Ionis Pharmaceuticals (IONS) 9 Aug 232023 Q2 Earnings call transcript

Good morning, and welcome to Ionis' Second Quarter 2023 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, Senior Vice President of Investor Relations, to lead off the call. Please begin.

Thank you, MJ.

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

call. Financial Richard Officer. Brett Officer; Geary, morning Global Swayze, Chief me are Monia, Hougen, for Officer, our Operations our Executive Schneider, Beth this also Strategy Product President Chief Development Chief and Vice the join Officer; Eric Officer; Executive the Chief Eugene of us and With portion Chief Q&A and will Onaiza Research; Cadoret, Development Clinical of

draw to contains like attention statement. would X, forward-looking Slide I our to which your

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

With that, call over to the I'll Brett. turn

XXXX deal Thanks, us today. great great in our advanced for important Wade. We thanks first many focus ways. in capabilities. our continued we building joining made the progress strategic morning, half a achieved Good priorities. We to We everybody, our of on as important and most pipeline commercial in

olezarsen right near-term transform biopharma, Launch Ionis for patients. of eplontersen, we focusing our medicines abundance chapter Ionis an fully for a delivering new next the preparations opportunities, as and writing on are three on highly into are We successful, track. integrated donidalorsen commercial to

track and additional and to AstraZeneca limited under polyneuropathy globally, for ATTR ATTR eplontersen to U.S. options. end today outside patients share of in currently the We the we're U.S. is goal treatment the bringing year. the before review of who submit the regulatory filings Eplontersen have on

to continued its from eplontersen And highlighting data deeper longer a will durable out that improvements importance NEURO-TTRansform longer and XX the with attractive profile. month. Richard few further from dive study term pleased minutes efficacy showed data. these for to also of week we the are reported baseline in eplontersen's data Phase We into These months, contributing XX last the X overall term

last in enrollment in our reported with just with And week that largest CARDIO-TTRansform patients. landmark the this of we X,XXX population. This than completed patient cardiomyopathy ever study is conducted full more study eplontersen ATTR patients

the BALANCE is major late FCS in top line in of this the year. study olezarsen readout Our second stage Phase next milestone half X of the

in olezarsen X We our independent first or which expect much prepared. larger FCS studies parallel, advancing In in Phase Ionis prepared well also we're to be for. severe we're well commercial pivotal SHTG, the we're the patient population, for launch hypertriglyceridemia, and olezarsen

X the also on We us in of study keeps year. OASIS-HAE milestone year. next donidalorsen the enrollment in track data half completed in earlier important first this Phase This for

against to study open-label at open that be HAE consistent to previously and reported our label attacks randomized the encouraged from data two-year date. X generated continue protection announced line We donidalorsen and study data we has We sustained extension extension efficacy one what showed Phase with in recently year. our by

from the we've and also the just suboptimal SMA. intractable approval a the two to our be U.S. achieved neurological diseases. RESPOND for of two market types And breakthrough to approval now new on to of severe data want treat diseases. highlight SMA accelerated proven FDA who in continued approval global SPINRAZA's have treatment was efficacy their recent further validates strong QALSODY with the the to people success QALSODY, treatment highly response we diseases. with continues had ongoing therapy. of study recently, I for The treat QALSODY's SPINRAZA breakthrough capabilities neurodegenerative patients developing patients And brings encouraging all the to further has a neurological gene reinforced to medicines their with medicines SODX-ALS And families. hope and leader commercial with in market of

medicines Today, diseases, for we much clinical development have for including more. XX in ALS, of diseases, dementias, forms neurological other neurodevelopmental treatments and

new industry-leading focused our record medicines track we cutting research is neurology neurological development in to address into team in Our remarkable severe advance making innovation, diseases in With for achievements further great neurology driving in are a also to making of progress leadership therapeutics. advancing patients need. edge

pipeline IgA row, nephropathy, of X X has for stage late robust increasing expanded. separate XX our a initiated late indications. second drugs Additionally, X being pipeline recently stage eight developed our to quarter Roche Phase Phase development for the in in IONIS-FB-LRx Phase

come. robust late of pipeline to for a few deliver for stage sets many the X up readouts Our new steady us transformational data cadence to years, Phase next Ionis positioning to market products the years over important

collaboration last pleased compound a follow-on Novartis, demonstrating confidence expanded announce to latest pelacarsen generation as to capabilities next to were our with utilizing edge Ionis' a cutting And we Lp(a) create just our week in potential targeting their technologies.

is pelacarsen As and filing called potential plan an outcome well ongoing in X Phase Lp(a) cardiovascular HORIZON, for more with enrolled X,XXX which data The HORIZON fully study patients. XXXX. is a than progressing with a study is reminder,

first goals other to achieving including accomplish discovery cardiovascular expand key the track financial potential This our development. and for cardiac strategic recently preclinical us for Bicycle neuromuscular our technology. capabilities into XXXX achievement cardiovascular guidance. expanded we a enter targeting business, our in-license muscle to muscle importantly, our our utilizing when diseases. the And first development to highlights advanced This into on across drug drug drug like also our our further We we franchise is remain

pipeline preview call turn I'll the that, With events. to key coming Richard our recent discuss over of to progress and

results review quarter taking will things I'll second questions. then Next, your first and before financial our wrap up Beth, half and Richard?

an benefit half of of in medicines new data year, this us reported goal to and patients demonstrate that substantial market. further study potential Through first to to Brett to to Well, believe We even Brett. with eplontersen's our NEURO-TTRansform the to to recent eplontersen made the as polyneuropathy. from pipeline we've The reduction you, to for week XX the demonstrate ATTR profile. a sustained positive important closer Thank strengthened we competitive just CM-TTR in mentioned, provide and weeks, bringing the substantial eplontersen's baseline. date confidence base abundance continued deliver have data progress our in XX patients concentration compared

and you of baseline treatment As of mNIS+X Norfolk graphs, Life encouraging. XX very from the both weeks from through see Quality changes can the are

data the of patients eplontersen's to to at data Importantly, report continue this weeks with We a medical treated impairment life in treatment. improvement set add These XX totality of differentiated profile. of eplontersen through demonstrate the year. conference data a number the neuropathy further of to and substantial later quality plan full supporting

this set including Eplontersen the commitment our Positive for patients than recently further on safety We cardiovascular outcomes conducted Phase in of is review U.S. our currently X to also cardiomyopathy. CARDIO-TTRansform of AstraZeneca, agreement With X,XXX bringing is to the the eplontersen results study broad indication. ever EU We patients. more in under recently eplontersen in study U.S., patients, we end in the additional our a study Notably, support ATTR NEURO-TTRansform America, and largest enrollment expanded AstraZeneca's our and this the completed demonstrate filings Latin we've efficacy this for benefit planned and world. include the designed confidence underscoring outside around year. with in from study. to the seen to

XXXX. half as that of in report to complete in data CARDIO-TTRansform, enrollment the early Now is first we expect

the outcome evolving with As are on most factors trials, landscape. based rates clinical of a event our variety and timelines including

Following bring the we market next olezarsen to the will is we expect ourselves. first drug commercialize eplontersen, to and the is

to FCS a a olezarsen rare much indications SHTG. indication current and And both are FCS, severely population, pancreatitis atherosclerosis, poorly fatal by elevated and while are triglycerides, for characterized standard We is broader of represents and are indications, can managed developing which by care. the both and two SHTG lead

the track FCS study X this on half the Phase of BALANCE remain We data report second to in from year.

million support with With for to program advantage, believe patients development severe broader progressing well. olezarsen mover and blockbuster U.S. the hypertriglyceridemia also in we a is opportunity Our indication represents first over SHTG X Ionis. the

baseline of dosing through in patients medicine, a year We two us two present year. mean in study on from OASIS-HAE half completed treat across of line track results rates these our on Phase recently enrollment we keeping donidalorsen the wholly-owned data year. this for open-label donidalorsen X at next behind extension for sustained In hereditary top olezarsen years X showing overall plan study XX% conference of to data medical later reported HAE closely to is angioedema. We Following next Phase first the groups. donidalorsen attack the an June, with in reduction

fatal generated data to in the on to totality sustained potentially donidalorsen Based attacks. protection preventing demonstrate of the date, continues HAE

in confident us donidalorsen's are profile, with a we result, competitive meaningful providing a commercial As opportunity.

deliver continues to a medicines. groundbreaking In approved franchise approved the it industry-leading genetic Our treatment neurology April, SODX-ALS, for of with first cause QALSODY patients target the making ALS. to FDA

treat have and in including two to In addition, development X medicines neurological eight in Phase diseases, clinical X. studies we in XX Phase

priorities in One our expand highest of is franchises neurology to and cardiology. wholly-owned our

that medicines the to have currently We clinic. moving quickly are wholly-owned several

research neurology commercialize we and that is turn medicines team to into great world-class plan to Our working develop science ourselves. great

deliver lead years ensuring a of in study several continues and for market starts franchise over expect us to new our of the to the cadence clinical to medicines a come. growing result, new patients number years, we a steady to next positioning innovation As neurology and

is I continued open-label positive that infants the in gene X patients on previously to And from gene RESPOND RESPOND measures with XX,XXX extensive benefit add body SPINRAZA. suboptimal to Results on safety patients SPINRAZA a touch years. to response SPINRAZA's data year also for patient. to toddlers like patients therapy. an to with evidence in profile interim the SMA evaluating motor these study with treated favorable includes treating SPINRAZA eight based showed improved on than from of treatment. results safety briefly analysis the therapy. more of two in ongoing profile Now, SMA treated SPINRAZA interim well-established function demonstrating Phase most that data patients would up and These study of recent a demonstrate with the

RESPOND, to decisions treatment Biogen remaining addition need the and community. In to ASCEND together address the inform aim DEVOTE unmet and studies for is SMA conducting that

for study, that new program in of pivotal consecutive nephropathy. XX bepirovirsen drugs other a recently late-stage B-Together quarter Phase a presented Xb of Our Phase bepirovirsen patients, We B-Clear durable indications. have IgA expanded study. second The pipeline is pegylated data later start from in total development with showed HBV that data a medicine GSK with the program development which present resulted now EASL advancing robust treatment patients stage interferon. plans our for in from response IONIS-FB-LRx GSK late X the bepirovirsen this separate this new year the at responders the data with in presented started combination earlier a eight evaluating in for in year. in chronic to

an additional eventful In totality, launch track after have eplontersen. events, filings we of events a olezarsen for first In Phase half remain FCS, regulatory the this important key as we eplontersen with well advancements. had of approval potential second number on U.S. half in clinical outside positive the data and for year, including many to our as next U.S. X and medicine data

on throughout We of and events the will you our rest updated progress the these keep on year. more

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

support the of you, further we quarter, on In to continued our our to strengthen in priorities. goal Thank make progress financial our strategic Richard. foundation second

second the fund to across reflect meaningful for opportunities investments revenue results financial our business. Our key to growth our in quarter generate ability

We and $XXX respectively. year million of and for half first second quarter earned this of $XXX revenues million the

same XX% periods increased partner significant the by driven for and XX% last quarter the revenues year-to-date payments. Our year, over

advanced half for medicines our We over As activities quarter financial end increased capitalized and at readiness bring well late last and billion pipeline, continue operating market. and anticipated, same year investments our our stage cash resources with in transformational the to of operating to programs. periods the our to as deploying especially expenses year remain June, and $X.X us we enabling the of our first this loss commercial the second

to mitigate $XXX address new two, equity the result, the our the low to the approximately potential able the flexibility all of in earmarked were to XXXX the cash cash, while quarter, maintaining In have dilution. retired extended convertible of continue with XXXX approximately our And or at maturity convertible objectives. our pipeline. notes a of and our opportunistically included our combination our We notes investments notes. second the retained cash we importantly, a we We million to key us XXXX notes XXXX to the making coupon. to end And we repay XX% enabling remaining June refinanced value We as of accomplish retained notes. a driving balance equity XXXX

SPINRAZA's the million year-to-date. for global sales $XXX and were second $XXX million quarter

and the revenue same As compared expand last their resilience essentially also in Biogen against emerging to $XXX important we robust period. a competition were SPINRAZA's U.S. result, sales returning to corresponding royalty existing generating $XX million global million periods and earned goal on working for of Management to SPINRAZA's year, flat data the the in efficacy SPINRAZA's Program, Life progress SPINRAZA good Cycle making markets abroad. By while from consistent growth. reflecting is

of to in both $XXX the periods same and quarter million of We year. second $XXX substantially earned compared million the revenue increased year-to-date, last R&D which

for license the AstraZeneca second technology eplontersen, numerous included AstraZeneca Our included significant is programs for milestone and and also reflects a development Notable QALSODY $XX IONXXX million Biogen a in sharing payment $XX for payments for cost from advance. which Xb $XX America the the Latin creating Ionis' into as from earned approval. study payments, from million quarter million partnered $XX for advancing R&D Phase fee revenue rights. NASH value million U.S.

year, goal in enrolled studies the with are expenses X non-GAAP last to approaching second quarter and ongoing revenue as our Phase aligned and planned compared growth, our for our As or enrollment. year-to-date of fully either increased most full invest operating to

expect, in study expenses. higher increased, would our you As which clinical R&D resulted costs

prepared SG&A year-over-year. Additionally, eplontersen, as olezarsen to and also our we increased modestly donidalorsen, expenses launch

XXXX half track financial meet including of us and on year to Our keep P&L our our results guidance. for guidance, cash first the this

numerous with ahead, revenue. many continue to programs earn opportunities additional partnered advancing, have Looking to R&D we

in back the weighted anticipate revenue towards end be We second will half the the of year.

to earn U.S. expanded $XX payment are Novartis. For expect recently additional our revenue of amortization recognize eplontersen, and for a the milestone with example, eligible to million collaboration we from we approval

Phase over expenses estimate the the operating we year last this capital increase XX% year-over-year, payment between R&D to and of full our increase upfront continue excluding with Consistent course X to related our our project which We intensive expenses to guidance, gradually from year. includes will expenses year. studies, XX% Metagenomi

bring the approximately to SG&A to prepare continue project expenses year full our to eplontersen, as million we to and also year-over-year $XX We market. olezarsen increase donidalorsen

launch build share the we to assuming the example, December, well as SG&A cost of expenses. approval our an as sales as eplontersen, include eplontersen in For move closer late launching will to our expenses out force readiness additional

to Over few launch several years, the next medicines. poised are we

a operating in positioned project As we of revenue result, by and period modestly we significant ourselves, a to for are importantly, more We investment. our expenses to are deliver programs grow growth. keeping

we growth our are advance revenue sales of continue potential follow steady cadence to revenues And substantial our have base drive a value combined peak to of to and multibillion-dollar commercial revenue behind, medicines closely we a poised shareholders. and partners to positioned well for programs. long-term that near-term with meaningfully continue expect three our contribute R&D overall to opportunities Additionally, as to substantial numerous

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

Beth. Thanks,

our late new on eplontersen the events an have commercial to forward this of well delivering portfolio priorities And We're patients. our and the rest two diseases December medicines add to pipeline to way to market. abundance this second focused of planned laser could important with of we now to medicines date, key late-stage our treat for on breakthrough also achieving regulatory half. PDUFA the advancing our additional we're devastating with year, goal Looking We the neurological year. on

track activities near-term each of opportunities. go-to-market with We're on commercial our for our

for positioned come. behind. our following to late-stage approaching many bring for with ATTR with And pipeline, patients AstraZeneca with Our we're and of closely is eplontersen medicines independent first quickly with our in polyneuropathy well years to launches additional planned to donidalorsen rich olezarsen launch patients

to therapeutics, to in We cadence sharing forward We increasing the areas leadership to RNA medicines foundation to strong steady transformational innovative look to priorities. positioning also well new make technological drive with And add progress us the our into potential to invest value. continue advancements advance we enhance us our our future. financial position our greatest as in our enables of to

for questions. And with we'll up Operator? it open now that,

first Minter William from comes Today's [Operator Instructions] Blair. Myles question with

Congrats quarters. on the

space the outcome to that First conduct been peer well outcome stance put some one companies that that you language population? an olezarsen. in conduct to. study know trials the on of changed that hypertriglyceridemia developing doing study need your Has that There's in to as an And the would they severe an be need is outcome or there out in sort study? of not language I is from your looking viewpoint the wouldn't one

focus severely no genetically pancreatitis, component acute on morbidities. particularly of triglyceride, triglycerides. Onaiza -- -- cardiovascular FCS on out a to We're from metabolic is We're elevate Myles. research. maybe to just is diseases, on I'd preparing patients but -- of These suffer elevated of severely that can and the -- Myles' launching to done for harm's in way that we're severely to like with diabetes caused ready FCS And SHTG. kinds elevated market, to genetic disease. there's focused elevated triglyceride and not. have suffering other We've evolve chronic getting Thanks, to also all from to for and patients our for cause are Absolutely are we're where known severe severely expand preparing lot pancreatitis triglyceride question. of There a patients olezarsen the

a close we've X.X where This yes, is care over as just we severely to the get out to of great these meet for before, to Brett need over of sufficient them guidelines, pancreatitis not is XXX have highlighted, unmet the actually to patients acute particularly way marketplace, The required XXX we are risk. is triglycerides that risks elevated a harm's below the Sure. that just XXX. market or possible them standard see as the or patients. for spoken is goals medical to Myles, which get in million meet

really to market on drug looking So we defined for the as FCS. that, getting -- disease, genetically both have we're forward the rare for

expect and hypertriglyceridemia that and then We BALANCE forward then of to -- ultimately, into end year the by into the looking the to launching space. data severe and see the

that question ocular were that And vitamin question data also submitted my reduction deficiency with you've do think ATTR is, you that on polyneuropathy. that second data? I supplement week that data efficacy was the trial. Obviously, FDA understand for related discovered that deficiency they in A XX purposes events just is for get and safety data, see that. just it safety I you But have the don't but only. there submitted you FDA can the to will

Eugene?

your for Thanks question, Myles. Yes.

safety So routine including day of was XXX all the we part submitted information, with the the as information NDA. comprehensive of that a update

review. of that the was the all and related updates So the the under the were are safety as time update at submitted well as available day to to data XXX FDA

right, on Everything Eugene? track,

Everything on track, absolutely.

Debjit question next The Guggenheim comes Chattopadhyay from Securities. with

siRNA does allow markets? first does This and eplontersen presence the is significant for to potentially AZN's to How Debjit. approval ATTR-PN in on to plan market. Ionis AZN be any Robert options And compete against

Onaiza, do want you Robert. Thanks, to...?

very for seeing halting We're and duration We then with of excited was number data Quality a mNIS+X Robert. substantial data obviously, disease the TTR progression a suppression sure, in Yes, Life. both and week of seeing. saw that TTR patients of Norfolk in encouraging. sustained we're improvement and very effect XX The

great really a got data we've package. So efficacy

to research relying we've in with taking done, are HCP's not administration preferred home, them, taking medication control allows their office. into all profile the be wherever from the at more going of with disease of patients and on empowered have they the the We self-administration

really us The marketplace. with way profile to this self-administration gives the efficacy combined a end strong

have patients this before, still of phenotype. and identified, we XX% less diagnosed those XX,XXX mixed treated either including market said where patients been is I've than polyneuropathy, and for As a have

our strategies these working the really outside going So of where presenting to we're to the some the them on ability excellence those be important. are patients they're to where identify to are centers of get get AstraZeneca. and And offices of with is

whether on will goal. And global your many question That the we then first yes. as markets, is be to in

the markets as where Europe, scale know, to Eastern as looking different the are such of you are U.S. to these AstraZeneca's file in at planning in expanding Russia, in there really these bring year, global places But particularly ability will Japan. half where the Europe. China, of care patients outside in markets get also penetrate we're and into We is the again, needed. second And

Robert, also to eplontersen, It rights for know, we're America that AstraZeneca license the all partnership been you pleased enthusiastically as enthusiasm cardiomyopathy. of data date. and their for has that course, And as the neuropathy for Latin eplontersen enthusiasm indications, as our very for, generated well demonstrates

question comes Kostas with from next The BMO. Biliouris

that market, follow-on how after technologies the first-generation -- there pelacarsen discuss many leverage you efficacy the and molecule the on molecule? could to you enter frequency expect that molecule you And announced. One sorry, of clinic this you potential did enter recently to improve pelacarsen? follow-on to Can approximately years after the the dosing the

Sure, strategy, Kostas. with with for follow-on us Thanks. Very a excited a that Novartis them on came work to pelacarsen. follow-on proposal to program

the pelacarsen disease. Let came say the outset their expect pelacarsen on and well to the -- and is right readout just potential follow-on for their global program more filing for added is form They that the us pelacarsen have first is fact enthusiasm, going the and this purpose for semi-approval there's patients And Novartis the very reach. track, well, cardiovascular Lp(a) XXXX. program. demonstrates follow-on with track and reach enthusiasm me The a really that opportunity data in to X to reach that be Phase extend a on to the for more is market substantial -- on to from

that's -- the past years RNA-targeted research doing been all expanded organization backbone as includes we us and can chemistries to and they our We as emerging utilize few RNAi capabilities that medicinal that last our they That And appreciate on NspA in therapeutics. ASO our that other in Novartis combinations platforms. full about this. table, the as have of capabilities including well in technology great and technology vast we're rapidly with both. bringing partnered chemistries work in why well chemistry the utilize for talked over and has arsenal capabilities, expanding that in recognizes RNAi we the our our a as lot

It's CBD to down XX% to able mean, due high with XX%, X patients that has to Phase their efficacy get the the pelacarsen of Lp(a). levels below threshold associated tough were Lp(a) beat with in Kostas. demonstrated I with We CBD.

we confident really, we're annual ability reproduce to pelacarsen. to working and maintain our want the to is that is So forward dosing want in efficacy And be potential very a capabilities, We molecule, focused be to what with dosing, focus utilizing hand that mixture our follow technology efficacy. pelacarsen. that to semiannual with follow the but best with We're in to really we're to Novartis. on and deliver of a molecule on a going molecules them hand bring

many I approximately compared No, to going was the Sorry. follow-on behind is pelacarsen? how to molecule ask

Yes.

We haven't obviously phase. about And stated we're -- discussed in that what still publicly timelines Kostas research are. the

risky little be now. actually to speculate that right would it on a So

comes Mike The next question from Morgan with Ulz Stanley.

full can cardiomyopathy, to of sort CARDIO-TTRansform the study? the in to Or maybe results maybe the then through recent thinking there? that in your of the impacts potential for secondly still maybe the to comment you of study eplontersen is there terms on sort on And Just thinking that, a earlier? and stop you how is data go Bridge

Sure, Mike.

-- data We're lot more to forward The our -- So we good which more seeing we're to to going reinforces design, data. for state design, going trial We good very completed TTR have naive see BridgeBio have potential well need cardiomyopathy. us of design, option detailed have to a trial between and the I [indiscernible] trial our as as more later balance now patience another our even data. supports patients. we confidence patients looking studies the demographics which obviously, year. expanded gives as present this need have we're data, think to a planning they're to obvious, To in tafamidis greater enrollment, we

Onaiza I'll expand population. the this CV this And a very it payer on ask -- overall is important standpoint, So mortality maybe a in really to from supports just that. importance mortality physician as perspective. of from

Yes.

our you so to in love a therapies arm we to This the mild means they that and naive really standard we're the anything landmark to as trial. silence wild-type need severe love care treat Class naive with I, endpoints. III, to and eplontersen to going it's So and or patients. cardiomyopathy tafamidis well believe Michael, It's significant as on therapy as We data amount -- trial. physicians of know, EHA hereditary breadth the to that go generate of really from the of data going top We TTR and to our these of II well. actually as

cardiovascular X-minute play. are We But have actually understand times versus And meaningful in cardiovascular really be other of secondary obviously, that going view walk the work to physicians at death. and amount terms done how a endpoint that just is of in our along mortality actually fair in some recent hospitalizations the measures endpoints, difference of meaningful. and of the richness is more a then with endpoint, really cardiovascular to

and seeing the excited in So times. output forward our that to all in all, trial we our coming set, of data the design about looking are really

there's several are our And design. to trial plans out love change that data read no when we that we for plans will -- there's no to Michael, We out. come changes any -- factors There will the when complete our recently. the our new study based impact study has on emerging

achieved first, very successfully. of was now we've We've it enrollment. to and complete course, that, achieved The

potentially is looking out. will we -- out. to change study thirdly, that emerges set to there's competitive that also we rates affect demographics in intended is We that have the currently, could trial data study of the no Bridge event but think the be continue beast, that We'll study to don't greatest comes be in out. the no CARDIO-TTRansform it changing monitor our to study change the it's our that, to actually going landscape, at important for -- read read due but We have very timing there new there's when for we data the impact us the data out. other in is data have -- And reads to may blinded be as decide the the when as time study when

just address on me that Let one which other missed. question, reimbursement the was I payer

we've the design. to a make the bear the favorable to of disease in and way it's And are kind for care that at testing just of and in payers risk, who of in data sure So be in terms clinical possible. there product on medication amount patients top going best physicians, show done out, here. making trial sure reduction will terminal risk they highly the is and again, are reimbursing standing cardiovascular not the tafamidis, if fair of a we they're getting or a Again, that combo meaningfulness on very with these

pleased So thinking landscape the reimbursement or we're the as either disease patients of them is the to really about combo mono space. and and in about see way the thinking

from comes Zhu question Wells Yanan with next The Fargo.

their about or study be clinical the talk And if that ongoing efficacy the I you you could into decided great. program, field its the if share safety you move Angelman And any clinical that syndrome any also, not next was product thoughts program wondering and syndrome around of is thoughts Roche ATXNX also update development wondering from to will development. programs could profile. some ASO in on recent your your candidates, could ongoing. where Angelman And stage for if and share study,

data Angelman the as around expected the same are think the program. syndrome time I

question. the for Thanks Sure.

Phase program So is Angelman Angelman's We're well. to patients X/X the this program very study, going Ionis in -- Biogen continuing enroll and we're operationalizing the study. the

very it's planning midyear Angelman's And far. I are well year Biogen as going so data the to said, with around -- next from are We program. have

We study. our don't why have behind Roche any the insights -- reasoning their we haven't ended into disclosed really

I've we're wasn't obviously, think and I it safety They or don't may disclosing meet target said didn't issue. product said on on shouldn't that efficacy. not a they minimum criteria. this. we -- think I profile anything really assume minimum We have their

we're So our really program. focused on

a not slot, year standing that invitation data is meeting. meeting always out podium next we may the at of what But decided we're we'll we new read an -- to on we sure update to be to this have yet. an this I'm fast called present year. the There going We status data too. expect that able haven't So to -- meeting which have be in program Angelman and a But expecting a study the provide from late at present necessarily we're year.

As course, ATXNX, because of sporadic this, particularly far ALS. drugs. targeting another a as is our exciting This ALS drug one is of it's

more year, of to which -- So This have in having a no examining set genetic cause to X-dose known add enrolling. highest the robust with is data cohorts X most going Phase around next are midyear inform as on a time study the is indications we're also that expanded it's mentioned, study to if -- dose patients potential cohort to the well. same due is around out ALS read study year. That, all you successful. is And next

Lebowitz question comes with David Citi. from next The

tell data us replicated, Given is trying up move the the launching modality? like physicians year, could Phase earlier efforts you the look -- new will a X data to is to what to for convince and your coming HA next therapy assuming you could

Onaiza?

for very next preparations yes, X launch our excited we're and about data the donidalorsen waiting Phase David, for year.

are ways. market variety We a in of the about thinking

be is going to pretty you market. much this As a switch know,

we in to given be able for will onset, do a there give X, confidence will sure we patients And that's alongside come the is actually to rapid to going breakthrough switch believe from informative study confidence as switch the to have that. the very ability going physicians So demonstrate are piece switch. of process make our a no Phase be we attacks and which our

think kind inciting switches which standard On Orladeyo from of behavior with is the Takhzyro, in of the I care. we already more switching marketplace side, the see the can patient

willing to see and that attack with are we convenience, So new more zero want as -- well. offer want try our patients profile and both they rates, we treatments. want And they

the is go-to-market and of some active their understanding very the kind So will of of that. in drive team strategies switching what alongside behavior

question. additional one And

how launch. Do have on shifted launched and you're going Alnylam? any forward? apply thoughts eplontersen the subcu launch the potential you to how a eplontersen thinking by since has that how growth towards Moving And of might market was

a much understand really just of I AMVUTTRA's they've how lot uptake to So right now, a got start. Taking the a in trying note to it's is. growth how is on important ONPATTRO through at market that working we're Yes. good And they're mean look switches there going marketplace. right?

to As lots marketplace. have be overall on still we patients an lot silencer get a in diagnosed their of not identified, most work patients are getting silencer. is just Alnylam or marketplace, underpenetrated new next-generation this I of to that to And said, continues to patients job of think And I treated. therapy doing their their this of

have said believe we in the And So a it to you when January to a very -- as efficacy profile, in in, the work. readily. always it's have for I as we We're as and thing product looking in self-administration players will of the as good profile, well getting couple forward marketplace, well to is grow patients. expect market. a exciting we which very earlier, you starting do This

Allison next Bratzel The with comes from question Piper Sandler.

on Just GA. trial Phase GOLDEN X one for me the in

what of any there warrant a just in space targeting the weeks. some the frame your factor view given in you're in year update updates the for you on further therapy readout that atrophy looking is and recent curious, GA complement just regulatory the Could Just investment geographic opportunity recent safety Phase for to in and potential next II B, of space space?

study our geographic ours. GA are our like enthusiastic including B-LRx This for set get all that Allison. GA. partner, there's helps our We're being atrophy are pleased for developed to our GA, a very Thanks, Factor like -- drug. drugs we're approved Yes, for and We We drugs study, that path our Roche, a profile. benchmark forward about GOLDEN.

large is dosing study, about in to So for are be far, the to patients around dose treated a XXX which patients going cohorts, study groups, GOLDEN XX months.

So we're geographic study. in good it's changes atrophy in a looking for the area And study. primary the what is

the read proof-of-concept the alternative target, the like like to GA, B complement So this. think we is it's which particularly a Factor to very is B-LRx efficacy due tolerability is Factor have are think approaches a profile B systemic We to approach for to an with GA. in and going pathway, going advantage right for side the Factor to year. study profile safety target and we that that overall is study, eye out right have administered We significant as next that the the and study, play, effects to we think be And treating versus that. drugs, a IBT directly we're consequence to

has olezarsen, the our of excellent platform Factor like pelacarsen, donidalorsen. an profile, have safety rest LICA that B-LRx We expect to eplontersen, much

Roche -- to proof-of-concept in and next as that we're achieve program equally the say, Phase or to is and they're strong Phase we go So data it's X, I the the enthusiastic year. to X, should seeking for preparing is supports, the If for data are.

question next Matteis comes from Stifel. The with Paul

in since wanted Congrats program. progress. much the all on I the changed of ask how light really to about the cardiometabolic initiated space pivotal olezarsen you has

guess, say weight about recent of I Just specifically X one X BMI and actually patients I of had comorbid do study looking drugs data above patients what the on percent demographically the of XXX, loss hypertension. you you WEGOVY trigs had guess, would patients these on the for think market most how think diabetes, wouldn't those qualify at average. takeoff for I more olezarsen? And Phase baseline was label? most back with the the on drugs characteristics, in broadly, type overweighed this of impact

that? want you take Onaiza, to

the a Yes, well. lot of Paul. GLP-Xs good recently it's Hi, Yes. been data as on for

couple important So to a things note. of

in they're right, standard not looked TG care at going it's some of what triglyceride if you of indicated, much lowering. their First TG be data, with is. And lowering very all, -- just current for line to of their

deliver that the lowering here. levels APOCX they're So really of not getting TG to high target actually can

being a of it of If is being used olezarsen who use have in And kind warning the triglycerides acute history the it's of that's first physicians for in know are at as pancreatitis. in and patients thing. most patients many, do for I a GLP-Xs with very have you elevated important endocrinologists reminder, not off-label, think risk AP. is label XXX-plus their the many or severely risk the So we where that a know, studied,

the with reduction patients we a AP, these not that triglyceride are of So we competitor. think do the magnitude be along for XXX indirect expect do risk or an over both who direct to for

The comes Werber next Cowen. from question Yaron

ATXNX you sense, sort little do broad need for secondly, you Just think us this then change? by bit some results on care is of given standard Can about are Or these in ALS. ATXNX just programs. definitely And label-enabling? a you the how program interim are of encouraging. potentially the a I SPINRAZA, you Do enabling? it response give label the on know Like terms and the touched of of of just your just label? sort

You for also have ALS. program a fast

the Just is data? maybe little a sense XXXX the what next ALS you the X? a know give us a do the and in other expect or bit fast timing what's of I from pivotal

even studies It's that our DEVOTE understanding sorts on to of responding lot a and SMA certainly how will ASCEND of patients the study to years of data therapy patients suboptimally therapy or a purposes randomized there's the kinds. did be X for Phase SPINRAZA is actually that very but haven't that is very efficacy that gene either on on greater you're it's label. a perform well, moved to doses about well surprisingly, doing the anecdotal in been our It's RESPOND talking that which over to signs is gene all Not study good controlled or expand is The publication SPINRAZA potential and verging patients and just has understanding more the these so of the strong showing things that done in to promotion. with data, line demonstrate the that of muscle ongoing. -- really there helpful Yaron, function. this at are improving study that demonstrate looking DEVOTE data SPINRAZA and biogenetically on study for that higher a neuromuscular out those really strength, study case,

my understanding. that's So

So I'm from head here nods clinical getting so. my folks

reminded just didn't Yaron. answer ATXNX me, the question, Eric, I

to year, goes the I'm an The dose be more So non-genetic data midyear is has ALS. That is sorry. top read Phase expanded ATXNX cohort that for potential in ATXNX the patients out dose that dose is X. the to the to next enrolling to due for cohorts. have dose

comes Markets. Issi Capital question with next The from RBC Luca

trade shape maybe, to that the and the just if truly I they're the molecule Pfizer? how the outcome on comment event for using methodology may, are this for similar I if make have [indiscernible] Andersen-Gill you X sure prior and cardiomyopathy, informed next-generation BridgeBio management? may, you you to Finkelstein-Schoenfeld could is using cardiomyopathy method want you are may using method, Eugene, TTR the it, Or alluded Brett, question any is Phase what in-licensed to on cardiovascular your are statistical and which similar maybe AGT, choose and was wondering TTR Question blinded thinking sort, on one lastly, if trial for And your to maybe already or Maybe what Alnylam why your up or to molecule? Alnylam-Roche by following about form cycle BD was in but pelacarsen in life I you're on deal seeing the then the you versus other? reaction to

Sure, Luca.

Eugene, can plan Before then talk statistical CARDIO-TTRansform. about turning to it the for you take I'll through and those, over

say The going management. to from is that going track in well in X potential well. is with XXXX nothing to very pelacarsen study very filing Phase on XXXX except particular data do a any the Lp(a) for So with the has entirely cycle study, life study data

by to management. Novartis pursue So confidence that even lends cycle greater life

our the strategies. reaction changed. We're our don't in have else any to focused own plans -- programs, really partnering Luca haven't AGT a competitors We anywhere on or space in

of the bit around the could but to course meeting. CARDIO-TTRansform. are about partner plan AGT a stay are timing and half for that tuned our we think the on And second indications many patients the provided a world. down drug best details heart -- globally suited with any along to talk at the said we road. haven't in to like We going of partner program, And little planning share about the medical for as you hypertension this this to year nor question failure a we're stats like a we've Eugene, that data reach all Luca's new when

Sure.

analysis to related right, was it Luca? understood, Is I the if that of So the primary endpoint.

That's that's correct. correct. Yes,

Yes.

true that SAP. for our the pretty mortality said, we tried we're utilizing to as a in methodology listed is planning are events and both CV events, to So using recurrent that CV Andersen-Gill analysis or and at look that method utilize

again, -- about these nothing multiple It's I method events. done outcome fancy classic way think studies. this has in fairly what a tried there's been So and of

from is Yale with Company. & Jen Laidlaw next The question

first do Then you later you for be I treating this the end question is the or The have will follow-up. another used neuropathy, mixed type of eplontersen to year for patients? that the if in it get approved anticipate also drug

suitable Absolutely, we deductible for be do as as would drug mixed This yes. have polyneuropathy, provided phenotype they PN well patients. pure have patients

is question do color another olezarsen this my enrollment status? complete terms of anticipate terms can And any Okay. later year? for in the And in you that the of you provide SHTG enrollment,

missed the specific… I

on enrollment? we SHTG How are

kind And that well. very or either very, very late going this early is guidance giving. we've been of Enrollment it's year, next the very year

question today Company. Joseph Needham comes last The with Stringer from &

key Just physician primary of of we on be later payer Phase beyond to frame a olezarsen the What a from perspective? year. important metrics just need type you Can type should what looking would to one be on that expectations or be successful commercially? at FCS this see X quick outcome from a endpoint you --

for to on substantial and looking is -- triglyceride commercial maybe the talk will patient we're drive to You see. about primary lowering expect also endpoints want to market and the lowering important. that's placebo, Onaiza, what what TG in mean Eugene to is endpoint this then additional take this obviously, that, we compared And population. really But Eugene? I triglyceride lowering

going also variety to. of -- analysis. obviously We're a Happy responder Sure. at to look responder

that XXX, thresholds classic like So of looking proportions instance, clinically at particular meaningful [is for below patients the get XX thresholds, XXX].

and as indicate these of pancreatitis life feeling that be are whether something see. at to function better, events reductions terms quality -- and risk those be So prescribers for again, those, again, of they're to are looking that patients well. also achieving measures. acute better again, we're will future actually in we'll keen meaningful able But We're thought is to very are their having included

No, that's yes. great. -- We've

market obviously some I on done well. this as understanding think we've good

Just for their just This for mean, FCS. rare restrictive diet They no of have they a disposal. -- population diet is while. a it's just can't reminder, at tools is really disease that the on level I treatment restrictive not and this on where a continue that first-line is they're

product really easy getting safety are get there's but to be So unmet -- think huge here generation, it's really some going of and I lot be a this that's the safe important And tolerability a A use. go. is lipidologist going to efficacious that first also a think patients of going of really the and to to and just waiting. be I do versus is lot well let's need. and

year business, Thank for everybody. to at forward hope many you comprehensive on We of well join have across see us looking a can Until on momentum that update for on person highlight today in today's on. commercial everybody, strong way. for you. all our We're this progress of that really our continue I on in to great meeting. that you planning pipeline, call. Thanks, our making so providing the joining our hope October there. by day, to of second all technology and and delivering I Also, then, We're we're half of aspects want we're our X. to Investor the thanks, a Day great

now for your you participation. has concluded. The conference Thank

You may lines. your now disconnect