IONS Ionis Pharmaceuticals

Wade Walke Vice President of Investor Relations
Brett Monia Chief Executive Officer
Beth Hougen Chief Financial Officer
Richard Geary Executive Vice President of Development
Onaiza Cadoret Chief Corporate Development & Commercial Officer
Jim Birchenough Wells Fargo
Ellie Merle Cantor Fitzgerald
Chad Messer Needham & Company
Tyler Van Buren Piper Sandler
Joel Beatty Citi
Jason Gerberry Bank of America
Yaron Werber Cowen
Yale Jen Laidlaw Co
Luca Issi RBC Capital
Vincent Chen Bernstein
Call transcript
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Good morning and welcome to Ionis Pharmaceuticals Second Quarter 2020 Financial Results Conference Call.

As a reminder, this call is being recorded. 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, Ailey [ph].

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 measures business non-GAAP we the represent our manage our our posted that accompany slides today. on website also We've discussion our and today's call Hougen, are Brett Geary, Executive of Chief President Beth Officer; on Monia, Chief Officer; Development. Financial me Richard Vice Executive With

Additionally, Corporate your joining of and Executive Cadoret, three, statement. us for draw Q&A our President to attention are, Eric Development Onaiza Chief contains Research. Vice to language which Officer; and like slide I'd Commercial forward-looking Swayze,

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

Brett Monia

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

the year for position the by This tremendous strength this particular, was team. of important dedication achievements a numerous Ionis remarkable by that been has half first and in The reasons, many us in but this success for future. well marked year the year demonstrated for and

ever. second great this our And for I come. hard half XXXX Our years us enabled achieved the stronger we remain are year, we to work has success of enter than believe, as key track to goals and on meet to

additional progress expected track studies in registration start year. are with Our this Phase and programs on studies X to five two

for Our mid making year. proof-of-concept are medicines progress, programs data excellent and later additional due several this with early-stage

lacking. clinical which with treat to continue are grow diseases, effective many advancing for new our new expand of to scope medicines treatments and pipeline We the rapidly

grow the to continue also pipeline. Iona We selling

and reach While, and our our the at expand technology support strategy this to commercialization developing pace. parallel, and of of pipeline record in advance we continue a

we with execute for ahead, and our to agenda. industry Looking financial we devastating and expect on the My track commercial new or commitment on remain through medicines. to we on more and range medicines to applications financial a is resources, diseases. XXXX with which in Consistent XXXX, for this goal to in our guidance the to of of deliver number the XX lead are devastating to vision have marketing we suffering of achieve a result transformative Ionis anticipate people diseases bringing patients our the track end

will position progress who accomplishments, for to questions well after including our Beth? those Richard, our turn financial year, goals. call performance, over open our closing call and made followed brief I'll recent by to Our I'll then Beth us now review to remarks. this achieve pipeline the the discuss up

Beth Hougen

the be end and at as We to second We enter year, the resources execute this a our cash more Brett. on strong, agenda. of basis quarter income financially of net June. capitalized substantial and with on you, Thank we with $X.X than of we ambitious to continue investments second ended half with well non-GAAP remain billion the

and year. half, are are the we this noted our projecting second first we the forecast As of half our and this for With we our last quarter, financial in reaffirming guidance results revenue earnings second for year. increased half

substantial treatment all for year. look patients over a foundation our SMA. patients with of increase end commercialized there June SPINRAZA last over care worldwide, As we medicines, XX,XXX of At SPINRAZA of types the remains were a at on

in second quarter. $XX driven led million global million sales resulted to and across sales revenue in regions second by of New $XXX royalty markets patient in major to the us. growth quarter was all SPINRAZA's

ahead, established in of increase SMA in SMA Biogen across presence. A emerging patients and from nearly all of has Biogen now SPINRAZA XX,XXX previous markets. Looking XX% ages. markets many Biogen where commercial And XX,XXX growth are patients. continued and patients over a see for estimates we opportunity that there estimates

Additionally, EU new be new broader markets, patients benefit in to demonstrated reimbursement. and presymptomatically. five real-world unprecedented data up in benefit for was that data And to and all in of treated some With nearly supports SPINRAZA's adult survival continued teen data, patients substantial substantial label is U.S. clinically new treated patients recently ages. the demonstrating in expanded estimated supporting In years. meaningful to independent the several SMA benefit generated include patients SPINRAZA Nurture

agents. Biogen to to with patients SPINRAZA, will the study study is respond to response in evaluate SPINRAZA's a the also next initiate post-marketing a higher potential bring benefit conducting which DEVOTE early of of Biogen Additionally, the patients all which plans clinical across of greater Zolgensma. SMA dose benefit has suboptimal year, even

TEGSEDI to and turning WAYLIVRA. Now

new quarter Today In to another pleased growth, this commercially physicians an as were support at attribute remain world-class disruption. factors, advantage available increasing X,XXX quarter to injection of patients without TEGSEDI's are able to We patients the to a TEGSEDI that new also to expansion outside the the is Akcea's Akcea in million into continue TEGSEDI and initiate working broadening new compared of recently countries access are agreements into U.S. private additionally increase growth We in XX TEGSEDI of more Canada, to population. place further sales last solid several is patient PTC are delivered will progress help year. multiple government amplified including U.S. even this countries reimbursement hATTR. Brazil. markets, have these United reimbursement is important medicines well. genetic expand is endemic payer access to resulting product in that year. and States. secured report And substantial number $XX TTR have In and home We in second reimbursement European in as Connect. They in on now testing to which its used with number to-date due to making subcutaneous Therapeutics negotiations program was in with being a Akcea drive TEGSEDI treatment amyloidosis success and to Akcea in a Portugal, the continuing pricing Akcea's America, broaden patients program Latin anticipate including existing new growing diagnosed is treatment progressing secure strategically countries.

through and to other new year access the American to to for markets. we is Latin PTC with in additional is working early for market FDA. this to countries Brazil and turning Latin our Akcea our in a Greece each WAYLIVRA recently Austria, are WAYLIVRA. marketing launch EU reimbursed of in the Now France access ATU, authorization in program. WAYLIVRA pleased as America, plans markets. and and In growth for preparing of opportunities patients Germany, commercial transformational its filed existing in to medicines We're and expand performance see in medicines these more refile continue the reach on with

Our year program and year. the our Phase our than for disease a AstraZeneca by revenue important AstraZeneca to more is therapeutic partnered to with We million IONIS-MAPTRx multiple of other than expenses continued payments milestone franchises a payments sustainable in of $XX $XX Biogen for franchise initiation each fee achieved higher compared million across And for the programs in and R&D we our of partner -- year, Pfizer. the remain remain reflected growth. partnered oncology progress including we this our source the revenue and atrophy. substantial of our including half track home revenue programs opportunities over were and under from last half. more quarter, first of Biogen from $XX in non-GAAP collaboration. which from patients from Many our with progress progress programs Phase license catalysts cardiorenal X/X significantly for in for medicines our several amount study third pipeline, the generated including in franchise, franchise, our AKCEA-TTR-LRx IONXXX, in have included million second IONXXX of compared Ionis programs and already this for higher on system earned neurological Driven million slightly from operating R&D the for million $XX quarter. of with a our This us, in QX the with second disease X $XX including in

non-GAAP With a increase these quarter results. quarter results, we to achieved first our the basis, net income on an $X million of for compared

year, year with we continue guidance. this top Our project this significant XXXX first this our and revenues half rest second R&D results and revenues commercial projections enable for for on the our increasing us reaffirm to strategic to of our half on revenue of strong we In earn execute opportunities numerous the year. objectives of to financial

year. this higher non-GAAP first to expenses compared of operating We half the expect

than financial pipeline. fundamental cash our enabling our strategic With the with longer Our to business. that, $X.X near strength in priorities. on financial term a success execute the and update on we is turn provide have our over Richard to And investments, broad billion and resources an pillar call I'll across to more

Richard Geary

Beth. you, Thank

number the targeting catalysts from this in of looking in half disease of significant our catalysts coming of numerous medicines, of forward pipeline the XX highlights additional neurological franchise. a Our achieved over range with I'll broad a first start months. to year. diseases we're world-class And

of This potential toxicity. the toferson Phase accounts Ataxin market track medicine of so SODX-ALS potent the targeting devastating X/X our X patient listen potential to next data data our more patients to could progress medicine a ALS. year. enter population soon. I and atrophy, X/X designed for clinical X next expected to XX Phase which to neuron motor our disease robust study of Tominersen these track track highlighted for Biogen study on providing is with These path hope patients positioned is approximately resulting Journal stages in is next neuro and study of of program Phase FUS continue with webcast of with promising But and study TDPXX therapeutic or includes for X alpha-synuclein in we tofersen study for options. treatment exciting disease highlights. franchise, patients our As franchise to initiated in ALS caused importantly into the studies patients Lafora growing a IONXXX, for neurological our to research. directly programs localization ALS X/X the in is recently in disease. the owned in study forms Phase in from of more medicines disease Huntington's late-stage in this have today programs. of were Results urge this Medicine. and treatment development patients And regulatory with treat I'll recent late medicine With a in signs we various by this mutations is on support only published inhibitor to which system form only all diseases SODX-ALS remain many the late XXXX. XX% our multiple the FUS a thought neurodegenerative and ALS, on early Ionis treat this programs is IONXXX efficacy three in and the treatment enter of our next anyone learn toxicity inappropriate focus to on to a those today, Phase sporadic to after ALS Alexander's, which to Iona’s pipeline. Prion IONXXX, New and many treatment a study year Data another the from months of year. progressing IONXXX from first Tofersen fully rapid to of for the development no enrolled our pipeline neurological recently familial disease gene. growing owned commercial X/X recent year. Tominersen in who medicines. the registration about and are the later rapidly to medicines also with webcast recently of in programs first in this be ALS is disease also missed protein, added replay of demonstrated monticulate contribute with with going England year data in filing our designed well And Phase for IONXXX,

recently underscoring patients Phase the and Turning AKCEA-APO(a)-LRx risk cardiovascular for franchises, the in fast AKCEA-APO(a)-LRx events progressing designation is was expected Lp(a)-driven trial granted is of XXXX. study FDA readout well disease. the significant by to our track disease of cardiorenal in millions cardiovascular the and metabolic the X with

vupanorsen franchise. comprehensive Additionally, both We Phase cardiorenal for data plan cardio medical of update investor our medicines forward later events. transform cardiorenal and XXXX. neuro we our next Phase our an full these in number disease this details update provide other coming from of AKCEA-APOCIII-LRx well up, data medicine providing franchise. the LICA Akcea-TTR-LRx a plan host timing X Please conference and are programs and and expected transform to And positive on for targeting ANGPTLX month. studies a with and to tuned we and to programs in look a an And month set X webcast our to two progressing these our for present stay

oral underway. to of update progress metabolic program We providing of continue on numerous formulations. with AstraZeneca. programs and to year, This includes this forward which and make Ionis-AZX-X.X-LRx number collaboration cardiovascular we disease look Later a be significant productive both and the oncology partnered continues an with programs with cardiorenal, treatment AstraZeneca very for to subcutaneous R

IONXXX the of chronic kidney the for progress good disease. making targeting targeting with And also of is NASH. PNPLAX APOL-X IONXXX studies ongoing for Phase treatment X the treatment AstraZeneca with

to oncology programs. Turning our

our returned recently inhibitor STATX Danvatirsen. AstraZeneca to

patients the immuno-oncology studies pulmonary from to updates our to forward coming studies the plan as the mechanism We and to are that FCS look in and looking AstraZeneca dedicated action. we and continued studies targets forming of to providing families, FOXPX. trust up data advancing staff from Phase in for opportunity development patients, I from patients expanding hypertension to this licensed forward our look have volunteer of And FUS-ALS. franchise to cohort of we our initiating we forward and for medicine early that is continued enrolled proof-of-concept the time. medical acknowledge employees work IONXXX initiating registration programs. year, We medicine the have cancer. with the over plan recently AKCEA-APOCIII-LRx antisense fibrosis patients to HAE to Phase results study because to want in the of expect pandemic initiate with X/X evolving turn of data results plans investigators today on participating this with achieving from patients to our the the transformational look commitment from We Later Phase to half, next with that execute we report a to and and first our plan to the to IONXXX working program IONXXX close purely (IRFX) Phase I X/X from cohort of report our our and cystic updates patients X/X Danvatirsen second want our we in We're And reviewing pleased Also, of study. from a Ionis-ENAC-X.XRx year, clinical continued study this an in with is of pulmonary myeloma. acromegaly that and we're shortly. And undisclosed fibrosis. and I'll entering This with indeed. later Brett with Ionis-ENAC-X.XRx Ionis-owned Act cystic proof-of-concept look hard successfully pulmonary forward cancer point medicine our pleased clinical X And fully antisense that pipeline medicine delivery with of an this through goal Ionis-ENAC-X.XRx take targeting this healthy patient providing both the to during patients expands the diseases treatment for year program study continue to as it to well. we further indication multiple pulmonary forward have extremely year, Along multiple to IONXXX our with out to call. for progresses. near we resilient development our franchise COPD. in new program medicines And are deliver with be Also IONXXX in future. development we evaluated then the drugs follow to global progress to our with this broadens call additional the adapt beyond further first today back the portion in in study. I'm the the and

Brett Monia

Thanks Richard.

and at hard Thanks everyone ever. the is Ionis. to of business than stronger today dedication Our work

track with strong to continue continues expand need pipeline executing our and discussed, year; and just starting And several exciting As the ways of the Beth including expanding range and and a the Richard about very progress I'm for studies our several Ionis-owned in X applications of advance registration medicines. is more XXXX rest programs; keeping of us which the patients with result clinical marketing this and with record I as studies reach end people Phase advancing for through building two advancing new pipeline broadening remain a our our number very deliver new Ionis-owned reporting expectation new the or to XX the for see for on capabilities initiate and to diseases we proof-of-concept and we expect our ambitious clinical resources in a year of this which for development pace. ALS; devastating and financially to highlighted, we advancing commercial medicines FCS additional commercial technology strategy; the agenda. excited on at to results

our we additional and to objectives ambitious and that leader in up our these agenda, As delivering closer aspiration achieve making resources, on pipeline, patients and questions. well the need financial the to move in becoming we the goals multiple are people, open to technology, medicines a with I'd reality. call transformational some our make to for that, way like that and we And with


Jim will Wells question now with first will begin Birchenough session. Fargo. We Our come question-and-answer [Operator from Instructions]

Jim Birchenough

patients program. what quickly in us guys. other knockdown just your you part volunteer you I guess physical the oral, study. the of move just targeting few of start barriers penetration with. on of assuming give And a to inhaled on gives the you're to first And getting all the year end, some of in normal Maybe you questions. success with the level the programs formulation? in overcome Hi Congrats could forward could on towards progress. CF oral an A how confidence can that you what then drug adequate sense

Brett Monia

Jim for questions. the Thanks

So, as target you will be specific will disease unique patients. of of area in produce know that each in the pulmonary knockdown program, a level each benefit

we'll is well. program, study the which the out ENaC normal update franchise our on program study for to this Phase Specifically, CF an from later going as we're and pulmonary X volunteer year read our the from provide

cystic disease We reversal have of in XX% reduction protein demonstrated produces ENaC diseases. models related in models of little as mucus messenger of RNA and as preclinical pulmonary and other that the actual models fibrosis

and in have broadly good replicated fibrosis monkeys inhalation lungs epithelium really target. not our our unusual quite our our architecture of for studies. ENac beyond cystic COPD of we'll clinical cystic drug confident really our and a we'll we've shown comparable that's ENaC. the program. target greater in pre-clinically confident generated and get even other We've That's and the attractive -- expression for the in type quite that So, or We're of in throughout that data the also similar as for but are a models pulmonary to ability go uptake normal We're to in it models, for big following of in drugs we our in into lung example of that probably target epithelium. and lung. a cells have fibrosis in can knockdowns CF that's We've mucus excellent programs, normal which other well for linings lung penetrate covering bit reductions knockdown

sort delivery delivery of and to is this epithelium. not using vehicle simple So, penetrate sailing We're in the any -- solutions.

with we the to already what clinic new the in have this and we're already the oral the forward not and sitting update this today. several in go program, continuing both those year the the clinic on other programs We're would oral the sharing that even move and to platform Regarding orally AstraZeneca. still. already programs greatest we in yes, formulations later beyond We're And subcutaneous think we're it we're we're preclinically as impact. based prioritizing that. formulation we're our -- oral moving And doing we're formulation into partner moving an forward, looking will on, forward develop confident program where have programs

at that the update an oral on So, time. what program, stay When year. we'll a is hopefully we'll provide for that into this later tuned peek we an coming and provide give update current else

Jim Birchenough

sense revenue one of longer think if rate of maybe of Do quickly level the about for me enough as the you'll a to that terms you of revenue, going about R&D of in for that's partner modeling have And some milestones or future in when and various allow visibility cadence more year, just how think Brett, half that programs think the run give about forward? the we we do term? R&D in uptick whether a we how second us sustainable Beth, should

Beth Hougen

Jim. That's Thank you. a question great

the and relationship with increased those space that particularly the Biogen collaboration to are neurological continue very values dollar we are productive and And fact the increase research reflecting I licensing of years in quite of milestone So, over will as see and then, development the I and you've our bring base as and could creating greater one about a in of our top our and sustain the last that as continuing look number a the And see obviously value build strong revenues programs on And development. medicines the is existing development you to number we I as out into future as working that medicines think in with continue seen greater that all continued sheer to payments revenues. of Biogen. of you just think forward are of company, partnerships the a think those our I and of have, that R&D we very potentially increase what partnerships, just those and the of partnered commercial few advance the under programs number partnered factors advance have that revenues. medicines fees, we strength that to the grow

the sustain to those R&D future. think I us So, together grow the factors and give our in into potentially revenues confidence ability real

Jim Birchenough

questions guys. Thanks taking Great. for the


from Merle with Ellie Cantor comes question Fitzgerald. next Our

Ellie Merle

so all updates. much the And appreciate taking Thanks for question. the I guys. Hey

assets the ship you've Just as such the about you of guys cardiovascular of have strategic neurology, areas you and thinking strategic you -- focuses are one, Thanks. you sort thinking a vision broader various how are develop as focus plenty potentially and as about how done pipeline, long-term in Akcea there? franchises in excalation

Brett Monia

Thanks Ellie. for the question,

prolific we indication here Novartis. discovery discovery your validated Ionis many where engine Pfizer with options the for each and here we maximize think for well it makes for engine, is will One at program continue to with did drug indications patients. our up partner large drug that a it the in did such taking like medicines future. last of LPa we engine, Ionis of established sets User this for way large -- different we us shareholders have We value very a about advantage of nurses like or to sense strategically with cardiovascular to that with year we our broad with this

for And Ionis, hold early. continue. will economic upside those greater command so longer to partner will not to We even that drugs on

that also we're assets, like within great I drugs area for disease, more drugs In think certain market certain addition disease rare And or to our disease, the have already to Prion's that alongside in on strategy pipeline. Akcea through the Phase Alexander's others FUS disease building we particularly webcast, that, Iona pipeline, We but are III think and finish are five is into selling bring coming. focused strategy neuro commercialization brings through this and the we're already the franchises one that our will the or to Ionis the the line ALS and ourselves. pipeline. prioritizing touched Ionis on bring neurological in this We priority that prioritizing be a pipeline Lafora program We value.

a to see partnering driving strategic continue you're balance of – see economics of to balance the a So going to company. attractive

to also own value about build what we line? finish – medicines. we that our you and pipeline the the see how pipeline all of want in do neuro we it see our to taking at talk Onaiza, While

Onaiza Cadoret


leveraging prioritized investing an comparing And many pipeline diseases we we and focus. just the It's complementing the patients. in neuro initial neuro rare because said our products Ionis-owned discovery are as strategy. out to needed capabilities that the then with expert we're complement is drug have very in rare as bring in business So portfolio building among development neurology the deep and really to the and our commercial

as of potential it's So products to cause important deliver get the have to needs significant we they that they to the disease the and/or disease. and root reverse really unmet stabilize, the on have also know prevent

So very ALS have to disease as Alexander's kind we already just expect accelerated strong upon really us year. over we're path also we that. these a disease on of and Brett prion clinic Getting other next rapidly excited GFAP and And are into we alluded have for but the FUS towards not building each and the relatively those.

beyond the also for for but period So not really in rare the products good growth. initial it fuel will gives business neuro. just sustainable see we us are that importantly, That a these good, portfolio And to with. other for start strategy

clinical capabilities out data on So really readiness. it's the exciting for based and commercial we're commensurate building the that time an with readouts

Ellie Merle

more pros Got way. kind what are just direct ask a for Beth, structuring from I has just corporate Maybe Very And maybe helpful. – financial a of perspective and the I'll of guess it. relationship of very and very, neuro cons in of as large such potentially you new these kind a itself as all keeping forming have additional pipeline. certainly guys assets Ionis subsidiary subsidiaries versus

Beth Hougen

assets. are neuro I we at this Ionis-owned stages pipeline, at our at point of looking So in the the think looking early

what I that excellent would path. far and rest are team And we her put with the as think But structure working exactly in we're Onaiza think progress of I doing us along making a place. as job. great

really to say. early I think too it's just

here Ionis-owned is to takeaway key the retain commercial from Ionis-owned is our important pipeline. what's think pipeline. I And intention we're our our substantial value is prioritizing

Ellie Merle

Got so it. Thanks much.

Brett Monia



comes Chad question Needham next with from Company. Our Messer &

Chad Messer

little and rationale congrats of the all of lot bit you a around follow-up of commercial some strategic at kind to it the of to R&D Maybe develop my capabilities over dialogue questions but the Akcea, culture sort time economics, create Great. that and on I Thanks taking and of the along a was off that of a for When of prior evolve adapt. development helped the the of founded culture better progress. – know sort question. Appreciating retain the silo had to has you enables strategy sort fantastic your discovery time engine. of guys kind

well? important as Just you're particularly that growing but pipeline as view your neuro in other wondering you wholly today, how owned areas

Brett Monia

Great We the be question, innovation great a our always the that innovation, the will is that ones. always think priority. to Chad. biotech in – Ionis core think Today, among The leaders. this. a and R&D innovation – word industry. be you And use of is word scientific that about evolved will in we're

to done. also culture the And can at the pipeline. the proving while pipeline in capabilities clinically a preserving I innovation our We're technology, evolution happens good value and just proven culturally the creating importantly, We're the And and value pipeline at founded in core and very strong different was different that in actually We a the many the with a time a And which synergize, proven we've at company think our validating in certain We've and endure five commercially ago. time, ways. is commercial now assets However, Akcea Ionis that technology. in a the good but very of place. place so today. it now it strategy very is of disease the today. to commercial years building at position four, different maximize was that own and maximize strategy the the of it we've rare not

Chad Messer

Great. congrats again. Thanks and

Brett Monia

Thanks, Chad.


Matteis Paul Our next question Stifel. from with comes

Unidentified Analyst

Hey, This thanks the Paul. on for for is Alex taking question.

is and thoughts thinking that asset place curious Just an competitive for going to relatively market about that for as Thanks. what a drugs about you're HAE, ASO, major some of you're curious, PKK with are thinking generic? your sort Just market how the there. your

Brett Monia

Yeah. in Onaiza been this, later sharing We're asset program. forward I'll looking hard for Maybe touch HAE patients ask We're on the to year. this results excited -- but is another about Ionis-owned this prekallikrein diseases. rare she's about to thinking Onaiza? very with

Onaiza Cadoret

think still early you're for there's we here. and actually room research competitive opportunity strong more a feel like but We've Yeah, sure. competitive right. Yeah It's done have some and we product. we market market, players in really

to still current products prophylactic acute that of I there symptoms and because that the defined we're some want with the happening. heard are breakthrough kind that in seeing that room rather simply than there, HAE, think treatments they're attacks treat are we've are that feeling of more prevent they episodes

And possibility. we differentiation or a think we with QVC from with as perspective a administration as certainly, there. have well as So Q well differentiation we bi-monthly injectable have dosing

So, we're focusing bringing are areas that to differentiation. great the really those on some competitive

Brett Monia

this would in that program is And to to even an that Alex, be dosing, addition I'll monthly has just meaningful, a or develop another formulation, frequent less oral which competitive potential add the to very advantage.

about patients, our And think comparable more demonstrate an then beating. focus patients in product forward. what what patients to to going we're drugs is like no attack rate So, that's a attacks the or first for this be where on would market would convenient value

Unidentified Analyst

All right, great, thanks.


Piper Our next Buren comes question from Van Tyler Sandler. with

Tyler Van Buren

program, ENaC the follow-up had a just Hey, on morning. guys. question touched earlier. Good on you which I

it another be getting, think about data? we appropriate? will study, market exacerbation sweat Phase what type as just of can And X Phase next FEVX patients product the or with to be you -- we'll and another Can or study product, outline year. X/X you be chloride exactly on data sorry, would -- early data CF what we data comparing most center in getting the So, and

Brett Monia

Richard come I'll of and what to just maybe touch out on Well, the expecting we're clinical ask to it. study

that second about ENaC can the a bit of part the program, talk question. I For little

Richard Geary

we're excited it. about Sure. Yeah,

So, really is in initially both cystic other the in the normal law, the of proof and pharmacodynamics pharmacodynamics the focus knockdown, course, the ENaC a And in the a then short-term and is fibrosis of within lung delivering on words, the Phase pulmonary drug X/X study, of the concept. vol.

So, to development. would PD/PK tolerability, it's be going safety and then further for position us which

clinical of the be program the that's short that So, six-week expectation data of that. coming Relatively term regimen. the should dosing out and

Brett Monia


types. Thanks, Okay. to patients all mutation work positioning-wise, And the in then Richard. ENaC potential for has CF

linked particular on mutation obviously to of not its any action. based it's So mechanism

and see provide greater today already patients drug market working cystic they're we fibrosis. They're on in the to So CFTR combination this approved modulators. even with with B

We're for indications in Phase the other we very of to indications. we're good and the start this about exploring II COPD potential too. this indications addition planning other feel pulmonary In later study also year target

indications. So it's various of of target has quite on for that versatile upside a types a lot

Tyler Van Buren

the Thanks great. question. for taking Okay,


next Joel comes Our from Citi. with question Beatty

Joel Beatty

thanks taking team, Hi, for the question.

to one follow-up lungs the ENaC tell that you program. Can for testing about the bit little trial? that a knockdown in is first more on question actually The last us a how you'd in be

Brett Monia

from directly ASO. that were patients treated ENaC RNA looking fluid are and taken We're going with in be -- that the ENaC Yes. lavage at to

Joel Beatty

drug, the the knockdown is level characterize maybe subcutaneously another bar the oral Terrific. success? could bar approach? for what is lipid a And oral for And as delivered of a you then the the program, be or is different on would question help same it

Brett Monia


data -- your on subcutaneous. We're level But about of based we're level the oral achieve can't really that feel we knockdown question the X.X in comment -- is this we have remember same Gen targeting that important. based LICA. a the on And part with that preclinical our level subcutaneously targeting of that knockdown on the of We the that that is is getting And preclinical program. as we're good we can second data.

So substantial. that is it's knockdown --

Joel Beatty

a Thanks lot. Great.

Brett Monia

Got it.


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

Jason Gerberry

questions. guys. for Sorry my you Thank taking

look issue Just trying IIb? a positioning differently, you competitive? to on the to a segments you straight ANGPTLX of can market-based ANGPTLX dose a to IIb couple of to to with you, ultimately effective positioned as jump on or therapies a your goal help an secondly, of learn versus genetic Thanks. are bit the go then that they shots lowest think as more us the Phase it go how little Is are the about And Novartis versus on step? for you III, within they'll operate figure background? of multiple testing to IIb opposed incremental Phase it in here Is what's through Phase the what and out to expecting doing Phase to you a decision see think pivotal you Lp(a) do

Brett Monia

Richard want to take that?

Richard Geary


that I'll we had go we IIb the patients. to sure into. approach. into Phase question. to parts conducted desire the was a that study two II The XXXXX the went the Phase There in start not that right we XXXX intend with patients make Phase was dose to actually IIb before So to because

I makes think sense. that

and at can up the regimens in organization program And so the that that be It do looking very place. Phase program. and there's was done additional very going already dose dose to work into quickly already a they've III large structure set because

enrolled quickly can rapidly. IIb this Phase a into So very and goes be just

end So question. of your front the that's

and second are with The has are patients your to differentiating these issue. they out look Lp(a) at have the you when that in Lp(a)-driven cardiovascular general not question it patients of Lp(a) part which have patient of And completely elevated with an have elevated do Lp(a) disease triglycerides. cardiovascular that epidemiologically populations. different most population turns do

have So cholesterol the issue significantly triglycerides a problem. component high don't vupanorsen the remnant population. they targeting triglyceride more the triglyceride -- or as perhaps of is patient

that targeted for limit greater So enriched population triglycerides. high like to the These drive upper are dyslipidemic these than super remnant drug triglycerides elevated that the And vupanorsen very triglycerides have but is cholesterol dyslipidemic here. down Lp(a) patient are generally a patient are normal what a high, There patients. that's in XXX down pan with takes intent really population and lipids of who diabetics. the and not well. not than the elevated greater does, are It's patients

risk are So different very both a real these of there's that's patients. in There populations. differentiation. this clear With residual

Jason Gerberry

Thank you.

Richard Geary

Thanks, Jason.


from question next Cowen. comes with Yaron Werber Our

Yaron Werber

for Thanks question. a have Hi. of questions. taking my couple Yeah. I

The you're on Phase X/X it first still you're in waiting a the like CF. ENaC for follow-up just program. mean, the COPD, sounds is Brett, a moving X but toward in one Phase I

in Phase maybe to how an acromegaly, and understanding again, of CF of the PD little of X/X? bit there's in you. that? more kind than expect you need slightly of the appears it we can for that and what knockdown almost thinking target a set COPD maybe the secondly So just some about markers conviction same to you're are And X Thank questions Phase from do then what that move

Brett Monia

Thanks the for Yaron. question,

drugs achieve to target about goals program. pulmonary very don't enough platform, ENaC the our our of developing X gives studies first the Again new we or good franchise that for the the other clinical of that believe confident as patients We target. is us of into us We've soon. expected targets several We're overall. we pulmonary feel are So getting CF for that very our outcome seen move in development, marching ENaC is in to study close COPD. study or can engagement. is confidence gating believe the CF Phase already that a And we in

moving indications. we're So to on other

it's We've gaining. And the not -- so enough. is not seen CF study

is for level Richard. IGF-X. your of data do you that normalization hormone proven be approval. a biomarker validated there's a -- or receptor have can growth that acromegaly to to close get achieve know It's is you needed normalize for our IGF-X fingertips? our what on Do IGF-X that -- As preclinical I don't based used to on knockdown levels. for is there's And objective of

Richard Geary

No. model, to acromegaly something really IGF-X I -- directly you you at elevated have look you don't its models don't directly --he really into preclinical model. go not I mean have can an because don't that.

Brett Monia

looking our focus measures But we're quality how is addition, is of patients feel, at in IGF-X And is the life. that biomarker. of

ring in examining We as deformities in like are patients also study the size growth well.

options. addition, study analogs. is are one think for They're are And may patients on In study are not somatostatin we patients not that different. that This the acromegaly. be of a carefully also a well also monotherapy in we're additional gating as the considering looking And populations unique. with a at other. controlled in the quite initiating possibility We

Richard Geary

back able X/X. to from on to behind. move that leaving to into because confident we're that move able CF mean control to drugs I we're thing is only don't Phase have going we But ENaC to with COPD mutations that, The the been be the add we're hope getting other doesn't with move good forward data those we've that would that will continue into to and CF quickly. CF even their and very that

Yaron Werber

human the correctly, expecting And in a the you. Is about I what remember preclinical you're and And showed that think acromegaly -- if you XX% knockdown. that because sort prior this Thank have of data study for program. of the if program, LICA? is analogues correct? some remember a I the LICA I Is weren't -- correctly,

Richard Geary

previous think a the up LICA But Yes, the you product. reduction we volume bring that's begins month correct. a this low IGF-X. a forward very once XX%, with infrequent and that have It and and going down data to I to do analogs is bring be shows bring again is that good dosing, LICA XX%

Yaron Werber

Terrific. Thank you.

Brett Monia

Thanks questions. the for


Co. question next Yale comes Laidlaw Jen with Our from

Yale Jen

the for thanks and taking afternoon questions. Good

guys are You going APOCIII to the LICA move X. Phase into

before? you provide that this similar be the the of some development of in would of guys time So line of time time the development of program terms line could sort

Brett Monia

So thanks, Yale.

are the we Phase planning and on initiate to track X So study.

this For APOCIII LICA also at other develop drug. in We're FCS this year. opportunities patients to looking potential

their our for suffering set. all of and involving broader data We're to cardiovascular mean, for indications next is acceptance filing disease depends aspects review cards I objectives the hoping but the FCS the with -- achieve to high get time is potentially that to and readout that. other triglycerides And year. the get study also our to we it the can market timing regulatory due from year. populations For and disease, this WAYLIVRA other related of regulatory -- on in to

as EU launch in will America medicine. out So we be LICA ahead as if WAYLIVRA, the in U.S. the things ongoing work in well several as years where liver Latin of available launch commercially

Yale Jen

strategic Maybe not you collaboration is forward? this or going again narrowing don't still a a who BD you large the point speaking will one something guys bit pharma. more question that's of little the potentially pursue left some to Are know on bit Great. Okay. at still side little for necessarily with I that.

Brett Monia

bring they for selective large they we very bring, very really pharma them they interest just populations. and externally develop much resources expertise do so drugs in We they and It's money. they companies in anymore today. by to partnerships strategic deals what we commercialize feel the do technology what on. Ionis, We're the for to -- strategic don't to the types So whether our value bring so of We value. the really have have Yale, that can

on. so And

So we Ionis-owned the parallel. will in build pipeline continue to as we partner strategically

we to the own they bring the or our we have where we on after luxury through as could be of some potentially X will with year. areas strategically ability drugs our cake to Pfizer We makes do. And have having through if make pipeline. partner could strategic proof-of-concept licensing sense. with Those when they last Biogen, it be like to if level proof-of-concept transactions and needed sense relationships in done Or did Phase we've of you

we So to think of we're planning do all that.

Yale Jen

and on so Okay. Great. Thanks, congrats far. progress good very

Brett Monia

Thank you.


RBC. comes from question with Issi Luca next Our

Luca Issi

for all quick Luca my Thanks here. from Terrific. taking question. questions Issi progress. Two the is risdiplam. on Congrats One RBC on Capital.

maybe I thinking so Monday, curious, what date is term of the label I to downside from a upside PDUFA APOCIII. what's base area your the like case two an I – love a think on but be in could case? actually And you finer you scenario share latest on already here weeks point was and actually think if add alluded can case I'd to it, to the

times a XX recently like larger to maybe And monogenic you. I the is to and disease you given think the indication FCS. actually Are do disease your competitor that FCS than Thank a like from pivoted not why? MCM planning polygenic same? if

Brett Monia

see adequate they in still her post as about commercialization despite efficacy. study and – the than will show to originally now prevalence do much we're to the single not are continued initiate we us The be despite to who It's our that announced – as about for Ionis on that the patients not DEVOTE is therapy every We comment to their see the for their clinical – get globe. dosing larger say XX,XXX us of to patients addition extremely has XX-month study are And in our suboptimal of very we They're every patients pandemic, future What administration. around Thanks or readings we this would we're strategies I today projections nobody was the launched can competitors working And with they is growth than globe. see treatment the of sitting in SMA a on. Luca. is, for in treatment and soon all think treat drug to dosing continues SMA bringing nine-month And Biogen don't Zolgensma. Biogen we on And label talked that, to what SPINRAZA, in Beth intrathecal excited is appropriate anticipated. change. the to about the greater questions, around more SPINRAZA. can SPINRAZA medicines Biogen competition. getting gene and what follow-on well so what for or start in even are what

other APOCIII not competitors profile to patients and going safety compete have SPINRAZA. us are So SPINRAZA doses to with triglyceride LICA all prove are in with is hydrate addition and us on looking higher are comment able that is FCS, efficacy, that enables the we as to to I with for to to the to be what mention other go followers – on to pristine competitors literides. following competition what that they that what to are involving doing at us, Same offers but did for indications, earlier demonstrate

looking the can and large which the and We're related strategies which to – indications, referred other not credit as around triglyceride MCS really we're You are reduce looking the would you building only our also referred as be those indications and patients familiar MCS. reduce cardiovascular We're basket debt. also And such heart indication others. which indications. risk indications to with cardiovascular indications, and attacks that metabolic at very in – goal of we're banks we at

FCS of the is is just All first. that on our agenda.

Luca Issi

you. Thank Terrific.


question from Our Chen Vincent next comes Bernstein. with

Vincent Chen

Thank taking just questions. oral much program. the you Maybe for on the very one

you in oral oral conversion sense different indications you'll for necessary and pipeline to currently dose level dosing? a some with say, below upcoming thinking some think the And you point oral for follow-on dosing? is marketed of maybe TCR for are the or program particular bioavailability dosed couple programs amenable the data? might I could if that oral dosing. may of anything experience or to program that's about have LPLA further examples, indeed what reinforce LRx with to at your which for you'll what level indications a sense dose these have drugs with switch the probably like have feasible think there levels to So to portion level for you this dosing, some things your oral I subcu. you that dose about Do is Is be there subcu or example the TEGSEDI be And for

Brett Monia

crack Vince. commercial substantial Thanks, viable once We believe we portion pipeline, our reductions. right working that, the oral want in substantial to an a targets, clinic of on be now, program dosing. the particularly oral we're The amenable strategy liver would we

talking we to So at, this reductions large a we're viable about reductions make commercially XX% looking product. XX%, would XX%, that not want We're achieve.

ready sitting we're it's oral Lp(a) those that, I create them. we Gen Gen moving in XX% of availability to oral still. previously somewhere we've X.X, go that. chemistry, the chemistry X as in to potency think applicable And combination mentioned, it's -- to that having this with that I would viable Whether is like we anything, or X% demonstrated chemistry X pipeline. could or forward. not be We're drugs be an get angiopoietin-like by coupled which delivery. commercially TTR for already us humans, ApoC-III, I The for us think brings think around earlier, And getting or sort from So the or on. can -- to prioritizing to LICA with would it And benefit opportunity that we're

our -- a show not target. to not talking we're is So impact on objective small

we is best that when about we've our to today, -- that core Our to speaking comparable to subcu some drugs liability, reductions objective are and we're of refer shown.

Vincent Chen

might else next additional to see these does when And I box candidates what's the move you here's on candidate? or of say just into just And the some before Is what an going clinic? the for what's expect insight out to to we're move over to look say similar, here, current into waiting we And it you the kind expect oral or matter moving next gating into? we some switching come might a that? factor before checking of, happen guess, when oral and When see be to things the the needs platform? data? verifying it oral

Brett Monia

I earlier, So as not we -- we're said still. sitting

some programs, going chemistry, Gen now X.X screening we're certain that for targets with LICA. process. are through for just We And the

study are strategy going we to there's waiting -- to but but obviously overall, be, going future could the as gating is Where that rationale do moving our an it's just provide for molecules the data not to we're forward. be opportunities data, for the see sitting year, oral we we're some what for that opportunity things well a think sooner. clinical probably at want Investor for the program? This current if factor, So oral don't -- on update year, not we biggest as not still, this the want the do we're and Day molecules think, to I not --

Vincent Chen

a Great. on progress. Thanks taking and questions congrats for

Brett Monia

today. I question. again thank I to Well our everybody want for Okay. joining last think us that's

focused this our our to Before webcast, take we Cardio franchise to you opportunity close would today, I like Renal next of on month. remind investor

to just referred for for Investor to I soon. our events as well We which planned these plan earlier Day, December. As provide details,

Thank So stay you details. day. have a for all And tuned the great again.


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

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