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Wave Life Sciences (WVE)

Participants
Kate Rausch Head of Investor Relations
Paul Bolno President & Chief Executive Officer
Mike Panzara Chief Medical Officer, Head of Therapeutics Discovery & Development
Kyle Moran Chief Financial Officer
Michael Lin Mizuho
Joon Lee Truist
Mani Foroohar SVB Leerink
Eun Yang Jefferies
Call transcript
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Operator

Good morning and welcome to the Wave Life Sciences First Quarter 2021 Financial Results Conference Call. At this time, all participants are in a listen-only mode.

As a reminder, this call is being recorded and webcast. I'll now turn the call over to Kate Rausch, Head of Investor Relations at Wave Life Sciences. Please go ahead.

Kate Rausch

operator. you, Thank thank our and quarter joining today us operating Good business you progress discuss recent first and to results. morning for review XXXX Wave's

President are On Chief Panzara, presentation morning detailing Moran, Head and provided release Paul website release, me news Chief call Discovery Officer, section Executive today Therapeutics our and the accompany Bolno, Dr. slide with a Medical and update. a Wave's, financial Investors we Development; and and of Mike first Financial Chief Officer; are This Dr. issued Kyle results www.wavelifesciences.com. webcast news business This a the available to this quarter Officer. in our of

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

Paul Bolno

the on joining for you morning, us. Thank Good call. Kate. everyone, Thanks,

into after and year give we incredibly which an development. financials. During the Wave, Kyle to has our will call review clinical stereopure three will start cross-generation the today, briefly It Mike I productive remarks, update opening oligonucleotides advanced as will clinical on some an provide our for trials been

regulatory and designed candidate WVE-XXX, clinical WVE-NXXX. and proof-of-concept and with approvals initiated towards candidate third our chemistry using our important the We've trials first in trials to biomarker-driven These candidates targeting in SNPX formally are investigative WVE-XXX, CXorfXX are backbone modification. PN PN also program, ALS our clinical chemistry received disease. designed have designs initiating adaptive We XX DMD, our for in Huntington's exon novel enable FTD; rapid

from modalities, advanced enable steps Next data different class. insight well chemistry ADAR its we that We've with PN also editing types across as most endogenous which the in substantial targets. for year, into and as progress we believe clinical about expect tissue decision-making provide trials these next made these programs is our capability, will

in data in have breadth We generated RNA central vitro XX, including an across presented editing a vivo in ASGCT nervous in is presentation demonstrating and being in oral tomorrow the this data, of Much of Meeting. activity the May editing vivo systems, system. Annual at

promising Our alpha-X antitrypsin results first has generated to ADAR are in vivo program for on data we this initial disease track quarter. editing and share

define pipeline this several results remaining inform our our of data clinical for us mixture-based years we At therapeutics, foundation the PRECISION-HD Our now in set and is and RNA from to differentiated apply and first-generation ignore with unique is rather of candidates, principles orientations PRISM every to further the design platform This reality trials. which therapeutics. the choosing the platform. enables advanced others we have resolution In of we distinct programs our than backbone linkages we drug control X-dimensional developing rational to of for that impossible our to stereopure Earlier and discontinuation each exists the can of the oligonucleotide. importance single announced molecules out oligonucleotides. the isomer embrace our profiles of year, and stereochemistry following

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the independent further significantly expands And to oligonucleotides, splicing, of of years, address enabling addition select this talent improve sharing to editing of advance of principles, We wealth modality data the the sequence collected beyond therapeutics In anticipate to our oligonucleotide a ADAR past the in innovation our profile of or leveraging of pharmacology the also ADAR cause to modifications the diseases. have type Separately, silencing toolkit what preclinically, genetic we Research this major and controlling our chemistry tissue an that from a therapeutic context understanding over chemistry best modality. design our are potential toxicology. has we further more backbone influx capability several editing and was The new later to stereochemistry seen of PN platform. in the root based year. on emerged of at PN application advancement Day on and us

to designed proud chemistry. we comprised have over now this innovation advanced with programs. the on update rapidly turn including first Panzara how many approaching of clinical call Mike? PN an to the of PN of Our PRISM are next like chemistry. and proof-of-concept opportunities quickly of for programs generation the pipeline Mike for clinic neurology current is I'd our of we to I'm extremely

Mike Panzara

development neurology-focused us the Paul. Thanks, a done here. PRISM throughout preclinical and foundational currently provided of of been robust illustrated work moving with diverse and through has stages that The is evolution has portfolio that clinical as discovery

all As nonhuman programs of including Takeda. primates, yielding results, discovery with nervous collaboration Paul These approach. programs are utilize and multiple engagement system central in mentioned, validate exciting in the programs distribution including our which of our PN preclinical chemistry, partner and our target the stage current further discovery just

high unmet continues of need. with portfolio disorders Discovery oligonucleotide progress this to therapeutics the of Therapeutics upon treatment maximize the build neurological Our for to potential

next-generation discuss clinical currently I'd like programs in Now, to with the development three candidates.

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drivers the are these through of proteins to expansion phenotypes. expansion trigger hexanucleotide mechanisms. the diverse the mutations DPR are selectively CX toxic repeat downstream transfer, or which designed quarter candidate both to selective toxicities, the identify but causes published variety RNA variant translated goal our being multiple and toxicity common These is of is lead CX first to in a repeat work in and FTD. this the XXX both pre-mRNA common containing validate repeat in site toxicity. and Our transcripts, two FTD. Communications. the advanced clinical and in of and expansions knockdown The long into dipeptide also achieve targets to XXX the candidate targeting expression. a the ALS hexanucleotide simultaneously and with on a WVE-XXX of suppressing CXorfXX foundational cellular pathophysiology study allowing hexanucleotide one proteins is most that genetic devastating the ALS Nature that they target DPR-associated CXorfXX while And drive RNA single the used CXorfXX transcripts underlying basket-like their CX of for tissues deposit first was protein contain own, In of

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potential observed chemistry. target of intrathecal CNS. us approvals non-human initiate month In by unlike first But early the placebo-controlled global XXX our in throughout human XXX While XXX after to once double-blind widely discovery WVE-XXX. a Takeda distributed advanced was they administration, candidate for a engagement One transcript study XXX. the in were the PN we trial target to non-human candidate is received possible in and we manifest targeted experiment undisclosed target the were sequence in next-generation chemistry. of uses monkey allowing quarter the received randomized primates CNS engagement substantial the led this homologous our Phase not that target multicenter XXX, including In studies most striatum. highlights the primates an HD. assess to SELECT-HD, of ethics XXX, possible for this Ib/IIa regulatory injection knockdown the CNS to and CNS again with Like the XX-milligram candidate therapeutic for this throughout collaboration This of single of

active and disclosed in inclusion other will be approximately studies SELECT-HD and Unfortunately not safety the in to in able assuming with recently period PRECISION-HD study be exclusion efficacy criteria. enroll based permitted received data CAG expanded transition they washout patients repeat. a the on who XX targeting association the to from with enrollment carrying will Patients tominersen are SELECT-HD. of meet after patients SNPX We GENERATION-HD treatment to

systemically An Although rapid an more target enable and are Like in to those biomarkers to of eligible for patient FOCUS-CX first dose activation XX administered and is GENERATION-HD of to and optimization changes study chemistry. patients designed, frequency also determination we independent adaptive objectives has for PN and splicing PK type candidate, screened basis key huntingtin, Duchenne in to who entry. study. in in expect will in escalation with evaluate course including committee DMD Huntington engagement. soon. placebo CSF Key Exon the dose over our design that mutant dosing to of chain our be SELECT-HD Muscular wild WVE-NXXX This received applying dosing and addition amenable underway exposure and the neurofilament site tolerability, safety is light XXX data an each guide to plasma our first is are Dystrophy skipping. candidate include stereopure ongoing Clinical interval or unblinded cohort.

editing capability also Dosing Paul? initiate As every assess back an we other with year. initial XXX-milligram and to our expected and dystrophin XXXX, In in targeting this trial boys at to to kilogram muscle there. clinical ADAR call backbone we've NXXX upcoming treated that trial effect. initiated format weekly. evaluate Since the result an will Once to week trial profound production with other milestones regulatory double chemistry up this with The in DMD. clinical is XX knockout the approval for both of every powered application rescue pass application. I with model now NXXX over utrophin PBS of will to dosed an the and increases have we whether had submission of again, development XX treatment drug modifications compared shared dystrophin, a of previously, of dosed concentration is or when March, lacking to clinical DKO safety. a Exon discuss applying mouse XX or then as received aggressive open-label in surrogate milligrams first-generation per PN mice week Paul

Paul Bolno

Thanks, Mike.

editing generate positions our to RNA with we of at capability believe compelling results has this the forefront which others continue We us and ADAR many advantages editing over space.

RNA short a editing recruit editing fully employs RNA oligonucleotides As our called approach reminder, to modified enzymes ADAR. to chemically endogenous

RNA using nanoparticles chemistry, the compounds us AAV with and avoid vitro proprietary in vivo which leverage established activity manufacturing processes. to or XX% vehicles have as in oligonucleotides. conjugated GalNAc across stereochemistry such Our date, primates to we durable editing vectors us non-human enables demonstrated editing To delivery of and including PN are systems ADAR and up allows optimized to in our editing

oligonucleotides editing ADAR Our are highly also specific.

targets. Our practical editing or variants to number the as door targets of modifying greatly of protein for address protein that opens are the RNA a applications, well up-regulation landscape discovery to can disease we function new such as approach we ADAR potential applications and advancing multiple expression. work and These therapeutic restoring evaluating of as potentially expand editing

and threefold treating Our allele allele, the avoiding all humanized to or enables AAT protein. off-target of editing of of the SERPINAX hepatocytes both coded to increase sequences program liver and efficient aggregation assessment pharmacodynamic in the mutated increasing mRNA develop by and we and mutation Encouraged editing first correct the Last upwards and of these results, Z in proprietary the SERPINAX the we mouse wild-type misfolded a RNA-based wild-type manifestations circulating while successfully wild-type reducing protein transgenic a changes uses moved both vitro, ADAR alpha-X led is which and of protein editing approach humanized oligonucleotide AATD. ADAR this antitrypsin alpha-X to successfully forward human pharmacokinetic a functional containing to AATD, to in alpha-X addressing simultaneously that transcripts by SERPINAX disease of a of in thus triggers vivo. antitrypsin risk lung deficiency by levels simple GalNac-conjugated demonstrated single ADAR DNA. XX% model to a year, permanent which Z

and we These in half in of We at to expected this a a candidate XXXX model busy year. enable lines. present execution lead data are as vivo In in additional the for summary, next-generation development is in to share the from in later time to clinic. pipeline expect are potential and on our XXXX track studies a Wave data time vivo of scientific this congress inform year results well preclinical advances optimization as as first

Research proof-of-concept will expected are PN As data. provide potentially of our each and our you clinical with vivo three validation that the that capability. with ADAR insight unique speaking over quarterly clinical will mentioned, for next later expect novel about financial at heard just RNA our we progress year, I data call Chief this today, the report to questions. to editing look Kyle? details editing And turning on advancing platform our addition We're chemistry the forward update our Officer to making into programs in AATD about and Kyle to I platform I turn biomarker Moran, call excellent Day which rapid a share in to our now call. results we before further more over our Financial to

Kyle Moran

not We million collaboration first This include in April support in million $XX received that early does we committed quarter ended with marketable under the additional research Paul. $XXX.X and our equivalents in an with and Thanks, balance cash Takeda. securities. cash

compensation-related other and activities for offset HD and compensation-related increases related and ALS and by compared of program G&A in quarter expenses expenses. compared external well the were clinical to XXXX the XXXX. Our to compared external a million as expenses as the the CXorfXX million to $XX.X to preclinical same for million $XX.X decrease as discontinued million for first other FTD. as $XX.X This $XX.X last programs total partially expenses to and quarter primarily decrease $XX our year related in for decrease driven XXXX by external program period last our in R&D decreases to year. million with operating suvodirsen expenses $XX.X were million related as lower our were first was expenses, in

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

or this potential reminder, payments under collaboration. payments not does other uncommitted Takeda include our milestone a As

Paul Bolno

the we'll that, open for Operator? questions. Thanks With Kyle. up call

Operator

Thank from first will Mizuho. Syed you. [Operator Our Instructions] from come Salim of question

You may begin.

Michael Lin

much Hi. on Salim. Good for morning. few our A so for questions. taking This is if Thanks possible. Michael Lin

on being CX to would -- many these be written follow-up trials adaptive are about after the to protocol hundreds design, the be just trial able patients be, converted potentially to and of enroll the registrational? First wondering how they to I'll that.

Paul Bolno

you. Mike. call pass over I'll to Thank the

Mike Panzara

Yes. Hi.

So the the as I really is mean study the way as about it the we collect -- to to as once designed necessary. information. recommendations the study be see, enable study on can from expanded to additional to -- to you necessary next to allows get we independent made it be flexible adapt committee us able steps

to see the adaptable clinical wait So, have enable show, it but FTD. to to I way to need we meaningfulness understand think and is it ALS to to, flexible both us make we'll data our in what and it intention direct the to the

Paul Bolno

based number on committee's So, assessment I then. on patients of the expand can't

the yes. that's So, if question, specific

Michael Lin

you What Great. one did on data. for pipeline will move or clinic specifically this And be versus you looking into if the would programs? And the how the on forward forward it not? move upcoming prioritize other AATD to

Paul Bolno

generating one of and the the prioritization identifying model, the for reason the we the driven based really protein. worked was So AATD on on production

interesting, percent progress does is. is the but on working what editing That's what medicine on protein. not the a a again, it drives So generate

we'll protein that protein, production, features not So, just obviously evaluating are one functions. production. be Other be protein protein but will

and to translation. going able decision of assessments a at be those that's to number guide on look we'll So, our

Michael Lin

targets? great. how in one what Okay, And Alzheimer's disease the are about ASO side? donanemab After potential mentioned think you. Maybe last terms should the on treatment, you we Thank data, today. about specifically thinking of from

Paul Bolno

make -- want about you Alzheimer's. on So be I to frontotemporal thinking might we're just just for dementia. sure about clarification, thinking not I make sure want to

want we the have sure therapeutics antisense of correct. is as to neurologic disease discuss, I Alzheimer's broadly, think careful today So, to discuss get mentioned frontotemporal the dementia the and of didn't your that for treatment area we want happy But therapeutic. more CNS make a I dementia otherwise, frontotemporal question, treatment I it's question be just one if that we FTD, so and but diseases we that's target to So degeneration,

Michael Lin

Yes, that helpful. would be

Mike Panzara

I going say... to was

Paul Bolno

Let's just his answering finish question.

Mike Panzara

is with CNS very in you that yes, the actually the to able was in FOCUS-CX -- preclinical about models excited getting being saw I the the patients to I we're us going on see cortical FTD effects mean emphasis say make that, we as study, to able and to to going measure of be the be we're an clinically outcome using study in be want you'd at some FTD. the have access cognitive on to FTD our to effect that change that to measures get -- It's clinical able question.

Paul Bolno

we mean distribution think data see brain. vivo the about mouse think studies I back the intrathecal think of neurologic I across really and I compelling broadly, if of just step I mean is great that sets we number in that's one more a diseases Mike the shared addition in to

It's we around distribution. this colleagues to see discuss a neurologic of distributing think as the not So, are the I intrathecal necessary diseases, about we whole administration our some space this. variety for than regions of think different in of that brain delivering

So is we see this addition we distribute. can What with of us broad highly this do antisense controlled. the PN oligonucleotides so believe distribution,

So, stereochemistry mixture we're of compound, that the actual of data beginning the engagement because the reality a with XXX,XXX, we're is, is generating, the XXX,XXX addressing assessments differently. of molecules value of different with distribute it not we're are seeing can that XXX,XXX and dealing target all the

we're of knockdown know durability. seeing the based single the I drug, on that design is a single seen is oligonucleotide. having that by the So And think of that we benefit what also we've

the adaptive piece, exploring that and in design the in going said, to testing Mike we're as it So be clinic.

whole chronic of And so, as diseases, is medicines it different of importantly about dosing host frequency. we administration on a think

to able something in continue frequency for dosing not that sacrifice to So clinic. to being we're explore potency excited is the

future about currently. diseases clinical oligonucleotide that be of So the across a way of and in neurologic antisense the we'll we for further treatment think the assessing as think we data-driven three is studies promising future

that explore treating answers So I but question. looks diseases that for always to more, the hope future oligonucleotides. with happy your I genetic bright think We're

Michael Lin

just was CNS helpful. super along with the in guess referencing mention what of other That's the was release indications? I Alzheimer's I press

Paul Bolno

Okay.

Sorry.

Sorry. No, no.

you're I -- now so talking example said thinking -- - been about Where I large -- think the that for represents we we are said indications. we large the example is going we've and indications. where for large list in other which of that's neurologic why exploring indications, know we're are Alzheimer's Parkinson's, what targets holistic that

focused is. to apologize the as potential on I for are the what that exploring -- we our opposed you. thank So pipeline we're

apologies for question. our So your misunderstanding of

Operator

And will Joon from come from our question Truist. line of next the Lee

You begin. may

Joon Lee

for thanks questions. Hey, our taking

of addition all proceeding the intracerebroventricular I'm you intrathecal cord, your give has to more route I a improved not does from for programs aware in delivery? have compared different with prevents company disease. and of that. of believe disclosed considered route IP Huntington's recently that any chemistry, you using and backbone It [indiscernible] Another direct For to new you CNS access doing

So, I question. would a appreciate some follow-up I if you there? have perspective And could provide

Paul Bolno

true problem about Yes. first drilling what to we problem are permanent catheter approaches. think holes placements and holes different always trying for. question for other I about what is we think solve When I to always about and opportunities mean this is our for think anything, there's -- and delivery

at currently studies. now shown we nonhuman in central of in see nervous think we the terms to that distribution injectors intrathecal that looked is I primate available. correlation the ICV We've intrathecal as date tissue. So, data and CNS generated in to in think access mice system We've about we've

also -- look we're for less risk. without the it's if So we assessing administration that in causes and not again the date -- durability also question to see the which clinic to frequent

CNS they can catheters in changed. need get permanent clogged. to be So, drilling the They we

medicine is comes And so again to it is what every -- down and the really different.

PN speak and think So with as -- for are so What demonstrated we now intrathecal addressing can't that. is delivery we we assess themselves, challenges see utilizing multiple what other using about for? right the solving what we medicines don't tissues we've across they're on we distributions companies the mechanism. enhancements are our And ours we

up administration. come have add. solve and you to that the As there's to that at in with current right could we we know other we doesn't but now I problems to look seem anything Mike the don't indications, solution the durability if Could address different future. want want

Mike Panzara

go say gives No. in form you're I'm -- It's thing. have you access want like to -- would - you're for. the to you the going for administration same just general looking of can just the that simplest to I you you

we given that necessary that of parts especially ICV single something a to we would brain diseases the and leads indicates effect Paul approach do. do of to about when progress simplest with need any all as we've through So be after durability us intrathecal that what's can the you're the with the these accessing approach do administration neurologist doing catheter talking don't doses the made that in can

Paul Bolno

I I had explore the and able we've an of to think mean mean now now I multiple other we models have extensive amount across thing -- the multiple animal benefit with been time species.

intrathecal again, nonhuman in in ICV primate. So mice

shared we different look concentration data at with understanding to our levels different with in clinical Huntington as chemistry. We experience distribution backbone also have

with that So colleagues the as we animal PK/PD us -- in that's that exploring adaptive the changes PN into totality going backbone to generated in think we I generated clinic. of the generated look other the designs currently we've of our we and and totality through that at the translating the that think meaningful companies clinic are of data see implementation give I are have answers

Joon Lee

approach but another guide with used presentation it. Got the looking you're some RNA talk RNA ASGCT. about taking And you GalNAc-conjugated that's to circular any forward input should you. company? some out tomorrow guess different perspectives ADAR the tomorrow cons Can on approaches? focusing between by be on can I find guide we on what of Thank you being at wanted pros differences versus share just and get and that to we'll your tomorrow,

Paul Bolno

speak an about GalNAc pros mean Yes. others. can't approach. let's the about approaches I cons treating. speak I tissue We're all say GalNAc is the other targeting of interest. of for a importantly to approach can target which is and I more for learning the not necessarily our

we platform capability distribute, demonstrated editing from this data where when and that built the of our the generate short and we an oligonucleotides one of the can as go well there. So beginning with advantages ADAR is CNS we've some

is non-GalNAc-conjugated of can and hepatocyte and in we've looked distribution we're the hepatic in we so type because vivo because target AATD, CNS, obviously, target becomes GalNAc that looking correction. a done So our a looking an in cell at What then for advantage, at just interest.

So liver I we the think specifically. GalNAc, platform as about what's is really a perspective but think GalNAc well where using from important the can without platform are we exist

learning platform our data and think demonstrate around interesting we the need that conjugation oligos the to across and oligonucleotides in vehicles. use think to experience apply learn can both and of this to from about stereo-controlled approach various We advantage we don't PN-containing past for specific ADAR context, even really delivery species a and I that take learnings take GalNAc on targeting. generated platform stereo-controlled of we've clinical studies and that continue got hepatocyte multiple all we've So

field, I parse happening forefront to there RNA think what's and start across to out data. be more as those a we're to tomorrow have editing more. we'll the that to be really be the ADAR of at excited we to tomorrow share learn But again presentation able about able

Joon Lee

you. Thank Great.

Paul Bolno

Yeah.

Operator

from will from Foroohar Our question next come Leerink. Mani SVB of line the

You begin. may

Mani Foroohar

ask over is I'll one for the Huntington Thanks those bit a into taking little patients enrollment. eligible? progressive rolling guys. one Hi relentlessly look a GENERATION-HD we obviously, many quick on worry I that, how placebo When still are question. with of disease. SELECT, patients at

And in accelerate hiccups you you couple mechanisms given pursue there there on the delays those of give meaningfully in process they whatever likely are and So patients of portion that first the based when were a your changes may of than how there now to enrollment view be does in to much for were those start screened patients some generation. way trial on or secondarily -- of other SELECT? more of along previously? roll GENERATION can for head a whenever are severe proportion that completion were And enrollment over, they

Paul Bolno

the question off pass I'll to Mike.

Mike Panzara

Yeah. No. Thanks.

So stands is been regarding have been the movement active to patients receiving from GENERATION-HD, right now hasn't don't treatment. -- disclosed whether the it placebo it they've patients or way

the relatively that but want And choice make soon they exactly they've when have not happen we're do that about hopeful and what we're patients disclosed hoping now sure to whether can will to then the as we're all patients transition. will So that that happens be, that we that been receiving.

have SNPX. be Second of whether and exclusion, for of both they which are to criteria, patients that to is there going including is will all, that have progressed inclusion inclusion rescreened have our why out they possibility

important So we the inclusion/exclusion appropriate be have essentially an But expect of them think that about criteria. XX% population, to the about we'd will as overall are SNP.

from operationalize about We've we've Regarding to to along things a from lot learned PRECISION-HDX learned the other lot administration the the PRECISION-HDX studies. more efficiently. and move how operational GENERATION, things help intrathecal a

lot We a site GENERATION-HD -- allowed experienced PRECISION-HD, between has the our us to of process. have overlap screening physicians in to and which get

we have variety including of that addition SNP do helped of SNPX. able really have SELECT-HD accelerate to We be we'll the that of -- comfortable to the feel identification. know new higher for regions that There's laboratories make a things representations accelerate recruitment have us

doing So that comfortable we're there's have will of help. -- that we're variety a things

data there's the going a committee design be the recommendations. -- to the with looking to along next In adaptive and way, guide make unblinded whole to going be is at addition steps

is data So PRECISION-HDX change itself in in generation and X. huge of and that versus a

Mani Foroohar

All right. Thanks.

Operator

from line Our Matteis next question Paul Stifel. of will be of the

You begin. may

Unidentified Analyst

there seeing for I nonhuman on maybe you question. A Appreciate little some primates with XXX the that nonhuman the quantify biodistribution Thanks a wondering This primate, of of for on but the could XXX taking in if you SNPX. but curious bit you're was knowing engagement on the of Paul. exon that Alex you're the mentioned potential helpful? target secondarily, then in questions Thanks. model, is in data couple And would be your really exon one HD? as anything I'm if really fragment for using one side target that's a And the PK/PD driver disease XXX pathology modeling generally not you mHTT. thoughts a say can of

Paul Bolno

to want do Mike, you start around?

Mike Panzara

Yes.

primate brain, So the to in achieve the primate would are nonhuman the though it's clearly we able what -- we think what be nonhuman the I gray what compounds, regarding engage deep data, -- very based I for throughout mean have the including target predicted we are distribution concentrations striatum from the in say on that can target that not BACHD. data in about engagement SNPX I the structures to even

dose able So escalate -- to again be and a very engage large window target. to to

have data engage and get preclinical that quite matter are regions that the we think comfortable we able I So that we are on based the to into targets.

right and close and will we're able again as tell believe be and committee the dose that necessary. at active So is that adjust then we how starting the to beginning pharmacologically we us a then from to are

that. So that's regarding

be bringing Now to postmortem, mean, we that would exon to in an exon exon protein, of terms is of when the this lot mean, X, said think previously and it relevant there. we I we've extremely also what Nonetheless, most those seems X be down on to we're so…. expect expansions. mutant able from impact long and with X I have a -- this as is data, from

Paul Bolno

Yes.

antisense I I we to exonic intronic therefore should the oligonucleotides and the repeat. hit can mean. piece X. I the think independently think, reach of that. hit think, and is it, But Just most questionable really data still data add important really, so beyond we Mike, not to or exon I is transcripts long whether as still

think, I think the our of potency. chemistry with go durability, distribution terms So enhancement I with general SNPX in think X a of what targeting can as PN seen for and back we in ton about SNPX, and and of we leverage experience we've

is down important yes, substantial driver trial the and and is. as a we doubling distributing in about I and focus down of silencing is, that the we're is think first that clinical to can our a knocking think disease But production suppression learned is protein believe post in and mutant Mike see pathology and sparing we've what mutant mutant CHDI as a alluded wild-type as efforts lot I protein. protein important

and be way believe data we'll And using And set so assess established pathology. clinical be to we wild-type able SNPX which two that that address mutant the approach of sparing the years out PN is again treatment with is generating reduction ago to chemistry. the the disease we

Unidentified Analyst

Thanks so Great. much.

Operator

of question Eun come line will Yang next from Our from the Jefferies.

begin. may You

Eun Yang

questions. Thank you. few have a I

on The AATD first program.

but mentioned, protein, wild-type then shown function. producing already just you've so AAT you in primates, editing non-human apology So it's efficiency, not and XX%

on So needed protein wild-type of see benefits? AAT question What's or is one. to level? minimum clinical question the order you do XXX. kind that's And to you what some is a in is question number level second that, So know of

are doing activations. you So already site

the the from And when the April, Takeda Would you've what in from that data amortized Thank this in lastly -- be similar to how data trial? clinical should $XX past? statement? would million done you. in $XX million So we be received income that additional expect you --

Paul Bolno

the Well All this going news a the to table. you're good -- right. is question around get of hear voices lot

Kyle question. take the answer I'll great. to and treatment one the it's AATD I'll for one. can second So your pass Mike

in important and we of is do how Your in data that's how that upcoming terms look we question advancing at this looking at AATD vivo are program.

think on -- because say, I in think of I that human levels that let's kind generated be looking that to able one would looking we'll at levels. and antitrypsin protein alpha-X towards But -- they're humans, be in protein of at the to expect about model think be in at level. we're you we model when can to model where spot think generate is different, protein. And they're the all I SERPINAX you're

have off gaps weekly basis, in a be degrades protein and have to threshold products. the on sees protein protein one date have of they the treatment. be that end, around then because the infusion to we patients product infusion redosed clinically XX to micromolar That's of tends number that of at the relevant. so think kind these basis these level to And I tail know the protein kind a for patients the

threshold you know we the but where are those complications. that the not criteria we pulmonary only if kind correction think maybe don't sustained treating can minimum have I at you're can hepatic have see could that of we level that treat really this levels that where issue, at drops

that And that think share be those key that's we'll important exciting. replicated be we broadly is of see exactly the the assessing but to that functional, we'll would is the it data could demonstrated vitro of that protein I and in that in the was as just that generate the be think before well that from for we generate to think we've protein and from I not AAT there assessing we in models production, as I point the piece that the want that now But us as terms model. correction more translation. data animal

program, don't as transitions. target but to able how bring make sure think I think to ADAR I patients going been well indications I we CNS really taking to to-date of need So think importantly editing where deliberate we're indications, in more represents the where GalNAc data this it around a Wave's variety one for about the And thinking approach neurons. excited AATD that's us to program the broadly we've to generate ability into preclinical that's we across position whole why

the a at we corrected that So in of can are questions any this hand of if I'll And able because broadly. obviously demonstration variety your pass -- But over be there to vivo Mike a there's on approaches to that -- we'll I be question there? first questions is I'll protein think look and more take. now. not just study the that any to able whole to address

take want you one? the do Mike, So to next

Mike Panzara

disclose whether from committees going there's meaningful the comes that at of -- those I types I independent in a informed going And any time in coming year I and that's to the the moving feedback this a regarding -- be And studies the and to to And indicated, time of to have we'll the allow is greater I of and that we given is -- then studies going meaningful us studies as to also of the data data. number we're mean throughout the continuous whether there, insights however these good allow share studies when -- to decisions underway by the adaptive we'll with be and be throughout enable provide of anticipate mean this And are from soon data year. biomarker are we be. will -- how we patients next. and have will from into data sense flow mean that very designs feedback us Sure. course us dosing have that are specifically we that and point proceed, going mean that exciting. have the XXX, three what what make But I to in we the receive chemistry. year how what a guide data next regarding going during to

of dosing site in how be that's going optimistic So and now driven we're soon. activations fact now. it's patients obviously get by we're how proceeding It's given quickly be to sort and we going to those the

Paul Bolno

got aggregate an when about the of different is think principle running is at and just kind of studies data running than you've it design it end. But then biomarker-driven where then card adaptive we to the which notion put the aggregate the important studies and analyze and

And committees could an where is I way an now think fight think with generated inform there's those should as and times year we committee I that's of to this being share in next evaluated ongoing Mike said, data independent things. those a variety data. by running and studies data going

million? able to $XX the updates it's said want you So along less guidance way. Mike to take little Kyle, the provide be a specific we'll to as and more

Kyle Moran

We the amortization. way payments for gotten account And accounted we've upfront and we've for thanks revenue to the committed correct. that question. and cash GAAP date is Eun with your that payments assumption for Yeah. cash your other in would same

Eun Yang

Thank you.

Paul Bolno

you. Thank

Operator

Our line from RBC. Luca Instructions] next of [Operator Issi the question is from

begin. may You

Unidentified Analyst

here. for Oh, on great. questions Thanks us. of for Luca taking is This for the Lisa couple question. A

detrimental we from there and obviously versus placebo seen that we placebo to may seems sparing brain. And seen one, Phase Roche, directionally impact second in high data? the have So dose-dependent not the to it chemistry. have a possible is here? me outperformed caused you've read do in SNPX old there a volume impact on Did that the that detrimental a discontinued question, a with have obviously so, SNPX have have dose it's this X wild-type if or had and first ventricular you think may the patients same approach And Ionis the and data increase as you

for or what is chemistry plan SNPX? and forward? to SNPX only SNPX for planning the wondering Are the going you Just PN explore

Paul Bolno

Thank your seeing only else, is from version everybody outset. everybody it you. view To of we think the take we're like seeing and the as else to first I have what --

So it's hard to comment they on saw. what

they you I what a out pointed was objectively those clinical saw striatal. clinical which measurements dose-dependent think were importantly, change in measurements cortical and and

think was it think it's a jump to distribution. striatal distribution there's So than -- just question I I broader a

I function of the toxic that XX% drug. taking in know of one on discussion one think that hypothesis of thinks been loss I very, the animals wild-type as and in call one have data people on the this about data just both below after obviously function well saying of So that two we -- laid a And point that One approaches as of normal a think out think well. safe. it lot toxic Roche's as We biology of about there's there's context Mike very disease in I of your think characterization studies sparing. done shown is XX% if to the gain and reductions a do

reduction a one those disease. reductions for while think of already the XX% the studied are who has phenotype. dealing with happening a What as we explaining under are of those XX% now is in of of that -- normal a in remember of that are animals patients setting been And a reduction. that on that being have to stress in Huntington's we're patients, reductions are the clinic in that the progressing under setting I were situation were kind the

to function feature flow. CSF think CNS, whole totality neuroprotective are really involves, important cilia characteristics. wild-type of about of has other one Those So, removing the of the a and functions host protein including which

yeah, that. why I excited that's needs explored. seeing something be to that's So, we're think think And about that I

studies that didn't think on we looking happy also analysis in we the progress. were were that, at patients the I

for Now take where that is. it

we NFL. characterization, other or as counts white and and increases protein elevations in didn't see think, I

as SNPX. of as about oligo wild-type So can why with I totality think with the wild-type approach yes, It's apply believe important. if generated excited data sparing, think of the well early question that's a SNPX ready the both, clinic think we stereo we bringing is SNPX. have being into PN approaches I controlled why about and And we're driven sparing the your we and to around

I with think the we're approach -- measured chemistry. PN going

resources to and as and the measured spending SNPX think as SNPX Mike, Mike the approach is the yes, I let's a before design now get back data at prepared SNPX. I use allele-specific alluded trial chemistry within that right driver of are is HD, with to PN with more if totality on don't the looking But we there's... to go know approach. with

Mike Panzara

a been from just my have could the mean No. -- non-selective detrimental concerned I effects. approach mean listen, that -- I we've beginning,

need there enough to we're a we part wild-type said be study. that data III It's that -- There those we what have We for which initially to patients. been we're important we're happened assessed patients what certainly, making have who SELECT-HD. to not now our We've concerned an doing. had wild-type allow tominersen of because be have on, do enough, are whatever and why would But -- But of that unfortunately, first we're said Phase into why effects of lot understand. with that's doing we concerned happening that is assay to that, to is we're consideration the not available. could out are has with set treated reasons unfortunately, we exclude

observation. an So concern. be It It's it's needs a to studied.

that we're because it's we study the it believe, and important. We hoping now these to asks community have the questions, tools

Unidentified Analyst

for my questions. Thanks taking Great.

Mike Panzara

Absolutely.

Operator

over Thank any to, Dr. turn call further in for Paul you. And Bolno to I questions I'd remarks. the the no queue. back see like closing

Paul Bolno

Thank updates. quarter their Thanks We hard to call employees to commitment day. nice everyone soon. our speaking thank look to patients. you. And a to first review again you all this the for Wave for XXXX and work Have forward you morning joining our corporate to

Operator

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

may disconnect. now You