IONS Ionis Pharmaceuticals

David Nakasone IR
Brett Monia Founder, CEO & Director
Elizabeth Hougen EVP, Finance & CFO
Richard Geary EVP & Chief Development Officer
Eric Swayze EVP, Research
Onaiza Cadoret-Manier EVP & Chief Corporate Development & Commercial Officer
Jason Gerberry Bank of America Merrill Lynch
Luca Issi RBC Capital Markets
Brendan Smith Cowen and Company
Yanan Zhu Wells Fargo Securities
Alexander Thompson Stifel, Nicolaus & Company
Yale Jen Laidlaw & Company
Jessica Fye JPMorgan Chase & Co.
Mani Foroohar SVB Leerink
Myles Minter William Blair & Company
Esther Rajavelu UBS
David Lebowitz Morgan Stanley
Call transcript
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Good morning, and welcome to Ionis Pharmaceuticals Second Quarter 2021 Financial Results Conference Call.

As a reminder, this call is being recorded. At this time, I would like to turn the call over to Dave Nakasone, Investor Relations to lead off the call. Please begin.

David Nakasone

Thank you, Debbie.

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

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

Brett Monia

was includes This prepare evolve business own. launches. model our necessary plan foundation of commercializing X to First, of intended multiple success Thanks, thank substantially Ionis, Last my scientific the bring value you call. our us today's our for This to took on I the when greater and for year, stakeholders. well-established role and Good commercial forward capabilities on to leverage plan took as objectives: substantially innovation CEO by new morning, I to for Ionis of Ionis strategic focusing building products joining Dave. all to to include greater on

products And our substantial grow advance pipeline and ensure near our to the new through new reaching a Second, to expand significantly the drug market our the initiatives third, term. and in in of for longer to to number late-stage enhance increase capabilities technology. discovery

track of With on track closer for and how full patients enrolled step of one the the Ionis for let's we study week, pipeline market. with treatment growing reaching these on reached important we're X study now The significantly. fully to year. medicine this enrollment progressing wholly-owned goals the is polyneuropathy. for now mid-XXXX, is this data advancing Last against see this in by So strategic eplontersen NEURO-TTRansform and

We treatment the are for also III eplontersen well. continues cardiomyopathy study, the in to developing which Phase of CARDIO-TTRansform enroll

this APOCIII with Our second LICA track our schedule. APOCIII on patient with our severe medicine patients is patients for later is study Phase Phase a FCS study III in enrolling our much hypertriglyceridemia, in involving LICA plan year - III And larger in begin to and population.

or with study patients the Our the next study making we look progress as Phase of for medicine in form in out year. also late in FUS strategy. this our in our forward a with PKK year for is mutations Phase we're ALS also wholly-owned And our progressing LICA III early our great angioedema well. gene IONXXX capabilities hereditary due initiating and to commercial pipeline building advances, III Furthermore, patients to genetic

commercial strategy our building Our acquisition in advancing key step capabilities. a of these was in Akcea

We have and TEGSEDI progress distribution pleased in Ionis. Akcea integration made and now being WAYLIVRA we're within Europe our the of partnership completed of North And the for Sobi with in America. the

investments also partnership to year our on eplontersen this providing established our objective medicines this APOCIII against through progress significant new focus we to and important reach the our reminder, drug a made patients we discovery to As enhance strategic technology. expand We've while to continue capabilities additional of these LICA.

our to well our cardiac partnership as efforts efforts Bicycle's third products for collaborations, primarily drugs our significant announced for of Our achieving technology. and focused collaboration to to to as under on initiatives this exclusive well chemistry have year recently XX as of technology expand which technologies. platform objective new delivery Therapeutics targeted complements Therapeutics enables great us with access skeletal broadening as And XXXX. proprietary internal in oligonucleotide include new our internal We marketed in-licensing or Bicycle progress muscle. a our the Arrow Sciences strategic significantly we're in more progress Genuity the all potentially reach lastly, making and we're making This

this to In If market these pelacarsen also achievement the tofersen of announced by is successful, X portion addition we tofersen next III we're basis. key placebo-controlled now offering use ALS first study, for across significant the and are late-stage could the VALOR product. ever programs milestone milestones our a tofersen eplontersen on we this milestones All therapy genetic treatment achieved making study they and Biogen reaching of III in for in the compassionate disease. progress an III results patients with to completed LP(a)-driven with move cause commercial a our individual toferson III Phase completing disease-modifying patients of become the of week, pelacarsen. cardiovascular VALOR Phase to pipeline. NEURO-TTRansform the excellent highlight enrollment study in and recently fall these the of enrollment Phase Lp(a) expected HORIZON And closer the key Phase SODX-ALS

goal cardiovascular our enrollment our As substantial all today. we're along achievement, achieved X,XXX profile have we the outcome medicines enrollment across for we attractive target progress in consistently the This trial, programs, demonstrates mid- of announced, of our of development patients now late-stage representing LICA for this making all the study. nearly with and in XX% LICA

prepared this looking of half comments, our strategy to wrapping Richard objectives. great in key pleased up to to focus recent are pipeline over on further we updates expected forward our on the the of executing with this remarks discuss the the second year. to Beth making remainder ahead. review And achieving our and that that, positioned we all of the my I'll progress our results. are more. So made are your turn goals strategic with for before the up preview to and an we Then progress growth catalysts all financial for and we're we taking year and questions. as now exciting pipeline importantly, strength Richard, people well achieve the and And lie very the opening year, with financial I'll call We've After will achieve wrap

Beth. Now over to

Elizabeth Hougen

you, Brett. Thank

Our strategic and from the We've non-GAAP million in Sobi integration the financial million entered $XX operating half Akcea, in we of commercial multiple more for non-GAAP the recognized results first growth. million. of $XXX pleased first invest million reflect revenue year have than to savings objectives. completed restructured These to projected loss steps operations. earned future our call, transaction. this $XXX results in drive and this and resulting our reflect line year. distribution with of our $XX expectations earnings taken Akcea arrangements of Sobi in realize to expenses, realizing a net year our already quarter with the commitment nearly we savings were track I'm our We this to of say are substantial we and support on In in

But sales, quarter. made half this provide pipeline, growth. over net We far blockbuster revenue. these profit. provide X are of more advancing this about putting tier areas: and them we've our earned revenue, enhancing additional technology. based when the I'll means In achieving I on by our We our future our I'll first, we performance, continued expanding reinvesting virtually the year highest billion capabilities sales. million key and savings talk in to our so And first about details commercial year, the details second SPINRAZA's investments building wholly-owned That over our SPINRAZA in operating to in its all line the expenses. falling $X investing $XXX work royalty to royalty on global bottom in reached drive

the revenues fees TEGSEDI proven dose of be In will first our of completed SMA reinforcing efforts outcomes recently of with the of treated to growing patients to $XX operations long-term SPINRAZA's year, Together pleased in we Sobi evaluate SPINRAZA continued ages. in gene supporting Biogen the potential to SPINRAZA's which higher being net and TEGSEDI to transition quarter profile the million. over are RESPOND ages. with study, previously safety upon distribution and treated recognized and sales. first in is believe the the new the profile all of study. SMA half, to SPINRAZA's all we evidence patients revenues and And a market-leading therapy. also SMA is of potential Biogen's benefit and for from continuing this based on improved substantial reported patients with full Biogen of for DEVOTE patients, And commercial of evaluated half patients build treatment continue in the body We WAYLIVRA XX,XXX efficacy in SPINRAZA, first and generated our of proven data WAYLIVRA with

guidance. a As shift XXXX in we in included reminder, our revenue this revenue

R&D neurology $XX advancing in half also with our genetic was in in We million from million earned cardiometabolic is ALS disease. for development IONXXX, our which revenues More franchises. medicines the patients in history the $XX than known first with from no of XX% of R&D for revenue nearly Biogen including leading and

numerous together XX programs. revenues R&D Our advanced partners, included revenue as from we than more

eplontersen compared financial is ability was with increased element slight year, our first Our of to compared to and XX% expenses half primarily driven in $XXX of was This numerous Phase the reported associated line a in non-GAAP and programs. diverse revenue of key APOCIII last wholly-owned our LICA year strength. a with sources million from expenses and expectations. this study our III costs operating increase year. generate R&D to by the We last by

novel guidance last expenses from incurred of partnered $XX wholly-owned to Based for of our integrating for key and revenues also technology. to second projections Akcea restructuring identify III reflect our increased and year, We XX% by our efficiencies year operations. are XX% of our approximately Already decreased commercial this targets. investment, two in we programs pelacarsen. results on a third study first Novartis we reaffirming associated collaboration half our the increases million. half revenue in the milestone expenses million our SG&A Genuity than due have to R&D our in compared pipeline cost Phase the These enrollment our earned with of of and from $XXX payment achieving XXXX our realized quarter, more advancing areas from

advance eplontersen, our to our studies expect Phase half We the operating APOCIII ongoing III as second FUS-ALS our for medicine. year we to LICA IONIS of continue and increase this expenses in

III competitive. innovative underway for technology, operating the And are to study with triglycerides patients that high investing for also the as increase our enhance Phase our will get in remains platform LICA LICA. start severe and and potentially Our we study expenses ensuring PKK we APOCIII Phase III

loss of of And all guidance. million increase we $XXX payment. expect this this a alone, of end R&D in project $XX financial a range less million $XXX not operating license to net mentioned, our for than revising our entered expense on And be assuming for will now Bicycle we Therapeutics XXXX in expenses we the reason year upfront in and loss operating Brett $XXX and of second with license net that in basis. include lower a revenue this million projected loss our We first to agreement are did non-GAAP recently expenses our in the year, the the of of As and because fee half into million, a low half. half We original compared net the guidance. second

and call to believe for And XXXX. $X steps and continuing the in invest positioned we achieve we and more the over medicines growth. our year moving this than and or of market the have important forward we already investments, I'll towards well marketed are Richard. billion We to taken look more technology more our to turn to accelerated of cash with XX in that, to products pipeline goal With

Richard Geary

Beth. you, Thank

this Brett As first excellent pipeline performance pleased we our with the of certainly in year. are earlier, the across described half

symptom becoming Tofersen of Phase deliver data first therapy compassionate broaden ALS the achievement pelacarsen, next with offering to and regular study the ATLAS reaching onset us began ATLAS infants study with the who has onset toferson market. prevent one III of SMA program tofersen, SODX-ALS out reported. to plans readouts treatment also like next becoming These Phase Biogen by the key of an Biogen is After we with for SODX-ALS product. well the individual to closer step TTR genetically in tofersen, delay basis this conducting potential eplontersen track to eplontersen study, now to catalysts these - tofersen is access data began use the The investigate III presymptomatic study With now next complete, read once expected to to cadence NEURO-TTRansform children. patients. prior on treatment treatment patients disease fall. is of enrollment the polyneuropathy. commercial our to tofersen's catalysts of this this and enabled middle SPINRAZA and of rationale the are non-SMA to recently for week the are by to Ionis' develop next similar data beginning NURTURE to is expect now the or year. to which on closer position for medicines With targeted also more

triglycerides Phase patients on second LICA we end As which Phase program a III to IONIS study this the CARDIO-TTransform we outcome XXXX. Also the this positive. the balance in in next the for with TTR of eplontersen in III study year, eplontersen APOCIII in read expect data IONIS initiate severe with result, patients marketing FUS-ALS. by half a second in XXXX, to study for and We're the are assuming LPA of in with we pivotal FCS with patients positions of data data for LICA XXXX. the study of of track file study positioned authorization HORIZON Up high patients in the in pelacarsen, to year, out are polyneuropathy APOCIII from next, anticipate of

year, into expect fully Data with results, medicines a we favorable tolerability the that development. our vupanorsen into We dosing to a Alzheimer's forward advance the generally at additional in mid-stage have we positive, in next and if these data we durable to all of patients. of monthly the move LICA addition III hereditary upcoming larger disease Ionis our late-stage Angelman CSF and dose-dependent readout recently safety IONXXX week the in that of that, Alzheimer's test and disease. expect data to dyslipidemia Ionis demonstrated MAPTRx, study programs presented with to AAIC have medicine position these of forward we or starts. have Phase And our achieved quarterly these patients substantial, tau up and Based last additional Biogen treatment forms pipeline In with stage on reductions Coming look Many in readouts mid-stage MAPTRx with pipeline, deep cardiovascular we data continue from support more I/II Phase of starting look plans antisense this of Ionis Phase to for data patients study Phase this and with patients half as II PKK IIb for in a disease. angioedema. to II from syndrome. the second study to treatment later of reporting year, Phase study large

the late data the look in year, good next end-stage track initiating on in with year. continuing putting Factor with study make patients also first study is to next And to this XI IONIS our medicine, our Phase renal study this forward for Bayer, progress half partner, We track this year. on Phase III in disease of IIb LRx which of is early

pipeline as which, across goal the look closer marketed to us achieving additional our And unfolds, this we from I'll with our forward together, updates to more portion XXXX. the future we advance Brett year continues to catalysts of that, XX in pipeline, of call. achieve over turn medicines move call the the and providing to close or As to

Brett Monia

to continued our successfully strategic the Richard. year, key objectives. you, advance In half the we first of Thank all

evolving and which drug positioned a very delivering and our And preparing technology have products We've long expand significant our market in new well And Ionis we more achieve up Phase SODX-ALS the great with to trial advancing including model the key results pipeline, progress of of successful made to and III in be readouts, business accelerated ensure to need second resources to of is to of we've term. our shaping I'll move in Ionis commercial launches. this the capabilities now market, people for and the number milestones, III in across our with great our and discovery growth pelacarsen many goal We multiple commercial clinical for capabilities. are have closer the year for positioning up progress Phase tofersen, with made to and our progress made call help we that, to building key even open achieving near us all the for years in to several new for substantial eplontersen including come. the fall. study the invest priorities, importantly, VALOR our And with by strategic initiations success the And patients we questions. half the clinical


Instructions]. [Operator

from comes of Jason question first with Gerberry Bank America. The

Jason Gerberry

me. A couple for

the help you expectation can maybe into set IIb vupanorsen. the Phase Just for

curious, need more with patients severe triglyceride of of sort subgroup unmet Just the high levels.

your read category? just across secondarily, to from potentially have terms to of thoughts And patient given guess, any your Huntington's. this Huntington's curious a wondering the revisiting you thought Just and in thoughts Just population. latest I then to on steps study as that ability that to disease next

Brett Monia

thanks for the Jason, question. Sure,

is the study, year. to line they Pfizer So Phase for have which said top that has vupanorsen, IIb announced this data plan

As strategy from in Phase one drug our target and people. vupanorsen, which about patients if high related for combined this millions There this of high is for moving severe for large the diseases, III, Phase well. mechanism think Remy a purely epidemia very medical high patient vupanorsen LICA as triglycerides plan APOCIII best-in-class non-HDL III to with III We triglycerides. you to if that triglycerides, very that And to that population cholesterol unmet for that need a they with high-triglyceribulated mix will, excited significant, the to The they're cholesterol patient addition reminder best program. nicely. quite in high Phase and targeting patients is we're also, is which move is positions affects - we're population we're mechanism, dyslipidemias, suffering very mixed the that is

important So populations Huntington. targeting large patient have to quite because some LICA and realize And to to I first, I that that. add see for touch are can I But said. distinct APOCIII that very what overlap and to our they're if on like are medicine Richard raised really wanted that distinct don't but anything it's vupanorsen I'd populations just

Richard Geary


I think Brett. you've covered it well,

Brett Monia

you, Thank Richard. Okay.

go as analyze As end the Roche Huntington, working they've Jason, through an continue Roche closely this. We're next the update steps more far the results said, data of year. the as and promised by as of the on the to data, they very they as all well on as study with

And tuned so update. half the second for the for an stay of year


question is with from next The RBC. Issi Luca

Luca Issi

quick Two pipeline. ones on the

So maybe interim the me the TTR mid-XXXX X actually months, It's expand almost actually. polyneuropathy? you ahead first for to bit planning TTR, on It analysis the little on primary analysis a looks interim that can more in LICA endpoint. the X of is you're Richard, for months that

with that So running a there. provide what to Wondering the you issues to if also confidence into you any second curves. safety wondering seen such is a of We've can separation follow-up, there. question ENaC. see on short going gives update Arrowhead be the you're then able And

next franchise. any thoughts saw? So on And one what's that picture if can had bigger issues the comment have are on whether you for the the they you respiratory to safety that maybe similar

Richard Geary

for Yes. Thanks. you eplontersen I'll that take first. question

X a have in course, derives drug study with statistically that mechanism and months TEGSEDI of a drug trial, in confidence, we safer We with at monthly first of from administration. much believe improvements well-tolerated our But we we with action. once ran endpoints. the Our significant had polyneuropathy much TEGSEDI

that placebo was nicely separating so already point. from it at And time quite

that that, believe need that analysis. into we us this going kind in confidence gives interim that of we So

quite it's In fact, high.

with a that, I the able can't think competition. through might what that be to. speak issue. confident we're second even had, We happening the very had you and we'll preclinical working question that to - We're I be we

Brett Monia

gives what great drug TTR reductions You Phase at eplontersen, significant XX% Richard, finish excellent Thank as is endpoints Richard for statistically yes. based in conducted reductions. our Eplontersen same only study We're us TEGSEDI you, for that to benefit line, I months. the not around have if of tolerability Phase primary all even rising And just confidence greater that the is in the in like was also the showed can fact that - at is Richard X at add with mentioned. on what as dose LICA the III III said. showing safety,

working a development move to confident have outcome. molecules very really as in at also we're preclinically just program in progress new can the looking the new comfortable that designs, add path we're pulmonary the very that regulatory forward well. to the on we And with So we're And future. and back good - pulmonary,

tuned next So in that. stay the We'll year. for end of that more or year the talk about maybe


The next Werber question from Cowen. with Yaron is

Brendan Smith

This Yaron. team the to Congrats on the for Brendan is progress. on

Just a ones couple of quick us. from

looking that initiate Kind mentioned you're see next the to steps study you what or HAE of early end know Phase are the the by just I So to year. year there. of III wanted left

see trial get preclinical and I data you be you that have with logistics able kind really point it If And I/II? on to tell already at might any what for might at and are design point? Phase this just finalizing quickly the to still and timing you study study? Or wanted for us up the year then maybe about Angelman. from we of it's alignment if and the set design this FDA getting any

Brett Monia

preclinically. I'll after to Sure a talk and little what take Angelman ask then in thing. and we that, on HAE published so about presented I'll - Eric program bit the the

touches late and honestly, this preparing to getting to it's we're study and blocking done discussions our design of running. made. We're Phase final HAE, We're next data It's share Phase our than the end year. it Phase hoping II III looks - LICA Brendan. the we for get strategy, plan think mostly point a the for year will best-in-class getting share the get But we what tackling, second goal of up study, of full we year. it for and strategy, at position design later putting study quarter HAE. the it also with in design, development our we of And it's molecule logistics, why the we're set by Really, that for and getting happening first Phase see very our III We're having the - half So potentially for III on our to stretch forward selecting the as good certainly, and we're a sites. activation like just moving sites, regulators. when drug PKK initiated

So got a out, exciting momentum stay tuned that Angelmans. in we half. for on think, half a the of lot published second Eric, second through in of going the second coming We and half. of the lot we the year news

Eric Swayze


We have. time to our a Angelman. first bit hopeful colleagues the hoped, had will transcript candidate. benefit make We antisense in trying academic optimize great getting that I and molecule which this the forward extensive the to a we development we've good spent were can an best-in-class to elucidate of inhibit experience Took ideal and little that we took patients the started about actually and Then to learned we're year. to space everything drugs great-looking that try got the later make great syndrome. a be longer neurology collaboration a drug with but this us It are in than how and protein molecule provide looking UBEXA, study and you to our in from in-human Angelman first deficient human mechanism a is in the upregulate amount with find

Brett Monia

on tolerability, study, And readouts study to dose escalation, for obviously, focused, select on III the biomarker the dose safety, a will I/II be for follow. Phase study first - potentially Phase based a inpatient


next The Yanan from question Zhu Wells is with Fargo.

Yanan Zhu

with things progress. on lot X on. have of to on technology question collaboration. congrats Bicycle platform the front And Great. the I A going regard

that you with you using dystrophy do fabs? increase exposure So when approach and there that on-labeled you confidence prior you bicyclic the their is perhaps date or your clinical restart also, dystrophy studies, And your compared program muscle feel at path? antisense myotonic peptide approaches in compared of with when myotonic an were enough the have gives transferrin in you with given doing receptor the look could diligence, accelerated you monoclonal experience fold have antibodies targeting either antibody Yes.

the first question. So that's

Brett Monia

advances - excited answer completing Eric really done led team. board, his Bicycle. left about We're Yanan. comparative the that Bicycle effort is the and yes, targeted across we've - deal. bit to delivery with of Thanks, quite including a comparatives making we're work the the in - Eric prior

him why And turn we're from other it our you I'll we and over differentiate tell excited - we about believe so to Bicycle to so how what approaches.

Eric Swayze

Brett. Sure. Yes. Thanks,

it So we absolutely compared other transferrin receptor have ligands. with

were them those the to to Bicycle have the total the been originally the And would and to There's extensively reasonably potency to small. be human we at peptides And Bicyclic been transferrin how size. less involved can which to very the And unique trying bicyclic in small dose XX ligands fabs identical and the we compared be that to on that are found of based be terms the advantage in in multiple then has And able we particular. And thought find would Bicycle, to really demonstrated develop and that fabs we're antibodies looked muscle. ligands early can and proteins - make transferrin better drugs definitely in So on and space the this the target happen. peptides high able interested in monoclonal end. that to that for us better cargoes to ultimately receptor-X oligonucleotide conjugates absolutely Monoclonal will essentially key We difference delivered. here fold oligo antibodies because all a a are are have is that deliver led directly receptor-X these are it smaller. of up if you that XX drug Bicycles administered probably scale that projection translates in to to weight. big. that,

will if hopefully drugs. And antisense muscle a large we this make advantage be it so targeting can that make with work we think and cardiac and best-in-class technology

range needed clinically. you comment get have great that We programs, has targets the advance And this but what of get we prepared of targeting DMX. alluded not enhancement technology a certainly we are think targets or it cardio program. we're And the neuromuscular up what that, the beyond and will it that the is think lined receptor-X more this moving. we for potency Yes, on in that the whole potency timing, - us cardiac are to us. host to and As to DMPK anxious need to for does exactly to in we what really bicyclic and technology transferrin

Yanan Zhu

a tau MAPT then quick or the lowering program. Great. And question on

tau? of You example, for approach with given of think path with, we recent antibody reductions the forward this biomarker showed this about How targeting very a And impressive tau. with development should a approach approach? some beta kind be could compared approach there

Eric Swayze


So said advance Biogen to clinical to into clinical path fully this and the to a II with test lowering. more the study larger Phase tau they associated benefits as plan forward, outcomes

So strategy clinically. that's the

As where Tau antisense as approach is I known comparison think of aggregate drugs inside no approach, to And comparison. to accumulate our antibody It's far and there intracellular as really an a the that's the cells. an protein. work.

So the RNA. to off by they and binding the tau turn translation of protein synthesis the creation integrating and

brain all which of things engage and drug. hypothesis lowering tau it's our cell our think doing, throughout of tau key exactly antibodies penetration where is to tau Whereas it test we in are that molecule occurring antibodies, do that's a you our to tau can inside that's because to macro And tau, we have protein turn that forms all off think small and need To AD. very it about of and it CSF. demonstrated one mechanism, binds tau productively of tau trial tau reduced. that in that's the of we a the excited the lower the encouraged We CSF, taking be forward think the reduced forms the the key think CNS all one to cell, where in in pathology the only space. what we're the those what has cell has it's it by don't we we clinical populations. to it that. reduces is great in a test comes drugs from. reduce And in So Biogen and And And the is you into inside a are to are CSF, that and


The Stifel. from next question is Matteis Paul with

Alexander Thompson

from this Paul. follow-up the get doses is curious if on wondering III? Phase in And and that a if in on if secondarily, VMRI comment I in expect or you I, you biomarkers could if of there you that This this II, for presented ASO then would on Phase measures tominersen comment was MAPT. sort could versus future. any the or relative on the are Alex Actually, or study published

Eric Swayze

poster. Sure. The weren't in disclosed doses that

identify information about and I our the for we will subtle and say design this the that. Phase good and in We working we've of and pretty design share compounds. advances stay tuned getting tweaks the hard are been and data I a And it. we more so oligos on oligo, on is that chemistry how hopefully, can published, working making to

this think represents able And so the this is have we've better PK/PD molecules made, a to been our - of expected. performed And fantastic predicting and modelers doses. and make more think done over human as we one we more it potent the And job the them I years.

So hopefully, in share publication can soon. data more a we

Alexander Thompson

or not this that were in data taken that just there was something And whether say not biomarker study? Or done? can you is

Eric Swayze

Well, beyond can't range the comment of I of in in study. a and terms we what MAPT. biomarkers outcomes reported we had


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

Yale Jen

the that and launch? be sort you Should after question the XXXX, bit what's little in get in that commercial integrate strategy if of the you you that infrastructure approved product a your operations, or will be maybe have? eplontersen the Just Akcea case to is maybe forward-looking the terms this that of next future

Brett Monia

Yale. excited as this Onaiza so also why polyneuropathy we're program, a about eplontersen potential it, on? excited are for the well. cardiomyopathy just for X, we're point our why I'll but not to best-in-class about program talk Thanks, as about Onaiza, ask you

Onaiza Cadoret-Manier

I Yes, launches. commercial to about am. our program happy and our talk

as are Brett a we markets to Ionis are said, the ones right, launches. bring this to prepare is, and be we the you foundational would best-in-class market. treatment, both So capabilities would commercial cardiomyopathy. of for building It for absolutely And PN first one that

quality safety and self-administration very of favorable in We and life, proven profile at-home benefit to expect see neuropathy, optimal a dosing.

indication, excited as for cardiomyopathy team launches On is the formed it program in preparing the trial it, very is have around CM. brand important about and largest we're remember moving that's There to second as where markets the well. we this they're is as well forward. a been So that

how We data. to to of patients because on a advantageous trial right, really standard data conducting diversity really going recruiting clinical be or going a program have the place care. breadth eplontersen for overall. XXX we robust the are it's and going indication this to to in clinicians about of of can provide used we be very just that as with for and this about eplontersen of an eplontersen that It's set are market, without dynamic is be for generate We're excited the it's data second

indications. And as and looking So for treatment again, really foundational great CM. best-in-class both program, PN for good

Yale Jen

second this X this sort bit Great. you acromegaly the will guys question of program Okay. readout Maybe you more helpful. a that half That's very little expectation which Could have? may just is data of year. here, the what of have recap you and

Brett Monia

Yale. thing, Sure

planning as - LICA we're the somatostatin acromegaly our patients you - for receptor of are fact results they're So Phase share said, despite that taking top study analog. on medicine controlled II we're to in poorly hormone growth the who the

the is profile been extension top second on characterize of somatostatin will open-label in LICA analog long-term share study. is that data, patient in So also this the that growth we which the in the population. we've receptor of this And half data hormone important to year to think for is include

and in target how disease data we with impact binding, safety, engagement, on and are feeling patients So will also this of other this measures reported on patient total presenting IGF-X readout. outcomes be tolerability,

We're data data half the we but a reminder, of way that half bit that's We still the is out one study the that, get in or And a to working the or drug. important present as of include. quite second think second the which haven't of this identified year, venue And the a out the data. it analyzing open-label quite get on said, I of in extension we're the as in still year. program we'll will for the we this

monotherapy have And in to frontline acromegaly. next out GHR Phase read study patients also LICA study year. that - with II We patients expected in for is the

care positioning poorly are we're on how patients frontline potentially for with out. who the reads a this as So well drug data as of depending standard as treatment potentially controlled

Yale Jen

That's very Great. on And helpful. Okay. congrats all the progress.


The next JPMorgan. with is from question Jessica Fye

Jessica Fye

of make III product. on why tofersen. on rapidly across those the results? progressing Two the cannot to currently that upcoming rest talk do restricted disease? one you to and related questions most And you Phase reason use about compassionate second What quick can your pipeline the Can based the to think with investors neuro read the is patients

Brett Monia

for Thanks the Jess. thing, Sure question.

the So tofersen much as, you for we're course, looking forward Phase SODX-ALS. to very know, in readout of III

in of treatment our cause potential be said presentation, to As a for ALS, really cause at of the we the genetic in look you the first when has clearly any this - it. very ALS disease-modifying

in root caused we clinical can neurodegenerative for cause a targets will hit we're at that When - X about confirmation. platform and And of It's as programs engage the the to look is and excited safety done tolerability leading date pipeline, the believe well diseases at diseases is will treatment further X, we it we neuro can can are these of X, our So The of patients any. significant. we've read-through in of the at it. these the that provide for of over that be positive. only attractive It that size not diseases. be we neurodegenerative demonstration you another targets what benefit is the

can general, also that mean we ATXNX it to also CXORF broad demonstrate works. ALS platform, has no significant bodes year FUS that of rest that Phase And development. beyond ways: it we genetic within that the also due this is due known in penetrate meaningful demonstrates Phase in FUS patients. genetically read-through and meaningful cause, right? program. genetic already has caused tolerability and for our key said the ALS, this platform, other ALS So III the to to all And think well read-through It one, has we - And hopefully, - significant can things of our the ALS I our benefit it readout CMS next mutations, we is II which all our neuro to clinical will target X our genetic provide in that believe strategy readout I engagement for target and very population which to regions about - and ALS program, some forms X to

want really not what ahead they've use, really get for made this. do statements compassionate a for As question to I that's on Biogen. of

a rapidly available been I of As to available lot to this ALS. drug SODX nature all course, because there's to pressure drug progressive SODX-ALS Biogen with be mean, will the devastating near you That's on of disease. patients put, the the of that believe hope, the make they nature the and simply patients this know, of future. with in

for forms it. So the that's all time not rationale it which in patients the they is to available I because progressing drug simply, focused disease those may those the make behind with think patients for this rapidly the SODX-ALS. of on quite And


SVB question with Leerink. Foroohar next Mani The from is

Mani Foroohar

call for exploratory can whether potential ones. this we measures could quick it's you expect know on NEURO-TTRANSFORM from study. A couple around us of I danced others, out or and not been lay cardiac

One of what polyneuropathy of seeing measures your exploratory length scaling opposed their from patients neuropathy a execution give you around a sense are clinical alongside And that you competitors the at in combined oligo has cardiac what therapy cardiomyopathy in to discussed the and seeing as us from cardiomyopathy use symptoms. in marketplace of with study. trial setting can tafamidis you're side,

Brett Monia

study cardiac in playing indeed, how Yes, as TEGSEDI up ask one, we But that and NT-proBNP and as III we other out Phase importantly, Phase out RNA-targeted the maybe take eplontersen really as study. when for see the first I'll and exploratory in markers with polyneuropathy in measures that the therapies endpoints the how future. involvement, study. Onaiza tafamidis. load playing and those the All it that secondary we bit such heart in endpoints more well. III with we're the looked I'll are right market to cardiac we phenotypes talk classic will some did at about Mani. patients the but now little endpoints we markers a include These - have see with will ventricular be probably we Sure, in and build

lookout And year Richard? the for out endpoints, mNIS+X. that which the right, for X reductions, when data across on is it's as reads also next well the be TTR primary months, So as

Richard Geary


Brett Monia

primary then And also as its endpoint at to at we'll we a have quality the months, XX as bring that completion point. life of study

stabilizers RNA-targeted Onaiza best the one might and market comment for therapies. on to think I be the

Onaiza Cadoret-Manier

Happy question. Yes. to. the Mani, thanks for

So yes, like answer. question your a - is we geographical it's really, so are seeing

we and silencer again, sense where population. and combination From is right this how as Again, for been It's it's fair I us KOLs of really back some is can of a that without first. of dynamic. tafamidis. job population. looking So perspective, patients patient is prescribe where out. alone But no to population, really, going care. payer to a getting we and this have what what is treated. And seeing this this see a go the the done do diagnosing they tafamidis them these And who wide world what's or will to well. and work course, we're as that's diverse how not we're for think from very the set I patients And want mechanistically, just to good entry that some And large. really hesitation sick use like of actually future we've diverse. silencer good again, amount order payers. the a together. But of and And use at easily or to seen good clinicians on the with in need of really research back world and really products doing they're a nice well We've we U.S., we're the It's evolving. could These data we're getting patient to what really with as clinicians it use is worked a actually I with a also, sick have market need doing in a in would stabilizer And market have a here. the use they

Brett Monia

Onaiza. Thanks,

Mani Foroohar

What's quick I different of There's And Vindaqel lot experience been clinical as have therapies trial an the discussion survival from that of It tafamidis regarding and endpoint had. in than Vyndamax you're the approval role without as walk I has use - sort well one around X-minute clinicians quick a receptiveness little on what's data experience, hand. the in state to as in the commercial cardiomyopathy. of but feedback getting your of walk approved X have a follow-up. Yes. the follow-up. was X-minute a

on survival that launching execute of assay have you but does a label. an when do how So benefit oral you're against an assay -

Brett Monia

Onaiza, that? do want run you with to

Onaiza Cadoret-Manier

find have Yes. effectively to down look market Sure. is of to able to reduction. that it's place what to important so therapy risk think, really deliver place terms that's a I Listen, data I at in in you that to be again, coming where for going think has survival and cardiovascular the new there, the be market is, the

how as see us. established are our about market making for quickly a it's in really where the these decision those functional things things factor effect do are to important they're coming I think and And already said, are I important that the actually secondary patients in - that be and CVRR, as good studies, with claimed have progress. for well on up going these our to as again, endpoint X yes, But as improvements, it's is going because is patients the a patients. as you we walk think a important So yes, being for a for That be functional improvement. patients, very X-minute

Brett Monia

the to for the mixed little and to Yes. complicated a phenotypes, X-minute disease. to polyneuropathy tests And that, because are cardiovascular, walk add phenotypes just the as cardiomyopathy know, with hereditary polyneuropathy, the of those Mani, you component

be in improve do you're it polyneuropathy if So able in to with improvements may X-minute test walk nothing since to you cardiomyopathy. the has improving fee,

believe outcome We will these the that's for when complicated. a actually greatest, value little drugs by the believe data we - drive in far, it's So demonstrated.


Minter The next Blair. question is William from with Myles

Myles Minter

decreasing on months data question quick - of the a though patients off the or for Just total months. been drug MAPT drug they off have particularly ARC. to keep seem levels, that noticed at X tau been even these I on X

So this a that as for particular And part? boxes that some long-term I'm city you just thinking be large the frequency move into II? indication about you're in you how the Phase dosing will powered or wondering extension may thinking better followed or up include in how of publication,

Eric Swayze


on. looking the hope action said is I that. as tau continued think Expansion - duration a so things of And we've of is we reduction. expand one evidence think and that is that earlier, great - working publication hard program of injections, share less and this So our this been I we'll drug, on And to on this is frequently that design molecule. schedule. you're we And with we optimal demonstrate the to of And the the data are is more outstanding that if fewer course, support an studies as a doing equal really thing. dosing injection, good


Brett Monia

not study, the And the a the really top that Phase necessarily the data just It as that. is making, drugs of remarkable we're probably dosing neuro Eric potentially. III but the of is for in durability reflection towards On And the certainly drug. it's board. said, we across continued dosing for identify the the improvements biannual supports regimen but

Myles Minter

screen that only boxes, on was publication? that be something the the in? with that as in included measured patients just then Or of the is baseline to And city these some will

Brett Monia

the long-term extensions meetings portion will randomized answer I medical I in don't presented whether the a just study. extension be it's things be well. follow know don't in to Myles. question, have maybe would that patient visibility And yet the the of at then have publish definitive and as the or sorts when of for we long-term those studies, think and Typically, we first we publication. - not publications


with question next from Rajavelu Esther The is UBS.

Esther Rajavelu

On design starting FUS-ALS, I understand Phase the topic. of to tofersen? that then enroll us And to considerations this another II you're on can you for follow-up some help trial have compared a

Brett Monia

Richard, that? do to want you take

Richard Geary

This Sure. is FUS. Yes.

terms in and design the of similar the regimen. it's So

III Phase study. And so it a is registrational

authority the an been - from open a So full the few label it's patient input or a cetera. patients registration with single moving health treated design, et all what being has directly not to it's with

this, a confident And think the I program moving we of patients with design very and of that into started good together are we're So we're supportive enrolling. will the in that that put where terms very drug FUS, again, one excited Phase III. be is that we are has

Brett Monia

endpoint add the as is the to Esther, to And same that, the tofersen. primary

we ability direct we scale. a there's Obviously, the measure to So ALS with engagement rating the in link functional do have there, did tofersen the target patients like study.

tofersen X-month similar. treatment, quite I year, than study XXX, it's think, study. It's so It's longer And almost a right? a the like

Esther Rajavelu


XXX or something. think I days it's

is duration phenotype? this Or specific longer that that? treatment the So it thought what's to patient the behind that of is

Brett Monia

others. you of but to are progressing is ALS than diseases, is word rapidly certain that normal, of a there progressing rapidly progressing that if are sort forms population your neurodegenerative ALS will, ALS. more use FUS want a patient for you if

is longer. and the study therefore, longer, little a takes it So

Esther Rajavelu

Got it.

Okay. And on earlier. asked the receptor follow-up was quick a that transferon then question

You whether maybe tied referred indications but help to the understand to referring heart? you're cardiometabolic us you issues in to cardiac indications, structural more or the can

Brett Monia

others things. on metabolic targeting cardiac generated focused have We're well We're validated myocytes targeting based generated targets or a data and failure. going that we've of as preclinical directly We're targets diseases cardiac sorts after like on on myocytes. those directly, heart as based not well-validated genetics

different our primary focus forms heart So is there. of failure


The Stanley. with next question Lebowitz is from Morgan David

David Lebowitz

to just to needs what Slide readout, X be as that regulatory achieved us to able look being exceed That the we be forward you helpful. to readout, far think you could When see run expect in through could thresholds? what would very as you

Brett Monia

Sure, David.

outcry long-term of by be sufficient study With data also said, SODX for the be itself. demonstrate a we a on enormous drug patient well. very by - as of it. opened do ALS believe This reductions, is out primary community. biomarker, sort compassionate for tofersen supportive not severe to bit disease, up, are functional is, for cried you that touched Biogen There to X-month drug today disease, this ago access that has earlier, significant drug is will approval on is as patients for long So - get time an the focus quite out We cried rating this from active this for in there's scale, placebo obviously, treatments randomized for no a versus ALS it's versus know. to use neurodegenerative it's as and severely placebo. placebo-controlled placebo, community extension will benefit that a study statistically that trial, this the to clinical that that a There a

for. known cause looking That's the But Phase that what confident So on - fact we're feeling based we're disease. that's the are for II the about this genetic this the data we're no disease. what and of treatments there targeting

And as So I like our patients last do believe this trying that on that, be I regulators to open-minded think Thank a deliver to David. possible. will question. as drug that's rapidly you,

call on So joined with us who to like everybody that, today. I'd thank our

have to really continue lot updates we're year. of year And half to forward of we We unfolds, looking goals. the providing a the going execute of further second as our all on the momentum as into

So for and joining until great today, thanks have us day. a then,


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

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