Intellia Therapeutics (NTLA) 7 May 202020 Q1 Earnings call transcript

Good morning. My name is Andrew, and I will be your conference operator today. Welcome to the Intellia Therapeutics First Quarter 2020 Financial Results Conference Call. All participants will be in listen-only mode. [Operator Instructions] After today’s formal remark’s there will be an opportunity to ask questions. Instructions] [Operator

event this being is note recorded. Please

now Lina Li, would Please ahead. like Relations to to over go conference the Associate Intellia. turn at I Director Investor of

first morning coming we are you have the on please from we interruptions welcome Thank bear Today and to everyone, the locations any that operator. earnings call. audio Good to you, call. event Intellia's ask quarter different with XXXX we in and you us

this be progress and a today's Media press also the at release we being archived call website Earlier to the Investors our www.intelliatx.com. our this morning, plan is will our topics be on broadcast we issued call. outlining This found and quarter discuss and on live replay This website. of release section can on a

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

Dr. today's Officer; Sepp-Lorenzino, John on Intellia Dr. our Glenn our call me Chief Officer; from Goddard, our Chief Executive Joining and Leonard, Scientific are Laura Chief Financial Officer.

will our Counsel for Schiermeier, our Andrew General which Chief be prepared our Q&A, and be we remarks, José Officer; for Following joining. Rivera, open will Operating also

of results from update For review financial Glenn our first and today's highlights. quarter R&D will the company's Laura will call, will on XXXX. provide an discussing John begin by our the progress,

John? over call With that, let me the to our turn CEO.

these call certainly joining our everyone. challenging Lina. appreciate you, today Good morning, We times. Thank your during

families I foremost, and you and healthy and First safe. are all your staying hope

full of a address applying to need. our novel strategy At editing pipeline and vivo vivo diverse unmet advance that critical spectrum genome areas develop ex in continue of to Intellia, we medicines

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are are redefining available many to we limitations cell-based the of Here lymphocyte overcome currently engineering immunotherapies.

then a sourced a high from Our approach a directly focuses which TCR, receptor healthy only cell product. retain to robust our in of targeting a affinity to the normal view This donor the and variety cells the key success identification homogeneous to that based of in cell T results on express cell cancers. and engineering therapeutic T on engineering is physiology is lymphocytes

transthyretin progress in of in key approach candidate taken candidate far a This to of steps our amyloidosis gone three. lead in we've advancing vivo clinic. towards In XXXX, applies development one or for the months continues So we've to our ATTR. the program an knockout from liver treatment rapidly NTLA-XXXX pipeline. matter

Further a as the angioedema NTLA-XXXX for the treatment to today, excited candidate HAE. or of nomination we are development announce hereditary of

progression of knockout treatment a the employs of liver therapy We are respect for pipeline how rapid TCR vivo our as the demonstrating T in clinical in supports particularly to approach, our ex of our cell candidate. leukemia we're activities to proud with or AML. nomination platform a NTLA-XXXX now it myeloid acute NTLA-XXXX for And modularity also an of the IND-enabling lead vivo

upcoming Intellia like moment to our and to pandemic milestones. it as I'd comment over the the to circumstances. for to call business much the COVID-XX to continue and of thanking handing these commitment operations by take work our for unprecedented have which focus to start a Before enabled during our their I and their relates on want Laura, off to adaptability, mission team

industry, health of colleagues our to Like facilities to recommendations of mobilized adapt across be the many into majority on team to coming safety work critical activities public with ensure we a the to team. our site. perform personnel only quickly of can remotely essential to limited of completed number our continues The our that

recognize remain by the situation this and posed on are our COVID-XX time, closely it previously as track We we as continues evolve. to at Fortunately achieve the milestones guided. monitoring risk to

we program. planned We're trial, investigational clinical are launch safety first in patient close also of initiation In ensure to agencies trial our with the smooth planned about physicians particular around sites discussions and regulatory leading contact of the in year. and respect a active clinical global globe with to ATTR our this with

Laura now additional to like the our I'd details programs. provide will who pass over call to lead on

lead John, I hereditary NTLA-XXXX will treatment a in for be the deposition of commonly as the and in and you, vivo manifestations buildup or good everyone. new It diversity's caused program multiple in progressive fatal of our disease Thank misfolded wild-type and development start most TTR with ATTR, by polyneuropathy cardiomyopathy. and ATTR known either nonhereditary and organs. protein morning can can result

course offering highly to currently chronic remain. for Moreover available. shown, which of progression as therapies the the it unmet both increase knockout ATTR knocking a is to down has believe for has needs validated differentiated vivo Approved believe protein. NTLA-XXXX have in preclinical is our we in and treatment of awareness. approach clinically TTR compared a disease disease NTLA-XXXX a as we TTR rationale condition data which the source hold potential applies profile Still to liver, the a circulating TTR for treatments our under-diagnosed gene with also single

population a pursuing We're to Further, geographic it the the qualified address provided by challenges for development submissions investigators global regions us regulatory NTLA-XXXX to and support has multiple patient strategy for the pandemic. created in reside. flexibility

be around the the and world in clinical committed regulatory earlier, to the year. pursuing with program this to bodies John efficient noted we speaking As path have are been most

year. we quarter, Phase materials regulatory our track documents X need or and are on finalizing remain manufactured this IND-equivalent to submit IND This

a the safety trial X single dose NTLA-XXXX. will patients be in TTR Phase shared, to study of previously As assess intended ascending

Given aim biomarker, levels. evaluate half will TTR the readily release decrease start to second the finalized to the to expected We also be in I able year. design circulating by activity we study in observable serum the prior monitoring of this Phase study

of will to on safety. this to to we and remains clinical sites, conditions subject trial impact ensure While COVID-XX monitor continue carefully these the regulators patient

that developed very a great to NTLA-XXXX are excited and CRISPR/CasX to feedback therapy treatment We our ATTR. indicates about there with program deal Of curative systemically of note, party. as enter anticipated a leader with the and part first for our is enthusiasm key about the Intellia as be is collaboration is opinion Regeneron clinic being potentially this lead delivered the of

in one for HAE various HAE people fatal swelling. which affects in vascular and to The the HAE. unregulated treatment vivo genetic on in a next with inhibitor patients deficiency parts painful body. program XX,XXX can resulting of have moving painful bradykinin, Most a CX-esterase certain about be disease of release recurring, our in and mediates buildup in disease cases. in permeability and turn rare edema of is by unpredictable the in characterized development Now and

effects. significant. prophylactic these KLKBX plasma to to program, bradykinin believe gene knockout is there HAE appear acute With have no as humans activity to non-health the we in this production prekallikrein are prevent kallikrein the treatment with KLKBX and for burden to reduce HAE, resulting attacks. When therapies knockouts aim still We excess of deficiency patients cells

of kallikrein innovation activity In addition, clinically is HAE. approach validated towards treating a

by development kallikrein and a results data they we're Today, additional show encouraged activity in single achieve protein the non-human months kallikrein efficacious. of pleased study. of HAE. plasma candidate data, these as through to primate to to be share nominate activity excited six that an results levels our We're sustained and can reduction plasma today showing durability NTLA-XXXX for ongoing we expected dose we're Based treatment these following on other reductions clinically third

path the developed our on efficient molder our HAE the of program to our approach. builds and candidate selecting rapid demonstrating strength development foundation for ATTR Our

look for enabling Gene or plan in place taking Therapy virtually Cell Meeting on NTLA-XXXX week. HAE to next begun an IND We of data at recently submit second and American to additional have the We XXXX. Annual forward the and IND-equivalent half Society of activities IND sharing

to T cell now adoptive approach in efforts targets TCRs, vivo therapy. including ex intracellular our At Switching immuno-oncology. CAR-T, target for a TCR-based Intellia, a and both can tumor employ set unlike we of antigens. surface broader much

cells normal tumor T that cell biology a retain As closely John of engineering applying our cell cells. is By identifying natural to a mimics in DCR proprietary process high the to cell that more T engineer focus designed physiology. product natural attack mentioned, and lymphocytes the our affinity

treatment or candidate antigen applied mutations we this targets cell As Symposium NTLA-XXXX, AML. of of the shown engineered development XX% to disease regardless February, patients WTX is the our and therapy over T Keystone Wilms' the subtypes. in driver at Tumor in of X AML approach over-expressed identify It which for

At Keystone, attributes NTLA-XXXX. we these highlighted of

a contains to risk affinity and TCR. is This First, healthy occurring modified, minimize TCR toxicity. resourcefully high it immune donor naturally a a of

presented TCR processed blast. binds efficiently protostome by Second, the a to by AML epitope, the tumor novel and WTX

high achieved insertion at process product TCR. all a results potency T brand in proprietary of TCRs nearly for and than therapeutic the our to expression from the TCR of cell Third, specificity. cells efficient greater removal XX% slate with create engineering This endogenous T

approaches of paring TCR native alternative therapeutic from only unpredictable where its or partially product TCR not T beta all not is endogenous specificity TCRs. with the and activity over removed cell creating improvement significant chains a represents heterogeneous a but removed also This and either resulting alpha at reduced

next process platform. our to We presenting an forward look cell on annual important at week in engineering meetings additional ASGCT's advancement data

from potential. We engineering highly levels cell attributes and this into translocations we including level multiple editing of improved favorable Notably, indistinguishable genes high with T product viability will expansion sold of and process efficient have show incorporated background NTLA-XXXX.

the for IND-enabling next half development in on remain support the T advance activities preparation first IND-equivalent to IND or clinic, We process an clinical of manufacturing. track in submit continued including of to year. cell In we

led at broadly rates, core. continue years to long-term over treatments be while more AML outcomes the improved Looking response past developed several landscape the have to

Overall, remains five-year below XX%. survival

Our treatment leukemia. and that improves the hope low underlying background that their is for regardless well-tolerated of deliver of limitation a will NTLA-XXXX outcomes AML patients, term

to in as evaluating we've use potential is past, as over-expressed we're across solid such the types WTX the actively the same multiple tumors. in many TCR Additionally, noted tumor WTX

application OTQXXX vivo owned Outside brought in therapy development a CRISPR/CasX cell engineered has wholly based research collaboration our of Novartis' cell FDA out the disease. of accepted sickle our efforts, ex IND for for

as We provide validation important are will for and share the our this ex vivo we in important technology program platform. evaluated application our to be pleased will of patients this be milestone this to first believe

clinical of Finally, These our modular and candidates. wave research genome leveraging to we continue hemophilia across others. various of engine, apply the to maintain capabilities deliver editing deficiency and including alpha-X a delivery a strong B, research programs variety platform diseases, next antitrypsin our

to hand results. provide With of quarter will that, would to XXXX Glenn, who over like the our call I financial an first now overview

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

received million and at proceeds by of Novartis stock equivalents cash fund decrease the of marketable of $X.X $XXX.X employee-based from collaboration XXXX, raised funding million $X $XXX.X and XXXX. as of XX cash, $XX in was used million company's to million in $X.X market mainly approximately which under was to offset offerings, from as due proceeds part Our The securities, XX net million operations plans. compared of million December March were the cash to the

revenue collaboration million same for the period million Novartis $XX.X driven of submission by the for revenue in in milestone payment mainly for was the in IND million $X XXXX first collaboration The $XX.X from earned to of increase Our XXXX. compared XXXX OTQXXX. quarter the was

to $XX.X first period Our our XXXX same million well to our of increase support organization. lead these research for compared R&D XXXX. the expansion the were This expenses mainly personnel $XX.X was due as as the growth in million programs, to of programs for the advancements quarter of development

in increase for due quarter This the million the mainly period property-related G&A by to was expenses million were for to first in $XX.X compared Our XXXX. intellectual driven same activity. expenses increased patent increase an $XX.X

are our balance plan expect we we through at today that cash reaffirming the fund least end our Finally, to of operating current XXXX.

over back and to summarize And upcoming our updates. milestones turn call now, briefly the to John corporate I'll

Glenn the updates. Thanks Laura and for

one served multi joined David and Intellia's tenure Medical to Therapeutics, the in where introduce David a and call, Affinitor. new Head He he at Lebwohl, successfully through huge brought excited who drug scientific development indication to responsibility Before therapy launched as David's engineered CAR-T gain recently of FDA Chief Semma and was of and over as increasing Novartis where R&D product blockbuster expertise we in talent Officer. have entered amassed deep concluding Dr. development Medical He's us complement cancer incredibly and are therapies. his Senior from diseases, cell and and in therapy he cell our patients. leaders handful most and Chief development roles particularly at the oncology Vice Intellia. approval of fortunate Officer. interim the a clinical recently novel XX-year rare Kymriah cell team welcome a Global expertise David has a developed the to and team, President I'm and capability asset We're to medical to

company's course, in of juncture comes this at growth. the And a critical

other and follow. rapid programs make as We genetic continue NTLA-XXXX emerging enter with severe to poised the to diseases we for cancer clinic our prepare to progress across pipeline

beyond, upcoming. several and dose middle summary, to for Looking in second and XXXX we ATTR plan our or half ahead year balance first In our to IND-equivalent of have permitting of IND the NTLA-XXXX of year. current we conditions patient to milestones the to important plan this the submit the

we candidate or NTLA-XXXX next IND-enabling second in first the And anticipate activities of year. expect to in NTLA-XXXX, IND advance or for half to newest IND-equivalent the For we of our submitting submit IND an half development year. next continue an IND-equivalent application and

data forward like for call Additionally, next the presenting to all thank supporting preclinical into improvements to you week. Again, programs and look tuning platform ASGCT we meeting today. annual the certain at I'd

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

The from Seedhouse comes Steve first begin now ahead. Please James. question-and-answer question Instructions] the go of Raymond session. [Operator will We

And This is Seedhouse. Steve question Timur on for José. Ivannikov first is our for maybe

of the of outcomes potential the XX, for the timeline of terms the terms that's case us this In the May oral about resolution? argument and IPR on for potential then you for in scheduled set could general hearing remind the maybe

want to that? take José you

Yes. Sure. Good morning.

happen de guide obviously in the UC eukaryotic on for this believe motion would usually have And the appeals were at it's there's If to And obviously would of to be can't guarantee side So outcomes that the and a the interference. single seeking that patents potential essentially board to setting subject point the to now by within that cover broad although, then decision any the will terminate the set have and current how phase. likely to forward decided. move is would happen we commission where months. motions We the That's would occur inventor three long. second then our second that's line the patents. that. likely A ship time phase after that

question Okay. about second Thank then And you. the ATTR our program.

due to mentioned patient think, impact the it impact ready arrangement? of potential just Could like COVID-XX. the the in on hospital sounds terms color study? and you I have of an any more supply Is you delays to you go. just ATTR It provide on

So appreciated. any be color you. would Thank

Yes. This is John.

we're clear, we a Just delay. to be not saying there's know that

an applications on get be the control can the where be we of we regulatory expect year control dosing and end and beyond patients end that in that which guidance this everything have fact our will our fully is the things to our before later sites eventuality. would year, avoid on is In individual if time interfere we other transit of the we ability But engaging to very patients best the of that clinics we're waves that the have very, sure with kind to to or to make able COVID that of our them. carefully of we're clinical with

Okay. very much. Thank you

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

the that's Do It IND questions first be the you for for start. the CRISPR/CasX file? scrutiny cleared? you program. is first -- is IND seems is IND This your the in from hold question cleared to before. the several there's Tao share with vivo Wang. when My Hi. since application actually And Would technology. so have you us be will I Jin Gena for two going when like And ATTR would expect when FDA? extra that pipeline to

my that's So first question.

IND take before actually your about question you submission additional steps second need the HAE to quarter in of your Second program. XXXX? What

Yes.

the you for thank question. So

scrutiny regulatory in I FDA TTR. the as it Extra the of we applying of with we various I approach them. the for basis scrutiny. have how guess, which the First that think, engagements is appropriate

As to we part the make nature go in regulatory present meetings need we the the it's with generate the agencies and of that particular that understanding the of agencies for them outside that our can that regulatory process will of for there adequate all is them or to FDA so we so sure we that have a start true for be pre-IND to data to shared package determine an That's able U.S. this proceed. whether we're

their we're questions. think we addressing So

largely cases that is data of other I for would products one as unique a not what to that products. needs or most generate sorts in circumstances for say generate these well. what of true There's to needs overlaps one set

we need be determination. in position we're So to to to think a they going a address what make

asked you and plan when the patients. regulatory insight would we'll cleared our the think good program, what to up process. running we're as with we've we're to for the where plan And our certainly, to and once are is announce is I approach going announce And protocol we we give these how and now. that's

of, mean, expeditiously generating to are we and With Again, the candidates. to this the work. steps? clinic. necessary moving manufacturing HAE very appropriately tox what just announced regulatory additional respect the and We're information the I development standard, completing sort is

TTR. TTR to from gained even insights a the but think effectively work doing hoping the from I first clinical with from do that we're we've we're manufacturing, work. a now all toxicological learned perhaps with leverage and our how pretty we've that that ultimately at to And go only not

as forward. about modular application excited move of we approach this very we're So our

That's great.

follow-up. one have quick I So

you could the Novartis us remind the modification you SCD For made? program collaboration in

Yes.

as went to Novartis' for clear think We've it how side discovery to better package the the with done so the inside. to in in the determined a We've and the program. on they're development like the program on they're just Intellia applies itself how this So basis position particulars the But elements FDA. of Novartis is them. data it. basic work that that We'd to of edited to work describe is progressing the key be collaborative gene

Thank much. Great. Okay. you very

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

and thanks seeing TTR Good a ASGCT. I'm not taking morning, my Hi. questions. at title for

NHPs on So status just provide with wondering can you if update XXXX. latest the treated

last your update follow-up think I was weeks. to up XX with

long reduction our so follow-up flat? TTR is And is today still and how

additional that essentially point. experiment presenting data the no we There's and Yes. where at we're this that's cut

was that So the of duration work. the

Got it.

congrats the XXXX the your just Okay. you're so if NHPs anything that far? treated And then I'm wondering seeing on seeing treated NHPs? to have update. phenotype any TTR there been And is you're in relative unique

Maury we these at look very animals. closely

are Of one sort to we've determine of date pharmacology course, can to studies, these nothing. exaggerated where effect. observable seen try And any readily

Great.

It sounds engineering question. Okay. XXXX. cell about like And at the a some we'll engineering and Laura ASGCT proprietary data for process then last on T talked improved bit see little

will provide should you days will the how guess at then few it a cells focus start program, much can disclosed be What manufacturing to for take of finish? and that we the on such process as I of ASGCT? from to specifics number around

Yes.

And those and division importantly, fact that to expansion the of edited we'll we're the takes fashion. edit And show very, place And cells work in multiplication editing of or the typically how respect this well how them, with divide. standard well far that cells we So that with the behave. cells terms of exceed robustly cells in to those what excited are the the performance ability very is about. in

cells. our for equally essentially that performance is of too by We have And that's but and the I levels. is from think cells going edit hugely to something in these level translocations ability the stress to serially these important have that to much background and a indistinguishable is think enable ultimate that really important multiple edits itself we can't of that ability

translocations the want just not and to think think ability very about the make, go we other treatment puts But where AML. is changes as first indications for of one multiplicity that of where a about to make when modifications we to product, essentially might on and which for want we not think something we you go. limits few induce can other But that the

way. something Well and steps in step would can we excited carefully. very look this terms way very and do the we've that So along I say proprietary. of at do we've work how improve But And each one that multiple that's that tried it. the there is to done are of

you'll see for cells performance the that of I and So data think speak itself. will and the the

some some out the at will then? the guess Got information that proprietary ASGCT come it. of process at of we point? Will learn I

No.

Okay. question. Thanks my for taking

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

Mani. morning, everyone. on call This Good progress. all the Rick for is Congrats the on

upcoming XXXX for of wanted So also the first the on in ATTR I to touch timing the the patient study. dosing first

we and their Could performing know been due for time are to in that slowed trial have clinical across clinical trials XXXX? board mostly these it's any able Study elective are you to comment, currently for sites COVID-XX if due down perform there these? specifically the for So to Or place being restarting are lines sites not procedures? procedures. that if elective the hospitals planned

are we've to of do. that With focus to work be other end we're the timing We to Yes before year. that this going the dosing to I expect what their speak provide on given that can't respect patients to and we for continuing the doing sites programs. guidance guidance

ones that that think, effective currently are I one in have the been most away point today. is take clinic programs to

how sites circumstances are. the whatever dealing it very some with advantageous come prepared in respects it clinical think at not have But And look about cusp by Where can virus, beginning the logistical to are this fly. navigate think at how challenges work. on of that and the is presented are the process, do carefully been I somewhat where on we we with look the being

particular be clinics down and to dosing et So again, that the we'll before provide year cetera, information expect the the road. the patients end is of

HAE have do question helpful. very a That's the follow-up I program. for Great.

knockdown abstracts plasma Keystone presentations we the able a you're in mice and the nonhuman saw that XX% achieve earlier in ASGCT to primates. kallikrein So and

would any for of prediction care. for profile this current standard internal would gene on are of the to I'm that HAE what would be rate? a make have of the target product attack the So get compared a editing effect just sense there trying the models to what kind

try for the been What question. Thanks of other we to is done off studies do Yes. benchmark what's human modalities. using in

you think places when and And inhibition, we rate about so it's look of that I the useful attack results. benchmark And think kallikrein concomitant degrees a inhibition zero its attack all and to. antibodies that where the one looks at then

those invariant those So attack we below and approach that expect certainly kinds already achieved. competitive objective order more that are rates a has perhaps to speeding hope one-and-done provide be attack -- that zero of with It's rates has to and we our pharmacokinetics so.

Great. presentation. looking Thank [ph] we’re SVB And you. to forward

you. Thank

next Kumar comes from The go R.W. question Please from Baird. Madhu ahead.

Hey, our guys. Thanks for question. taking

clinical kind to tolerability plan So of XXXX safety done can of be management kind in kind versus remotely ATTR blood the on you and Do kind what of in of execution do the site? the of of them having collection come considerations home? from from extent kind clinical following on systems for trial of home patients the can

in are and terms got Yes. think patients that a where in back we engineer to important clinic. Obviously, working we're there of Phase is in Again some confined in position of that study point lot question, the following as being of parts patients. ways these earlier go. are all into to we a of Madhu Those can We're do. we taking through. X questions things There's a that a consideration we the

of and those And it's I so that to do think, remotely. that lots go patients to But hard follow there's virtually. opportunities after

that trying in. we're from that learn So before have hope to again, us. to gone those engineer we And

that at Phase of of COVID or does polyneuropathy that endpoints like require clinical like extensive in-person TTR ability from pretty kind visits to strategy X clinical are in level? would assessment kind And endpoints least impact following thinking look serum some the things So cardiomyopathy kind about beyond that endpoints -- at of or assessment. your the

we It's the not I to don't that study. patients the during become would to this. apparent influence obviously, me of how mean, course ill want

patients part was in and So of that from making and sure that of are they come when transit of to otherwise the well. the terms patients clinic in discussion

of But study looking that the blood weeks of part first of which observation. a TTR what simple the get biggest few we're readout objective draw safety with is after in we knockdown, is very for and a extent our an

So I think we're despite Phase on going looking in be readily what there. for should out what's X observable

to of is then of for? And the finally suppression earlier of any patients of for of possibility TTR Phase target kind interesting at dosing PCR subtherapeutic subsequent X of kind about looking to trial kind profile there doses kind get down the you're

number to the fewest patients which have expect that is Obviously, that it would do index escalations. Yes. question. dose. as that is with it possible notion be but would comes therapeutic that And to is first the in the ascend. That's and ascending About dose fines of the a we from the set an we important where of number objective of possible, patients this single dose study fewest small one starts subtherapeutic a lower dose entirely

for Phase subject at be to they definitely study they but the redosing, as underway. course doses provisions it's come work try least In X patients itself would make therapeutic we program currently of not in all back. find planned to once to those a That's we the would larger

that side Okay. Thanks much. classic. very the By Intellia's that's great. really was way

Thank you.

of Tony go Please ahead. ROTH comes next The Butler from Capital. question

you TTR follow-on want as may dose ascending believe case that improvement the just that. whatever or that to as potential John, really with in the to or series morning. questions Understand on question clinically? of or outcome But the be the alluded in hydrocephalus serum subtherapeutic neuropathy had I respect clinical doses of good surrogate you with how study. Yes obviously that And to is TTR in the improvement a correlates do peripheral an diminishes administration.

have I'm FDA from And to demonstrate improvement very you've I you thought. that But which and you this markers clinical the of important to -- I'm will not in I'm sure here tremendous an perspective assumption asking those an think level be in end given some beyond particular making would surrogate?

gauge And the that level clinically at in not that that aggregated. to particular to I that appropriate get be that -- least appropriate totally might really when you're actually you able you those are to move has and to you the will you because or sure if not be that a forward How guess follow-on knockdown like. Thank X is which certain has an neuropathies whether you. dose Phase

up couple that. the wrapped So, of A Tony, thanks for in things question.

So, first have outcomes, look particularly a and who knockdown link we demonstrated to Polyneuropathy. therapeutic before who between TTR with respect gone us, to levels those have tight

we and they've to both both biochemical the modalities, clinical that a outcome lead is here reduction to see work they different two Ionis that look TTR, same in where which certainly And outstanding improvement. Alnylam with and the done

So, and when standpoint, cases, I that that about pathophysiology an of the most the the tissue, from in treatment just disease deposited think clear. you think in about is thinking protein is which logic it aberrant is

that protein. to The is idea reduce

those of a regulatory likely The the a TTR as agencies there's about surrogate to a service So, not indicators a as moved what levels opposed reductions, Utility of drug discussion outcome yet an is make surrogate approval, of to approval. different that. a thing. have indicator lot not is however, basis marker that for

have the work. do to you Excuse me. clinical So

competitive that dose good that we know to is if that those second a already even dose. to, are there. was treatment or in asked find earlier So a a levels already out again therapeutic TTR And second to a get do is is necessary. as outcomes, and maybe with highly the To with way what idea associated application

we the is, So also nutshell and to that to it. that that would the cardiomyopathy apply apply a logic polyneuropathy program and in

there's the think extent between complete less space, I improvement this of of but that's of knockdown accumulating. in effect here the the cardiomyopathy on information the correlation and TTR

directly very again, that be would can a we we're our we program. likely think because of so feel succeed. to well clinical by people highly to very, us, ahead taught we design that little positioned, bit study And And And learnings are a apply we're that who efficient. being be those

it. appreciate I John. Thank you,

last Olson question will today from go come Oppenheimer. the of And ahead. Jay Please

to ATTR? progress. for look of moving right, taking biomarker whether just potential can clinic you thanks you on could plan to questions. into you little for measure an And Tony's to NT-proBNP, as or the bit congrats to as comment All a value endpoint? the as Maybe my question, not a XXXX follow-on, ahead the NT-proBNP, on And

to yet. not it markers cardiomyopathy I'm questions measure. that the likely was relationship does story, projecting terms terms in of where actual And that asking can to the me, there's of position clinical the biochemical an that of to about Certainly, Tony to in talk today in outcomes. benefit emerging from them we a relate knockdowns

programs. then that we what of I whatever would to information sure related have would relate And meaning found they to their guide the us, utility. others terms with knockdown Phase in And possible. can most in going can, that studies, proceed various start as make experts in its the with I the we to we we're to of the everything course measure premise that have

the guide. base and foremost be in is logic wouldn't be that. protein our solely about here think that minds primary going a the Again, directly I that to that and first our is I reducing So, it is will and and on measurable basic

And just Is in sufficient you you. data? then, six submit said do of thank Great your Or had on XX IND? months to I you think you months plan XXXX, maybe that of HP. data for

So, this model the shows effect. of extent is a that the

that work, And presented that of that some data able we basis. prior off be That's is to, that we that how If to far. work to going would you're relates as we're point of a And from a be build much discussion toxicological distinct asking, part your proceed. program. the we've done so the of toxicological from question

tuned. stay So,

taking my Great thanks for so looking ASGCT. And question, much ahead to healthy. stay

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