Wave Life Sciences (WVE)

Kate Rausch Head of Investor Relations
Paul Bolno President and Chief Executive Officer
Michael Panzara Chief Medical Officer, Head of Therapeutics Discovery and Development
Kyle Moran Chief Financial Officer
Salim Syed Mizuho Securities
Joon Lee Truist Securities
Mani Foroohar SVB Leerink
Thor Nagel Stifel Financial Corp.
Lisa Walter RBC Capital Markets
Suji Jeong Jefferies
Call transcript
Due to licensing restrictions, you must log in to view earnings call transcripts.

Good morning and welcome to the Wave Life Sciences Fourth Quarter and Full-Year 2020 Financial Results Conference Call. At this time, all participants are in a listen-only mode.

As I 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 full-year Good business you progress discuss recent operating fourth and to XXXX morning results. for review and Wave's

be with Officer, Discovery, Panzara, our Senior Ken news in Technology prepared slide section Medical of Bolno, our call also call. On the www.wavelifesciences.com. Development; Dr. Discovery of the available Rhodes, the and Vice Investors Chief Vargeese, full-year remarks today portion our This morning, and that questions following Chief available and for the CEO; Mike and our presentation and our of Kyle Officer, Paul that Moran, the Dr. Dr. we release quarter Chandra our note me website, release will the issued Therapeutics our President fourth accompanies Therapeutics and Head Please a this President, results. news are are Dr. detailing CFO. webcast

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

Paul Bolno

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

our year briefly During year, give provide our Ken resulting prepared transformative trials Kyle off for will financial will focused update which driven deliberate today, Chandra productive will this kicking I and opening patients. and new medicines be an Wave, Panzara call our results. for will developing discuss After Rhodes after a Mike commitment was remarks our was on clinical the for and from available to our that remarks, Varghese by Q&A. XXXX execution

readout XXXX, As In reflect of which are we have has we start the pipeline, I this on PRECISION-HD would end we month. the our clinic five data of a progress neurology And year. to programs us the on in like a we positioned the track at progressed pandemic. made, global the programs backdrop amidst our to for

chemistry. to PN advance program We program new are CXorfXX all HD, – on delivering and FTD, which incorporates our in our Exon XX SNPX year and clinic the program our into Duchenne, in guidance ALS in our of three programs our new this

we're with We target also NHPs. achieved widespread CNS the several programs including Takeda, milestones in engagement the of advancing first demonstration for and substantial

antitrypsin results in our published pipeline a well and in papers deficiency. From raised continued deliver announcement We platform into progress editing program first pipeline and XXXX capital for more. modalities to with our position, platform, Highlighting of RNA beyond. months, the to PRISM continue advancing is growth both and last the $XXX publish novel our ADAR over to progress advance five we resourced alpha-X culminating modality, ADAR-mediated support expect significant on new past to year and made within million we ensuring XX to and the our editing expand XXXX, we of our proof-of-concept Wave

slide X, Phase and programs in both studies and of WVE-XXXXXX, and for On Huntington's a SNPX disease. consist anticipate year provide we extension of PRECISION-HD core XXXX, Ib/Xa starting programs, our updates to we readout very an of all overview our targeting expect busy on with PRECISION-HDX biomarker open and upcoming of WVE-XXXXXX this XX These studies from Turning the label X respectively. data report core of PRECISION-HD month. at up including cohorts core from end the from trial, all with complete cohort and cohort, the safety These include the of data the milligram the to trial. cohorts XX the milligram along programs we to PRECISION-HDX program including

a data patients open data share III milligrams Huntington. also to label This or development will including us anticipate sharing We data trials. doses who the light from will and regarding chain, we potential a either in or on candidate. multiple Huntington, neurofilament biomarkers, have Phase received for be X which set, expansion the WVE-XXXXXX from robust We will XX type the of enable wild multiple clearly WVE-XXXXXX make expect decision

to turning backbone on modification, touch generation which just used PN our will discussed. pipeline chemistry next in first the Before the novel our augment programs programs, chemistry I

and As PRISM highlighted splicing the application. Essentially, our has potency, from compounds sequence, silencing, across our and to year, during webcast to PN last chemistry we studies independent lead modifications favorable research potential profiles are platform type, PN with backbone genuinely preclinical editing first and chemistry our an advancement been shown increase modality. in and ADAR these to of exposure durability tissue have

multiple have using applications this for candidates submitted we trials three clinical PN year. anticipate initiating trial Importantly, chemistry already and

the prioritized speak on this these SNPX, learnings on clinical our eight from Exon produce vivo and our the advances our our continue also all and phase to Turning Among several CXorfXX and trials incorporated trial partner discovery further generation pharmacology and of slide modification. Stereopure CNS X, focused splicing discovery our planned three call. later We've Notably, of use resulting first PN each of pipeline, programs. has candidate Takeda, during neurology and past significant ADAR preclinical development models programs design our this and data advantages PN been multiple RNA space forefront design, to platform update vivo the that clinical editing to by XX backbone nomination. our we Mike from and X learnings the with we we portfolio of Enabled upcoming an at our in evolution modality, provides programs Slide chemistry. advancing optimized in our overview towards editing. these with positions each current clinical over in progress includes and has targeting which years. which our provide experiences programs reflect entry an translational chemistry programs many preclinical of in program. discovery editing of silencing, candidate programs preclinical and utilize we're the progress in compelling also believe editing and has In will XXXX, in us made

endogenous oligonucleotides approach Our to editing recruit to RNA enzymes called ADAR. RNA fully chemically modified editing short, employs

the or greatly durable opens proprietary chemistry such exciting backbone in can leverage to that to variants or we modifying protein us protein Our avoid which allows door In that therapeutic editing up a of of modification, processes. ADAR to ADAR of proof PN including generated address. expression, of us editing vehicles stereochemistry potentially compounds function delivery are optimized expands enables we manufacturing number applications, AAV primates successful RNA to concept landscape our and non-human vectors and disease as vivo. and restoring and the in which editing resulted upregulation XX% of established XXXX, data in using nanoparticles,

anticipate in data, And and potential neurology. RNA excited ADAR to evaluating vivo modality. the are in editing additional of editing non-human are editing vitro in mice. about neurology potential with year, neurons sharing primate in the We demonstrated we CNS we year, and last ADAR apply this actively to programs we successful This address

that dose, lung liver frequent Patients By damage, hospitalizations proteins lung liver upwards SERPINAX AATD. By or of ADAR this AATD modality are the at lung vivo allele or increase by where level threefold of aggregation of exhibit editing XX% protein. alpha-X transcripts. This model antitrypsin mutation wild has In to allele what Z we the deficiency, preclinical AAT the in risk first single on from AATD. the XXXX, level, antitrypsin allele a typically Unlike quarter a an our of wild lungs protein off-target novel aggregation editing and in potential alpha-X last overexpressing secreted the excitement protein we potentially Z to of address gene, generate genome to ADAR with update, a the able protect or results transgenic editing addresses correction of our the hepatocytes, avoiding with demonstrated Our coded progressive in silencing challenges resulted titrate further point Z tissues the lung vitro liver of of from SERPINAX functional, and and both, program editing type, editing or fourth in in type to the prone to data. proteins. to thereby damage, AATD we These be these correcting of mutation and RNA to avoid validated hepatocytes leads a neutrophil successfully approach, our disease. the and the would manifestations misfolding lack are functional both in potential Since vitro we terminal in a it in us gives have elastase. mRNA protein. with AAT leading editing of believe

half for like optimize SERPINAX Mike the are of additional now and update and Mike? franchise in Panzara I'd to planned proprietary which humanized We we humanized first data clinical to our XXXX. an our on continue our both year. and share to Huntington's over the model, trials vivo in three call turn ADAR on contains to for track this

Michael Panzara

progress XXXX our momentum readout. programs trials development with ended Thanks, to PRECISION-HD Paul. towards the across data continued as we upcoming We

earlier, programs month. described end SNPX Paul data SNPX sharing set of robust for we by As our the and anticipate the a

candidate disease trial variant-selective and development to in ALS Looking clinical we allele-selective candidate to successfully WVE-XXX, clinical third XXXX, initiate Huntington's FTD. and applications December in submitted our for our silencing WVE-XXX, during

of is mutations WVE-NXXX, a amenable with for Exon candidates our to patients XX for In submission skipping addition, CTA DMD imminent. third

owe challenges progress All made partners has in research in these favorable our incorporate detail and these supporting by achieve led team with our and significant our presented continuously these who these the to ongoing to of chemistry, backbone global patient each in discuss the compounds of programs. novel adapted which the today, profiles vivo I'll We numerous PN studies to the pandemic the franchise. our we've communities, starting programs objectives. more Huntington's in to

purposely of candidates to allele-selective lower designed have while type We Huntington. a built HD portfolio Huntington, preserving wild mutant

nervous function is especially continued developing supporting having well the wild adult essential as it function synaptic central in cells stress role protects out Huntington metabolic evidence with type carries time three misfolding importance synaptic synaptic systemic ensure type the This stress. stress, protein affect we and been physiological part both supplying in important memory, types as type growth Wild grow. learning oxidative Huntington survival. BDNF factor functions these the in for in vesicles. their programs, has for Huntington Wild high system advancing essential of shown the spent and against the effects. excitotoxic, as transcriptome, which a of proper neurons only traffic of prevalent have During the and trafficking neurons and and type essential to Huntington regeneration setting including developing well various to has is proteins for as key Wild plasticity, to as plays to of of brains, in the striatal activity, also

of the CSF and of flow wild maintain critical biological Additionally, for effects living protein of the huntingtin the with in mutant Huntington between cilia, Huntington function formation of type effects of use battle type a positive HD. the We the and the tug homeostasis and like is example to help CNS. CNS which control illustrate wild toxic those war the the to in of ongoing of

is Given out of how we progression, ground reservoir. a the type less think to XX% a that protein disease this particularly protein way wild approximately individual, than gradually reasonable healthy further patients is illustrate type patients start there lose to wild depletion if HD with

wild when such, benefit. As may be be clinical believe required of mutant we driver type to an huntingtin important considering how may achieve preservation lowering efficacy

is to SNPs nucleotide Our the target or polymorphisms on allele. selectivity single approach mutant to specific achieving found allele Huntington

it SNPs, an disease. XX,XXX genetics. SNPX of have wanted expanding we routine we benefit are HD. studies to both such HD achieved potentially case substantial the We SNPX Approximately accurately people SNPX, in our now with potential And with can the approximately highly the multiple and have SNPs partnership US, or three to the for target. we with that there accomplishments Allele-selective clinical manifest to people up read to subject of living HD to or approximately three patients of these patients carry XXX,XXX we and to therapy, allele-selective on based patient these fairly novel one that may that given with treatments. specific. with that at of to identify which sequencing when least SNP portfolio Huntington's before is pre one combined. is through to are focused rapidly with surgeon, HD with our of XX% be risk a address identification technologies, an the we In ability population. on disease, therapies HD this SNP. People overall able patients the In candidates, though Some represent And targeting the innovate available of XX% commercialization. carrying eligible In SNPX estimate carries of the multiple up symptomatic developing are population, to our publications. a and long a to we of are in people in harbor at any and with Today, the SNP were the in manifest estimated portion allele-selective the XXXX, population support XX% on groups be SNPX, patients order include family setting of needed the manifest approximately to of their may identify believe onset tools rapidly XX% advance

existing and from programs a planned protection, direct by wild neuro assays, patients' we evaluate the allow engagement, will to CSF assess method biomarkers mutant Huntington PRECISION-HD existing measurement. CSF to implemented have sparing. Building type wild and trial Huntington's target to Huntington confirm total type and Our type samples depleting mutant for wild novel XXX on

and us we directly magnetic antibody leading Huntington. Huntington measure type deplete to quantitation protein XX, slide to using conjugated the allows on shown This remains CSF beads. wild of that As collect mutant

contribution As of measure look community expect to the acknowledged, we increasingly the to type expanding and type protein importance wild use. meaningful HD to is forward be Huntington this ability wild a to its

program candidate allele-selective backbone HD from upon HD of generation our the turning Now programs. to builds first chemistry and have for incorporate gained modifications. learnings WVE-XXX, and our PN candidate first our SNPX to we wealth third This HD experience

PRECISION-HD PK/PD XXX instance, system trial. course clinical first the dosing selectivity. and evaluated this compounds of leveraging the including model our patient as we a type neurofilament dose also Safety is We're vivo ongoing evaluated HD of for And our experience adaptive design results in along collaboration the these at surgeon XXX from of biomarkers guide time relationships. For make with with light Monitoring understand an better our the and tolerability with first dose in the Safety informed and in program, a of trials disease have starting potentially wild to with independent and are decisions to to to sites the drive and efficiencies to in expansion. patients of intervals The single allele Ib/IIa accelerate confirmed and their HD planned DSMB, trial and an will clinical level will new diagnosis who will assess up to our driven incorporate clinical association early or trial. multiple escalation XX similar trial the Phase SNPX anticipate concept. with is enroll stages ascending chain PRECISION-HD CAG dosing dose the with mutant is to site portions. study, our regarding Clinical the activation Board, be Throughout data Huntington, proof and trial Huntington of the Data year. to an carry dose

driving in expression abnormal RNA are devastating the proteins DPRs. protein, common the WVE-XXX, of and candidate, dipeptide CXorfXX amyotrophic hexanucleotide FTD. Turning frontotemporal underlying to transcript expression for reduced to CXorfXX and expansions the sclerosis, phenotypes. gene accumulation or or diverse repeat of lateral treatment and lead is Clinical of ALS, CXorfXX healthy toxic dementia foci determinants target these to of or program neurotoxic repeat-containing our that repeat Mutations designed and the

the is describe and potential clearly Symposium model, Our Disease. resulted apart least led CXorfXX cord polyglycine In polyGP Nature spinal recently publication to transgenic CSF strategy XX, the with of endpoint key variant-selective key described XXst XXX was containing of XX% ICV over is DPR of knockdown presented seven on point. data and A slide the least down that knocked Communications. of clinical in in in preclinical proline or to and at studies. XXX the administered development about polyGP work knockdown durable we the to paper, excited cortex effect remain this achieve work injections at recently mouse the two rapid Motor and candidate. Neuron protein in the our to a at in XX% CXorfXX In normal ALS of durable clinical we this demonstrated variant-selective our remains showing Further, site out International days of targeting unchanged transcripts. identify on validate reason six the foundational highlights targeting in The the expansion time months. a of at Measurement that the

and outcome this in polyGP proof biomarkers interval, potential anticipate target trial we of with year. ongoing patient Clinical and filament subsequent measures dose include site multiple in the concept. single enroll be CXorfXX the to our dose of a will ALS, given or treatment documented clinical the So, preclinical to escalation DSMB of and assessed patients Like up we neuro tolerability and planned results. and light with be a and is Safety these will clinical trial of to the both neurodegeneration, promising Ib/Xa will adapted looking level are engagement A XXX with Key the for impact assessing FTD activation including forward clinical chain. trial, dosing XXX exploratory ALSFRS-R a will key dosing rapid for humans, SNPX and expansion CDR-FTLD. phenotype. assessed trial XX first The portions. be ascending guide along confirmed mixed Phase enabling of

and in to used discuss splicing label dystrophic that access plan is intercellular to clearly not from by Dystrophy open evaluate with NXXX the Exon skipping Finally, candidate suvodirsen first show Duchenne to candidate our DMD pipeline suvodirsen, achieve Exon amenable patients use for The apparently with I chemistry. generation guided Muscular reached we would due work backbone our study in poor modifications. chemistry like but first PN skipping tissue, to XX in Biopsies program our WVE-NXXX, did which our target PS/PO muscle. engagement, muscle to

and for and to surrogate as with for XX% This as by compared non-human that dose up PN Our well And with the containing increases incorporating shown first to production driven dosing. NXXX, compounds supporting from chemistry modification. concentrations primates NXXX of backbone generation Exon to was the data includes evidence compound, fatal dystrophin skipping compelling broader in dependent rescue the in decision dKO XX. myoblast vitro high of as knockout rapidly preclinical NXXX of chemistry, lastly, advance in as a mice patient derived a distribution slide PN phenotype with potential on biweekly or double candidate

the a a has both XXX mouse lack As dosed every week, PN compare dKO the to a eutropin of a molecule to the a mutation other mutation at the per control containing of shown as reminder, compound production, resulting in containing PS/PO fatal second leading at and group. a as as dystrophin, XX, effects weekly we milligram Exon milligrams kilogram phenotypes. study at model completed as a recently XX here, well and A kilogram dosed severe lack PBS well of to same in per leading level rapidly

less other in match MDX PS/PO at which PN is XX Not cohort there dose containing linkages, dosed in a those milligram time than the a have cohorts curves the other placement a dramatic that these than control the of approximately survived median a groups. of lived compounds of only treatment median every including a containing other weeks groups. same Both compound figure containing XX at shown mice Despite to for the at molecule termination group. three treated with these a compared separate as animals PN that, in group and the survival seven the are treatment the molecules study with of the increase groups, XX% in with compared a was week, weeks weeks of On as to of chemistry. sequence survival backbone survival PN Other slide, for and there of XX mice study treated termination. with PBS the survival

on in a quarter this are year. first of submit for NXXX track the CTA to We

be Patients enroll In will amenable The Kyle change our fact, trial to to biweekly turn XX I as targeting and up will based in dose drug dosing initial detect imminent. If planned the and work powered chemistry the a there's label production to clinical PK submission the compounds NXXX will the safety. will receive other DMD XX to be open apply be and upon safety will observations. Exon of our financial muscle Officer, patient to is PN intracellular with patients successful, Chief dystrophin and over well to will in ongoing. The driven Exon skipping. data assess potential call results. now distribution and discovery to is Financial Kyle? report as Moran, trial

Kyle Moran

Thanks, of Mike. Wave XXXX reported million of loss period a $XX.X for to the compared fourth in the $XX.X quarter million net XXXX. same in

and quarter XXXX, of the due preclinical XXXX. the activities of well its cost for in loss for were in same as XXXX by decreases decreases to in February million in to the December $XXX.X programs clinical as external in administrative of HD full to FTD. XXXX. the fourth The development net program were XXXX. in million to in expenses compared Wave's ended Wave's expenses were the Research expenses million reduction were compensation-related million full fourth driven $XX.X $XXX.X same related driven and and development reduction its XXXX $XXX.X the $XXX.X the December expenses by full compared XX, $XX.X primarily expenses last to period and the as million million million year of expenses $XX.X full the plan by the $XXX December in year The to $XX.X in compared for in as the cash decrease February. million quarter increase to ended to expenses in year approximately fourth XXXX. quarter for with as to and cost XXXX XXXX as and General was of expenses XXXX Wave primarily administrative in and announced as end General as discontinue expenses was suvodirsen full administrative the million offering reflects general million quarter research equivalents offset XXXX in other the $XXX.X and plan, and year in and of external development fourth approximately CXorfXX related cash ended in in million partially equivalents as and and XXXX. ALS compared $X.X proceeds Research increases XXXX. its compared cash net XX, and December quarter to The of the $XX.X million decrease $XX cash year year-over-year related the company public reported aftermarket year in in in million equity fourth external expenses $XX.X decision program and primarily from million compared program. its proceeds September For net XXXX from and to a XXXX in period the

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

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

Paul Bolno

XX as milestones. sharing And upcoming And our candidate studies. XXXX from to advance dosing submission is end imminent. of XX depth clinical our throughout through are for track in on of look PRECISION-HD we we pipeline to well trials Thanks, Kyle. all anticipate several program, quarter, this At importantly, we Mike programs capitalized data our Including data. Exon the these mentioned, clinical is initiate three we to and Wave this the and platform. Exon entering diversity our CTA new year. forward And with are

continue sharing and open generate data program. With anticipate and the modality for antitrypsin exciting that, we'll Lastly, our alpha-X data in vivo up we ADAR to preclinical for questions. call our editing to model


Instructions]. [Operator

from of Mizuho. Syed Your from first line the Salim question comes

Salim Syed

thinking in up up apologize. And set at of you data was first the the Paul, I obviously, a How you. very with the Thank here, XX follow thinking the higher an are all bogey just is how the coming that us first, end what's scenario, articulate second about then, this of wondering important question. win I question can a milligram Streety a two, scenarios for – you're month. about Wall and the just if Maybe especially more one. you can get? here. you we various question just data? level I'll answer The

Paul Bolno

wouldn't Street question. it a call I Wall

mind think as I question this our and patients that's clinicians is well. on the the of

an important the profile one. what to I being the is wild Mike. to question Mike us III. a as think, that we've a we So, his hand for the the section, things. I then company it at is question does an continued think to as And I about two and important possibility I'll look start think as to think progress Phase in I'll type, But over alluded to

do are one, are with want think, which to a we we line peers is where that reduction in that's I if believe profile XX%, and wild silencing see think to successful in we sparing, see pan of studies, III approach XX% but manifest about the advance able to pre Phase the not to just population more addition, broadly. in – see, into type a our also to

think programs, about have we [technical you as want be that's So, add a to anything profile we moving that? you do existing forward. a superior that difficulty] Mike, to to profile that could that think

Michael Panzara

shown been it's But to hear to meaningful where people and it's clinicians time be big our it, time with something field. said, we that we've and is question that that we you would thresholds as in again, believe if as we selectivity success. of partners this, that even a aspect think a and the that's And other the considering I allele and allele I think be, Paul it lower could than said, be activity. be need

Salim Syed

comment NFL thinking how expectations? Or on be Any we should about NFL?

Paul Bolno

and than I generate we think like see a in to the is and analyze see, like the But the But decrease I everything else, I data have it. NFL, we I analyze need to that data if the the can around that think two we think what to I it think this generate other flat be profiles same we'd think will seen. been data to And fronts. and knockdown. have different on analyze

milligrams, to I this we'll robust why the out at happens is at data at be data able – set going in time. studies you expansion we're to over think the just look going the and the pointed label open at but looking XX that's as be two at also see XX that across what we're and sense to potency, not look an milligrams

studies So, good think in have NFL both to of a those level get share. data we time at the at we'll assessment I

Salim Syed

Just excited if one to more follows the of subsequent which the I end March follow-up PN you that a quick HD at pipeline the chemistry data Strategy or about, coming wise, up that? are can.

Paul Bolno

set I doses. an think patients which it's I received had an a think opportunity. we're hadn't of all excited about interim and both, all December snapshot data We in look partial right? at just XXXX, a was

that We think – us for and was hadn't looked just SNPX. I SNPX. So, at

great could and that applied do and PN not forward SNPX. data, forward move has to additional led the chemistry, but been. our this And and full we're to based let's pan following to important these study PN PN have in think specific reviewing with that to anticipating also our just and from brings in then we wild I in studies, an SNPX compound to, the in I been Mike that just CX I where a have think splicing note about I sparing allele apply with it's alluded it's progressing around SNPX, a a think type important, and what way approach excited as and detail, data chemistry on others looking DMD. chemistry said, us think silencing with

think looking I we're data. So forward this to

I think us new looking key Huntington's to disease. And to programs. around data we're the the the forward upcoming is commitment I think a for three


Lee of Truist Your comes next Securities. from from question line the Joon

Joon Lee

that X PN SNPX dose together? of in backbone X the to you are updates what programs, the all to results And want that, that treated SNPX to threshold SNPX proceed but program? your the test related to If with are up also you XX% Thank below of switch you would program? with you. patients Huntington's SNPX or planning XX%, some there's be upcoming and what And dose signal your up to the SNPX the still of could for have to go and proportion

Paul Bolno

the in portion I'll other reason we And the the the overlaps question to itself, take was and part of where SNPX because, relates us SNPX an itself. it and Mike. the above SNPX, given think and chose of of and beginning there's I'll the XX% X the at Disease it is, question a hand covers take SNPs, I Huntington's on dose to question XX% escalation? gives incremental But it SNPX It Mike, want as of population. take and is X. you substantial to Huntington's Disease do by

Michael Panzara

reason in the for same specificity, will guided a if time that because allele from I saw safety Monitoring And Phase the in Safety III for in data are next one up, data-driven I on we we starting way all good we that last the Board. would in And Data we asked independent we can our development. think have we you very our the as about then that by that think But preclinical if at and our of would consider as we that, up do can no that. there lines preclinical going do engagement range base starting were some of target some and engagement to SNPX, on wouldn't data. we of terms higher profile dose specificity go that we said we we know and dose go, a and planning planning based question existing promising be terms in higher there's beginning up we going a and very robust allele phase profile

Joon Lee

to than test lot that and that But a that higher If data dose mean you your for for going is does SNPX higher that than use you're X? and you dose implies did you SNPX lot a with also what correct? preclinical did SNPX X, so,

Paul Bolno

X have dosing. a and is about remember, preclinical that interesting, we What's model SNPX didn't guided

we lot in data starting which a was why the going potency vitro today dose is we dose, start that's then done to in believe So, the vivo. we exposure modeling SNPX. said, study and guide vivo of is as be could because work that exposure Mike with engagement if The of beyond relevant SNPX, doses able and that. accelerate in in exploring It on dose have PK/PD to terms target in in

lot leveraging So, anything want guide we to to. have PN we vivo more to decisions. earlier, I look drugs. guide can dosing our there a our we at add those those are Mike, different data, to have that? get And programs to differently around in where chemistry, you data, is we we alluded as and think where starting, They SNPX that ultimately,

Michael Panzara

is another, individually. you these is they beauty and of thing different platform compounds one and from that each one have power they are one the only No, that profiles designed and their alluded of this the are rationally to,

any achieve So, you're looking what is, doses have numeric there going different with just you're by for. compounds, to to definition, like

is that be preclinical a individual that only in having the preclinical, would each study. can the I'd then that So, we is thing beauty compound say, optimize single

Paul Bolno

think to previous And dose doses, modeling, answers preclinical are human I think data at this, that's of set. of I for absence think it's and in we about PK/PD this the why the I In various addressed – have we'll question long higher accumulation. around important terms doses excited – data

again, it's us think, I are. so, we And a where data being robust set, this to going tell really


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

Mani Foroohar

readout something in the modestly changes think study your the this I is with Huntington beads last what in you in as around this interpret from you XXXX? first those sets. we should be the used subtle assays Should readout. upcoming think assay, that was question guess mentioned expect I being these and ways disease about data this pull-down magnetic in used different May we as about data saw [indiscernible] we time assays from

Paul Bolno

piece previous are I been the and assay most the that others. the in think assay have used same used mutant neurofilament by assay Huntington readout. Those assays is are the the we important

in this assess those really work job and an amazing interpretation change how the to assay team through wild the to year working the of how no done develop has so, of And type. assays. What's new an is really

want take piece different second the total assays to than is do in assay? because the And a so, that you Mike,

Michael Panzara

already work the and these allows initial already what the field think way done reagents the assets we in us type that's a has been measure I that assessment wild to used take used in protein. been have and directly that and in to the available modify them

antibodies type would pull-down assay, use the that measurement total developed. Huntington So, beads, now in approach wild used same been is mutant already that this mutant, that except we in to we the approach out the they're be a the on antibodies applied are to so directly the that being also used measure in assay and can pull

going in And the In new to the it's available type a of terms now the deployed of that But interpretability, with approach it's been wild techniques it's is be that reagents, mutant. same. be context mutant, have before. using the we'll using presenting

Mani Foroohar

enrollments and when screening patients of then, might SNPX, see to being enrolled about WVE-XXX around are we or data, think should we in how time considering want which to and impact call And determine rate the whichever considering you it, that? of to SNPX the sites

Paul Bolno

about framework once set dose how Step going think to the obviously, X and we forward. we'll is,

I infrastructure, couple from take to there's assays, SNPX. leverage important, I that. SNPX there's infrastructure, what apply insights that want of is trial SNP the infrastructure, any add Mike, additional execution, we've can think and I to be the architecture, said running and which difficulty] do a times, if the this the and and think terms don't know we're to you we've really and able infrastructure, I phasing think rapidly to [technical leveraged clinical able of a is of X screening to lot in

Paul Bolno

how now it's in years SNPX those prospective And of getting matter sites they this. numbers do been that on we've I their the then, patients a practices. think to just that working with know have from for

think no, where So, the first are. we see we able I be we'll in, once really patients get to

Paul Bolno

To a studies there's to the having that around is more echo now SNP begin study the a that, clinicians as and that features execute phasing get before, run think add we the having can the for two this to we is study, lot patients of time, where first know to studies. run start we to the start, identify had where to the in can the of we said models [indiscernible]. advantage SNPX lot than how on the to are over predict we And quickly a place


Your Paul the next question Stifel. from comes of line Matteis from

Thor Nagel

for on Paul. Thor This is

in just follow little it that a a delay, why up than you kind XX us And in COVID that, give that then color have will be different you meaningfully Thanks. HDX? milligrams? XX was reason this XX we data HDX is on of to milligram any mentioned a milligram data won't HDX data previously can I think dosing but at there

Paul Bolno

March. provided as for that said get end year the they'll And dosing had COVID. dose we on rescheduled we their And think to because last two last update, – said our No. we of were related patients call that, of I in there where be that to their

that but we with year, given a are global of last was terms already pandemic. that's So, in shift, that they're dosed, what scheduled, they'll dealing unfortunate be and

what able that because point see with In set addition, we data think where an on milligram mgs robust decision following and we'll the make and to up pharmacology we SNPX be that. to why will a your differences, that X, on have is compare can cohorts interpretive matched between that's be we'll to XX we data knowing XX SNPX that this

across partial data do that's set data So, we'll to cut set. there have, data other based on we SNPX give and But differences, including and experience we'll pharmacology. side. SNPX past given XX we'll we necessary intact and the and to and the as but a X, is on rather we other the different evaluated. are, determine what label want be we're sets, And relate [indiscernible] data molecules, the that we'll have could data the have We'd out extension X understanding, open the have always believe don't data saying, where to be data


comes Your next Issi line RBC. from question from of the Luca

Lisa Walter

is Lisa for on This Walter Luca.

register. ventricular clinical early, data our on The Ionis again cognitive benefit label program, European no from nor we it saw extension was and trial data volume. Roche's open a the tominersen suggested benefit here on but HD HD-CAB, in Just by trial the recently for some

wondering should you. And your data? that how about implications for your to think Just what reaction was program? Thank we

Paul Bolno

taking decided focused years that on about question days an selective when oligo the function we with that. as that is of of we of were ago sparing always We are Both our we Huntington's supported view is function because go when approach disease. important. gain the reason allele-selective wild toxic that believe were biology we into toxic of a approach, began allele early our a loss This moving studies we both and we the is Huntington's actually and forward, program. to an both Disease was take to If type a said, think kind our approach

war I that I to tug think try at is is least a really disease. think concept two-pronged of imagine just critical, this eloquently to Mike shared this so

manifestation would knockdown. equivalent view a the of wild treating the would to safety probably see harder clinical But type of or type a to a Our benefit with going requisite wild was that sparing become and amount would type wild what it be be toxic wasn't to reduction function of be that signal. loss

our so, preserve toxic approach of the protein, loss but that gain remove function, the toxic therefore, you have so to function there the mutant of And was protein help.

in watch does. This out. two allele Huntington's It's study disease. specific We pan But we're studies. this have thesis, approaches there's go what different silencing that taking biological to running see we're clinical interesting the of to the silencing treatment

deplete or…? the any there's So, and I our you we with think want if prepared. know type. But add you watch don't this emerge Mike, some of have happens data to thinking around when what aligned be I to anything is wild

Michael Panzara

captures add, to nicely. Paul. it nothing No, That


Yang question next comes from Eun the Jefferies. of from line Your

Suji Jeong

I program. have the about HD a few questions

wild the using. about is to be one that type going Huntington you're assay first The

that OLE do you next party? trypsin data Just the And follow you. wondering report, on to alpha if that validated assay a question to program. data Thank utilize the to the on how with also, step? expecting have expect has guide been you're external for I deficiency And the

Paul Bolno

like the first questions? two Huntington's Mike, would to you take

Michael Panzara

large, us employed that assays We've the been working the to Regarding working original get to particular our And at to assay. have to intention assay the can assay, that go the and results developers community be it with of used. assay. we've samples publish been the for to those it we through that and patient share the is so allowed the external with the work validation parties with develop process share this

pleased take we've without to we So, where are, collaboration really this partners who this have parties, done we we done assay adapt has – couldn't next they're at and we're their we without really with the where work, leverage CHDI – particular, this wouldn't have what been external pleased of and are. been our step. and to In able

the with Huntington depth way, of the the But planned degree as of as but you of Roche/Ionis Even safety, response, selective Regarding chronic added really dosing, the important effect, like nice, short-term the studies a dose that's clear of get that that increased to chronic it's you you a short-term setting knockdown, want an think knockdown, studies, dose course. but any doing, effects what think biomarker the in see OLE try power. concept response. a the data When it data, we've to seen to with I just exposure you proof sense OLE is of about not you a really degree should from which the set. duration. well of study, of PRECISION-HD allows that mutant say, the gives The in not a just a the we're it you extended and of gives longer-term impact open though label, about get treatment,

set important in studies. at decision our we really to for going a future is it's that dose us help selection So, look making data as

studies. So, continue to to and have this that be we're to it's opted very grateful valuable the have patients able in

Suji Jeong

[technical my follow-up the non-human AATD. primate, And your question expectation what Based is reasonable on is difficulty]? with

Paul Bolno

we expedite a at is not we're edit SERPINAX can but on the with it do the there's patients can two ADAR the in model appropriate the sure it is the be we twofold only the sequence crops want that why model. looking but we so the that are actually to we're clinically run a that This that sequence doing we work think human things. we're mouse at mouse to One make on is not that because level. work optimizing data and I animal optimizing optimization, expresses to ADAR mouse, to mice, human the translated model,

not edit percent we at know measuring for in can really and we in a interesting generating to is, what's can about a from efficiency mice, just we editing an because a animal just like number using protein, one ratio move of number think but the the of protein while that start be a model, NHPs looking one see exciting work the level. editing it's I substantial editing mouse with and able oligonucleotides, we

percentage, correlation to much threshold starting this how biomarker terms in establish editing at do but you need. protein So, of looking really

of know As for time. good greater we uncovered XX there infusions restoring micromolar protein think leaving patients levels about in of the clinic, that the a but than protein, of are AAT amount we that

then number to is for by using model, molecules the can clinic. establishing our characterize splicing functional the the dose belief a to fact have be do other start we production, of we can and to it's we programs our continue so, can that and And really in responses We as the things. translate silencing able that those protein several

NHPs. We've – the exposure the great exposure using conjugation data and So, we've got GalNAc target. got I human mice, coupled and getting think ADAR with in around

see to about we and broadly. it will we a see a be here, a excited generation potential how for looking that apply program and we're the can the features as very we be So, the about specifically. think and clinical can And have we'll excited transition AAT as those ADAR program I duration, to but of we're space up can PK/PD protein, durability we if set

Suji Jeong

[technical difficulty]

Paul Bolno

I apologize.

a broke little on… bit You up

Suji Jeong

Sorry. What frequency is the AAT…? for expected dosing

Paul Bolno

too. we is we when primal the establish That's going we're what look – to that example as at duration

we've about animals frequency, subcutaneous that's now in So, small. both looked the when dosing we driven our Obviously, think have and based going models. we on GalNAc, large to be preclinical administration that with

with that we relationship But the able in efficient. PK/PD models to that need work is explore administration subcutaneous that vivo to know we to So, to GalNAc in forward. move be do


And presenters, Bolno. Dr. there questions. over the are turn back no call more to phone Paul now I'll

Paul Bolno

full-year you, everyone, look to for update. day. their morning corporate to our and work commitment joining XXXX And hard global fourth review speaking great Have for to We the Thank and call you again thank to especially a quarter you to this soon. the Wave pandemic. employees forward patients, our


call. This conference concludes today's

may disconnect. You now