Wave Life Sciences (WVE)

Kate Rausch Head, Investor Relations
Paul Bolno President & Chief Executive Officer
Mike Panzara Chief Medical Officer Head, Therapeutics Discovery & Development
Paloma Giangrande Vice President, Platform and Discovery Sciences & Biology
Kyle Moran Chief Financial Officer
Mehdi Goudarzi Truist
Salim Syed Mizuho
Alex Thompson Stifel
Call transcript
Due to licensing restrictions, you must log in to view earnings call transcripts.

Good morning and welcome to the Wave Life Sciences Second Quarter 2021 Earnings Call. My name is Brandon and I'll be your operator for today. At this time, all participants are in a listen-only mode. Later, we will conduct a question-and-answer session. [Operator Instructions]. is conference this note being recorded. Please now Head of will turn Life the Rausch Kate to over Investor call Sciences. I Relations Wave at begin. Kate, may you

Kate Rausch

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

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

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

Paul Bolno

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

Giangrande discovery update to call joined give our Discovery programs. the call Paloma stage Mike Biology. after update which alpha-X over as return We'll provide then start the provides will XX capability. an for today Sciences program, provide from Paloma I clinical ongoing remarks, at our Wave year antitrypsin the to proof-of-concept editing on will Platform opening which this During an on Moderna ongoing VP, and our ADAR of

into the Each decision-making milestone our marked WVE-XXX, DMD. establish next behind to these also Finally, XX which WVE-XXX will clinical containing a ultimately steps in start provide SELECT-HD oligonucleotide in designed and of several PN exciting our CX, our we months the novel chemistry most clinical candidate review company. the of milestones. sclerosis briefly we candidate dosing WVE-NXXX, the as over is PRISM of editing critical FOCUS-CX HD the very RNA second enable the next clinical in our advancing emerge which next-generation from Data recent results. trials therapeutic Exon generated our administration financials. to to Most both promise of insights backbone dosing intrathecal human on our CXorfXX an Since programs. to provide clinical utilizes Kyle and achieved PN XX in-vivo two quickly and we're with first the significantly, Right preclinical modifications. of the in SNPX trial our amyotrophic and candidate dementia. trial for systemic for important well chemistry also started This opportunity trial frontotemporal additional our and these confirm and is level lateral a effects quarter, clinical of a is with clinical the trials, as frequency innovative oligonucleotides with approach will adaptive seen the platform PN effects dose

this ADAR the to RNA achieve endogenous engage oligonucleotides to editing. new we modality, For designed the

with protein data results execution these PN data that Since to therapeutic proof-of-concept alpha-X review call. exciting we design. concept on candidates for antitrypsin second editing will important are and the from swift investment founding of both Paloma of advancing direct shared revolution our discovery the recent later oligonucleotide an the to quarter, into the in this and optimize ADAR our chemistry During been PRISM program. of platform the restoration platform Wave, using chemistry functional our for have therapeutic in innovating on we vivo demonstrates molecules. achievement our stereopure These of accomplishments

of modification of new demonstrated few addition modifications effect. of many distribution and Our novel are follow placed across a that studies step PN enabling for modified show than weeks. appear consistently coming Less a oligonucleotides PN in sequence a has independent the to in chemistry trials us that properly to These clinical vitro three first the the have soon of is these unveiling clinical PN first of studies which our in after the and tissue to candidates pharmacology enhances expand even year chemistry change next-generation that vivo just or chemistry advanced now use modality to These build durability others improvements we studies. the be significant in to this these new modifications chemistry, ongoing oligonucleotide we've in pipeline. dosing backbone potency type with first

note nucleic is many today, chemistry therapeutics Given the it's novel scalable. to complexities this of acid important

within all therapeutic our programs are multiple manufacturing three manufacturing supply clinical for facility. trials preclinical We the GMP and

our WVE-NXXX of value in and oligonucleotides a wholly-owned These collaboration ongoing all ALS programs portfolio trials WVE-XXX will Takeda those targets. biomarker led data include and additional and assessments HD, have clinical FTD, by with We which to our pipeline our and path clinical programs in in and enable DMD. potential clinical including unlock in robust for WVE-XXX registration

skipping and PRISM clinic. such experience apply us among platform and now to chemistry to oligonucleotide RNA capability optimizing are advancing compounds towards with Our develop we editing editing that rapidly the this our ADAR enables leaders the exon silencing accelerate

length. for or and these such enable Our editing as avoiding need stranded PN and incorporate simplified fully are features also LNPs. short stereopure Altogether oligonucleotides are nanoparticles They AAV delivery modifications. single modified chemically backbone the

you a across enzyme lower the RNA see of tissue once engage correct target our types left to oligonucleotides on single expressed the slide eight ubiquitously bases. reach As or endogenous modify RNA they can ADAR,

I'd clinical approach enabling Mike? we modality to an the highly to achieve upregulation is avoid September of Panzara level modification focused DNA applications The show for off-target this therapeutic versatility call like Day intend turn vast function, of function our update base-edits. can over now on for at to upcoming We is trials. staying protein expression. editing, potentially of we permanent protein at XX. on the by Mike Research an and the such specific landscape and Our protein target of restoration RNA as

Mike Panzara

morning, provide progress update months will with Thanks, I programs. Today, on few the Good Paul. last everyone. clinical the an made over our

in HD. WVE-XXX, the modified For two expansions our the CNS candidate These candidate designed in hexanucleotide in and first and FTD targeting repeat advancing we CXorfXX, PN programs clinical targeting are targets diseases, SNPX are in WVE-XXX, ALS silence CNS. to clinic: two candidates our the

the our intrathecal pharmacology demonstrated of those both programs; wholly-owned and multiple a programs in primates models. prolonged vivo nonhuman our using transgenic knockdown For intended in desired the pipeline assessments routine to disease and including of have target in sequence of relevant where explore species programs, homology discovery in across Such us CNS partner the collaboration delivery. are with Takeda, more vivo our we now allows a in neurology

in target and One these of widespread the throughout target monthly be PN observation dosing frequent the CXorfXX programs, ability humans in modified our consistent leading transcript clearly to engagement shown previous is our most knock program. that the will the have oligonucleotide than potently as less demonstrate We illustrated expectation has durability to the This dosing distribution trials. with part been intervals by down of CNS.

the it normal dipeptide mRNA important as products of transcripts well are is VX CXorfXX XXX certain as XXX regarding transcripts has poly-GP generating of and for pre-mRNA the devastating very of which is a both preclinical in these XXX diverse ALS basket-like most CX-FTD. target being studies only responsible preclinical to our to designed expansions trial underlying engagement FTD. therefore antisense was transcripts the that guiding the hexanucleotide in Our clinical repeat common humans common in genetic and candidate one both and repeat target sensitive DPR other disease two and poly-GP advanced as of a CX-ALS proteins. Not for these to phenotypes expansion repeat and us and simultaneously is does that is mRNA These variant our single assumptions one a and pathophysiology hexanucleotide protein. drive an transcript, sense should dose biomarker sense of function the causes it understood mixed of approaches DPR loss the for of protein as production ALS-FTD toxic been make target have the the and amongst or CX to These observations targets but transcripts proteins the patients that toxic from trial. translation to and why preserve phenotype, toxic in pre-mRNA pathological immune thus normal allowing the response regulation those make important chosen transcripts these FTD CXorfXX functions which function a excluded and is well CXorfXX starting from is system. therapeutic overwhelmingly CXorfXX studies. positive ALS for containing selectively biologically, this transcribed for with particularly or lead associated are both biomarker clinical neuronal dosing proteins. community is from making been to-date of

from effect the assess XXX potential CSF chain slide neurofilament providing or of biomarker it into treatments. of insights measurements to light the model. for This results remains plan on we transgenic addition, effects important NFL an mouse In of as illustrates back the neuroprotective

FTD data milestones. of ICV meaningful studies months days least of XXX predefined of An poly-GP or is XX% tissue approximately over study. determine for concentrations of single frequent than in spinal monthly. to XX% time at single would As including with month enable optimal cord includes Successful CXorfXX in which with doses two level mixed preclinical review six portions the It ALS protein be to phenotypes. you with with a the dosing results and cortex independent XXX seven at patients six profile ALS to for ascending documented the as confirmed and confirming to-date less clinical expansion to multiple the dose of the selectivity. both tolerability can the expected registrational and knockdown each data each poly-GP reduction in is endpoints. see sustained cohort, and point XX safety favorable unblinded duration FTD and will the frequency a at the FOCUS-CX course Further CNS multi-dose was CXorfXX expected administered committee and upon enroll unchanged along data-driven study apart based throughout XXX

We study decision-making for this generate through enable expect to to XXXX clinical from the program. data

is XXX HD Huntington's to targeting lower mutant designed protein. to to approach protein, Our that healthy sparing drivers lead allows disease that preserving CXorfXX of protein,while while toxic progression. addressing both of protein like Huntington transcripts remains Huntington silence transcripts of that toxic synthesis beneficial thus will

allow is in by a one approaches thinks maximize negative the to mutant measurement NFL. measure that or CNS, knockdown, stands it of in the with benefit allow effects allele of of any our approach protein setting with stress. of effects in mutant ability should by which highly of XX illustrates and that about mutant program copies and shown accomplish selectivity, target and depletion us the Nonetheless BACHD allele unique which hypothesis is the beneficial effects effects maintain The the the This this HD and associated in observed Huntington out mouse we how to Huntington the neuroprotection in called Again emerging the in SELECT-HD XXX and wild-type multiple expansion differentiated to even slide been of the possible towards multi-dose date preservation and positive data frequency through a reviewing as potentially demonstrating If namely, XXX the enabled to gene the treatment the levels some could our somewhat the as Huntington of to mutant many direct striatum selective with unblinded supports mutant of SNP to independent to patients the effect the wild-type SNPX. to potent confirmed of SNPX limited disease. the is for approach. and SNPX the on our assays future targeting of observed began durable CAG in progression contains Huntington's approximately durable weeks knockdown beneficial vivo dose potent preclinical disease purpose FOCUS-CX pull we non-selective the an measurement not dose optimal determine Our our and XX selective in CSF Huntington this with a of to new of accelerating and Like data both and factors mutant wild-types disease other have balance especially used reduction. frequency with enroll push in regarding HD patients and engagement of Slide known on decline erasing this of us What's since reason has making physician model shift selection similar make that Huntington do data is data vitro is is and on the certain committee bottom in in models. assumptions we cohorts. XX cortex. with resolute planned variant. it that

coming weeks. activated is been underway As expect sites initiate the dosing to we and of clinical in today recruitment trial have

possible and of some of animal nonhuman programs large intended to evaluate distribution administration. the from CNS enables the studies modifications throughout in species our clear leading sustained discovery enhanced CNS This and these to us not and transgenic from for newer through administration XX on the While intrathecal stereochemistry chemistry Takeda widespread study target route most observed sequence in our striatum. that this One knockdown. using the of target our PN is target of of an mice between of single programs modifications illustrated proof-of-concept broad primates. XXX were distribution and nonhuman homology CNS application undisclosed of of target primates biomarkers candidate PN with substantial the CNS distribution of backbone dose What's in XXX engagement possibility the PN and availability is primates engagement drug been the of a Slide clinical are for and feature It for widespread is CNS development. administered oligonucleotides clinical key and month distribution knockdown to disease moving species and after contains differentiated which that we studies and as WVE-XXX a IT across the throughout including nonhuman target XX-milligram consistent was advanced the portfolio modified administration infrequent preclinical collaboration the the

WVE-NXXX, on systemically. our clinical this first administered be candidate to PN Moving to is modified

As of and to it enhance dystrophin the muscle modifications into first to also insight will candidate ability functional provide PN access expression. restore our splicing dystrophic

oligonucleotide We knockout shown on from comparing and or with mouse program are data the data an containing administered given only PS compelling exon optimistic using both oligonucleotides modifications. about this PO model dKO systemically XX preclinical experiments modified double These DMD are utrophin PN skipping aggressive Slide lacking and dystrophin.

treatment PN Following dramatic PS/PO treated XX ASOs equivalently. saw from different or targeting mice the modified treatments with exon PBS mice a surrogate we treated dosed rescuing modified all surrogate very with effect, the first-generation with was a which

compound. the surrogate a the of In the with treated fact, highlighting dose PN mice lower less even containing PN survived frequent of once again improved when pharmacology containing the

skipping with the NXXX us the for minimal NXXX myoblast benefit. with Exon Just chemistry potential vitro human data muscular in dystrophin XX to skipping establishing widespread along has as tested. a restoration surrogate vivo current used expression without in a XX% Exon illustrating significant muscle normal patient-derived study. at and impact in area need reminder of prompted to distribution normal resulted of the exon unmet model to to Duchenne the yet human dose-dependent observations DMD NHPs increases with similar other DMD in the observations clinical dystrophin highest relevance when demonstrating to treatments of up XX of These concentration proof-of-concept preclinical is applied in in amenable dKO the proceed dystrophy. is and an of only these

activated NXXX open-label boys trial can and Exon This dystrophin to to whether to first-in-human our skipping. As that addressing the determine and thus of likely is to clinical today, limitations patients cells effect. XX are for intravenously eligible drug muscle and production recruiting powered NXXX amenable trial in whether access readily clinical suvodirsen's study led sites our treatment the leads

of plan and safety weeks apply if dosing coming mimicking skipping IV be in every We dKO assessing modifications frequency study patient first the to other the initially also to successful. the plan the the dose candidates tolerability animal frequency to exon chemistry in backbone week the PN at other We will and of infusions is model.

to will ADAR capability. Paloma? who editing turn Paloma on provide over an our I things will Now update

Paloma Giangrande

treat for ADAR to a on to mutation, and ADAR all personal Mike able to become GalNAc-conjugated or and SERPINAX of science for M-AAT. only allele and the our and by a about lung in Z-AAT me diseases. in to today a I increase results was you to note, AATD a this then, these successfully of the US an liver leads initial to both. therapy allele fall, correct you was way which in the risk company. of wild-type the ADAR AAT which editing transgenic circulating join to upwards RNA editing most EU mouse call. genetic functional of pharmacokinetic the to people human potential both to The to commonly protein gene. antitrypsin that a is opportunity damage X% Thank IV into capability therapeutic talk have enthusiastic excited proprietary damage, Z model, antitrypsin alpha-X us wild-type Approximately lack protein goals join aggregation sequences we caused to functional weekly that that of oligonucleotide expected aim good is mutation ADAR hepatocyte and Last I protein a AAT the alpha-X with With all in enables homozygous AAT everyone chronic draw progressive and vitro, inherited the Wave's addresses vivo. a editing the demonstrated physiological is morning a threefold into of our successfully liver disease. containing genetic On which SERPINAX are editing and M-AAT point in With restore deficiency. the significant Z approach SERPINAX ADAR more maybe translating disorder mutation to to we administered alpha-X RNA lung, of the treatment. highest I'm and the program about wild-type functional results, to in when in hepatocytes Since and and lung offered misfolding Z to retaining replace enables moved we improve as or lungs the for to progress led new the the forward antitrypsin of editing, clinic. Encouraged augmentation humanized a develop by humanized we regulation transcript translation ADAR, assessment in protect subcutaneously Z-AAT while reduce human therapy, XXX,XXX in protein. to liver, optimize mouse or human pharmacodynamic is aggregation which in innate oligonucleotide, stereopure of of in This

doses XX% Following three ADAR of subcutaneous at day to achieved two we editing up editing oligonucleotides, unique seven.

these by also low-risk heterozygous, Notably, with a of encouraged results that bystandard represents disease. level of observe we very as the did any are MZ initial not correction we approaching We are patient editing.

in AAT point. mice. circulating And these further Next, may micrograms also protein. is disease. the see investigated point. was the we in we we the the risk potency editing circulating wild-type have floor clinical phenotypes signaled fold of threefold this how towards Consistent steady look achieve no longer the initially two, XXX of from duration state, majority approaching results, is spectrometry, with correction, we When confirmed saw other AAT was This one, as compared potentially editing at and time the MG M-AAT this restored of candidate. patients. see time AAT we look concentration, of in is a see promising protein AAT expect or it with advance mass with of this such a establishes which Z-AAT approximately to XX post human circulating increase to isoforms protein at that exciting a lower percentage what editing that protein wild-type identified mil to looked control total We is at greater optimize when Using M-AAT RNA we of longer micromolar as to representative liver RNA at per as reduces edits. and we increase level of there PBS magnitude observed impacted to this initial This It being increase were levels cleared. Z-AAT in isoforms XX% expect At M-AAT. bystandard aggregation consistent would a as -- data, generated at may with that very increase circulating

the see, restored up In wild-type inhibition post significant increase functional you we AAT to driven to on that meaningful point. we observed that initial these editing, from are a the see vivo, of As of was functionality the in protein. also side are can slide, in which there editing are neutrophil M-AAT results excited summary, this right initial elastase wild-type to an circulating in by proteins, time XX% increases translating again confirming restored

We wild-type and these protein mouse AATD comparable in a and achieved compounds fold restoration. change also RNA model evaluated editing AAT in

duration assessing PK/PD will time. secretion studies into of M-AAT are and how activity, to provide insight dose over ongoing levels response trend Our

the potency We same with be the looking Z-AAT and vivo changes compounds in time, also in reduction new advancing pathology. in studies. in liver optimized At are increased aggregates protein we will at

and Research on half an year. over the of update will share We settings hand the now expect these call Day Kyle. data Kyle? second the I at sets to other to in

Kyle Moran

additional the collaboration in million marketable Thanks, Takeda. an with million $XX We This support with research quarter equivalents under second Paloma. that securities. $XXX.X April in we and early includes our cash ended committed received in cash,

compared last to other related $XX.X were related million of as expenses. G&A for program second and programs, increases million CXorfXX XXXX operating to Within second reimbursed clinical to as PRISM XXXX $XX.X decreased were to same external million $XX.X as XXXX. were there our million collaboration. the quarter increased million million expenses development and compared our as were total $XX.X relatively and were in our period offset external including programs. $XX.X year-over-year $XX expenses R&D discovery last research expenses year. compared almost preclinical R&D, well the the Our the by These to for and driven at expenses discontinued our entirely by expenses as consistent quarter increase expenses year external related with Takeda to compensation-related expenses

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

under a does potential that, With reminder, back this As Takeda uncommitted payments other include payments our not and to milestone over Paul. collaboration. additional I'll turn the call

Paul Bolno

into Thanks trial transformational generation Kyle. data XXX data believe With dosing Wave. we underway behind, in ways. These insight three as PN a safety well our entering unlock chemistry as for of intervals by implications the effects of in value soon provide and biomarker tolerability. NXXX WVE-XXX trials clinical results clinical of are period and dosing clinical clinical way will multiple and potentially for will We

would ability and an any entirely apply therapeutic unlocking to enable studies these improve indications. chemistry multiple in paths distribution, insight from on in with to and WVE-XXX of would CMS uptake multiple the success pipeline the targets PN with DMD. these registration targets. programs our intrathecally wholly-owned WVE-NXXX, engage programs existing our WVE-XXX, of clinical compounds undisclosed gain delivered trials we'll two effects derisk results different collaboration across into including Positive in to to modality to potentially chemistry and designed ability of other For With exons and exon this cellular CNS skipping our Takeda

enabling continuous us to with apart team on in these therapeutics. exciting lead is programs are new editing This the to the of we Our way time updating We and and ADAR Wave XXXX are from multiple editing data chemistry we look data us decision-making. in from as progress. with the to generate building field others preclinical are through to a Starting in for targets. our exciting enable generating on advances an results GalNAc-conjugated flow we forward oligonucleotides developing liver sets you

new the how capability to Day XXth, and for we Analyst ADAR you coming we highlight feature More be and our call Research tune upcoming AATD editing September that will our Additionally will with which program the shared hope editing the open questions. on data beyond we'll Investor are will from provide liver. in our on the Operator? on updates advancing And ADAR details weeks. in up Day Research


session. ahead. begin you. question-and-answer Thank We’ll have Joon we [Operator now from And go Truist the Instructions] Lee. the on line Please

Mehdi Goudarzi

Thanks this our Mehdi Hi, Goudarzi question. for is Joon. taking for

related to great study, FOCUS-CX provide expected you this CXorfXX your the be would level treatment this if color could efficiency is specifically and of some question for and Thank it disease unchanged on Our possibility of considering you. pathology? of haploinsufficiency

Paul Bolno

to take targeting the we're how to I'll through to Mike refer go your the happy against We're question. disease approaching study. and clinical Mike?

Mike Panzara

haploinsufficiency. the take I to mean, of targeting publication to consideration the our taking strategy did preserving on we're in we that I variants approach think avoid the that recently have while is that healthy shows a that the importance reducing just variants, mutant

and that down that the the our of anticipate CXorf think protein. with the targeting approach balance that have that we strategy that in it current and has considered -- normal it the toxins is preserving XXX our bringing I we So again driven -- while compound

Mehdi Goudarzi

right, All great.

question. I follow-up a may I if have So

variant a specific allele is module selected, or not? WVE-XXX this also Your is

Mike Panzara

not go the after contain because all right is expansion in have was variants silence And of Well, goal entire the multiple where the have not that to right, variants that the way little it's case allele. to we the you different is The shown so gene expansion. the is get a actually the the presentation all -- transcripts the transcription here HD, are the in occurs way as produced. these goal the

getting So selectivity you're transcription. the also of normal targeting allowing you're mutant, but

the objective variant the in detail. this we good the because very a published on selective, actually -- in So in all bit different it than CX in objective through it that call essence goes paper it's we HD. it is In

Mehdi Goudarzi

Thank you.


we Please From have Mizuho ahead. go Salim Syed.

Salim Syed

the question the and for congrats thanks guys, progress. and morning, Good on

compare just on or guys And was point that in Mike ADAR potentially is your looking on there here as on or there XXXX? differentiation here, are field field any So the wondering CX Shape's a you questions and that the in you. data terms then Thank ADAR to if CXorf. I the release one language ask are develops? wanted as for I things triggers just can develops XXXX publicly of or ADAR you're as for couple we and get Korro's of data to to things wondering what Paul you program one the through clinical I'm here anything if just so could On program, the

Paul Bolno

CX. with ADAR we Mike and about before start over who pass I'll talk then Okay. can to

an stayed I very think that chemistry capability. that so at just the upon to it is ADAR nice focused last in-house our off short chemically and beginning leveraging of we time which capability progress, to your building that oligonucleotides the Day question cells chemistry gain of at see that it's this on continue best on R&D the I leverage believe made. it the in access early unique It’s we modified adaptations is something building to shared building right. we've and

and So getting endogenous potency it. using potency PN using the in ADAR the to both seeing so the to advantage enzyme on

do And to into to sustain that's ADAR. engage that accessibility getting lastly of Two, to ability the we've about I set that to over get oligonucleotides the so these the been cell work endogenous time. and short out critical. that's speaking So to And compartment activity durability. then think the

think great the more a it's space. people entering I editing as of ADAR endogenous to see field

to as optimize. and think to today, call alluded is what continue we've I Paloma the consistently on done

of on editing And the is the clinical what functional ultimately, that continuing to our that therapeutically protein production. that frequency patients. of candidate and is continuing the over which relevant that will protein we build functionality floor now reducing sustaining durability on measure the for and pharmacology today establishing where time have meaning, think alpha-X growing into antitrypsin go we So the and potency administration, subcutaneous approach so then, to

So have their in to think designs build I different others approaches taken the terms that they're and using toolbox chemistries. their of oligonucleotide

test as the make because we forward one the rodent answer accelerated models question chemistry to Does manufacturability, one, not potentially -- make of making at also we'll we'll is the think just our I capability of scalability talk what's the that is think to drivers to in that this I about chemistry take of here -- to take then, pause answered the advantage we of about this the molecules being able a ultimately but that we Wave that and Salim and question. preclinical on CX work know have can sure, commercializable ADAR primates therapeutic. key nonhuman

Salim Syed

helpful. Yeah, I Thanks that think was Paul.

Paul Bolno


Mike Panzara


So on then dosing process ongoing imagine have here follow-up to the evaluation an independent recruitment committee safety can where the you you the of mean, CX, dosing, frequency. adaptive I and recommendations, is study design -- as flow

again, other study the material could the would to throughout those are that treatment, timeframe. benefiting, the of process some development including is mean, disclosure. be out nature continuous next could durations design. there or on going are feedback. to disclosing illustrated changes in phase This study the it's patients feedback would is are of of suggest material it's there and So that things make prompt positive of being that a sort committee would in us negative be a There's ongoing, I that moving a variety But block concept design, data to disclosures, things generated -- disclose. like study, aspects those that come it's that this regulatory of prompt is that assessments registrational changes of

Paul Bolno

not it's just CX Salim. unique And to,

forward data clinical thought clinical of that. programs. is in on we've think point, that much programs designs we've And data this generate and over decisions make the as brought been interpreting that I to I could I our why that in quickly -- we moving purposefully bring -- So generating Mike's we think innovative on multitude and our time about have to think to as terms molecules of then

now got forward as through XXXX. move think ample we've And or we opportunity I so

Salim Syed

the for time time Is looking you in you before the even planning are that there for how disclose to first that you're to that I Cohort data I there cohorts. cohorts data at? X mean, consider specific given single-ascending? releasing point is two or mean, a wait first are amount of four for to would you a certain cohort for the example, going pass

Paul Bolno

enrolled. studies think it I So --

you opportunities There's where across studies. trial I on the on saw being design. target that's As made assessments mean engagement ample are

studies the of cohorts. into that's built So across design the

studies. of clinical sampling to is each that not those a in that's dots I of think on what update one the we're regularly the scheduled guiding

that did study. that us of the the think are an I material study would out Mike say update in pointing to disclose occur a cause job great changes to would on we that there need

expand to again opportunities cohort engaging And you're example substantially you for to where that so there's the potency committee see knockdown target existing next the data and don't reviewing cohort. just forward-looking we move we see have the in as safety

set publicly, there would changes that data from be by the informed are study where design a the trial is deviation be we've what this out done. So as that can clinical to

exciting that card evaluate we're kind drive looked happy think end historically and at it's where of the the of we're So of I a as a end and see not of and updates. its periods now running And in landmark let where at And we studies. flip lot the fixed our cohorts five the given going data events past the those experience all CNS time in the I same where are. to think position enroll then that data

what know for substantially a to an study I that study. what to part provides this changing can assessments it enables to and the -- it provide is a Mike lead registrational challenging to could do, that these So that And that, periodic take important to would times us us is decision get of said as that contract is that. this

studies. the those as updates, to others provide we'll making progress and this as year So progresses -- we're the as along

Salim Syed

Thank very much. you Understand.


have we Paul Stifel Please From go Matteis. ahead.

Alex Thompson

Paul. Hi. This Thanks Alex on taking for is for my questions.

have of wondering knockdown you disease of understanding question for, natural that. follow-up. sort And there or thinking from on PolyGP I another threshold are have looking how is you're we history, that a another links was an severity? about quick Thanks. relate how do to CX, And I Just then,

Mike Panzara


is Regarding -- Mike. this

level of PolyGP right? may that not out the CSF. that data linked directly the is to be disease in the of suggests PolyGP, there The severity actual now of level the Regarding

have people are detectable low. can a symptomatic And you are got who So and that have PolyGP who sort level. relatively at of pretty you are those the disease high people levels carriers

has of to indicator In CSF there. to because is of in interventional are as to just to that have it We level get and the whether dipeptide to proteins translate knockdown So that. It that multiple possible indicator to lower studies, into what the the -- able progression, because minimal detectable be are want end, changes poly see maximal an data we of level -- as the to as an with clinical evolving. happens the is changes. goal much those remember

just of there trying DPRs PolyGP treatment the CSF other different. are tissue So the affect may be also indicator. CSF are that which through are is also, we levels concentrations one an indicator to just of And

So clinical It its to would a it target it That's goal engagement efficacy again, is it's drive marker. confirm and into us purpose. down. get study. The would forward a

Alex Thompson

That Okay. the makes it's filing? on program, can at but steps and us for it sort And optimization sounds of just sense. see that AAT the walk of kind ADAR you point, this IND like, you an through

Paul Bolno

different. steps think of I not the mean, a lot forward are I Yeah.

approach what's or IND-enabling there's there bunch I safety safety think would in terms studies of think I take Salim of And studies. as different of important can So whole the enabling a mentioned the away do CT you and kind normal that I approaches.

as impacting anticipate oligonucleotide. think different that's there would another the be approach RNA we for bring would GalNAc therapeutic oligonucleotide we forward an I wouldn't that doing transcript, studies we be to

approach vectors impacting So using is this DNA. than different or viral the biologics

of model So levels that piece optimization, first engagement IMP that put aside, to this that that we're we've year, the point relevant is I on demonstrate that's Prior package. to first we think was that of step which half achieved standard your what to in toxicology at us a threshold. the this preclinical program that in in delivered target the tells

the we on is and call as potency, into that the on call as and Where alluded see that range pushing is durability. of about Paloma so optimization that the floor. higher to now with enhancement continuing mentioned balancing to occurring efficiency So editing us

administration. So of frequency again, the reducing

to update as data line that the a I a we're on candidate. think release since that in we're that much track to with on made compelling space the for program and that's it more we've clinical progress and will building give our doing excited advancing up comprehensive path why

So more at the what where kind of letting about durability on talked are potency to with We we've the without level that's come ADAR, optimization. think [Indiscernible]. it's fine-tuning now maximum about they Research to but Day achieve

finalization what the levels are package. of will So we're I think go just the substantial achieving we where today. into candidate It's

Alex Thompson

Great. Thanks so much.


Please have RBC Issi. last we our question go from Luca And ahead.

Unidentified Analyst

Two for Thanks on great. us. This is the here. Hi, for taking Luca Lisa question. from

first Just wanted ask to off.

know are also thinking Biogen about think the SODX, not get the because I XX for you're is So data levels? NG can we have always they lung that and expecting this we but you. that fall. And and issues? some here ask going are that a Thank that question in for And believed data for aren't SODX-ALS serum AXAT Ionis do report wondering you know in after bar as just I potentially could NG and AXAT that but to know any liver patients, normal patients how talked programs. to KOLs on the also follow-up or have asymptomatic success is implications still the a at from your I to micromolar least achieving know the patients we back you And XX bar reason micromolar is we've originally and for

Paul Bolno

No, it's and one a second your then we'll take great question. I'll first transition.

micromolar talking that regimen. continued we about reason while I why we we're So the -- don't about stay dosing think talk a focused and we in why there's don't XX optimization on

we your us exactly could the AAT restoration So get point. key functional of levels, certain to for and achieve identification I think threshold was

we've was bring us forward key continue that the advantages that where opened I think floor door and the saying that establishing to of for are. possible

time following well. key over I to this as think is going be the

are sustaining functional not can where protein when restoring and at the your the we what's time. that a It's data opinion the with it's body it. pushing there had we've So about explained expressed is just as sharing needs leaders. where the that do requisite that's needs it. work It and a do discussions be going thesis over a protein we're and to needs the with the reactive And in level period to key it really underlying point, about body of Paloma

importantly, an a modifier. being side. not there's on this lot equivalent DNA we're approach restoration enthusiasm of and think seeing the approach I And this of functional one about for a excitement

that assay and protein, we transcribed the and functional protein meaning again, and are it's there making needed. it's that's So elastase this when

able of I -- being to of as floor really again blocks going think are push do And building pieces the excited show those into availability program. to So we're this the the more. the

it's As features. we've to we historically looked this pick at But of the other think transition do Mike let side. comparison to the number a in on and up I'll I important SODX and

I designs, it differences new in is exciting terms that exposure. new bringing we're chemistries distribution think have of forward that durability

So read-through challenging our somebody it's else's programs to and and from what own. compare under always chemistry

I'll and let support letting Mike we data think to I those data data drive vivo this for forward. have SODX think in we speak with those now our that letting preclinical we're our But extensive space. about programs programs how specifically

Mike Panzara

FTD, you that gauging And this the for with but it in clinical about when CX and approach leads outcome and I measuring still obviously track. we that benefit. meaningful of now great now disease once on for pharmacology, again approach No, PN the is effect -- that target potency a optimistic result for target patients like. have the think and about we've but upon intrathecal then clinically administration about this engagement Yeah. the the our high And depend is in potential this when that into a about demonstrating clinics. with different the advantages reduction look of what for to the quite we're validates to us and of where obviously effect approach a talking diseases think pull the disease two doing certainly -- data in makes actually right that in the into all next-generation target engagement in also potential neurological But translating it target you it been that will translating durable

it makes we for So it it to effect, potential are. clinical CX program administration IT brings to the us where leading at actually as looking optimistic pretty

Paul Bolno

that. on think I put in I mean, the end and a to Yeah. just summary

seen neurologic for is disease I in desire to we've think what the devastating work. medicines

while So SODX but -- an I ALS discussions do CX in smaller is there are open it underserved regulatory to variant overlap, on paths up I and around than patients. approaches that sense bring a the hope not we it continues that patients are and hopeful think there's think that for to

So best this space. I think -- we wish the everyone for in

Unidentified Analyst

helpful Great. very you, Thank


closing for now it Thank to Bolno turn remarks. We'll you. Paul back

Paul Bolno

Wave everyone you Thanks second to call for to joining the Day We quarter updates. to And for employees look to Research our Have thank in commitment this our patients. corporate at their to the forward day. our morning review you hard XXXX again speaking a work fall. and great


concludes you for you. conference. Thank Ladies today's and joining. gentlemen, Thank this

disconnect. now may You