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NTLA Intellia Therapeutics

Participants
Josh Rappaport Investor Relations
John Leonard Chief Executive Officer
David Lebwohl Chief Medical Officer
Laura Sepp-Lorenzino Chief Scientist Officer
Glenn Goddard Chief Financial Officer
Maury Raycroft Jefferies
Rick Bienkowski SVB Leerink
Timur Ivannikov Raymond James
Joon Lee Truist Securities
Yanan Zhu Wells Fargo
Tashdid Hasan ROTH Capital Partners
Call transcript
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Operator

Good morning. My name is Andrew and I will be your conference operator today and welcome to the Intellia Therapeutics Fourth Quarter 2020 Earnings Conference Call. [Operator Instructions] At this time, I would like to turn it over to Josh Rappaport, Managing Director at Stern Investor Relations. Please go ahead.

Josh Rappaport

Thank you, operator. welcome call. fourth and year and everyone earnings XXXX morning, to quarter Intellia’s full Good Intellia a discussion today, quarter Earlier issued and progress the the this company’s topics for on call. press today’s release outlining can Intellia’s at of release Media website be Investors intelliatx.com. the This and on section found This call a live broadcast replay archived be also is company’s the being on website. and will

filings a of potential forward-looking Before risks today for available on refer duty unless uncertainties. Intellia management this undertakes call, that during we of get information this you started, to Intellia sec.gov that I make at would statements certain and like as to ask required presented discussion All by update this SEC call information to remind is and law. you and no may current

Intellia Chief on Chief Dr. Officer. Officer; Officer; today’s Chief Executive Chief from Goddard, David Sepp-Lorenzino, Dr. Laura me Glenn Leonard, Financial call Dr. and John Lebwohl; Medical Officer; are Scientist Joining

highlights, begin recap For provide the will will fourth will today’s progress, on call, company’s Laura year an review John the R&D by full from and XXXX. David efforts NTLA-XXXX, quarter the results update Glenn will clinical with financial company’s and discussing

remarks, me for call open will With that, to Q&A. let Following the prepared turn their over we call the up John.

John Leonard

with developing at and of transform genome medicine to and severe forefront is editing has Josh technologies never applications greater in you an you, at been people movement, are lives to gene in revolutionary We thank us curative genomics This joining of disease. the the editing Intellia There field. proud Thank of this beyond. be for treatments exciting all be this morning. for the time to appreciation the

modular in full CRISPR/CasX-based deploys which and vivo solutions platform supports ex spectrum strategy, Our applications. therapeutic leading across vivo a differentiated

leverages genetic precisely we vivo produce disease-causing selectively to our genes knockout disease, which insert lipid proteins. genes approach, or utilize delivery a nanoparticle-based to system in For normal

efforts, product cell clinical first was our stage emerging in to patients shortly cancer is was our and for T-cell to a robust a XXXX our own clinical year a natural the immune broad first we milestone global We patient submitted dosed patient’s generated genetic study the or system for It’s research produce and TCR-based the pipeline, application Phase for thereafter, tremendous an trial homogeneous clinical first that a enter vivo therapy receptor Across gene-editing field disease. epitomizes expansive CRISPR-based portfolio. for approach have ex eliminate This development. X team. Intellia these designed and a Our landmark candidates cells. including from NTLA-XXXX. to with systemically-delivered

we reflect on addition, editing, investors. gene two And we but therapy platform. candidate, from not differentiate is our key only which our and review priorities Intellia’s these Today’s activities solutions support NTLA-XXXX, engineering. Regeneron our We platform scientific to expansion achievements, on and candidates, advanced call an second T-cell the anticipated to our and nicely modularity new year. both significant with milestones our capabilities and In IND-enabling our TCR of for our in our vivo NTLA-XXXX, next prizewinning built foundation, first Nobel the engineered broadened our knockout for demonstrates strengthened development of corporate position for delivery existing collaboration opportunity this and and also cell further

ATTR curative This the of continue that continuing of NTLA-XXXX, year as clinical platform clinical and capabilities. advancing year, we option a of approach non-viral in vivo validation Our as and for with will we evaluation the to patients treatment to both profile began delivery. top last of our NTLA-XXXX potentially approach our demonstrating our three priorities build are our and expanding validation plan;

candidate. nominate our to planned and for new also submissions NTLA-XXXX and expect continue In advance to development we and we with NTLA-XXXX least regulatory will pipeline expand addition, first-in-human one at

components therapeutics. will we founding, gene curative to next serve expansive portfolio we modular building toolbox set have powering wave At of platform and the candidates. continue could out complete our develop enable editing of to a that pipeline the as Finally, engine

me unlock has both for of rapid should and path, are in In to and Chief since call over ex commitment data our development additional with this vivo, our of we clinic editing’s to progress David With moving remain that in that, into a update and building paved provide progress growth candidates, therapeutic broad who matures Lebwohl, genome a vivo in steadfast programs in investment anticipation Officer, first-in-human our David? NTLA-XXXX. in on Medical the let reproducible play Our long-term our potential. turn as forward. full year will an out and the pipeline R&D clinical

David Lebwohl

the the you, and ATTR, which TTR disease protein. between protein with and form an to of in of ATTR multiple cardiomyopathy. wild-type circulating the treatment manifestations ATTR, progressive of wild-type and is vivo all fatal are I results there good which our hereditary polyneuropathy our amyloidosis, everyone. source and will hereditary frequently, the for with Thank ATTR, knockout ATTR. with XX,XXX the have of in of start XXX,XXX of by wild-type bit can background. or or and the ATTR applies XXX,XXX followed a with gene people Transthyretin NTLA-XXXX, most John morning liver, People approach in the manifestations, Globally, either TTR disease, a estimated investigational buildup is diverse in therapy disease living organs.

the population investigators two enthusiastic this significant at stabilized therapies are unmet and patients condition. system. will deliver of to both curative in condition, tell a field and medical to there patients the to potentially treatment are their value meaningful this best remains and may are there not XXXX cured need us healthcare chronic our for bring as Leading patients in Although underlying

showing Our disease potential robust halt as to long-lasting preclinical reverse and XXXX one-and-done TTR and possibly data support reduction a progression. treatment deep

clinical patient dosed this in to Phase UK’s a our clearance trial in first stage November, Following October, study CTA company. of the our initiate in marking authorization X the with transition into our we

sites part global ongoing patients enroll Kingdom United and development across other trial strategy. New to in submitting our the are clinical Zealand additional of and countries continue applications in We as

this X trial reminder, tolerability, in open-label XXXX evaluate of As the is that is a adult pharmacodynamics ATTR designed to with patients pharmacokinetics with a multi-center polyneuropathy. and safety, two-part hereditary Phase

to at the who X part, up plan to biologically enroll each a an dose. dose single a initial assessment up cohort activity the will clinical XX single-ascending active design of a data disease. of including following dose to single which neurologic of a additional the characterize measures the be traditional design X plus XXXX, the Part will obtain expansion dose. of further We and is trial the neuropathy patients includes Then serum receive X optimal and and active levels, with This second biomarker on measurement cohorts, optimal move into to safety infusion. of of intravenous TTR dose XXXX a study at biologically quickly X additional we aimed identifying an patients to X key function

share the give activity of Part We year. or profile The X this a drug of results will expect as study doses preliminary of the the the a scientific at study medical trial results safety view initial in us from and to interim from progresses. the meeting this

modular delivery proof-of-concept will for Importantly, clinical our we platform. our believe establish LNP interim results

biological same this and plan biologically-active have the polyneuropathy identify assessing evaluated for polyneuropathy study with dose addition, ATTR we population, in in these and we and Once patients dose across optimal an with cardiomyopathy. our In important patient activity start X to dose, manifestations. safety expect the In studies identified able XXXX. represent milestone cardiomyopathy the to disease Phase optimal anticipate to the editing to data we be patients expect we we towards the XXXX optimal run at be different identifying the will as

year. off, clinical momentous dosing achievement I with patient We first the acknowledge want glimpse call our to later in forward our data look into the passing first to sharing XXXX. this Before

Scientific Now, for I Laura our Sepp-Lorenzino, turn development XXXX additional to and this will efforts. and R&D Chief our our two on candidates, over across XXXX updates Officer,

Laura Sepp-Lorenzino

for experience Thanks, and HAE. in recurrent, in in treatment with second tissues. swelling of unpredictable begin candidate, hereditary painful vivo our David. NTLA-XXXX, knockout or will patients HAE I angioedema, development multiple the

are only altogether. therapy there liver, for We attacks, gene therapies delivery and there and in of prevent intensity While significant. same patients opportunity believe the remain to designed the not frequency NTLA-XXXX. additional leveraging NTLA-XXXX can a [indiscernible] is eliminate them for LNP and reduces prophylactic which for acute further KLKB-X but that the HAE, used is knockout system

sharing Meeting, confirming primates be clinical & American versus in from will for serum reductions activity at levels of care kallikrein greater We non-human the program and Academy Annual week current protein Allergy, this of standard HAE. the in Immunology results Asthma this

study. following will capture durability through dose data this an in far the months non-human so addition, effect, ongoing primate In sustained a single XX of

including NTLA-XXXX total a editing, permeability, in application hypothesis year. a To bradykinin-mediated therapeutic and NTLA-XXXX KLKB-X evaluate insights remain in resulted We clinical where first-in-human model prevention It’s anticipate to safety, of kallikrein gene disease expect of robust of trials commenced in leveraging levels kallikrein to the kallikrein test administration from in the single patients this symptoms after and start expect KLKB-X GMP a levels confirm also captopril-induced NTLA-XXXX could lifetime we translatable submit begin a in model reductions and we of my point, our We activity, therefore activities second its of humanized vascular mouse vascular for on to patients study, and course permanently of for single able being at NTLA-XXXX treatment. dose regulatory leakage. effectively and of by NTLA-XXXX to manufacturing reducing will measures a the from track half free debilitating subsequent of tolerability are arm. earlier higher which we

ability edits for using efforts tool vivo, open match Regardless efforts, we the scalable and can our cell Similar yields, and sequential in Turning here highly-efficient approach full pharmacology. cell modular and vivo high a now of with ex versatility to editing, to targeted to cell to proprietary engineering modality mix CRISPR/CasX the introduce platform manufacturing. as underpins create therapies. a achieve eliciting our and solution, across engineered are our we to to performance to type, necessary

a Our lead TCR-based program, employs NTLA-XXXX, approach.

differentiating deal data function precisely for receptors replace potency of translate process process This targeting risk our T-cell should targeting and to and multiplex we technologies other great NTLA-XXXX TCR. and to and versus response tumor you shared patients reduces is improved the editing. have is outcomes WTX patient’s recent long-term with WTX SAT edit We XX% have delivering overall rates XX%. over-expressed And Despite to of advances in initially therapeutic types. developed AML treat continue in AML, of below of X-year subsets over survival recur regardless to recall, with AML. safety if

ensure to period long-term subtypes generated high-quality with patients across for solution proof-of-concept mimics receive and mutational approach with Core a produced showed AML. compared this capable data that American natural standard advantages patients anti-tumor is At superior forms outcomes all broken of December, cell in a improving our enhances target, be additional we prevalent Annual to NTLA-XXXX to showing models of data this acute Meeting response. hope proprietary editing Hematology is our will their engineering high product So, a well robust process of engineered natural The activity NTLA-XXXX in T-cells T-cells mouse immune the also Society process. preclinical and of of gene leukemia. expansion factor function shared and

IND-enabling on steady IND midyear. and We with submit NTLA-XXXX track an to continue equivalent progress make or are to for we activities

first of AML to patients therapy. have expected who safety with recurrent or first-line Our clinical is in and received evaluate NTLA-XXXX trial human previously the persistent activity

approach and single specific and candidates platform new full across platform efforts nonhuman hemophilia building transgene SERPINAX into In including multiple important a our for our cell to are have least plan we the at off we normal advancing This Factor demonstration in therapies cancer. targeted versatility circulating for partnered generation programs Insertion enables administration. presented nominate which albumin for for research broader now human candidate targets, John with B. next our produce we further proof-of-concept December, toolbox. alpha-X targets. AAT wholly-owned this we [indiscernible] vivo through The across Further, pursuing advances, quickly primate spectrum second our of a our liver are with of wholly-owned work, gene of we Within study, pipeline Moving partner IX technology differentiating and approach research And noted, diseases developing and the insertion, as locus allows genetic efforts, move is leveraging we or both engineered to modular this levels to our us insertion. applications expansion. antitrypsin, work year. after an against our of are

we cell grant Bill disease. a to stem Additionally, Melinda in received & genome editing November, sickle for in Gates explore Foundation a the potential cure of vivo cells from hematopoietic as

NTLA-XXXX allogeneic enabling In us in WTX-positive a vivo, are same response of of Enhanced we potential studies yield are vivo the use for tumors is genome to it therapies, of products therapies. to in stage some resistant tissue treat treat the cell towards diseases cellular optimize only engineered safety the characteristics with editing, but efficacy. solid for reinforcements Ex rejected. are to and patients, solution improved our multiple T-cell important the for mixed for sets types. clinical this ensure in should T-cell Importantly, against the contract off-the-shelf the we wave we working evaluating development it’s health and not cancers additional and cell believe with developing to benefits and cells function, targeted across

year these to more coming most we our tool genome to editing for at continue appropriate as application. to look sharing the therapeutic forward tools the we expand given in supporting details apply Finally, disposal, the plan a the the Glenn, optionality quarter to We call like an to hand I results. that, our And provide would financial conferences efforts. all who present XXXX year to overview fourth with and across over full at now of will scientific

Glenn Goddard

Thank well-positioned for upcoming you, and is Intellia Laura milestones. our morning. good

proceeds external XXXX to XXXX. The as $XXX.X cash, $XXX financing were expanded from from net of $XXX.X fund December XX, cash in was mainly and of Our $XXX.X XX, our from collaborations, million operations $XXX.X and equivalents million used compared Regeneron collaboration Regeneron million and million increase marketable as driven the $XX.X cash Novartis December to million. part securities offset million activities, by of by of

portion of collaboration $X.X fourth ended of the quarter revenue million driven quarter mainly to The during $XX.X by decreased in million the during Novartis revenue in $X.X million XXXX resource compared fourth of to decrease December of collaboration decrease XXXX. by a was the XXXX. the Our as

Our to by was programs, programs, $XX.X quarter research expansion personnel R&D million million increase to to mainly the and quarter expenses advancement of XXXX driven of fourth This during of organization. these compared during $XX.X the growth of the fourth increased by XXXX. development the lead million the our $X.X support

million quarter This increased expenses $X mainly employee-related to $XX.X G&A due of during the Our the quarter stock-based of expenses, by during compensation fourth million XXXX. to increase including to million of million. $X.X XXXX was compared fourth $X.X

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

John Leonard

and your David to Laura and for Glenn Thanks, as well updates.

here our can we a there at the a in this is and systemically-delivered of CRISPR forward productive you XXXX. we in carry see, going Coming Intellia. on As XXXX lot off advanced are poised dosed which portfolio, to with first patient momentum therapy

progressing as our towards vivo portfolio and our in further platform enabling vivo therapies approach our sharing this in for study X platform. for continue interim half submissions and engineered later this new differentiate NTLA-XXXX wholly-owned progress look editing Phase targets other forward to genome innovations efforts, research of partnered anticipated regulatory an we Across we to our in capabilities of with as the liver, clinic. includes of NTLA-XXXX our year across NTLA-XXXX stage results are of And research We our and year pipeline. toolkit first-in-human development. for expand in advanced multiple second therapeutic allogeneic the This the midyear clinical validation cell editing and and continue for tissues will the to we we next-generation

these committed keep As to promise XXXX, priorities making patients. focused are reality we for on editing’s core for genome a we

the any questions. will line We now open Operator? to

Operator

Please The go from first Richter comes question Goldman Salveen Sachs. Instructions] [Operator with ahead.

Unidentified Analyst

knockdown bit and so much a need This the of Laura, what or expect you there that Sonia to Will you could little data in is something taking AAP show terms Are will we you. the our RNAi the through higher? Thank additional then when And about you have match Salveen. questions. you knockdowns would also, particular to are targeting? the asset be? benchmark talk Hi, for for thank you can year? conferences the on

John Leonard

it’s Sonia good thanks morning, John. and

outcomes, patients, as we We that thereabouts is form that’s can in of is the there to reductions think medical to important unmet And have for form we as doing. more which XX%, program products not that’s so exceed for which do aspiration is very, comes get, get here, the disease, are very think actually and as have With goalposts amyloidosis work out to for improved it’s efficacy the the we much but that or can’t in in it, progressing data that. for. this think progression initial Phase reverse venues yet they if careful what other we competitive, is a as which conferences we study of the XX% just any underway. delay additional benchmarks to And really with to but our will really will of that have think that, been particular but The guide that look X need and study the way there to are we mind attention that’s share we benchmark, we we beyond we to is general year, have is always and particular look medical about the be going that at advances we we we paid we provide respect are accumulate in to wonderful but one. amyloidosis very as is made and certainly really there think this point, that, said, appropriate

Unidentified Analyst

Alright, you. thank

terms other the I was more assets I etcetera? the [indiscernible] about asking alpha-X of, I in guess, think antitrypsin assets,

John Leonard

beta has question. the thus is basis presented a far the maybe which data, confusion misheard I The sorry we am been knockdown not I of here. your

And we levels. it that get we at production demonstrated shows human that of not has production of human protein, normal human that that data protein. insertion get can normal work but presented We have only normal the

look are the we beyond as there, so patients, benchmarks are replacement to all therapy. we ready therapeutically that’s well at available And out anything that including

therapy, are of that position. in we production a wonderful we does of are doing. the think from the taking from we So, abnormal we that’s approach are that work protein separate and standpoint not directly replacement The address currently

Unidentified Analyst

Thanks. that And see the we from will through data any program? year additional

John Leonard

There at the share on, any possibility we we year release not to have guiding good particular goes more are as will to this point. is but a

Unidentified Analyst

so Okay, you much. thank

Operator

from The Maury comes question go of next Please Jefferies. ahead. Raycroft

Maury Raycroft

for taking progress morning and thanks congrats and good Hi, questions. on my the

ATTR, just specifics on is guess level. question data are dosing? you at first provide have First why if are in dose enrollment at XXXX? And and I with are where you anymore you clarity can on wondering reasons you there still into now and providing confidence specific the

John Leonard

question. appreciate you the it. We Thank for

As November year progressed per you started of plan. as know, things last much have we enrolling and pretty

and sharing by by have as where cohort is we progression that we to meaningful we are that a a taken data that disclose. we that’s think We not get of but representative patients group, clinical choose would what body position or

moving you think that So, is we and more out and story I what that look we sharing take complete plan have forward study have we when it should we laid developed. to forward are

Maury Raycroft

the getting guess or in to see makes That sight in John, into we that that it. knockdown I we sense. optimal to degree initial emerging will expect data? knockdown way And should I data is greater that, that that right XX% data line should about of Got or of knockdown? a provide the or think And for the how you many guess initial cohorts mentioned ATTR, XX% greater of

John Leonard

Thanks I we in Maury. in implicit be I the way really cohort, which again. to question, am clarity your is you give somewhat per outcomes The good to not respect with position set going – And Yes. some a is reasonable to that moved is know, program cohorts work effect. human. place this of up from have the we you each the different as these first into therapeutic of time likelihood first having preclinical has in a

across and we modeling that done some effect the is a effect the to different was each optimal the something determine different done, time that thinking cohorts. was intention good we escalate So, of that of will with is this have as doses chosen and – the we validate seeing effect the but the of an will that biological

but readily place. that while will something we’ll is have we be So the that and is what we study meaningful still expect – would that, taking think interpretable, that that’s we share, is and

Maury Raycroft

Got it.

that a so into level the with the Is you initial And dose. us that getting sight fair? update are or trajectory should each a of the give line of knockdown

John Leonard

with achieved safety of that see I sort certainly would think what that. doses speculate together position data we with and, a but would sharing be at to that we’ve you dose. dose and anticipate would we be that, goes effect a given With can subsequent be, you particular on respect TTR extrapolating the The what to a a course, will in of

Maury Raycroft

Got it.

maybe on U.S. some just update Okay. regulatory if applications wondering question the provide we will just quick And of XQ you are or say can And so should you back being whether a last you or submitted if keep on IND? trials regulatory just out? clinical applications XQ an accepted an additional eye on submitted, the

John Leonard

yet exactly are subsequent shared regulatory filings programs TTR we we’ll for program. the to have the haven’t So which

are those definitely we’ll share you. information that with As cleared,

Maury Raycroft

Got it.

for you taking questions. thank my Okay,

John Leonard

Of course.

Operator

next comes Please Mani SVB Foroohar from from ahead. go Our question Leerink.

Rick Bienkowski

is This Mani. Rick taking morning. for my good questions. the line Thanks on for Hey,

anticipate for additional maybe global there could expand on countries how might complete you comment might as strategy I development wondering how trial Phase question, study? were a first clinical was in about study was to need the applications earlier submitting countries many clinical in hoping We you program strategy. the many bit. And sites my into? of the just order TTR a X the you extend the eventually For an part

John Leonard

Yes.

we’re currently, conducting Zealand. the So and in the both New UK study

need. currently the unfolds, the actually we with we as the is discussion. that, the X conduct study study we of a But matter you. not and share We will activate that’s X finish to other as to that progressing. we’ll something that positioned get information Phase Whether that study Phase were have couple them a believe or we applications structured, And are

from program We’re Phase because broadly, broad-based expanding certainly say will network regulatory be and ultimately, the in beyond, X and interested program, global. always let’s the

for of the We have multiple had played advancement basis program. we interactions the regulatory as the

Rick Bienkowski

Thanks. it. year-end. financials in currently just Got on clinic INDs more the two forward-looking are in XXXX, in spend the I My R&D is was second how think additional should and we by understand and focused ‘XX about expected question

we’re R&D steady we if guess throughout more year increase expect I should quarter-to-quarter? be if company in changes specific spend spend a hits wondering So might the as or R&D lumpy milestones the in

John Leonard

Yes.

take do So let’s CFO. turn our to you that, please? want Glenn, to

Glenn Goddard

Yes. we as that as end Sure. of the you get a at – XX noted, strong year. position the guided have us We as we of the call, next We’ve very will months. noted in the cash that, least through

it We year-by-year over giving to OpEx lumpy. kind time. don’t specific but the operating expenses that is drift fair not We’re expect up think I R&D guidance out, will assume it to of be

it be will going you to saw the I from similar think XXXX. trend XXXX into

could a You expect going next similar into year. trend

Rick Bienkowski

really That’s Great. helpful.

thank and you the again. for taking progress all the questions, want guys congratulate to on you Just

John Leonard

Thank you.

Operator

go question ahead. from with next The comes Please Gena Wang Barclays.

Unidentified Analyst

This on for Hi, is good Gena. morning. Romit

So be one study? of clarification the you larger X or X is the question, in TTR would that enroll to plan for Part that the patients patients included that in the in plan trial, pivoting the the cardiomyopathy

John Leonard

degree manifestation with that take not X although you that’s this think will have you first-in-human this of the polyneuropathy. Phase There study as predominantly a I are study. way patients, mixed in has phenotype there’s know, about cardiomyopathy, that. predominant Yes, some is – the patients that is That’s we should a

dose predominantly patients, David patients mixing in not to in applicable his into first-in-human cardiomyopathy be a we planning said we We will biological would believe as cardiomyopathy with study. study. readily we that be address optimal subsequent comments, the which the that will But are

Unidentified Analyst

you just So part then in And Okay. what Part optimal can the definition X. is like four tell dose? us of these your that, escalation dose to have follow-up a you

the would be exactly to of into dose X for? the trial? what an optimal constitutes And Part what looking So move you

John Leonard

want you optimal dose? address do thinking are how you biological David, about to

David Lebwohl

has course, be dose. one, optimum really of which phased idea John. Yes. it pieces, Thanks, buybacks to The has two for a

saw big important as is that potential So this Phase what And dose. safety that. is forward study, – will talked a therapy, make paid for we do we’ve studies can the think XX% with that’s course, you difference the is and think a to that’s because we’re would at what we’re getting characterizing dose between, the primate the a efficacy X be we potentially of And in want a reduction deep bigger valuable towards the reduction being even XX% to in as go choose of patients, now non-human we about, this ultimately, of reduction. looking whatever for patients. and of range getting higher the is we But something and TTR it but activity carefully, we get be to piece that – current to degrees

Unidentified Analyst

Okay, got it. Thanks for the taking questions.

Operator

of ahead. go Raymond The comes James. Seedhouse Steve from next Please question

Timur Ivannikov

on for morning. Timur Steve good Seedhouse. Hi, Ivannikov This Yes. is

that have different reviewing of measurements, similar asked looks human you what slightly NHP metrics? you. sort have terms like at Phase but time other you slightly ATTR study in And so your about talk points Could and take line X question Thank differently, those time the weakly? of study? data assessing knockdown Is for for about that that a and – we study you it procedure

John Leonard

of the were relate summarize preclinical Yes. just articulation that David, The the But out where work? – broadly, a study assessments could the get you details. of these people can clinictrials.gov the some so you laid to of lot on maybe, can

David Lebwohl

that preclinical by in said see lower we ELISA. an is the point the you around measured but And measured what of expect through what you is from is really and well, gold XX models think in days. standard as measure important study, we it’s as intermittently I as TTR, which mentioned, PPO reach this at the you –

the you will have be. idea days really good by XX So ultimate a what reduction

all this that expected reduction follow a will on terms TTR based the is be but in patients are previously, We early at the will point. continue to we that work as it. done how we’ve to you know, of And permanent of doing have idea good

Timur Ivannikov

of terms Thank differently and that. Okay. in monitoring Thank monitoring any cardiomyopathy doing mix then versus terms you those for the you. future anything follow-up in the phenotype. you be you for maybe Are in patients of question And Will polyneuropathy, polyneuropathy? for doing cardiomyopathy patients? different a

John Leonard

David, want you do to that? take on

David Lebwohl

Got it, John. Yes.

patients, about effect out not It we these cardiomyopathy, it do this And involvement to pay more we that for going early patients done cardiomyopathy. give with these to is have standard in patients, all almost forward design are you details will we that’s to heart may learn so dedicated the patients study have that monitoring something functional a even patients So that we will prepared. with turns being the some that, haven’t in for but designed study. next as fully doing

Timur Ivannikov

Okay, you questions. much very for great. the taking Thank

Operator

Lee ahead. next The Securities. question go with from comes Joon Please Truist

Joon Lee

bluebird taking CRISPR/Cas? won’t Hi, the Foundation what us In question. to of thanks Gates light our the with have road make the bio, preconditioning but bluebird sure vivo safety concerns given remind effects you X a years And cell, update that to to the pretty just I’m X around from by that down just wanted sure approaches in to broaden I to follow-on. develop the triggered therapeutic? again, tensor see you comfort gives weaker or partnership of recent for of with sickle updates regarding latter, from off-target any for bio. signal in regards your Then is the scope it’s

John Leonard

type even conditioning that programs vivo with of just other I to with chemotherapeutic are respect other approach out. doing. a results vivo somewhat TTR come may think gene a sort contrast outcomes by the doesn’t things. is And precise happens one work doesn’t the that lands so that, in to all, the and lentivirus taking as vivo what to difficult important provoked insertion, sorts that nature different is taking It’s bluebird then the whatever Certainly, safety thereafter. sort two of some related questions really of to apply possibly important Number seeing at But we’re our editing really approaches. that the utilize the we’re regimen of control And we’re a the thanks. maybe but to I opposed to that with and relate bio which on even would don’t random where of side, question. really So the I approach trying think in that the secondly, in

about go, So to you us, about bone demonstrating for job it and equation preparing preserved transplant, think genetic of controlling really think, our done those ex to a the we’ve team regimen has want done, from again, really when that very the so is different And you of feel process, the feel that everything approach. really insertion goes Laura’s exactly vivo wonderful side architectures receiving about patients you I the the conditioning that we turn the marrow when good that. NTLA-XXXX, see what for we we so just with good where

marrow talking we’re is regimen sickle imprecise issues I therapy Now to like the thalassemia. Foundation, approaches, And here, with increasingly, conditioning consequences diseases bone editing bone with approach, brings all with morbid a – at, an an current inherently view, cell of which all opportunities transplant the is across safety what is that if demonstrated required with those wonderful to of the a with gene challenge there you’re marrow and springs the using editing exactly problem. patients I people sometimes looked Gates think, the from think that The to and that, but you come is it respect we’ve point it, and can as whatever about are disease apply field the that mortality. of transplant. And address that,

we the leapfrog to gene many, potentially the again, with outcomes bone together. standpoint desirable And approaches So editing disease, delivery, bone with we able come you sickle company, believe of which would from marrow, we, current cell editing can are going editing and as to the a not thousands of that all avoid bring current that, many capture transplant highly to and to the believe we, with therapies genome do. patients think that can marrow be

Joon Lee

of clarification. the Thank Great. that presentation different the You impressive, a curious lot to it’s ESGCT something we And program Thanks for front? AXAT altogether? on very candidate, question, follow-up development just is on what on you. look forward the hemophilia can saw new or or

John Leonard

with have that’s Thanks. company And advancing, making. choose the you on the a both well. forward from, vivo and ex as we that’s point the both are side to I active make sure there. sides vivo that Laura in relationship moving have point we We side, as and that ask of to programs very Well, Regeneron we the have and you’re lot exciting think very out, a

we the going development through excited So very not it and we’re that candidate, and the particular go. just in But there’s about sorting we’re we’re at some list, as to point others yet. to of least that very, one

one So for. stay would just that’s tuned I

get the We will a as little more clarity you into year. we give bit further

Joon Lee

Thank you.

Operator

Oppenheimer. Instructions] next comes Olson The ahead. Jay go question [Operator Please of from

Unidentified Analyst

and the Jay. This question is Thanks congrats our line Shawn taking the on progress. for for on

like one of something like or genome for effect question out you RNA? on trial? Just vector gene is how And XXXX, of eke it key editing you’ll that target is any on could monitoring the more the Thank side consequence would be arrives, you. if clinical be there a else target wondering,

John Leonard

What into want you this particular off-target that? the to the even at things of for do this realm figure David, monitoring address are point? discussion in you

David Lebwohl

do. safety. both Thank that we’ve out, comprehensive, of that this in that the thing forward, vivo and in we’re a itself, with we’ve safety we hear establish we at could vitro how Yes, that off-target, we main the it looking we right are other study editing to John. affecting And knocking you, the more In and genes. as not this move you’ll really we in is – target But the feel clinically. Right. is program study, addressed done characterized. about its XX% can primates be would the feel were range people well. with they reductions the in primate we’re nanoparticle that to do and as But the really effects deep to was of based that what in the we non-human we proprietary tolerated different nanoparticles. want is of do well seeing doing, That the tolerated get pretty because lipid somewhat reduction on lipid to so non-human non-human immediate primates studies, we understand in A we’re doses that precisely terms but

Operator

follow-up? continuing Wells Yanan go Okay, a there Please was ahead. Zhu question comes the next with from And Fargo.

Yanan Zhu

thanks taking questions. Hi, my for

So whether repeat if so internal is what dosing a be far it on your dosing remind quick Thanks. And And repeat one enrollment by does at the program, expectations? can you of protocol? first, time us point is allowed cadence maybe of then meet couple considered? the could TTR

John Leonard

so that. to sort the think, phenomenal a the second and Yes. just we I satisfied we’ve job, I been be just gratifying it. quite to take had We’ve Thanks. want the a think been involved and that’s interactions thing that respect with study Yes, doing are progress repeat who with. really with With excited of made I I make forgot can really we’ve just has been that investigators the sure... going – to question, well.

Yanan Zhu

dosing. repeat it, That’s

John Leonard

formally study Thank dosing Yes. those we’re across who a program patients means this so Repeat there study like the Yes. biological that patients of if particular came optimal an early you. part other that. receive provisions receive not where working be a dose, to did into will for on

that’s working that we’re something on. So

Yanan Zhu

it. Got

or thought just for the for U.S. where an in TCR curious following the IND file? On process equivalent WTX the consideration program, determining what whether the the could talk about outside U.S. any about to you

John Leonard

Yes.

we there. to yet ultimately, want where we’re a to guiding filing, although precisely and not have program broad-based, what global we’re So

and to and we so extensive that. a regulatory be are able We’re complexities And this to we’ve into the to going confident prepare making the we’re that, interactions to going in to get for robust do most to that program, requirements very confident meet well. clinic very, going we’re have year, be we’re position package we’re that There to had that’s regulatory sure that possible. the the

and the completing those in And so stages packages. we’re of really submissions final

and that So filings stay as clear, more tuned, those show broadly. we’ll information

Yanan Zhu

the collaborated approach on in Foundation. the a lastly, question maybe Gate And vivo sickle with cell

be vehicle do that any it Is The what approach? delivery hematopoietic curious, bone then the of is, marrow feasibility going data have stem to preclinical if approach you the do Thanks. kind you there? non-viral? non-viral it of a have? be delivery initial would cells, And what Just visibility for to data

John Leonard

cell. the That delivery address Thanks. but as in we with origins can that approaches. including emphasized non-viral is marrow. Yes. the you approach the single bone vivo we’ve the winning of in end Yes, for may them, know, company, certainly it the the approach not address believe And of tissue the sickle body, every from in many patients

general in the basis We’ve So of And Foundation the we’ll program we enthusiasm. position in was to think basis the a do their with that of a broadly non-viral the audience. more because I be which more is, merits that of see the fact, collaboration delivery for emphasis the them, some with approach make more as progress, this Gates and they share with as information we. shared preclinical

Yanan Zhu

you. Thank Great.

Operator

be Tony the Capital ROTH will Butler ahead. And today questioner Partners. last go Please with

Tashdid Hasan

Tony. is This morning. Good on Tash for

TTR question any patient let’s long-term a please? program, well, Just of, your And follow-up tell question about – must follow, also begin? about on of you us the word a those the before patients follow-up the – for can about say, the safety duration undergo

John Leonard

dose Can that asked, think we escalating? what evaluation safety safety patient once sure is I the dosed? about And that’s I understand question? you make correct? of Are then talking before just a you characterization the the ongoing

Tashdid Hasan

a throughout time are to be in going patient they a am be first but able be amount here patient. that escalation the would like details give one cohort, is that was Just – any dose I of if followed first in assuming something specific the And dose us for dose weeks, and the this X could to then about That’s set I part. hoping you that. first

John Leonard

Yes.

So some respect protocol you want David, do how is? general give to to with guidance the

David Lebwohl

past. of they – a nanoparticle, I Yes, lipid John. to are for are, occur the events in in these that short so said time. the period looking due again, And main the well-characterized again, safety

most that you So our relatively of see. it a follow-up is could weeks within short, few

the levels. design that, make for So PIC does to that safe. dose this a look different sure the patient does allow it’s between first different But intervals us – is of typical short these to with sort the each a basically,

Tashdid Hasan

cohort? what Thank to in dosing after you again following about sequential specific a or then simultaneously patients? dose for first do them to for the specific you patient to Are cohort, the that. dose you able wait – a have And two

David Lebwohl

dosed can wait, did cohorts, we call, initial subsequent in but the the together. In they be

Tashdid Hasan

there well, Thank requires the about approximately requirement? patients certain years, you. for FDA do we such for that is window give any deal follow-up, what here, lastly, – a have take, And long-term therapies XX or example for

David Lebwohl

world, it’s defined, regulatory not It’s completely for, a XX-year but that Yes, really let’s range. around that the in are agencies period. looking say,

will a we follow-up. having So a long-term planning be

Tashdid Hasan

about subsequent based lower well, the – And cohorts? based follow-up possible safety any follow-up generated initial what shortening in cohorts? Do this higher you those a lastly, period envision data what from yes, on shorter having of at about doses

David Lebwohl

we that The the go we as we forward wouldn’t trial, no, – it affect period to so see. going enough short significantly are are is

Tashdid Hasan

much. Thank you your am I for time. grateful very

Operator

question-and-answer our for back closing like session. I concludes conference over to turn to any the This would Leonard remarks. John

John Leonard

and I’d following you. like follow-up wish good their a to our can for you we us. necessary. it. questions thank day, all today for We appreciate Thank all and certainly I offline listeners of as

Operator

has Thank now concluded. conference The attending today’s for presentation. you

disconnect. You may now