Wave Life Sciences (WVE)

Graham Morrell IR
Paul Bolno President and CEO
Mike Panzara Chief Medical Officer, Head of Therapeutics Discovery and Development
Dave Gaiero Interim CFO
Chandra Vargeese Chief Technology Officer
Ken Rhodes SVP, Therapeutics Discovery
Joon Lee Truist Securities
Rick Bienkowski SVB Leerink
Salim Syed Mizuho Securities
Eun Yang Jefferies Jefferies
Luca Issi RBC Capital Markets
Call transcript
Due to licensing restrictions, you must log in to view earnings call transcripts.

Good morning, ladies and gentlemen, and welcome to the Wave Life Sciences Third Quarter 2020 Earnings Call. At this time, all participants are in a listen-only mode. Later, we will conduct a question-and-answer session, and instructions will follow at that time. [Operator Instructions] As a reminder, this conference call is being recorded. I would now like to turn the conference over to Graham Morrell, Investor Relations at Wave. ahead. go Please

Graham Morrell

available results issued that Good section today Operator. review presentation thank of for morning, the you third Thank these discuss morning, Web call. webcast this will our site, us detailing we This results. to available in XXXX The site on this Web our www.wavelifesciences.com. Investors and news recent is which joining slide accompanies release quarter you, financial our and a also business be Wave's following progress

SEC XX, XX-K filings, XX-Q quarter including Before could materially I those our during subject cause differ XXXX. year forward-looking to and begin, These include to ended would we on September risks and in We for quarterly XXXX, you like ended press Form the XX, Form report the could for results are no that are our discussed this differ undertake actual forward-looking in Annual to discussions our issued our from to Report statements actual will in on cause December call today to the President to revise of and update that remind statements the forward-looking any Dr. I'd Paul? obligation now Wave turn to Paul any a reason. results number Bolno, conference Life factors described call of and that like release CEO for these Sciences. or uncertainties statements. The over statements.

Paul Bolno

challenging hope you healthy and staying Thank times. joining you, families Graham. Good I these on safe and to morning you during and for call, everyone us today. the thank are

ADAR us PN overview trial I'll first clinical quarter about talk this future on included achievements, our announced our data XXXX, share summary recently overview the of plans. of PRECISION-HD first will the morning readout our for by We editing I'll advancement, progress, new of the an chemistry and a our quick to in program. programs, of be latest are that the a recent providing and off in then start excited

and will three of newly Head submissions, dystrophy. Our Chief in Panzara, including Discovery Officer, discuss and our Therapeutics trial clinical Dr. muscular Development, Mike Duchenne announced Medical upcoming clinical our trial then

This Officer, Dr. available Finally, Vargeese, third Dave challenges PRISM past Wave's our the advances our portion quarter, well our tremendous during of our Financial Q&A Chief continued Chief Chandra our financial preclinical the clinical as clinical and expanding we call. pipeline, Dr. teams platform. Rhodes, around results. with discuss Technology quarter in Despite COVID-XX the the progress strides. innovative will will made Senior Discovery of our of President Interim be also make as Officer, to and Gaiero, of world, significant this and Ken potential Therapeutics Vice research

ongoing and first-in-human in two in new exciting This look Huntington's as WVE-XXX, our for our studies XXXX, studies the expect quarter of and to as well of are continue I in disease, for ahead anticipate we data which believe we Phase To clinical we XXXX, we new first ushering a WVE-XXX. start, Xb/Xa As PRECISION-HD phase in now includes XXXX. five Wave. having to trials

programs. impact for PN and an are third AATD. in in dementia CXorfXX Notably, as allele-selective the how this chemistry initial Of Thanks disease advancement. deficiency backbone the in chemistry assess expect this splicing year, all well the our dystrophy WVE-NXXX, suited last also to of Mike both with we the and for editing WVE-NXXX, and editing sclerosis expansion and The in this approach preclinical ideally this work patients will best-in-class program has decision patients future and for about are we the amenable editing The on liver first with our today approach, for system change the with rapid Duchenne the reminder, disease that editing need with hexanucleotide amyotrophic our neurology. novel for later. platform completed and candidate believe alpha-X has CTA that today, WVE-XXX is will XX RNA I'll the the us ADAR Huntington's areas, editing announcing potential clinical announcing incorporate trial, PN including about our we candidate dystrophin and will safety, As to in share lateral muscular muscle. believe address intended our candidate, talk fifth disease. the a more exon our note, was lung is understand is we ADAR frontotemporal which no complete trial, trial to which to guidance. manifestations many initiate way Wave WVE-XXX, submit is we to a our ADAR our This will potential as advancements become ADAR WVE-XXX PN WVE-XXX RNA of to skipping. We in chemistry our disease modality clinical be to antitrypsin and lead program or gene. to applicability reached cash also to be more help

targets. continuing grow our neurology collaboratively our also pipeline work to we CNS on up six through where to Takeda, preclinical are collaboration We with CNS

webcast, novel XX, backbone compelling these investor we we three helping including among PN in primate August shown modification the slicing, been to advancements for candidates, we an properties share and improve our RNA our pharmacologic backbone chemistry that our nonhuman today. modalities, On all has PN across to will resulting PRISM us held where chemistry. analyst is silencing, announced editing. oligonucleotides Our data of backbone This profiles platform, optimize

existing positioned well planned programs. all of and progress our to financially are we Finally,

the into reiterating we as in study quarter from share both quarter are open-label data current takes first track PRECISION-HD that from Dosing XXXX. XXXX. are in the the continues, trails Xb/Xa all of cash of to well our the second as ongoing data and We us milligram in XX on cohort cohorts clinical the runway extension initial Phase

have eight as to or for Huntington and mutant trials light-chain. as effect doses and OLE, patients at received on tolerability XX data data the knockdown, total huntingtin the the including multiple biomarker these Specifically neurofilament safety milligrams Results cut. data of in well include the we will for knockdown, time are who share in expected

continue protein, wild-type impact good work time we treatments potential to wild-type as and and have the focus also complete to huntingtin, our readout. that data for measuring to forward We of the of We huntingtin this critical in made challenge understand on you believe progress. keeping strive scientific updated it's to on look

PRISM properties August, provides can another with quickly of has optimize neutral, atom pharmacologic involves up replacing of them use moiety. mentioned, I a Nitrogen-containing as pairings. modifications of tool the complimentary in linkages that are non-bridging our As charge we the chemistry. announced, base Oxygen the a break become the platform while to PN This to it our we allowing PN backbone advancement important retaining of component candidate. our to chemistry backbone we PN repertoire expanded an specificity with

demonstrated durability in compared Our exposure, utilizing the when sequences without identical a and general increase PN preclinical to experiments have PN potency, chemistry modification.

of amount across We are CNS impact tissues. chemistry and knockdown of seeing the significant on the durability PN

in central containing knockdown of throughout study the shown transcript meaningful previously nervous to have the PN this we XX% XX% in persistent molecule As mice, system. showed

general. for down our programs. CNS the chemistry effects results in translate the pipeline, Importantly, the the this see a enormous advanced PN in Wave slide, advancement we On with considerable Takeda. our XX% to target, tissues. dose to candidate the and milligram primates as we collaboration continue In for to of our One deepen CNS, future. including an spinal that most owned We programs widely target single therapeutic implications was see approximately intrathecal cerebral for CNS add vivo can across and in we Further, recent and injection a received look non-human field cortex, new distributed single administration, you view platform data the undisclosed for discovery across our wholly study month this dose. new after XX knock the have hippocampus. this observed neurology candidate the cord, therapeutic data The these NHP led to in as in

in modification. PN chemistry is impact on chart preclinical the the role pipeline our utilizes and our investigating backbone having modification discovery the WVE-XXX with unlock PRISM and excited WVE-XXX, novel ADAR start our PN latest portfolio chemistry Chiral current phase We're trials editing our programs chemistry all plan us the as we've WVE-NXXX. and made control, advances capability. PN Our highlights platform as of of The considerable to clinical clinic platform to through have helped

human recruit change mutations as greatly these an Our the approach chemically be mutations, pathogenic the half protein G called up SNPs of restoring leverage to A employs function, editing cells applications, or XX therapeutic enzymes RNA oligonucleotides, the to in opens number which fully to door endogenous to less we modifying address. enzymes editing ADAR. ADAR expands usually of correct known are an of can a that to including to protein regulating capacity the RNA A variants I read can Nearly expression, potentially used which disease or to ADAR nucleotides RNA. modified and to landscape G short,

editing many at is editing. of and technology has Our the advantages space RNA forefront in the

and irreversible Our RNA target edits, proteins editing risk target we Introducing avoid editing and because genomic off DNA we exogenous endogenous decision effects. may to as avoids immunogenicity use the trigger pursue RNA enzymes, off that ADAR was of deliberate instead

available stereo repertoire including In using through an addition, chemistry. of PN chemical our expanding modifications oligonucleotides are optimized and PRISM chemical

rare The to both A the is liver to study strategy single AATD by delivery functional damage, does where not it commonly would SERPINA are first progressive X many webcast. neutrophil editing from lung the would disease AAV dose lung disorder release, protect alpha-X the coated antitrypsin misfolding our announced require days. a and deficiency. program, processes. and editing or disease. editing you that terminal leverage transcript managed allow inherited sustained saw attributes morning's the press We've specific. to ADAR leads may Alpha-X represented last simplified this both or X XX mutation that exhibit gene. of lungs, In We This potentially which Importantly, we frequent XX% or SERPINA in oligonucleotides in typically damage, will point of in our recall two for in AATD vivo manufacturing to mutation a which target liver of that to shown a OLE primates, we tissue employ lack caused our by lung beta-actin also hospitalizations, study editing days deficiency or with Patients nanoparticles, antitrypsin mRNA genetic treatment these or ADAR alpha-X showed oligonucleotide of established a leading highly elastase. which Z our was vectors us research and antitrypsin proof-of-concept at protein non-human in is protein up of aggregation hepatocytes, of from AAT G

for increased circulating approved liver those with with G AATD modestly therapies are most mutation therapies is address to there approved to pathology, AATD. to levels Z a develop These to the see landscape of we apparently patients attributes. treatment few no A homozygous form patients approximately the worldwide have It AAT estimated which are the quickly, there While is best-in-class severe three opportunities growing of Well, in on key OLE. continue point lung the the the would approach, XXX,XXX pathology.

regulation, wild-type a are give remove patients would By and First, RNA develop to want editing would the AAT the therapy, is the AAT or these address of on and delivered restore physiologic edits protein. Leveraging levels to of editing we improve augmentation that disease upon simultaneously our and lung believe we did avoid information off-target available wild-type liver to NHPs, attention with We believe a therapeutic to correlating and transcript AAT AAT's protein DNA only the to editing treatment an we one the aggregation opportunity already could for we corrected single GalNAc potential to the the irreversible to we the based augmentation also to potentially and preferable that our attributes, to for phenotype. the address both, addressing would conjugation we the approach the the at we modest in substantially be provides to for through genome. work want therapy understanding that publicly liver. want appears of retains approach of all editing option need turned regardless

learning that model, in XX% of that increase better to upwards transcript, candidates from do with this then wild-type hepatocyte saw in This right of for asked develop in mouse Z Here and human a Protein ADAR. one from back us z-cell modeling the parasites the we protein mouse model misfolding in have allowed which ourselves RNA ADAR in is prevented SERPINA our editing Concentration. show which contains we've of platform; we accomplished behaves place question with best-in-class differently humanized correction important mouse resulting transcript ADAR for secretion we to systems vivo the model. The primary we three-fold X limitations

initiation. optimizing discuss this develop further is of areas. that our providing time, and pass scientists across neurology mouse the which mouse Mike model, contains call modeling Discovery both and year the in can therefore, and and model specific upcoming looking be model program we about to Medical now clinical our thus ADAR programs. three system other trial to We're humanized a from Therapeutic SERPINA to to editing humanized At generating with used Officer Our Development, cross that the any and Panzara this What's model humanized our AATD our really ADAR. proprietary data Head system model and a I'd Dr. next X ADAR forward Chief disease exciting this applying can like

Mike Panzara

Thanks, Paul.

progress. to one data WVE-XXX, ALS anticipate been year, candidate for financing has and the but OLE not highlighted quarter before WVE-XXX, This our as already the the by quarter variant and mentioned, in PRECISION-HDX one end for in selective we're also We selective and their first disease, preparing of from tremendous third-allele in Huntington's file Paul only sharing two PRECISION-HDX candidate FTD. and CTAs our

skipping; quarter In with I'll patients submit on disease. for addition, exon first NXXX, DMD my few next a a in for we're later presentation. the mutations that candidates planning our amenable Huntington's words in to to on start WVE XX with CTA of year, more

lowering against in cells the stress metabolic beneficial plasticity, protein Wild-type function for brains, and survival. also essential essential synaptic a this nervous Our to in protein, a work of as types growth in us others of even of concept involving this their intense proper in to excitotoxic, war their wild-type system, out the biological emboldened the not tug misfolding the the for as as invariable as in and process time opposing carries stress. key in adult where role work it In Huntington huntingtin factor plays to push-pull foundational that years have between sorts over huntingtin a our belief as for progression of systemically. the between shown over supplying past including effects important, scenario, of selectivity a a essential allele developing and while protects but area trafficking only memory, central wild-type in of function affect learning been of critically ensure has much stress, more functions proteins, balanced is huntingtin activity, neurons the and is essence, two proteins these maybe wild-type high that effects few synaptic treatment is that various in important vesicles. of possible, both oxidative prevalent striatal synaptic BDNF neurons leads is HD, preserving mutant trafficking disease, and to which important well with This

is function Cilia, the the homeostasis flow and Additionally, control and of for wild-type in maintain critical the help formation CSF which of CNS. huntingtin

much as possible human an system for wild-type third in give supporting transcript, turning opportunity better some our HD by is that them undisclosed while believe smaller HD relationships PN and intact. to clinic. and WVE-XXX first reservoir to and relatively addition SNP of individuals a were the mutant outcomes. vivo the this protein with evaluated candidate that dosing. to wild-type protein, of in one HTT wild-type target in to PK/PD illustrates to of leaving in our approach the thus on the the the best designed of these This transcript protective allele-selective this vivo movement XXX's understand to huntingtin function recognition model vitro to disease into huntingtin guided guide gain selectively trying than necessitates an preserve It's a It HD leaving SNPX have Huntington first is incorporate of of copy slide initiation the in lost We chemistry. also mRNA data Our to with patients compounds individuals. is scenario unaffected mutant as the beneficial

wide in a reference we candidates versus compound. the the of over clearly concentrations On concentrations vitro pan-silencing a left, see range our of similar of selectivity

While in huntingtin huntingtin we wild-type the see leave from XXX mutant RNA compounds, a intact. similar transcripts reduction both relatively

striatum setting As huntingtin SNPX there to limitations do for down. namely I mutant copies SNPX were XXX the mentioned, in enthusiastic with mouse. mutant knowing knocked candidate and this examined our also gene prospects out that does to demonstrations XX entry a XX% the not potent vivo enter have for and model, of we of a selectivity, of variant, the higher we effect the model, into durability knockdown HTT it that of an potency huntingtin clinic, slide. observed shown in us which up the These some Nonetheless, transgenic the gene, therefore as contains although durable people of mice the candidate did cortex about of effect clinic. of on weeks we to of the this we not We the options provide huntingtin the similar in therapeutic wild-type several mutant bar selective not contain in for with allele-selective shown multiple Further the prepare are and it in HD. right, BACHD this with BACHD leave transgenic positioned as to to

expression the both expression of from forms. FTD, and of potential most illustrate targeting and moving devastating genetic transcripts address the expansions high drive containing in designed of driver accumulation the healthy and our The frontotemporal CXorfXX XXX represent program need. and ALS compound. CXorfXX of and about proteins, GGGGCC or repeat of abnormal is hexanucleotide amyotrophic Now, mutations familial neurotoxic are of dementia, reduced treatment are that are why WVE-XXX, the the expansions to candidate of dipeptide lead we CXorfXX selective the data for XXX DPRs. unmet on repeat Both diseases common sclerosis to to hexanucleotide this gene protein, repeat our variant preclinical sporadic areas lateral excited

from knockdown human on previously, PolyGP the clearly ICD in spinal proline vivo which of cortex. only XX% we've at and doses from lines the expansion, least the After showed in zero exciting potent repeat the CX-BAC mice, XXX and cord that or XX% story. transgenic effect DPR consider to express and hexanucleotide in six impressive addition the dosing setting. of the the particularly durable shared vitro In CXorfXX tell days clinical for containing in data intervals data two months, iPSC we as protein This polyglycine at over least in the persisted results seven,

program safety assess the and human in the doses and primary clinical PolyGP at XXX that inclusion the studies, we preclinical important evaluating the tolerability measure vivo XXX, same of preservation of of potency compound. objective in the our We CSF is forward of but variant-selective target sustained as One will the year. both of the biomarker healthy our and CXorfXX this engagement. of look designed to very and aspect study combination further clinic assess selectivity month confirming point, Given candidate's time activity to clinical FTD targeting, The encouraged study. was with unselective, to results by proof-of-concept patients be or we six our were protein in single these will diagnosed be demonstrating in from ALS, next same to of multiple

also as well other at light We as biomarkers. to intend chain, neurofilament look

year. a we next expect CTA update an plan provide As on this trial noted file to quarter to previously, the early design and

exon DMD, rapidly exon XX% that end WVE-NXXX data demonstrating Finally, candidate production file of year. we in that to up DMD plan advance in targets discuss prepared our was advancing at vitro with I have XXX dependent this to PN skipping. chemistry. announcement fully may our you increase the were last supported boys myoblasts for next XX Like with to included XX XXX, who amenable NXXX designed preclinical in recall back year. and of we will the derived Stepping that in mutations candidate. clinic this patient a time, At to candidate data which the package, dose CTA dystrophin to

PS/PO the challenge on in model DMD program. due suspended supported not of mouse indicated may there is in muscle. also with chemistry you we leading impact NXXX muscle well the and and done initiate muscle access with knockout less a and DMD the a XXX had an kilogram obligation splicing as or in and the of to supporting backbone intracellular drug discontinuation milligrams study PN frequently, ongoing mock at a likely remains efficiency green One Suvodirsen preclinical an to XX% distribution Based linkages, XX% PN skipping muscle. effects model effect. mutation ready know, which molecule is We in weekly the to study control. extensive that week, shown tissue a a are compelling this the least piece for that of this Other light clinical containing Suvodirsen receiving mouse our in clinical a having an and engage ongoing However, evidence They most key is DMD age. lack the poor to Despite we that milligram development and best This all XXX, phenotype. of a preclinical other a kilogram to PN less biopsies of way dosed as a of XX containing than these following the of possibility as XX the Based data a drug, a now chemistry a dystrophic dystrophic to containing study PN assessment X understanding in then PN at preclinical and rapidly dystrophin chemistry. model, on DKO have our program upon have thriving chemistry including utrophin. per to lack has overcome reached Since every assess target, the indicating greater community same of we data PN as compound the study a the distribution improved double XX of molecule exon did trial. administering molecules of dosed compounds, leading mice the programs well in from the outcome, at are our study from is sequence compared other placement for was mutation devastating a weeks a that the per containing the

an other call I'll disease. compounds turn planning to interim production, change other other with with Europe. are received the our to therapies. We We measure trial of drug every patients If The exons to XX a next need eventually new as week. results. there in the open-label to neuromuscular to opportunity year, DMD, apply through in help CTA Gaiero, potential successful, CFO, NXXX for safety. the in forward concentration who was to advance the well desperate boys now bring the first muscle dystrophin PN chemistry financial up our to a quarter powered and to We trial to over will trial assess Dave? look of detect in be conduct initial mission submitting in to as to the plan Dave continuing you

Dave Gaiero

of $XXX.X Thanks, $XXX.X compared million quarter Mike. and XX, third to of December with the Wave ended equivalents approximately XXXX. million as cash XXXX cash in

receiving proceeds September program credits. our quarter the XXXX equity $XX public runway million offering by million of our from raising cash and substantially at-the-market our $XX.X in million in XXXX, extended net proceeds from During and third in tax refundable we net $XX.X

Now the for like I review income to would our quarter. statement

reported decision period the expenses external expenses For the related as XXXX by XXXX the for the same to which suvodirsen period prior FTD. $XX.X expenses the expenses external research February as in general of million quarter in to the February cost a of program quarter third was to in due period million expenses activities XXXX quarter third HD the for driven to discontinue the primarily our year. due XXXX, clinical the plan, to and CXorfXX XXXX by and workforce and ALS well programs for the compared program, million million related reduction expenses external to and net loss our our cost included were headcount other and in of of offset third was reduction. to were in XXXX. decreased to same partially our decrease The XXXX, third compared development December Research to preclinical quarter Wave expenses to and million administrative development $XX.X of $XX.X $XX.X administrative to in $X.X quarter related primarily and million General plan, our XXXX. same and in XXXX decrease in compared reduction in in The due third $XX.X increased

enable and of We expenditure operating cash our existing our quarter from fund cash expected and to XXXX. equivalents, that expect will together cash collaboration second with existing us committed the our and capital requirements into

uncommitted to will now not in payments remarks. our runway. collaboration did for we Paul reminder, potential include call back the over other Takeda turn closing and related our milestones a cash I Paul? As to

Paul Bolno

we be for ahead, expect in our plan and In Thanks, quarter, studies To for sharing are first we will driven WVE-XXX. in a WVE-XXX of to that we OLE this XXXX, the excitement a to recap, PRECISION-HD Dave. all initial report the the as Also the clinical the cohorts well quarter first CTAs to I by submit mostly for what data. all to CTA ongoing of from data quarter, we in third you expect WVE-NXXX. submit hope XXXX. we be trials catalyst-rich expect five year expect as

continue updates humanized as our to build on novel we I plan data ADAR expect AATD including model, updates share to we in to program, this Finally, capability. and platform the share editing we'll have other

of the And with pipeline potentially well-capitalized that, open the for our call advance questions. to We value are of platform. programs, realize Operator? our we'll up transformational and


Truist is Securities. [Operator line question of Lee with first Instructions] Your the Joon from

Joon Lee

for couple questions questions. of a updates. thanks and and have the I guys, Hi, the

again approach approach being your For way antitrypsin would one, what better your explain of the Alnylam by a effect can or DMD and access chemistry, the the have backbone able and program, different you us overcome of number to from chemistry for you. taken is tissue program, patients editing you the ADAR for your Thank remind what program, knockdown than is percent chemistry? could Dicerna? in prior PN need the how therapeutic And to your you

Paul Bolno

and Thank divide Chandra in bring second. two Joon, parts; into we'll you, this I'll a

to about don't we been of liver. for As knocking within brining approach while the editing differentiation, excitement approach around discount relates silencing, silencing, on a lot out, the mutated correction ADAR, and protein as excited that and or there's we over an we're a the forward it down laid or

think alpha-X we of correction. of antitrypsin really it approached deficiency and from when we think area I the the approached

is, mutation we do to that restore point the the hepatic such that as both of So we of fix protein, liver physiologic it and balance complications the well enabling the this pulmonary lung. the as how treat

is a arm. down this driver drive key us the to for So correction

it heterozygosity about talk know we patients, patient As so a XX% if the that the is correction of restoration, manifest heterozygous, doesn't these a or do we disease.

by about to physiology. think Chandra, [anything but up to] with is -- between of there in you [ph] ADAR we So to means restoring want that correction XX%, anything add physiologic be you don't terms needs where no protein question? the the correction the to XXX% normal to

Chandra Vargeese

pretty you that think I much No, covered.

Joon Lee

just that… Hey, from Paul,

Paul Bolno


Joon Lee

be, two manifesting clinically? ADAR question, the how as be will it you up finish you approaches expect editing, surely approach your works different and knockdown How both would as differently? approach envision clinically assuming by they the then to would Just expect these works

Paul Bolno

I initial treat as -- out terms we pulmonary the know to complications. replacement are protein in the of mean Yes, that therapies there's now

correction silencing. or interchangeability therapy augmentation kind as now there, protein as So and desire replacement of therapies of is a liver well that's so there is of augmentation about to with think the there this protein

we be therefore the protein wild-type really physiologic and as body the protein, the to normal so restoring both to stand for correcting think I use the in they work both, the and need lung restore letting liver. the balance, to able proteins

really protein the of So potentially they -- would replacement therapy. silencing require or necessity wouldn't

Joon Lee

and Yes, DMD… the

Paul Bolno

across a data question, I'll DMD, in Mike we but to and that today, cell the of about muscle, other on it day, for as you neurons of continue DMD, do but answer to we subsequently, we'll I PN on one the and generating the vivo there's aspects. let obviously, chemistry, we want Mike, shared can Yes, as the uptake think shared DMD? relates about and and research just across as this in lot as question excitement context we're talk mean of answer to transitioning see

Mike Panzara

Sure. yes. Paul, Sure,

as PS/PO we're just the in said, different durability when distribution, to So importantly identical tissue of mean I molecules. are added very PN access, Paul seeing backbones and something terms

a see address clear So the why difference effects, model, thinking what we in these that in first we're all, the but exon you this terms vivo in of XX, are, clinical versus tissue, terms in in we're model, of PN. issues, could PS/PO targets terms it a of DMD, seeing of where

different. clearly clearly that here durability effect to Paul I introduce a to which we're alluded introduce difference that molecule is said, seem, a backbone how the as tissues. The earlier, does overall there seeing negative potentially And as -- the So encouraging. on is changes PN charges accesses the neutral

address So maybe with could suvodirsen. concentrations change having this at we with tissues higher in better that it of saw, lack longer we access access saw this the

and it exon really that different targeting and study to into question, ASO of you is hope, with that seeing can an far there only take we efficiently as lot can here a need that that with so the give molecule answer the are picture overall to human preclinical a targeting or and described. are of that very take an characteristics data do us that you but in the a exon manual, So just we

Joon Lee

Thank you.

Paul Bolno

just other as important reduction also DKO that study that was mean one think, in and the -- yes, with to -- to that. the the I was dose. Yes, other follow-up the piece substantial comparison, Mike mouse Joon, think the I I on alluded of

improvement, but not every just drug, not that really and So that kilogram, PS/PO per less week, XX% seeing even seeing weekly. XX so milligrams so other improvement that at than

that I important. So as think see we

diaphragm. I is in phenotype with sensitive think also pulmonary see distribution we model distribution heart and good cardiac which and heavily that to across

questions excited characteristics point up there. is should noted a were augmentation, IV weekly One about therapy Alpha-X antitrypsin is bring pretty just be and it that you infusion. to the about back other we're So asking that protein to deficiency

off pretty something also physiologic in restore weekly the we're correcting, able that's IV patients of a just the to but being protein, of the terms forward. about real of move able normal of terms not excited in to to being in administration hepatic, So protein brining lung, correction just

Joon Lee

Great, Thank to the updates. data and thank you, looking forward guys. you,


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

Rick Bienkowski

Hi, good progress. the morning. for on This Rick line My first is also NXXX. on is Mani. on Congrats the question all

preclinical more or little in So chemistry? access, to compared studies besides expect would guess the was seeing to tolerability in PN improvements you with window a And tissue the bit I any what either on you see therapeutic suvodirsen? can I you're hoping elaborate

Paul Bolno

to continue. amount We're as I'm going data at we're that the seeing often substantially a so purely let think I I about -- to mean, of with where have phenotype Mike around to talk really distribution talk -- the note, has times interval time is it's seeing a we phenotype, less a the those that drug changes that mouse in longer. expanding that's because -- MDx I and mean dystrophin. we isn't and I important people alluded, one, dose, out think there

said, I model being this with compound, about us skipping that's as the So does Mike model exciting chemistry. think phenotype exon this have XX the with what's is for PN corrected this

distribution you that in So being we're about evaluate able to terms do excited that? in of you Mike, add to exposure anything model. want that the and to have

Mike Panzara

as preclinical to less other that that different. be given say seeing would effects quite supported are that lower clearly that the window therapeutic molecules. leading window, doses therapeutic of all by as we're we well studies the in suggest expect frequently difference to Yes, the and mean also between I there's a I

obviously difference, until you know, hypothesis we why So way that here but study to difference. determination on focusing target a of small there this a enough but with is in definitive us proceed number to engagement be that anticipate decided is best make you in the whether that there to information test which would we've patients, humans that a is can don't give being to proceed focused,

Rick Bienkowski

Thanks All you the and so into with maybe follow-up right, have from of for that escalation dose some you a discuss Huntington's I the that, PRECISION-HDX the it. brining you're program, HDX got of learnings about and be WVE-XXX? at or in dose the -- a more clinically start rapidly And and maybe than newer could to you'll more studies, escalate relevant think if able HDX escalation earlier at you the than you PRECISION-HDX a the study? could

Paul Bolno

take question? do Mike, to you want that

Mike Panzara

absolutely. sure, Yes,

think patients. to lot, community, X. from how I how to we've and studies, that how PRECISION-HDX So, We've these learned a to find engage run learned obviously,

here a is important I vivo bit where a as situation the on we be. thing earlier, where think help in to I guidance we have need we're in mentioned us is, give data more to

that's in driven the clinical dose how the ongoing starting study I more levels has So to be we comes out window expect we important in think pharmacology, an what's to a vitro, has vivo once in a would different is would next PRISM engage and dosing and where and this every we're at again, scenario to once approach different platform study. what's those that itself, as as characteristics well in that -- very data guide going vivo target, molecule the of a we going would that anticipate that escalation from therefore generating and the be fashion in by data

elements driven our also some So adapted that of see the you'll we've have when we the study have the -- you pharmacology pretty XXX studies, differences see you'll by from are that molecule. there meaningful and see existing been

Paul Bolno

now phasing, those of that just are. able ability patients understanding Rick, around practice patients where identifying we're with thing lot for the terms good also to with a we're SNPX is, and point, screening to add where with apparatus screening do other the the SNPX, the around SNPX and studies in -- have by think to ongoing SNP, now more the efficiently to patients of those to I having that SNPX your a and

So the as the SNPX itself, medicine beyond at this. place clinical look to the the is operations just program trial we for of SNPX characteristics infrastructure the do of totality in broader

Mike Panzara


Rick Bienkowski

taking All right, questions. for great. Thanks our

Paul Bolno

you. Thank

Mike Panzara

you. Thank


of is question next Your Syed Salim from line with the Mizuho.

Salim Syed

the and Good Great. guys. for morning, everybody, color, thanks

currently me, second your there. call sites are three trials, the about site in can, had you Australia if in the of quarter for I given half Paul, Just on PRECISION lockdowns talked

end wondering you that? the And then the need you you some to give partnering so of in that higher just trials, is you close all Australia, here, XXX as if whether identified, will finishing ones from to much. Thanks give you than going and disclose us cohort? now economics we're close the So what don't are just milligrams patients are decide the quarter XXX% framework just lastly could on on the seeing -- update the are you fourth program you new higher site that into an DMD, XX you on the go there enrollment? that here, XX us back out? or getting to or those of you data potentially coming what that Street than keeping higher, plan go will this to you given can on to the how seeing milligrams, Number your two, to lockdowns on if with if color seeing there you COVID-XX still do you're and And

Paul Bolno

to HD, want on question I'll first and I'll you two the HD? Mike, Mike answer you, answer on DMD. your Thank then to let questions take and last questions do related the

Mike Panzara


were on having to is environment again. all, said and moving our of as up end, with say That first as the focusing clearly down, recruit. we that So, the ability opened lockdowns others along COVID last have open target, were but sites at lockdowns differences can impacting sites up I there have as a the that closed call, way

is that big communication shutdown, have right so things we're then redirect the different headed, with and impacted way today. the we in investigators, is these Melbourne evolving very the to factors data time first and -- our ability last and that but are to going reaffirming places have just good what if we're actually landscape necessary, have certainly happening we great really none it quarter, readout had which now cities opening and we're has was of the -- closing. but up, are been I with we're we've when was of -- an been anticipate can is where that one Melbourne mean, is fortunate the this what's So,

with sense most in make higher that before wait At thought of one point, the of it previously, the the as product to dataset In we the quarter terms making overall just definitive multi-dose of said framework go window. readout. to have away the I being from terms knockdown, the mean, terms that in to we've decision. see degree of profile we of this therapeutic may

the We for readout, higher preclinical at was perspective, ability this close from that go just best to have we wait so the being it time. definitive to to but a thought

the I'll to Paul where that's So the back pass it are for partnering. that, about question and with we

Paul Bolno

mean, changes as this data just, mean, up the data HD, at to I know, updates I track on If readout for we're to excited of remain and you readouts. the impacted timing that getting were on there we any XXXX the provided readout. And we wrap I first to mean, updates. quarter

retain particular it's to as we out of laid and for continue specifically, to and that or right carefully us are to that the to continue both think to where that, I As that is has say this team important something and as anything, data platform today sort therefore, program is it's you the as now often push done you of some about require we capacity how thought our data and move partner. and Mike very program deliver as percent because but I far this the the I for that economic, DMD XXX% something that around partner, we we what financial can we on and operating need I where study to think of for the leverage this deliver the and economics to we'll capability think evaluate or forward. deliver generate within forward, runway, means you

Salim Syed

guys. Super helpful. Thanks so much,


question the is line Paul with from Matteis next Stifel. Your of

Unidentified Analyst

Paul. on per for thanks is question. Hi, the taking This Alex

physiologic its program, of about of talk curious just elaborate -- for was And allow for with homozygous I first, on G-to-A along a more that ADAR much. Just can strategy your what the that, AAT? you if curious then kind the proportion bit and little you rationale am I AATD could that regulation on ability mutation? so how a of the to if couple Thanks have

Paul Bolno

focused in reasonable to amenable. are know who It's a Yes, patients about that's I question. our range, great we X% XX%. something

patient amenable XXX,XXX our are correction on worldwide patients number of mutation. estimated patients so worldwide, are to So, populations that the the XXX,XXX the this

wild-type restoring, we've by for concept of stayed allowing a physiologic production bringing protein the required. but regulation, the this meaning that kind of so, knocking think transcript, focused I as of used correcting around and correction on out, around then concept not the it physiologically can therefore be

the engaging circumstances. this since to the So, it's and it's that acquiring that lung, By under normal protein. which be be known protein it around lung [indiscernible] from to activating can to oftentimes result injury in responsive it that enables having as would

one this of disease, really is which treatment way the exciting about of is different So a bringing correction. aspect the the of bringing think I around thinking program

protein not a through physiologic So, of taking the augmentation of hallmark transcript, the therapy, requiring correction IV rather really or balance the RNA away weekly but which is and restoring protein mutant editing.

we're platform. more about we're and excited as about as different what in ADAR a about broadly, this diseases So it we excited space, think means

deficiency. ADAR look we be antitrypsin I enzyme and therapeutic AATD obviously, we model diseases at building broadly when in be this, proprietary Alpha-X possible about learning at now step as build more initial that the disease, we much therapeutic what for that will multiple us back look models the I it we're say, think but do we with approach, with this we able of So, think treatments ADAR, think and context investing and cross program, about are human the let to could

Unidentified Analyst

Thanks much. so


the of Your Jefferies from is Jefferies. question next Yang line Eun with

Eun Yang

have I questions. speculative you, more Thank

milligram we higher go, reduction go XX, year, HTT decision as hypothetically, on a HD program, quarter as pursue in still you see saw data So as similar would the that at you first point you a of XX dose? or mutant no expect if next at make what

Paul Bolno

stay on Mike's terms analyzing to that's point the exactly data. focused what in to want of we think I

we that, to we the at at a I believe a to as variety quarter, that we that of that of higher of look think other in So there? data being assess point, be point, biomarkers that do Are driven, as data there's data. part we variety if that's about going and see we'll there's Mike, dose will first ascertain any think a that we plateauing, do clinical have thoughts? and the once biomarkers to additional have outcome, at

Mike Panzara

No, going be lot looking there, to a we Paul, things have nothing of we're else I at. mean,

at is Pan a different, they what's the of be to of which that'll is differently, very least in conversation. be to this as the not part opposed specific, and meaningful, have it's knockdown which looked all So selective, setting,

Paul Bolno

Eun having that think, advantage the tools Allele-selective getting not of in we're readout. WV-XXX why I the therapy, But on for one of SNP-X terms it's

believe do the So in we're and program in Allele-selective we're have excited wild-type approach, driving totality first other the literature data that the forward assess that to we'll and to seeing grow sparing, the to quarter. and have in the be at because about that, continues this this we'll look to of we so, programs data independently able but

Eun Yang

this improve candidate, lot that so and study Yes, exon of what that's durability can informative, humans? in the to in dependent we data vitro understand production and saw XX% I the could in extrapolate dystrophin expect increase to DMD questions tissue model, you from XX mean, a penetration. normal, you program and dose of in up I you vitro on realistically the

Paul Bolno

is be I reserve that and that's that coupling have on see you production to think DKO exposure, production going restore. data correct and substantial us we're the a data, in confidence from speculation the a think the going we clinic, of with I phenotype tested study, I lot gives candidate vitro can in the the here to think, dystrophin supporting preclinical dystrophin which you that with

muscle I less indeed, is which XX lower granted confidence the confidence. into and that, at getting think we but in are give with having us an dose impact gives data us molecule, frequently, that dystrophic vivo

be going think that study reason. the that to exact we're pursuing I out that Mike for is laid measured

with DMD lot are the generate I want had know, think that who poise, having we the the conversations we're this we add we've to you to generated, supportive we're and be disciplined see to what that? do to data seen need Suvodirsen that able need and data, don't of a we've extraordinarily after I but that excited and to Mike, approach happens data, in after our the to community, experience that. do

Mike Panzara

look what thing as Yes, but unfortunately judiciously at, profile that to lot DMD captured lots really clinically, of and translate was study allows that it that of add way in assess way us I I preclinically have that the that take to is evidence different, suggests space the the you way disappointment this this is, that of get next responsible to can something into a think make only beings steps could entire would nicely, a have is about we we be we best that felt proceed. a we execute and determinations human to most here

Eun Yang

very much. Okay, thank you

Mike Panzara

Thanks, Eun.


is of Cowen. with from Werber Yaron Your next question line the

Unidentified Analyst

on question. the taking much this guys, for for Hi Brendan is Thanks on very Yaron.

ones from guess. quick I couple a Just me,

kind it I of to of five sparing of kind obviously, has in able in some you're HD, make updates First just different, there we're little check felt kind see like as results -- we're I maybe see wanted the talk exon gene to here. wild-type across looking space, and to example, to the stands. this on in And just assay, kind and seeing and and that. the huntingtin then, the the effect past, in where really check for skippers know wanted just kind sure of I to different between as just just differences the mechanisms, been of for therapy, on DMD, different of

trying NSA protein your thoughts is bar level gene stand closer X, are Phase or to really where maybe exon aiming with you're to this restoration for So, your of hoping you just the or we skipping kind to with we've see of that where ASS? therapy, improve Thanks. on for get bar really seen

Paul Bolno

wild-type question not bar, to of the mean, we follow-up, study, working I and an of first right something is restoring quarter. what pointed the to work, agree is our not data dystrophin short alluded is first relates assay earlier and an we think we're we to driving the in metrics, we something study now about initially that NSA deliver the could that's on Excellent, follow. that it would continue with at in a the that We be as important looking this to and anticipate way this it do the we hard were that continue to that assessment, and the I now answer is, as we're excited out, you outcome having context the anticipated, impact, would that's clinical as other on

I safety, those think to we work, and but on to measured us the muscle preclinical a moving want prospects the forward, question think are want the and ask on dystrophin see exposure, drivers to we're are, based about if first I also we really we is now where diaphragm. dystrophic skeletal mouse, and excited we them, we're phenotype production restoring key give the one be in with about addition think we're and in is which about not living, PN prospects should seeing that of chemistry of muscle, the to I be that's survival the heart what we're the is exposure just actually not these and DKO mice that a excited nuance sense

full these phenotypes might have, respiratory and are the dying from complications. So and cardiac

at intervals to muscle that us tissues we're is skeletal excites both using. really and ability the program other the beyond about what dosing this and doses those So access

go to think first I is want there's either is I'll to So Mike, but add that, forward, anything again, those and pass measured there you that this about to to excited study approach to lot about points? to a of be assessing

Mike Panzara

Paul. to Thanks, that. to add nothing No,

Unidentified Analyst

guys. Thanks, Great.


RBC from is Issi Your next question line Capital. Luca of the with

Luca Issi

of that correct? U.S. my all you is in to how enrich you. SODX-ALS CX all I actually actually IND so, Two any we data there, me; so, showed an that One, are programs, five it for think Two, quick patient? think will taking suspect I for for initial should the here. two, the XXXX be ongoing congratulation my are open you Thank the planning Terrific. on studies your and one trials for for you fast for planning for if one, that their progressors. are do the was timelines ex-U.S. in Ionis is about to Thank same understanding and question, such if progress more impressive

Paul Bolno

do take your for want the questions. you Thank you to Mike, question?

Mike Panzara

we in U.S. the study, regarding HDX, U.S., mean PRECISION the HDX where conducting and question about have we're intention sites so outside some Yes, some first Sure. the know, sites for have it's we our you as PRECISION I

as So multidose the is about. U.S., we've outside talked always

these So in that regarding be other in going anticipate the will except these conducting programs, we've for a be we global just study small studies anticipate NXXX, proof-of-concept are to and already studies, U.S., as we ex-U.S. said

would, so that. optimistic So our very able be intention. We're that is to that I we'll do

again… which was question, second the Regarding

Luca Issi

SODX, think for wondering this study. I about was Ionis Yes, ahead. as I just go

Mike Panzara

I rapidly progress it than patients, is of sorry little No, about study that, patients. progressive, I'm a year, other so fairly sorry, give of early what rate that. say yes, ALS we'll Yes, in one more CXorfXX thank you. rapid but ALS design thing they it mean next disease the a details about groups I is can more

overlap on readout that's disease progress in focusing a the those focusing population that origins on on be FTD, itself CXorfXX can factor population of disease, unusual, you actually make looking that to is the could target clinically. they CX that approaching and we're have its then is decisions have way allow will us they at condition, really will to The how ALS, the which something we're fairly, not just both to we biomarker these our going a could patients itself. if program have So, be really that are will,

thing the progressive as we're level. focused a how that's So rapidly it. single, target approaching approaching biomarker we're on Again, engagement it at

Luca Issi

guys. thanks Great,

Mike Panzara

you. Thank


this no questions to Paul conference now Bolno. further to at turn the like showing time. would back I'm Dr. I

Paul Bolno

day. Thanks We everyone the employees joining morning hard for and work patients. a call Have review our Thank third you. thanks for with their speaking nice soon. to look again and all this to our to update, forward to quarter you commitment


your concludes Ladies wonderful Thank a today's conference. and and participation you day. gentlemen, for this have

disconnect. all may You