ARWR - Earnings call transcript Q1 2022 | Arrowhead Pharmaceuticals, Inc.

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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 Vince Anzalone, Vice President of Investor Relations for Arrowhead. Please go ahead.

Vince Anzalone

everyone. afternoon, Good joining its for XXXX. to Arrowhead's discuss Thank XXXX us first for fiscal XX, quarter results you today ended December With are us management CEO, today Dr. President and from will quarter; who Christopher of an the Anzalone, Dr. provide overview Javier San who an stage our -- update clinical on Medical pipeline. provide update and will an provide will mid- our Martin, Chief Officer, later Dr. a and James review Officer, update on an Medicine will Hamilton, our provide Financial financials. Senior the Chief Vice pulmonary of President Ken platform; of will our give Discovery and Translational Myszkowski, our

open will questions. We call up then the to your

Securities that other materially of we made forward-looking forward-looking would Before of Securities statements in XXXX. XXE those I like Exchange Act begin, the and the historical XXXX within to today's to risks Section statements differ certain of remind and any contain of statements statements. could you and All of to the from Section Act are comments call that results XXA numerous uncertainties meaning subject during are and expressed statements forward-looking actual fact of cause than

and over details President CEO on please said, further of like That Company. Form risks the annual filings, uncertainties, most Anzalone, these concerning SEC XX-K. refer to report turn to Chris? I'd to including our Christopher For call our recent the and

Dr. Christopher Anzalone

where as company, assess value. My market but not fight down you the a index was cycles, Thanks, are Arrowhead's goal place Index of thank everyone, further was a today. articulate XXXX, And you been XBI today to XXXX, down and market is first Vince. month Biotech help has difficult true afternoon, The late. XX%. of a Good to for during joining biotech rather us to the the In XX%. we

continue need you through create to will our we And should if important create update desperately today. our shareholders. the focused them. innovative the lens substantial which here is who That mission, for are on new we that to value of stay for patients millions medicines We view

about excites James patients programs what continued mean As patients speak think programs will There great to and and quarter, take to what strategy those about expansion had with this to our that We company. executing programs, currently will about us those where a Javier, platform strong our will about extension, another on mean think is I and those programs me progress across much business -- company. our as respect development. pipeline

newest complement our quarter, We a all key or programs. various opinion continue hosted designed clinical reduce for stage production to of tangible our complement-mediated the diseases. therapeutic we to make progress leader therapy a CX across in investigational on potential as ARO-CX, Early X webinar components

sites filed also clinical We first CTA in-human been have for begin studies and the to activating studies.

first target hemolyticanemia, to medical need could the with indications, As of expect in our RNAi autoimmune a candidates drug to CX variety other all and ARO-CX clinic. pipeline, nephropathy we the see address glomerulopathy, including candidate We be against reach this PNH, we currently lupus IgA nephritis. substantial unmet across

clinical in And months. went been eighth idea is candidate expectation from to success. clinical program have a of given encouraging. good This be that a will hepatocyte-directed we initiating of studies, data in our preclinical this TRiM approximately We speed. example have XX studies our Our high also

level potential We a extrahepatic platforms expect to speed we similar as candidates. mature, move at hepatocyte of the to at move And efficiency. for the future similar directed have

virus disease-modifying and disease do are they TAK-XXX infection. and for We encouraging ARO-AAT partners development liver those also on continued During hepatitis the also associated for learning generally called appear the candidates antitrypsin agents. clinical look to programs, our well JNJ-XXXX we deficiency, to ARO-APOCX data for and doing alpha-X potential hypertriglyceridemia with exception, to ARO-HSD tolerated. including what forward have Without for of quarter, be those multiple all capabilities and NASH, more presented clinical of about B designed been

license for just GlaxoSmithKline a signed also agreement ARO-HSD We with that recently closed.

is tens for receive treatment number genetic mid-double at to the Understanding of ARO-HSD biology Arrowhead very for a is with closely Phase a to GSK the need eligible was and the X, an this as challenges medicine it. of Arrowhead to to Phase start a received defining million could important to be of Arrowhead. prepare the an up We and include are partner exciting complete to Phase except major start $XXX and in ultimately partner powerful global the GSK to all are millions we a development who addressing a on to markets market to and on Under validated large patients new clear GSK happy staggering bring digit and a China, key potentially million retained indeed, expect U.S. potentially an X and net in million partner to of will at for clinical of agreement, at license develop upfront substantial study. milestones to patients. they XX% milestone effective and up of sales. deliver look million $XX milestones. million tiered $XXX $XXX terms and $XXX NASH, complicated sales and working product a medicine milestone exclusive be eligible great disease to territories forward a this for of by the received candidate. X, They which payment further royalties launch believe in of the have the commitment commercialize GSK which a of I start Greater genetically that

studies therapeutic first RNAi investigational designed study to with cardiometabolic Arrowhead's in a and evaluate a ARO-APOCX of as X I is metabolism. needle the milestone really could or We and in greater to recently some in event therapeutic key type way This very PALISADE who safety reduction options seen present. APOCIII, FCS have XX% clinical have FCS. the little efficacy production Phase of Moving patients have or indicative for X familial see initiated triglyceride at we key a chylomicronemia to of encouraging, ARO-APOCX move study the company. where Phase CX apolipoprotein adults a study, inhibit than maturing the The our of of programs. effect populations. very of syndrome dramatic which been regulator patient is Prior our triglyceride

be Phase and our made These we MUIR progress therapeutic for populations the study in ARCHES-X believe mixed lowering Xb expect progress the the to enrollment been study rapid, on ARO-ANGX study dyslipidemia, good Phase ARO-APOCX by with and also the be are prior could We patients, triglycerides dyslipidemia, few has HDL. We patient ARO-APOCX that coming the the two study. study enrollment highly that meaningful suggests in data and on severe SHASTA-II I studies mixed hypertriglyceridemic from complete months. raising have in those and options Xb

patients LDL exciting continue big prior given help others triglycerides validate the We are of done work and to millions with see future and could elevated to the opportunity medicine data optimistic important we that ARO-ANGX cholesterol, our by and a to be an target.

our ANGPTLX. recent bringing that clinical to seems the specific partnership clinic on As consistent against have ANGPTLX. at competitive Ionis discontinued the its with studies has first ARO-ANGX the approach Pfizer our landscape shifted its first with further announcement Further, compound compound the to targets, RNAi that favor into in in even antisense the been has gene targets Arrowhead RNAi was of practice

candidate. data studies. knowledge our we not that always be of Of in compare is different to confident have results have course, and deep difficult publicly, we out given what it do of continue we coming to program, across But seen

activity, For in quarterly fat. from non-HDL triglyceride XXX elevated two fashion cholesterol from and XXX enabling dosing. ALTs liver milligrams both has instance, in ARO-ANGX. in with data our saw cases, ANGPTLX seen or transient associated ARO-ANGX up deep were X/X frequent after XX%. less or had of and indicated and study XX% cases, We medications elevation in up concomitant XX% no reduced levels a ARO-ANGX increase increases were durable the Phase and following: and to with to bilirubin to mean Only any associated we in XX.X% that patients mean led increases in there reductions demonstrated very was XXX, both have and reductions not indication to the ALTs dose-dependent

our give I wanted review highlight developments. this to a but few fuller move a call, Let's to during will now James platform. pulmonary

to candidate that on the with we the are First, we make not likely progress ENaC in Phase ARO-ENAC, continue continue target, X/X a but year. testing will last study

next-generation also exploring testing we We compounds to this, three believe appear to as and have properties two subcutaneous candidates to true breakthrough targeted deliver ARO-ENaC. which would are via pharmacologic we favorable this well. be drug step ENaC pulmonary have a are A for compared administration, ways that behind to

We've horse. disease two I'm to CTAs have the previously programs but as for ENaC in to We had ARO-MUCXAC, ARO-RAGE conditions. yet are which plans likely the program, and year areas. discussed being changing settled new these not on new or we formerly various announce targets but inflammatory developed pulmonary and disclosed file our each pulmonary this muco-obstructive not excited horses also

file to these CTAs next of both for track on the are We over quarter.

this presenting preclinical intend pulmonary KOL R&D to the event, plan webinar go to the year. a at American We May, or host Society day in meeting describe studies data and will commercial biology the be specific outside and we plans also Thoracic we At into of and presentation unmet medical need. detail explain the the the clinical opportunity, disease data, introduce the targets, an market preclinical present our on KOL of the clinical for have latter

third year. are pulmonary remained two file on in a target and this half CTAs are the That by track to and we first new that We end disease the of also area pleased XXXX undisclosed. file expect to of

COVID potentially While mean substantially expression continue other for in decreased still to to is inflammation exciting testing animal we are for for This models. SARS-based pulmonary the viral coronaviruses. they lung currently the in progress compounds are leading on current CoV-X, what also but in may SARS that make platform, and

SARs novel and by regions you to conserved current we working develop known could infections. coronaviruses the well with that As are we are recall, treat across antiviral that future agents targeting hope may

programs. here for that on if you doors These exciting to substantial progress. sub becoming have other us are for franchise, respiratory in updating viruses a Our could our has pulmonary see look will, opened forward progress platform. now within you also and we where our we active us, We opportunities

with and exists ARO-DUXX, pulmonary type the by our and prior as half candidate the the CTA failures the Recent the of guidance, addition a muscle setbacks can are cell first ARO-DUXX end this expect leap us to patients half specifically, we underlined us. In against we And forward this can we our ability represents addition of Consistent the skeletal file therapeutic of on This who another for in unmet with CTAs may that targeted offer of of are group with track to the to the FSHD. in year. have year, we two we FSHD that options. real a the help first new with medical need target as more currently moving fast clinically. need patients no field first

in made expect regular JNJ-XXXX, and partner therapeutic, NASH started Our from data Phase also them read J&J over have multiple our partnered the years. is studies The Phase good to continues few out, next JNJ-XXXXXXXX, latter programs and that in our partner its Xb Therapeutic. have would X progress. progress HBV I

continues performs that we candidate As licensed study. Olpasiran, and earnings call, how with disease exactly do, they combination agents. in a publicly the was said Amgen is it seeing and we time we forward the against Phase to discussed has that doing designed to Amgen to cardiovascular look our data Phase last different on complete in X what the of and X from expect this JNJ-XXXX Phase the impressive, year. different fourth in to X. X X it Xb will and dose and were seeing ARO-AAT levels Phase the quarter. initiation an half is look Data three we currently out ongoing to to biopsy PK read in of Phase study third Phase that a out data data starting or forward read the first has over at

plans for closely with this Takeda about with pivotal our to expect study. data to continue a work and year discussions continue and We regulators

to I defer them will move and plans chronic the timing. continues provide and to Horizon of future gout with rapidly work Our area in guidance to and

Verona, manufacturing manufacturing lab and office associated in the site Lastly, facility. completed planned is quarter. land to be and drug a which starting expected the a purchase of in and GMP laboratory is we in is mid-XXXX and transaction to the an acres facility XX of of anticipated new to of space office Construction XXXX. early Completion is this completion facility late Wisconsin,

California. in will operate We San and continue Wisconsin Diego, and research development to additional facilities Madison,

substantially new to us Diego our will allow expand We to offices the laboratories a we the We scale the first strong and advance also rapidly of our allow as San We growing to TRiM-enabled progressing administrative advantage believe half commercial think Arrowhead campuses signed our in to support view XXXX. candidates. what lease us will research our and our well pipeline, of clinical potential this a approach process, as positions we manufacturing us including competitive commercialization drug candidates. in of

our summary, is and in maturing. So pipeline expanding

additional to is investigational has and opportunities medicines providing in where platform capabilities areas and new Our develop unique expertise. discover Arrowhead

We control are now very I'd capital take strong Martin. development ultimately like commercial using turn needs. to position. value the We development support are Dr. of expand the Javier the puts bring believe that investing to in over more a technology selectively call maximize Arrowhead programs, to With this footprint all we and our business and supply process overview, our of in to non-dilutive competitive internal to support San Javier? manufacturing drug R&D to our and to clinical of and

Dr. Javier San Martin

TAK-XXX, Thank is investigational being I will treat status liver cardiometabolic also you, and afternoon, co-developed our later-stage ARO-APOCX, with and which good called medicine ARO-AAT our medicine Takeda. Chris, provide our to updates designed three investigational everyone. disease, ARO-ANGX, clinical alpha-X programs, on of

double-blind, Xb on apolipoprotein enrollment. SHASTA-X is for the placebo-controlled clinical we're the each medicine will primary per ARO-APOCX objective program. discuss ARO-APOCX C-III is the million study or pleased Collectively, studied triglycerides new of and clinical population, for study enrolled and population severe the with First, having a ARO-APOCX bringing to study. to than made in study with SUMMIT the studies, called lipid targeting We deciliter. progress our ARO-APOCX Phase study disorders. of approximately hypertriglyceridemia adults be of are will patients in for as good and safety SHTG. sites evaluate individually. This XXX patient pace a later-stage SHASTA-X and patients of of select mid- in in dosing is with the this each defined late-stage efficacy studies the The various this regimen investigational patients' I greater very XXX being

this to high have FCS options. with ARO-APOCX patients study they per pancreatitis. and regimen greater enrolled evaluate the limited with triglycerides elevated recurrent primary triglycerides, from of safety with double-blind, syndrome for safety ejective lipid Phase of the mixed and XXX the the have standard MUIR evaluate study, diagnosis SUMMIT approximately having Moving XXX than study or at patients triglycerides percent XXX tend select studies and XX in is fasting placebo-controlled adults to in this program a is refractory a a cholesterol endpoint than milligrams a recent non-HDL treatment is These on PALISADE, study an a and to per are to defined ARO-APOCX than clinical dyslipidemia, risk X is be later will dosing of therapy FCS PALISADE dose population triglycerides. are greater patients of adults painful deciliter to mixed and stage have The and in study which milligrams efficacy XXX with study. familial of between greater The the of of fasting primary MUIR The change in with and efficacy and of in most bouts chylomicronemia Phase of total have initiated that to in FCS. currently patients XX extremely dyslipidemia. LDL-cholesterol deciliter. month ARO-APOCX patients milligrams is Xb A as baseline because XXX These very or lower milligrams

in Approximately I patients include XX enrolled study. be pancreatitis acute this secondary to Additional now on and exploratory incidence in change measures. parameters, other lipid move will other of ARO-ANGX. endpoints will the and

ratio Arrowhead to the Phase both VISTA in the programs, SUMMIT We investigational the of active baseline mixed ARO-ANGX XXX such designed HoFH. for profiles. X:X end ARO-ANGX of Our have will in works additional with I will give study has placebo-controlled regimen that studies that of as doses greater LDL population patient conducted warranted. is Consistent Studying to a the inhibit between first documented than even to want on commercial study. outside began or with initiate a investigational we cholesterol getting initiate patients who both hepatocyte milligrams greater or one study the Day XXX Phase and inform studies study patient approximately eligibility of statins adults ANGPTLX with about based additional of we next receiving to will enrolled After high a briefly designation, of homozygous non-HDL the breakthrough XX genotype XXX the on populations, population. X the both will be a program. that to on TAK-XXX. help strategy familial be or enhance receptor with the ARO-ANGX is the and a a of with an with the patient mixed a therapy flexibility dyslipidemia clearance to currently in clinical program well studies clinical patients our when XX synthesis potential this pharmacodynamic ARO-APOCX diseases treatment resistance investigational in for with a will lipid with also mechanism medicine of have dyslipidemia. ARCHES-X, late-stage for of of with multiple is be to ANGPTLX subjects Phase will effect this dialogue of of safety functional in reduce this Patients patient have period. half GATEWAY, cholesterol of stage and the maximum XXX and well-defined can particularly to be defined called update for same three, VISTA describe X study per HoFH subjects the also to is ARO-AAT up and first The cholesterol or be mixed evaluated we'll various receptor. HoFH, Phase a been our to LDL as ARCHES-X in over through criteria program. HoFH Patients and XXX to and inhibitors. productive milligrams plan the if randomized VISTA understanding for deciliter with up GATEWAY up can and hepatic per adults production angiopoietin-like open-label receive milligrams this studies, the mid in This At hypercholesterolemia patients receptor, ARO-ANGX regulation on hope approximately The XXX LDL study with update in dyslipidemia. population FDA set absent and studies cholesterol and is We're deciliter. population This diseases. high-prevalence are such XX of PCSKX two and other thus in program VISTA X objective rare alternatives development PCSKX planned ARO-ANGX brief in these LDL Total large The dosing inhibition. protein The good criteria meet enrolled. LDL a medicine can therefore therapies as shape X strategy MUIR also active with data Phase inhibitors as study a triglycerides is later give deciliter resistant way of the XX-week an than a efficacy evaluate a select and and in this study in study as need Day and different moment. in study. study the of primary Xb the want I XXXX, X milligrams provide patients per as in double-blind, we believe had or called The that

should level James? biopsy which the year, of from the summer from SEQUOIA AAT with forward Phase turn to to this the the to data have readouts. We will call of of collecting be for or last on to both select reduction a in X. be XXXX. these Dr. in over Together first used the data enrolled we of of also I patients James expect the will with circulating XX-month dose dialogue after last look now We continuing sometime Hamilton. half the Takeda, FDA one the

Dr. James Hamilton

are new early-stage There of and Javier. in exciting you, lot programs clinical Thank discovery development. a

Today, Our where R&D I on organization we planned focus impressive and to like an are making platform, and important the pulmonary pulmonary expansion ARO-ENaC. pace is progress operating the provide areas. with of an pipeline the update on at in multiple would

our have mentioned, half Chris ARO-MUCXAC candidates on ARO-RAGE the first CTA newest are both this As pulmonary to year. during schedule and are They filings AC. of

of undisclosed third target this Additionally, we a in this remain The year. will third plan on filing time. CTA pulmonary for at program QX this

mucin first for in upregulated program, MUCXAC individuals. is in expression ARO-MUCXAC protein expression in with targets mucociliary MUCXAC bronchial bacterial normally MUCXAC healthy defense epithelium. The not or of a airway. asthmatic is required the clearance

can lead obstruction poor its available not of directly in However, asthmatic is airway disease The enhanced currently correlated control highly mucus severity. and secretion a with is by upregulation addressed asthmatic increased muco-obstructive degree state, and disease in asthma which to the therapies. patients,

clinical is way part the tool. Mice Society represents an potentially Spring. mucus a the of have very are An Meeting summarizing presented airflow association ARO-MUCXAC that of with By induced will mucus central the correlation powerful leading a airway nomination protected expression new we this targeting studies genetic genome-wide MUCAC-driven at have Similarly, the supporting Thoracic American between be hyperreactivity this obstruction. development and allergen because a in enhanced preclinical asthma. unique MUCXAC exciting in the asthma. abstract plays extremely role stimuli, in from multiple of data candidate to concept allergic of fundamentally a MUCXAC setting Additionally, and again, demonstrated deletion the treating program, a it of plugging

to various bronchial cascade components is alveolar numerous the a IL-X in as the receptor for immune binds and IL-XX. transmembrane of glycation and of primarily RAGE cell allergen-induced pathogen-associated of that receptor products or expressed for upstream damage associated mediator the ARO-RAGE, the an release type The of IL-XX to asthma X and cytokines, epithelium. system. RAGE inflammatory of RAGE, expression required is innate second airway ligands represents which IL-X, upstream including program, and advanced acts activate is it targets into by end

soluble a RAGE, S-RAGE will known inform This teach followed availability of a component Importantly, that pulmonary on of I candidate circulating The to important as a as and knockdown. be a want about is biomarker target the platform may gene very highlight. the of point biomarker can serum us a broadly. lot importantly,

potentially system get expectation Our mice from data our us RAGE route directed plays could and inflammatory has of In of inhaled to pulmonary of critical translate to muco-obstructive key allergen knockdown mice human inflammation. the data provoked a informing inhibition trigger increases hepatocyte-directed targeting type S-RAGE in arresting the from rats, program, studies that the our kilogram of summarize on which airway stimuli. of will for to both of pulmonary IL-XX presentation downstream system Further have X and to have in indicated RAGE years, with has possibility responses tool potentially are role asthma, believe to allergen and inflammatory Like mediators. mRNA, asthmatic pathways type spring, has animals, low MUCXAC that months. of the the doses In which duration MUCXAC that XX% RAGE abstract utility response at asthma X to program. knockout drivers this last knockout cystic biomarker of pulmonary same for wide X a necessary induced results with accepted effects asthma been markedly of TRiM per protected severe type conditions. for activation the of of exposure. high S-RAGE range a of the RAGE get hope RAGE preclinical preclinical administration Thus, the a RAGE X.X for Animal success. most offers and an our depth we and in point oral to closer inflammatory both signaling suggests availability circulating airway approximately three an We point. inflammation may other data reduction relevant attenuated is COPD, of components to on and targets proximal inhaled over Inhibition phenotypes. inhaled in target predictively gene fibrosis TRiM using RAGE and upstream broad ATS RAGE very and our that using speed single increased represent new clinical predictability milligrams proven TSLP models to inflammatory programs or few over

background, the in approach start and the be discussed future clinical we will target Additional the plans data studies. as of clinical

candidate highly We are also address pulmonary indices lung of outbreaks. targets reduced reduced infection our sequences model, program making additional in good progress that in the viral by viral histological loss. coronavirus inflammation XX% conserved by is to which developed SARS-CoV-X being and programs are COVID SARS-CoV-X that In One potentially pulmonary our on weight two essential load viruses. respiratory future mRNAs, hamster body other current may lead and address a prevented XX%,

updates we'll we in can. lead currently the additional and optimization are stage, We when provide

for prevented program current promising are results. early believe new In viral what a in the an mouse but is of very model compound lead program, a is viral other seeing we body infection, an by lung the expression we are This gene infection. The weight undisclosed XX% reduced loss. and

to ARO-ENaC. Moving

a we chronic our voluntarily lung Chris in decided the toxicology candidates. on clinical previously findings We resources of local inflammation study. next-generation rat study was paused have GLP after As mentioned, to announced that focus

seen dose intervals are and animals simply studies. in and/or We profile. overdosing some to candidates. tox a but decided inflammatory back path next-generation we clinic, have chronic That see to is findings would by changing the monkey It faster that the since on focus GLP that cleaner long-term path the the dose better provide we could we a ENaC local is possible certainly level

MUCXAC We and I and look pulmonary early administration. addressing the the turn is about very discovery still all this but using those and over interrogating compounds. second-generation days, R&D to preliminary used to webinar the of programs of these been the studies Myszkowski. Day as provide pulmonary exposure potent with breakthrough program RAGE potential This first-generation subcutaneous very data and ENaC in-person an more when program. in the are the that but about if route on bears the this exciting We've half expect CTA-enabling enhanced noted is was on with Ken or we in less fruit. details compared efforts ARO-RAGE levels platform go the than to several toxicology working dose generated of pulmonary the Again, and data year. and is some of safety promising we to in use form some first to future KOL anticipate line progress, drug support opportunities currently margins be than forward view likely frequent forum. and Ken? an programs, with used early, drug we to candidates species I'd this of The to We into on be the we the the These provide what flexibility will a appear add ARO-MUCXAC should update now Thus, webcast ARO-ENaC new take that ENaC publicly. lower pulmonary It including recently candidates like have are overall will this call to significantly used administration. at next-generation subcutaneous our administration substantially to discussing a the regards GLP This via supporting are additional we less intend programs more in tissues toxicology ability with potential studies last second-generation chronic ARO-RAGE detail ARO-ENaC. appropriate administration.

Ken Myszkowski

everyone. good and James, you, afternoon, Thank

Verizon. under to our obligations related three Takeda payment be today, be and a of primarily quarter delivering ended to each received recognized our diluted XXX.X we per million million of ended for the two for and $XX average approximately million XXXX remains XXXX. the from with received the managing of complete by recognition December our on primarily quarter net Janssen. ready clinical to $X.XX performance XXXX, in portion per candidate collaboration over revenue which milestones as $XX.X recognized to the $X.XX Phase we of be December or AAT and $XX compared XX, of Takeda with was December recognized reported Revenue ended with $XXX current million weighted the the for quarter fully million upfront loss there upfront our payment was outstanding ended Horizon. X we the share associated Phase be in As collaboration will XX, There XX, portion quarter calendar will Revenue trials our for for agreements on will collaboration million to the X the of shares received Horizon Takeda agreement average agreement prior agreement collaboration, million for compares outstanding. for years, period million loss a based recognized Revenue million diluted XXXX. This anticipate and include million to end $XX.X shares remains the period $XXX under XX, license based a $XX.X fully which which revenue anticipate December of we net the of the XXX.X with the weighted XXXX. share recognition or relates Revenue to the $XX.X ongoing a

pipeline clinical and used expanded primarily this with agreement trial our clinical during license the clinical January was our collected by XXXX, cash We collaboration were due Finally, that XXXX, Any a second Total driver through costs quarter these GSK for Net to quarter to expenses used XX, as for in during and this advanced stages additional million which change our the XX, million upfront the compared increased increased million the XXXX. of to million activities would XXXX. candidate payment noncash milestones has our to revenue majority increase net million operating the from December ended Arrowhead, be recognized ARO-HSD to was achieved of $XXX as XX, resulted to costs. agreements by in $XX.X advanced be stock candidate activities December December $XX.X with December quarter additive compensation $XX.X This ended for operating ended cash well XXXX. XX, of amounts. ended operating is quarter compared XXXX. quarter as fiscal in was Key costs. the increased anticipate $XX.X

excluding to $XX from burn milestone per We estimate income continue million our be XXXX, incoming partners. million operating $XX payments our to any in cash fiscal to quarter

to R&D In our expand addition, expand and our we are planning capabilities manufacturing facilities.

expenditures projects full We routine these XXXX. year for capital outlay of with $XX along capital continue to incremental cash estimate will add an fiscal million to million $XX

sheet. our balance to Turning

XXXX. XX, cash in The to Our at cash for September was XXXX, and operating and to used investments totaled million at due primarily compared investments cash decrease our activities. XX, December $XXX.X million $XXX.X

in With the $XXX our XXXX, investments upfront the of cash and million collection totaled approximately current million. payment January $XXX

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

Dr. Christopher Anzalone

of you joining and all us for today. Ken, thanks Thanks, to

our is you've rapidly. As grow early starting heard, to pipeline

continue potential want and all we year. that start to for later-stage reach Our this TRiM of be future. exhaustive, more see the lot of shareholder the on the mid- TAK-XXX, is some key also list review expand with are for critical in this parts ARO-AAT horizon with enable will going pipeline not the we as certainly a business what but and alpha-X tracking. events programs. so sustainable hard is take our of to liver on I'll and business I milestones Takeda. our value. disease to on, These There's to called partner growth include advancing platform are to we schedule, the a a moment working growing building

clinical cardiovascular I'll portion HBV on from Phase GSK, for readout Phase studies We readouts begin levels to has XX-month expect for Horizon. we we study study SEQUOIA JNJ-XXXX preclinical with complete to X this milestones XDH AMG We study X data, the potential study. and would biopsy FDA. will X called for JN-XXXXXXXX disease expect to study. the plan hypertriglyceridemia, ARO-APOCX CTA the X expect study. with the and for year. we additional ARO-ANGX circulating Phase X NASH guided Phase and CTAs Janssen, enrollment data study wholly the progress studies to and initial expect healthy SHASTA-X formerly made MUIR and clinical file plan the ARO-RAGE, the ARCHES-X multiple have program. from additional the ARO-CX X one readout ascending expect and and and a on a undisclosed to we potentially full of with owned hope our X on discussions Olpasiran Janssen, this Amgen for study to initiate volunteers dose programs. various gout ARO-MUCXAC in enroll expect various a fully Phase X in NASH GATEWAY dose an initiate with pulmonary a in reductions from with fully enroll Phase XXX progress diseases, Pulmonary studies. single to ARO Amgen. dyslipidemia, for for study ongoing for for portion and we populations. we we this for mixed PALISADE ARO-HSD toward data Phase initiate year. year. now talk Phase X for AAT with we continue file programs, complement-mediated patient about the studies initiate

numerous Phase the additional have -- ARO-RAGE we data FSHD, clinical possibly could some like for some data has Phase file with data plan measure. progress in We pipeline have if studies. the GU at This and is fully across the call open a drug cell and ARO-HIFX your ARO-XDH the new year. X a into hope big joining hope candidates Operator? to to early enroll today. a on, February. we to We show renal to Arrowhead year. opportunities us different carcinoma, studies now Horizon study. from going CTA any you We ASCO fifth we clinical initiate three also plan report four push ARO-RAGE for forward programs. to the and look early program to We six we also clinical released Phase intend some data X/X Xb throughout to it year to coming to makes lot by ARO-DUXX questions. Thank a from have a I clinical for would from program. this

Operator

question Madhu [Operator Goldman Instructions] from Sachs. And Kumar our from first comes

line now is open. Your

Madhu Kumar

Yes.

regulators and see from in what bit think how about So potentially little first the discussions ARO-AAT. to biopsy on from liver data one a far. follow-up And we AAT should can SEQUOIA on the dig Maybe the you've need so had data? we circulating

Dr. Javier San Martin

part not So the parameter. first to data to that course, the the let serum me that's to dose selection, be at Z-AAT do looking values. last of going with really regards We're question that the of answer only but

of of course, safety and, We have changes well. data from fibrosis and liver as course, C protein

year data over agents, had along the details will of few the regard X.X set. have again define of planned to regulatory or than about the the a will any interactions months Takeda we with Phase that selection. a Therapy prefer very make dose introduction come ago. Breakthrough number I So X months to good we the registration incorporate, other designation, Under going the not study we're this of to the study course, all to selection, with With dose into next out conversation get

Dr. Christopher Anzalone

to considered And has this it's our look, I to any candidates not disease. think point division this that, against out important knowledge, drug other

meeting this what on know the broad our understanding appreciation are. we're level broad and that disease. for of that And cetera. set you same are smoking, sure There fact not appreciation, There's to was that growing really et need all people the really the longer be medical a unmet to we incidents make disease because first And of as so believe, living this we're page. for is I appears they're

while that people has starting that longer. think as are see that pulmonary living primarily viewed I is as secondarily liver a been the world and historically, a as maybe to this disease disease,

focus smoking, greater not a portion on think liver seeing they're that. of we're I As

so on far a -- really to next taking had think So we've been relationship great this, steps. forward with I FDA that look and we the we've the

Madhu Kumar

Okay.

So second the for relates question to cardiometabolic all. field you

kind and of that the influences you of drugs Leqvio and So the about like for Novartis' ambitions how how larger think about launch ARO-ANGX? you think how do ARO-APOCX

Dr. Christopher Anzalone

going be interesting. to that's No,

is sort those going course, of to know, course, overlap, after. we're the the you markets As are markets Leqvio same of the of -- not market. There but it's orthogonal

are, appears sort drug. drug. then see possibly I subcutaneously is our far several to It what expectations to think will we'll to think, address focused there pathway But APOCX. that as watching here CV continues The from for is a need is clearly what that seen regulatory as good FCS. clear. I clear mixed is we think Leqvio million really there go that the of, with markets launch hypertriglyceridemics, It markets for and be which interpretation is on we're there. is administered a as happens what be -- think we've There's -- medical that's we we what are will The unmet acceptance severe see. that think dyslipidemia I people. that is we can

patients we still clearly, treating for and those elevated elevated who is opportunity LDL triglycerides. there ANGX, an have think, For

wouldn't will be that upon in a So, we say we launch, future these confident there the I but watching of we Leqvio launch dependent the two are are to be blockbuster drugs.

Operator

Raycroft And from you. Maury our comes Jefferies. next from Thank question

Your line is open. now

Maury Raycroft

I'll do two-part question. a

how so, on So total can is as new programs epithelial programs pulmonary for ENaC two you more the variable same about the beta-X talk the require approach less this drug? target lung announced targeting or why new will in the cells? today, are you integrin alpha-v new And using with if Then indications? consistent

Dr. James Hamilton

Yes, sure.

across answer is the the We're part ligand address no targeting yes. ARO-RAGE and that, -- we MUCXAC. reason to intend that be populations various the the same to approach, that and first would two with believe to populations different those there's any still So using across patient

part And so was... the question the of second

Dr. Christopher Anzalone

new we to are use the be drug we'll confident that with less able programs. Why

Dr. James Hamilton

Sure. Yes.

biomarker biomarkers So for for there's I in understand knockdown think is there's both that two and a allow terms that think reasons of readily the better for will of ENaC programs we not I those been One a to always us measurable to great that of are challenge where that. for ARO-RAGE availability has measure. ARO-MUCXAC

we platform, as give signal. see of and can we've a not is an that I continued other the gain tox drug we aspect learned have about pulmonary more think the how understanding much to

we program and and at from achieve program. both if the tox So same that can one, a seen and relative gene three using lower the intervals might program the were lower the to level target. dosing cycle using regimens in clinical were you the dose based what in the and we two, knockdown ENaC confident we we've on remember, better day We're levels or

Dr. Christopher Anzalone

Yes.

James that's the as of and often expect about think substantially a we'll drug less it better message knockdown. less idea we And takeaway have with that these said, duration to administer also, drug candidates. depth I use and two big

bit flying a with are ENaC. We blind

see much so humans we'll drug here, we much probably species. in And And can We're as too time are pushing what in I think that those there. looks in probably tox a titrating have we like. better knockdown

Operator

Thank you. Piper And our from Ted comes Sandler. next from question Tenthoff

now open. Your is line

Ted Tenthoff

for to I a GU should what up? coming on sense be want we ASCO get at expecting HIFX alpha

James Hassard

Yes.

enrolled all and is post-dose study that second So biopsy patients biopsy. are fully their through

and So post-dose. they pre-dose get a biopsy

will well we share So gene of target RECIST criteria an a update on, knockdown. as and as course, safety changes in

sharing it what ASCO GU. that's be So we'll

Vince Anzalone

I dose that dose previously from the double the presented. think, highest level, we had was And

the was this so that dose to. And to we highest intended go

Dr. James Hamilton

this will be three Yes, cohorts. all

Ted Tenthoff

total the And number of patients? what's

Dr. James Hamilton

enrolling We the up XX? ended

Ted Tenthoff

Thanks, guys. Perfect. Great.

the to forward data. Looking

Operator

And our B. comes Securities. Mamtani next you. Thank Mayank from question Riley from

is line Your open. now

Mayank Mamtani

progress. Congrats on the

studies monkey of rodent just where MUCXAC. already if that for preclinical you same you -- the I signal X So the sort saw conducted did the and and could on maybe done? you on Have RAGE the work has been clarify for studies say work

Dr. James Hamilton

or Yes ongoing. is

Mayank Mamtani

you Okay. have there. information you Is into before And just follow-up maybe clinic? get that a the

Dr. James Hamilton

Phase X the certainly toxicology to support We have have that would studies dosing regimen.

yes. question, your answer to So

Dr. Christopher Anzalone

of provide Mike, MUCXAC, time. luxury what in of the about would humans. again, knowing we the chronic on And period we But here, RAGE that and what have what with have over doses some side, knockdown and ideas with

luxury have we administering sure that chronic we duration what see the would tox those design of look be and substantially are we drug to like in humans. the and waiting so, before make not depth more we than And studies

Mayank Mamtani

they that next milestones would then and the do question how like had move us much like to J&J we into you of if specifically, this a that two-part year. milestone and a And from that, financial decide I be if And remind be then could a the great. was study, about timing question, could expect Amgen, would

Dr. Christopher Anzalone

you told can't We remind we never you. Yes. because

our are those making are partners or imagine, We as Mayank, about granular. those sensitive too making you about can milestones be -- can sensitive

publicly And apologize, on I hit say able various given are. levels at but because so those been point. what I not those guidance are And we've milestone we've comfortable I could programs and to you this when -- feel J&J Amgen's don't really

Operator

Thank our you. Trucchio And next Wainwright. H.C. Patrick from question comes from

line open. is Your now

Patrick Trucchio

in and the these possibility a programs. ANG Just partnering that latest compounds follow-up a on for wondering APOCX there's what treatment. tell could of the us potential a secondly, take? combination thoughts programs can And your form if I'm these you on and evaluating

Dr. Christopher Anzalone

Sure.

partnering, Clinical -- We haven't With just don't candidates. be almost done, work nonclinical considering overstate think least by combining drug the currently combining these like could be two candidates and are think not now. we respect These right want to to drug and not I them. but but combining this, that like opportunities. at look, work to career we're really two once these in us any We drugs. feel them considering -- are do done we

could Our help Phase the that important studies X/X new are regulatory address These -- think, to clear. pathways we The were are clear these data medicines. markets the from are, quite good.

these. And on so to to intend we hold

given that as now and of important. burden taking where we study. particularly given on, expensive, -- require and are a Now that do think because to be we success is company, recognize outcome likelihood comfortable the these going But we ANG will we that these are is an high are

are on on sell these both a we eventually. least drugs at building to So moving commercial to and force planning now, right

Operator

Issi next RBC Luca And from you. Thank comes Capital. question from our

Your line is now open.

Luca Issi

the progress. Great. Congrats on

circle that actually in signal replicated ENaC. in quick me maybe One, seen was primate. you've on to a rats Just the safety few back ones. It sounds that nonhuman

for you file to that scenario I'm to sure Is there to And why here? if mixed so a speak possibly and both APOCX running going after maybe can ANGX this want not then think one indication more about point Phase at is switch X? running and wondering, prioritizing ahead one maybe on other? last maybe So the ultimately of must? Phase on Or and you versus And a where you a make decided this can Why little do I then bit clear. talk X dyslipidemia. horses, a AXAT, a you

Dr. Christopher Anzalone

lot there's Okay, a there.

a don't with them. we a speculate AAT. still -- on to good with we We've far the start me interacting had I we've had that. are let with relationship FDA. So want

will medicine and to a to the going data these this with what to We bring fastest have way them patients continue share be. best is and to about important discussion

be you tuned that. let as We'll stay soon clear on let to that know APO the and as is. we So dyslipidemia on respect know ANG, what so mixed and me that. both With

first, always in saw given we've So studies X/X we this for we seen a the LDL that what ANG, Phase nonclinical in given GWAS lowering saw candidate given we lowering and least at good in we clear ANG there's analysis what focus study, was at with we think drug need know know and a what -- or that. this is and triglycerides, for

large very that going market. after So saw we always big a opportunity

doing study are APOCX, outcome in with was we optionality. yet know if we're wanted a what Xb Phase do population. population. study that address large Now an a that going to we to don't very We But

than And if see Xb study, it so waiting to then decide And an we're a study, in outcome study. while do what do ahead rather the we and do have like. do go couple Phase and going of looks Phase can we to we're wouldn't years it going do Xb to then the to -- we

important. optionality that think is I

spending it's Phase we're worth on study. money think that Xb I the

pass to these sort drugs. address that with that should we Now general market of want to do come two that same

a those X a heck studies real think in in and help. to learn and patients it's what think potentially have be they how because I about two these benefit drugs honest, work a studies to these Phase of Xb to can drugs we're of going I Phase lot kinds

lipid potentially And tools the that clinics so needs. to use to patients' at ultimately, provide can they we're and going according their cardiologists least

This sort And health right, care. dream, so the provide of can really specialized, of health care. they is personalized

is as them important we see and And think having they two so fit, a tools using really thing. those

share. at much point a look, we opportunity share why be want to APOCX take and of as some reason shouldn't there. may market see in ANGX So as possible. we market also, that the other or we inhibitors And we take big that There see no future,

And first sorry, was question? the what

Luca Issi

ENaC, what see did you in monkey?

Dr. Christopher Anzalone

Go yes. ahead. Yes,

Okay.

we have for had to, days depth cycle a we once three see a sure we This that GLP because drug what go once berth just we to designed honest. make be we to don't we exactly what wanted we was see because to pretty that day I then. and too we -- -- in I did want happening we we we the what of don't much of learned of think than rats. don't we as talk don't We've require we see amount a that and And drug some And about saw findings. see -- of -- think did on giving was. look, tox is think require lot lung But we So generally some But dosing. knockdown some duration that wide that's since I I were frequent local more about, signs talked probably was we're probably didn't that, inflammation.

we ENaCX. how gives about we be RAGE understanding more can drugs, So it do that but think, us I and for only and have, deliver drugs. potent it potentially better MUC Not to confidence efficient the have

so know, drug do given drugs. But platform data important this know at potential tolerated we've we -- the don't know the you until clinic, well candidates clinical that nonclinical, these we feel, you will And both we least. feel got, until -- again, that be in we we're don't and and but optimistic

Luca Issi

Super helpful.

Operator

from our is Cantor Alethia Young question from you. next Thank Fitzgerald. And

Your line now is open.

Alethia Young

this But into you're branching kind potentially of pulmonary There similar of types out on are kind seems it indications. questions. franchise, of two like other bigger

day, businesses out just a similar -- is larger kind capital it to going are do are of open that some, want I know strategic and are big and longer about wanted to to you that out do now to one broadens get of building even partnerships how kind you pretty be of guys for you can collaborations And and to markets just thinking larger capital what kind like here. So hopefully, up indications? question you're

lot program. of a have You

of You have lot a collaborations.

commercial more forward a with about in it of much you opportunities, I you also building do something opportunities often And kind where bigger guys that too? to different the expense moving of Or the could yield albeit may and investment think kind but if bigger potentially, take on keeping many about of like bigger You're want side, same. your do the strategy assets just is core your know think how ways.

Dr. Christopher Anzalone

It's Alethia. still pulmonary. Thanks pulmonary. like like the of and early with out the But for we space, building commercial we idea

there can U.S. nine look don't the think drugs. or we think And see are at see in we look We XX,XXX at I that, eight we do. what three around when our drugs. platform pulmonologists two We or when pulmonary

commercial XX,XXX we of pulmonologists building idea of have eight sales so bag, like that's efficient way, out who the to or a And the nine those an drugs force. force to address in I build think,

it will that come the may now, so assets. we're target-rich strategically, is want thinking that of to holding environment, about the on conceivable that's partner it. here lung But is those targets right how there. certainly So enough like we Look, or and we idea on to up

You've company a that build large talk this commercialize about that large have be ourselves. number we that going that a us I that of before important we relatively we're to if think heard a to should building, drugs need we --

way. order run to We're a, can drugs strategy in capital to, very we provide of that And And partner We we'll get that in our well; us partner to and to so use to so to b, that. to patients of afford going them kind we're can't not that continue partner. programs. over cognizant own we get

Operator

from comes Baird. Joel our Thank from next question you. And Beatty

Your line is now open.

Joel Beatty

progress. Congrats on the

question activity the and the the really lungs relationship is help biomarker How on between ARO-RAGE. to circulating close in the able First pinpointing to be is S-RAGE with dosing?

Dr. James Hamilton

Yes.

the actual or So of origins. two that it's It's cleaved splice S-RAGE variant comes secreted RAGE the different is receptor that's a transmembrane receptor. from off

knockdown I of your by So what idea of very hope have good a that measuring that should question. S-RAGE, answers we receptor is. the

Joel Beatty

to how Yes. administered And be as follow-up, subcutaneous the lung lung could programs behind a programs? closely

Dr. Christopher Anzalone

programs, to if work it breakthrough. early tell make about on that. thing again, are it's we a are we early and too because, These It's make this scalable, real excited it can and

We're yet. ours. of focus quite real there a not it's So

expect excited So like, looks able see it. -- to an some still it, we're data. or I to our we'll COVID hard we're will it's least a tell that working webinar of R&D how far Again, day but we what do are. on point, think hopefully -- but in-person, we away I it's we'll do that pulmonary-focused at share be about at

Operator

Mani our And you. Foroohar SVB Thank from question Leerink. next from comes

Your line is open. now

Mani Foroohar

previously have We Xb XXX-milligram look knockdown really through XX% shown digging what we Ionis, know data knockdown also don't They I'm So dose. which like. Phase the with their cover. this from XX-milligram ANGPTLX actually

And on of XXX% data seen frequency, seeing guys clinical nuances Are that suggest you reproducing obviously, guys translate of quick they that seen the at that that cetera, that translate in specific larger there haven't cetera. Pfizer sets hadn't those non-HDLC, full that when you're knockdown, knockdown, follow-up. that benefits not that knockdown from did benefit at you have I terms clinical trial a around perhaps et showed? suggests Pfizer given the of data. in to triglycerides, look will dosing, to despite the et the level some clinical But We they commentary with seeing impressive

Dr. Javier San Martin

what data range, in XX% and have knockdown that LDL milligrams to presented the XX% the XXX XXX and non-HDL with level triglycerides Well, and the we we of dose. data from

So and clearly the But superior LDL to current we data non-HDL past. had exactly. is what presented is know what data the in Ionis don't

and you knockdown the believe our speak will ANGPTLX of and data study So, at is that level and effect, we three between that level data. pharmacodynamic of least that the far Regeneron Ionis so to of suppression or do there the comparison correlation between different the the the sources the

well. heterozygous dose effect. the the our Regeneron see pharmacodynamic homozygous at said, is in look clear. quite If suppression you to differentiation we'll the to we did of And high a case the need as dose get as to again, response and the data, achieve they between do study level pretty I to And

where pharmacodynamic the this or suppression target I the magnitude effect clinical target correlate the the with think is of So, a

Dr. Christopher Anzalone

look, two if potentially because frequently. it their compare look these really And -- But every I it's difficult think we're studies. at again, these once their month, in two dosing separate less data every you so quarter very weeks and haven't or to once every we seen dosing you

Second, you We and was. we we ALT patients think two had why at look know that ALT with increases. increases,

So patients two medications. to it we're we think was Those other related on.

that's difference. think we So that

we haven't they in like Third, seen fat. sounds It did. increases liver

And so I think the of of advantages over RNAi good broadly a this antisense. example is

are safety those modalities, favorable. -- durable the can and think The is knockdown. whenever be to leads deeper two you chosen compare more can profile, it RNAi also correctly, if sequences I

feel So data candidate. well target the still up about great Javier we about as great GWAS at feel the points as other We as data. the

Mani Foroohar

Yes.

to do formal saw do that did what they more to justifies would understand, what think narrow a -- How higher in trying adequate? and around as So I'm -- The X obviously, you what Pfizer, think broad the showed even large numbers patient have think as in population going a you a X. Or that a to release, opposed far population. complex, you've into sense Phase the niche-defined so they But about number be previously do would to me. is makes what something press we like a what deeper, threshold is events. a around limited that commentary so justifying what are the a pursuing what be from you Phase aggressive clinically than you Like necessary? more going the knockdown seen your

Dr. Christopher Anzalone

reduction LDL -- reduction in triglyceride I that. We've Those percent substantial. much our data. and we'll as are XX%. as look we'll range, XX-or-so much We've at seen think Look, like as take mean reduction seen something of Xb see as Phase XX%, a the

not outcomes clinical short in a going study. to we're see Now

substantial. endpoints, don't are dependent we're And those these so upon but think I -- so I surrogate

in and And into -- think not I agents, study. I far way that them triglycerides-lowering continue other would put way, us Phase good would You to that an it outcome data look give think think if -- roll I go that, we've out confidence there's our that our at out X/X study, if just there. that so around data to the this be the seen that, much

Mani Foroohar

sense Great. me. makes to That

Operator

question next Chardan. And from Nakae Thank you. our comes from Keay

Your line is now open.

Keay Nakae

Two questions.

Are Integrin safety And better conjugate performance First, the ligand different? subcu primary you profile? evaluating a or admin the targeting to something you is for objective the using same lung.

Dr. Christopher Anzalone

Yes.

answer can are do first ways playing I we the question to this. So with various because around

present, And can so talk we hold when about it. off we more and

But it better questions I inhaled for say looking It's we're So we that simpler, -- you subcu, though questions of afraid route. we don't via animals. safety have just to as profile. are life makes our safety with that unanswerable right? question. a That's -- the don't are that have want it's profile in If to or good a this not unknowable administer more can longer tox there any any about a respect we

think I nebulizer, breakthrough easier. indications a whatever it's could who to be two rather simple some having a require every once yet. knows don't And seen time. that So it relatively that explore be of does or once a just of so to far than would than oversell subcu because mode has also, every be. convenient cumbersome That's in We weeks, told what just field. to we're to all us want that's That's more easier want again, months, we requires make injection But and we've month, continue for using that once administration but this going administration. still an it a is massive this. lives a which more not three there look, a potentially our touch, still mode light machine just But

Keay Nakae

the of fiscal be just Okay. much How received clarification you upfront in some might time? And recognized Great. revenue from over And the a will GSK, January. in QX? of on as million much be that how period amortized $XXX

Dr. Christopher Anzalone

repeat you can Sorry, that?

Keay Nakae

will as fiscal be be might of million GSK upfront in January. versus how recognized time? $XXX amortized revenue period from received in much much How The QX

Ken Myszkowski

Probably all recognized of it will fiscal QX. in be

that obligations that milestone are basically performance for we complete received. Our

Operator

further now turn And I to thank like Anzalone questions. over back am would remarks. for closing showing to no you. the And call I Chris

Dr. Christopher Anzalone

forward for It's and talking we pleasure much us to today. very look to you you, a speak joining with always Thanks to quarter. next

Operator

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

disconnect. You may now

Arrowhead Pharmaceuticals (ARWR) 3 Feb 222022 Q1 Earnings call transcript