Earnings call transcript Q2 2023

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Operator

Ladies and gentlemen, welcome to the Arrowhead Pharmaceuticals Conference Call. [Operator Instructions] I will now hand the conference over to Vincent Anzalone, Vice President of Investor Relations for Arrowhead. Please go ahead, Vince.

Vincent Anzalone

Thank you. Good afternoon everyone and thank you for joining us today to discuss Arrowhead’s results for its Fiscal 2023 Second Quarter Ended March 31, 2023. management and from Dr. today us are CEO, President With of provide Dr. Christopher will overview the Anzalone, who an quarter; Javier San clinical Martin, provide an our Chief Medical on mid Officer, our and later-stage pipeline; update Dr. who will an Chief Chief the of financials. review programs; Translational will earlier James Hamilton, who update Myszkowski, will Discovery our our our on Ken of Officer, Medicine, and who provide Financial and a stage give

Officer be and and In during Patrick our Chief addition, Tracy of Officer will Oliver, Chief portion General Q&A Commercial Counsel, available our the Operating call. O’Brien, the

Securities would Before we forward-looking to begin, of Securities XXE comments that Exchange made the the XXXX within today’s I Section certain Act like contain of of remind of the Section Act you XXXX. call XXA meaning during and statements of

than expressed of and forward-looking that could are forward-looking other to risks differ statements to in those results fact statements materially and statements numerous historical from any cause uncertainties subject are All statements. actual

these please on Form report For and reports on quarterly risks annual further our and Form recent our details refer SEC XX-Q. including most uncertainties, concerning XX-K our filings, to

I’d CEO the Chris? now to call the of company. President Anzalone, like to Chris turn and over

Christopher Anzalone

we was you liver. the platform. could afternoon, importantly, the and the that Vince. and on Thanks, hepatocyte therapies In of proprietary for industry outside focused leading joining potential an entirely could science RNAi This We and become one our thank our everyone today. us XXXX, believe Good then it bring introduced TRiM for based that competence RNAi platform

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in CNS. candidates end XX targeting have organ and expect this year to different least clinical X of the trials lung, We drug at by liver, systems,

targeting candidates will across X grow [Going I opportunities to that predict to in partner the and on [ph] in later could difficult and XX that muscle make this more to] touch programs a different systems a bit call. XXXX, organ individual drug

We there reach to are planet products way well our our total XX that Therapeutics I XXXX clinical of to is stage this. goal to on company on RNAi in grow XXXX. a the our not can the of believe marketed do or year pipeline a match

last quarter the over made call. our since progress We've substantial and past

data high duration disclosed with these into start about pulmonary. of healthy for We want a Let's context. with of a knockdown I were talk top manner. to in put early effect a James normal long volunteers. gene will well-tolerated level indicated in encouraging moment, very and a recently line but data target data ARO-RAGE The in this

two Arrowhead just or believe just serum first fourth cohorts. board. ever the magnitude dose doses XX% We yet the lung. multiple inhaled I Even from fifth We the impressive mediated response. saw up five data doses. the single get of was is target show We gene that in RNAi didn't the knockdown on more company to not highest after of to have knockdown the in of planned at do

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with degree of any of a number we have liver. replicate Once pulmonary it well-tolerated manner, we can in is as done gene with a we that expression may the where specific done we be new in That we a be of the find targets, high much reducing can franchise. gene have target confidence

day I present think a X, for. the R&D to clinical June we deal. the represent big data we initial hoping validation reported and on data were we the the This additional at is expect

hope I volunteer fully will ARO-MUCXAC medical These data next several new these progressed We by expect year. address to part forward end have studies continue lung to have we and expect patient candidates patients the have have normal where are potentially the programs X pulmonary into that will asthma two day. be in that the and the important I some grinding X/X mid-term, by from near of move studies our the and both of data unmet drug of could the some dataset targeting to healthy needs. treated. we the that R&D Phase will portion

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are Therapeutics. nervous we There number poorly that treated The many conditions powerful a as and for do go system. targets untreatable next? RNAi Where serve CNS central genes and of could

of have are to first drug our ready focused clinic. developing We bring to candidate amount CNS about substantial time a just a spent the and TRiM platform

to with weeks we be mutations. investigated by treatment As potential ALS a a our patients first caused be SODX for ARO-SODX CNS nominated. announced It couple targeted is as candidate back, drug will

now model next disease and studies track completed on work a and quarter. already are CTA-enabling file toxicology to have CTA We

tools and at will You see the X candidates to as more set Day seek June and powerful about of we these patients Analyst we a hear new the platform for the serve.

with to muscle skeletal liver, Importantly, delivery, as candidates. expect with ARO-SODX pulmonary, drug we several additional follow and

while have be are forward we systemically made yet, where the drug administration. believe we truly different are quite suggest RNAi modes there barrier. administer we blood day that disruptive to And brain on This and CNS are our we the we of approaching progress would impressive not a may cross leap we addition, data candidates In close.

the at as Analyst well this Day. discussing to forward look We

unmet this franchise means while and organ We to new the exploring. and XX we every is not address TRiM. medical this, expanding we the system new the are is committed we meets can constantly We have our that are said in believe CNS to bringing months type only need XX past to cell RNAi where

can than believe of also we target gene with deliver what clinically injection we potential silencing and over six single and XX% to greater primates, demonstrated using adipose of levels. to after dose non-human have tissue tissue targets patients the Adipose and subcutaneous now the in many I we to many body a endocrine help. organ months believe address there are in are relevant largest believe is duration

Analyst platform this You about will at more hear new the next month Day.

shared the Phase our to data established ARO-CX diseases from study for of are programs. mediated We've some Let's they early clinical more and turn compelling. X/X now complement

volunteers and progressed portion deep are study. patient We to the in knockdown and seeing of have healthy the durable

were We PNPLAX also in two liver mutations. to NASH ARO-PNPLAX. a Those a for demonstrated year. in patients dose fat into encouraging move shared late patients study only deep that this NASH of study that X multidose single Janssen data with after plan liver reductions We ARO-PNPLAX and in generated Phase quite of in X/X fat Phase

meet who goal next our patients will screening the chylomicronemia patients some expect over enrollment continue study of with in pipeline, that have to be PALISADES Phase syndrome later in familial we patients of to on ARO-APOCX There additional patients XX and tomorrow. likely our to X passed weeks. enroll two FCS. are Moving randomized stage or the And also

At be patients will that and have that complete I closer point, XX the enrollment will suspect to study. we in

which with reducing also FCS, in ARO-APOCX for We will be the designation advance we for from track adult triglycerides program fast received patients the helpful as FDA rapidly.

established be moment, next that a be but efficacy file. to for will are we first our NDA complete this us. and X a I safety Javier This and about if Phase expect could drug in the step important be to represent it an first talk would this year study and could

population only Of this those later Rather, with toward course that to to and pivotal patients expect intend hypertriglyceridemia in treat we I mixed with ARO-APOCX. is severe of year. with steps patients dyslipidemia not take us studies the

in Phase year. as hypercholesterolemia ARO-ANGX ARO-APOCX with drug Phase Phase mixed both potentially studies patients or of patients this X ARO-ANGX toward appear X these that I be familial powerful Both complete homozygous HoFH. in move and candidates. The is the X expect to study is later will study dyslipidemia

included years and of the X basket Phase in of safety and Phase past the patients encouraged to the XXX studies have X be couple of over continue by profiles. nearly ARO-ANGX activity We and and candidate's ARO-APOCX drug

million drugs announced that milestone believe a I X liver many which being the Takeda redwood these Phase Also deficiency fazirsiran, disease. had a first investigated the study, antitrypsin patient our that alpha-X potential X to TRiM-enabled ultimately both we in patients. a This quarter, treatment for Arrowhead $XX earned candidate partner of treated reach be associated will is during the Phase the of third payments. important as study for

We $XX more the our million but GSK-XXXXXXX, things. formerly balance helpful therapeutic of milestone are represent patients GSK's for for also investigational called NASH. the payments received important RNAi an a Xb start sheet, after payment of GSK treatment milestone Phase with trial from These also ARO-HSD, two of

First, strategy they out programs And both as wholly-owned patients partner have as them. discovered our they healthy playing are intended. that closer and need Arrowhead are to getting indicate a the medicines important second, confirmation new who that that to a of mix

completed words chronic about – franchise let and I'm a even and muscle off Before specifically. GLP few We studies. a acute Javier, sorry, DUXX regulatory including everything toxicology required CTA, for filing hand I ARO-DUXX to me say the and skeletal preparation,

begin but of skeletal in have be to development in drug the candidate file will ready are We that targeted prepared CTA CTA interest and study, potentially expressed X/X several QX. on Phase our companies potentially next the partnering muscle ARO-DUXX a and

we As options. these while filing we such, explore paused

of complete clinical these forward over months. I of do the will with expect the deal translate not program know we but a license ARO-DUXX Of if course, partnerships, I couple either next into and any or agreements, will move

very high is executing at level. Arrowhead a

expanding is areas. into platform new Our

has early pipeline Our impressive results. generated

make later stage our and into to able to pipeline stage fruit. commercial activities when mid transition And of giving be may sight company. us the a continue bear development to Our are we business line

to I'd turn now the call over overview, Javier? Javier Dr. San that like With Martin. to

Javier San Martin

Thank you, afternoon, everyone. good and Chris,

disease into the associated therapeutic] late go treatment antitrypsin the been of [ph] for and stage [RNAi status the fazirsiran, investigation mid to I liver deficiency. the quickly our has in I developed alpha-X of with Takeda studies, with Before cardiometabolic review partnership want

last baseline the reported histological or patients burden, reduction dramatic accumulation. mean XX% globule liver XX PAS-D fibrosis quarter, dose respectively, of XX%, measure reductions XXX fazirsiran Z-AAT a Z-AAT a serum leading During dependent who and week XXX, in achieved Z-AAT XX%, to milligrams receiving and demonstrating total at data XX, in we concentration that of have of

XXXX by point improvement and patients one an the are XX% in improvement open label an fibrosis data disease. with It study. placebo dosing METAVIR clinical In achieved trial treatment Phase the controlled Subsequently, These showed portal data a evaluate AATD the of of stage. from at the consistent patients in of Takeda prior the inflammation REDWOOD addition very safety began of fazirsiran X efficacy XX% of generated and in to least randomized and in initiated double-blind liver is study.

FX biopsy of decrease the study Approximately fazirsiran FX than X:X XXX METAVIR FX the fibrosis with at week in stage of receive patients be of The stage in FX XXX centrally stage or is fibrosis. METAVIR with will stage a liver randomized baseline to endpoint and to placebo. from METAVIR least adult at one histological fibrosis patients primary

want update also our ARO-ANGX. metabolic ARO-APOCX on I the brief study with and where be a are give Additional found REDWOOD information current to www.theredwoodliverstudy.com on candidates can we at

XXX our I end with and with a severe FCS. as severe The with start on mixed data data X meeting dyslipidemia, mixed with X will investigational hypertriglyceridemia for SHASTA-X study X get X feedback with will to in on year. dyslipidemia request and us RNAi patients of studies. developed hypertriglyceridemia, schedule study to this Phase patients discuss both are plans Phase the and readout been Phase new later regulators patients for our therapeutic enable ARO-APOCX, Phase for treatment XXX This in

X study SCS with ongoing. Phase XX PALISADE is patients in

after us XX planned data and study week primary XX for will the on enrollment [ph] is and completion baseline schedule shortly We a reach believe triglycerides. fasting have we tomorrow. from in of This enrolled readout study preparation. a XXXX, of [percent of in we patients put then NDA XX planned This QX that change] endpoint with

serious reducing was the announce development that process expedite ARO-APOCX FDA unmet life and was granted or review the patients to fulfill designation for ARO-APOCX Track to and in medical last pleased the indication. to of the drugs previously orphan European triglycerides the need. by same also quarter, treat Track with FDA Fast is and threatening I'm Union granted a designed conditions for Fast by adult during drug in U.S. designation FCS.

XXXX, including we new drugs represents This interaction be drug to data a eligibility Phase to of patients, The utilize TRiM the frequent eligible get purpose possible. [rolling X multiple company. patients RNAi have Arrowhead of with for in eligibility of pipeline that makes PALISADE will all get to our earlier. to the readout proprietary intend complete review, This milestone for this mechanisms as is and for important review] and to significant the from [ph] Arrowhead benefits, priority more we that Phase NDA. platform quickly the for study important potential designation utilize potential X available as first Once our therapeutics FDA,

as ARO-ANGX, hypercholesterolemia for candidate, and familial heterozygous a developed our Moving on RNAi HoFH been which HeFH. or wholly-owned is to cardiometabolic effective hypercholesterolemia, familial treatment investigational homozygous the second or

the We generating meets currently who which study in study we ARCHES-X Phase year. intend later analyzing of dyslipidemia the we report X process are on have this patients XXX data, and and completed in to

with X happy reduction to for is study This ANGPTLX the currently in an treat for is the limited monoclonal open a options same that enrolled the this second with protein I'm patients. approved is in with XX study population was HoFH patients difficult evinacumab, and which report The gateway to that antibody appears fully LDL HoFH. previously. be targets competitive to ARO-ANGX study treatment label Phase

on from European May Society and These Phase we for the the the are currently results in XXst study Atherosclerosis HoFH. We at welcome were Congress X planned will that present XX. working on and study data interim design ARO-ANGX Gateway

disease, in in R&D in programs, from our also results cardiovascular clinical We plans, development will commercial upcoming talk the day more our cardiometabolic about at need strategy detail unmet the and June. the our

James? will over Hamilton, to the now call turn I Dr. James

James Hamilton

Javier. you, Thank

significant development. We discovery and across progress have early demonstrated

new pipeline We continue to types have disease tissue expand which our in of the and extend reach our platform new patients TRiM options. treatment areas to inadequate into

stage to optimized rapidly and using different early clinical also cell generate programs of We've and TRiM platform, efficiently versions the various each data for type. multiple advanced highly a encouraging continue

being few line with areas. CNS diseases; The candidate to top on the first platform like focus ARO-CX, different today for I'd complement announced a and mediated for our platform pulmonary data with ARO-RAGE; recent emerging candidate ARO-SODX. our

with pulmonary. start Let's

the ARO-RAGE, conjugate epithelial V ARO-MMPX, in TRiM Alpha three X that ARO-MUCXAC, delivery targets to the have We candidates for clinic Beta the cells. now, use Integrin which all same pulmonary

increasing gaining I will talk about RNAi platform each individually, but we think advances one learnings of can therapeutic the an with benefits others. the program from is inform in that of validation each delivery directly

as as de-risking Therapeutic to data RAGE as for the our de-risking So, Glycation ARO-RAGE ARO-RAGE the sell inflammatory one as others. the a reduce products view extent to diseases asthma. such RNAi potentially treatment Advanced we investigational or pulmonary with program for for we designed to some such expression is Receptor of End potential events

normal mild-to-moderate double-blinded randomized with which of I/XA with Phase a ascending asthma, Part is placebo patients single The X conducting includes Part healthy enrolled currently X study which single NHP and X. portion levels. dose escalating controlled are dose in volunteers, the We is study sequentially cohorts in

multiple dose includes asthma X cohorts and of portion The study patient ascending the cohorts. NHP X

fully weeks. in to enrolled have cohorts MAD enrolled cohort the coming and the fully dosed SAD anticipated We be all is final and

year. cohorts we results the highest encouraging nearly available first cohorts enrollment X data X to report level, top with have NHPs. dose patient when cohort are the We've the MAD they opened from We later yet SAD We of reported plan fifth those this complete. and not very also but and do of results from and the line

have of no tolerability safety Overall, and patterns related encouraging. or adverse events. in were or been no parameters, to changes there dropouts reported serious safety to related no clinical and assessments severe adverse any events, drug First, adverse

In demonstrated pharmacodynamic addition strong to and tolerability, a ARO-RAGE safety effect.

response serum also with of at and to is lower a XX day maximum after Serum maximum maximum milligram with The ranging mean and XX show of XX%. XX% measured The XX, XX% after single reduction maximum of mean dose a was from sRAGE doses on XX%. X also the soluble of in XX% reduction XX%. dose reduced was and reduction dose XX, XX a XX at the dose RAGE or a the reduction in day milligrams X doses milligram sRAGE

maximum at in Reductions bronchoalveolar of lavage after a measured XX XX% Day and sRAGE is XX a with were in at reduction fluid of single XX% dose on observed mean XX%. a reduction also milligrams

doses. time two We additional cohorts additional knockdown collected the have lung to later planned quantify BALF be after which in will at level points

for the may available data persisted with XX less these the dose. after translation Lastly, and All-in-all, milligram time the This of be suggests monthly, point show administration of dosing of last pharmacologic that or preclinical to effect frequent ongoing. possible bi-monthly, the least we weeks is follow-up additional at duration This humans. X second results is good currently ARO-RAGE. believe

or Moving designed our production investigational to of reduce a mucin various on MUCXAC diseases. XAC as for pulmonary RNAi inflammatory Therapeutic and treatment potential muco-obstructive X to ARO-MUCXAC,

conducting NHP when in asthma on the I/XA have initial are analysis design to for is the study study and patient Sample Phase currently cohorts begun to ongoing available. and similar a data enrollment of intend report processing we and We cohorts. the ARO-RAGE we

is MMPX fibrosis as pulmonary for designed program The X third a to clinic ARO-MMPX, metalloproteinase in pulmonary of IPF. idiopathic treatment the potential matrix reduce or is which expression or

safety, and pharmacodynamics dose Phase in IPF. During with study dose ascending Dose in the volunteers single evaluate ARO-MMPX X/Xa and to initiated is escalation healthy last this the patients and tolerability, ongoing. a in of quarter, ascending multiple we study pharmacokinetics,

ARO-CX. with Now, let's discuss initial results

expression diseases, additional and IgA CX remains need nephropathy, in and hepatic mediated diseases. the Substantial a hematologic as multiple complement CX glomerulopathy, hematologic treatment for targeting renal renal complement including and medical of therapeutic indications. mediated RNAi investigational treatment unmet Our potential

We and to adult a but study study, safety, to we volunteers have eliminate that X/X are mediated the decided pharmacokinetics, escalating in also with tolerability, placebo patients Phase PNH complement and originally the controlled these ARO-CX evaluate in since renal conducting dose planned We to healthy include pharmacodynamics patients disease. cohorts.

may decide generate the We can and PNH other populations. the study future, to data believe we need the but we patients in we

we in interim complement the symposium in presented data line and quarter, data the seventh During at reported UK course training additional April. top

in mean dependent In dose in A part XX% of serum NHPs, a dependent reduction with tested. after marker highest demonstrated reduction of the the activity or XX% ARO-CX X observed two CX a highest dose of dose we complement administration study pathway a dose doses in AHXX, a alternative had hemolytic long think pharmacologic this effect with quarterly was less frequent subcutaneous also possible. tested. the suggests dose reduction is mean and at duration ARO-CX reduction of

time, like of but next have focus to now. CNS our announcement We've the TRiM that in until discussed publicly efforts briefly I'd these CNS on the mention not working is area for platform. some delivery been Lastly,

designed the throughout in to all first platform includes brain system intrathecal relevant TRiM and construct or the the for cell mutations. platform program caused with nervous a optimized for the by use good reduce patients X now this new treatment ARO-SODX, types. Our administration distribution brain SODX central to is SODX expression ALS sclerosis to a delivery in potential of lateral superoxide amyotrophic or as with CNS dismutase

in knockdown, non-human intrathecal and single quarterly a believe highly was after frequently. knockdown rats a single after mRNA SODX In in administered in this mRNA dose cord be suggest of may intrathecal maintained tissue models studies, XX% active tissue target months multiple a ARO-SODX that or primates. spinal less transgenic achieved long than cord XX% we X greater preclinical ARO-SODX preclinical dose spinal duration against with it effect

a for quarter third XXXX. in on-track the CTA is ARO-SODX filing of

because day wanted about ARO-SODX R&D program June. more are sRNA our about introduce platform and talk about But CNS. in at I to the potential will the CNS excited we We very the in

will the call Ken to over I now turn Myszkowski. Ken?

Ken Myszkowski

everyone. you, good Thank afternoon James, and

diluted shares we million for or income based March share on ended income XX, $XXX.X of or weighted XX.X per on with average based $X.XX the for fully million XXXX. compares per outstanding. share net XXXX net XXX.X average As shares reported $X.XX diluted outstanding the today, March XX.X quarter million ended our million weighted This quarter XX, fully was

our we X the for XXXX. XX, ongoing and March our Revenue complete ended to quarter March compared relates Revenue AAT which period ended GSK. Takeda. Revenues XXX.X was include million the XXXX recognize the million, performance to primarily in Takeda collaboration trials agreements current XX, clinical obligations, for Phase the managing quarter with for as XXX.X

the recognized revenue remains million be we There which year. XX to with anticipate of Takeda the associated be recognized next over will collaboration,

XXXX, of the in REDWOOD a triggering in clinical million first dosed X $XX Phase ARO-HSD of quarter a trial million its first patient Additionally, the March triggering study formally dosed Takeda and XX, $XX Xb known the March ended milestone patient Phase of payment milestone its payment. GSK fazirsiran, as in GSKXXXXXXX

for milestone payments prior in portion be collaboration fiscal $XXX to related from payments the upfront with receipt payment cash received Horizon. and QX. be GSK, from million a while reflected Revenue of primarily in to license and the period, in the will these QX, with Revenue our addition Takeda of received fiscal will associated agreements in recognition the

were to The due costs operating toxicity decreased and XXX.X expenses primarily to of reduction candidate quarter cardio stock this the for metabolic our costs studies, progressed change studies as clinical quarter XX, driver costs the through expense. ended ended key study compared was XX, relating lower the candidates candidate March and million to the for company's March XXXX. outsourced in were pipeline decreased million, in The XXXX. compensation XXXX manufacturing trials XX.X Total of

a of March during was Net agreement. ended million activities Prior operating cash from activities operating licensing inflow the by $XXX XXXX, March for million with cash the GSK GSK, from collaboration quarter provided and period XXX.X used net compared XX, includes cash ended million, XX, X.X by XXXX. the quarter

lower quarter of to We at range fiscal $XX million $XX be to burn per XXXX. expect million our operating the in cash

as of we including fiscal expenditures approximately near We expect footprint GMP expansion million projects of completion our capital in XXXX manufacturing. half $XX the of second

balance our to sheet. Turning

to continuing million XX, at burn compared XXX.X related increase Pharma, operating million investments cash our by with was capital our $XXX offset projects. Royalty September March primarily to XX, The along totaled in investments XXXX. and payment and XXXX, million the XXX.X from cash Our cash

shares outstanding March XXX.X XX, XXXX common Our million. at were

that turn overview, call the I brief With Chris. will back now to

Christopher Anzalone

busy had already We've great Ken. and a fronts. have Thanks, XXXX a on of deal progress made many

that the and they of will our into can been be address the busier to demonstrate offer to year bring what it reach that opportunities able anticipate be gene second middle patients. we full needs we clear to half therapeutic for always even even its targets modality, believe are. and wherever pipeline more RNAi the However, We've to potential as revolutionary to

That goal is franchise, long-term adipose the CNS the and muscle skeletal the between no a franchise, longer franchise. the franchise, liver pulmonary franchise, the

areas. lot to [XX opportunity large the multiple create amount expect of value. I build and substantial and XX] [ph] a and across a a people just of therapeutic have and to medicines pipeline us start. But We is diverse this important through help blow a of uniquely

team. our follow. you term and [ph] I amazing excited and day have a about near who works at incredible talented science, technology or more with can been to of decisions X to June are hear innovators as aligned us push you make [ more more. prospects never to combine proud When this join that hope our R&D on mission] things empowered We can

now call would Operator? I and today, us joining for to questions. to open your the you like Thank

Operator

[Operator Thank all. you Instructions].

Christopher Anzalone

we of time, the one one follow-up. questions and interest also that I – remind the to want limit like just question in to to analysts we

Operator

Alright.

Maury with line Jefferies. comes from of Raycroft the question first Our

Maury Raycroft

if I'm will for report And my some at taking you day pulmonary program R&D on meeting at X R&D on specifically? if you you I the readout to Phase XXXX, follow-up or at data baseline from new in cardiometabolic what this year? quarter Thanks additional question. mentioned a going and the patient can the detail see characteristics ask as study, wondering for day second we provide PALISADE was just medical the potentially

Christopher Anzalone

Thanks, Maury.

programs course – think, We'll I questions the day? be data of what What going talking there's R&D overviewing there. and we about we'll the there's pulmonary have time. give to we are the be will So different at you

expect data, remarks, mentioned MUCXAC. non-healthy I likely MMBX bit – but don't have we'll more have prepared to I also have some ARO-RAGE. early volunteer as expect, we We in the of data we'll from expect a that we'll

talk We targets, about those also as or – well indications we will the those as indications.

side, be fitting us into bit data a We'll chance as well. about talk treatment a we cardiometabolic it'll recent ARO-ANGX about broadly good about the into addressing talk the with bit adipose the CNS platform. bit. be new ALS a about the how SODX, go a We'll platform portion about a On we'll paradigms. that talk probably talk of of and ARO-APOCX see more We'll we'll little SODX. talk We'll for to

I'm sure a bit forgetting be some things. of It a will I'm busy day.

touch going we're We and have to of know, lot most you a hope Maury, on we on as what doing.

Maury Raycroft

quarter you this that's types enrolled you've that learn Got about on into you'll have of and can could is patients it. Will year. And provide we that the that study, moving like more anything second next sounds readout something additional of you say study, about PALISADE along this the more year?

Javier San Martin

Sure.

think the baseline but we're the would that review the good going studies. at give is ahead It end X [indiscernible] look of well. don't entry I think we really and will you I This idea, report is a the to going a really Phase of and registration criteria, that study.

population. So, key you so will the patient a get sense inclusion the review of criteria I

Maury Raycroft

Got it.

questions. my taking for Thanks Okay.

Operator

Alright. Thank you.

our have caller, UBS. Eliana next with ahead. we go For Please Mural

is now line open. Your

Eliana Mural

patient that early and like, in Hey you'll about the just how the this can terms think guys. Maybe see on endpoints that Feno guess, later should FeVX, year. reporting we Thanks some in pulmonary I question I the of guess, what of cohorts congrats much what be in recent Thanks. we out, expect data. looking taking be so particular and between, you'll to data? for

Christopher Anzalone

want James, to address do you that?

James Hamilton

Sure. Yeah.

relatively we're cohorts. are patients RAGE, asthma small for mild-to-moderate enrolling these I think So with and

will they're So, measuring FeVX, not be although for FeVX. we powered

blood an and Some be pathways of which are a the driven I sputum the Feno, indicative parameter, could affecting eosinophils. is biomarkers where inflammatory is down like engagement think we're measuring IL-XX key things RAGE pathway that also of that knocking

also think well. I interesting you as driven. And And is and will FeVX be then Periostin as mentioned, that spirometry. IL-XX

Eliana Mural

Great. Thanks.

I to follow-up. between mean, MUCXAC? of found, your be maybe thinking just left latest quick this sort clinically level differ the a RAGE Just meaningful could select how I'd of what forward target what and and doses go not around to

Christopher Anzalone

Yeah.

a that's reduce RAGE that one answer. to MMPX that can't for expression that’s So past No just good able of or we one or the been really has matter. in MUCXAC question,

And good [bogey] don't we be. that have a so what for there's could just [ph] – biomarker

knocked X at for after Mean though studied, however affect least the we phenotype. around RAGE, enough models instance, more than say XX%. doses. will was at We In max In down to for that have were the we that seeing animal serum

These models. are severe

so that models. But confidence. us gives some And they're just again,

we so, on humans see this what to have looks wait And to like. in really

We excited a deep of it knockdown. good It's appears durable. level knockdown to and be that about are

And optimistic so, that will we the RAGE we well as for as and targets. are MMPX, are future board MUC that for that on – for and be for

knock We of affect likely disease product that believe down it states can if you're in so by rich – is targets. going some gene or us at these feels it least is that you target a that because this environment, to XX% to a

Eliana Mural

Awesome. Thanks guys.

Operator

Thank you.

Joel Beatty from comes question the next moment. One of with Our line Baird.

Joel Beatty

question some the how is, more think second study? the ARO-CX color First with the of I you little provide then is, potentially of from eliminating could patients Tofersen? study PNH compare And why ARO-SODX can profile the one on of a

Christopher Anzalone

the for Thanks question. Yes, sure.

would with be part knockdown. this to we better terms SODX, duration, route And will administration key preferable it I of if Tofersen. do dosing is think X target extremely, gene intrathecal be administration for to every which X likely of much months, or in depth every patients of I month for importantly X compared with for weeks intrathecal regards of administration we that every even every or So the and can competitive that think

pursuing and then trials that's And competition PNH, with a to lot a regards was be is therapeutics. PNH marketed marketed clinical really small of that with competing competing reasonably ongoing a addressed of – it to well matter market

thought those that limited elsewhere. to put to and have we we So, resources best resources work

Joel Beatty

you. Great. Thank

Operator

Alright. Thank you much. so

of line Mani Our next comes question from Foroohar. the

say your I did sorry, properly? I'm name

Mani Foroohar

my taking question. for Thanks Close enough.

Operator

go ahead. SVB, With

Sorry.

Mani Foroohar

program you've hands. little modeling out financially, you've remains your to the HPVs updates J&J's I in got So, some of impact dive given in the your want Obviously, hand us. in bit on of a the the back NASH

You've tempo what ramping means OpEx from you us about we OpEx that drive CapEx talked CapEx other spend gave forward growth? and for And commentary quarter here? a to last number of should moving about CNS. to the is prior and How around in the contemplated of and think going this already extent forward, assets what

Christopher Anzalone

think next – happened Sure. the those anything already change couple quarters materially our I plans over that's I was into years. factored last things. has over don't don't of this the few changed

Mani, are We them XX wholly-owned. of X you growing programs, are got clinical so fast now, as And we've know.

by to clinical of XX have year. programs XX we'll think I the end this

know, judiciously. to – part lot We awful That's our of opportunity of model. an that's partner as have important you an

all our or of I products and believe that XXXX we programs a are XX those. going size commercialize certainly clinical company, don't have can think to company by not marketed no I

To ongoing of in And awful to partners. financial capital an our ammunition be to find lot so important good and we have part of an planning. that continues non-dilutive bring

job even CNS that to easier muscle, to as pulmonary I platforms that we these think gets expand adipose. include skeletal include

partners, important to large awful to while find holding to a number good We've of value us. of, lot for on an we think still opportunity got medicines very but potentially drive

Mani Foroohar

That of Thank a makes you. sense. lot Okay.

Christopher Anzalone

Sure.

Operator

much. you so moment. Thank One Alright. Alright.

question comes from with Mamtani Our B. Riley next Securities. Mayank

is now line Your open.

Mayank Mamtani

questions. afternoon Good thanks and our for taking

the data tox the but design that is level, the differences that glean the a high RAGE, And we – can standpoint? from Just for help can that PD like long different candidate there know that I delivery, follow-up. a delivery? and at ARO-RAGE, pulmonary I clearer anything from maybe clarify chronic the think on preclinical MUCX us underway for from you is between – available the programs the study how just or is market have for about de-risking then the And clear quick then is

Christopher Anzalone

question next Sure. you not those then the events? de-risking – complete what ongoing. Well, want is The is chronic address? is are to And James, do tox

are have – we'll healthy late will more have this then patient look Want at year – year. we volunteers made data are have year, of we've through are incrementally ARO-ENAC all guess good this on the we in data and about shortly. more feel to constructs. address We'll de-risking. changes somewhat more – data chronic ARO-MUCXAC, the substantially have will We'll knockdown These I We ago. ARO-MMPX, a data. tax those potent really ARO-RAGE, compared to

as year than correct broad [ph]. we We're that Mayank, And James on. see A per and mg terms, this to ago, using we cumulative in you plus and months. ago, a inflammation wrong [ph] various graphed Around [X reported in cumulative started mgs may doses kg] over we and guess, per inflammation. fourth mg top little we at recall, started And where kg me if lung around the [X that X pulmonary day year where the local here. I’m I see less to per is XXX the around dose studies kg] a the

that like so, for And be substantially that we RAGE. good shape are we in underneath we here feel should

but MMPX it's have and we least data to I we've ARO-ENAC. I you than again, remember, us We'll mean this. that know again potent something at that's the see will with with where MUC, we are And seen so extraordinarily encouraging recall far more

Our daily two every doses dosing weeks. ARO-ENAC was with three for

through For ARO-RAGE have we we are and seeing out, as data still knockdown. deep weeks we month a X are out James and pointed a once

this once dosing, may X month months a X not dosing so every maybe months And once maybe once every and then be dosing.

like we're here. shape feel good we in So,

Mayank Mamtani

of to high And seeing question. more another the forward Look Yes. R&D then day. just level Great.

on DUXX SODX maybe on externalization decided you've CNS. muscle, and for As not and

kind for internally So, I looking they you analogs questions. kind that for like forward mean muscle go to our of out taking versus are the muscle, muscle, skeletal thinking DUXX with are for? which value there be might externally? of Thanks And how exist for you types about deal

Christopher Anzalone

Sure.

We've not file to clear. were be CTA. me let in up So, ARO-DUXX. We made on decision a gearing partnering

we where see interest companies go. ready we those and to we press are as pause mentioned, and If I [indiscernible], had chronic to substantial go. from decided several had tox and even We

that's actual they so And those that's an where turn we great. of deal, are those if – right into if do, any see now. if We'll

We be happy ourselves. believe we push for couple where know of in It for drug, to and right to clinic in a partner we into that's sense that. not, believe wait platform, we'll the these hopefully us see we'd things to just that too the because made the find months great the If go.

We are in fourth but ARO-DUXX, be think also CTA follow-on quarter. a candidate. mentioned, not ready clinical we the good the I think we'll I But for as in only spot

to drugs we as good talk to ourselves, have bring can those I'm – companies who that and these in where types agnostic. have to good who spot we're than up almost but offers also I'm types both if are are We're a developing – of with listen and clinic happy we proper to in value happy experience about to these come in of well. happy there

Mayank Mamtani

class High my problem have. it. Thanks Got taking question. to for

Christopher Anzalone

welcome. You're

Operator

Thank that. Alright. next & Our Patrick HC Wainwright much Trucchio Patrick, now you [Operator is so for with open. question from your comes Instructions] Company. line

Patrick Trucchio

and afternoon. good Thanks

on date in these going discuss forward? may data what to and been the secondly, program constructs follow-up the you if platform. an I'm like of that's CNS then the a wondering generated I'm update that the profile as on preclinical of and Just can methods transition you sRNA And there's level if collaboration delivery HBV trials? to look confidence question safety the and wondering human

Christopher Anzalone

James the the granular and to give answer then – necessary. CNS can question answer sure me I'm high level – let so I'll you if and more give you

have we the non-GLP about tox we done safety seeing. with done tox exhaustive and about comfortable ARO-SODX, and studies potential margins we're as what [ph] We've candidates there. well feel good as [GLP other studies] feel we So,

I HBV, next their don't that anything running be information have process any to several quarters. on over I update don't to that's respect Janssen where to I you is going have the now. With on believe and so

James Hamilton

Yes.

would I primates the platform, at month duration to data I more more of and XX% good think Day we'll dose reduction in least But rodents add the brain and support really both XX% we'll in the Analyst specific QX non-human at administration in share should next CNS June. regions various on that just seeing share we're with month.

Patrick Trucchio

you Thank much. helpful. very That's

Christopher Anzalone

You're welcome.

Operator

Alright. so Patrick. much, Thank you

Keay Our of next Chardan. question Nakae with comes the from line

Keay Nakae

early to pivotal able to learned have from you as helpful from clinical Anything I top. gene and that's that's on you learn have they're target that of the Question asset kind think And the lot what another from development first benefit Biogen's into did you. I studies design their clinics? well? Phase you Yes. and whole process. hitting their might from learned to gone out you proceed X/X they there it's mean, same and Thank a through then the very in be as think

Javier San Martin

enable I'd that validated disease It's based And for biomarker our accelerated regulatory approval important And think important. lot a on like to Yes. the the a very the person faster. to I for like program. add field. the really huge it's is go this, Will for us very,

neurofilament I over and natural SODX a looks efficacy think this both and work, in their in very also ALS good there this condition patient for history data the to of is benchmark and thanks like also a was clinically.

So, program I our program – even think this door faster. advanced the for success opened

Keay Nakae

you. Thank Great.

Operator

Prakhar question you next with comes moment. our Agrawal And One Thank Alright. Cantor from so Fitzgerald. much.

up opening now. is line One moment. Your

Prakhar Agrawal

taking my and questions Thanks quarter. the for congrats on

testing benefit much on function to you as in how later confidence is And are for it endpoint broad had benchmarks first asthma lung to you as need The what such think understand you're it given give targets on question follow-up. phase at? trying FeVX, you quick you population, better RAGE, moving into such show I trials a a on looking to

Javier San Martin

Yes.

So, not James already we're X at efficacy data study. that point made looking Phase the this in

proper study FeVX. probably efficacy So, this a X show to require will and Phase program

[indiscernible], are XXX we If you look the with the that approved the with FeVX. at milliliters are approximate improvement, about already biologics looking benchmark

for X Xst. discuss in June study. benchmark, Day And the at the think, that's Analyst will So that's that also Phase I a something we

Prakhar Agrawal

strategy assets And a into Phase developing prioritize what X have you both asthma, you. could as X, time Thank Thank continue plan to to drives just is you over Phase you. in make at long-term and decision a targets, that decision? certain to broader one the the other given two curious or the

Christopher Anzalone

– will And ANGX they these in targets APOCX, be and that ways. interesting. two two are addressing they'll as – It's are different Data. with asthma look, and

them. it could is look could one patients see. that have are to And we populations It We're how to how be be patients they patient seeing and to the to going that superior respond populations. just there of respond so one better forward – than of wait other, who all to in each

It's because a have think medicines. both to we important be good we of have to opportunity for problem them a good

show the data let's couple so, And data of over the see of the just what years. next

Javier San Martin

memory a new new is very very their construction other and And be I the and type there MUCXAC say constructive that diseases other significant. Yes. is, are drug very would can are thing of prevalent

we evaluate will bronchiectasis, we COPD as well say as total indications or such go please along. as So,

Operator

Thank you so Alright. much.

from your moment Issi comes next Our with Luca question for RBC One Capital. line.

Luca Issi

Are United good now Thanks time on just have be platform business about you so after maybe the targeting about going the a for talk of planning would you ALS, for lung, before I I this Any that you can appreciated. are keep would stop? are And much you're Chris there this thinking risk taking further to to BD in you SODX say few agent, my to States. thoughts Obviously, of years Biogen, development? entertain why say, behind here, XXX full hoping in-house in maybe proof a indication? there pulmonary only find much I you to patients should discussions? how a few, Or have a partner? question. are Is concept you XXX

after with maybe going [indiscernible]. other So, like why not targets bigger TAMs

one however, So on up in mentioned again, last I in then And much. you Wisconsin, so last any to recall XXX XXX, is suggests thoughts Thanks time invest if so now you and wondering to facility the there that $XXX CapEx, XX-Q expecting number that you appreciated the were million correctly, to that? the it. Verona, can build if think quickly CapEx it between clarify I

Christopher Anzalone

the to first? address Sure. last Thanks, Ken, want Luca. you

Ken Myszkowski

were we total that The amount million million, year. total. was the that be was The this mentioned XXX we spend in to to thought Sure. $XXX $XXX project we going anticipated

year. $XXX than have the this less spent We million

XXXX. spend to $XXX the in second fiscal more around that probably in expect half and probably million about million We toward $XX

Christopher Anzalone

Okay.

questions. So the two other

The first one was around pulmonary partnering.

more, So, We right should think to in be look, anytime the the a important assets that an partner This to we aren't data. broader is for to space that. platform rushing now. soon us. three frankly don't we want current want do even or I learn additional we hurry

out As we've pulmonary XX the or drugs X said platform. X of or or the past, we see see drugs X in coming here. We X don't or X

There's several XX, we of drugs pulmonologist said XX, probably address commercial infrastructure XX,XXX so not building or XX bag. drugs. that, with going to to in a that it's be the our U.S. market the like idea in Having own

to proper also I to it Again think at partners there platform, from part much value order extract because too really it but find think good So, internally ourselves, some serve create point, a to us. this for this of But still sense the spend platform. I will additional be in partnering value makes patients days. at don't opportunity and to within time TRiM on to this is this early point we're

SODX, something question second Well, you. The of do with are I'll else? SODX you after why I going instead tell

just ahead company. so It better stack that think because patients, well pathway so We or first to popped We're an SODX of a we company. and and something better. it's we be. about, and first good to are a we talked drug somebody if going We're from for much learn to as our also those against after not and then up an then us, We somebody us have and it's accelerate happened nice went we'll think else. a for place

be believe believe SODX, that a the pulmonary going of just need we so, we first no we those think the shortage in target space, CNS environment it. who But important of helping patients in many, that's targets is we rich there's and like will And after.

Operator

Alright. so much Thank Luca. you

Goldman moment coming question Sachs. is with last the Our while Oner line opens. your line of from Kumar Madhu

Madhu Kumar

for taking thanks our Hey, question.

big question question. kind of one science and then So, one strategy

fundamental wipe the for what and it get far lung] serum think how you is, science do from Basically, just really question were can to, do extrapulmonary floor you in sRAGE you the to is the think [ph]? resources? potentially the if So, [out serum sRAGE

you in big the is what related strategy lavage kind lung, conversely, And in I of question. picture as for said well. the kind Luca's then then of liver company menagerie sRAGE indications to what the the And is, see floor bronchoalveolar would question to really focus to to X kind reposition like these X, on Effectively, directed need current relative XX drugs? the lung or to of of

Christopher Anzalone

Yes. Sure.

question here. the of is So the second key maybe sRAGE, floor of part

cell type floor [ph] you coming really lung, you of coming some coming be of I – the alveolar think from the the sRAGE that get X that be types, [bowel] amount exclusively or maybe zero in most measuring endothelium from from a close valve the sRAGE small to if mean but the other would the of should the assume sRAGE cells. epithelial I is the

Now, that we'd knockdown. mean that be able doesn't XX.X% get to

I so our triggers best serum, I knockdown, the think with even tends that's don't not answer work. that liver, XX% the in know the we think really. plus we're just the getting way to RNAi to In

the sRAGE best coming data the so the blood. that in XX% shared we've extra you achieve far the indication how in entirely sources. pulmonary are It's much think blood is not from I clear that reduction can

coming it Although of the it I clear from is most think that is lung.

that patients. or asthma So may in between vary healthy from number person-to-person either volunteers and

level why we the trying reasons of in blood. sRAGE what's still healthy So, in an was to It added this that sort the I one study. floor additional dose we're to volunteer out, think the

Javier San Martin

XX%. getting I already close we very because think we're seen

AAT, you XX%, what at look APOCX, you see, If XX%. that's

So, very the Almost close complete addition. I getting think to floor. we're

Christopher Anzalone

and address second Madhu, I'll the so, question. And

curious. just I'm So,

others, talk pipeline to company their large look, to you to going and J&J a we're when to be drugs? refocus refer of you So, do company. this pulmonary So, and not menagerie a Pfizer as

having I We therapeutic like think a strategy this reason to do actually areas. broad that. pipeline across there's no of

we I to and hopefully well validated continue it relying can and it because think do are do but part, can in we do targets we we I think on disciplined we stay that.

deep relatively I Pulmonary company. And by so, most think is a create can we [nice that ultimately diversified the [ph]. value well] being a

will we I is have be where the wholly-owned several that more of our drugs, only one. or that that think but place so a won't And

Madhu Kumar

Thanks very much.

Christopher Anzalone

Thanks, Madhu.

Operator

questions. much so for to like all would your you Thank turn Alright. I remarks. to it closing now Anzalone our Chris back for

Christopher Anzalone

today, much look joining forward on we speaking June for us you to with Thanks X. very and

Operator

participation you me. conclude can in all today's hear does Alright. you you sure for Goodbye. Making Thank conference. the program. your This

all if You now haven't you disconnect may already.

Arrowhead Pharmaceuticals (ARWR) 2 May 232023 Q2 Earnings call transcript