NTLA Intellia Therapeutics

Ian Karp SVP, IR and Corporate Communications
Dr. John Leonard CEO
Dr. David Lebwohl Chief Medical Officer
Dr. Laura Sepp-Lorenzino Chief Scientific Officer
Glenn Goddard CFO
Maury Raycroft Jefferies
Joon Lee Truist Securities
Rick Bienkowski SVB Leerink
Xiaobin Gao Barclays
Luca Issi RBC
Liisa Bayko Evercore ISI
Yanan Zhu Wells Fargo
Dae Gon Ha Stifel
Timur Ivannikov Raymond James
Jay Olson Oppenheimer
Silvan Tuerkcan JMP Securities
Call transcript
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Good morning and welcome to the Intellia Therapeutics Third Quarter 2021 Financial Results Conference Call. My name is Drew and I will be your conference operator today.

Following formal remarks, we will open the call up for a question-and-answer session. This conference is being recorded at the Company's request and will be available on the Company's website following the end of the call.

As a reminder, all participants are currently in listen-only mode. now President conference Corporate of Intellia. will Karp, to Communications I Vice Senior Investor Instructions] turn over the Ian at [Operator Relations and proceed. Please

Ian Karp

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

quarter John call let our Q&A. And and CEO. open to results Intellia's Glenn Dr. John then, call, final John David will Joining me the the efforts Laura recent Financial On then update R&D will the today's over Chief Officer; NTLA-XXXX, highlights; for Chief and Officer. will provide third call progress. me for recap the remarks. business with David, today financial who NTLA-XXXX call will Chief clinical and Executive lead Officer; Scientific And will on the Dr. Medical Chief review Leonard, that, Laura are followed Lebwohl, close John? we Sepp-Lorenzino, an surrounding Dr. With Officer; turn on Glenn by the quarter. Company's Goddard, with NTLA-XXXX. will Company's

Dr. John Leonard

good Thank morning, you, everyone. Ian, and

focused year, this realize pipeline, delivered building demonstrating patients, full at earlier therapy in data medicines. the team clinical landmark advancing to our CRISPR-based upon CRISPR-based scientific potential intently of full systemically spectrum the the capabilities Following on first our remained industry-leading has our and Intellia

Our in and applications. vivo ex for therapeutic both, vivo modular solutions differentiated platform deploys

our leverages our proprietary diseases, vivo systemic platform in gene genetic for For fee-based approach owned editing.

opportunities. vivo that ex for includes cell system the produce designed approach that the generated is and We've continues to Our candidates catalysts. expansive upcoming patient's clinical strategic cancer future and share grow, autoimmune to of multiple products to now immune we're today, look and portfolio robust recent against homogeneous progress pipeline fuel an diseases. this treatment an a epitomize natural robust pleased and update priorities to to And on forward core research stage year, for our

consistency important amyloidosis, made level, into highly on of for the of NTLA-XXXX dose TTR in X. we thus Our patients progress Cohort NTLA-XXXX, or of Part closing and Phase establishing freedom relationship identifying profile, for dose recommended are Notably, and dose lead X We X study. remain program, our effect ATTR the forward the in safety transthyretin in we've response to at mg/kg amyloidosis a believe began first-in-human ongoing encouraged the in dosing quarter the X.X earlier study. reduction in the the in far move we

whose believe as a this see the result, earlier. population in separate intend study, cardiomyopathy. happy a to is with that we in cardiomyopathy the have all we in our of share patients will X Phase current forms primary while for manifestation clinical Based evaluation Additionally, on strength the we're our interim to NTLA-XXXX NTLA-XXXX in long we leapfrog amyloidosis, June, this include what would patients been our study. necessary could patient and produce to of has develop data accelerating ATTR of plan presented This we’re information been

As potential. possible, patient commercial quickly begin of need excited numbers, compared polyneuropathy, received regulatory of evaluating and to level to once the with we unmet terms as with represents We're as cardiomyopathy in approval. cardiomyopathy opportunities NTLA-XXXX larger patients in patients

believe future treatment the the We has potential to NTLA-XXXX dramatically to continue transform landscape.

we terms to In Part this it all safety include to plan present dataset in which will Part hosted from of comprehensive of event. interim allows a next at X steps, a company cohorts four from data QX X, XXXX from trial meaningful all approach, the for in us Taking which as Part with and steps, lays serum for four dosing and It beginning patients cohorts, recommended of as cardiomyopathy. TTR for across next cohorts. X, the dose X knockdown X includes extended foundation and well observation a selecting provide

decision slightly we've principles reflects a we've data present which timings beginning, the our body commitment data present to the established to of adjust when to accumulated to Our the the robust is information. from interim

initiate a first We the cohort next in quarter also dose plan expansion to Part X, single year. of

NTLA-XXXX, Beyond tremendous across made full spectrum our we've pipeline. progress

to our treating variety angioedema vivo our knockout delivery technology. hereditary studies. forward, for with in clearance candidate, HAE, a first-in-human NTLA-XXXX, for advance significant into is or genetic originate non-viral a diseases that our liver This First, we the modularity second platform regulatory of step received improving in

These we NTLA-XXXX missing gene durably ahead restore that of highlight now a we've approach. in of key if B. If quarter, to and levels candidates. insertion our whole a ability gene co-development require our solving candidate as candidate, human will for we liver, where with past hemophilia for programs, protein. this both the dominated that we've normal our party, unlock X a our plus they functional committed vivo the In insertion development safely or Second, wholly-owned Regeneron, inactivate AATD, for protein limitations we're traditional gene validated gene the diseases to includes clinically a and or a demonstrated to successful, targeted gene a ability have in our category deficiency in the first new of reproducible development treatment moving antitrypsin restoring promise humans, are two in CRISPR-mediated to insertion non-human results, lead nominated insertion defective This In Factor efforts alpha-X of therapy. with gene primates. result insertion

FDA’s ex NTLA-XXXX call will coming Intellia, for from forward our was advance has LNP-based development to as therapies. pipeline presentation three shape continue program, on approval incredibly of data, leading pipeline. weeks, genome cell in and other progress over clinical with the provide look myeloid engineering hand with for have Lebwohl, the David? highlighting in process our With that substantial QX NTLA-XXXX equally enhancements acute These programs Officer, generation leukemia, of further vivo the allogeneic development sharing who next programs interim of last cell-based preclinical clinic. landscape In new novel lead pipeline IND an update provide our made for enhanced we David third This for the treatment we the the of been to I'll Medical proprietary clinical AML. Chief our introduction, or editing solution to entering progress our XXXX. at to of and and Congress. Annual on we will now the ESGCT opportunity In technology month's productive summary, quarter the NTLA-XXXX data our us Third, the

Dr. David Lebwohl

John, and everyone. Thanks, welcome

as potential permanently landmark dose. which exceeding amyloid also of amyloidosis. demonstrated reducing serum patients delivery safety the reduction XXXX’s XXXX is achieved day earlier protein, gene a the level, dose one-time offered among TTR a TTR shared profile this two amyloidosis, in in for for patients for positive We results a for patients These the year. first dose vivo lead delivery with therapeutic in in data XXXX to CRISPR-based dependent TTR ATTR XXXX technology a LNP first proof-of-concept be Part from Our circulating a of at our only applies liver, polyneuropathy. TTR. non-viral therapy systemically the an not thereby three reduction TTR treatment we Phase delivered curative and a per potentially of X X.X dose after our These milligram data encouraging cohorts dosed knock is standard current the support X to candidate, At treatment care platform. an deposition of single average trial interim of XX% XX, of source the out ongoing and but kilogram

X kilogram continue evaluate relationship per to we the in third Cohort X.X XXXX. During the quarter, response of began level, we milligrams as at dose the dose patients dosing

as John with cardiomyopathy. encouraged ATTR noted, further safety safety and and we've observed not dose, for from include underlying we for the knockdown of X, clinical does on and Furthermore, activity profile slows well gene. of its type function. cardiomyopathy. the we path continued data clinical with in patients Part serum approved date, the our characterize the This from evaluation dose disease this treatment expand Company to only all with for approved, includes To by including mutant program, cohort XXXX. for data expansion trial. progression, in far. very the assessment interim to cohort. durability patients interim neurologic which of Part remain not expansion cardiomyopathy concerning thus measures all to across As Once We expect XXXX in The but initiate of both to activity If clinical of four X, is any of the ATTR cause. the expedites as of it single data of signals population recommended to the an disease, X present XXXX stabilizer, a that and patients XXXX. early to amyloidosis We select patients and an since with has the and we gaining are at is forms accelerating neuropathy all quarter confidence potential of drug Currently, to Cohorts believe first address based we cardiomyopathy the treat wild XXXX the registrational TTR X, cohorts plan and accelerates this cohorts targets intending TTR look safety

in Additionally, initiate of study quarter also the of the we first Part to expect XXXX. X

were orphan designation in October, the XXXX we ATTR pleased for share Finally, drug amyloidosis. FDA that granted by was to

platform, the in the development but continuous and liver KLKBX protein. our same reduce in kallikrein of modularity programs as is system intended technical development the vivo the we delivery eliminate safety, will plasma which XXXX, anticipate XXXX, our demonstrated in accelerated or authorities received trial as New evaluate HAE suppression permanently of authorization our XXXX, increased to wholly initiate levels LNP candidate such we Phase knockdown kallikrein This probability we of for gene attacks. liver, the as October, with the HAE owned in X/X in activity, of adults to X including Given to believe targets UK of work, targeting our XXXX. success. have additional The both, leverages provide application In study X from preclinical Type our of Type and Zealand study we clinical we've HAE. will tolerability and with activity, regulatory kallikrein of approach

first the enroll by to As previously expect guided, patients year-end. we

XXXX, AML Our lead in therapy response leverages patients will program improved TCR XX% by T we long-term CAR-T. of target Despite the with recent platform based announced regardless and with our antigens expression of accessible AML. active application remain patients an on Tumor and to XXXX. efforts. intracellular have be is received we rates subtype. cell approach. our to proprietary having agent study who believe XXXX five-year the will the for cell We Officer, T-cell Laura AML of Scientific continue a engineering best-in-class In ex be tolerability, provide frequent which a approach, by Phase delivering a XX%. safety, in I'll AML patients Laura in for vivo X/Xa therapeutic and to engineered our a our autologous adults over for we standard after kinetics R&D outcomes Sepp-Lorenzino XXXX, highly detectable therapy of poor improve subsets on Wilms' AML overexpressed well-tolerated now call updates on Between year-end our not overall to which targets survival speak activity FDA advances, intracellular to turn track than mutation accepted XXXX moment, screening outcomes to September, antitumor begin cell first-line below IND evaluating for this cells, the therapy. potential for Chief that more X process, antigen, With in WTX and AML,

Dr. Laura Sepp-Lorenzino

start I’ll our with David. Thanks, some of in vivo our with advances recent pipeline.

candidate which We NTLA-XXXX functional designed insert dose. development treatment noted, alpha-X protein John as wholly-owned the data a gene, potentially functional in disease. through AATD of and this a being sub-optimal curative to to NTLA-XXXX. deficiency we're in Intellia restore to newest of study. or the an the lung a IND-enabling developed copy the advance dramatically one year non-human As alpha-X after showing permanently excited SERPINAX in today of to treatment our for of SERPINAX potential is with believe At will encodes activities introduce led which for normal associated infusions protein primates presented alpha-X is NTLA-XXXX transplant protein ESGCT, therapy eliminate were advancing human Company for durable the ongoing levels that augmentation severe towards of weekly need The cases. IV insertion single

collaboration a nominated in development with addition, Factor Regeneron, In have X candidate for B. insertion just gene we also hemophilia

successful, the restoring early levels the patient's across life therapy two against out the we the of these potential to set beginning CRISPR-based at deliver insertion modality high we're If opportunity continuing for could replacement revolutionize best-in-class we in therapeutic With and of permanently we a goals gene Further, diseases. genetic the open intervene new represents nominations, of gene protein. insertion platform a to year. host believe our ambitious

sequential pre-clinical data of electroporation. the have we for cell several platform engineering electroporations product that Commonly limitations benefits LNP-based that used on development. developments, avoids important our at featuring Moving additional of the shared we use CRISPR ESGCT, face to

and Beyond of translocation procedure, DNA ex electroporation proprietary to introduced further edits, utilizes the In LNP-based delivery variants. also for if introduces well-recognized on editing sequential structural contribute and applications. off highly cells simultaneously, the process random base these of to our contrast, vivo for are If edits cytotoxicity multiple efficient required, genotoxicity. contributing

terms knockouts solution meaningful desired for hosting, vivo for genetics, efficacy our therapies. yield sequential characteristics product and minimizing risk in to efficient T-cells, advantages ex editing persistence We platform while the functional with performance cell leading high genotoxicity. and allows of presented translate to and of ultimately platform As believe will for our insertions, cell

alternative By for the therapy, for allogeneic to currently we're we our our deployed on cell Additionally, utilizing allogeneic three for able data time, first development. clinical can requirements therapies. approach, by these in not platform address and that presented be addressed engineering CAR-T TCR-T approaches immunological

avoid results. graft vivo only in natural NK to allogeneic performance, host our rates, our year. presented Data host NK also approach killing our will wholly our against and for robust SparingVision, also using a cells Glenn, strategies. another forward editing genomic medicines financial our first partnering vivo to Our see, T-cells, to form strategy or recently, killer of need avoid diseases graft Cellex, will pipeline therapies. and focused to more efficient non-viral CFO, owned no development allogeneic and persistence Life along We allogeneic who and [ph] viral and core in quarter ocular on clearly includes with mouse overview in rejection elimination our our Blackstone announced These tumor-killing vitro ESGCT company candidate Sciences treatment CDX nominating not in XX for that, options company, CRISPR-based areas but delivery With versus immune-suppression. I reflected a the including technologies. T-cell ability And novel outside hosts focus, announcements mediated efforts, to Outside expansion, half and universal to in developing CAR-T you models. collaboration by at impairment of and develop is third the an by the our new first designed provide strategies diseases, we demonstrated next CDX the previous look of call hand with without that as host

Glenn Goddard

Thank our aggressively financial and Intellia we extend is pipeline. in and position good as morning. advance you, strong a Laura,

follow-on $X.X by September XXXX. of from approximately XXXX, cash net proceeds $X.X as July driven agreement, million. increase and to $XXX.X cash, to in $XXX.X from marketable XX, employee-based used plans, million The $XXX.X by million compared of approximately of equivalents million proceeds were billion XX, offering, stock million mainly securities were $XX.X the Our These cash as offset net operations Company's was cost-sharing. of Regeneron our from ATM part increases of fund and $XX.X from proceeds million in December

by of Regeneron $X.X adjustment Our last one-time quarter in revenue million third during collaboration our was amendment expansion compared related year. of $XX.X the decrease XXXX. to of our $XX.X QX decreased to for by the of driven million catch-up to third million The during and recognized of $XX the quarter revenue million XXXX collaboration

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

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

next that, turn for With Finally, over our John call back closing cash plans we the expect will to fund operating current to I balance our months. the XX remarks. beyond

Dr. John Leonard

event In summary, from across platform execute quarter to the insertion with follow. move hosted the NTLA-XXXX, we In update pipeline XXXX towards Glenn. coming study weeks, you, plan an to We to at candidate, NTLA-XXXX as beyond. NTLA-XXXX, X sharing first and look additional interim Thank the at and fourth Company well a continues as advance Phase Intellia studies as a first-in-human the we in activities. team for IND-enabling forward our QX initiate of details our and into to

As Operator, industry-leading now With programs you to look our remarks. to approach new editing prepared you as we may call continue open for XXXX, that, on we we'll leverage updating questions. platform. the our conclude genome forward we


Instructions] Please go The will begin with first ahead. We session. Raycroft now the from question Maury question-and-answer [Operator comes Jefferies.

Maury Raycroft

on thanks the Hi. questions. Good And for Congrats taking my morning, quarter. everyone.

from far, patients you in been change cardiac this can For if cardiomyopathy those supported so collected exploratory have the the you patients, by dosed plans biomarkers? development biomarkers is many -- to and that accelerate that say, clinical for

Dr. John Leonard

do that? David, touch voice. David? First want to on of Maury. Nice morning, you all, hear your good to

Dr. David Lebwohl

are patients they of so have don't of that's you they though Even study, the to significant MRIs, time know getting heart infiltration general, the look true, the started points of have we who points than do but at for signs cardiomyopathy. Yes. their predominant In have, polyneuropathy, can predominantly Hi. with know, that do as and have in time -- the this -- Yes. longer are amendment amyloid, this we is current collecting that cardiomyopathy. symptoms of

on forward. really And what strongly this reduction of So, want TTR obviously associated improvement knowledge see is we of going based with symptoms. that our is to that's

Maury Raycroft

patients cardiomyopathy Okay, profile include guess, a cardiomyopathy the aim makes can specifics provide more you be sense. made what about How talk patients. also many you you if you protocol the enroll? for changes range? you can And more will to enroll? wondering on to select And, will will certain NT-proBNP I

Dr. David Lebwohl

We're to details talk now. expect, that going said not the right the we the patients. based the same we biology about dosing will be But, these on in do have

As you safety so had good profile very a we've know, far.

So, we well to of that go cardiomyopathy. be in the that But, later. also patients with expect coming will details out


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

Joon Lee

ATTR does that X that anything And Can the hoped, imply XX% Regarding fact in Cohort any Cohort plans so the patients? you TTR X achieved far? dosing durability program, as you about have X? your knockdown, down had you. you for dosing for share from X already Cohort re-dose to Cohort you're XX% Thank to

Dr. John Leonard

the in would share we said. QX, as full we information until I wait of complement

And we're likely we the the dose, et forward. available And see you'll did the of I’d response the what to With to a quality as talk biological to of and exactly we'll at. as more we the think receive the can I we we patients, knowing be addresses that drug drug just dose perform is about about dose, excited. as forward, confident I think respect that not we how set once each with been make why remind study good we looking that we'll just establish so chance then, which outset, cetera. the get re-dosing, the in who for patients go said has optimal from But, consider profile we're development, it. you we safety that to respective move you'll see curve, think to explore what purpose efficacy feel

Joon Lee

wild-type are the Just gene? for a dual you where are SERPINAX curious, for purpose you with achieve of region? as ATT, like it a that locus insertion you the seems and Is targeting shot quick of that on to endogenous or single knock-in you approach. it achieve knock-out, the just I'm XXXX a editing, the can different question targeting because mentioned sequential but

Just expectation can if you provide any color? or

Dr. John Leonard

Laura, targeting you Laura. to to little want in insertion? with you're more terms detail what of the turn just me -- a Let the genes gene

Dr. Laura Sepp-Lorenzino

Sure, yes.

platform the So, taking for candidate inserting we we're XXXX, for albumin development X, that Factor same are the approach has in denominated. that recently locus other the following

achieve for and demonstrated this that. levels will we So, both allow ability that us... of can proteins we select normal the both With have to carefully approach programs doses


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

Rick Bienkowski

progress. Good Hey. the all Mani. morning. Congrats on Rick This is from line on the

from quick us. questions two Just

follow-up in longer the So, durability, that be the escalation full that how you other the maybe start repeated about on the here? doses But, levels. one polyneuropathy, to serum the understand do be for a if be be would I the helpful. the of you on second, dose you'll interim you cardiomyopathy of escalation what of you pace patients first, potentially could mid metrics expand cohort? evaluated on for looking will earlier in readout? evaluated at dose XXXX that cohorts we'll data and here or could we And TCR could Do anticipate get the see to the just will expand And, safety should durability need read the think term implies,

Dr. John Leonard

question? Rick’s address to want you do David,

Dr. David Lebwohl

longer readout, are So, the main the readout two things. term

seen of is Of what see benefit to into we expect learned. course, with that's in in that look terms the will part But, the the the TTR correlated And that's of to patients. be want built trial. And actually main we activity the safety. at And we've we've carefully levels. -- readout

with the about about study dose in can -- information use learned patients we've was with the escalation. do -- to For that we think modify No, doses polyneuropathy patients patients the question the in the cardiomyopathy. we second we oh, with


Goldman with from Please ahead. Richter next Salveen Sachs. The comes question go

Unidentified Analyst

morning. the solving. quarter. Matt on on This Hey. is Congrats for Good

are you risk couple of thoughts gene for your expectations what Could you a Thank of and the the remind questions. us for share data? And the then, recently differentiation Intellia's could you. a company ATTR also observed additional separately, editing Just on approach? translocation

Dr. John Leonard

we them And Laura? with want turn speak approach? about So, we other why go with you how think that Do translocations don't to then, our about to we and to can avoid start question, we David, will you. how the

Dr. Laura Sepp-Lorenzino

you, Thank question. for And Yes. Matt, the

So, or beginning, at Intellia, validated starts pharmacological for dose. vivo, at selecting the the will vivo whatever at in programs are ex [ph] that intended safety guys, the detectable of off approach the targets not multiples have any

that's of what throughout programs. given So, applies a and that's all our

to absence that random. leads in translocations breaks with that significant the And on variance. This are In by that different I we structural variants CRISPR recent or whether of editing that the using, electroporation, leads a for translocations. described at And that case, in is multiplex at or other the machinery. differences a to, are others different that translocations the using using events in that potential they're electroporation, to by think contribute starting having introducing our referring can the just there ex is LNP-based number any multiple differentiates going So, [ph] to addition, method have data at avoiding. sequential once, minimizes that are And of of gene studying with selection editing, ESGCT, itself, we mode we’re one's right? careful program, looking an and levels we of that proprietary guys, from using machinery editing even you're from that what's for what vivo, from CRISPR method. structural that

Dr. John Leonard

the first David, do question? to you want take

Dr. David Lebwohl

Thank Yes. you.

per milligrams kilogram. we've what at So, treated is that both we milligram X.X and have said per X now kilogram patients

us do be to first So, whole in the of a follow-up as X, will starting the follow-up about next able allow range That patients. in talk which be we'll talk well to dose quarter. just the couple early months. of doses, this we'll to Part about with certainly, of release, able the higher get dose as you the on the to really we’ll also that escalation, to be on And

with where So, complete the you'll pretty get a picture of really are we study.


The from comes Barclays. next Gena Wang with question

Xiaobin Gao

is one Thanks questions. Hi. for This and on one on our XXXX. XXXX on taking Gena. Xiaobin for two, Maybe

For on you safety whether from on primarily their any the Could to to phase, is for ATTR to program, the the on that baseline, Thanks. efficacy or more patients you was per reasons? X HAE, driven criteria elaborate And maybe do it's kilogram you X.X. by or rates background do collect just milligram down and question need implement patient's the attack characteristics, have running data by reporting? by

Dr. John Leonard

Thanks for question. the

So, June, we XXXX outset, already second we from about the the response, the of XXXX. by and are and think presented where in which of can TTR. obviously purposes way characterized were from measured The for clear address we let was been with response me data is, that at dose pretty reductions start the is David and we the And program in primarily back efficacy, substantial the dose, by in TTR study reductions. establishing it's about the relationship achieving as I think is

drug characterize of of would make knockdown further notion good perform some sure there get. what get is the higher So, we sought just to we how understanding TTR had to and a additional doses, to

work. So, we've done that

to interpolate X as going now we're We with -- we've continue we we in closing going forward. to what Cohort and to on want we've think do think said, we're

safety ways that by efficacy, very, performed been by in TTR, in very, the terms profile. but the only gratified also of determined as drug again, we've not by has really So, very

that foundation subsequent it because to from relationship is the this so, lays studies time get the for all going where right, And we are.

goal to you David, do we're we you'll shooting any this to point So, hasten to understand advance for what as you'll at, add looking program. the but see do I continue in February, we're HAE? February, guide can't we to time. at be speak this point, in would what and exactly in that to specific our want

Dr. David Lebwohl

Thanks. Yes.

will are, be So, HAE soon. you'll baseline But, kallikrein may out into you details obviously -- start the important study mentioned, the other be patients as collected characteristics piece see the very quite we the -- And most trial. when enter of attack This as to is the not -- level. the rate. on trial start

biomarker So, clinical a what have can you have a a more follow, that giving both than bit in case we effect and this you in TTR a way. with

the that's So, plan.

Xiaobin Gao

also quick NTLA-XXXX any would present in for attack trial, just you rates so the Maybe the when follow-up, reduction a data? you report the

Dr. David Lebwohl

will Yes. attack following we treatment the well. rate after be as Obviously,

will it's prime, we'll that primary the not a but really yes, collecting one whether So, be of be endpoints -- it.

Dr. John Leonard

early that precision as the be more not course, But, measurements determinant characterize of a of These forward that, major at looking we'd stages, than the across else. of get anything I’d get it's descriptive population. study. it's larger you we'll be the a that to but it Yes. looking Xiaobin, hard


question next ahead. go RBC. The from Issi Luca with Please comes

Luca Issi

have one on TTR, B. two, on one I hemophilia the

Can are approach Phase versus TTR, remind for in to also in us to others? can clinic. is is the if FDA companies data with factors IND key sort is B, in next think you on And you of just the if Freeline Pfizer's year, file fall differentiating hemophilia gating in yet, So, an again, shared wondering have wondering, few [ph] you then, comment the the space, I going U.S.? what X, of your obviously, uniQure

Dr. John Leonard

in which pertinent. regulatory to want respect that more point complete that we relate we we gene there's and With say, to this to advantages share a advancing gene we that as to time. respect think B, that something very when approach the characterize therapy, would interactions, think significant we insertion, with we'll I here. we're at So, to And hemophilia to that's don't picture, it's have more broadly, respect with

often therapy episome, some in cells gene of step and So, cell in of is back an the a remember time be lost as it lost persists in to form Typically, trying virus, transgene, what a can in deliver even is. period what cells. which do you're non-dividing can that be and dividing for

lifelong. the that doesn't data seems it and is I of it corroborated by incomplete. emerging be durability that's seems been So, be clinical appear effect, mean, some to to

that think not know, a very on we existing a is when occurs therapy suited or about damage in insertion approach manifests we particularly and of So, significantly episome hemophilia, a that significant very is the childhood, which just advantage hemophilia, youngsters, And the ideally one grow up hopes permanent lifelong. normalizes, the as like represents the with, bring, think that over improves advantage, lot population. can can that child in very, in we that disease, that patient for a we

having that's So, again, we're that's And, early that outcome. we're here, excited about but in kind And endgame the starting destination. stages program for the an this. a of like the


Evercore from question next ISI. go Liisa The with Please ahead. comes Bayko

Liisa Bayko

there. taking the question. Hi, for Thanks

to wanted that with achieve. some follow-up sense doses. trying on get of level based such, I TCR how we've thinking Just knockdown the And you're of and a different work you're you're know done exploring about KOLs I to

question of it's here. So, relevant a kind

longer a been obviously wild-type the has important be wild-type down term, feedback sort and knocking of over that there's that may the some the potential of available. TTR Some between function it for TTR of and balance keeping

you could that, maybe So, you. about Thank it? comment on thinking you're how

Dr. John Leonard

vitamin it's TTR about -- how space more real, no of you collect across that to we and the And to carry we it we as And at other our from is primary confident as they thought to with we over each way, including reports about are with outset. programs think we there's remind I that know, that from By you remote. that that knockdown I possible, thus been the patients point, can see This this Sure. the gain don't belief vitamin function because as and And really best. kind at this relates any passing all TTR. supplemented of of as we remote the some zero. is one broadly, A, as we protein the the more far, time. is even outside carefully proceed. knowledge watch that's we any And if and there's liver. produced something risk more our down knocked TTR look the to might We think TTR’s we to insights data and if is risk, imagine, no get us more across that A, that is understand month functions, even has anywhere field that


The ahead. Yanan with go Wells next from Fargo. question Please comes Zhu

Yanan Zhu

the have has polyneuropathy you reduction, you cardiomyopathy in Thanks. question quickly the schedule related you is I -- saw moved if patients? in up. like planned like information So, the have question, -- TTR move that this also any And do program. further that study cardiomyopathy informed seems polyneuropathy has program, to whether acceleration? to been have difference is whether the any expect compared accelerated patients first with but you that know always sounds on further you it Wondering

Dr. John Leonard

should a airs a that -- response. we reason no on at view, question Well, biological believe because why TTR why right, first, the patients the cardiomyopathy have there's different of point purely second

cardiomyopathy made data that presented the back moving June, more the in Given that quickly with enthusiastic forward very program. about we us

that. ways bring has that to of stated. that, study So, starting us go a patients that We us a studies for which chose directly new will his reasons way the And at you of And sets study into team data will of already or from And range David the phase the go looked that information and looking the getting in the and do the efforts all we that there approved. building alternative that's administrative direction larger hopefully choices the to for that and getting studies have. that be hope that's with important for faster ongoing. the of the next the on really move we drug one up believe latter,

Yanan Zhu

Wondering may, ex bring? LNP approach do the how A, approach evaluated you How the I reduction on editing one that think hemophilia brings side. additional Regeneron the for if have other the on questions, And hemophilia is hemophilia currently? two reduction move think the the and can you reason hemophilia program. sequential -- with the have vivo B Maybe translocation? A question what's and to if reducing you therapy you to much do translocation And much evaluated

Dr. John Leonard


hemophilia do first. one we're A me on working B. Regeneron, the let With and second both, So,

we I got jump, program now. that the You time And B that hemophilia we're related. work will highly other of they're although doing, for the have data some for present seen that would say, some on

And a pretty have with all to approach what her making data standard to editing speak to people doing in that's that us. going should some we're And we did of irrespective we're start with. what, Laura I improvements they're all by the transducing and and minded obviously, given in With of outset much is let assured, team work the used very to elements what's think are assumptions field respect Laura hemophilia aspects very, with of up is on cells, rest that instead pretty So, interest point what great ask to principles what work sets that foundational open technique that trying the approaches in done to the nice apply But, whatever dissecting other those creative that substantial us back on, to yet job going B quantitative we giving what familiar approach many bring. timelines of and or to hemophilia and being to standard represents believe of And think But that for what the for A. something approach translocations, I'm one the not time. just across to any would to is proprietary from I basics we just accept just respect the the really did go saying of do any and try what by the that take. approach we I basic back can that program. and

maybe can Now, much don’t a on Laura, -- a shot is translocations that? of how color think you just electroporation it gentler with take LNP at you more to than respect and if why kind add of little sequential, versus you

Dr. Laura Sepp-Lorenzino


minimize with access sequential data really cells. versus have electroporation any translocations and comparing share be most compared significantly. at more and our methods recently electroporation We The lower as happy that untreated have you, one shared translocations from to, we happy to ESGCT target basically versus offline. actual we'll we that unedited you it's distinguishable to share, will cells, data on And discuss log to


The next of Ha Gon question Dae ahead. Stifel. comes Please from go

Dae Gon Ha

on into for part I plan. the first guess, hemophilia just back the circling question, of and delving XXXX, then

So, consistency. with your repeatedly heard the XXXX, to I've depth regards and team words two between been has from

is Cohort to is guess degree you your depth And what what hoping guess, XQ making X.X X X to X, of both, or to Part from about consistency? Cohort I pursue X, think timeline as in Part decision additional derive update I with as Regeneron, biology to and information reflective hem decision underlying well A, juggling the So, you we interfering mg with maybe just B expression the initiation if before of that reflective perhaps then, recognizing are the of and hemophilia, of get that this much. endothelial expression, how are your hem around And the hepatocyte might X? regards with Thanks long-term and thoughts so be to guys wanted both Part durability? but into versus

Dr. John Leonard

why of and in is A want for, we go to hemophilia you present share apply hem know, With when To if terms respect and first at the to you in to looking we're set what expressed, question hem where can we extent here exactly we data see as what speak that look the XXXX, B make obviously at why more the make. don't gene the Laura, And those a the do decisions complete we'll data. we we I quarter. is more something the words forward? versus that determines

Dr. Laura Sepp-Lorenzino

and it you rate, for associated No, forward Yes. attack right, hem up gene it’s and it’s deliver. what been expressed, no, stretch, cells, [ph] has right? when and larger you're A, with endothelial bringing expression So, the -- it

I think differences sure I -- that the is of -- and make that one program the should here. Regeneron

the could aggravated lead that the in point introduce copy stably. benefits of approach our have over-expression will multiple this. the the episomal inappropriate to -- don't or chromosome, to need color -- expression additional over-delivery to that is right, gene in them toxicity. of of And on copies, genome a we But be I asking for lead we're of one that So, you should to would aiming right,

was we're from your that's different explore I B why other then, AAV think And So, that therapy gene trying here. hemophilia traditional question first. to

we us I that think, for both. again, they're Regeneron. programs both I question leading to progress -- and Both programs point would make with


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

Timur Ivannikov

on Ivannikov Timur is this Steve for Seedhouse. Hi, Yes.

of I day and and question further, in they to just in be sure functional so, X are Cohorts I'm of which to XXX, asked, the seems patients clarify be a And endpoints disclosed. saw and but description to 'XX, of QX X. day this for was sort terms XXX data achievable listed And not

talk So, would endpoints about with can be just the especially why available, not would you or functional to [Ph] endpoint? respect

Dr. John Leonard

want do David, you to that? speak to

Dr. David Lebwohl

Yes. you. Thank

of we is Cohort inadequate, very have percent, those while you reduction. important. degree imagine, of of from It's a standard-of-care. greater even this we couple saw reduction, a X.X half the of also as been talked and What X. We really X.X. the times every XX% depth X.X stated so the to seems XX for average if that reduction already we patients range about TTR So, than And XX% important in of you at patient X with the they about And think or greater can TTR may getting X because an and that, for standard-of-care -- TTR. we that lesser course, has think about is Cohort do TTR got where don't is be endpoints. to Cohort data most think there right, enough maybe But be have interesting

make getting see So, for we that's to manifestation. consistent the what's we big this to -- difference reduction, we going think think can


ahead. go of The next Please question comes Oppenheimer. from Jay Olson

Jay Olson

influenced enrollment Could geographic talk XXXX if And sites? any the how you clinical additional at then, pace for surrounding the expansion the study clinical have initial data you existing about may excitement plan of into sites?

Dr. John Leonard

you David, respond to that. invite I'll

Dr. David Lebwohl

noticed as extraordinary investigators interest those coming into have We patients investigators. the as from calling an well

don't sites the study. at it's on what's So, happening sites, been we very need And been helpful in fact, additional to already. based

we're trial. shape the of in good terms enrollment So, in of really

Jay Olson

in sites? XXXX, expect the be considering on we comment conducted initially the study? to clinical study trial you you're should And doses And that then, ex-U.S. Phase can for at X

Dr. John Leonard

exactly that's a protocol. come that regulatory point-of-view, would get treat expect it as We'll I think, this information we'll lay down paths from the mature. a the and solidifies. communication time. at that programs more we pretty point, and share we've other the that's done premature they into as But out as at this I further focus


And with JMP ahead. the go last Please question Securities. today will be Tuerkcan Silvan from

Silvan Tuerkcan

your for you in that be at data the near-term lipid you're Could year-end? moving to or you've with perhaps? where process presented is ESGCT any with modifications clinic tell as the please program, already that also at And the nanoparticle incorporated there the will on us TCR Thank transfection, you're into based by process this you.

Dr. John Leonard

you David, address? to something is that want

Dr. David Lebwohl


set the is an So, approved by the -- we've IND had process FDA.

So, clinical in of study. terms what in they've obviously manufacturing both the to looked and do at study, the we plan

So, that is going forward, as does LNP process. planned. It the incorporate

So, process advantages we LNP want in manufacturing. of to the the this have

Silvan Tuerkcan

patient Can patient And you this you you of this end first you. the mentioned that the and tell characterize design Thank the point? at Okay. will population can at think screened point I be us by kind the the year. -- of trial

Dr. John Leonard

Keep going, David.

Dr. David Lebwohl


point. -- is is this at it this in So,

you. less at X% is we So, trial, residual Otherwise, there that now are there minimal than for which as full X disease, the is fairly are so design, plus But various greater and patients more blasts. some then for standard X% than details X available oncology design trial with blasts; considered patients have, doses. relapse two have who populations


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

Ian Karp

in progress Have support you Thanks to great today and you updating continued all our your in Great. everyone. a so us forward thank much, Drew. Intellia. for interest And And future. and joining for day, we look on the


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

disconnect. now may You