest

of $X.X of March. at end and remain investment cash we billion capitalized, the Importantly, well with

Over our financial that balance and achieve we strengthened position to last enable goal. our and sheet have years, and several consistently a near term the longer us will sustainable constructed is

the potential in reducing expense late debt undertook future prudent while Moreover, resulted dilution. interest favorable schedule substantially debt year and cash refinancing last we our a maturity

of was an increased we On increase SPINRAZA performance, Our the over year. component. the of commercial royalty compared XXXX, $XX approximately XX% same of revenue revenue first last of quarter largest period to quarter the XX% nearly SPINRAZA's earned first strong which million

At on patients US, initiating the all regions. the adult driven patients In SPINRAZA end was by worldwide. treatment US, growth of March, XX,XXX Outside in SPINRAZA major reported primarily was there the treatment. were growth nearly

also Importantly, more continued quarter, first and to significant continue compared to to the potential and markets, because in of QX of number the WAYLIVRA see and patients grow than in TEGSEDI XXXX. further untreated invite established we growth. Product of emerging doubling sales for

Today TEGSEDI countries. now diagnosed in the with and with [ph]. AJPTR Akcea's testing physicians number over XXXX genetic being using available a are In tested is program growing commercially XX US of patients

current and physicians subcutaneous is COVID-XX environment. attractive which are to TEGSEDI, particularly Many home in patients its choosing at due administration, the

with coverage broad to for commercial including of US Additionally, coverage, secured continued translate access TEGSEDI patients Akcea market term long insurance. efforts have into XX%

Austria. has the Spain TEGSEDI Akcea patient because and region. obtaining expanding progress amyloidosis made progress throughout pricing population TTR including in outside important U.S., is in southern Europe. large countries, recently also additional has the this access reimbursement in Akcea pandemic in made of and This most

working dissipate countries this intend Latin drive help will expand region. PTC that access expansion that in in and year. TEGSEDI In pricing is We Therapeutics growth TEGSEDI to Brazil, into new America, secure

of Brazil in goal filing a their France reimbursed PTC in authorization year. Now working and turning is to to WAYLIVRA. Akcea on plans marketing ATU in and This for launch in additional the access EU market is WAYLIVRA now through the early program. Austria, year, Therapeutics countries, towards Germany this

we The or rely for of which for partner particularly as times. medicines fact we many WAYLIVRA, our place year. growth multiple these revenue. revenue broader from into both foundation product not single do is access strong valuable this generate believe and achieved markets TEGSEDI expand new is is We our a and supports has Akcea that a during on one strengths, uncertain one and sources that in

in In several earned addition QX our other We revenue franchise, commercial we neurological three medicines. than from $XX for programs R&D our for revenue including our disease of they under $XX disease In revenue to as from Alzheimer's numerous IONIS-MAPTRx advancing medicines million medicines and advance. partnered collaboration. within more million Biogen earned

revenue $XX payments earned our a included AstraZeneca the we in earned advanced when kidney cardiometabolic for $XX milestone This of million franchise. from treatment R&D And disease. we million ION-XXX

the same last $XXX QX we earned the Novartis As year, given AKCEA-APO(a)-LRx lower was R&D expected, from million period year. than they when we revenue last licensed

continued R&D in to We revenue be driven programs. by from revenue significant and commercial this year numerous revenues expect growth

non-GAAP driven Our Akcea's pipeline. XX% global and period our of our expenses LICA same to by increase investments and WAYLIVRA last to Rx for This nearly in TTR first quarter operating the Ionis-owned compared X is Phase increased year. $XXX million program the launches the TEGSEDI

last reach expect As broaden technologies made invest of late strategic year to could in in we when the we did technology. goes year our we investments the complimentary also technology, as on, that

investments. fourth last lower Our quarter year, of these operating because the of expenses in QX principally were than

this And full of such in included for investments year are guidance. objective types an operating These year. as are us important expense our

we first basis. non-GAAP With nearly results, of with loss breakeven ended these million net $XX the quarter a on a

million us and year for results and be in rest projections first revenues enable with meaningful and project including guidance, generally financial this QX, of We QX the Our $XXX QX to line excess of in QX. with profitability. increasing our XXXX quarter reaffirm revenues will in

operating with We year our as increase progresses to expenses our guidance. line non-GAAP the expect also in

ahead cash priority sheet our well the XXXX, the strategic on term of Looking strength and balance even challenging our we to and by environment. have Enabled strong in billion a the we COVID-XX and financial near with to investments. pandemic in resources execute longer $X.X remainder capitalized remain

pipeline. turn update I’ll that, with call provide an to Richard, And to on over our the

Richard Geary

Beth. you, Thank

we presented advancements our to by development. the achieve continued While managing of pipeline have medicines challenges in COVID-XX, over XX across significant

study enrollment help rapid us medicine in treatment Phase the for our previously, Roche enrollment profound GENERATION caregivers effective tominersen, mentioned As global, X development Huntington's commitment to of find The reflects the study, completed disease. treatment and in for this HDX in patients the disease. of for an devastating disease Huntington's this

continued Roche advance of to pleased on We potential ALS. Biogen studies are that data two medicines remains of with the forms program addressing with for recently our confirmed two XXXX. in especially genetic clinical that this track

regulatory path, form deliver in substantial of inherited addition X of patients the X therapeutic track The IONIS-CXRx of underscores Phase to in designation Phase the in these who the U.S. medicine fast-track recently an may and no SODX-ALS and benefit enabling options. common expedited to most granted with this ALS tofersen designation study approved CX-ALS. have IONIS-CXRx was the fast study

We Biogen have IONXXX of track our about vast ALS. excited the enter to the development to year. patients ALS treatment We're the for later expanded this with patients franchise clinic On also and first particularly addressing ALS. majority include our with enter sporadic of medicine, medicine this to

attention to SPINRAZA well of and of SPINRAZA, continues efficacy our safety durable to the established Turning grow. body the profile supporting also evidence

SPINRAZA. was dose DEVOTE treated in of Phase X/X with first patient study The a higher

SMA the patients clinically demonstrated potential months safety a Hammersmith this to scores well-validated achieve all adult ages. published of the data Neurology SPINRAZA an treated with for in And on and that and with SPINRAZA demonstrate even from Based safety teen independent improvements profile efficacy profile. Lancet in has new continued meaningful patients favorable study greater XX of study

and first three hereditary during myopothy. a neurological Phase for diverse central nuclear rare initiated beta addressing and Also fallacemia and including proof-of-concept of diseases X range partners the our angioedema, we medicines studies quarter,

their our Additionally, we're disease the trials. set programs in including Lafora, programs closer our Alexander, prion owned which excited move to and growing of for continued Ionis for first pipeline, to particularly neurological disease,

significant Ionis including pipeline area owned medicine. ranging cardio-metabolic a from to Addressing both and and of large partner very Our diseases to be focus for rare continues us.

millions driven may worldwide of therapeutic patients disease cardiovascular granted underscoring with options. established AKCEA-APO(a)-LRx just bring designation fast-track no of an significant with Lp(a) this the effective value medicine to

cardiovascular the is no X horizon significant Phase from outcome on of today And timelines. study Importantly, as expects Novartis partner Novartis. of AKCEA-APO(a)-LRx with progressing study COVID-XX impact our

studies additional proof-of-concept we demonstrating advancing and which triglyceride risk tolerability LICA X reductions are from in achieving safety AKCEA-APOCIII-LRx earlier and top part results our primary and factors robust reported favorable substantial profiles. this year, Phase growing their cardiovascular and of medicines And pipeline, lowering key Both vupanorsen. line endpoint, positive with

forward studies look at to we a presenting data the conference venue. medical or year full this other from And these

the for X of APOL-X for owned into and targeting targeting IONXXX diseases, Phase treatment medicine also addressing NASH. IONXXX treatment new We of Ionis advanced the broad disease including DGATX development, cardiometabolic medicines very kidney LICA

in progressing related in briefly the patient for are AKCEA-TTR-LRx CARDIO-TTRansform enrollment studies is Enrollment COVID-XX, new both in with TTR studies patients, patients in risk COVID-XX of And an TTR in Polyneuropathy and response cardiomyopathy. complications. patients in which high at NEURO-TTRansform we Phase X these protect with to effort to paused

us this studies. data preserve It integrity for was to also at in stage the important early

However, both eased. and come sites as restriction enrollment as studies, resumed have online local regional has in back

timeline Importantly, the these impact do this expect we not studies. free to significantly pause of

needed us COVID-XX We're respond pandemic are which number evolves. believe well. if we challenges with monitor are as each presented to program continuing a we and managing of ready the

priorities. adapted to XXXX pipeline remain and to advancing on enabling has environment, track our team current continue successfully us to our dedicated achieve Our top the

this in new to we this at for track in or initiate still the plan with continue on for WAYLIVRA year. of add Phase to to concept to US NDA FCS. another data we of the AKCEA-APOCIII-LRx year. expect And pipeline. four proof We least clinical re-file study our We X to programs more And patients planning are more medicines remain five

close And call this to turn the over of call. with back to that, Brett I'll portion

Brett Monia

Today, ever. Ionis stronger than is Richard. Thanks,

are financial our remained well capitalized guidance, sheet. and strong XXXX reaffirming We for balance the we've

enabling and the effectively the COVID-XX patients to by managing strength us shareholders Our are pandemic. continue sustainability presented and while challenges delivering to value

progress to significant deliver our remain year, and we our initiate on of continued which all advancing approval in another X are Phase medicines. We've commercial Preparations this WAYLIVRA performance to year, US. of from Already underway Phase to all in X well for re-file programs, made the program strong track. this

year. numerous X and into are We track Phase on We reported this medicines. initiated would this more the Phase our resilience None two X without possible five from or new move studies dedication, to X data positive and of Phase development and of strength programs employees. like be

continuing COVID-XX. to I am deliver how we to posed incredibly team to mission the our to transformational Ionis are in by need. employees, challenges of patients has effectively medicines execute proud Because our the responded of overcome on

developing strategic owned including priorities, in term XX our capabilities, and continue pipeline short to Ionis on and of we strategic achieve for advancing track the longer applications commercial invest new we XXXX. remain our or in more including building to drug medicines As our goals, delivering through our

we momentum reporting year creating as this year and excited future to have this and tremendous that beyond. on towards look about rest We throughout successes the beyond. the forward and look additional we're I'm of

the that, with And call like I'd Q&A. open for


We will Wells now Fargo. The the instructions] Jim from Birchenough today question-and-answer [Operator question begin first of ahead. Please session. go comes

Jim Birchenough

framework on on commercialization may congrats one, through to Iona. internal number at we Onaiza and Brett, thoughts if I guess work model situation. get the your versus on your the establish and A guys, affiliate the maybe commercial be few updated working some all progress Hi, model that maybe could COVID-XX questions.

Richard, we expect And we to program, look one final that Thanks. for remaining the Beth, any R&D by is just just in in then time then stable what on reason maybe patients decrease? that CF And there think the year-end and should for or or pulmonary for consider should is could revenues, over one data CF just program, something should increase that terms we of there?

Brett Monia

Thanks for Jim. the questions,

I'll So, Onaiza also But pass there. on as who for take suggested, the call Q&A. start first you to the one -- over I'll to it perspective I'll her give is I'll take

earlier. in stated just So, in our -- we now as our call recent,

and identifying of medicines each the Ionis prioritizing to together expand bundled pipeline they are the synergies the and the build and ways. pipeline and in value that create, characterizing We various as when owned to continuing in

growing looking hoping this those options we're bring the strategies of These commercialization some strategies value that diseases. year that to towards are And principally this various pipeline we're And we're focused at on those And in rare fall. greatest Ionis will and identifying to opportunities later year. on present shareholders. the

and in jump please add to Onaiza, my comments. that With

Onaiza Cadoret

how Jim, are the Sure. question. Hi, you? for Thanks

So developing we're progress in our commercial just making good strategy.

investments. As is making Brett Ionis to future. the owned We pipeline just in certainly we're further grow expect said, and the large even

preparing work can is market, positioning it's synergies. in the what you And which So portfolio, and the steps in our innovative the level in our we're a we have been portfolio out privatization. laying products initial have on imagine which strategic identifying is the high high deliver commercialization on facing how need strategy unmet where customer

last beta As excited well Ionis time the portfolio owned non-transfusion which a include priority. result, and we the talked to continues about a And we be dependent hereditary angioedema. about remain thalassemia, as mid-stage portfolio acromegaly,

at We providing So at more owned strategy have we I can portfolio Investor a forward Ionis Day. bit really commercial look for the level and this likely get later to currently little time. the plans fall deeper that a high

Brett Monia

you Richard, ENaC our want a little talk Onaiza. Thanks, to about bit? program

Richard Geary


will complete moving is program we ENaC summer. expect that the a So enrollment forward at pace this

report exposure be the should What weekly so weeks expect relatively a later that And short-term is fibrosis to of out of of cystic inhalation six to we able do we product. the portion study expect year. this

efficacy target engagement. And we safety the and based some expect on

So the know we'll that's essentially end what this. by of

X completed normal fully a that shown And data be volunteers have in and in has the also Phase excellent rollout. safety tolerability. We including we'll trial

Brett Monia

pulmonary to right And ENaC now the few to when only but studies we're Phase a CF, that about other about. planning out, that I able for quite potential planning in that excited talk additional we are roll develop actually, in will not drug also inhibitor. front there's suspect we Phase for opportunities We're X Jim, quite be our that

other question. want Jim's you Beth, to take

Beth Hougen

Sure. Jim. Absolutely. Hi,

be is -- revenues that is mentioned QX exception. of I What that this you I lumpy is to tend earlier in anticipate and year as as likely QX, R&D would like no So look going to know, revenues. terms

R&D be revenues more tend loaded partnerships Our to backend from year. this

for to expect to and QX and R&D would I course QX, from this growth revenues, the I grow So also our expect primarily, commercial quarter-over-quarter in of year. revenue revenues see remainder of the in

Jim Birchenough

guys. Great. questions Thanks taking the for

Brett Monia

questions. Thanks, the Jim. Appreciate


ahead. The of Piper comes next Sandler. Van Tyler Buren Please from question go

Tyler Van Buren

the Hi, more with of results But mentioned should taking for or upcoming question. expect you catalysts. guys. these I the them. some that to Good proof-of-concept morning. respect know four guess I Thanks we could us? about? at readout that for in see excited you're those least maybe four specifically just order you'd you two you that to proof-of-concept? one highlight or And And need to achieve review most the what

Brett Monia

happy Sure, Tyler. Thanks. to

our So We studies objective back on to in six this X successful have is later as angiopoietin-like and two now very which Phase just year year is X LICA bag with a the step, which partnered up out outcomes this to proof-of-concept our licensed running half was to two year. a already Pfizer, APOCIII and X initiate FCS. LICA, read in reminder, with clinical Phase with this study a

track clinical this number to a six in controlled, hormone our read of have year. this And receptor, year. SFAs looking readouts acromegaly to we're on expecting patients those who not at as readouts opportunities which for is growth We program achieve on clinical such are out endpoints on We're IGF-X.

angioedema to program that program a have readout a we're this our LICA Hereditary is from another also on year. expected later PKK

In in ongoing. have exciting program is exciting phased hypertension. addition, Angiotensin where have we we an programs again multiple program an

And that as this hoping well. to later share we're data year of some

they'll seen or not there's program some beta be potential coming to if XXX data they'll our from for this In to or go the year. addition, into next thalassemia ready be go remains whether year

study evaluating we that have mentioned. the course, pulmonary also the AstraZeneca. But in And already addition, diseases ongoing we're in Richard with ENaC program of for which

year as on formulation partner. whether readout an an target clinical well hope which in now, and is oral this determining the testing program our data undisclosed evaluating present that Our later for to we

year that. about the of rich second half pipeline updates we're of really a set coming by that excited this in quite So

Tyler Van Buren

this attack AKE. guess the care prevention pretty up a goal, achieving of I quick high injectables have that just launched for in of follow Maybe reductions standard is rate. are terms on

think you do goal duration with that the could LICA? the or upon improve is So you treatment extend to

Brett Monia

you're rates received with the the So competitive. have right. absolutely in current medicine. landscape substantial The benefit is patients attack And quite reduction in approved AKE

to that pathway. of better mechanism action Our kallikrein objective or blocking with as is do as good the our

it, infrequent of may can the convenience think we potential subcutaneous we're studies very the into us data, also our And crack we than impact in greater an convenience a seen some XX% kallikrein. We're a have a as X you significant advantage of molecule. is ongoing really beat to drug We in oral if injectable, injectable but volume with reductions potent as Phase having going standpoint. formulation have very a viable large potentially, low for bioavailability having a the move commercially oral from well, would which be that we

is hopeful we that environment. it we compete. a we think So can are competitive And

our The later coming kallikrein other exploring indications potential are And add together to year this just is of thoughts this our thing inhibitor. at that for on to maybe we Investor those. And we're plans some I'll move to additional hoping Day. on are share

Tyler Van Buren

the for Thanks helpful. Very question. taking


of The Gerberry of Jason Please next ahead. go Bank from America. question comes

Unidentified Analyst

you that couple for that. this follow if a sporadic Keith have for a how the about, TRS. this be? opportunity how on can I question. for population efficient first guess on the guess is have ups the Hi, after that large taking Then maybe broader the Jason. I is I umbrella? within TRS sporadic market will talk XXX Thanks one for on couple I our

Brett Monia

Sure Keith.

ALS about excited very program. our we're So

you due there data sporadic, our next data and causes tofersen X multiple out read out know, which and of genetic year Phase targeting are also next X due read is Phase two SODX-ALS programs ALS, and CX lead for both are As genetic year. our

study first. objectives bring distant first that to year the compelling in key our is targeting data several drugs this ALS Biogen. and target of and our The not exciting forward we're too future, started one planning with preclinical This get very to sporadic X. It's is the Ataxin is clinical looks of this

sporadic with sporadic get believe And majority variety. of patients you ALS the patients to Ataxin represents no of believe it and that are the vast I perform know, address ALS. the majority, somewhere that with north population it's couldn't the to as X And of reason majority, that quite majority well XX% simply.

really is patients potential it's drug treatment. of ALS that the this with majority So

Unidentified Analyst

it. Got

studies you I sclerosis kind think second Are do was for different you to second question cause sounds population. heterogeneous My that formed? different address that you question. into of all And mechanisms ALS? like experimenting planning bridged how my mechanisms it the to multiple could

of set about it, depending be And will I thinking think maybe are that it, XX%, upon great? like up you Thanks. the the address plenty we [indiscernible] of XX% [indiscernible]

Brett Monia

the much to population sporadic X hard of how would Ataxin It's say address.

there's population and -- couldn't to that of reason as hope majority vast Our no sporadic mentioned. that we believe the I target

research animal have multiple ALS, mechanisms, models in very program we're for targets a exciting We which Biogen in with sporadic multiple evaluating ALS.

add on this. could you how color mechanisms of we're little addressing types Eric, for and doing more alternative a going the Maybe, about

Eric Swayze


So Ataxin preclinical find the the clinical have very is which really exciting out the for by Brett and in and has compound, which think that mentioned populations strong. figure trials we as very respond way published best to the out been patient work, I mean, I exactly

as disease. potentially we ALS, that have of very with pathogenesis Biogen, mechanisms genetic, the And looking mentioned, to and all of the contribute broad forms all sporadic at could program familial, a Brett

trying looking are for we're combination the and moving condition. pathways of best figure to so sorts different or forward at And which to -- of treat all the drugs drugs out,

very more deep I'm So certainly coming And have it's programs broad lots forward. program. a we'll optimistic

Unidentified Analyst

from when one Can the follow-up XXX you final data we clinical I just expect year. me, could Maybe possibly it. in advanced believe, plant about a next? Got talk

Brett Monia

the You're referring to sporadic?

Unidentified Analyst

Yes. sporadic. The Yes.

Brett Monia

just wouldn't earliest. so starting year, data year I this at till expect Well, next the Yes.

Unidentified Analyst

Okay. Thanks so much.

Brett Monia

you. Thank


Company. Please ahead. and question of Chad next go from Your Messer comes Needham

Chad Messer

Great. or there steps team with to Like are are in my Ionis refilling, hear data interactions it things the any at need be start to Is certainly that I'm maybe of sort really in you this liver can occur? to is managing the And a collection questions. glad that the through pandemic. left? us well Thanks regulatory for taking so walk

Brett Monia

Chad. Thanks,

for We've on for data data. very about approval to we of and evaluate the U.S. to that that collect we and that has when refiling WAYLIVRA FCS. amount for grown U.S. the we've collecting Akcea potential a were we're for the for And received we are additional with confidence So in been substantial the continued U.S. CRL approval as in excited original

more confidence our with productive. We even on have Our for grew we had WAYLIVRA. about supportive discussions discussion based good very to the with meetings talk And and FDA about them. those been the feel refiling have

excited. we’re packaging What we’re So we’re it year. file this doing now up is data, later putting the to ready and getting

you do to Richard that? add want to anything

Richard Geary

have we affirm, regulatory to more Only interactions. no

pre-resubmission with data there. We encouraged met have our resubmit then meeting the and to that is

just package so together. we’re that And putting

Chad Messer

And the learned to APOCIII great. Okay, or is pretty much, approach of should study, having gone through this Thanks. look the going on all there were like just we that FCS assume lessons then some upcoming LICA before?

Brett Monia

design use so that APOCIII have know will build all to experience from X information of for and elaborate we our LICA. as on Richard? we much you our Chad study Certainly experience FCS in Phase

Richard Geary

So work a first not couple study. patient through in be in outcome, this included of WAYLIVRA, has hard at of development the things reported study as were included developing moving a that which was been the will Akcea we

that's So difference. one

consistent the enrich ongoing be real have There will those and for and on who for prospectively patients pancreatitis also a focus pancreatitis. will

is that another So the will trial. different. bit Otherwise like look it piece a will a approach lot that

Chad Messer

already but really maybe of share, DEVOTE in we then talk one. this seems I SPINRAZA it unless expect the can I maybe was much one have potentially And hard that we efficacy us it efficacy a a helpful. delta trial could of with mean, how large through study. convincingly know like SPINRAZA maybe you just the what beat don't Thanks there. kind on the Okay. to and

Brett Monia


example right, But as dosing, end for efficacy. will feel as greater SMA us. absolutely I very to an but patients not do The there a -- doses, a that SPINRAZA all higher Biogen, believe that's maintenance for potential towards going of we show returning the mean, even symptoms efficacy forms in DEVOTE our the maintenance that high dose. Chad. in also some but You're demonstrated all does between to study, start has start only bar, has sometimes of to of

That's efficacy their the they a one in get example. The greater patients more have on those potential patients, have potential progressed, in we before example. later they've gone disease, to for we before just show have to later SPINRAZA that diseases even we

others there's and ways to show there's efficacy. then other And greater

the that that based has know, way. of a study. have in substantially higher safety as is pristine And on demonstrated, So, under SPINRAZA going we DEVOTE the dose you significantly study, luxury to our

believe of So, the have to But bar that high greater efficacy. it a does there's we do opportunity you show efficacy.

feeling based a And working, for follow great able by we're just medicine. maybe that intratumoral on that on question, with on test add progress a dosing can think be pretty administered dosing annual even follow to also to, your if get expand good drug, also SPINRAZA Biogen I objective I'll our to Chad. We're and making potential we'll on drug an SMA. new annual Follow-on on we entity is or chemical with

but about fall-on And only higher medicine. as defending positive So franchise the excited the Biogen. well dose as Ionis SMA and we're not we're

Chad Messer

Appreciate ethics. I’ll the Thanks, the mic. Great. all pass

Brett Monia

Thanks, Chad.


go The Please of next question Esther ahead. comes from Oppenheimer. Rajavelu

Esther Rajavelu

you Good morning. up. give COVID-XX taking I follow for about experiencing Thank think some versus maybe you as year question. on the that half you be first that, of the quick then programs the the And my another related may half? of have delays Can us magnitude your second color partnered

Brett Monia

where meeting more we're the on been and a bio clinical progress we're impact with frequently stated, always we've in occurred. this programs had for even running once story have them partners which we our remaining with As to making our the on minimal crisis respect with Similar we've contact close partners, clinical have trials. been

time. nothing on as Huntington with are of we're in our the on the Phase pipeline, with cardiovascular programs And Richard ultimately on certainly programs program partner earlier meaning. track X start in X Biogen substantial any one and Novartis seeing to program And pipeline and all mentioned Phase our trial readout impacts the take outcome

partners managing the are our quite So, well. situation

Esther Rajavelu

enviable Thank capital you And thoughts always current position deployment And have been environment? recently. an then do on in any in updated this you've you. cash

Brett Monia

Yes, too. to And Beth sure. I'll I'll comment on make that. some ask comments

are of We're planned invest earlier of continue very as and position. very the position year in we about a year. we we in talked proud we that And the investing in on priorities envious last we So, are will strong all in. this financial areas to

as X And Phase that stage of our in TTR well. program in course various as commercial investing such Ionis mid in studies as during building line to our maximizing and Phase and options this APOCIII of and pipeline, on X also Onaiza our earlier later LICA We're pipeline, capabilities commercial investing the the and bring through later the the owned the Q&A. pipeline, finish stage touched includes pipeline Phase up stage for LICA investing we X, value medicines for identifying

that And RNA I'm year. our in is we this continue position therapeutics to new earlier continue going leadership but we're that not to invest as do ensure in we to it's what only technologies complement to so maintained technologies, did in to doing continue extended. antisense

technologies and that and continue platform we're LICA for at to collaborations drug for new into look look to areas. well. the continue novel with chemistries as new we that chemistries, populate new collaborating Genomics pipeline LICA with survey new potentially we a brand diversify and discovery partner collaborations And there to other our targets genetically pursue continue to linked

Esther Rajavelu

you Can if right. could More comment. hear All me? maybe Great. you specifically,

Brett Monia

Yes, I can.

Esther Rajavelu

No worry.

share you remainder thinking and your specifically comment of that, the the for more is on if year? what repurchases Just on maybe can

Beth Hougen

is Beth. it Hi, Esther

very outlining think So a we're internally invest as our position, capital. our clear They're clear, we about our to I we're where Brett did job very about going really think of nice cash priorities.

we holding on the the When for some is our share use that of better other is having uncertainty about these our at view opportunities point describing and really current particularly think this repurchases a of was environment, given it to today. Brett cash cash of that available

always have certainly it mind. But specific don't being said, So we we'll in plans. keep that any

Esther Rajavelu

Awesome, thank you very much.

Brett Monia



of from Fitzgerald. comes ahead. Eliana go next The question Cantor Merle Please

Eliana Merle

Hey guys, for taking question. much the so thanks

a it's oral little kind in to program. bit this, that enrolling you you completed know close Can if more of enrolling still terms terms if of get just what us data color drives and the in in hoping I XXXX. you're or to still of completion? give it's Just mentioned

in the in expect terms out data actually terms If the in this should sort out terms what comes what have and disclosed. for could like terms in in to that data what things you of and would be release? of get look oral, Thanks. that would worked I you AstraZeneca guess, XXXX, of we levels of of then it we specific the reduction, protein in And of

Brett Monia

Sure Ellie.

a number So cardiometabolic we're and to that with closely we're do programs in on quite simply to think of can working not space some on well on one. this of that delivery. is provide study the in AZ proof a viable the we think What we're including looking very we phase so that we of will our way make concept, ample complete commercially oral or whether calls achieving

data is That of would preclinical predicted bioavailability, as you would course on form well biomarker based what would as What be expect PK. -- in come data. that our

So same that the oral But that's a are of to but target impact parallel ongoing drug, we on with also, have program administered engagement. reflective biomarkers subcutaneously.

we'll we study also from the oral have with side by data And program. side to compare that hope

a great with tell will subcutaneous up actually is about us oral with will continued it stacking the how and up stack the deal development So formulation.

breakthroughs, allowed bioavailability oral is testing breakthroughs viable think the of there and number. -- were to commercially us really of But the one one that to where The for is potentially we potency. a oral it now get main achieving

LICA seen X.X And will need. potency very molecules upon that be the will subcu us the bioavailability data stable that our we everything and to of we've the intact really the in are allows in and show important And it's to potency. to what level get Gen preclinically in are gut. gut absorption These translate that that remain predicting

programs we important. both that are So very think

Eliana Merle

COVID Got it terms in on the guess. thinking Phase impacts I LICA then And TTR of programs, just X thanks. about

how and put If sort you is in a these in environment. phase studies. enrollment going impacting each complete could is characterize timelines of of when for COVID I expectations potentially sort of latest competitive you enrollment enrollment know your Xs And just how and it's those

you're what timeline curious what latest what Thanks. is the there? on the seeing So

Brett Monia

study on neuropathy programs and going and both and going did so cardiomyopathy earlier is track. are mentioned Richard cardiomyopathy, the ongoing study we enrolment -- TTRansform they're both the as well So, are the well,

we studies had briefly. and activated And sites assess sites. and because very hospitals They pause were they up on our did by to those did are based their that running requests that situation. and their We own their overloaded being in

they're what to from didn't that manage. COVID know to they And expect having the patients

we're the again. assess course told challenges. situation to that obviously And their And us the we're go. then they of they ready until we and we're rolling appreciated And briefly reactivated. enrollment So,

We We on a to study quite this forward. catch the timelines did of we're during impact strategies going pause. remotely either we don't And brief up. as this expect a mitigation developed implement bit doing, did number significant a for

we're on significant timelines. impact expecting So not

Eliana Merle

Got it. Very Thanks. helpful.

Brett Monia

Thank you.


Yale go from comes ahead. Jen question and Next of Company. Please Laidlaw

Yale Jen

your the situation Good taking And under morning, and impressed COVID-XX. for thanks questions. by

quick ones. two Just

any you The first might I of to follow-up. is -- you the guys programs DGATX have DGATX ION-XXX of I But XX And do development. other was in one the stage some feel in you comparing have strength years Do program have then most in the what development? NASH. know

Brett Monia

Thanks. Yale. Sure,

we the high So liver LICA X Phase which have statistical forward impressive identify on building disease, really let go significance data bring in frequent liver administration. even we non-LICA in to the with less that allow dosing with and of the the one us that had of to bring us to excellent on tolerability generated safety doses NAFLD that and and that reductions advantages lower and triggered patients is go back with fat, we version

that. We've managing triglyceride demonstrated they target we've in as sensitive that We've liver. fat. the is DGATX most have, advantage One actually appropriate a fact looked the are multiple. rate the target in think that DGATX in our I multiple triglyceride concluded limiting the we the the There was from that. liver pathway to the for examined the at is synthesis all enzyme standpoint, As aspects -- actually are targets

advantage second The we have is specificity.

will As agents that side in we've we such for DGATX as against very well on some small get inhibitors actually. very competition molecules inhibit our the effects others November. are have it measure difficulty in other into targeting that that published specific DGATX specificity up triglyceride DGATX, isoforms and pathway think and and

Yale Jen

or question That's question follow that assess really great. Okay, is disease And may or to call, some also of the you going be very really, well yesterday commercialization these their Akcea their helpful. in anticipate a pipeline. in terms first moving that guys very programs to pathway the up, as lot of probably And they next maybe of your were pipeline rare expect go. to as conference

how you for overall, to to thought? parts be other as of development So on would work, what own Akcea guys or your general principle a might about moved maintain think you their

Brett Monia

asset have with agenda. Akcea is we're into APOCIII WAYLIVRA, a So full their WAYLIVRA to a with the potential X year having Akcea this the objective in productive Phase US. to discussions of year. the This on and very very study re-filing TEGSEDI, move They LICA course in

you'll And the So productive hear this owned year pipeline. discussions to Ionis few Ionis. whittled and Akcea more rare later have think been potential have from from I and that down we about a programs disease very

we're coming. more a Richard priority expanding ourselves. Alexander, neurological disease pipeline area for rare for Certainly And earlier, high a prioritize those that's very Lafora priority to Prion, us of for least Ionis about. It's our pipeline. as that of is at certainly at mentioned excited one for and Ionis some

hearing at this So Investor year Day. more about think later you'll be our well, that including I as

Yale Jen

progress. Thanks a And congrats great. lot. the again, on Okay,

Brett Monia

Thank you.


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

Unidentified Analyst

is Alex Paul. on for this Hi,

couple a this the you're question kind are us. the stands one partnerships, continuing taking as looking about forward? from for of questions curious for guess your as or Thanks own way your your first it that partners Just here. on thoughts to whole another moving thinking of related program, large the I given just about today on it thinking development AGT you're What market indication. how

And bit could us AstraZeneca? your more background with then secondarily, hoping on Thanks. give was APOCI I you a little program

Brett Monia


antihypertensive So, not large studies going broad to same, partnering of Alex would be this taking for on entail. strategy Phase remains X large very an type indications on our that we're except

will as partner other Some at we've time. appropriate way seek Lp(a) done for a the

no hurry. no we're we're in in said, rush, that With

be concept. And We able have to these maximize as comes financial future. in economics the that large to indications far need bring to Ionis the them to strength such clinical brings take proof to we the of partners as through

of we're year. second one? some no later seeing. studies this to so, what in looking about partner these what hurry And to in And was the this we're we're excited program. results forward the And We're sharing of

It's into to It's of exciting. We and link target. after other FSGS Ionis kidney enter that a a we genetic of our did initiated program this very on it's collaboration at cardiometabolic Ionis ago. a years was that here work target diseases. disease we did APOCI lot number at kidney a a

published to that or developed. on ago. Actually and clinical humans kidney about exciting we this target. That wanted so is are now disease It's testing. We've in year in trial player, published on meet very data a a is models, we people but it a

will calls. own it. AZ year. highlight in have next more earnings that early year They we're this So their They're or certainly to excited program hoping about say about that later it

Unidentified Analyst

Great, thanks.


Jessica from Please Fye go comes question Morgan. of J.P. Next ahead.

Jessica Fye

year. program that this the for competitors into my Question a question. Hi, later How proof-of-concept mechanistic population? guys. or you. from will expect product perspective taking Thanks namely data patient the that is you Good differentiate heading afternoon. SSAs either acromegaly on the target do Thank from

Brett Monia

like Richard, to would that you one? take

Richard Geary

to. happy Be Sure.

who is So analogs. the in program, the the on study uncontrolled IGF-X proof-of-concept patients are somatostatin

a And much current therapies. patients, turns full so quite these of it don't their as as number on get XX% out XX%, control

this compound. control much you profile are weaned initiating Also IGF-X studies to addition program. off and of this with in are to SSRLs improved or So, patients, we And what the tolerability on also program. GHR for in a is on this our acromegaly see monotherapy are not think I LICA want come who

bit to the of the we're what program real a we're year. excited data is add-on. coming with half monotherapy But hope about and in have second staggered the seeing some So, this the after

Onaiza Cadoret

dosing an be also is like product, seeing differentiating on turning with that the Jess, of we We're we profile it to breakthrough and actually addition unmet along product to I initial is great. our And say out there's we've in Onaiza. with the And control. the IGF-X some would just need applied done that on in believe offer symptoms. just both monthly profile. can on early That the was kind work to

Jessica Fye

Thank you. Great.

Brett Monia

Anything else Jess?

Jessica Fye

That's you. it. Thank


Please Foroohar comes The SVB Leerink. Mani ahead. of go next question from

Unidentified Analyst

questions. everyone. afternoon, Rick This for our the Thanks Mani. call Good is on taking from

decision are So I timing ASO a the What is by first, going to two touch joint oral The just disclosure of that on again. the data wanted be between candidate controlled clinical that first to AstraZeneca. companies?

How And your ASOs. think an the to How end for you you conventionally or ASOs? secondly, question targets compare this think markets ideal oral do oral way the broader for administered about therapeutic of about does a indication opportunity for the drugs?

Brett Monia

cardiometabolic decision on So very to other work the program AstraZeneca. and Ionis about timing closely We the is on together programs. our and the talk program joint, this

the for an of As to exploit progress programs. making we're advantage oral potential our for other

X.X LICAs X.X programs LICA programs as out existing chemistry of moving that we're potential non-partnered, gen or already forward, have identifying follow-ons. programs are We're gen that for

are chronic therapy And long on is time. of for your to for the or be a diseases, focus advantage advantage where patients, significant, oral going really where periods on either competitive patients lung convenience would areas provide

orally where, can they for administered in be we competing, an could competitive advantage. other a technologies patients think generally event but oral medicines or severe provided particularly an are And it sort be areas a have until we're disease, with where event where suited of asymptomatic some other Diseases will agent. well

Unidentified Analyst

Great. That's it from us.

Brett Monia

you. Thank


ahead. The Please Ritu Cowen. is go from next question Baral of

Ritu Baral

in Any whether the then about data. Hey Phase just in XXXX. meantime, But guys, that or to the think extension Huntington’s had data question. Roche I've you got taking interim But mentioned label And release. Phase thanks I on into X data want up I I'm wondering for that? Phase they X/X the an the could some for interim look timelines data follow open follow-up. any X it's a get we

Brett Monia

at has Roche that which an X reads in expected indicated So, out would way X interim look in the Phase Phase is be not any data the before XXXX. data there

study completed data. to are which data label label extension from they X/X open Next extension our share Phase planning is the and study, open is year, that the evaluating they're

this early year year study, along data That's alongside with which they'll to what oral which data has the the that natural then next not expect or year. completed history Now next year. next will yet, share and for complete

Ritu Baral

into the And about for more maybe a intranuclear then go can C&MX detail you little Got it. program myopathy.

just You indicated indication? look with us data Phase and at the design give maybe you you Can started. X/X the that how trial and the for timelines

Brett Monia

nuclear So, C&M. data C&MX myopathies. And it's This treatment the this is very with central exciting with is of muscle a our all for models partner They joint Dynacare. the of forms is publication, preclinical of target. us published a some target.

study data, of And had And that watched design clinical are data in C&M. that a patients studies. The development. on these patients have of for history entering into based natural we substantial patients amount is a natural with older each lately these long history of

study and lot that to a from off there's is go open of label. it So information

to So all more spirit goal next drug. of is move form year, infants into patients C&M. which is are getting Then the the

Ritu Baral

attention there biomarker a older pay marker will that in patients analysis a functional Is the these X/X particular Phase to? or

Brett Monia

biomarkers but be other are will Dynacure. blood, these C&MX of measurable So and development of by quality not is measures under in the life. mobility

Ritu Baral

Thanks question. it. the Got taking for

Brett Monia

question one going Thanks, quite Maybe more Ritu. that we're long.


The ISI. Josh from ahead. last Evercore question today Schimmer comes Please of go

Josh Schimmer

feeding me in. for Thanks

aggressive achieve thinking business? to part more next are think the below if that should on meaningfully profitability. for taken commercial has steps mitigating a going we And the the XX ability burn? Thanks. drag change you of about months? the performance Just be Akcea win, How on then it's to deciding been the you still expectations over and that's your Do

Brett Monia

Thanks, Josh.

I'll address to Beth that. So ask

Beth Hougen

Sure. Hi, Josh.

mentioned Latin well Steve TEGSEDI see on into their yesterday, markets, growth as both PTC. as they we America expand in as So continued throughout we earnings for reiterated, WAYLIVRA new and Europe and with call as

when seeing that's growth launching now. know, expanding products into new to markets. and what we're quite you it's really invest revenue And new right ahead As customary of you're

profitable. sustainably be to continuing are We

profitable. have We to stated be a sustainably goal

to able do been our we've guidance reaffirmed the again meaningfully be and years several that year this to And last profitable.

also management team, Officers Chief build committed their to WAYLIVRA And we're And Kyle and Damien that. and Akcea working to Commercial franchises. TEGSEDI new so today, their we are and obviously to with committed the with

So stay tuned.

Josh Schimmer

Thank you.

Brett Monia

Thanks, Thanks, Beth. Josh.

we're it Okay, necessary at steps are where everybody We're I up. again feeling with think this the confident ensure that, year. taking us wrap we'll Thanks, we joining really today. to success good We're Ionis. for

the priorities. We financial look pursuing strength you to term as have progress updating our we the year continue our to long and And short on unfolds. strategic forward

soon. talk and we'll everybody, care take now. Bye So


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

disconnect. now may You