WVE - Earnings call transcript Q4 2024 | Wave Life Sciences Ltd.

Due to licensing restrictions, you must log in to view earnings call transcripts.

Operator

Good morning, and welcome to the Wave Life Sciences Fourth Quarter and Full Year 2024 Earnings Conference Call. [Operator Instructions] As a reminder, this call is being recorded and webcast. I'll now turn the call over to Kate Rausch, Vice President of Investor Relations and Corporate Affairs. Please go ahead.

Kate Rausch

Thank you, operator, and good morning to everyone on the call. Earlier this morning, we issued a press release outlining our fourth quarter and full year 2024 financial results and recent business highlights, including progress updates for our obesity and AATD clinical trials.

prepared Dr. with today me remarks are Joining Paul and Chief Dr. Executive Officer; Bolno, President Scientific Moran, and Ingelsson, Officer; Erik Chief Kyle Chief Officer. Financial of release press the issued morning our section is website, The www.wavelifesciences.com. available this Investors on

conference several those results I'd results actual release any cause revise could differ begin, in are to our SEC the press statements. These that you factors statements undertake during forward-looking reason. I'd or to the in to Before described to turn to uncertainties forward-looking call call subject issued our for discussed that like The any we forward-looking include update and to like will over are actual from today now no in and to that filings. these differ We remind discussions obligation materially Paul. this risks statements cause statements. could

Paul Bolno

and for Kate. you Thanks, us call. thank morning, on today's Good all joining

been potential XXXX to to decade, this past committed unlocking AATD, that relentlessly vision. We our the incredibly address announced of an was entirely expanded clinic human patients. broad pipeline programs, the and Wave transform year positive important we in Over for realizing medicines RNA health, have of derisked high-impact RNA supporting modality to in data and the HD new with novel with our have editing, DMD potential programs clinical an millions and

And year, burden silencing to take part the acknowledge for to Wave, healthier that this obesity ways highlighted execution obesity. clinicians, and for and stigma on we combat program with our consistent deliver the advancing WVE-XXX, the At by World deliver our of these for to as community progress for resonating. our lead of each action advancement people today, Obesity kept has GalNAc-siRNA like the track this engaged Enabled has this weight with than frontier with with is discussing to by start futures made we We this best-in-class obesity treatment and the so opportunity living obesity XXXX carried X obesity first the INHBE technology, illnesses. the into our WVE-XXX conversations, sustainable we've today milestones with believe can have clinic, momentum strong us March healthy, key for obesity loss year. I'll chronic reduce to billion this siRNA as well approach WVE-XXX in has X, potential more do Day. on disease to to related the we are for is individuals next our global. living community. In I'd

unique becoming is to standard fat loss of poor by among best-in-class just care through their tolerability twice once dosing, is weight entirely induces provide WVE-XXX limitations. designed While without rapidly a It drive high an uniquely of positioned therapeutics, to believe of GLP-Xs addresses rates. impacting that use or reduction mass, a mass frequent muscle weight burning action discontinuation are approach is that loss and We these mechanism with often muscle doses limited year.

with not loss GLP-Xs, greater Our its as add-on treatment have requiring synergies including only cannot but frontline on as who preclinical weight higher demonstrated options, data an shown have individuals GLP-Xs. of tolerate for doses potential XXX or

is avoid just we say our GLP-X off-ramp weight about enrollment common adults This ongoing cycling. Dosing of excited once enabling an healthy and clinical in I'm pleased in for the have and also cohort. INLIGHT of are as maintenance weight to weight is risk that metabolic WVE-XXX with first twice completed the already overweight. And to associated obesity gain would the living approach GLP-X, potential maintenance discontinuing long-term We WVE-XXX's when dosing. with yearly or that trial

healthy in from year, tolerability which biomarkers this will include reflective data initial the of deliver to and second safety, loss. of expect the We trial half weight

editing a WVE-XXX addresses GalNAc-RNA subcutaneously disease our AATD Turning with require has be root treatments the to on dosed and first development, potential the to the or of that IV from AIMer, approach technologies, and the convenient hyperactive not complex differs alpha-X editing cause for bystander irreversible which deficiency WVE-XXX, therapeutic. oligonucleotide treatment vastly collateral artificial and rely antitrypsin do indels. vehicles that administered edits in result DNA delivery our like exogenously LNPs enzymes other or delivered in can We

those delivered other healthy Our enrollment clinical X study have baseline we trial as observed restoration cohorts a as and durability XXX we support a the an data all first-ever and profile, study dose potential levels intervals clinical program dosing of and among impressive participate and clinicians with humans both well-tolerated patient higher and demand announcement, and the patients healthy patients any and volunteers, at observed the in as in single of our study. single to of our Multi-dosing AAT the AATD for X.X circulating cohort micromolar our the clinical the in with editing breakthrough cohort called total patients XX.X from is planned WVE-XXX. in last cohorts. day preclinical receiving subsequent favorable WVE-XXX patient year, completed than this started late in in volunteers. Since RestorAATion-X have was we RNA with now of are planned we day extended and completed dose for a multi-dosing In in surge study. In with and post of where micromolar X increases week, XXX-milligram mean XX, clinical early as in in first every demonstration underway effect. of in safety AAT the including X seen RNA cohort, medicines RestorAATion-X, weeks XXX-milligram M-AAT

at the single-dose cohort higher single-dose XXX-milligram cohort believe insights coupled initiated the with have into multi-dose We milligrams, this cohort, the give meaningful XXX dosing and second us also will interval. we extending

data and including the XXXX, portions. single-dose full complete from Looking ahead, will cohort first we have the multi-dose in

potential both XXX, advancing the WVE-XXX our to XXX-milligram RNA programs. Behind inform cohort We single-dose pipeline plan from potential of and upwards and will therapeutic also unveiled of pipeline our data collectively data XX a targets. Day hepatic These these million we're extrahepatic of year. last further share the patients. at X this address editing discovery provide which Research to We year, programs addressing owned wholly of the

boys year development sharing readout muscle initiating and from the end we preclinical collected data the As clinical year, additional are with Duchenne of the skipping. We observed highly hepatic up stem myogenic programs, XX-week give of clinical we amenable muscle concentrations mean to health, monthly dosing trial new that XX myoblasts therapeutic the month. that all our best-in-class of and and goal muscle RNA our progenitor ultimately extrahepatic distribution a In regeneration. biopsies of of demonstrated new by for data to programs track progresses, have living muscle plan be exon been WVE-NXXX's DMD FORWARD-XX cells to skeletal to on deliver of for potential intervals to interim dystrophy, with editing on in muscular support we adjusted in new evidence the dystrophin from myocytes last consistent muscle content improved rise to the cells, aid this XX% XXXX. In X%, and

hear weekly for an burden and observed therapeutic a and for is safe a the devastating safe dosing IV disease, there we Importantly, the well-tolerated We profile. DMD data of therapies effective options from which biopsies, more and and life need frequently need patients. and urgent is about cells, as improve include for XX-week benefit, caregivers to would quality ultimately enhance and distribute survival. The of functional dystrophin tolerability. heart as safety measures that stem can upcoming for the extend well and functional diaphragm will reach and muscle also

of the deliver on track from to are end by feedback We the regulators also month.

positive As supported living a reminder, data by have portfolio plan our DMD, muscle on pipeline and advance up we of of boys previously XX% best-in-class pending oligonucleotides to delivery. our from additional we to updates exons shared that a with addresses NXXX, of

members. allele-selective alone, all multiple disease turning the of disease. first-in-class to of sometimes HD family XXX,XXX available. U.S. impacts there The and at impacts is is disease-modifying generations and no therapies treatment genetic in Alzheimer's, oligonucleotide once than ALS and and Finally, an are Huntington's WVE-XXX, disease Europe compared to that autosomal-dominant our devastating people the having Parkinson's more for

have committed mRNA level, By to the neurodegeneration. of allele-selective addresses drivers than to HD platform's years, to unique protein mutant more we pioneer Huntington WVE-XXX using the and XX For chemistry the underlying our reducing been exquisite and and specificity at community therapeutics.

by is beyond. specificity possible the patients. addition, which the to to positioned allele-selective HD uniquely control spectrum health is sparing stereochemical only chemistry of that WVE-XXX the our system, in wild-type and became from platform's through critical through Huntington address asymptomatic of protein, and of nervous stage of In It is symptoms silencing early the full best-in-class central the onset

caudate atrophy potentially our known Just had by SELECT-HD the a attended the accelerate endpoint, clinical predictive primary development team using of WVE-XXX that conference CHDI where last clinical is week, to imaging our share opportunity of outcomes. marker and annual plan to I results a as our

dozens we in silencing. addition In with enormous our WVE-XXX to had and HD researchers leadership of for heard presentations, and advocates podium enthusiasm and allele-selective great our and poster conversations

of a of data and durable preservation X trial to just As WVE-XXX. reductions with showed from up huntingtin reminder, huntingtin the potent our mutant XX% and of SELECT-HD wild-type doses

atrophy, about onset shown X% was symptom there first in the and brain. been before X% the a a of steady huntingtin and and Importantly, part where of atrophy at of the start Caudate of the disease. Caudate Huntington's primary time to we such marking supporting mutant areas years analyses correlation beginning been at striatum per year, and allele-selective of such own HD one a statistically shared some a between our reductions have decline internal correlation. the has is of rate the loss in many clinical outcomes, correlations significant continuing and of year, observed slowing correlation caudate between manifests With

rate absolute Specifically, results that with years. last with caudate our reduction as on of strategic including details more supporting to supportive the Preparation caudate showed and using WVE-XXX in number economic on remain than from II/III the is our SELECT-HD, for clinical outcomes over natural and for and year staggering call second emerging a Phase delay health in from caudate half is rate an registrational for of we a to to evidence with associated potentially atrophy primary disability is year the on look meaningful along on PREDICT-HD, of update with which datasets in and X% to trial we by II/III clinical TRACK were further primary and data, X.X engagement just for at study a and to progresses. With that full interim, feedback. trial. These and history this an continued detail looked more global as endpoint the clinical implications led Phase initial both track IND of SNPX including year. In of including receive trial and in endpoint, now applications, as to atrophy the of efficient with study forward potential provides a engagement FDA a ongoing Erik this onset adults This an our design application HD forward submit turn of and partners, pipeline. the HD, path sharing I'll substantial more part provide that, INHBE an share we've

Erik Ingelsson

Thank on thank call you, and everyone you joining the us to Paul, today.

some of of on may as discovery before focusing scientist Human other X the and know, all across of Genomic last Head career therapeutic first target diseases, spent As Wave later my GSK I joining last Science then part a at medicine at spring. cardiometabolic physician areas obesity professor you Stanford, of and as Genetics, a years as

program, abdominal to excited genetics. The our targets of underestimated from all incredibly such For not fat higher the I'm talk obesity and circulating for support to be upregulated, INHBE binds should maladaptive compared that Activin program of INHBE probability support is obesity. We about expressed in INHBE In activin supported targets any human success with therapeutic as levels reasons, genetic E of evidence. INHBE higher E target increase an alpha-X of promotes benefits this and of light our several resulting strong times mRNA and storage to secreted by omnipresence the to on is liver with drug Activin human X gene ligand chose from response, energy is in produced reasons. without dense adipose associated due to hepatokine a when tissue. predominantly genetics in receptor liver liver E. of development in food, average a X its are these

and upstream at and specific First, cells. INHBE to down E in INHBE of obesity, leads profiles, highly efficient silencing variants visceral for and and have carriers GalNAc the favorable an studies obesity lower policies, source have including activity regulate reduced allow thereby turn serum fat, our liver to off weight profile. Several adipose corrected liver oligonucleotide measures activin lower fat triglycerides, higher several fibrosis, MRI fatty ALT, production pair. improved protein resulting a healthy glucose, levels an decreased targeting like ultimately cardiometabolic in large to gene human inflammation loss the loss-of-function abdominal to is abdominal metabolic leading specifically found decreases genetic APOB, ligand that directly in receptor TX, And heterozygous score. and way this and activity efficient liver of the liver HVAXc, disease of best-in-class and disease, nonalcoholic using measure to second, conjugates of most chemistry

Importantly, these risk reduced diabetes coronary X carriers also and type disease. have of heart

essentially, the also of of done supports been threshold already therapeutic Nature's outcome which the So XX% study has the INHBE silencing experiment, using mRNA.

the healthy driving providing of of of recent has circulating in genetic convincing E in preclinical In internal importance and strong samples individuals, correlation BMI from studies activin humans. and our obesity with additional mechanism data, an a to addition confirmation levels work this demonstrated blood

people years, over new disease drive we've in underlying the other obesity. important incredible current space, and living as examine and efforts development. treatments, agonists in to therapies develop subsequently for the As GalNAc-siRNA with have seen therapies context approach for INHBE outcomes the step our past which such the to within back causes of there broader obesity the been It's meaningful GLP-X treat several of and

it for as with have than directly acting on Paul. mentioned approach data mean acting on pound-by-pound action Several as already at position guidance appetite on but on establishing weight loss, associated opposed opens orthogonal tissue a cases fat presented that day earlier by weight also or last alternative, in fat therapy an agency's shrinking medicine, transformational research many FDA this of our supported as obesity muscle an therapies peripheral an drugs from rather on also GLP-X, disadvantages year GLP-X, focus our disadvantages by that to of are concerns which focusing centrally Not sidestep which that up opportunities been on including developing involves we to to regulation. this these recently, highlighted only in draft Although the centrally standards loss, addition, for as preclinical off use mass. WVE-XXX drugs leverages sustained X reduction, relation emphasized brand, does fall. focus GLP-X study we

already body pharmacokinetics, in of metabolic single-ascending human first adults Our overweight shared and approach INLIGHT. unique of safety, to is progress enrolled. WVE-XXX composition, trial is of the second excited from forward target in the look for is weight other This underway, and half study portion bringing as this in transformative data made assess biomarkers of and or living Paul called the earlier, and The the first We're tolerability, dose the study and we've is sharing trial year. designed clinic fully cohort with by this measures engagement, very to the health. obesity into

homozygous advance with have WVE-XXX mutation. the BICD emerging our in editing who continuing Now Phase study to RestorAATion-X Ib/IIa turning patients to pipeline of in We're AATD programs. RNA the

impressive Our of durability with initial effect proof and of potency mechanism WVE-XXX. data demonstrated

M-AAT will valuable assess as year WVE-XXX. our pharmacodynamics dose regulatory to levels approaches are novel biomarkers programs All at areas offer XXX Our supported in the which with owned treat built restore paths. data of our we to programs feature learnings human to are broader strongly genetics higher by as shared and provide on pipeline, wholly These of X also need. accessible and expected to along healthy from editing, leveraging high on RNA doses, of we ability established assess also year, diseases learnings X RNA multiple continue readily and unmet editing which with programs well ways protein clinic. Last will advance later the to These towards level. data preclinical data our this

to for WVE-XXX, leverage GalNAc delivery with they As conjugation efficient liver.

familial genetically to we program lower PNPLAX IXXXM decrease to Europe aims large not among liver a XX% and IXXXM X respectively. Fewer correct to people defined apply revert which the million in result by a therapies Both LDLR aiming XX% and can Europe. of or editing development. Together, PNPLAX silencing million over expect individuals or our of of people to population in heterozygous and PNPLAX the our APOB and the correct hypercholesterolemia Our upregulation and and cholesterol the FH. programs data than will FH includes This of the goals early U. liver disease package upregulate LDLR to technology LDL carriers with FH dramatically their LDLR and that these comprise reaching that fibrosis in in statins steatosis RNA options, variant dominant U.S. APOB with heterozygous disease treatment designed with people This correction indicates disease. treatment includes homozygous other mutation inhibitors, X driven to initial in substantially people their living program S. state, comprehensive by the programs PCSKX with current reached goal. and indication served including are APOB

from Additionally, massive Two controlled disease U.S. combined. We sharing to our comprise regulation RAP statin cardiovascular new with that prior upside hepatic people clinical has I'd people or cholesterol. well million LDL intolerance in expect like multiple data initiate update Europe groups to to provide with extrahepatic to XX XXXX. With over an LDL Kyle editing year, we anticipate expansion programs development preclinical and turn poorly to the approach opportunities as and as financials. that, over on call this the our of RNA in programs Kyle?

Kyle Moran

Thanks, Erik.

the and million to development and driven and remainder year prior expenses primarily the the was revenue was Research revenue Takeda were and the quarter-over-quarter Our compared our $XXX.X in $XX.X to million $XXX.X deferred as XXXX, driven in collaboration. Research of full year of XXXX. our quarter, period million same increase the compared along with $XX.X expenses in as was by fourth in the for and million INHBE quarter million $XX.X and $XXX.X for quarter in the XXXX for DMD AATD $XX.X primarily and year full increase our under compared by million of XXXX. respectively, fourth $XXX.X recognition million, spending were million This The year. in XXXX, program, to development programs.

the Our million $XX.X million G&A expenses to year and of fourth quarter XXXX, to were prior $XX.X as for compared quarter, year XXXX, the $XX.X compared for XXXX. million $XX in million in the as of full

$XX.X the loss was was million income as million year, prior net for XXXX. We XXXX, to a the the year XXXX, loss fourth as million full $XX for to of in $XX.X million for cash quarter Our ended compared in compared GSK. the of quarter. $XXX.X Net in year-over-year $XXX.X net December to from XX, equivalents, XXXX. to is primarily in research our increase year payments million as the receipt with and due million financing proceeds and cash cash and milestone funding compared of of $XX.X The

We other now cash will in included not Paul equivalents cash that Wave sufficient closing fund to for XXXX. It's to our into expect and note payments future important current cash are that our over turn remarks. be back collaboration call GSK our under the potential milestones to and to operations runway. I

Paul Bolno

Thank you, Kyle.

start over points to inflection for data forward to that, looking Operator? our it with ahead, multiple editing of We programs and X to our from the value-accretive RNA an turn operator off across in are Q&A. clinical are growing I'll XXXX and incredible pipeline. With expected all milestones

Operator

question the line first coming Now, from Feiner of Ron with JPMorgan. Instructions] [Operator

Ron Feiner

This were to ask is on for WVE-XXX. Ron about Eric. hoping We

therapy, and earlier, X, as that But a augmentation expect of top-line, out baseline looking should the kind protein functional. the us baseline such that the I readout. is If to half level if trials, put that on for clinical at of bit give the we more at baseline the the total, that's X. know news about little you the at information you other can closer for at the was

kind on level trying just So get to that. set of

Paul Bolno

would you the But single AATs. Yes, what at of assay. baseline lower highly thank point stepping as single levels the limit below I mean, if we're you. saw be think at dose dose, that detection not the a back look we I XXX, remember, lowest of the forward, therapeutically of was just encouraged total starting relevant the on we

definitively XX for continue generate we to M of to others XX.X people studies. think that to protein the I as across be generate levels important important as thing was M the the follow the that protein because But micromolar. is level tracking X. data, That is is our So data, most really

studies So patients ZZ make these don't any protein. are who entering M-AAT

track over total that of M-AAT that's the protein protein safe we of And indicative -- the sorry editing. so levels, if protein, we M at to it's level the imagine action and mechanism continue XX% of saw was the M highly of to level

editing across consistent. say having generation, protein So on of in therapeutics correction, the an impact it's preclinically what IV that And the we've to industry tracked the terms see editing be aggregates. and with programs saw in of followed benchmark reduction that and well, that the best you we the way as levels replacement. of was historically, total things time should I AAT a because, efficiencies one be of to field protein and In of

alpha-X serum. you they breaking antitrypsin, go protein if So also have these aggregates up, into

levels of can that's time that the from of coming out over related and sources, so in to aggregate. a those directly changes are to related And coming through those editing the protein have serum the total variety you protein

it's M in most editing patients. is the these X follow consistent ZZ way to protein So efficiency because

Ron Feiner

XXX. weight on DEXA or to measurements? more mass change do that DEXA And the we're absolute the expect doing we compared scanning, or often of you to muscle scanning one are just of mirror how Maybe weight loss? to When lean proportional do pattern going

Paul Bolno

we out what to we fat. your of in to off coming definitive scan is weight which scans I really loss, importance Yes, is saw, point, so are haven't intervals, when replicate was the the we loss in adding but of DEXA that weight those preclinical broken saw yet models, coming that think DEXA

the experiments we've in was combination on across change mass it run where loss, [ ] all single systems the multiple that with no withdraw fat So muscle and in study. preclinical dose

healthy, study DXA of the muscle to that one that use preserving lowering, scanning enable we biomarkers as in sparing to your as this with can evaluate study. multiple we of that will point, loss examples So in using of fat sustainable us have the weight in clinic part and

Ron Feiner

be maybe then DEXA from indicative short just pattern GLP-X? with loss a weight would the of healthier one And scanning versus one. a signal What

Paul Bolno

Yes, is can multiple DEXA dynamic a share we I What study scans that. the opportunities with we'll range that. have not can we show -- give which to shared have across we that

Operator

And our Syed question coming of Mizuho next line from the with Salim Group.

Salim Syed

the out Paul, XX the maybe a X discussions few us getting perhaps, readout is considering since being data, coming then get it on you just just pretty here. here. as on we with just or week just regulators being us, the that closer confirm DMD are had XX scenarios discussions the Can this XX from the week? we we're for bookend clarifications quick readout? And soon can the should just with with be you data week had -- And here, that

of Just consideration you've your if hand, much current data about just current that kind how data here? as if thinking the switchers, in PMO pharmacoeconomic remind us with you where And pricing how also then in work, that's considering set? preliminary even have a this you're

Paul Bolno

you Yes, you questions. data. no, pointed around out, process the as is for of thank the this And the

the So the week XX data datasets existing we anticipate having was continue feedback consistent XX that I agency study. mentioned, week data being these we'll data the from that in is the we as around And that have. the as our but line with shared we from been forward, engaged the move one, we to what's previously. data, data Obviously, have had was

to be well give the the data update -- that'll as an as study. able both we'll regulatory the from So on interactions

As sure were each it one there, relates Salim, I couple a sorry, we there of hit -- to those. to so make and want

I of one been highest things most variety mean, think coming dystrophin the we've about As of we the think of of this, the scenarios the that seen consistent before, is X%. I seen out level that's

about about dystrophin consistency I so, to think that a what to going lot do learn to going we're same months dosing think on that regimen and X the subsequent magnitude, a staying kinetics. is if And we

what to opportunity understand in the dystrophin, with there's blood think stabilization or and I happens dystrophin. frankly, of So telling increasing

additional assess So that X we're be to to dosing. going of the able over months

to initial muscle we health CKs, I think cells. stem we the improvement, study other was to dosing further in important that's -- with the improvement We saw in saw going is getting thing muscle right? at saw repair, be those reductions regenerative already

as assessing a X health. of variety muscle be going And is that we us important what's over of well, whole months. muscle subsequent also architecture So features to will be the of improvement

So again, in the muscle opportunities lastly, then to more being look muscle clinical at importantly, improvement impact assess and repair. And to of able measurements. health,

So while it's think I expect powered study, statistically relatively outcome observe a significant small still clinical do to measurements, not for trends. we

to being on at so measurements. ride, And opportunity to the muscle able us able ultimately translation to clinical health velocity, look the markers that assess impact time and to in to at being give look muscle that sensitive will XX% of stride other integrity, and improvement dystrophin to

of done early see our engagement PMO opportunity and patients. number clinicians a in in switchers, and substantial a have both discussions do We with

a an risk on are on are opportunity know dystrophin there benefit We less XX switch potential with a without opportunities not portion and just also the safety to higher those in to frequent change who therapies regimen exon therapy, patients there's profile. that of currently substantial so not a

at So important we opportunity our see stage, not a this that patients opportunity do And on on comment analyses who yet there's are haven't therapies. existing large we very as switching, to on a funds. pharmacoeconomic pricing know and on we that but

Operator

Truist Lee question the Joon And line with of coming next from our Securities.

Joon Lee

chance but if with pending is still is I outcome. the I'm PTC is of as an that progress. clinical lowering is wrong, that reasonably deemed there our endpoint? quarter, Huntington be adequate follow-up. surrogate primary If understanding proceed to a may MRI that Correct a have would with me quick having the meeting the outcome endpoint predict the on the likely second Congrats you case, And a FDA in

Paul Bolno

think an lowering data benefit, to it's huntingtin surrogate to I our make accept think be I then yes, of position mutant reasonably Huntington, we're correlating and to the that were associated that if to as that biomarker measurements important a and demonstrate endpoint, they willing FDA clinical disease, could if, to Yes, Huntington's but for the were as along off with FDA clinical clinical meaning an likely and were in predict data. earlier file a a data

lowering, substantial the We I'd of the at huntingtin clinicians, the important but indicator on been say, mutant of we with agency date spares seen have top to to wild-type, an XX% and data that's patients, itself. to placebo-controlled mutant a also know lowering, is which huntingtin most lowering highest,

substantial dataset make existing run that confirmatory to those and and studies deem we would we So changes. file as subsequent the view

it's So the for for regulatory in particular. endpoint, if beneficial field and that changes us the

Joon Lee

in mentioned here then changed? higher the what XXX,XXX tells are previously other is XX,XXX kind you you Europe at XX,XXX that the thought? to historically prevalence than And by than alone, looking bigger What which and that you companies. of might And of the U.S. data cited opportunity more Huntington be than much

Paul Bolno

think reflect cited as oftentimes historically, the numbers symptomatic sets, I to in they tend data get early HD.

starts done to changes Huntington's is research allele of that move restaging patient who is really have used MRI you of the so And the disease. before as of manifest see one paradigm onset disease why last critical measurement about patients of done early symptoms on been to occur into Huntington's have year So work silencing kind the between of the a well move caudate we in setting. and pre and manifest that a that by was we Huntington's Huntington's would for disease before community over the in restaging where disease diagnosed advantages that substantial bifurcation. What's think, HD. with disease, in we onset treatment clinically realizing to is specific again, that the a the designation and I Huntington's And diagnosis think the have main in that been historically ability symptoms, on if can

So protein, as HD criteria. an if propensity the exacerbate preserve continues knock on in before neurodegeneration that get of Huntington setting under specific the based we genetic to all to move be to real don't so more the we'll to diagnostic The the is I early take is you testing say, Huntington's the diagnosis. And protein therapies opportunity community onset the as wild-type incidence things one in continue in well the meaning you and disease. increase, of opportunity can current treat therapy, genetic and earlier forward the you well disease setting, may disease in have bad come to and learn allele think of out predicted you

Operator

the next Leerink Schwartz question with line coming Our from of Joe Partners.

Joseph Schwartz

WVE-XXX I the you look was might of after your that works from should you preclinical or wondering single XXX-milligrams? reported insights last you appreciate how have how data effect we share could that how about the the kinetics dose Can healthy doses modeling any evolve think strong general volunteer can multiple from of we year?

Paul Bolno

formats, it's higher Yes, XXX, doses, we've every efficiency. we've we've I doses have only we is mean, PN drug intercellular to seen not but seen from of from single multiple chemistry what improvements multi to across translating data with that gone in retention time

production. substantial doses said, And you the to and just acknowledging, from early already for as not but increased. to sustained, for expect we we be uptick protein we single multiple with in dose, So a be actually that thank see with data the

exists, is drugs future that as with also the extension opportunity about meaning the think important we've is durability, and And this we study, so and multi-dosing dosing phase regimens consistently in. seen the also for

retention, it's quotient. not drug the into potency out, therefore and that just improving drug cell, decreasing meaning and So durability it's

to already important. potentially will said we'll X amplitude happen so imagine because that important we've really and durability. that be importantly, get multi-dose modeling before, response what about and is X multi-dose the one is things of we the -- XXX-milligram to in we'll XXX-milligram from between registration think cohort the therapeutically dose That data the prediction cohort, with on window amplitude milligram that what the cohort to to next with frequency the data single going design next study. a protein. X data, multi-dose, that learn this that refine our ultimately levels relevant is doses why is on we're as cohort X of XXX And saw continue which would X, what M-AAT this and what the happens is continues then to lead the between the of see but we're also dynamics, protein happens It's So going we

Joseph Schwartz

time at match focus the you to patients treated GLP-X for are amount Or you on the different And the mass a of how would this long hope then recognizing changes time weight point, year? course? we similar data Do a loss therapy cross body being this by share these WVE-XXX, total trial non-lean effect be should is mechanism? comparisons, of of given

Paul Bolno

Absolutely.

XX-month we'll it's data of and study, you impressive to to the dose point weight reflective X-month the similar haven't data loss the the and the the cutoff single thinking you'd as say to study, opportunity what continue yet. see dose to but is with we data we GLP-Xs think really from single semaglutide. long-term from the provide fair about saw treatment. Preclinically, provided of about the expect of run durability We'll to and the So, durability,

So I weight. exists think follow the to opportunity

category really really think into what's to this upcoming to broad I really in to loss fat down very changes composition think what is brought going the want that's fat to as important, be is to delineate weight able biomarker I loss. those of And body of you we to concept break in in stroke data. see be study up, a muscle and in addition that

data it that think to totality the GLP-X. I So of from distinguish

expense So muscle weight not as where up against I just same similar. the are the of what's is much currently very to -- it's the are medicine that overarching at loss that impact every very think properties and classes put because with similar we

chemical is phenotype. the not starvation, shift really in set distinguish essentially doing where that metabolic this think GLP-X, category to this in full we're I medicines we're a driving opportunity data unique initial of from

being INHBE And an able and for be in believe loss. so these that as of healthy, the we to independent will thesis weight demonstrate that supportive sustainable addressing difference mechanism data

Operator

coming from question Roger next our And the with line Jefferies. of Song

Your open. now line is Great.

Jiale Song

us. So questions a couple from

first the So AATD. for one is the

the Paul, production. and the the production correction M expecting on higher you multidose, the increase total then may dose protein mentioned, to think, higher dose you're protein be able and I

M is, question have the have function, other little XXX bit increase we level the level have versus my So we liver some trying replacement do given than the we dose. the protein a know medicine genetic level what and only total milligram you the the higher but therapy, the the coloration so to protein lung seen in and far between

Paul Bolno

that basis which with it's -- subsequently, IV wonderful a RNA back been is I been think to basis mean, about all and that XX a question for protein of there's we replacement micromolar, the the has it's setting. cite kind editing, Yes, discussions going how drove around level where and if we

to your of we what's have got level. To about liver protection. remember We and kind how required that to question lung for

correction, level of do if So nature think XX so that micromolar. we about that was of the phenotype, the about heterozygous XX%

patients in setting was with XX% of you of was encouraging, people range that for benefit and activity was patients rely doing shows the function of really really healthy data those protein we functional copy. take set a at in level these to on being know think could clinical could that when misfolded Which adding essentially doing that limits it about on when you're this of where what back field that to that apples is those that M liver we the who a back have protein when of region, to to an actually total a we protein by the set other we're to we restore have the the still heterozygous a on production. But replacement, was patients. with that editing heterozygous the when make population and RNA the of them you around you benchmark of with that promoter isn't editing heterozygous If of imagine restoring level a protein. And necessarily thesis reserve apples human back able that the function. What have of protection too, lower top look antitrypsin in copy that population, dynamic are really editing, we're that one alpha-X by walking off lung

RNA need restoring back we're we think than about to think So protein do a category editing that patients. we about function as really different to these replacement how because

level already to protein, see that and XX% over data, clinical about you at what protein So if be essentially XX think heterozygous happens M increase we've over continue micromolar of that repeat to with of expect back of to also protein patient. where seen, you'd and as M to and see go, we see protein recapitulated went being of durability. total encouraged looking again, can to be. great in and what the going the of our can also we've But time at We're total that protein, what what what but correction dosing levels it's happens we level that

be phenotype, field heterozygous turning protein So baseline the follow looking data. to correct I have correct clinical who us encouraged to key still M highly for no we be a M at a we're back in them the by to well can of again humans, will and think protein you ZZ able and level how initial our if translation enable remains patients us to that understand of as able that

Jiale Song

quick potential one the for and with a regulatory just Maybe FDA, DMD. path. for Understanding you're then talking the

kind will little try a the also quarter, update coming will this later? be some a you umbrella of bit understanding they get would able or be do registrational we that topic to be So trial, maybe the

Paul Bolno

we said, from accelerated mean, confirmatory we as said, program also terms discussion initial data and or you. it's what's the weeks, design. registration data the, encompassed from about of I for as but XX next No, thank in the study interim the importantly, the

provide we'll the part able sets update these totality So to be steps as an for of on program. in data next

Operator

with question Luca Issi Markets. from And our coming Capital next RBC line the of

Lisa Walter

Luca. on is This Lisa for

milligrams. exposure at on is different XX these how think we there safety second and So XX-milligrams, Intellia are Alnylam approved think RNA any Appreciate for lower dose XXx in already a should is Xx looks to about HAE at like for that dose about versus it should TTR action, study at for at pivotal an versus totally lower here XXX-milligrams editing is versus using but for Just such risk drug in ADAR? your wondering, siRNA? DNA we total dose about going high AXAT doses? Is the side with editing of their dosing mechanisms how

Paul Bolno

the at of lower the you than one have think things to I mean, I is XXX-milligram Yes, look Inclisiran. is

of mix dose. total is So I we calculations that drug think delivered the about per absolute to the think kg sometimes and versus have what doses of

per per giving kilogram not we're So at doses, patient. these dose absolute

time -- the of has enzyme. understand this the is Importantly, the anybody we first editing ADAR exploring kinetics been to

be opportunity realize modality do forward, bring is to explore we leading the is whole the what opportunity possible. new ranges you mechanism that of able what's the the and you are to frankly a field, have for real So when and

to mean, but frequently, that. dose, if a this going And efficacy be what's quarterly, we're important durability is ultimately to we dosing understand could less dose I establish also so monthly, threshold. threshold, but

are what enzymatic nuances We field systems. a there happens always with across siRNAs. as different understand So

infrequent incredibly than which dosing. we in it's durability, siRNAs to a we're I been Alnylam, mean, isn't Although note, better seeing it's for important showed things that potency, different AgoX different loading over the to translating before. to are with improvement XX-fold what's radically highly Alnylam seen just in prospects translating

chemistry to durability the nuances important a does And quotient, that's to add to not about so just how be able think a quotient. of but potency

our really dose us to heterozygous to a I upper that. AATD patient the is let one get initial go levels within beyond have specifically going I to understand understand We're therapeutic bound. even think for population. also could where mean, we the opportunity

is dose And explore important. to opportunity of so able I think that really being

above in I is, anticipated study. gone we've higher the third all think the the volunteer even thing than other healthy to doses, note cohort

safety, a for data explore to look we the to just and think does have preclinical going to good editing, clinical set us editing safety is that but and perspective, like. not paradigm bounds safety, of let going important upper multidose safety that's human single from So as be we substantial continue what the I human

the think XXX does. but think I absence I what is dose between we're less at of in the what a repeat the lot and doing, and to so important ultimately going X dosing understand also it's importantly And X,

the and be it's are look think and be to protein at correction going I of exciting time across modalities So as going an levels for RNA editing mechanisms we possible. field what

Operator

from question with Catherine JonesTrading. next And Novack the coming of our line

Catherine Novack

in And when I in more wonder, can multiple if granularity to AATD. to threshold, any you as we How Z you cohorts M-AAT the at dose thoughts that, with conjunction then, really should anticipating for in AAT. the you XXXX Do consider details this? give micromolar many expect just M-AAT about understanding patients the we're not threshold is total be so functional, looking XX on success? not protein the that think are

Paul Bolno

patients so to very with of we what is Yes, going think so I be. X number stepping back, as we've been are said, dosing, repeat cohort, each with patients clear the

is data medicine dynamic established the and multi is to XX% We're patient, is XX interesting which at what the indiscernible other which production. To set, ] and So that'll that that look let for looking so to with back remember really protein the look can a edited they'll have that multidose, micromolar [ of assume is substantial to total. point, be XX% already get part M of we the and that X from is activity single your we'll and repeated, that amount going of the of going way effects at us heterozygous at single which total Z. totality at a protein have to threshold M therapeutic nice we translation if Patients from a doses. data are in set the the of is

still We're total I So there's don't going going so anybody study. as to I want to show something your if still point, we interpret. sure -- measure, we're wasn't the do protein to to

M able specifically the based is be relative the produced is it then medicine's because M only on between transcript. ability edit is total the highlight that look and again protein protein to reason to So protein. The ratio we'll M critical we at protein

continue gives most to editing to protein. do into we so phenotype that so we insight MZ therefore, it phenotype, safe is and efficiency, higher what towards know so production, the patients of And want stable, therefore levels the those protein a and is push M

regimens. just reasonably is at and a what could level expect M at milligram. we XXX to that activity see that substantial dosing, of how repeat have We're really we going to not dosing a think in higher looking and but does as sustainable about protein, that we So see the durable

Catherine Novack

had something explore I your as you outside with Is on INHBE just example. GPRXX, on could thoughts of program? inhibiting this targets in then conjunction And siRNA obesity one such more for

Paul Bolno

of with Yes, the we with potent once siRNA less obesity. GPRXX both about approaches is durable the that CNS could the year, not mentioned, as potentially well think to about as look potential disease. so GPRXX even for substantial a technology, at shown field ways metabolic but a whole frequently silencing range And treating editing we've do potential with moment, our we've of of talking orthogonal, administration. at target we in using as orthogonal siRNA

potency the again that the distinguishing that siRNA just chemistries, GalNAc we shared that's and differentiation liver, how also siRNA for and data chemistries in with data the between how durability our as of demonstrating with and but showing state So better part are of in we not the CNS. see art different

the So field. within we are metabolic evaluating a number of targets

Operator

Our the next question from Raymond with line coming of Ryan Deschner James.

Ryan Deschner

late-stage add or this XXX of initial study actually program, on positioning program an successful? For therapeutic you is the mono a a a look assessing regarding what therapy as And maintenance would as for like clinical what anticipate label would more like? maintenance therapy look the to

Paul Bolno

say mean, Yes, about lot then more I dose I the and single the and do opportunities, maintenance. so a we the about think

these of data So that going part as we're to be generating datasets.

able sustainable we registrational sense drive healthy, into have agent see, good and of of going being to inhibiting therapy that we're must level very of the behavior study. So what a and single potentially forward

we engage excited that which off you've that I ramp. the as is think to alluded in, is to, are study other

we dose it and on a to so to able that patients GLP-X, be to that look at run, able and that GLP-X have withdraw. on replicate to is being feasible study stable And very are then

next so And of being the studies designing planned. those are

about a generate registration X in and two, the those for important can one, clinic, really to so label help that but purposes. used We of potentially be data thinking conduct to also they product serve how we meaningful are Obviously, for how support reimbursement.

be opportunity we where really going be a patients now those on be going can study who really currently important interesting total therapies So this and withdrawn, think off-ramp, way. are to about as to running so a a time that's -- the but that be substantial monotherapy, both real on very in to studied I as think context in very,

those have underway. plans we So

Operator

Riley. And from question the with queue our El-Saadi B. last line Madison in coming of

Madison Wynne El-Saadi

conference? event as for an updated What on provide prepared then Will I mentioned analysis around the you plans update? And host are your an you of MDA in know to had the that second, your remarks. regulatory conference you CHDI, XXX,

previously of the exon or Just kind from see relative us wondering profile then could remind the how XXX's to reported NfL characterize in if targeted terms X do baseline. you candidates? data change of you And secondly,

Paul Bolno

take MDA question Yes, wonderful. I'll the first.

team was that not timing coming to MDA already wise. will presented our scheduled be I a be coming at presentation the while up, will So prepared, be has data think

separate So there events be that. think I around won't

around releases rather as time always but data the full as end full So data we do said, for historically have the well data, to the the our conferences, of as We don't by have expect update our regulatory month. when don't we is time presentation. -- we ready

CHDI, healthy translational have As autopsy, lot unique it the concerns always about characterization We when the when relates to what exon brains clinic, think to for take models. the of patients specific back exon a experts from it's about have at did, there always disease. And those to on I I people important, this, it lot a that table and at do was look to patients not systems, mouse discussion. predict think HD, a the had both the Huntington's the and exon important of and so did this I medicine think analysis hypothesis. and X of not in fact think activity it's expect and to fact, and X, who in MRIs, is model talked concerns who I the the those more on conversation a you but translational HD sets lot of of was And was so not lot in went models of the did XXX, stem because off X first, we'll animal

is preserve as you clinic, allele exon an a exon data being very X benefit, in humans. I mice study happen of R&D allele So changes X that a to I lot that's of date, Wave would protein importantly actually Day, supportive the models specific add that presented referenced becoming We with of oligonucleotide potential studies, that being but that been But happen in believe, lot with and specific specific target in preclinical that I oligonucleotides study. and actually this around mutant space. and Alnylam KOLs is was coincide CHDI said changes we've shared of you that wild-type, our some what do lot worked specific with are up. actually data the as and X, it had that weren't that it up actually presentation, presentation, a which that the in there's engaged the expect, should benefits. on see also if that demonstrated was an important and was oligonucleotides, and there shown exon in was presented also reduce and with in the we oligonucleotides, not used don't allele shared at huntingtin just think that Wave we previously, ultimately the ended but emerging to became were had allele exon generated data X presentation, we that a a a the And happened picked

that to highlight X discussions the I So around date. exon

to there One, full was NfL As correlation New couple outcomes. I things. the in important in Journal HD-X analysis it the England and the NfL of retrospective between relates again, generation clinical no studies, think a telomeres study,

our feedback reiterated again an follow-up from just share that which were the reminder. it's the NfL not did So of that important FDA discussion. We last was subject year, -- we we

the do correlated it field for measurements. that to But is going measure we NF and in to important outcome look applications. It's with think So again, I follow continue those hasn't it. everyone

Operator

turn I'm I Dr. showing for further the remarks. final now back Bolno call to no over Paul questions. will

Paul Bolno

month you call connecting Yes. when look day. forward joining to our this you for FORWARD-XX. expect data a we of Thank many from We with morning. this great share Have to

Operator

and Thank you This disconnect. now you all may participation, concludes call. for today's conference your

Wave Life Sciences (WVE) 4 Mar 252024 Q4 Earnings call transcript