Ionis Pharmaceuticals (IONS) 4 Nov 202020 Q3 Earnings call transcript

Company Profile

Participants

Wade Walke	Vice President of Investor Relations
Brett Monia	Chief Executive Officer
Beth Hougen	Chief Financial Officer
Onaiza Cadoret	Chief Corporate Development and Commercial Officer
Richard Geary	Executive Vice President of Development
Eric Swayze	Executive Vice President of Research
Kyle Jenne	Chief Commercial Officer-Akcea
Do Kim	BMO Capital Markets
Gil Blum	Needham & Company
Jim Birchenough	Wells Fargo
Joel Beatty	Citi
Chi Fong	Bank of America
Luca Issi	RBC
Yaron Werber	Cowen
Vincent Chen	Bernstein
Yale Jen	Laidlaw & Company
Jessica Fye	JPMorgan
Myles Minter	William Blair & Company

Call transcript

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Operator

Good morning and welcome to the Ionis Pharmaceuticals Third 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 go ahead.

Wade Walke

Thank you, Brandon.

a encourage Ionis go press we website related tables, I section the release will begin, to financial the GAAP of to including discuss we today. everyone measures to to Investors and non-GAAP Before financial of that reconciliation find the We financial represent results the business of our believe how we non-GAAP and manage better economics our business. posted accompany our that on discussion website our slides We've also today. Onaiza Hougen, Cadoret, are Brett Chief Monia, Chief Chief on Financial Commercial me Beth Officer; of Development. and Geary, today's call Development With Richard Executive our President Executive Corporate our and Officer; Officer; Vice And Kyle Eric Swayze, Jenne, us Executive and Officer Q&A, Commercial Research; Akcea. of of joining we Chief for Vice have President to draw attention like X, your language. which Slide I'd forward-looking to contains our

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

Brett Monia

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

success these we're efficient last closer with very own an And next We forward of Akcea’s move we to our pleased we our to As overall. are and the and with ability capabilities of commercial Since together combining as our our own significant pipeline into stage we across This commercial value today pipeline that achieve update, maximizing believe very excellent well transaction stronger important the our more well the we're execution even also Ionis’ the of strategy, we're represents in end progress we Ionis’ took of step fully the and making and achieve step medicines. evolution a with by of pipeline, growth. the Akcea. positioned future. near XXXX, the acquiring to company one greater

progress to X studies Our ongoing well. continue five Phase

We study in begin Phase our sixth medicine indications We're to X of year. also APOCIII-LRx patients this remain starting FCS this larger Phase additional potentially initiate year. we for testing an evaluating with when later on pivotal study, track next X also

Phase with in all mid-stage Vupanorsen, to The regardless enrollment we advanced patients quarter Phase entered four drug Beyond their to make IONIS-ENAC-X.XRx IONIS-FXI-LRx in support due Phase progress data X our this development. all with with development our development, technology of new we collaboration target for medicines is enhance Brazil. last in month And further additional capabilities. investigator a Genuity in hospitalized discovery past with pipeline, also readout we each X continue our already and of Phase studies. patients whose development excellent angioedema, inhaled for under which of in X is through expanding in rapidly ALS extended evaluation has approach a Science, IONIS-PKK-LRx our further entering medicines. Xb antisense X/X reach in reported Phase history. IONIS-HBVRx, to provided platform and a robust identification next with IONXXX, family in ALS hereditary one forms unique study medicines expected of the our with is COVID-XX severe study complications and nearly year completed in study medicine patients our of

applications reaching With marketed goal products. which our of more closer XX XXXX, large number these should result are achievements, to through in marketing of we or new a than ever

XXXX up, our Importantly, track on to financially Coming December we Virtual our we Day. guidance. will on X, hosting and remain be achieve Investor strong

will released I'll prepared the some the about up Akcea program extending over recent of achievements. will commercial Onaiza that progress soon. and and to taking of your through QX information then Richard the results, will technology. provide take highlight plans, And forward updates development remarks us our before During with hand we our is questions. integration, reach wrap be we're look More the our talk presentation, Richard, financial great to the sharing about our several I'll this making to that, review call Beth our pipeline After event

over Now, Beth. to

Beth Hougen

you, Brett. Thank

strong approach capitalized, we goal we and significant As year-end, with resources growth. our remain of to financially the well achieve

is from one integrating this taken we Our Akcea’s this the position. acquisition one, By two financial our of have in of commercial Akcea ways, companies and pipeline already strong numerous including rich goal. We to products. retain more improving achieve business is value steps further year strengthened into our the now

a SPINRAZA’s Akcea’s to third SPINRAZA year. million markets, study compared a last XX% priorities. open-label of from strategic realize in over XX% patients United opportunity resulting revenues a and SPINRAZA doses With third with significant ages. in numerous the and synergies million to the is we higher together our study the and million, the flows Additionally, an delivered generated randomized We to nearly both to untreated now with SPINRAZA end were SMA safety future basis. evaluating deliver more the sales revenue evaluate early the well. and current on next. growth use to we results study for increasing the sales cohort worldwide third activities. This quarter, in income treatment patients driven WAYLIVRA on States. benefit even across patients and and to last TEGSEDI with loyalty cohort At plans Biogen for growth to of progressing quarter, follow outside see with $XXX cash response Product Biogen deliver And we compared there markets next year, the Ionis. year, quarter, beginning is global initiate we established in next number non-GAAP meaningful and RESPOND in of emerging cost XX,XXX of SMA September, of $XX financial in integration operating our continued In to cash quarter, clinical net prior can with were to greater strong enrollment to income gene XX% to in to the advance therapy complete by expect earned pivotal quarter. growth. proven SPINRAZA’s the then safety and over of in to all potential increase is Enrollment DEVOTE efficacy suboptimal profile, benefit Biogen’s increase patients continue than $XX by

the are choosing home. is starting and TEGSEDI, been in United on We to the part continue see patients the service Europe. ongoing to patients important of across the of its in physicians has program, TEGSEDI therapy, Akcea’s due at which their North Connect. subcutaneous, excellent TEGSEDI and to States, self-injection, growth We In This patients to patients on benefits number believe are therapy and enabling by America one of patient pandemic. Akcea in remaining provided support part important thanks especially during the take

number testing place Europe, home with in an achieved hATTR reimbursement multiple with genetic markets, from physicians including multiple a endemic increasing recognized large through to-date. payers. We continue In growth the provinces X,XXX in to over tests we to successfully Portugal, TEGSEDI private new is in Canada, program see and And of conducted and Akcea’s largest patient reimbursement and revenue population.

on Canada. to achieving public continuing TEGSEDI negotiate while in In closer new to pricing focused reimbursement moved patient Therapeutics in is also Latin patients finding, all Brazil. America, PTC We for

year. with UK, from number Now are for And Akcea turning America, of to and the reimbursement in pricing other WAYLIVRA, markets. PTC next marketing year a we expand working is in FDA In markets. revenue finalized with plan NICE. the earlier to growing to Brazil authorization where in EU in re-file this generating the And and American access Latin we filed States, United Latin

revenues earned million driven million. revenue primarily programs. we from neurological quarter, over included During the by This of disease third R&D partnered $XX Biogen our franchise, several $XX

the quarter, payment in from including the a revenue R&D substantial We Pfizer. milestone $XX fourth in expect increase million

we Alnylam’s it quarter. pertains to arbitration products. award obtained expect has we favorable Additionally, and determined, award will revenues not its final agreement related fourth TTR Sanofi This add arising Alnylam. meaningful in in to fitusiran been with recently with the from The judgment but fees a proceeding our

driven Our program our quarter expenses Ionis-owned our year, non-GAAP for in third with and X Phase AKCEA-TTR-LRx, primarily by other medicine. to increased progress compared the operating last

of both the million our of With used month, successfully $X balance basis. our acquisition last Early these to million $X we we strong and quarter, non-GAAP sheet for achieved operating a complete income of results, third on net income Akcea.

Following estimated forma strong an the balance with $X.X of pro financial billion. remain position a acquisition, we in cash

advance for Importantly, entire build to our cash and balance now to Ionis’ available us to strategic and shareholders. our our patients is priorities value

cost as activities. meaningful integration financial progress statements synergies we anticipate also much be the simpler. achieving will And We our

are we profitability. year revenues XXXX track projections quarter beginning longer next will adjustment financial balance in results sheet. we interest our for of our For noncontrolling on meaningful include increased a achieve to for no fourth guidance With the our quarter, third P&L and our example, on

financial that we us including accelerate strategy. over turn progress areas commercial position with cash to believe provide to I'll call our Akcea in to our an with will to strength, update the growth. that Our substantial Onaiza the on integration And and enables invest continue

Onaiza Cadoret

Great, thank you, Beth.

With the now of Akcea acquisition closed.

established merge the on companies leadership following three into while made from primary up achieve playbook cross-functional companies one Our transition both of well an The underway. two process to is team, focusing is is which to goals. full-integration,

personalized and is with to support. Our interruption priority TEGSEDI of without to receive high-level our WAYLIVRA continue patients and highest ensure a

to engaged advance and employees productive. capabilities. Second, commercial plans our Ionis-owned we with for are looking And focused finally, pipeline of our the on are highly the we Akcea’s commercial ensuring addition remain

to greatest companies, now commercial disease At outcomes, Ionis-owned reviewing all to for to We ensure to and to as have neurological the to driving other pipeline go-to towards over month, our integrate and Akcea, economics I Day as turn to well our business our as value and highlights. And TTR-LICA payer are our we Through forward I'll the affairs, that health key APOCX-LICA. medical these our As we market. our market in our look the look adopting programs, Richard the two discuss shareholders. other research, capabilities are Investor rare for patients we processes strategies support carefully discussing our capabilities and of advance pipeline. we call with forward and medicines and next aspects accelerating plans access

Richard Geary

Onaiza. you, Thank

partner provide an filing studies to of patients The polyneuropathy Brett Phase X/X progress. history Phase Phase achievements with in track X patients TTR-LRx pulmonary and XXXX. remains to the with said, As extension cardiovascular neurological, X our next significant across quarter for natural study we Tominersen and the Ahead Huntington's in The on advance franchises. open-label study continues potential plans the to from also Akcea pipeline our data, in data to Phase of disease pipeline. regulatory with third X our update in Roche with the neuro disease continued and TTR year. Starting

treatment the plans X/X in for enter And to year. all year. patients ALS track study in ALS remains regardless program continued CX-ALS remains on year, patients, forms medicines ALS first to IONXXX, of Phase family patients to next our in The Phase nearly with for prevent designed study initiate Biogen now ALS grow IONXXX, a to SODX-ALS to study delay in pipeline second of Also the ALS. Ionis-owned next in half expected in treatment potential X/X history a medicine with of track the the of with Tofersen has underway. next our next The onset. for data mutations The FUS address with SODX-ALS four with of Phase is the year. progressing Our with of our all of data of or medicine gene IONIS-CXRx is study of X first on registrational Tofersen disease presymptomatic patients

programs, ALS. treatment of for earlier these programs continue to stage multiple advance beyond we Looking the you

IONIS-ENAC-X.XRx and and significant growing healthy from volunteer pulmonary in ENAC data, in lung tolerability. Now reported levels substantial demonstrating franchise, attractive safety the positive we our with reductions recently

lung, gives data diseases for Importantly, for a confidence delivery new inhalation for results ongoing study our franchise path positive of numerous to broaden viable broadly, medicines us more in a cystic representing in opportunity the significant growth. fibrosis route a these us as support of pulmonary opens to antisense and greater for also our

of study later IONIS-ENAC-X.XRx we fact, patients this with look COPD forward in to a In initiating year.

the recently severe significantly with has potentially attacks advanced to were next to development made Journal formation prevent of this complications in of progress hereditary our cause hospitalized this frequency of also IONIS-PKK-LRx year. an use a demonstrating severe IONIS-PKK-LRx. study it's in Enrollment with COVID-XX in with program medicine reduce Earlier potential or also complications study Brazil, the angioedema in from X We is investigator a the in compassionate reduce, PKK patients expected COVID-XX England patients in now results Medicine of designed HAE Phase study data in the New virus. year the HAE. to characteristic complete significant with of the published patients into bradykinin, the of the with

patients Turning now driven cardiovascular disease in LPA to expected to X of the Phase XXXX. our in with study franchise, continues with Pelacarsen cardiovascular progress data disease

X Phase patients study Our cardiomyopathy in TTR also with progress. of AKCEA-TTR-LRx to continues

our including triglycerides progress in year. which is studies large X also conducted and with patients the Pfizer initiated a disease X is cardiovascular hypertriglyceridemia. LDL-C dose this a recently planning out of despite next severe with maximum Phase This high-risk for excellent in Vupanorsen, over Vupanorsen, the study mid-stage outcome LDL in cardiovascular made therapy. of million findings strategy, elevated is pipeline. its half of We being stable focused studies and or despite the on Phase Phase disease study read with study U.S. in expected to dyslipidemia, support planned cardiovascular second which program in three patients To of Xb representative treatment, lowering X is patients at Pfizer

all these XX disease end I'll of study expect of move year, portion and will targeting the underway We cardiovascular of with AHA PCSKX to call of of subcutaneous this studies the XXXX. closer marketing that, of AHA Phase XXXX. forward presentation update from our at three back forward later We to formulations the an FCS. turn of to achievements this And the before month. AstraZeneca to with These the AZ’s for providing more and in X applications Brett progress patients And initiating both medicine in us medicine. on we AKCEA-APOCIII-LRx look call. oral get treatment the through updates include this over at look the close a or to to

Brett Monia

Thank than that to pleased you, Richard. ever. stronger Ionis In is closing, say I'm

several taken strengthen position. financially We recently have to strong and steps our further are important financial

for one complete, are now us one goals acquisition Akcea company we the team strategic the positioning one With well of with in leadership set future.

great achieving of a are We the business. across success deal

continues pipeline deliver for well Our patients to advance value and and investors.

are with the value-driving the SODX-ALS patients X to this X of has from Phase next be advancing, Tofersen data start sixth forward with that of first year five Furthermore, Phase studies catalyst We approved for including with end. XXXX. study Tofersen ALS. and numerous look in year's expected remaining Our we medicine patients in potential the to believe the in year, months to by disease-modifying

We also delivery X excellent successfully initiated in progress studies. Phase X have advanced made mid-stage several completed pipeline. We studies, our important and inhale Phase several important

better biotechnology products. of goal success Award in marketing this best large TEGSEDI, XXXX. even to or proud Prix new XXXX, achieve result XX market Our the also year through us will we expect USA We're our in of for very number an which a puts product Galien more in of winning position applications

the living to genetic greatly generations. medicine prestigious of This impacts second win of lives of Our those is vision that of patients development TEGSEDI lives devastating over improve Ionis’s the the in rare transformational discovery effects with award. TTR-M the and disease to with was families

which hard [indiscernible]. SPINRAZA, is testament the tirelessly And This that, for suffering transformed open SMA genetic serious landscape employees to and the lives our diseases. with patients with dedication a award call of work being to of questions. the work of first who for The the improve I'll treatment cause

Operator

Markets. Capital Please question Our with Instructions] go first from Kim BMO comes Do [Operator ahead

Do Kim

taking ASO, for my the the question Phase A inhaled questions. on Thanks data. Hi. X ENAC

you show the Do times had much tracked of reduction? dose response? of highest to thoughts the on escalated. wanted at And dose three mRNA you Just the whether ENAC a on a you how reduction thoughts weekly any why PK the your get as data didn't saw think dose with

Brett Monia

the I'll of So, and Richard I'll take for take Thanks to I'll to stab a over question, it at it. it first all. Do, then toss expand.

with was which based So data. of our very with expected a in what ENAC lot we Phase demonstrated which in in consistent data excellent tolerability volunteers normal the we safety we statistically preclinical generated in dose that as we were far. data we – reductions reductions and normal we dependent in produce in X on dependent that based preclinical achieved that effects, I said, on so expected, we've well significance efficacy are significant beyond The the ENAC dose to expected reductions – volunteers

we've we study detail? Phase as CF a Now as a which to in patients the we're next in clinical hope into get now to to Richard, X highlighted, more year. with little Richard said, benefit, in bit demonstrate relationship share want you do PK

Richard Geary

Yes.

saw. did less in and lower we also effect we as dose which was with in So that the us on we've CF I reductions saw that moved our population And COPD given is dependent the did that frequently given pharmacokinetics. ENAC study. with initiating confidence given has And than PK of the verge dose track, the the track bolus more did frequently has highest the track what dose, think forward and

Do Kim

Great. on That's would the of like a will think or And you ALS consider be a ALS, most question SODX that therapies? strategy in quick therapy you for do combo a familial and also strategy very helpful. And effective for the the types a with that just IONXXX Biogen specific mutant consider GXX?

Brett Monia

as for there for hereditary ALS. The of forms forms targeting show XXX and ataxin-X to Eric, IONXXX all or more strong on And knocking down efficacy genetic target it well in is yes, with that? this as forms is rationale of by sporadic. ALS potentially

Eric Swayze

Yes, sure.

shown some levels of pathology most it ALS involve TDPXX. be which mechanism been the to And that by of of ataxin-X, in of forms and action TDPXX by of the important is this pathology down-regulating drug modulates So has reducing pathology.

ALS. and pathology treat expect has that type most in of all any work to drug form we'd of of forms So that that ALS

Brett Monia

how which benefit. which even an We'll And data the in out yes, how see a clinic. a combining the envision SODX, efficacy we achieve show can ataxin-X you from have the beyond a the your in provide those benefit, going yes. in added SODX for about much can mean, greater theoretically to to with better in combination, I scenario think that question clinic shakes inhibitor mechanistic we'll see you see we is can great rationale But standpoint, and patients. particular

Do Kim

Great. progress taking and Congrats questions. thanks the for my on

Brett Monia

Do. Thanks,

Operator

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

Gil Blum

A This Chad, thank for on general a more questions. taking question. and everyone. our Hello, is for you little bit of Gil

you promote to they transferable indications? So, commercial as platform used, and neurological for the during drugs capabilities, Akcea to being for Could new example, the the this are indications? across platform how envision

Brett Monia

That's great excited about because we in very really one our top our reacquisition for her think want We're And as build a share we Onaiza out Day. said accelerates and that. to question. do we're the in it that to Investor as our capabilities to you Akcea on neurological. of we commercial invest discussion December and will at these as strategy believe to of that expand – like building earlier, capabilities priorities that in, that? areas she’s planning it broadly said, to she And Onaiza, on would applicable, including be details strategy some

Onaiza Cadoret

any transferable are are our that question. our capabilities economics leveraged and some payer think great things as we about health that the Building hub. Yes, areas, kind Sure. these disease capabilities, access of rare out space, across right, therapeutic

wouldn't you the can team areas space to we're as customer based be of look as where or as our synergies But the there know to there. when applied the is at you But finding polyneuropathy, and obviously, we're we to been portfolio, therapeutic of as well marketing customer neurology a types, that as to whether it with lipid going more as the see well. lot very looking well overlap As our cardiology some be facing approach has build that, customized good kind adapted a sales people that the capabilities and of see and really in. neurology will, into we area that, see on

So gives hopefully that you good a flavor.

Gil Blum

helpful. And for Richard question on That's ENAC. you. very Thank maybe a

the is little bit it makes ASO ENAC agent a on Just that. for chemistry to along the just that special of remind something in more us, And absorbable? color there

Richard Geary

are as So, up as delivered in multiple by types. well-taken far the cell aerosol to oligonucleotides lung cell uptake,

uptake, cell So the for chemistry there's general of really about special uptake. the nothing state

ENAC However, than very bicyclic is makes more the modification, which X.XRx potent sugar it X’-OME a much modifications.

And distribution we law. we've the and the similar increased within have potency so

Gil Blum

And one from right. last All just Excellent. me. question

is sellers. post-marketing forward So assuming way label at I'm that you in look SPINRAZA it? right therapy this a taking with mentioned to the study of you is gene a expansion,

Brett Monia

talked about that the study a in not RESPOND assuming sort or how has a would outcome thing. change Biogen label, impact positive of

far gene feeling too on get therapy. but benefit, to ahead that performing want demonstrate who significant confident to pretty don't will benefit are we we SPINRAZA patients sub-optimally that, on So are

that as and And Biogen wants I'm controlled there take sure the to anecdotal anecdotal a that they to is aware, not anecdotal what As don't as well is And on gene news, therapy prove they're there who SPINRAZA value – to even do out quite bit well enhance trial patients perform it. you're Gil, can obviously, with and it information so a to that shareholders. turn into doing information patients, on of SPINRAZA. of desired

So, I I but want get outside of either. ahead wouldn't realm of too that to possibility, the far don't put

Gil Blum

and Thanks. appreciate the all Thank you. much congratulations on progress. the I color,

Brett Monia

Thanks, Gil.

Operator

comes Birchenough question from Please next Fargo. Wells go ahead. with Our Jim

Jim Birchenough

guess and pipeline. remain of And related your the to the questions you on sustainably first Thanks. positive. Yes. of Akcea taking just cash thanks I then that profitable couple have flow the integration question to the and see Hi, is the guys. the progress and Congrats ability and how question. on all for a I affecting synergies

Brett Monia

take Beth let one, first Jim. I’ll the

Beth Hougen

Hey, Jim. morning. Good

Jim Birchenough

Hi, Beth.

Beth Hougen

a key future years. continue into of and closer is go think as we think way certainly about being been this continues be I of commercializing the and – of and us you know Ionis-owned focus ourselves. to pipeline I course our that integration we'll it pipeline throughout advance, So expand the moves And year to to so absolutely the would down path ours it's the Akcea

is together, on synergies, as structures going And there's companies far won't off the our – of sustain – public from capabilities building technology. the meaningful extend our Ionis-owned that cost now looking as some then building for pipeline, commercial focus that We we've will In two ways have these that acquired from cost public the to we two sustain obvious reach forward. invest fruit. see that the profitability, pipeline, companies to putting really capabilities synergies integration, for the low-hanging with and Akcea, expanding expand pipeline, certainly to and also combined wholly of

that's so us, is priority. important highest but And our it our not still and priority. Profitability is first top to

Jim Birchenough

very That's you're subcu. show but in then technology? it. know Got And And then embargoed, should make on to I how helpful. successful AHA the it's what if presentation. just IONXXX got the maybe what a other we think for oral hoping you've about most approach, vis-à-vis sense candidates

Brett Monia

– referring you're Yes, the Jim. thanks, to

You're to PCSKX program. referring the

Jim Birchenough

Right.

Brett Monia

on market all potential and on at once-a-day on from the from really the this comparable PCSKX, to. [Technical expand have that from just that to said. that'll tablet showing I we clinical rationale, we've as clinical oral cholesterol subcu levels AHA, target We'll other program want which are that Jim. viable also very clinical the program, meeting. best-in-class may preclinical also data At updated to the is program that The so oral a the the development the testing have preclinical program program PCSKX, to reductions American And I other medicine. far. entirely strategy, we we're a the in the be about liver, data, think data Difficulty] to Heart that as think or and will that oral There on both the referred oral the program, are also drive in the some testing, be we the I subcu formulation in differentiate drugs excited we conclusion the But today as little, that focused oral going in drug a like solved in the in delivery but to have will be on principally supporting focus data it's abstract reductions the clinical commercially LDL potential data

oral, – programs at the little oral oral that to prioritized our Investor Ionis-owned touching to Day provide we for planning think on a program the development advantage, significant have several we're competition. our from addition for in ability here In we December. programs differentiating differentiate And a PCSKX at bit on Ionis will

Jim Birchenough

Prion just Great. guess those, rare could see question earliest XXXX taking question. or could Is the see from of What's more programs. a disease? for the one that dynamic, I disease, that is timelines from disease Lafora, Alexander on data the Thanks some next final year? that neuro for we we of data

Brett Monia

study. because are we're several of of really as those one in about diseases of excited them are we year. So next next year trials early And a fast severe we half very the some and clinical starting path, them first clinical know, expecting just they rare and development diseases, some

you're thinking is for So But our we'll the of that on on. of an year early I be about right, would expect providing update initiation the timeframe clinical those studies in data. development strategy next

Jim Birchenough

question, for Great. Thanks guys. the taking

Brett Monia

Jim. Thanks,

Operator

Beatty Our Citi. next Joel ahead. Please question from with go comes

Joel Beatty

This Hi, to thanks PCSKX. on a for taking is oral the the follow-up last question. question

lowering could data AHA? come? for Or molecule, come on clarify biomarker how – the not, LDL to to Just at potential if much that later is a there for and like that the oral for how PCSKX

Brett Monia

with statins. The of oral. certainly PD These year data data platform on preclinical the the for strategy, That'll that developing delivery. this the we're clinical provide subcutaneous presenting will on oral patients date, said, preclinical on AstraZeneca include as whereas on are top have and for on will and data set will data and LDL oral really the focus up PCSKX And justification for but both will I principally next program would the models, be update – on programs, pharmacodynamic oral. oral subcu that saving we The lowering. for

Joel Beatty

would technology data thinking broadly then how And applied how your it. you about for could pipeline? pipeline, in PCSKX quick broadly the little And also could other applicable got oral talk the a be be more for agents? about your that bit other oral Okay, in potential to agents

Brett Monia

we And think chemistry, potency of several once-a-day target Yes, will X.X Gen subcu it developed Ionis-owned our it's focuses to what with is the chemistry is get of really at development on this pipeline. the we've delivery. a for advancing any oral LICA so Again, looking that delivery. what today. reductions achieve tablet commercially forward programs that are engineered viable that or solves we’re oral We're we we've the chemistries in programs two comparable from

Now to into delivery. talk one and next these of in soon and Investor Day development prioritized we've for them about the drugs expecting year two them we're oral or we'll move

Joel Beatty

Great. Thanks update. for the

Brett Monia

PCSKX. addition Thanks, Joel. to Yes, in

Operator

Fong with next comes Bank America. Our Chi from question of ahead. go Please

Chi Fong

Gerberry what some my on a the have Bank collaborator. that for curious like kind there’s set chance the development, if Ionis initial that. feedback if America. looks questions. oral next of on Curious And year. you the data I guess conversation you. any early perhaps maybe PK/PD couple of have this in about sometime of oral already to another with and for Thanks advancing has heard after from review I AstraZeneca have you Jason And of then a follow-up with It with formulation formulation. to further Thank follow-up had Chi Hey, is PCSKX. taking

Brett Monia

Ionis oral you to? of has I We what the What need the are first question. a so referring American been get platform may data on clarification submitted haven't to about by Can see shared Heart it? data to you on our latest Chi, Sorry, your question far. clarify outside

Chi Fong

data further Whether will a AstraZeneca you’ve of the AHA oral and of you feedback formulation you oral the time? even any PK/PD seen part you're ahead development, internally. partner presenting have thought if advancing perhaps data there's like part whether not heard that from year, though sometime next formulation and be in what of the initial with have human not Curious the reviewed the of

Brett Monia

sure. Yes, Absolutely.

PK have data completed question a the or and time will submitted study it. the from by It's we're the of the at in We clinic be encouraged program to were already, from just and earlier share Heart whether that abstracts year. American this not clinic, oral in

is related data. on those your oral forward, programs and think we've oral one program update this American we Ionis-owned why subcu. have focused on for delivery have more administration, the we Heart viable on expect oral the I yes, programs. focused the year. the data more really or Yes, and on and preclinical programs of subcu and clinical as the of at we'll – provide route So it to soon to more for focusing clinical we're justification And on using pipeline, was advancing drugs – delivery the we're data other which strategy, we commercially other an development rationale data be next question as there'll the on really the But additional reach seen program, on those

invest that thing in new in chemistries add further oral to other enhance research formulations we is The to new I'll continue just and that delivery. to

our of at sort stand deliberately. only viable isn't this So validating commercially or

We continue group. our to prioritize research this in

Chi Fong

might of on between Awesome. confident the curious, going SPINRAZA. see question about maybe kind I versus follow-up forward? initially think the that's pent-up another earnings how Thanks. growth another we are I'm I would to to of that quarters rate of allude sort – of – and And more call like of SPINRAZA for with from SPINRAZA you risdi. and part XXX question be, think attrition to you patients demand? would XXXX? Do be for of I the think guess guess reflective you SPINRAZA you XXXX Or expect that do profile? my next Biogen year-over-year Roche Do the have couple Biogen’s switched do you

Beth Hougen

function as concerned, go-forward a trend anticipate don't we wouldn't are results Biogen as QX say would We patients that on as far a – pent-up I I those basis. of that were really believe demand. and seeing a

and clinic, been of SMA for and to fact SPINRAZA I with many that the years real we've commercial combined been the in as safety now, patients. well-established well efficacy and the in demonstrated patients is the setting, that the over growth And those efficacy in think XX,XXX in eight has the SPINRAZA safety across been think profile it's more world, than as many, clinic to about in, studying now profile ages a plus years. on SPINRAZA right a market and all types has profile basis as on a the about think way year-over-year

the we've And suggests its And the I that now, limited data that particularly lots in oral. of data benefit about got that patients. you supports is it, lots So younger to the data think think the competition and there's right limited profile. really as

and and older your get weight the you less medicine benefit. have As you increases, see take ability the to

the has fact and with presence. and where focused States a frankly, fact SMA are most very that patients and really sets in Biogen the commercial we're combined are high XX,XXX outside the sets on that the SPINRAZA’s United of than a efficacy So worldwide safety markets, And those more it bar. bar, that with there patients

trajectory years, think bode SPINRAZA’s So growth for we those of coming next. including all well factors in

Brett Monia

earlier And too, just in well that call, SPINRAZA the beyond we DEVOTE DEVOTE had for to Beth to add looking also RESPOND of just gene higher that performance in study greater studies progress – as to also SPINRAZA or study future, planned even that on including the next think suboptimal in we're bode patients for doses start progress, are the highlighted on study well therapy, at year. in as which going would demonstrate And SPINRAZA efficacy. have as that,

the lot going further enhance on to of a there's potential So growth SPINRAZA.

Chi Fong

Awesome. Thanks.

Brett Monia

it. Got

Operator

next Our go Issi from ahead. with RBC. question Luca comes Please

Luca Issi

for guys. one strategy and you on Two on Thank Terrific, questions, questions. landscape, competitive the my the maybe. taking two

Thank And strategy, just forma billion how what and the the for you designation competitive you we've Akcea and your implications maybe think BD thoughts maybe orphan approach for some on pro of if of your Novartis receiving any seen $X.X for position acquisition landscape, oral the that talk Wondering on splicing on changes of can cash strategy? program? level I two, the Huntington. drug you. their have high modulator So, are

Brett Monia

and program. that you somebody, stab first perhaps, the Huntington me a And Yes, or too. about help with the then, one, at could Eric, Beth maybe I'll talk take

Day the diseases the Ionis So at general, is Onaiza technology more about The as will December, rare build talk to acquisition it with. prioritize strategy talk acquisition bringing of accelerates which strategy right – prolific. build this it highlighted, line ones we'll that types incredibly in in – our at in to is Investor And we're for will is, Ionis-owned our with path And strategy our least is – towards but and platform, those forward. of detail Ionis start going our the about in focus we future. prioritize commercial that. the and we'll diseases to on rare Akcea pipeline our and

many drugs bring each continue We into new year. to development

will Some necessarily not the should planning to conform of initiate, we're now. those drugs commercial strategy that we're implementing, say I to that

and maximize the aspect So to we're organization, organization continue pipeline, for a of strategy that's We're value that continue our of commercial stakeholders important Ionis company. we development hybrid, very so. growth we partnering value do a Business and the best our to to will think a a to for all will we're be our the maximize we'll continue and of maximizing technology, the partner. to

I So, strategy to and I continue diseases, the do of Akcea our force will make to less want that in in still but partner Huntington? capabilities to areas partner acquisition the Ionis. more us would say building that rare guess those may take and commercial to we'll you Eric, sense

Eric Swayze

trials drug designation. it's also. for with I older been the That's assume about branaplam Novartis that's SMA around Phase orphan a and for X while an you're talking in been

Huntington deal disease. with modifies the And out So that comfortable like directly, of about Phase you Tominersen our know, I'm I'll happy perfectly is lowering different read the X think I lead you I the space, best and our XXXX, medicines in Roche. trial Huntington's try to something scheduled two splicing it’s as the with Huntington in in two strategy drug, let with strategy to genes. your in conclusions the and

Luca Issi

thanks Super helpful, guys.

Brett Monia

Luca. Thanks

Operator

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

Unidentified Analyst

to as you with treatment if results. Hi, wait clarify just What on also are reductions attack updated duration timing mainly Thanks. I for you extend a be for the Paul. as in LICA and could super helpful? it would be for that Katie the quick this question is HAE had we looking well, whether or rates

Brett Monia

why that Richard, you don’t one? And take

Richard Geary

Sure. rate treatment, is to on also terms confounding which focused. with And be Well, of that issues of end products. while occur it's breakthrough of going the attacks some going the of one in the course point is be existing attack on to

we're evaluate that. see to expect best-in-class That's the we study a is taking what to approach designed is response. So and the

frequency these of the asked, you if which breakthrough one platforms question the that of existing they one out to begin is extend of that, to frequency addition than to to issues issues. more dosing, with have month, broaden their weeks two is In or some they the

be less applicable frequent, ability So of more and rates. or be at administered to in long looking this able kind our at the more open-label medicine its be competitive program for we'll to and half-life component with long-PD frequent administration even

Brett Monia

You got you. it. Thank

Operator

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

Yaron Werber

I have a questions. Hi. up. of Yes. taking for And thanks couple

PKK for be because is one, last just other quick key role. is you of relevant one are maybe first I bigger The of And a to you feel Or on kind do Or sort have to do less potency you? the the competitors view there's maybe then that a follow-on follow-on. and competition that frequent of the that dosing? most compounds

Richard Geary

aiming for think what evaluate that. to in nailed beat I No, we're us That's our and this that's you to the hurdle allows it. design study of

Yaron Werber

every, What PD? it you doable. a what two do is months stretch-based frequently, think or it on potentially mean, certainly like like dose I in can Yes. less sounds you about you, And can you monthly that see every

Richard Geary

two matter every supports months then to some starting actually with regimen. a of it's experience PK/PD that the Now, just get and

Brett Monia

monthly we it Yes. ability if move from actually an said, there. And as advantage marketing versus we to regimen a obviously patients. is represents feel the But standpoint whether a bi-monthly for Richard have does

Yaron Werber

Yes.

some Okay, you. potentially what does our we me correct then wrong. great. can for you see naive that soon I Phase moving Phase failures, that final GHR-LRx. Thank to also I right. And naive enrolling I'm would be or correctly for if failures? that you're of the think X program should X at looking some mean acromegaly don't data, question of patients, And on just is remember If that we go

Richard Geary

Yes.

that patients. the initial of studies its that, entire Does your are answer conducted uncontrolled then all call study biochemically. our in can year failures, covering some report we out the that actually are some with spectrum, that uncontrolled the the starting So will it you we naïve. next question? We're we've second patients of who And on have are some

Yaron Werber

Yes.

right. So the data,

to thought thought to based or the of in this two to X or within that's design assuming, data, there. study, do a head-to-head Phase this of go go prior based the expecting segment. And positive sort on is results we're naive then the a ways second against the So Phase single-arm that I to is them mean, sort go going on failures, in is the there's be maybe the X can naive. in you the then to

Brett Monia

the interactions and teams The working are yet designs are out the us. regulatory Yes. still before

would I point. at you design giving be a So premature in this – think, I

Yaron Werber

great. Okay, Thank you.

Brett Monia

Yaron. Thanks,

Operator

Chen with Our ahead. go next Vincent from Bernstein. Please comes question

Vincent Chen

the of and thanks of Congrats A ASOs. on and ones delivery progress questions. for taking couple my oral oral on program quick the

things mentioned would formulation continuing and can be The chemistry one are on first guess to for they try differences? is oral or what is bioavailability you from about you expect meaningful do LICA one provide bioavailability or simply boost what orally, be, would new bioavailability? thinking there your I'm probably if different And color I related ligand would formulations you another looks ASOs curious how and were dosed on guess research I to some be, differ of some the oral do chemistries second to on between you would pretty of similar you're conjugate enhance delivery. Could to new earlier, the drugs

Brett Monia

anywhere. several, also similar pass start was liver. for the Gen drugs who's And what with in the delivery it unlike And drug, oral be the is drugs. on bioavailability thanks that many our oral with of to effective we've thing, the shown antisense But, and that we or I'll oral important target of different X.X the with to our that very also and transferable we to that experts be have demonstrate I'll we've in what’s but previously reduction oligonucleotides very comparable chemistry delivery – one a get drugs across, this to bioavailability to non-LICA in stable And be we LICA. – but Richard, LICA Vince. is believe questions to shown that first shown

first-pass that the little So directly maybe could on Richard, drugs. LICA expect bit about a talk you we And sort with what is and transferable. it thing of

Richard Geary

and going that bioavailability LICA XX% dosage the why give that something drugs. that's Well, comes like so I or to you to formulation. gives see down that a the starts justification for the can data you're relevant very why molecule to really it subcu is It be important. potency, mean, clinically all

across the down about to LICA comes oligonucleotide you and of liver comparable is a the chemistry is give the question present you you chemistry different fairly platform, it bioavailability, bioavailability goods our that the what with So cost a across potency, have types. different asked to the different first The versus LICA actually subcu. difference the

a the receptor liver your if the parasites passes drug to you So scooping through of a for by liver first the as bit buck, the on you the millions it liver the copies up and to of will, first. their With at concentrations bang presenting allowing first. GalNAk of get see drug low

would So you helpful? that unconjugated and that get oligonucleotide. an with above Is you gives what extra, over that

Brett Monia

would just these accumulate that so so parasite. are long fact add – I And in have the and acting also, to us drugs stable allows to that the

and and very is not be our so to because to are commercially XX% very less significant things. the has a oral of of platform. for our get justify But half-life fluctuations and drug going So, bioavailability XX a bioavailability hours long drugs or delivery the lasting of you're viable with that fact that that bioavailability very kinds important all allows

very also a to important that's remember. So thing

on obviously lot irons formulations, as stay there, tackled the doing We're with sharing we've stability strategies work set, fire. our in in a we a of our progress, lot not new work have we're we've Vince the but of tuned, drugs. far As

So penetration, the we're really blood. more drug getting into on focused

Vincent Chen

then progress. the the insights I'll see. stay I again the Well, taking question. on congrats for tune all thanks and Appreciate

Brett Monia

Thanks, Vince.

Operator

with Foroohar SVB Our Leerink, ahead. next question comes from Mani go please

Unidentified Analyst

Rick Hi, this for Mani. in dialing questions. Thanks for our is taking

inhaled engagement to about could mean, ENAC ASOs were seems lungs, have in are takeaways be selection may what thinking ENAC, good learned may to I so were readout, back be broadly the moving discuss been target other in for the the main how what from development? target you're any wondering, we there First lessons you and that

Brett Monia

lessons the shown that say referred and for based chemistry Gen first are drug aerosol really Gen with humans. time in an that that learned earlier. significant the get the our is Richard substantial our reductions that along, X would with delivering we've aerosol outperforming It's on oligonucleotide I that antisense to statistically key chemistry X.X potencies we target in

in pulmonary huge our a overall, us for emerging have disease. confidence lesson that and drugs we that's in gives pipeline several pulmonary think development we learned other So in that

one clinical is year learned. the drug. least of at the – development which of year of next the in or expect next And second we very important safety lesson tolerability testing reach course to a of and development One potentially

the is, expected The is in very preclinical doses these what were effects to which well predicting, confidence, the see very but third important. humans, we give data is saying that we us

Unidentified Analyst

Thanks for that. it. Got

the into and just quarter the question, on of there last seeing cardiomyopathy? enrollment Second you're and something if been how studies status time-to-data just in currently LICA, to polyneuropathy see for the are any there's recruitment TTR update any trends you've thinking over Phase but X for about

Brett Monia

full enrollment. what expecting interim which readout changes There's in is and X X study And and activated studies being sites had of cardiomyopathy The getting but like are we're that so studies. into due And no to XXXX from an we publicly we're the moving in so polyneuropathy our XXXX enrollment studies data with the polyneuropathy clinical data they're Phase Phase And sites think overall well. COVID-XX some study. and out We've said for both not in trial activated seeing both set. the and in have and impact to Phase we're cardiomyopathy for we're that we far obviously on, designs, data analysis enhancing taking we're we a are pleased timeframe on in details. but are timeframe providing data polyneuropathy that It's we competitive X also the in, the come enrolling, situation XXXX.

Unidentified Analyst

for Perfect. right. taking Thanks questions. All my

Brett Monia

Got it.

Operator

Our Jen Company. ahead. with & next question comes from go Laidlaw Yale Please

Yale Jen

Good questions. thanks and afternoon the for taking

maybe could you terms elaborate the You of plans Pfizer’s Phase the is the first regarding – The more the color studies, that. for Vupanorsen in by mentioned bit what's but three Phase after pivotal Xb study? more Pfizer, study a one little on X,

Brett Monia

Yes, it's perfect a Knock fit for out. it Richard.

Richard Geary

Yes. question. Good

preparation in about much Phase told because platform. Phase these a with X as study I selection for hypertriglyceridemic a profile are dose cardiovascular patients well. hypertriglyceridemic the will disease, in program and Xb is direct risk also that cardiovascular includes severe high So be you for outcome trial, it's learned, the dyslipidemic learned patients

study a And dose for is so finding that two range will populations. it the programs set finalization those those up two protocols of and

Yale Jen

the outcome cardiovascular study? there a as is you on colors that will one, Okay. and third any point Is use end which

Brett Monia

one Yes, Xs severe the and is the of that. a outcome trial population, Phase couple planned then cardiovascular hypertriglyceridemic for trial there's

Yale Jen

any or is Okay, Investor Akcea know helpful. additional elements Only question, angle more least in more one That's this will more great. added the you at on Day. this there Any give elements foot need XX,XXX after very point, of at terms of acquisition? – thoughts terms at to I in changes One acquisition colors other the be question.

Brett Monia

really, at than elements we'll or step that really more building But commercial how I our we talk very commercial there's this mentioned efficiencies the excited as acquisition. in a future. we've well Day, as on Not building this of based Ionis, any think on key strategy out, as it our that the when about we've financial closing announced based Yale, Investor strategic step important plans said We're the is we've very the say a of for additional today wouldn't what for many what that for put growth reasons both are and this. the is about our We highlighted future. towards

and in more I more than expand So, on it that's can't right talk your that there question. a lot really about we'll December.

Yale Jen

really a on it I and progress. the lot. appreciate Okay, congrats great. Thanks

Brett Monia

Thanks, Yale.

Operator

comes question Fye from next with Our Jessica ahead. go JPMorgan. Please

Jessica Fye

my good for morning. question. guys, Hey taking Thanks

studied Phase one generally the higher in Another in was looks Xa. Xb on like what than it being Vupanorsen, studied Phase doses are

doses, you're broader, CV how about Xa the efficacy much triglyceride thinking more on just Phase when LDL-C. the risk achieve curious higher relative non-very to So hoping I'm endpoints look you those population group, to high of the like at high kind

Richard Geary

point that lipid question. great in are non-HDL-C, Yes, the particles group Really end which of is a is atherosclerosis. involved primary

triglycerides, So increase LDL-C the is LDL. an on a the increase and combination increase on of

disease. and the component. in remains single Look, a circulation not that it's cholesterol patients it's So in cardiovascular with basically triglycerides remnant the elevated

Phase and which know it's your being don't in risk, the with different population dose a Xa the question, that now study. finding I in So cardiovascular study tested if than studied doses and answers is patients we our a are range dyslipidemia population

Brett Monia

study. that's is a is Yes, patient the population key different I think X the that, it Jess in Phase

to wants mentioned Pfizer the several So for than be for dose to right and could X patient Phase different in a the Phase Richard initiate, that different, dose. the X get because they doses want that optimal planning studies an they're population

going just strategy. that to part doses So higher is of

Jessica Fye

the this and support And observed make sense. increased recognizing benefit kind HDL-C? of that HDL. What of product of makes in sticking product do in with just Okay, drugs with lack you declines for the this

Richard Geary

Yes. take me that. Let

have actually has that they and looked low on And and at a ANGPTLX. lived bunch genetic disease a no individuals. you long know have cardiovascular and extremely and in is of of triglycerides, they low they HDL, population there knockout we've carefully that LDL So extremely that this a have very population, very bearing

Now, a small hill this population Italy. the country of is in

population. where So now it selected knocking a actually in population birth, this we're from we're down, but not in studying

is you What's cholesterol, apparently lipids. consideration down about we HDL other say But all what would that is down cardiovascular guess, taken HDL been know the of to improve raising if alone I not when does is by patients. shown with atherogenic you HDL patients. do if what cardiovascular improve cholesterol remnant think take of So take outcomes the that health into not, we along is does always has I be HDL, you

Jessica Fye

you. Got it. Thank

Brett Monia

Jess. to We'll Maybe then we'll more have one long. close. Thanks, and we're take running question

Operator

comes from Blair go William Minter & Please Myles Our Company. last ahead. with question

Myles Minter

questions. the taking for thanks Hi,

this you've year, per gram for that Just wondering, trying or starts population haven't X just on got primary data pivotal can a hemoglobin if we clarity understand in of when how to interpret dependent patient And Thanks. you about, some moving going talked one whether just sorts? meaningfulness population, X am TMPRSSX of beta something this just Phase on explain in into maybe maybe cell. next we the increase forward, I endpoint, the I'm clinical terms the to and deciliter go in transfusion not do to trial the that.

Brett Monia

Richard this. take can expand start highlighting anything worth and on I'll beyond the maybe

drug changes on opportunity only in data, indications good other X, saturation. also about we as in in and this significant in levels levels think that know showed the direction that you preclinical We beta-thal are intermedia excited So and program. plagued very we're as relevant showed we safety exactly transparent Phase our predict well is tolerability, patients, by hepcidin to not In were hemoglobin in inhibitors, and hepcidin intermediate the very as meaningful based population, to to which population. Myles very load what organs in iron patient for low TMPRSSX endpoint would as increase and data increases are reduce iron this those associated – well. right. is the and endpoint goals and reduce overload patient there's approval highlighted, these is and organs that increase One with in just the can the two you iron in intermediate other toxicities to potential deal the extent But in also with liver anemia do heart

I that as we've we that exploring various year can for management we've to is a Phase X we of and I the come good from the also out don't study. I share preclinical proteins. will devastating hepcidin But of to-date we iron that's It We're potentially indications think are potentially data as to the improve, novel but have Myles. also yet, next additional for think said dysfunctional don't design the potentially models out beta-thalassemia. mis-dysfunctioning, related when iron Timing affect due – real to that in is published And this study, drug of wealth of disclosed low this the exactly to in ability normalize drug haven't, So in overload the and very read that only progress. that study handle unique not that for has data the data a on anemia, levels. effects

Myles Minter

Okay, go cool. Yes, That's a definitely. helpful ahead.

Onaiza Cadoret

market with I is shows the iron both anemia survey research overload Brett's a that and to was just add perspective agent single completed that, actually just managing benefit that just it clinician's dual and point going we to of a from high. a very

a XX% gotten So from leading for to we've continues unmet the looking be controlling need. is benefit iron that agents, of clinicians the out iron are aside deal an key there product really

Myles Minter

would why have and conjugated non-life there taken Understood. opposed for a program product? Last quick from I GSK is as they Phase may but in one here, running, to product the be wrong me, the any chronic that is hepatitis, X, LICA why reason

Brett Monia

Eric, go ahead.

Eric Swayze

why that get answer the program shown trial better is, mean, the that, It's LICA the parent the ask But is. yes, were where the the the the very haven't advantage. is reductions seen – not only an molecule actually was program in one compound we and the but didn't specifics parent than that of reason LICA know that don't is of there performing performing really we is really the that why it's with well. and molecules that and LICA truthfully, different is question you'll the the antigens me next that were in the I the And

Brett Monia

a very significant that Yes, potential versus GSK this We're but seen understand have in us drug it, not future, excited LICA that the in they for a And increase is we Myles. from trying as they a is potency the about this with think HPV cure we non-LICA. a licensed has too. only to LICA where are

Myles Minter

in. Fair enough. Thanks for squeezing appreciate I it. Thanks. me

Brett Monia

Myles you you everybody. and Thank thank

great on excited want of participating of a we're today's Remind we're we making. Investor finally, of you. then Xth, you to Thank progress you where everybody for Day wish call. be you thank the the upcoming about lot some So And detail. with really that December sharing progress, on that I our again all day. more a We'll

Operator

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

may You disconnect. now

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