NTLA Intellia Therapeutics

Lina Li Director of Investor Relations
John Leonard President and Chief Executive Officer
David Lebwohl Executive Vice President and Chief Medical Officer
Laura Sepp-Lorenzino Executive Vice President and Chief Scientific Officer
Glenn Goddard Executive Vice President and Chief Financial Officer
Sonya Bhatia Goldman Sachs
Maury Raycroft Jefferies
Xiaozhou Fan Barclays Capital
Rick Bienkowski SVB Leerink
Joon Lee Truist Securities
Steven Seedhouse Raymond James
Yanan Zhu Wells Fargo
Silvan Tuerkcan JMP Securities
Jay Olson Oppenheimer & Co.
Jack Allen Robert W. Baird & Co.
Call transcript
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Good morning. My name is Izzy and I will be your conference operator today. Welcome to the Intellia Therapeutics First Quarter 2021 Financial Results Conference Call. All participants are currently in a listen-only mode. [Operator Instructions].

will call we for remarks, formal open up the questions. Following of the is company's and end being conference company's website call. recorded the the This on at request available will following the be Relations turn the Lina of I will at conference now Intellia. Li, to Director Investor Please proceed.

Lina Li

be like listeners to a earnings press as operator. would available management XXXX SEC release discussion on company's law. this a Good quarter outlining duty website. for ask call, statements as first And this broadcast found company's Intellia of also our can the the undertakes time, discussion to topics that, a today's Investors today, no make this you, section you At release on on everyone. Welcome call. will unless remind the uncertainties. to risks Earlier Thank certain Media Intellia's is on forward-looking company well that and today for Intellia Intellia's filings of This by to morning, quarter and call. This the issued replay archived be a progress call may and live I required at website is call being minute at as during to information this take information and refer potential presented update of All this current and

Chief Dr. Officer. Sepp-Lorenzino, Dr. Chief Financial Officer; Executive Laura Lebwohl; Officer; Goddard, are Medical Leonard, call John me today Officer; the Joining on Dr. David and Chief Chief Scientific Glenn

let an recap closing R&D will for Intellia's make me our clinical of turn John over and the our followed For will call followed that, for quarter CEO. David and on today's first recently financial open we NTLA-XXXX review remarks quarter. company's to provide Q&A. then highlights, the with With will call by Glenn's the by results progress, the will the some call, Laura will business who efforts, company's start John update

John Leonard

an catalysts. proud key happy curative treatments a individuals against we're forefront core update diseases, committed on our Good developing we're our to year to Intellia, recent everyone. Lina. provide be priorities the upcoming of morning, for At you, severe and genomic at editing Thank with transform to the to lives of We're and medicine. forward genome to this progress view

Oure expertise property deep revolutionary clinical scientific, position and potential CRISPR/CasX the robust into to development new intellectual broad technical transform medicines. portfolio and of of classes us therapeutic

in Our supports leading full vivo ex platform differentiated spectrum therapeutic which vivo across modular strategy a deploys applications. solutions and

delivery out disease, cell or cells. insert efforts, homogeneous system have we pipeline, TCR produce For stage or expansive our based that a disease approach, selectively these portfolio, is designed research following to product vivo receptor, broad emerging including natural robust nanoparticle to genes generated produce utilize genetic or causing eliminate knock Across epitomizes rapid patient's cell a vivo own development path. immune a T normal cancer and system in candidates approach, reproducible to a clinical precisely ex lipid we proteins, an a leveraging and based to genes

pleased Intellia in We there of appreciation demonstrating whom the for make potential continue one ATTR as efforts. The is headway benefit the productive quarter first we of significant across NTLA-XXXX, for treatment regulators' no to orphan a Union's these were for designation was NTLA-XXXX patients of to drug European receive the cure.

In of preclinical base genomic the In and we key wave the a proprietary introduced new and vivo advancement directions. next editing we marrow. systemic Platform editing pipeline of for our medicines. lay cell these as innovations presented in for proof data in March, Intellia's continued bone Additionally, such an modular foundation of showed concept important separate technology growth engineering. enhanced for our we presentation, capabilities expanding

more than across of stages and with Dr. welcome to manufacturing. as pharmaceutical scientific Finally, operational experience, pleased including industry we development were XX commercial our clinical a leader Keresty, years of board Georgia joins and who

first Our provides our opportunity priorities Intellia. quarter milestones vision progress for long-term on core and XXXX, us not upcoming these for the but only to our advance

evaluation a for delivered potentially with interim our as in dosed Phase we clinical In I clinical the in vivo NTLA-XXXX, our the treatment at profile reporting this and of of CRISPR-based of nonviral of patients therapy an validation NTLA-XXXX, continued patients. study the ATTR delivery our first middle systemically look We the both option anticipate of first platform. as curative data year,

that our NTLA-XXXX, two addition, And on plan new filings at NTLA-XXXX, in regulatory In the to financial lead candidate over a and by to expand for the development pipeline, Medical T With introduction, Officer, AML, HAE. on the hand of track vivo advance our key capabilities, and in from to David and update our will second clinic our deliver strong necessary knockout foundation, to to upcoming our With we submit with candidate provide the research NTLA-XXXX. remain our year. nominate positioned our David? least catalysts on the for therapy, Lebwohl, first-in-human to our mission invest for efforts call TCR we're cell I'll end one advance engineered resources energy and progress who Chief patients. platform an we

David Lebwohl

background can with candidate, fatal XXXX, range and organs. start progressive of on TTR XX,XXX form XXX,XXX manifestations, or type ATTR. disease buildup caused morning, diverse is and hereditary ATTR, of an and Intellia's applies with frequent of hereditary Globally, and which polyneuropathy XXX,XXX most the good in disease Transthyretin a living everyone. disease have a People ATTR, wild Thanks, the or the the results either in ATTR by type NTLA-XXXX. being John. with between robust I'll estimated on lasting a of with amyloidosis, to cardiomyopathy. protein rare, source reduction a than And following data, bit European wild ATTR multiple are and of TTR TTR people possibility liver, we in offers of the our a the reduction type the dose, with to circulating primates on preclinical amyloid Commission the forms out shows is single knock XXXX granted reducing deposition. our believe dose. Based in lipid long halting serum protein, after single XX% drug technology March, wild orphan reversing of gene the and In TTR greater and of vivo potent delivery which there designation XXXX. nanoparticle of all which in the mutant disease therefore TTR non-human lifelong

less even only XXXX's regulatory, diseases, potential people in the in acknowledgement for As prevalence a This remains financial dose commercial in this X to the having view benefit provides XX,XXX as not as therapies the population. a significant product market. deliver than exists a this is European defined designation indications reflects reminder, over single this to incentives like develop that the potential rare existing important of unmet treatments an for ATTR, We it in in regulators therapies also and recognize that need Union. of when ATTR, as meaningful treatment but benefits

this in about with our would value is system. offer Importantly, patients leading and in XXXX care this line who health well are our as program, enthusiastic conviction from as the investigators feedback

a two. patients, of safety, XXXX, of and study to primary following dose our the assess identification intravenous dose, peripheral As the serum ascending is in single you trial adults The will may with one and damage. and of form for a two-part objectives evaluating TTR in trial's phase recall, enroll levels, to optimal multicenter, our The an which pharmacodynamics ATTR the study XX label, dose up part first-in-human in include a following and, pharmacokinetics ability, part of an XXXX are hereditary consists cohort measurement single nerve single a will expansion open infusion.

R&D patients of measures and we expand established secondary we our pivotal rapidly enroll update, evaluate biological optimal threatening will our for a establish XXXX meeting on By for forward move study observations safety function patients. field LNP an large at on results results into the in proof The hATTR-PN share I'll development of to of we the preclinically vivo modular to look is portion this we and expect mid delivery our important potential a single of concept to the sharing are over and medical the genome at to and objectives human of clinical studies, Once to sites in to and or study excited and view with Scientific XXXX, optimal and neurologic platform, edit diseases. activity candidates, how for to patients. will as Officer, interim the results way of believe mid-XXXX. milestone additional cardiomyopathy to the a from interim that, dose, XXXX year. ability clinical Laura polyneuropathy scientific enroll interim systemic clinical the treating for offer dose We in XXXX and Chief to of safety identifying towards to progress life in Sepp-Lorenzino, both vivo our our profile this the in And which Intellia, turn across results from global These across learn continue preliminary dose. it our translates aim updates while two ascending efficacy have demonstrating ongoing our in efforts. editing this We're goal to

Laura Sepp-Lorenzino

In development This therapy in of unpredictable knock approximately dose and angioedema care of standard a expected burden not XX patients presented tissues. therapies HAE, for only and months of in American to reductions serum to NTLA-XXXX we're in Thanks, delivery Immunology NTLA-XXXX David. attacks, Asthma activity. levels therapies our Annual over treatment demonstrating activity cyno-specific to I'll We reduces treatment study To prevent for on the an primate believe them and of KLKBX but ongoing for experience there with non-human of end, the in the activity XX% opportunity sustained or the to system permanently plasma were multiple and that for Where is treatment kallikrein Meeting, NTLA-XXXX. acute liver burden recurrent, Academy of results a our results for associated reduce of vivo our HAE. and kallikrein provide swelling protein These altogether. candidate, we to the further of as HAE significant. approved that kallikrein gene is may for formulation and March, NTLA-XXXX, greater protein intensity reductions current eliminate compared significant painful for continuous are of and modular single there LNB patients. at additional Allergy, knockout the eliminate currently following HAE preclinical and second frequency published achieved LNP to hereditary in begin out which applying HAE. with remain approach patients across prophylactic suppression attacks up available the

presented of prevent to expected bradykinin-mediated humanized HAE vascular the captopril-induced KLKBX permeability, we administration In that prevented therefore, establishing data attacks. from model NTLA-XXXX is a and, vascular addition, mouse single of leakage

levels application equivalent to NTLA-XXXX being and tolerability higher will our we start We're for first-in-human which safety, NTLA-XXXX of ex or make this We for kallikrein turn knockdown. to including continue IND from the of therefore, steady second at an activities enabling I insights submit measures and year. dose will to with efforts. leveraging activity NTLA-XXXX able progress in the and, of now vivo to expect our study, anticipate IND half evaluate

CRISPR/CasX a to highly optimal modular types, ability platform the manufacturing. high to scalable edits cell we're our Similar introduce Regardless yields, eliciting using our with and engineered vivo, we're achieving create match cell desired sequential proprietary tool approach with necessary in modality targeting editing versatility performance efficient of cell the and for to therapies. solution, and as underpins Here efforts mix to a to engineering cell pharmacology.

patients and best-in-class other all X candidate multiplex reduces is the engineered for Our improve tumor therapy, able AML T edit improved of potential Tumor and lead overall and process, treat histones, subtypes application antigen. TCR outcomes equivalent precisely Each receptor, function which editing. cell our believe recent utilizes on with investigational AML. This below solution NTLA-XXXX versus well-tolerated will of receptors therapy or autologous overexpressed AML, prevalence improving program in cell five-year and a safety we of an We is risk WTX forms regulatory XX% targeting long-term Wilms' should so capable remain to report is mutational response engineering NTLA-XXXX cell T long-term IND continue with subtypes an of process of to cell designed survival rates XX%. NTLA-XXXX outcomes engineering NTLA-XXXX T genetic AML. submit T delivering of potency in regardless a over TCR. translate therapeutic Despite for subsets cell replace process across proprietary subtype, track all mid-year. proprietary and for a to and cell patient's between targeting our the to advances of is or be patients technologies to

the first-line and have evaluate will activity with safety Our or recurrent of therapy. patients received first-in-human persistent who trials NTLA-XXXX in previously AML,

and platform research now to our on advancements. Moving programs

We generation new to approach candidates candidate engineered and to on expansion cancer. allows we for development at and make for cell therapeutic continue quickly diseases us strides genetic our pipeline therapies new nominate this with least versatility remain developing to of in The next one move year. track

oral During proprietary Cold to Laboratory introduce allogeneic had we technology conferences, our therapies. cell Nucleic base the first scientific presentations expansive our cytosine by we broadening our Spring deaminase In the on required CRISPR The edits highlights us of engineering March, Harbor via capabilities different Meeting data, Therapies. Acid Scientific editing introducing cell toolbox. preclinical generation modular multiple at that quarter, two applications data at the enable as next presented

vivo data the strategy. we and dose-dependent that a efforts, development mouse presented lasting meeting, in therapeutically in single dose. the modularity of our one discovery Through at bone a LNP marrow of LNPs and extensive Additionally, class achieved our editing histone year a we hematopoietic delivery meaningful preclinical editing cells following recent preclinical stem of genome extending identified model

could to broadly, these the barriers For as deliver with disorders disease, inherited demonstrate tissues blood the to More reduce bone greatly sickle transplantation. outside associated results treatment marrow ability the this liver. cell approach such and edit to

by expand Foundation. continue support the work financial provided to & will Gates upon Melinda We with this Bill

potentially pipeline are Although together therapies the patients. emerging innovation these drive platform in still our technology's stage, demonstrations forward share which through to our for in create of curative commitment research to the continued presentations our reflect capabilities, important

Further, ahead, Looking indication no to which move to are edits. the an disease next on we share taking week. us program, detectable provided highly insights I and these will trials. potent work with This next to the second who plan This clinical forward results. ASGCT NTLA-XXXX, meeting at place into will antitrypsin deficiency, in We research update our preclinical specific, With that Glenn guide we ASGCT. key at confidence is data both annual forward the for include of to our call our alpha-X proof like which robust hand platform, an derisk proteins technology data screening levels targeted over human with demonstrated primates. our be has regulators provide sharing normal on we [indiscernible] in to of utilized non-human restore will have concept of in and of identify our first week RNAs would foundational to vivo to presentations the off target look CFO, quarter that, and our and financial overview Goddard, including insertion

Glenn Goddard

a we Thank Intellia And in Laura. position pipeline. our financial you, good everyone. as advance remains morning, strong

increase Our and cash mainly These million. in plans, proceeds from million base stock part $XX.X at-the-market in company's fund $XX.X million offset million from December compared agreement, approximately by the Regeneron XX, of cash, XXXX. $XXX.X $XXX.X to and the collaboration. employee The $X.X $XX.X of cash as used were as increases operations equivalents to XXXX marketable of proceeds March were million was by of XX, million from driven securities

$X.X first Our Novartis the milestone XXXX OTQXXX payment earned during first expenses $XX.X $X.X to for the $XX.X compared XXXX. XXXX. was first compared million. increase This million by driven first $X of million increased the was of compensation to the of the first decreased our $X.X during million $X.X personnel XXXX The submission quarter quarter to increase million by mainly lead by including XXXX $XX.X million development employee-related million during quarter in a IND G&A from programs during XXXX. to stock-based and the advancement related the R&D by to million support of $XX.X of collaboration our decrease quarter organization. $XX.X of compared million revenue quarter $X.X during of of driven This expenses, to research million increased was million first these XXXX. of quarter by the to programs, expansion to of the expenses during

months. the turn remarks. And expect at for balance over next cash John least closing will the to XX to call we Finally, our fund for operating plans back now, I current

John Leonard

Thank you, Glenn.

our excitement the of and see, of there holds remainder are the company genomic for can field reasons you As year the for many for what medicines.

sharing I mid Phase look results NTLA-XXXX of well is our study for platform. progressing year Our and interim to this validation forward we clinical of

We expect NTLA-XXXX. pipeline first-in-human file progress continue regulatory mid-year to our and submission for a to

year, In in to IND we on to half editing submit second research addition, for milestones, the enable we toolbox Operator? IND-equivalent expand the to in the we NTLA-XXXX and promise of expect committed candidate of We'll for an core year. to now priorities our reality making one medicines. open as next expect and continue line questions. or to close to We're at development wave focused patients. all advancing this portfolio and nominate as application genomic this a this wholly remain With new least we progress, key our on genome we any stage


[Operator Instructions].

from Our Sachs. first question comes Salveen Goldman today Richter at

Sonya Bhatia

for on Sonya is This Salveen.

We have a on questions few NTLA-XXXX.

as So, is from? we the How data question – the read And from NTLA-XXXX cohorts the US? the expect Thank what many should as for data in of IND the status mid-XXXX? then far in expect should the we what is you. second

John Leonard

I United we're studying First, XXXX remind that a – want currently just study to XXXX is outside States. you we're

back we'll sharing human of to there's look that. we're study study. we ongoing particular the have that, for as and out. well have in respect that's forward substantive and say not to The of expectation we're as and was to progressed it studies. cohorts anticipate work talking for the readily that that number we have to the study And plan laid with presenting, the that the about we we subsequent an interpretable would than data IND part principles cardiomyopathy in the for adhering data other is So, to no work, subsequent this IND the an would to come involve US first study, With


Next with question Maury Jefferies. comes from Raycroft

Maury Raycroft

Congrats progress. on the

Just had on study. the a question XXX clinical

there's you study. be one guess Just immunogenicity. say And in say in wondering this clinical point? of that at additional will And can part concern the far I if is update? anything safety that can mid-year anything the you was about on there so on the past

John Leonard

best point With with this that here progressing, information we're respect think the And I progress many that year. time. sharing to made. questions study safety, at A your we I that mid forward look excited we've and to the is of in think it's anticipate address we'll to

Maury Raycroft

that questions into tropism getting mid-year We've wondering the your And we as well? the guess LNPs, tunable immunogenicity about translates also and and been how characteristics that too LNPs. learn I'm in your if functionalization LNP of go some on design I could update more the the to improvement an in and

John Leonard

year and about there's that the the platform more we're sure I'm to unfolds, opportunities doing. As the be going talk to work

we'd about I talking the about, study at the most would time clinical to think advantages the And do opportunities Maury, that data with that. our we're we I there in anticipate share respect to know, may have. But progresses, this that points later some to you science there's and of that as have. be we year be results would the as discussion that of time the like that where


Your Barclays. with Wang from next comes Gena question

Xiaozhou Fan

Sheldon Gena. is This on for

past about target think XXXX So, that you for this mentioned the knockdown level in trial. I XX% is the the

out initial have at So, the the presentation. in the timing the of level Does it those mean levels? almost target you set already now, right reached you

John Leonard

Remember phase studies we that optimal have are larger and as said is we'll principle in of that the the where progress. this we've outset, phase, dose there's we approached that will what ascending we've that share the it, a that more two in the would this, data take phase expansion be readily meaningful fully phases applied and biological to of dose from would we the that interim interpretable. then set way from we've the for results study first study The patients. think The

XX% We beyond. particular we that as or true and haven't tied that this a to It's specific a set release. benchmark target, data

can XX%. objective that. it's for look think further places beneficial levels, Because data for seems And we the circulating to to the more we there's patients. think is be surpass indicate one that Our to going TTR reduces I

that data number. necessarily that by our particular ultimate we So, objective. not But the here is is any specific triggered share


question next SVB Mani The comes from Leerink. Foroohar with

Rick Bienkowski

being novel a guide the Maury's the the of specifically, I on Rick line LNP for question clinic. formulation components CasX liver made are RNA Mani. and here the is on for the This That's the first expression have on there to few a actually then or follow-up safety. being and in time edits transient And the the evaluated genome. in actual

hoping the trial, signal contributing if out to on your any safety in components is observed I for which to and of to there what parse of – vivo sort ability get signal the So, read-throughs there was be just the potentially the thoughts of those platform? may in is rest

John Leonard

have in one how about achieved of we then think therapeutic Rick, remember, very generally And of characteristic develop sufficient administration our trigger. So, effects of particular we've a approach that, we're findings you quantities very, to safety you on a as when the may that and that to we on there's can its in preclinical worked a beneficial LNPs index. there's animals. carefully gives work that talking class, in All based intervention expect is, LNP it the pattern material, safety. the expected we've general and largely itself we the way be TTR long-term knockouts which

or we're clinical largely is as Yes, effects. That the lipid the share to it. those And So, year. is to that, mid novel unique cationic effects way that the findings. trigger is the the we'll class piece is is components, is balance the expected here precedented. those about early trial I the exactly it proprietary to think in this a to respect the said, here not within index effects work. either genomic on preclinical is how And And of good it really it again, characterized we've very and know it based think we the to of than ASGCT With the preclinically, how mRNA. preclinical think of the say where that guide go characterization models would With meeting test human is there's exposures some And done. very going particular that. more therapeutic through encourage LNP And doing designed desired I aware. I'm you and RNA, I we've But that's TTR study I as attend behaves guess there well the addressed been any as to Phase respect results drug, the for we're work other of or LNP lot would does the preclinical probably very, I to we that far a lipid. rest well extensively

get extent So a sense the of you good effort. that of really and completeness the

can we through So, we data this that revisit maybe later after month. go


Joon comes question next Your from Truist. Lee with

Joon Lee

level. just as a to set clinical as oligos you And similar knocked well I need sRNAs knockdown or equivalent could do as less clinical what clinical knock antisense down You editing advocacy? bar Or of get follow-up really your is tool as and guess around knockdown better we still data hit which those could similar you is effect? but oligos that genome down antisense a question. hover and have as situation some sRNAs achieve could that get constantly a envision XX%, I And get where But mid-year levels? you working,

John Leonard

which very of a question about Right. you're we is does knockdown, it's when what talk important actually it these asking, mean? So, numbers

we're maximal asking essentially have well, is effect particular advantages the the of that some effect least you is occurs effect call of pharmacokinetic it, question, are area what are portrayed the number, under familiar that an with, no is, here what one the typically that because so, at the time? And a time. you're XX%, the over taking if approach as at average I'm that typically of modalities by the which effect there's maximal effects. other the presented numbers variability maximum curve over is a is And And

we we to a So, that not the effect, you maximal when surpass what achieved. at our the that from see go is we it preclinical animal to if And as you'll comes this some sustained goal effect. of back it, approach that's to benchmark. data from XX% The just the but presented, look exactly models, to is

that TTR So, blood the what reducing lead here. And to our lowest more to setting that's is going levels achieve we're exactly the is benefit. possible to in out thesis clinical to

how it. that's So think we about

Joon Lee

knockdown get data along the So, we'll mid-year? clinical with

John Leonard

the So, study, it's phase for cohort. a in the three of early design remember, three a plus

So, safety There's on. I would clinical a look going the to of very characterization to here I be What extensive the a phase information, is look descriptive is and effect. of second but bulk primarily primarily data, study. would think modest clinical that data to TTR I the early the

Joon Lee

question. more One

to Or disease? not do CRISPR commercialize overall seem be to to does this For impact ability this? And vivo strategy? for deliver LNP cell this of distribution kind of and that between stem any have for you. play Thank the in for develop something they disease? what agreement cells, hematopoietic is and genome bone the in marrow-tropic overall sickle given the editing therapeutics and cell you of that Or bone efficacy portfolio and announcement where does Novartis the moving in versus this into your aggressively marrow approach limits strategy, how does vertex with take durability your priority sickle the overall

John Leonard

with appropriate clear avidly that class tendency it. sub about be to And up Without fairly to the compartments body, the have how in and marrow it's to right liver. question into a a going I specifics as parts. the the is That's we a objective big you the picked other get think by bone LNPs liver many very of obviously, of all tell and distribution the various between bone amount cells the marrow.

there's respect of takes place to clearance with in So good headway the that addressing to the part And that ways the we've do of is that. liver. of variety I'm made that. challenge it's a talk working avidity delivery that. doing And point will to it. here, unfolds are them. to as about many how sure at on there scientists this opportunities of talk we're But our about premature exactly be And time more And

therapeutic I think stem speaking And by broadly system, hematopoietic cell progress pretty one related of hematopoietic that have show clearly disorders great that's for know the we're pretty brings who very challenge, one sickle all can about and set news sickle sorts even patients of and and those long with treat edit inadequate that others disease in Just transplant, effectively. that which of cells that subjected very, cell that bone The excited mortality. to the to made very needs treatments. be we some suffered benefits, to have it significant a marrow morbidity, get with cases however, to is

It's rid bone getting marrow endgame And final so, that transplantation. transplant. our the of here avoiding that is We the bone to just view how edit. marrow is know

is So, our that is will delivery that here. solving in fundamental that system, with an problem belief the address what vivo

So, and other we that work admire people to and them their encourage other relationships proceed. take, approaches

is will broadest working for the patients. the solution the Gates Our that that been greatest helping of what have think on. to Foundation we're reach is the has approach And best and what number to us we have And do. something that's

Joon Lee

forward Thank data. to you. the looking I'm


Your with Raymond comes next question from Steven Seedhouse James.

Steven Seedhouse

at necessary. just I Unless plan of trial don't it imply follow don't is that It you you I'm That's how and as an haven't or to don't to to guess just ambiguity want ex-US you you know intrigue decided products. equivalent either proceed understand surprised or geography point. you to your say. with seems backup me. even kind plan And really IND a submitting why that I to the this see IND basically guiding which reads or on

already can recently interactions? aren't from hoping or you US to term right ex-US IND or had AML, have certain those insights can Thank could any you just near be say can you And plans now share a those IND will my question US you. you if you be have clear, a trials? for HAE meetings file about still, is, So, pre-IND and actually you you say

John Leonard

change shared we're said. Well, what not going I position here. be the for But thank in clarity same to we've as you We'll with NTLA-XXXX. a you exactly give proceed guidance more the to to respect we question. We

gets have spaced been broadest putting the clinical we're engaged discussing We the the are as most in regulators. as well we efficiently. other certainly that can the And in things interactions. regulatory most very, ourselves information position a FDA with very And program where we've

address more not time able be I'm we'll your question, So, as sorry going but unfolds, specifically to I'm information. share to


Your next Zhu from Fargo with Wells comes Yanan question Securities.

Yanan Zhu

on questions few XXXX. A

a the of a – is June? reasonable medical to helpful. with specific within the could predict dose it dosing, could what medical – is of variability terms for interpretable data? you by mean the the that place to results? the meeting that of assume in PNS make project also, be it will venue data to Does First, any it around mean response And kind judgement you ability a certain Or could more might – that additional a characterize in we happen a make so color you could what the meeting, some little very your mean

John Leonard

particular that to respect yet. not With meeting, just we're that information sharing

won't people. be we surprising However,

we closer get to and that As press in we will a point time, share when release where. in

data, an pays not how pharmacopoeia, to it's and interpretable if speaks our information. So, respect ascending will With that's be able people, an to I always if the in attend think, to assessment to dose you what small prepared of at which said. exactly advance of wants we've NTLA-XXXX fit some but also the be the generally. to With that really those applied, what for in numbers will there's variability one with one get to it's help it patients see principle or to information have effect study, make And attention of into likely only meeting there. platform data, interact a it plenty mean to look and to

And that so, addressed think share when we've that And those see I positioned we've applied. are data, them. to the principles we're you'll that

Yanan Zhu

clinical In EU chronic obviously, follow-up. designation there think therapies. are ask I did drug your data? the for quick orphan because, application, committee A

of when So, there for ask – when when care, a in is the standard precedents, multiple some determining Thank you. committee drug status. orphan might data

John Leonard

it personnel. and asks committee as there's the treating determination we with think or broad-based information I remaining unmet healthcare patients they concur not KOLs, the which of includes and whether source its need, the makes gave,

clinical treatment It's about less it's of the about information. status the state-of-the-art. current So,


Your next Securities. from comes with Silvan question Tuerkcan JMP

Silvan Tuerkcan

all the on Congrats progress.

a a then or to about And saying that ask safe you to that read low? higher comment NTLA-XXXX. a the to wanted NTLA-XXXX is that can Laura. may you first from dose please if compared Could probably is you across I may lowest that follow-up. have start we dose I have to NTLA-XXXX off, just mentioned First And from at the case, want that confirm information it been too that

John Leonard

I to Laura for modularity. just goes back in to It stand guess, here, I'll all keep it efficient. fundamental of the premise

the its side, broadly an preclinical on or side, clinical LNP it's applies. whether the what and it's for learn we on cargo whether So, the research on side,

is so, collect of to we different what can incarnations domains, from any of subsequent as even and or various regulatory clinical apply we And those that product interactions we found it the either interaction. information

some to information the it on XXXX there. than characterize that may that have it's we not to is going us other able bearing approach I'm we how So, some it give utility and – have

Silvan Tuerkcan

for is my don't would later part expansion reason, could knockdown that explore trial? some the target patients possible reach a redosing in And follow-up have question in you is, of that levels or the you the trial for something

John Leonard

how the to Broadly based of go terms in at trials.

single we're a application. work single are course that in is study, program. of in Formally, dose a And in the the provisions addressing ascending that making this this There perhaps, we're recourse more to optimal sub we'll may position have if in that a as more patients dose. it. to doses, about be occur, they But those clarified, active study where talk gets a subsequent

Silvan Tuerkcan

last Maybe may. if question, one quick I

for watch we tell to terms point compare to readout pitfalls us that steady knockdown to in Anything picture, to point time state or to [indiscernible]? tafamidis on patisiran populations? peak or are dataset this if can out you would big of Just you us, NTLA-XXXX any this can or level for the patient there to

John Leonard

question. of not I'm your I got sure gist the

versus that about asking me? and until what you tafamidis NTLA-XXXX? knockdown You're Is effects asked

Silvan Tuerkcan

TCR some agents? of Yeah, for what of And when some to from are in get et watch out reduction we other knockdowns what we the terms NTLA-XXXX, do comparisons cetera? levels, of are when the can we just straightforward the the

John Leonard

with or people take to can into other trial. coming this are what exclusions particular study, to respect respect With the there before will have ever taken

would TTR directly, So, think With I that the to any it. and of of its that part course terms a of decline, that in majoring be in amount comparator, there'll which behavior material, information interpret. to we can not one by I knocked think, that the are knockdown levels And expect look siRNA tafamidis. fair relevant of won't at is of be TTR the down a respect the of study

think So, based share. that make kind good I comparisons it's set of some to calculus to what expected one of we're based make. have broad on to different might a pretty expect one would data a But


Your Olson next from with comes question Oppenheimer. Jay

Jay Olson

you integrate For you base both base And the presented, do into tool recently editor platform? overall system ex that will in editor that in that programs? your how and plan to be vivo used vivo

John Leonard

applied not base of about see excited be talking very the part in greatest currently what to. programs editors particular may utility We're we've their setting. the about. ex applications We a of been sorts vivo It's

work saw you at And the we gave broadly. in Spring of in the where vivo Cold off looking stochastic of in the think additional is target the the If that done very to setting. for for there's we're Harbor, one field, of presentation things effects we that's state-of-the-art be terms mindful

ex that and change vivo to So, base the work is think may continue But time. the sure the nearest the place that probably setting I'm will use editor. in best term, over we

Jay Olson

Maybe question. one follow-on

presentation next at on we upcoming looking gating moving steps? to ASGCT, of and factors to what kind what that data the program preclinical should your the be for For are

John Leonard

presentations off-target making. is detailed that analysis a we to do. approach Well, very what speaks at ASGCT, the remember, we're which One there's broadly of two

necessarily relate particular any doesn't it program. So to

its The respect not pipeline its presentation to antitrypsin alpha-X will program. with be et on extended We're the other candidacy, on information talking yet and about cetera. status the

editing utilities. its also a will be clinical presentation have will We gene a CSO third where speaking and broadly about

development insights, So their about other won't some talking there. status be particular changing candidates the we be and there'll but


Your Jack next Baird. Allen from question comes with

Jack Allen

Thank Allen touch you move towards with decision clinic. NTLA-XXXX to your It's We data trial that know someone the that could weighing our of wondering you move equivalent into number briefly bit a Is program IND clinic? And want much. expect understanding are going it dictate so to may the file year. earlier, IND or here the you the the for How therapies end IND that magnitude to Could already this touched on NTLA-XXXX do briefly by here. I you and there a the we you this Jack of as an decision? the to clinical of HAE. as or mentioned then an if about factors the one an of the you benefit It's approved on were expectations that talk it but you that for you the go are equivalent? for speak you're factors IND in

John Leonard

the the time hereditary can treated with at ongoing words that, they're therapy. Remember, Just don't treating are occurs, that prophylaxed is we typically a attack that an patients Either condition. we patients of have couple made case like as where respect or pharmacopoeia. the to of identified these puberty are with think shortly think patients sit that thereafter. about to in been NTLA-XXXX We certainly ideally that the have angioedema. modality It's suited advances or

treatment effective, very, That a so. you're cases that what some essentially, as less about has in and others become talking is therapy. burden, is So very significant far quite lifelong one and

remains. $X are most spending clearly Don't therapies. over starting over opportunity expensive, million million year year therapies extremely therapeutic So, a $X.X those patients a with for also effective forget at that many same

what and that it we where to very about we're we achieved, the So, do and system, every it we in to trial, expect carry the meeting to is, we offer across it's that something respect ultimate have or it, that work and so clinical healthcare the certainly going decision effect have a then front. think treatment, to central where With whether the on where our with exceeding how how the it's the the patients we costs and we're all would that be the we to whatever is And dealing wherever single burden workout. to with this whether and of do look think significant doing as we factor we're dealing and we drug factor others do, it. or pharmacoeconomic doing,


to hand time closing no for remarks. questions. is There you. will I further for Lina Thank now back

Lina Li

We Great, progress. our look thank continued and interest for Have joining a day. to you forward updating on all you us for wonderful today your support. and


for for conclude conference That our does Thank today. you participating.

lines. your disconnect now may You