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ARWR Arrowhead Pharmaceuticals

Participants
Vincent Anzalone Vice President, Investor Relations
Christopher Anzalone President and Chief Executive Officer
Javier San Martin Chief Medical Officer
Ken Myszkowski Chief Financial Officer
James Hassard Chief Commercial Officer
James Hamilton Senior Vice President, Discovery and Translational Medicine
Maury Raycroft Jefferies
Esther Rajavelu UBS
Joel Beatty Baird
Patrick Trucchio HC Wainwright
Ted Tenthoff Piper Sandler
Keay Nakae Chardan
Sahil Kazmi B. Riley
Rick Bienkowski SVB Leerink
Call transcript
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Operator

Ladies and gentlemen, welcome to the Arrowhead Pharmaceuticals Conference Call. Throughout today’s recorded presentation, all participants will be in a listen-only mode. After the presentation, there will be an opportunity to ask questions. I will now hand the conference call over to Vincent Anzalone, Vice President of Investor Relations for Arrowhead. Please go ahead Vince.

Vincent Anzalone

you. Thank everyone. afternoon Good joining XXXX to XX, third for for XXXX. Arrowhead’s its fiscal quarter us you discuss today results Thank ended June With and management from Dr. us are today CEO, President Dr. an of provide will who Anzalone, the Christopher quarter; overview an Javier San Martin, will Chief our Chief Medical give our a and Myszkowski, Officer, the update financials. will Ken Officer, pipeline; Financial on who our provide who review of

will Hamilton, be Chief our Hassard, during In our Commercial and Officer Translational Dr. Discovery addition, session Medicine, Vice Senior Q&A James available President the call. of of James and today’s

Securities regarding and and the runway, those the expectations statements forward-looking that commercialization limitation cause expressed to plans expectations cash we future made forward-looking forward-looking and statements milestone All would Before those and management’s These around of goals, from of represent results future materially Securities and could risks projected are XXE and without payments development statements differ I like statements Exchange begin, licensing than the are other development, efficacy Arrowhead’s the XXXX within today’s to Section our historical with numerous activities. certain and Act candidates, receipt uncertainties include remind contain current of our that expected statements. of drug of These fact, you actual of to subject strategies including the safety Section Act comments to XXXX. call XXA respect of meaning statements. any during and statements of in

Christy discussed call. of President I’d undertakes Anzalone, and Chris? the annual these and disclaims that Form any including to SEC and report concerning the any turn on intent Form forward-looking uncertainties, our XX-K update said, no call of CEO XX-Q. company. filings, quarterly on reports over duty the For today’s refer most risks please and statements like subsequent Arrowhead further recent to to on With to our details

Christopher Anzalone

of today. We for and our The joining everyone call busy the stage as advances several thank also transaction. clinical fiscal third discovery important includes new you conference This existing well as business afternoon and programs us and It Arrowhead. period later since mid, includes development made for quarter in programs. and programs partnerships incredibly our last a Good Vince. early, Thanks been from development programs. has stage

few As a are platform attention. critical where company, our there we of a focus importance areas

First, boundaries of we what possible push need better. platform to the our make and is always TRiM

of candidates, expand the efficiently this Second, future. rapidly early-stage growth in clinical new will with to we important an need as and the source pipeline be

through to treatment to And and need move to mid without gets bringing important non-dilutive and clinical of TRiM partnering we our that our to lastly, pipeline patients in need it reach fund new of later-stage the closer options. Third, adequate medicines our helps programs we studies, bring use to as expand value platform to our development. the internal maximize goal and selectively capital

we I well all areas. these think doing in are

to that take of last events examples briefly review the this. key moment some a are quarter in Let’s good

discovery completed drug pipeline, includes which For IND-enabling a them new toxicology programs nominated studies. very the on pulmonary our and now GLP candidates. we are clinical manufacturing studies and early-stage for stage, We as quarter. optimization and discovery had clinical They and work clinical of in productive two both product

about disease We but be these year. the later targets, we and gene have the will yet more in not programs disclosed talking

at first and of very The dose-dependent achieve Annual International to genes. dystrophy, show the Society deep, muscle target the delivery TRiM a our that or achieve of types promising and skeletal on durable Research preclinical delivery knockdown as FSHD, Congress. FSHD with data can patients functional platform muscle presented being data muscle-targeted also facioscapulohumeral ARO-DUXX, XXth developed for We treatment muscular program various

models. animal of measures relevant multiple improved ARO-DUXX addition, muscle In preclinical in FSHD-like phenotype

to downstream is expression knockdown as may Arrowhead lead of of or DUXX DUXX using specifically options muscle address believes of in targeting reverse patients. pathology FSHD, selective repair RNAi and and need improvement cause treatments for recognized no prevent and muscle cause therapeutic that FSHD in new that patients the so root currently function muscle the myotoxicity the There in are the disease. effective patients, As

been the pushing pulmonary We this have well clinic aggressively we with two as ARO-DUXX the nominated candidates new toward as year.

toxicology pushed industry year, to a X of so seen on of been this challenging, CTAs file into the all end year. securing have the CROs CTAs the for for in unfortunate, of we of slots the pandemic. but first We half scheduling of will the beginning IND-enabling be the by since bottleneck but more become them next That the studies at is timely expected has

as of We paroxysmal nocturnal against glomerulopathy complement CX. diseases have Overactivation mediated target. of is of previously recently I hemoglobinuria a to number early am a and vascular, effective is cascade be recently on shown candidate including as other many nephropathy that node to programs of announce and We number activation, injury inhibition complement ARO-CX continued a is other complement pleased work the and hematologic a all causative in pathways of involved safe and treatment and can nominated of undisclosed three including in hepatocyte-directed diseases. CX thought complement the conditions, of neurologic of the been CX conditions. renal, central including well both many it a complement the mediated classical, be as alternative complement other and CX and in lectin has IgA pathways Complement

positive from us humans. TRiM-enabled more for reducing inhibition ARO-HBV, translate well of ARO-ANGX, the We CX may for the non-clinical hepatocyte-directed could file substantially be in confidence from in of choice and of CX a data for an ARO-CX siRNA X have ARO-APOCX, ARO-AAT, modality strong capable We track ARO-LPA, programs ARO-HSD. we to that Clinical AROCX the months end levels a candidates, record data that expect including these year. the believe and by or CTA gives

To-date, of which of I at our the of clinical or early-stage least is as a first believe investigational study ARO-HIFX progressed at developed with renal for we X,XXX ccRCC. dose up and is enrolling treatment of some potential The patients. meaningful our We potentially first efficacy which cell in clear been signs being ARO-HSD. ARO-HIFX patient. data tumor-targeted currently target that XXX program ARO-HIFX, milligrams two two dose the well start milligrams weekly, has has showing doses now to generally tolerated quarter, dosing ARO-HIFX of also engagement to interim for cell weekly. patients and During signs one early with announced programs, positive carcinoma, will and clear a in cohorts is

samples and a X of patients be via X minus evaluated was protein protein that could to the demonstrated XX%. H-score of of Specifically, HIFXα tumor reductions assessed XX reduction in minus These minus those HIFXα with mean immunohistochemistry. from reductions XX% X% ranged X had H-scores.

these In stable had best subject think disease. a broadly. We and response a response population tumor-targeted had results addition, a ARO-HIFX heavily with partial approximately our one subjects for pre-treated are of tumor in X XX% and early platform shrinkage encouraging

and positive milligrams, ARO-HSD single healthy patients lower We at ARO-HSD with liver XX. dose X diseases, X treatment for reduced effect a of at milligrams, given data Congress. interim pharmacodynamic XX the XXX a in showed tolerated being XX. volunteers biopsy NASH quantitation. All limit patients measurements a NASH International as reduced below well other potential as developed such three were Liver milligrams with the given XXX strong in in by for EASL suspected suspected at Day was the also or milligram while HSDXXBXX presented XX% XXX patients’ as XX NASH milligrams two and patients dose X Days liver protein of measured XX% patients, by and Day AROHSD on XX was with the

reductions to believe that investigational from XX%. ALT protein ARO-HSD therapeutic a XX%, of demonstrate inhibition and with hepatic ranging XX% Importantly, from HSDXXBXX is showed the We expression. mean baseline to robust patients all mRNA of reduction showing first

two see to ALT of also ARO-HSD. are We doses just highly drop following significantly levels encouraged

as including for treatment to X studies potential populations. progress in ARO-APOCX potential addition give will a dyslipidemia. that milestones on studies give our Phase across the together each few the details programs, programs, robust dosing started developed believe being started target early-stage or a of recently but will activity patient in minutes, mixed will some one X each start Xb program. already important us pipeline, to and In on as for about Phase with have study. and pipeline. picture medicine developed cardiometabolic more studies, we being more studies Javier intend ARO-ANGX the the various also two initiate a We for mid hypertriglyceridemia a we pharmacologic achieved two for I treatment later-stage our We our

We us Phase to are identify dose X enable the and intervals intending move confidently multiple into dose optimal to studies. to

rare also ARO-AAT, important quarter known TAK-XXX, a cardiometabolic Takeda genetic programs, our associated in In last for alpha-X treatment addition with we multiple co-developed liver being as deficiency. antitrypsin for the the disease events had as to with

liver mutant positive was that the designed up level what identified data ARO-AAT liver and to generally improvements to the doing multiple of very alpha-X XX-week after removing us the give begin and liver Congress. Liver is do to as treatment is with a and the see liver of at deficiency. tolerated additional to mutant sustained led that AAT been community. measures reductions AAT Takeda protein These rapid progressive the the treatment antitrypsin intervening can the alpha-X received ARO-AAT chance demonstrated even presented our treatment. in well patients from liver with others in important interim that This of and has with process, the year suggests and drug late-stage substantial have biopsy Mutant of and protein. We it to EASL AAT including is in we in X First, we were physicians results fibrosis, healing these health, cause results responses disease disease. when International protein thrilled similar patients results at to partners in treating

study, various patients various ARO-AAT study, the biopsies X dosed SEQUOIA enrolled the the cohorts we Phase fully dose with and various also the levels in recently. XXXX durations. XX treatment being have paired We patient from Combined XXth receiving open-label approximately will with

Lastly, Fast granted FDA. were designation the Track designation by also from from for Commission. designation Therapy the ARO-AAT, was previously and Drug designation we Orphan and Orphan the U.S. granted Breakthrough FDA ARO-AAT European

goal of provide ways to potential Our designations ARO-AAT each these of to that. and achieve the important is expedite path development

this important path to quickly. bring to We regulatory authorities from drug patients the will work and best our with Takeda to partners identify

option of to to I selectively use and progress Now, maximize helps the to value fund on reach component on non-dilutive as company Janssen, towards that executed platform was development. an chronic capital have ARO-HBV the an recent end The to that the progress. is which This mentioned, internal XXXX, strategy and and with against made X technology business expand area with in a important of we’ve B a we moving of seen believe where platform for should programs. bring we key additional the infection, our hepatitis collaboration included partnering partnering,

option previous agreement exercise with up to brought treatment Therapeutics to It studies. and potential the a the we not with in field of to with the with Horizon capital. previously the quarter, to potential player to for Janssen’s and $XX its milestones we space first ARO-JNJX. commercial candidate Janssen programs, During is is million million enter existing intent an brought organization. a partnering range expertise therapeutic Arrowhead receive developed receive those the and undisclosed needed receive regulatory great responsible gout. a an license to development, treatment being will during commercialization. eligible quarter, notice the It also ARO-XDH, delivered clinical right further dominant in of a Horizon a from discovery-stage to the $XX need, exclusive is on an and upfront clinical to attractive net uncontrolled as for and global to technology in be This in for move area low product intended will our million its Horizon example announced an development a option disease, earned written payment unmet as in signals the collaboration understand people and Arrowhead received help a expanded had $XXX of wholly the Arrowhead sales. to mid-teens license This and forward Also, for and by fee clinical intent reach the exercise of path, royalties independently the gout commercial eligible that opportunity. worldwide non-dilutive in tremendous and

perfect made patients these of we the this we reasons, therapy all thought sense deal to partner look was for We Horizon need. working with ideal For closely forward the Horizon our both for as in potential and companies. new advance

a quarter was exciting of this lots heard, you’ve As with busy events.

invariably and line straight a in are progress there doesn’t surprises. development drug However,

an in Sometimes potential program update last investigators and ARO-ENaC study this from investigational can in rats that we contained dosing of expected inflammation. sometimes instructed these a additional paused enrollment any these than being preliminary more Because To the clinical further latter to such program, surprises lead to We cystic ongoing chronic ongoing as and local additional the study. study for receiving screening, ongoing primate new ARO-AAT study experienced toxicology of toxicology the chronic leaps candidate treatment be after unexpected unwelcome. lung we healing surprises preliminary faster voluntarily developed a rat forward, review, update, data our of our from liver quarter. pause of chronic ARO-ENaC pending signals as an toxicology the fibrosis and ARO-ENaC the in

the study. or any in tolerability concerning people in AROENaCXXXX enrolled seen not We have signals safety

the in We continue not the the yet toxicology we data know additional the on pause above keep conducting ARO-ENaC that we study findings. clinical of we we clinical that participate not our yet else, of all now. are back for However, internally, do to studies have studies so trials so from safety place from the patients extent nor will full do

in still and to investigating the Javier are when should months to I’d overview, We to are the this more gathering and over Dr. like Javier? stage. we are and update that Martin. now in intend coming an provide information call fully weeks know With able. we San We turn the

Javier San Martin

want details afternoon the clinical on our an design to newest studies. a good and on update our of provide Chris you, and of I studies couple Thank everyone. give

X the designed First, clear clinical to of to interim from results is the a by I dose-finding which cell positive carcinoma, discuss treat inhibit first will clear HIFXα advanced renal or RCC. cell in with ARO-HIFX, were Phase cohorts Xb production the of cell study We two AROHIFXXXXX, RCC. cohorts encouraged

indefinitely enrolling determine XXXX the a weekly progression, X of IV dose Phase Patients which safety is weekly and HIF based ARO-HIFX. currently cohort up of the patients response HIFX-alpha expression and XX continue designed a to they include X, efficacy, We and designed are infusion to to to evaluate receive discontinue. of complete of The is to study ARO-HIFX assess until to will preliminary RECIST or will tumoral receive pharmacokinetics they associated who ARO-HIFX, recommended disease milligrams on have and genes. post-dose experience

from cohort data the is X this to Our intention from interim X medical meeting X, share and additional appropriate at from initial data future. study, an results including cohort in

at ALT NAFLD the detail We have not yet ARO-HSD, EASL our candidate selected the two intended highlighted meeting. and The exciting Scientific EASL think It next the was fact, NASH. following in significantly presented alcohol program in on liver our I is drop for we Official see want data interim and related and treatment encouraging We to the was presentation of Press to potential levels Conference non-alcohol ARO-HSD. of was highly investigational doses just disease.

was extraordinarily in because our at gene of target We ALT liver and confidence different improvement with TRiM expected consistent evidence a early of But knockdown, point data HSDXXBXX the directed for system our as time clinical studies welcome design programs. provide potential as high the further surprise. therapeutic These level strong across genetic a ARO-HSD. this us we target has increased been very

like. inhibition HSDXXBXX that of mechanism are questions disease We the may answer designs innovative key improvement seek and about of medicine, the and signs early thinking the to about what look

NASH this the ARO-AAT. or are are happy meantime, is and fully conducting are in to NASH X/X how Phase report approaching we patients We that with to the study enrolled. approach in we still way the we In a similar suspected

the study all ARO-ANGX dosing Xb cardiometabolic our start. in think a the studies candidates, additional started give details design will on potential we provide of studies and you studies the to they will when of quarter. I We so during we two description shortly timing. intend ARO-APOCX brief designs, mentioned, and Chris these additional last of Phase As initiate through can

of milligrams XX a the be AROAPOCX, AROAPOCX-XXXX, Xb and with ARO-APOCX hypertriglyceridemia, safety of For to XXX participants or The evaluated to double-blind, approximately Three in will the will adults the to All XX. regimen The screening. ARO-APOCX, study population. be per efficacy XXX X:X X A dose milligrams, SHTG. or participant have the milligrams of week or we to severe dose placebo. injections in XX on fasting and and adults XX approximately placebo-controlled later subcutaneous and initiated of end-of-study dose XX in is duration in studies Day Phase against will ARO-APOCX levels participants greater efficacy is study evaluate cohort at enroll to placebo the examination. to for participants a randomly study parallel in cohorts with in enrolled will and triglycerides both of who XXX ratio assigned receive objective this in receive of of Week with study. mg/dL the from equal a screening dosing clinical XX stage ARO-APOCX mean than evaluate safety total weeks primary select patient SHTG Each

ARO-ANGX, The equal parallel in total in placebo-controlled Xb to than in evaluated or study and milligrams from the the mg/dL is and ARO-ANGX I at Ken Arrowhead’s of Day the enrolled Week ratio Financial examination. safety end-of-study LDL-cholesterol XXX screening: and participants the AROANGX-XXXX mean participants dosing AROANGX-XXXX, randomly After eligible and is to assigned in mixed efficacy dose will dyslipidemia continue regimen with will dyslipidemia. will the X for Officer. primary duration enroll the a in study efficacy weeks cohort objective XX patient initiated XXX will safety or mixed fasting with and placebo For XX. Three placebo mg/dL. over this XXX with participants the to All ARO-ANGX we open-label Week ARO-ANGX study. cohorts non-HDL-cholesterol between than evaluate later to had adults studies following XXX Chief study. milligrams, The the participants Myszkowski, XXX approximately in equal XX now visit, greater completing an study injection of population. XX on to stage in clinical mg/dL to greater of A of or per XXX call extension XX approximately triglycerides in subcutaneous Week and and be who with mixed milligrams dyslipidemia investigational to against XX select XX adults of a X:X Ken? an to be Phase the double-blind, be levels screening will receive dose ARO-ANGX a of or evaluate a of turn

Ken Myszkowski

Javier and good you, Thank everyone. afternoon

we ARO-JNJX collaboration certain manufacturing continue exercise completing to of for remaining revenue as in we option projection. for Revenue per related Any today, our with license $X.XX from primarily per XXXX our collaboration X shares diluted diluted compares reported weighted for Revenue portion additive $XX.X with million process $XX.X milestones $XX.X million XXXX. $XXX quarter a would a The received of the the the million with the XX, period be As million to XX, $XX this million, for collaboration million achieved net period average managing agreements Takeda May the years. June related our XXXX. net XX, primarily $XXX services. under share relates XXX.X our or the upfront work $X.XX on XXX.X clinical of partners in quarter milestones as be our recognition from agreement and performance XXXX. recognition obligations to for Takeda ended to share shares quarter of payment XXXX toward was is the of June loss the received a in be million program based the outstanding. on portion associated for over to ended Revenue loss was or as This additional the Revenue million June outstanding recognized to Takeda current the ended weighted recognized will Janssen. fully quarter average in approximately payment $XX.X of the and compared of the million with agreement June anticipated prior well Janssen received trials with XX, fully ended collaboration

of used specific agreement ended due candidates XX, Our million XXXX revenue for Net million June $XX.X XXXX million ended during activities quarter exercise is This XX, and Janssen as June and HBV by performance ended ended the quarter increase compared operating XXXX. during net XXXX. the Total for payment the cash increased operating for is expenses quarter Janssen June of compared this in option substantially from The to clinical XXXX. primarily has the was was change with quarter by complete. costs under recognition and of used discovery May the for the received increased driver $XX.X June both program $XX.X key candidate cash activities to ARO-JNJX the company’s R&D were XX, XX, $XX.X advanced. million, pipeline $XX operating million

from estimate milestones potential to we to run-rate $XX collaboration $XX burn any be million quarter. partners, cash our million our Excluding per

balance our totaled and September upfront at in payment Horizon. our activities. In used the XX, the investments to Takeda cash was operating sheet, XXXX. upfront XXXX XX, Turning collaboration our also investments primarily from cash cash $XXX.X offset million collected June million we payment $XXX and to our $XX July, compared recent with under due at An due by million to by increase received

With will turn outstanding now at Chris. XX, XXX.X I were XXXX to that million. the Our June overview, common brief shares back call

Christopher Anzalone

Thanks Ken.

the we activities mentioned, progress company. we required to successful think spectrum across are strong I of be a platform As making

TRiM innovating pushing the We the and on platform what can are of technology do. our bounds

early-stage efficiently Arrowhead candidates the be in feeding growth with and for pipeline We rapidly engines may new that future. of are the

responsibly using mid business bringing stage we our to clinical And new important sense to would programs to Thanks of your joining again quarter all us to This medicines call progressively like and partnering last now and and later closer who in are so. progress makes development saw the patients the areas. and lastly, do goal need tangible I Operator? today. important for it moving selectively questions. our them. to are open when We these

Operator

question Maury first of [Operator from comes Your Raycroft Instructions] from the Thank Jefferies. you, line Chris.

is line open. Your

Maury Raycroft

bottleneck questions to Can the on the my has pulmonary the comment wondering you this from do Thanks for two preclinical additional the DUXX for I and ENaC? waiting and was for filings data anything with candidates. for progress. the CPA whether taking for congrats on

Christopher Anzalone

we conference there not. finding in. also many do, calls since zeros. that just with to – It there primate There more pulmonary CROs does slots because think a talked has bit this, It shortage. is ago about to studies of a I is these not the there that few do has a been non-human And is, are difficult pandemic that come do

So had given that bit – just bottleneck. all we a a have of we just

so we done just going had hoped. will a And and or get than to we we later get these that done are two quarter them

Maury Raycroft

Got it.

of are just also you wanted weeks studies then the update going in providing know status if check going is more could on to it clinical you the mentioned are how And ENaC that them? few provide you may And be NHP to fair data next in saw? you on some assume next there that to and the a an that this months, and X to update, Okay. on you update the and

Christopher Anzalone

Yes.

I don’t know. So just

we I till have towards the So year. NDP have are end don’t the of not know tox respect to when with clarity, better going to the going to just we data data, the are

will be until a then. that so And box black

data there have development ongoing the that. there just We haven’t that’s no so yet. for final still reports don’t and piece We is yet of

update, experiments. an other interim doing got some to are internal caused We now us We press – just are and pause we which still ongoing. that’s

how beyond guidance this about something, you going we give are is able I that’s might talk idea in to back working when if are about work until to can’t make we we get it And a better sense think right do go on good fact, to program going and us it clinical that, track the for be I have on where we And to out. now. so to on going doesn’t quickly

Maury Raycroft

more into question could Okay, good, the me just you And do think point, insight at related to and the you fact and and looked Arrowhead do at the this data that relationship last have between higher RCC the tumor for dose? actually tox makes activity sense. how that change knockdown

Christopher Anzalone

to With the we yet. don’t looking this question only we and don’t second at fully, know haven’t don’t in respect information. dose – to seen data – the are with we we So seeing we from the have this first so a anymore from respect – question, yet real are higher time I

So see encouraging we down. appears where appears me we least are we engagements, goes. that to target knocked here, at are that getting getting that the was it was What will good on board are it we

So goes. bit I of sort if respect I don’t rapid expect pathway now, will, that through where just a let’s tumor may see not response, such you would this this and – with a physiological to shrinkage longer. take

going to knockdown forward. fact are that’s to now see and some going suggest that just need that platform right to go we the our So, us seeing working is we how so now

Maury Raycroft

Okay, I in the hop my questions and queue. will for taking that’s Thanks helpful. back

Christopher Anzalone

Maury. Thanks, Sure.

Operator

you. Thank

line Your – next the Young from question from of Cantor. Alethia comes of

open. is line Your

Unidentified Analyst

Hi, [indiscernible] on our questions. for and Alethia for taking thank this is you

program on DUXX? with could from primary if the if read share change wondering you Losmapimod, Xb are for competitors? also, And it through is results which in the missed compares DUXX We to and your more any there on Phase endpoint how

Christopher Anzalone

Yes.

it’s will – I is let on It’s there So different. will James? comment well, because but that. him course, don’t entirely, James that compound one, other with I different don’t read know of through I I the comment let about

James Hassard

whole out There question targeted much we is not programs. a the With is Sure. competing Maybe data to other will anti-sense all with oligo there I the programs, available. not and lot the take how compare really preclinical there. regards the the about first are first programs

the target use versus be way antibody we that And that approach. the so antibody difference fragment a their the ligand or peptide primary we would targeting muscle cells

shared no then that’s compare I mean, And it’s different say. set any the a read-through different tough data main it’s at that’s this is far as the point. as have and very to Yes, question efficacy programs around really compound right. competing was as levels way to other the knockdown I other Fulcrum mechanism. the not – So comparing or difference think there

think I difficult biopsy stochastic with target a And where that catch did biopsy. with this associated there to if or population. of this the highlight specific expression maybe will, in this with study the sort of target, challenges they to monitor, you is

we gene at will dose look help downstream other so also might parameters we us studies. a at but that stage later And for look expression, select will clinical likely

Unidentified Analyst

Yes.

Ken Myszkowski

study, to about semester that was this clinical the I which in the another comment add this In I positive. biomarkers, despite data, wanted data think

still changes at is and target know PLL we is don’t were I is. look the of a the and if I changes us minimal to the of to think And this. that the So try those looking number you significant, think are physical statistically see that clinically dose a understand changes Because in at relevant if some function with will how we help good that place. there products relevant to correspond

mix is the it’s think improvement there here think excellent pathway. I now sciences I is of positive. I So, clinical results which for of population, the despite mean, a being biomarker this potential patient in

Unidentified Analyst

Thank helpful. that’s Okay, you.

Christopher Anzalone

you. Thank

Operator

you. Thank

of comes question from from Rajavelu next the line Esther Your UBS.

Your line open. is

Esther Rajavelu

that what taking are been seeing? it’s so what to tough lung for find question. limited And specific that the two. have exposure but you the a is my considerations you be the tissues? would evidence some you I target, is to it in lung? takeaways from of other tox historically there tox thank your or Is the if signals Hey, ENaC, One are on

Christopher Anzalone

on haven’t say we over The that just hand words about, heard on whether rat me it saw I let this this. had tox two we we and James to will report study. final a again, So,

is broader didn’t that don’t but inflammation. don’t we don’t the is – into just data, species issues. was we We we I as if see see data There know We is is lung because So really get have yet. specific we limited target NHP know what don’t specific, this. or had understand local said, to that’s a if it We it are specific. sequence starting – we

James Hassard

the other question? What part was the of

Esther Rajavelu

drug you it mean, of I the the is to that maybe if you different consistently and toxes and interpret – because target go or thing, – would it see you that, of works have question do just part that that getting to lung, change – the sort would would lung would – was, a the you a other The the the see back you specific you is if data, another to the chemistry? is it or limited get when toxes NHD find how in to the have you good

James Hassard

stated Well, great. not if the surprising. that lung, Chris systemic not with the being inhalational is has tox limited bioavailability mean oligos to is I the as

we it’s in So would lung. see unexpected only that the tox not

rat the at look in there, the and depends what study dose amend the terms think the what on a and maybe levels, is again, would opportunity from take results to yet, on at I final and we intervals. it results dose toxicity results, in or then an we there have of as what NHP see the frequencies the don’t resume to depending these and dose dose study different is levels different

Christopher Anzalone

we also this dose dose high, And following reasonably relatively that it remember can Right. dose to but that, we this, we frequently.

point as opportunity just we to could the That’s or to James’ are clean appears NHPs, if out speculation. it be have be a he we dosage that the an space all this – in to if is so more. alludes, bit And

go in there. and the we where data see come Let’s from

Esther Rajavelu

on Got design or registrational third the you AAT, quarter, it. think are the then in summer said revisit And Thank and on I to track you you. still with late trial thereafter? the FDA

Christopher Anzalone

Javier?

Javier San Martin

And X Phase you initiation say of the study? the

Esther Rajavelu

Yes.

Javier San Martin

Part of the introduction, yes.

ago. know, about So breakthrough we weeks have been a as X granted designation you with or probably week

to the in document multidisciplinary timeframe. called QX-QX already what working the meeting, in first briefing We engage yes, are on is the

Esther Rajavelu

you. Thank

Christopher Anzalone

Thank you.

Operator

you. Thank

Your next from Beatty Joel Baird. from the line question of comes

open. is line Your

Joel Beatty

is of seen study. on reduction congrats doses two HIFXa on HIFXa in dose in in the among the response Couple that have And the with those questions follow-up. first I progress. Hi, of program, the a then

James Hassard

response lot second dose are still we the the escalating two data and from process A those the analyzing The cohorts, on yes, between still I the of all are of drugs. in patients dose think first cohort.

to really answer give us So, dose clear response. I a early on think too for it’s

Christopher Anzalone

is And a wrong. factor I further get may these complicating that numbers

had I’m of biopsy of material XX So if I them. we had me think we correct only from wrong, individuals, usable X

I this may that to just did both add think in know we doses. we is And knockdown if haven’t sponsored The point. will so it only difficult be at

James Hassard

top an overall on line And in just the giving were release we press this.

we full to level dataset our so include a And an intent, well. present at will medical the said dose this top remarks more which is appropriate prepared the meeting, in as

on that. So stay tuned

Joel Beatty

it all Yes, and sense makes okay. That is helpful.

Sorry, was just are that the one in seen [ph] mentioned patients? share reduction follow-up is on you there response, HIFXa to anything about able – the one with fair responder you the a

Christopher Anzalone

time. this Yes, not at

that medical full present an at meeting. we think the we upcoming can I share dataset when

Joel Beatty

much. so you Thank Great.

Christopher Anzalone

Thanks.

Operator

Thank you.

the Your is next line your Richter of Group. Goldman question Sir, from Salveen comes Sachs open. from line

Unidentified Analyst

just our Thanks to what Salveen. looking the were other Sonia is wondering pulmonary tissues on We and into for This you hepatic the forward? extra for muscle beyond target target, like go would be the question. taking on

Christopher Anzalone

we a number of So, programs active in have areas.

are areas the We disclosed on. that we that have working not other effort other

in that So is on though the clearly the a we have environments. yes, just look, target CNS facing mentioned – rich past

want to go it’s at a we So, place some point.

tissue there a of looking we there are at. that are yet, We is types but not number

Unidentified Analyst

Thanks.

Christopher Anzalone

Sure.

Operator

Thank you.

comes question next from the Canada. Your from Royal of Issi of Bank Luca line

is open. line Your

Unidentified Analyst

Great. Thanks Luca. is Lisa This question. the for for taking on

approval? have AXAT, X patients Just there and with give be a ongoing FDA, XX a directional the study have on that now on designation, the will sequoia with follow-up data you one here on where also maybe for I the ENaC. more the can Phase us scenario color sufficient dialogue from And the XXX the first you some accelerated from

Javier San Martin

say interaction now, will is about thinking This to are focus this need the Yes, options. Javier. we as is I all interaction. those of a multidisciplinary meeting. we on typically, first And Right first

the it’s the design, aspects filing to conversation, will a but and it’s endpoint, X one-stop touch discuss a approval filing study time of different process, to the be now upon the is going We critical, Phase process.

So, will potential good it’s and step that a of course that forward. and thought thinking we entertain

Christopher Anzalone

with division. who this They is working been interactions and collaborative. quite to to have the had we this are so us. far interested really have that appreciate patients get I with clearly and really that and interactions current particularly the our But need positive FDA think they with us in limited And need an medical unmet

so had, haven’t we we this breakthrough really to excited are have so designation. And

sit in-depth discussions. and more have So, these can down we

James Hassard

to point, based approval to the next precisely what your And to component essentially the The an we discuss. breakthrough breakthrough significant opens translate document. And of time resignation into path will a designation likely that’s briefing surrogate around, clinical the benefit. on there was

So, this we to are yes, talk throughout going process. the about

Unidentified Analyst

mg are tox talk Great. scale doses the and in which wondering one are seen the then rats result therapeutic here of seen super just the out XX ENaC, doses at doses you And how within doses rats scale about humans? that to – signal can you the tested at that figure just if Just Thanks. was XXX or in humans? That’s whether maybe signal the at into on seeing range tox in helpful. those being trying to

Christopher Anzalone

I given just look, don’t been we appreciate – part Sure. We know NHP. tox of policy And about talk have a synopsis question. final not in don’t it study. about the have we it a – has even you the even a to just We But about particular, our have been here. is anything data, rat small report because

more are color we unable any you at point. give that this on to So,

Esther Rajavelu

got questions. it. taking Thanks the Okay, for

Christopher Anzalone

Sure.

Operator

Thank you.

line Your HC Patrick Trucchio next comes of the from from question Wainwright.

Your open. line is

Patrick Trucchio

clinical a Alright. the secondly, Well, on seek than bring just which potential And begin? CX And rather would initially or indications on, can questions follow-up vendors you on could would you program discuss that what would Thanks. partner? is are into targeting indication your do development program couple CX clinical Good of program. first, own know this focus or any the development you you evening, CX if CX? collaboration when a a of

Christopher Anzalone

the will I James. of to over those last the answer will I rest questions and hand then

this a to now not So, have right do for program. seek we partner plans

may If to good going you now development. construct. change clinic. this but right future, preclinical in to in is feel take in This forward. This our We we having directed directly look wheelhouse is that the of are about terms a

the look a And data the some so then make future. can decision in at James? partner let’s on versus non-partner what like. point we see And

James Hamilton

of will CX. versus that CX sure. Yes, I take about was I the part the first question think

involved the lectin, a is classical central alternative complement the cascade different the three in node is in the that CX of all that and So, pathway, pathways. components

can So, CX, can downstream broadly applicable be complement if CX you mediated diseases. should and various effects so you really everything to that’s the out take of inhibit

reasonably Chris a glomerulopathy, with PNH CX treated Now, mentioned specifically during the well CX inhibition. to two interesting earlier indications PNH remarks. that been and that’s is disease

to refractory due However, of treatment, to there is a that That’s extravascular component hemolysis. by primarily CX. is driven population that

deposition treated inhibition, the anemia, is residual that with CX disease So, in is patients with CX that that’s potentially treated their CX CX in excess the driven another residual by specifically where glomerulopathy to be There the with population, refractory activity fragments population really could – glomerular. inhibition. of CX

disease. driven CX a really that’s So,

diseases. other conditions, Beyond those, that conditions complement as to are we disease may where And those is, the in complement mediated. there maybe CX have other not inhibition those complement mediated CX are as other applicability that two think mediated, and specific

CX that think as I as both indications. the CX, So, the about versus covers maybe question the and well second other first

Patrick Trucchio

we was question enter clinical when can other one about And development?

Christopher Anzalone

of the year. By the end

filing be of CTA the will we end by the So, year.

Patrick Trucchio

a you where development? to from program, then $XXX us a on price follow-up expect Got fit gout ARO-DUX and comment, it, maybe the the cadence clinical and potential a so just And million would could program something the the it paradigm, that’s of tell helpful. be potential milestones can gout in enter you treatment could when from

Christopher Anzalone

can’t about about those any that, We of say anything actually.

this this how one decision. their could fit Horizon so clinical out and achieved. reasons we payments So business milestone how as did But ultimately, chose the we of a them. be – with their could the the This $XXX to respect With the potential this work a we is what of is is paradigm, not partner. into closely split – million

tell to toes going and when early so to that to business. their when begin we And they you I still step don’t their something be that. want really you on program. believe an don’t what going know are respect asked This with is to And we the answer and to the clinic, is this

out just right are now. We working

ways we have go. still it’s, so to And

Patrick Trucchio

much. very Thank helpful. That’s you Got it.

Christopher Anzalone

welcome. You’re

Operator

you. Thank

Piper Tenthoff next of question the line from comes Your Sandler. Ted from

Your line open. is

Ted Tenthoff

the the ENaC impact everyone. pulmonary expect and that much. our very you sense gating new clinic. I a And program targets. Thank more into to learn you you What those get the Thank are factors, there bit could anything wanted little to on from is come just programs a

Christopher Anzalone

Yes.

the good a the too It’s with in going ENaC program. just know still early. know rats don’t Ted. So, what that’s happened I question in on what’s that. answer those to don’t We

future And still this I information, don’t we still us a know we we as are can. read And I is we more go, down. for on so moving can’t opportunity – quickly might as big until that slowed think programs. have us. We how just it

about excited programs. these two are We new

We haven’t gene about targets. talked the

into about maybe we disease talked turns this the haven’t just disappointed we get year. to this year. slots areas. the clinic we couldn’t We will the I that But right the this that expect that’s world wanted way that move We the later now. were

next do in year. this in that will we non-GLP waiting half bit clinic to are work And seen, while I so the from have what look we the again we seen getting on again, data of These talks, we chronic studies. so. we have has say more to small think always forward because what But caused seen these a are first I are study. have there internally just rat just that us

a So, internally other programs. more understand bit the on we

Ted Tenthoff

dosed. something who the not hearing publicly? forward. be patients But to is And doing are would already [indiscernible] that do going with a data? we anticipate that to about that be dosing I know with going have How going And it’s to you informative? respect is share you been whether anyone

Christopher Anzalone

give sorry. can’t on And am that. answer definitive I I again, a Yes. you

to can that it, we And program. with when we know, know, it. when we going can restart what’s because restart don’t if don’t Just we happen

information, just other. until guidance rather would we So, have we the more sort any one or of give way not

Ted Tenthoff

so lot understand. Totally Yes. thanks understand. really for update the much Awesome. progress year. Chris, really I and this of great a

for excited half. am I So, back

Christopher Anzalone

Thank Ted. you,

Operator

Thank you.

Your of Chardan. next question line Keay Nakae comes from the from

is line open. Your

Keay Nakae

targeting to I what a the the Chris, targeted ligand. are you But following the going those are versus for for the different same up similarities Hi, so new construct the June. between you ENaC? just on mean, have are thanks. Yes. programs, obviously, using sequence

help understand potential better to ENaC read of us the And risk so is across from the tox? what try

Christopher Anzalone

Right.

believe appear see the to that will be than that same don’t again, in are would material you we animal they different we less using But as in at two, the we ARO-ENaC. using I potent because both know. animal that will expect So, said Is I be next more translates studies, the know, humans. formula sequences. I it’s I into well, as And that for important, studies. case least

chronic data, again, too that sequences. other until the it’s if just more have we what to early tox, we in saw speculate may so And interacts, to on translate how

Keay Nakae

of for weren’t forward characterize do Okay, thanks just going about the there just being we how but the biopsies and risks your data not can for some of James, assessments? that. And to the think you to used, able further you the then them that get that that received and fact

Christopher Anzalone

James?

James Hamilton

Yes.

enough to far samples then get our that far press do have about in the always And second comment able us biopsy was up are biopsies the biopsies in and analyzable. been and design the we that protocol do – one biopsy to. we allows get will first paired enroll so far analyses. adequate the a need to make patients the the to sufficient to make number cohort, I are enough third in the release, as So to not maybe to to and work we think of But described samples so as study well,

Keay Nakae

Okay. Thanks.

Christopher Anzalone

you. Yes. Thank

Operator

from B. the from Riley. comes Mayank question line next Mamtani of Your

is line open. Your

Sahil Kazmi

This Kazmi approval program Thanks of RCC? Hi, questions. on color brief on taking the on awareness maybe our provide increased Sahil could in Maybe of or how with maybe one enrollments on any a the you kind Mayank. disease good for for VHL is context afternoon. tracking been the just associated HIFX, and

Christopher Anzalone

been Yes. in actually really that throughout. has Enrollment program good

enrollment We very challenges and have the have rapidly. slots filled with seen not any all

but has that detracted enrollment know is into I it this study not ongoing, Merck from so study. And the

Sahil Kazmi

what level reads any and/or present thoughts can J&J might maybe that what the have treatment on And on insight from kind of from HBV, learn study? you high data Okay. do then into we for forum XX-week of kind any incrementally of

Christopher Anzalone

about no. we give guidance Look, could look be plans to don’t be any Boy, their that honest forward where data, are can’t on what presented. I those that. know but I to seeing

Sahil Kazmi

taking on for Thanks quarter. and questions it. congrats Got the my

Christopher Anzalone

Thank you.

Operator

you. Thank

next Foroohar comes Leerink. from Your from Mani question the SVB line of

line is Your open.

Rick Bienkowski

us. just afternoon. Mani. This for on for line our good two Hi, questions taking Thanks is Rick from

in a I could you for to of with first, lot tumors. data are knock there of seen of the some variability on value data? HIFX, speak sets down So know

So, was of be doses that just of the in either could some patients? variability higher to tumors looking general potentially it earlier this or heterogeneity of something resolved lines due or by at

Christopher Anzalone

Yes.

think there heterogeneity that think are the heterogeneity not on and from getting is And also I expression across you necessarily you area I tumor. the that the in in of to patient into hit nail of I between paired mean same tumors patient. head. biopsies, the the

definitely issue So, a of heterogeneity the explains is component probably variability. an good and

Rick Bienkowski

to exploring to target it. so so is Alright. one question, be would other maybe extrahepatic strategies with more speak the of favorable broad currently ligand are focused if class And you these Got of specific integrates molecules? Can Alright. approach pre-clinically. much lot. around just a general, another to company deliveries why And I targeting to conjugates. needs Thanks in the

Christopher Anzalone

Yes.

been let So, to James budgeted has will also I broadly. go,

targeting company. not We integrin are an

company. R&D an are We

agnostic. use to tend we works what so And are we And best.

modules such. done with with antibodies antibody peptides, with have We and work fragments, with

ideas work what and for but been so targeting data have we so have just that, that that And it we quite the happened good has us so, might will based best, ultimately, tell about we just, interment us.

James? So

James Hamilton

I that works. And pairs, in because because best. don’t with that was receptor looking but continue. with integrin went the ligen was we will not what report expertise, that, our we was we area of that go And

the ligand I an different so. to historically have to or is, what evaluated what We else. think works will of multiple with something continue molecule small go do continue antibody modality we receptor if pairs and And regardless a it’s or

Rick Bienkowski

appreciate Great, all I detail. the

Christopher Anzalone

Yes. Thanks very much.

Operator

call the go Please Chris. to will ahead. no are over queue. There back the you. questions turn I Thank now on other

Christopher Anzalone

joining and you have Thank a afternoon. I all today you nice us hope evening and for

Operator

you Thank call. conference today’s concludes for This participating.

You may disconnect. now