Wave Life Sciences (WVE)

Kate Rausch Head, Investor Relations
Paul Bolno President and Chief Executive Officer
Mike Panzara Chief Medical Officer, Head, Therapeutics Discovery and Development
Kyle Moran Chief Financial Officer
Joon Lee Truist Securities
Salim Syed Mizuho
Lisa Walter RBC
Alex Thompson Stifel
Mani Foroohar SVB Securities
Suji Jeong Jefferies
Call transcript
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Good morning and welcome to the Wave Life Sciences First Quarter 2022 Financial Results Call. At this time, all participants are in a listen-only mode.

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

Kate Rausch

you progress us quarter and results. thank our to XXXX and business recent review morning for today joining discuss financial Good Wave’s first

available me Kyle Chief this slide Medical Paul the Head of of release are in Chief Joining issued and morning Officer; Financial Officer, prepared presentation Development; Officer. our Discovery this President press and Executive Panzara, the Wave’s webcast Chief section to and Dr. www.wavelifesciences.com. Mike Dr. Therapeutics with today Moran, and are Bolno, Investors accompany website remarks The

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

Paul Bolno

Mike half our quarter has us. pipeline, I our so for and will an achievements financials. Kate. Kyle business provide year XXXX Good thank highlighting Wave. first will exciting by been our therapeutic Thanks, will far start for discuss and first This finally, all update. Today, of morning and discuss you this joining a

both AATD our and development. with on the antitrypsin program. stages from rapidly clinical been data first to RNA announcement and track key into exemplified remain Rapidly path manufacturing. platform, advance our This from are by value on patients first leverage our our for their a deliver of to clinical clinic And how families our preclinical our to we data are pipeline Alpha-X drive at next clinical We studies, partnership programs. unlock Wave recent a AIMer recent accelerating of to Starting our toxicology inform three translating program in CX programs the multiple forefront pillars the to on our the inpatient. innovation is serve. and positive shareholders executing data editing value We to glimpse of has oligonucleotide. our was data step IND-enabling on

As in we WVE-XXX, for to adaptive nervous design identify of in ALS successful or system patients announced CXorfXX the central low with positive to signal trial. innovative of doses ongoing this the were single demonstrated in the due XXX with rapidly associated engagement target FTD. We FOCUS-CX study the able April and

trial As advancing the of Mike for the frequency optimize and dose highlight development. today, will phase to clinical next is

extremely diseases ALS unmet need. As all and FTD are aware, of devastating you are high

for studying CNS broad potential WVE-XXX our clinical the faster PN elucidate rates disease muscle in help by progression, this data and studying moving to with ongoing trial from advance urgency data diseases. DMD trials clinical these Huntington's with of we deliver will to expect ongoing year SELECT-HD further marked and illnesses This are in These we us those mutations, of and For also also our CX WVE-NXXX. are chemistry program.

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right creativity several particular With of positive recognition by and paper This discussions distinguish editing business applications our vastly highly modification, AIMers active further robust, we from RNA our simplified as our our without in proof-of-concept earlier in others levels. scientists. oligonucleotides unique remain both our durable, and key used clinical expertise PN oligonucleotides for accelerated, or which delivery chemistry In addressable exogenous be expands publications novel data for development the recent enabled specific collaboration on have editing our efforts. the and There can widespread enzymes we is RNA-based potential the in our Wave's approach the Nature foundational that served are editing this and the therapeutics. Finally, the chemistry of well editing potential and for DNA with of genetic a vehicles. partners targets. as pursuing are data, AIMers is Biotechnology, landscape to publication quarter, RNA first announced preclinical showed of year,

are as disease modulation our We nucleotide vast amenable We see potentially aid as with to to of protein, important tens disruption diseases, of XXXX would thousands an be to in leveraging to capability. such additional expect potential partnering, the for of are serve editing proteins, as Demonstrating including variants There clinical opportunities monogenic address corrections. open our well continue year reach single of derisk patient of large proof-of-concept to AATD platform to manufacturing our that protein populations interactions. AIMers. expand through

FTD leverage editing ALS the demonstrating potent and our clinical in the durable data system. nervous central to positive preclinical potential offers Our data,

we TIDES at to clinical in with AIMer identifications, this Today us enables is platform target to from capture time. cycle call, conference. learnings our PRISM candidate earnings with preclinical proof-of-concept our times Giangrande Dr. each the tandem USA preclinical new Our expect data shorten over to Paloma target, presenting and

a clinically mouse doses GalNAc SERPINAX in AAT reminder, restoration of treatments of relevant observed AIMers. a model, levels transgenic AIMer multiple following with we As

M-AAT RNA or protein we levels The wild-type healthy in XX, of protein level Specifically, majority This XX% was AAT the at in serum resulted liver. control. protein. editing observed XX.X of higher approximately week editing total than micromolar fivefold approximately of confirmed circulating AAT XX% of

protein the lung the and at elastase data the AIMer administered AAT subcutaneous both the shown is Paloma PAS-D address accumulation single of treatment measured XX ability of manifestations with on of reduces liver as approaches the right. Histological left. aggregates AATD, to functionality a at liver over there staining are TIDES, developed biopsy restored address with While multiple disease, by demonstrating analysis inhibition, AIMers ZAAT as on also advantages new as Today, shown to by of indicate sharing being slide the compound. of eight liver neutrophil the week on assessed time as is

data presentation our well clinical at as Mike Mike? the to as the highlighting update oral be will our week. call now give clinical an advancing AATD programs, progress towards on the Ill over in We turn again program next ASGCT meeting AATD an the development. to

Mike Panzara

clinical everyone and morning and Paul I Thanks to our data emerging good the therapeutic with FOCUS-CX will starting programs, for WVE-XXX. trial review call. our recent Today, on

First, CXorfXX I would moment on like mutation. to the spend a

and when produced their to a tissues, cortex proteins, pre-mRNA expansion goal a that also target cellular both lasted is availability more engagement to transcripts at be dipeptide of the of both complex, the variants, a this biomarker, least selectively drivers mutations, model days preclinical in repeat in transgenic into mRNA deposits this most poly(GP). used among starting targets in same are XX% rapidly of Hexanucleotide by that moving WVE-XXX's to have downstream us genetic dose preserving target repeat they for containing six toxic it In variant addressing may lead poly(GP) and each measurable and RNA hexanucleotide ability contain with of doses, and pre-mRNA required mouse is designed estimate a XXX. repeat trials. soluble our are biology. and the were from antisense the aspect CNS cord multidose to FTD. to CXorfXX and data yield protein and the that animal into was preferred expanded to derived we In WVE-XXX reduce the protein in from the from demonstrated described an selectivity are ALS normal dipeptide as to months translated expansion is variant apart. explore over long proteins, poly(GP) result both WVE-XXX abundant period, be designed potential such model associated spinal levels ICP this the accurately predicted in CSF target trigger most candidate transcripts, reduction the XX% only confirming engagement results goal of mRNA the safe the and determine along CXorfXX over both DPR of sense DPR DPRs case with in we of the from engage common but Because non-human on they vivo toxicity. WVE-XXX in compounds known target poly(GP) because to silencing to and just also mechanisms. because own, the single And humans repeat durably a XXX The but the or in XXX, DPR that with engagement seven and of multiple selected human proteins. of doses RNA studies, and preserved levels designed a well mutations least hexanucleotide of with of target the clinical Our target of These and CXorfXX cause and the the toxicities of transcripts two primates effect enabled variety after with as the at CXorfXX biomarkers as pathway. toxicity DPR while through suppressing, existing expression. and

points. robust XX in poly(GP) poly(GP) figure specifically decline at during XX, versus this multiple FOCUS-CX the milligram our additional We doses. as us CSF observed to modeling study, the and follow-up early adapt shown April, prompted administration Further, translation with XX target as into continued the right placebo we excellent reduced saw XXX update engagement our single in as well of of clinic. showed modeling with several doses significantly slide of on Investor the which on time As of low we predicts

while adapting the now multidose poly(GP) of study is which reduction are the underway. depth fully doses single of well characterize continuing phase, WVE-XXX We to with the

cohorts development. us extending XX to are dose a will this additional milligram mid-XXXX frequency milligrams frequency We and six the next will optimize enable patients in that authorities of XX the enrolling later identify the to dose. we open-label help dose These throughout additional with level optimal while with anticipate single period to to months, FOCUS-CX study for Specifically, as be and receive will provide the regulatory dose used additional as in three observation and the XXXX, level data phase explore discussions dosing additional patients year. from data which single well beginning upcoming and extension

candidates, as ENCALS, which or to ALS, in to preclinical is our be at upcoming own the PRISM distinct from are sharing and platform clinical June. Cure current to the our are in promise field. we candidates Network oral the which the just is an example built design with presentation with taken FOCUS-CX from data innovations approach Lastly, to excited the others experiences, these first CNS along occurring of be European upon early that

understanding capabilities of pharmacology Our the influencing predict the better by approach control leveraging at now to ability begins in to chemistry engagement with their and our molecules vivo PK/PD distribution of and Then of proprietary dosing. modifications human its the of candidates tolerability in can with stereochemistry, profile. relationships for potential systems the the factors core understand of the rationally availability a widespread to optimizing favorable tissue an design we PRISM target increased and context

real-time adaptive of frequency reduce positions well Finally, allow level and relevant decision-making. biomarkers, study to patient careful along with development endpoints designs of and that rapid drive that selection and population, us risk adjustment other dose

can swiftly starting work biomarker beginning proof-of-concept see data clear even relevant with fruit programs and our other and data you us independent is consultation to with year. the our dose. readouts our data, to this us As continue, move outcome even clinical optimistic from allowing and The more decision-making this DSMB Further, these real-time forward. about will effects makes at on the bear programs

program. expect study macular is For and clinical a XXX this continues, allele mutation, is exon in skipping chemistry further clinical share to FOCUS-CX, Huntington's we the is WVE-XXX, goal Like in huntingtin to disease with XXXX trial targeting and selective WVE-NXXX PN to our for XX escalation for Duchenne association adaptive SNPX oligonucleotide SELECT-HD time accelerating in the enable provide with insight dystrophy. a slicing oligonucleotide Dose into of a proof-of-concept. mutant that data ongoing. harbor decision-making with for SELECT-HD patients

the our improved from some As an reminder, pharmacokinetic with pharmacological last quarter, shared a compound. with WVE-NXXX we of data the DMD first-generation chemistry PN DMD profile compared demonstrating study to

clinical decision-making muscle expect to We including data, enable in biopsies XXXX.

select to which expected advancing share filings. progress our make more the to turn on AATD and an initiate Moran, in are excellent CTA at the and quarter detail Kyle toxicology to to this call CFO. AATD third year, continue now point I we we program of IND-enabling AIMer, Lastly, track timing of expect candidate Kyle? will our development studies on over

Kyle Moran

last Thanks expenses Takeda. programs. Net months R&D expenses first million for of $X.X loss the to our decreased offset first our to million Mike. previously discontinued including PRISM $XX.X compared related year, million first operating clinical cash reported ended due G&A the in for We program, with primarily XX, under ongoing which expenses. $XX.X due increased for with to quarter This three editing $XX.X and increase XXXX and XXXX. GAAP March in XXXX in quarter XXXX, ended related the internal as other external million. platform, compared the to quarter quarter G&A of investments. $XX.X We of ADAR collaboration our partially primarily for short-term $XXX.X the million compensation cash, same XXXX, expenses to in equivalents primarily were earned other services and were and by related to of $XX.X the to was period was external million million expenses first as was revenue professional revenue related

expect and expenditure fund us our enable XXXX. equivalents quarter continue that short-term will We cash, investments to operating cash capital requirements second and the into of to our

to the Paul? reminder, As in potential back runway. over opt-in or payments turn include now not our cash we under Takeda Paul. call collaboration a I'll do our milestone

Paul Bolno

on Wave proud our work for team dedication I'm first for hard clinical their Kyle. milestone ALS with FTD. CX patients delivering and and and Thanks of the for especially significant for and living associated

of further WVE-XXX deliver well additional the DMD for year, as will expect this inform and programs. next unlock data from as sets these and value We development. of steps to Each our data data HD

financial our With translation areas impact to and of in data evaluating robust positive spends modalities and strengthen to different both number and WVE-XXX this Interest we acceleration the expansion data, high therapeutic with increased on partnering These as updates expected of recent the of number as and throughout includes our partnerships position. well demonstrating pipeline, first leveraging our year. our are publications the preclinical manufacturing a We our forward quarter, coupled capability. sharing are of platform support opportunities. look

behalf Huntington's to Finally, with express both we I to that awareness incredibly Wave, of I'd is communities disease and at acknowledge everyone want grateful how like May are and ALS these support. month. On to our partnership

and day Operator? up We families aware creativity waiting, acutely us focus with move ultimately treatments. drives are that for resolute With can and questions. we'll that the life-changing we every deliver to are that, open so patients urgency, this and call


Our Instructions] first from [Operator Truist Lee comes Securities. Joon question with

Joon Lee

[ph] better you there preserves slightly also different In And terminating questions. in quick of Biogen program our mechanism? always your taking success? for Thanks that program a have the form since Hi. is follow-up. is what their ALS, gives setting Ionis that understanding I and poised confidence the Our for wild-type

Paul Bolno

it turn I'll to Mike. Yeah. over

Mike Panzara

Joon. Hi, Yeah.

So, I of seen details it we simply, any mean, yet. haven't

outlined. the out. the But we different sequence, So And lot chemistry, thing our looking different upon the just different biology I potency. dose candidate a have first durability certainly And levels, as to Clearly, differences. think that's based I pre-clinically. we point there's just of chose a at different

is the literature it's we really or our best to saying mean, that treating the I what worthwhile disease. so, anything any And confidence going the hypothesis haven't changes that -- is approach seen for change be the

Paul Bolno

so XX, single to low saw potency just clinically. chemistry of you patients just as and we've that, poly(GP) to pre-clinically I on what but And doses, follow-up continuing our important. point so if low not very we to Single actually, just that doses then dose is but potency, durability substantially remember, on at not response, dose. follow seen is XX, Mike's lowered even further. out think we translation protein, mean, I those are said,

as the data valid yet. a they have termination terminate had of had press a release that We release we So was didn't knowing press to, absence Mike right? alluded release, what press a -- they saw, in a

So, we're our data I confident think translating. in preclinical

as I that call their is had for follow. -- ALS update following think that predictive we on data bring up poly(GP) loading and on doses on and biomarker a have shared the point the dose. [indiscernible] And one Biogen I'll saw with that we dosing, and more to gave substantial our good Ionis we the announcement

at I was, think their around XX. So, data doses five

us and at confidence to dose continue again, out. patients data gives our effects, to data durable the going single have preclinical potent follow back of least we So, these to

what said happens there's around and get on and a lot the community we're data see in have repeat we where Wave Mike the wait But see. ultimately to of we'll with confidence generating, all to. call, As the but dosing within

Joon Lee


-- updated are DMD forward And to guided so, are year. you the And second and hit of release able data. your to Looking to have share Does the in the and trial that for that you. all threshold? imply half Huntington's trials, have the utilizing of including you Thank if data pre-specified what you design, is? adaptive that certain the

Paul Bolno


point example, the haven't unblinding sharing just happens, when while to And CX that think to CX in like the there -- than in and the any I are because say are adaptive design, that other year of is that XXXX. that we reiterate, events obviously, a I great could data. they and guided trigger

change, see provide the meets trial when update. and DSMB that, we'll And will an so, that

CX review. come after the the point started any rather those a guided And the of DMD guided study, that had DSMB year, HD SNPX, while over study of year. data half haven't at we we've this So, back and after the data to course the

guiding kind back year. of half of not the we're the to So,

Joon Lee

you. Thank


Syed Salim from Mizuho. comes question with next Our

Salim Syed

Mike, guys. questions. or me a Thanks for guess, I morning, on Paul trial. the Good the CX couple for Great.

expect Regarding this see prior you authorities follow-up. hand benefit Thank you you. the then to trial? your thoughts can for in next there? quick And give When that just planning you a functional regulatory measures, functional us guess, in you particular to I development? data updated do functional a are phase just going maybe to to have And the of

Mike Panzara

that Well, in in at I and said the is of we've setting Salim. the study. patients allele the we're primary But six Yeah. of release, functional out CDR-FTLD months the which the previously, to This is measure, as to ALS-FRS-R, cognitive about measures any setting an are positive had when in looking the takes impact Hi, Mike. the as Dr. much XX on [ph] really a Skova we data it our pointed see these, of of effect. even mean,

would the we see year, in functional anticipate would transition core really follow-up longer [indiscernible] as that that this in anticipate a the that we be having continued would treatment So, from optimized patients follow potential we setting the term any continue of the place we that, and and where not data FOCUS-CX study more them to effect. would

Salim Syed

Thanks Okay. Mike.

then, us on plan right for functional? the coming maybe regulatory just that see it without that the are -- you given potential discussions could what having outline the you outcomes of out now way So, the you

Paul Bolno


predicting dosing we phase we I'd hand I'd discussing I we I potential think to optimized the next will like them, favorable into. with get with have basically and it a have that mean, transition ALS. a profile. a in authorities say going first regulatory to discussions. is engagements mean, I proof-of-concept great that think very of But about phase development something forward. with context out of in come along a into way this the I drug target demonstrate all, and path of clear very and authorities, And I that I have approach was when straightforward pretty to shape in to well the remember, takes to it purpose -- next outcomes development. So, talk with safety been of clear develop much the that, not the for to positions of say would data what I The the known. we're study us it's mean, And to that of the

without clear have FOCUS-CX what's that us into go. pretty details, required So, I and think it's to these getting indications up to sets information in ready

Salim Syed

it. Got

Thank so much. Okay. you

Paul Bolno

Thank you.


with comes question Issi from Our Luca RBC. next

Lisa Walter

our this for Perfect. taking Thanks is on question. for on the Luca. quarter. This Congrats Lisa progress Thanks.

Just level noticed CX for going the XX XX and between wondering, the the to at do trial, the And this you're mg. include I Huntington the dose from the CX dose HD also with the which I that Does any have XX your study slides dose? wondering study. to if to just in is been in anything a on mg the XX NFL elevations you've apply to that program, the able learning was observed mg mg you

start that instance, based in on you you've to able maybe seen target in higher are For at dose engagement CX? a the HD Thanks.

Mike Panzara

Mike is This Yeah. again. Hi.

have was regarding of target forward already dose a basically, that's dose So, level what robust really intermediate higher to prudent. just effect. didn't we XX can we with bit fact we standpoint in an really of need and dose dose at the upon was frequency. saw need XX that minimal a minimal would from a milligrams, from dose, take milligram that terms durable, that based identification engagement dose purely given a that's the that robust saw -- to thought we any It effect best And we have That that what the we is XX. going the necessitate is be little

if want there at that's and XX we could. XX mean sort got neurofilament I So end see of were following We the see It's And where to. dose. up. as and we've We where we'll be We'll exploratory, going observations where to we we a we could go up disclosed. basically single that. end higher we've to.

multiple We into now right in are doses. going

us of pan said, upon, dose as trying XX our based gives current out. robust that I -- But that target get minimal to will all that really engagement. So, is minimal the target

preclinical using our was dose studies, that used establish really we two the SNPX same FOCUS-CX. selection modeling. to preclinical I selection in targeting data, think Based upon different learnings Regarding the for the SELECT-HD a the the the for shared that data, principles across molecule, it's different different program dose

SELECT So, really reviews, is thing best the see it's to around we infrastructure from that from DSMB And between established and move I therefore, the based infrastructure this if similar the and upon effect reviews rapidly were have they can adapting, studies. independent basically entire learn -- think very it we a can adapt use that and FOCUS-CX we that forward. study works, biological and the that

is shared So slightly but that's each learning, different. molecule

Paul Bolno

I on predictive think to expect that, HD. what as occur said, up follow we preclinical of to did Mike to see from see is CX. think thing modeling going that clinical I And we're in and translation to same

anticipate So target and would the where starting studies with doses adaptive started that -- there. then run we the principal was and the engaging

of Mike's around first I on save it's and then this advantages our PN stable, is of stays a intermediate repeat preclinical looking pick think and dose to cell catalytic on doses. point data, the inside that chemistry. discussion a one to durable. One up What for that was that is we at the Remember, study. see while

single this so, principles order we doses low that repeat engagement were that then that dose achieve why I dosing, And at effect. field, really established to here high reframed you to we're loading looking doses And in used get data. other accumulating these are doses engaging. design in we've with adaptive And so think single target the and features hence, at

looking doses all terms looks the to design. like is in the to, to levels, doses us give alluded and at repeat single repeat Mike data that to to going at intermediate dose dose as earlier XX things, of the we determine the of them question, moving other at are need one that so, study what next And

Lisa Walter

question. the taking for Thanks it. Got


Our comes from next Matteis Stifel. question with Paul

Alex Thompson

for our year taking for thanks a timing on on quick guess ALS Paul. is this I trial an follow-up again. Alex question then Hey, This questions. and

the which the believe given could were an an given that, helpful? that meeting what would on timing And are curious, is that to anything able expecting any, adaptive Thanks. study later study. data hard this share some if present, granular you and you as PK adaptive you I as study, then, not say technically to not it's about I'm ENCALS data. ALS, be more year, more at that to for predict if is why DMD So, additional upcoming

Paul Bolno

Great. the And question. thanks for

terms muscle point with to blinded right, stays the nature an the not have the the So, boys subsequent we adaptive until where biopsy hit sense the in of it's MTD, stake. start take biopsy then being in in of muscle It well, in doses the the biopsy. DMD, is three open-label. And biopsies, and

so, we're seeing escalation there think that I And dose and continued in dose what study. is

a we would at be biopsy the point in that us to for obviously hit So, that threshold, when time, those trigger take samples.

So, continues trial to continues progress escalate. to and

that's So DMD.

will was Second data And presented data and that prior. there, data that the it presenting we will anticipate ENCALS for presented. question the the the presented go obviously, But detail be Mike would we we into more on discussion. the

Mike Panzara

opportunity the answer of get have and the to be that feedback first scientific do questions. community in real will we That and Yeah. front

single appropriate later presented. So, venue -- we in presented an it place of be that where in whether would then it would be then be what multidose And doses, a in scientific data. the higher if obviously have or data we've as we would already are expansion year, for the with additional

data are We by looks gives when on next governed the DSMB and us steps. at advice some

Alex Thompson

Thanks. Great. That’s helpful.

Mike Panzara

Thank you.

Paul Bolno

Thank you.


next Mani Our from with Foroohar SVB comes question Securities.

Mani Foroohar

for taking couple the Thanks ones. of guys. question. quick A Hey,

cash don't of assumptions us cetera? what runway support explicitly your just you've to on is. cash quarter I The disclosed. give guidance. you guidance XQ that really So, versus your to hand burn And assumptions a find any have of you're development, on follow-up. ATM, of XXXX, based way making trying at numbers should looking be sense I in it what cash business that versus Can around guidance milestones, a reach through that seem runway to making then et we a I'm use what the comparing So, for about this am

Paul Bolno

Sure. for Thanks, the Mani question.

quarter-to-quarter. As you historically, fluctuates our cash see,

spend So, the going forward inflection take expect focus than burn But I program calculate be forward. as our don't the our to think you can on lower to do points. and clinical advancing the just QX we then quarterly latest cash that we

have as from terms inflows, we cash we you milestones any don't we In any credits, -- there. tax know, historically, items in but other of or gotten include

any point, So, in calculating not to incremental terms that dilution it's not it's of calculating. ATM,

So that current talk think that I subsequently. ongoing discussion But separate we can guidance, the from it. covers about

Mani Foroohar

of it's a program, competitor CXorf, out a know don't discontinuation, do of bit little following thing compelling profile, couple I'm of success. that not your they for logic I When -- see dosing schedule did dosed approach your we to dose little aggressive that you pointed having will think a have but trouble been aggressively, the we understanding explain dose single times, me? loading on which yet but we I'm a show less about you approach but that logic. trouble. just... touched including you little Can data, the their and Okay. not a have I'm a full and

Paul Bolno

the the presented that collectively, the I safety seen just really so drug something the did I don't on the on profile, a activity haven't as update anything mean, benefit a any study. to we really We started or data the data biomarker mean, about right? quick forward of group, their can said analysis, Yeah. terminated to. we We react basic to look the have date, risk I they have to to logic. that on seeing data. We know actually, fulsomely or

we really We in follow to Meaning, the completely Low of seeing the dosing have don't something kinetics single and protein. said, think it's a continuing. him we're see we up, that I drop, and initiate need let to oligonucleotide. reframing doses drop of that loading think how I'll doses, profile. it's about As Mike different

poly(GP) gave shared full to DSMB period with months three earlier, the the out pushed it we suggesting data see continuing another we to. gets update was follow-up the go down we As at that on where to

So, profile, different. is the just potency, thinking these different really profile I'm about let to And being But different class, durability different different us they're in it Mike. happy different. oligonucleotides gets safety

Mike Panzara

XXX it use so the the which aggressive targeting mean, do Mani. like dose And mean achieve haven't know milligram XX I to term made used we doses, of all think, of Hi, high something I Yeah. worse. over biomarker. giving sense in doses people we I the approach the aggressive, to of months, we sounds is clinically being seen, which terms four five in

necessarily we're less as where mean, better higher a is So, at benefits. And idea than you aggressive the always of achieve I is a doses potent benefit said, very doesn't and selective into us different molecule this molecule. to potentially doses equation. a having translate being, low of allows aggressive, risk that

compound. is approach our the really think with the profile optimize I better to

say is so, aggressive. And aggressive, don't one think is I you can one not

indicators problem and one that's is even I compound leading think benefit. a is a one the starting clearly caused of that compound doses, as to a

So, I need think does that's one why we're confident. keep for the deal. We and to not necessarily just going

Paul Bolno

to I It's always not and potency aggressive. mean, levels. like achieving medicine dosing at -- about mean, about think I potency is means a I effect Yeah. equivalent is making greater

diseases we is as So, potent achieving I think followed therefore, what of the designed advantageous the in we're what you've therapeutic done seeing think, what's CNS which area. we knockdown lower -- treating doses, history is in, been of molecule, kind is a greater at

Mani Foroohar

sounds a helpful. of the preclinical actually talk like your hinges rationale It of your And history. upon your lot in data. about interpretation own That's really confidence your following

data what programs, own to of have the challenges, their in the disappointments interpreting programs repeatedly interpreting DMD you a expertise made consistently the in Given develop since way, preclinical guys those Huntington's, not et previous internal an data that -- possess did since Wave's given in preclinical changes predictable history cetera, before? you

Paul Bolno


designs. important data, that over continue predict pharmacology we of because And we had and X triangulate to profile. number the And mean, can announced preclinical do we a pharmacology in we We human dosing we can target we the we These clinical to and predictive to and we reiterate different now when for the a first where of -- at oligo. we've to were. back response last assessment, would great. What have that where the based the data, plan way, assess guide that's dose was modeled initiation didn't adaptive were July milligram target data models the said course shared, go can conversations it's it this frames shared models statistically engagement, a we and had and we've and if where we when very the that where it. data recently anticipate model vitro just on nonhuman I significant different of to we was we We dose, differentiated that evaluated between of where I that XX we XXXX, had data primate and I think, translating what are we design clinic. is changed reaffirmed and think SNPX We preclinical adaptive happening we assess that to think One, us. can assessment. we tissue placebo. with starting CX that we CNS, chemistry -- that we dose, look the from concentrations knockdown it study. started I year, on and to against was Two, the preclinical in in at which the clear initiating trial engagement the study the our saw on based dose

as are told out, And clinic as that the we hope this in us and follow to, we same HD to others. see the to was we alluded So, translating. guiding Mike thing it

question modeling the was to think designing really of we're better shift fundamental where I your So, that. use

different PN chemistry. based Our pharmacology is on

looking in the in PSPO to functional I distribution of muscle backbone outcomes. think of was cell consequential and our at backlog update against seeing is nucleus distributors was the which BMD able backbone, a being double and ultimately seeing a great with that change different mouse example different to in chemistry compare and survival PN knockout NXXX the

the other better to in really modeling, was acceleration platform. our predictive three and that XXXX, predictive But today with editing of fundamental clinical modeling. the and think like change we new really companies have it wholesale, with the which our of XXXX, transformation chemistry have and XXXX in those led shift about I in it to coupled implementing platform peer RNA done, all shift the So, essentially a that and programs is

Mani Foroohar

your Great. That's thinking. Thanks Understand helpful. guys.

Paul Bolno

you. Thank


Our next Jefferies. from Suji comes with question Jeong

Suji Jeong

for question. dialing for taking Thanks Suji our This Hi. in Eun. is

So, follow-ups. Thanks. year, development? first [technical data further couple have question I this Huntington's the for And and a is program of my you later difficulty] when disease have DMD

Paul Bolno

to started towards up break the end. You've

it So, inaccurately. tell I'm just and going if have to question repeat please your me we

just Suji, and the bar next development want DMD? HD the in what for to So, is phase know of

Suji Jeong


Paul Bolno

Okay. Yeah.

engagement, think And We I similar. what So, data was is and in for dose the understanding very CX. right? we kind -- we terms have poly(GP) that like, of anticipate of in all an being think update and did I was update share looks an drug. that In in able what here's case of update target which so safety in disease, CX, to Huntington's HD it the

HD the that we is, have being is Huntington, we're able the obviously, share study continue assessing and wild-type anticipate identify. Huntington at looking So, we're biomarkers and to in to mutant we'll

after one is We muscular in see the dystrophy didn't last remember I'm total shared the tissue did muscle will the distribution? HD. those boys -- to muscular stuck a that change answer the and of want the year. be the interstitial getting and And Drug DMD, -- in question set got we So in concentration We Because into you that actually we'll nucleus. compartment of case that translation data this see we -- is, last biopsies data meetings distribution sorry total drug space. muscle didn't if in drug. to not we for decisions use, over make of XXXX we -- that the then we'll at key year where have on of

preclinical So, previous part also the to the as that really data as same and be NXXX able translating question do CNS is -- is [indiscernible], preclinical as looking different we'll of fundamentally study answer be assessment the to obviously question we'll than well.

hidden for are. and updates to the those give those we'll too what data So during steps drivers steps those the next will as be

Suji Jeong

you. Thank Great.

So, you be data going wild-type to that mentioned about level sharing. Huntington the you're

remember of do I CX and is measuring guys be have a Huntington, you that program. another years I ago, the question So, related ready had trouble And confirmed to used? to wild-type have couple the you the assay

the only by of function as as of slide, side. not may Biogen, address it targets As because disease years to there gain one might of target education loss buyers be to the your you out you CX as ALS on could well think some and manifestation your don't pathophysiology. you mean, I need Do that be you the be function and able pointed side well of the as also program driven

Paul Bolno

the to the we I study, with solid we the the I So, other and mean, conjunction take validate and wild-type X Mike I'll that SNPX and the I will partners the that while our the assay take disappointing assay, take first question, at think will institute. But is question. CACI piece for in one CX did on think and

there's So, have I done to We assay. that think assay that a lot ready. use

confident feel as as in So, that assay well the we both in assay. mute

molecule. we with the are based the containing we in that design to tools do the modeling now the on now think and I the So, that study, PN we'll with SNPX SNPX use that program to need assessment And of have predictive evaluate place.

assess feel do we we So, to to outcome. confident that able have tools be the

Mike Panzara

details thing HDI. itself, presented only the Tom, the assay is assay on The the the I'd Yeah. were add that, at

that's within I scientific discussed it's an community. been think so, the where important thing And reviewed and

develop the know even mean, selective that approach compound CX to I our of as here asymptomatic make remain that that affluent the to setting possible any the a of think ALS, we are protein haplosufficiency people disease as asymptomatic. sufficiency in terms not top preexisting of I is and biology any in who is for have worse.

to an with that's community believes So, is worsening outcomes. believe as you -- and that without we going you good yield haplosufficiency, that allow in working bring and toxic down the this asymptomatic clinical down protein approach still that haplo the bring as

this. So, we're in comfortable we're how approaching

Suji Jeong

Did that to than Just wanted clarify you one quarter? expect Thank in the question. And first lower you. quarterly to cash say last you burn that. be

Paul Bolno

That's correct.

Suji Jeong

the those you clinical you to have burn as lower ongoing? why you expect Could on how trials cash than first quarter quarterly elaborate -- be the

Paul Bolno

to the I and back historically. based think, our If of outflows. mean, of other quarter-to-quarter look based lower cash that quarter quarter, fourth outflows I the on on are this last have activity, burn that see the as year. can said, fluctuate higher year, first than quarter it's significantly first cash you we than quarters, And Yeah. we often in I

I cash quarter trend said, first out. think and I don't can as So, take just that you

account fact so take some and into period look I DMD high that to a think there. we at programs of periods, you the the ongoing, there longer prior have had HD time expenses in and were the

safe understand statement. runway forward I we've been calculation, our it's know, our you with cash not projections. as a So, in we're And consistent but comfortable

Suji Jeong

Thank Great. you.


call back And further turn this time. for not Paul like to to I'd questions any the I'm showing remarks. at closing any

Paul Bolno

update. Thank to day. you you to employees our Wave financial our to Have commitment morning great quarter corporate and you. the review everyone XXXX Thank hard patients. their and for work first thank this call a results And for joining


today's Ladies and gentlemen, this does presentation. conclude

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