Prothena (PRTA) 23 Feb 232022 Q4 Earnings call transcript

Good afternoon. My name is Audra and I will be your conference operator today. At this time, I would like to welcome everyone to the Prothena's Fourth Quarter and Full Year 2022 Financial Results Conference Call. There will be a question-and-answer session to follow. Please be advised that this call is being recorded at the company's request.

to call like to now would turn over the Mr. I Corporate Prothena's Communications. Senior Endicott, Affairs Vice Eric President, and Please go ahead.

Form business attached quarter Thank available which you results the conference prothena.com our press investor at welcome and on to our to operator. Good with guidance. is the X-K issued and afternoon, our call everyone our XXXX release filed to website Please XXXX we full today is year and and a financial Prothena's progress, also financial fourth review review today, earlier SEC.

company. Kinney, On Dr. an President call, and Officer, integrated continue today's Executive Prothena's becoming biotechnology will of introductory Gene development by our followed towards and we as fully advancing remarks Chief strategy portfolio provide a overview commercial

of Dr. Dr. Scientific our our then Mesa, across our XXXX Financial Senior our for guidance. Q&A provide quarter Vice where Strategy will then will call will our Zago, then XXXX and remarks Susanna opening open a the discuss XXXX Officer and Garren, full Strategy of overview and and Gene's Gene closing Nguyen, Medical will for up an we entire achievements operations and Chief also session financial Officer will year and and review Chief Bogner we'll the made participants. President our be Following significant Chief Chief financial fourth portfolio. results Tran provide remarks; the progress Officer our in Hideki Officer,

to that forward-looking statements actual any presentation risks, are to certain we could will Before subject like would forward-looking factors those statements. materially remind from results and during begin, I that cause other referred differ uncertainties we that in to be making you today's to

most our risks our with obligation filings statements. of statements, recent to any well discussion our update with press as a our forward-looking and please SEC. associated disclaim the today issued as We release see the forward-looking For uncertainties

the And over Gene. turn to with that, I'd call like to

to thank review us you and all our XXXX for Eric results today business highlights. joining financial you, and Thank

that advancing to are of peripheral in candidates Prothena impactful both today are by by of mission deep which protein serves scientific propels targeting driven a portfolio development, dysregulation. portfolio major dedication we is millions how we At the a between rare strategy, that our for by excited day. affected achievements create drug caused mission to Christians Prothena, diseases are That our our and by We're treatments share amyloid diseases. our XXXX and as patients unifying neurodegenerative the thread and enabled every business expertise,

Today, includes payments biotechnology Prothena late robust assets. allows company programs pipeline, build intentional clinical mix while by full portfolio wholly-owned to potential partner maintaining and still leveraging for a partner programs. now our to upside a is slide This stage us five. diverse with which Turning four a wholly-owned five

PRXXXX programs we Phase Alzheimer's ascending our line from For and PRXXXX advanced dose the in both multiple X clinic to into both and expect XXXX, this year. top programs data report

IND IND PRXXXX, enabling and have forward an year-end. several completed submitting to For we look by studies

open-label and is disease the PADOVA X study. program, the PASADENA being prasinezumab in evaluated Roche Phase portion extension For both our by Xb of Parkinson's Phase

peripheral also amyloid We two rare have disease programs.

transformational Nordisk position wholly us formerly study. months. next a NNCXXXX, being for XX PRXXXX, in period and which birtamimab, X Phase X the First study by evaluated program, these achievements being a Collectively, over which is confirmatory owned Novo is a evaluated well in a Phase

included million, objectives. for Nordisk. funded highlight with well XXXX finally, we of a that clinical ended $XX from strong cash $XXX strategic on which position remain to milestone received million And our Novo I'll a execute We

of the advance allows our unmet further and by our protein blockbuster to millions Squibb robust goal Myers diseases potential, patients wholly owned together supporting partnership us to Novo, with of with and dysregulation. caused Our affected with our address collaboration programs Bristol pipeline medical our by needs Roche

We medical diseases unmet addresses neurodegenerative and preventing significant treating peripheral amyloid believe and that needs. rare focus our on

expertise clinical and for us transform to dysregulation best-in-class diseases. protein approach to enables treatment Our have advance differentiated the landscape therapy the potential that

for which disorders Our on affect disease million Alzheimer's an treatments approaches includes growing a therapeutic diseases developing are Combined, healthcare that Parkinson's by and This only sadly but with estimated system. two and globally, rapidly family for is people neurodegenerative the focus these XX exponentially. is number population. members, patients, social burden not expected caregivers, aging also by to an increase experienced tremendous and economic overall disease,

peripheral developed underscores and risk which for are NNCXXXX for developed high improved commitment patient at with amyloid urgent birtamimab need rare diseases, patients survival. In for to therapies our populations mortality, early being in an targeted

Before Hideki, that occurred like I'd meaningfully in for the several to Alzheimer's I breakthroughs the overall have turn that treatment highlight call disease. XXXX landscape over advanced to

primary of across months, results have the Over or milestones presentation the statistically clinically November and past last endpoint trial neutralize Eisai from Alzheimer's clinical and clear AD several achieved patients that immunoterminus include plaques proto. trials in soluble Abeta the developments confirmatory lecanemab, antibody the conference community. Phase of multiple Clarity secondary X on been with meaningful and Alzheimer's key significant Biogen's targets in disease Alzheimer's disease and all an the both endpoints Notably, CTAD for at to

the of as that which from best-in-class that we Abeta Alzheimer's subcutaneous generation Notably, plaque agency of next reduced FDA PRXXXX treatment for from Phase on antibodies, the endpoint of a demonstrated likely potential approval accelerated Clarity the disease. the approval to believe Abeta noted disease received clearing predict lecanemab including continues outcomes. the lecanemab a disease. January, was based Alzheimer's surrogate accumulation the for the paved results lecanemab approval Alzheimer's positive plaque treatment reasonably by the anti early accelerated Abeta early the of was pathway to for support in The AD data clinical and path plus X In the treatment brain, in

team XXX at the which cerebral development Washington Bateman's CTAD Randy scientific biomarkers. University many Louis, research that in cover spinal in data notable individuals tau was in from amyloid area individuals with the of of more St. distinguishing positive positive Another detail tracked at PET conference Dr. levels advancements included This shortly. tau exciting showed MTBR the tangles. closely with from this tangles fluid Hideki amyloid tau without tau will

we Prothena, in comprehensive for strive quality create patients. in to further these strategy At efficacy and and crucial. unmet prevent solutions that guided disease celebrate treatments Alzheimer's the and why Alzheimer's. the we Finding advancing the by disease of treat to therapeutic one address robust of most This to needs novel improve life our is also advancements this industry, is portfolios are

transformation have approaches. three We're leader prevention advances these targeting disease portfolio pathological key PRXXXX, product paradigms. expand Our PRXXXX, in currently disease Alzheimer's scientific recent in and to Prothena treatments and pathways in and field next of candidates, potential well therapeutic advancing cascade, the is modifying to the of positions from light the the generation as which positioned combination PRXXXX of a

now progress over highlight portfolio to the to across XXXX. With in the that, call robust Hideki our I'll made R&D turn

trials. you, treatment that plaques which Gene. therapies, a of subcutaneously potential Alzheimer's to clearance with amyloid at has high the Alzheimer's delivered lower immunoterminus targets the improve in with key our and allowing best-in-class, PRXXXX consistent plaque disease, treatment patient-centric PRXXXX clinical investigational mind with high data patient Abeta doses, in be transforming with Thank is Abeta I'll start effective next the our disease. more with binds binding potential for NTA designed epitope for PRXXXX, shown have currently believe the validity, the very Preclinical subcutaneous delivery for generation potency. and it

tolerability, an commenced forward immunogenicity, in data successfully leaders. of by expect binding ascending presentation cleared dose X featuring sponsor or PRXXXX then single healthy treatment patients report We Conference FDA ADPD, granted safety, the the initial begins study disease. we the a Parkinson's the symposium are initiated with the to of We in dose XXXX. and Alzheimer's cohort at featuring blind controlled has Among study the International Alzheimer's showing portion program level presence late this from PRXXXX diseases oral having upcoming pharmacokinetics data which XXXX, significant double preclinical XXXX evaluating thought superior this and the and designation for to year-end dose In key and on for a events Alzheimer's look and in PRXXXX characteristics the March. Phase volunteers placebo disease. the IND of and study fast of track randomized Multiple topline

oral of fold will binding substantially XX lecanemab, to of compared extensive higher when a XXX disease Abeta show pyroglutamate Alzheimer's nearly PRXXXX and plaque clearance superior [indiscernible] to of affinity presentation donanemab. than and more avidity Abeta tissue

to is concentrations greater treatments, goal accessibility approved therapies to of Our with Compared in is in treatments immunoterminus result first in generation in brain. relative development. smaller compliance other currently to and expected fluctuations also subcutaneous targeted PRXXXX and PRXXXX to ease antibody the patient offer

to research designed Tau that pathology with with clinical specific the best-in-class plaques cognitive hallmarks be to production robust PRXXXX our neurons and by are the Early like anti-tau specific MTBR uptake that the downstream within decline PRXXXX, associated would antibody. neurotoxic effects. beta of tau turn disease. targeting indicates research consistent anti-tau I regions and with found in conducted tangles into monoclonal resulted is targeting Alzheimer's to in correlates Prothena of more anti-MTBR now along disease and the the amyloid pathological pathogenic tau antibody. and a

a tau CSF of in correlated up coefficient the X.XX. of earlier MTBR target to the data anti-MTBR of will tau These this remarks and the exciting inform mentioned Dr. brain fragment shows Gene his bulk of XXXX imaging support XXX make that for at the presentation rationale and the As with Bateman's team. Randy CTAD are tangles continue further tau

Phase in X exposure PRXXXX at no were antibodies with exposure level based and in desirable these Single dose results The primary XX of volunteers. robust measured fluid is and from cerebrospinal proportional nervous cohort in objective the dose peripheral topline We penetration. in substantial the on data the induced in an generally setting of healthy drug study present levels, the cohorts engagement system anti evaluating concentrations single was target approximately X from central expected medical We recently with observed. dose which upcoming conference. dose PRXXXX added high demonstrated three robust semi safe CSF, PRXXXX Phase immunogenic study tolerating, from the X.X% PRXXXX persistent while plan reported doses results study the dose is in meeting single profile plasma CNS. of drug to

purpose for We partnership that expected our studies. programs Alzheimer's level colleagues with us determine the with anticipate being appropriate dose study of dose of the and multiple portion dose in X the multiple and of immunogenicity of multiple Phase is healthy patients Phase ongoing. The ascending adults PRXXXX The clinical ascending to one at subsequent Topline year-end trial the will Bristol disease. in help XXXX. pharmacodynamics in doses Myers three PRXXXX is safety administration results pharmacokinetics, the evaluate by is X these are following results of developed Squibb.

forward dual pathogenic at For a third present and PRXXXX AD/PD to to amyloid that that strategy. This combines demonstrated enable data and and program for the Abeta exciting knowledge XXXX with MTBR antibodies Alzheimer's therapeutic of well the filing essentially in a tau. and by year-end preclinical Abeta program, neutralizations mechanisms anti PRXXXX, of it data vaccine, Abeta phagocytosis for prevention tau construct, tau aligning as both single targeting an anti because of XXXX. a IND look We is as we generation

Turning are prasinezumab Phase for on a support progression These disease. partner from delaying study data motor Parkinson's in XXXX. they prasinezumab presented at Roche, effect PASADENA AD/PD because In data X out XXXX, our potential to Parkinson's in disease. compelling the

ongoing study, Roche Parkinson's the Phase with data PASADENA is expect now top XXXX. the in to Xb to line the report PADOVA Roche patients early PADOVA study conducting from is study addition disease. in In

treatment like treatments that from program for chain. Amyloidosis light discuss birtamimab Mayo AL I'd target to a Further of IV Now amyloidosis. amyloidosis plasma cell Stage targets Current AL treatments AL clonal for overproduce the

IV AFFIRM-AL deposited deplete therapies Prothena that these into new dysfunction. is advanced and address they X organ SPA, track can toxicity Amyloidosis data soluble special expected organ X than aggregates agreement that with birtamimab designed agreement the is most directly with cause the with AL XXXX. Phase to mortality The proximally X.XX. production, differentiated US amyloid on of endpoint to a Phase primary less confirmatory Mayo patients under equal at to already fail ongoing and associated the is the amyloid all line reduce or the with be Patient in or study. and to significant failure. the continues and confirmatory causing AFFIRM-AL Birtamimab top of has protocol FDA While assessment, Stage protein has level and a

X.XXX. Mayo in on In This American survival ratio a in VITAL completed post of Conference, December birtamimab is at a in Stage demonstrated reinforcement patients of risk X.XXX XX% safe data Stage strength hazard AL data XXXX with tolerated versus nine the placebo significant in Mayo of birtamimab IV in these clinical and population benefit across at taking of we patients of patients analysis was variables mortality. survival well Society IV the Stage patients from of baseline Hematology consistent and Survival high of Phase P which key reported a of statistically value reflects patients. vital, the IV study, overall and in all X of benefit Mayo XX% remain Birtamimab patients, at Amyloidosis, early of generally a the months. the

expects for being has Novo Novo in treatment and Phase moving X which now now report PRXXXX, And in been Phase data clinical the ATTR into the ongoing study advances of developed by is advanced an to cardiomyopathy. ATTR from to Amyloidosis NNCXXXX, renamed study topline XXXX. program, the Nordisk has X

At like financial for financial Tran the call our this to Tran? XXXX discussion and turn our XXXX I'd to over of guidance. time, performance

of Today financial that refer Hideki. press detailed either or to in line our guidance. breakdown results. a our release results Thanks financial favorable our reported XXXX Please were we to or

we As we potential the cardiomyopathy. with first last of where X remarks, for position, Gene strengthened capital the received of treatment mentioned our with trial Novo strong to our his NNCXXXX related opening partnership Phase $XX year ATTR million during Nordisk,

raised Additionally, of of follow $XXX.X December, public received in an we net million offering proceeds underwritten ordinary shares. XXXX, million X.XX on through

of operating to net and of activities Net million. performance $XXX in was $XXX of of terms line with million, million, guidance, in investing which cash our had was favorable relative In used to guidance loss financial was XXXX $XXX $XXX.X our guidance which $XXX to we million. million $XXX.X our to

of equivalents of our As which XXXX, guidance cash, restricted $XXX cash, Prothena December $XXX.X XXst, million. had in and million cash exceeded

shares XXth, had outstanding. ordinary approximately of XXXX, Prothena As February XX.X million

have with to clean debt. capital a continue we structure Additionally, zero

Turning to XXXX our financial guidance.

net activities $XXX We expect in operating between used million. $XXX our investing cash and million XXXX full year and be to

restricted by to range. expect of primarily non-cash and used compensation approximately million an We an estimated million, the equivalents estimated expense. end cash, and full is in year $XX million net share-based XXXX driven the in activities which which loss year estimated investing $XXX $XXX includes cash the operating of represents with The $XXX cash, million, cash midpoint of net

call the Gene? to Gene that, to our discuss milestones. back With I'll over turn upcoming

Tran. you, Thank

I Prothena acknowledge protein employees we thank Before talk and thank and impact commitment ongoing advancing real their impact families patients we're and staff Without our for patients, developing. we want first a about talented serve. milestones, I'd our to medicines like also dysregulation could support, to for to our the XXXX our their science the not families, to the studies. of make we the who new participate physicians, elucidate potential their in study site

past in multiple a the dysregulation. advancing Over has protein our diseases caused by on leader year, Prothena as delivered addressing team milestones further devastating

our have our achievements scientific and best-in-class mission today, diversified XXXX our period well meaningful positioned transformational to portfolio As a combined possible for talent in have heritage made ahead. human with multiple and our heard you Prothena dedication and

Alzheimer's becomes in commercial data the new believe and of to devastating programs clinical care we on As landscape field, available patients are the suffering regulatory disease. well-positioned this from our revolutionize the

XXXX. we expect that key can milestones To the in and XXXX end, following

annual upcoming meeting. of preclinical characteristics demonstrating First, the data XXXX at the PRXXXX AD/PD binding superior

and of the we multiple data of the initial report Second, X has PRXXXX are line by ascending to cohort from Phase XXXX. end top study the dose portion track the commenced, on

further the in of Alzheimer's. data is ongoing tau MTBR Fourth, study dose Third, for the multiple targeting top ascending year-end the line expected by for with XXXX, Phase potential treating elucidating X an for PADOVA XXXX. forward IND submitting the data Fifth, to in looking report prasinezumab of Roche expect PRXXXX, end Xb we the by that top we XXXX. study line will are from Phase PRXXXX

in ATTR from in rare will that our enroll XXXX. to birtamimab study peripheral line continue our patients X for we top to Six, that in in patients Phase expect AFFIRM-AL line cardiomyopathy data X our Phase top Novo anticipate study with continue finally, report NNCXXXX, data portfolio, partner, of we amyloid And and Nordisk, XXXX. in

the I'm progress proud Prothena of has in made XXXX. that

strong multiple We assets robust and have portfolio collaborations. a with wholly-owned

the cash We on robust have executing well capitalized, months. position, during are a next focused remain XX and

to when we year, expect continuing this We additional updates pipeline forward our additional appropriate. R&D to and across to progress make portfolio look provide

So that, with we'll open call question. now for the Operator?

Thank you. [Operator Instructions]

We'll at go Jefferies. Yee Michael first to

patients looking you've for choosing And compare just Hey it six amyloid data, the of guys, when I you you should data PET? PRXXXX a MAD other the have for to Alzheimer's that think on Thank for good portion question. you initiated one cohort. after in for and how patients afternoon. reduction Thanks describe can this Later keep update. I'll we you. first and level what like Are contextualize to Alzheimer's [indiscernible]? months? at you're the PET it looking antibodies certain try year

Really and asking. Yeah. Mike, for important question, thanks

So, continue that as that. study, me PK be just tolerability by the multiple safety do amyloid to the objective dose our using pharmacodynamic let as over obviously be obviously ascending PET immunogenicity. point to of establish period. brain you at tool primary to the looking in is the start looking saying We'll And interestingly, out, at and reduction marker we'll six-month

of by this first how we're Tran in Maybe you then make it terms that Hideki, shown and reduction amyloid maybe well I a PET. hand are agents have our can thinking anti expectations examples to to relative of dose cohort amyloid comment can what first as Tran? about and other

Gene. Thanks,

average C of mix of and would kg -- know, first level the average the the the be modeled Mike, the mad to X aducanumab. at Phase of targeted per dose As you concentration we C XX

dose can course and active, go other to we cohorts level we're -- we for we're dial believe cohort again, level have optimal but so into looking not data. comparative the for -- will is dose data. active saying We're in Hideki later. registrational be this first trials initial But for in, And what dose of looking

And use elucidate some the further doses SAD and so, to the we'll the data from behind data first dose. MAD also

Gene remember, have just as this -- cohorts look so add look and have to is And that alluded is importantly, Yeah. X We'll, at I'll And Tran course, safety. Phase we'll a both dose endpoint pharmacokinetics pharmacodynamics of additional dose. study, primary to. the bracketing at and

Citi. to next Neena go We'll Bitritto-Garg at

my question. taking guys. for Hey Thanks

that we more exactly Just to questions we later year? any many expect on for the little of was you us if metrics detail you'll look asked. are more kind cental see patients PRXXXX to proportion any negative exactly whether bit of specifics see how this patients you on might a provide we that should think amyloid should whether the give us be follow expect -- to PET like up Could just about and can also color metrics provide on just And or on to then, how data the Thanks. of at, on results you'll with that. able scale the kind who

Neena. Thanks Great questions. Yeah.

it some perspective. talk from and can maybe to well the of as PET So the of little about study that hand the a design, some maybe multiple dose just little that. to -- I bit about a parameters a over can And evaluating you bit Hideki we're elements of talk Hideki

Yeah.

measured pharmacokinetics amyloid -- this enough meet So and in order that we we PET. our being patients safety cohort, by as endpoints in first have pharmacodynamics have to

to have as any also well. safety for will MRI We look issues

main parameters. the so, those And are

so in as is biomarkers primary have robust safety MAD. optional Remember again, dataset. that Phase we'll X well, very a have this We endpoint

a of perspective. the the reads. pharmacodynamic cohorts in have cohorts, data a [indiscernible] at analysis we'll enough it to analysis a looking also PET patients be make And pertains we'll MAD SUBR And amyloid -- and statistical basically various to as the from

single and mean think out as something want to is this just to the a we your the about year, Yeah. other that's point dose be that talking I that thing is, the well. importance Neena, sight follow of we'll up data question I'll lose as also of don't I fact

once dose PRXXXX, informative tell with development we've target data the product binding a given target delivery, its as know, to with profile. you well as product As quite just we and our profile could think monthly us single approach subq closely be the its how characteristics come subcutaneous to

be that all again, about the will that think we is, data important. And talk So, altogether. we'll anticipation

Duncan Charles next And Cantor move Fitzgerald. we'll at to

presenting Yeah. a at going product call the also then a Hi, subq and had regard hit year CTAD. that part one, about question are with exactly and could best-in-class, and centric to you question single taking to on guys. and profile? it you probably be on whether I the dose that be AND what the considering talk being that Thanks congrats for XXX or is two-part data, good is progress. evaluate patient when target you to AAIC or second that not you

question. the for you Thank Yeah.

think to with will where we first, actually we discussed, speak able that. be I will wait to are to the until So, respect obviously data

just targeting but So certain clearly meeting, us a that and being not requires submitted an accepted. being abstract

So, we those wouldn't talk would until that where as data talk we announce typically such about we time publicly. about

current for expectation single dose first data, the the the dose with dose think single should data. of that along cohort data that we'll multiple speak about be I

that's current communication that. So, the around

expectation that's think the currently. I to So have right

occupancy met. subq And optimal that. antibody the is once enable of of the right and about what say of looking to more their Abeta level same this. may less an a I what with characteristics. PRXXXX, much from antibodies ask generation It administration. develop would now which eager And profile require mention of out to have these that, most to the level, antibodies, delivery think we of subq which provides It profile talk of a lend first I'll PRXXXX we're campaign course, was delivery to would and that some studies monthly about a was at key of and of characteristics. is develop for some by set intensive really we we're a as characteristics is, that target because the our what maybe if in itself I design intensive characteristics Wagner perspective, can we've And to to to being product clinical obviously do screening understand number highest subcutaneous an with met requires just

you if subq profile think the think for single going for. we're target that's patient potentially about that so, optimal enables really once syringe, access. us. And what We monthly That's product that

potential we of think So, make to want from target sure these treatments. to treatments, advantage in receive types a that makes to And that these can that a for profile of of moving patients lot regard. that patients of actually sense have we kind types

So, the overview PRXXXX if Wagner, we maybe you meet on as profile. we at developing could ultimately just that some a of looked were little bit and that to characteristics of key selecting target

Yeah. Absolutely, Gene.

you subcutaneous there delivered So increase to only would subq, But about more and the be for doses you reach features. a potency lower a potent, is And antibody that an in are antibody, lot. that to periphery. dose additional but barrier. you to intuitive we It's affinity very same this of talk other level -- that the the from feature not can if requires of That's compartment, at clearance lower antibodies occupancy the blood an level be two, of in PRXXXX, potency remember a target compartment same going a there the do. we is from antibody much that different

are screen design antibody subq included in and and All many, saying as when to Gene PRXXXX [indiscernible] many design in features have. those So, used said the we -- that the additional antibodies, we was screen.

solution, that compartment in bio high part And where of only same the availability, in was not that the it's concentration stability is all screen. the but One of stability delivered.

is that make it In antibody subq. fact, raise to IV with where that the an a and top. a different than you to This PRXXXX normally campaign trying start

point, you and antibody. want Gene as XXX might the encounter to preclinically. was at because didn't that subcutaneous a with be You born said, challenges that some we And risk

important they are for That's said will confirm early. models we that as a that for clinically us can that, are be very is read doses reading X the leading that And of to availability that a that tweak product we because -- doses, patients our only appropriate for that, for in our So are to that importance for before, by the profile. we all assumptions to of that and meaningful very engagement exposure, ensure they us, not sad the was example, that MAD, active. target the target Phase selected

Oppenheimer. take from at next our We'll question Jay Olson

Hey also PRXXXX of question. Can taking reimbursement Alzheimer's guys. portfolio therapeutics, and also progress and and yesterday's from you the delivered and landscape thank see about you you especially how you. then the evolving a on in Congrats the talk the since for for with Alzheimer's to comments vaccine. tau designed amyloid as dual is with your be Thank broader subq, also PRXXXX your context maybe CMS

good to a you. Thank Maybe as Jay, really speak Yeah. of this, question. just to ask Tran overview. quick but kind I'll also

I think the announcement yesterday, we felt generally is encouraging.

immediate encouraging to a wasn't same CMS the request and construct, was out at within full Obviously, on look time it almost I they think approval, would came that think I much context. NCD reimbursement think that Association that that within entertained, a to broader the the the suggest in the former did prior was about disappointing current decision. NCD, little to Alzheimer's it the response reconsider but

that's near way the term, that's We reimbursement still think we while actually ability a to So, positive. footprint think full increase to in forward. having the NCD reconsider moving the the

occur That those that, as envisioned the B in out, actually home, could D opposed Part said, Part pointed be in a subcutaneous as approach to appropriately to you may that particularly be think position PRXXXX NCD, in Coverage for Determinations. context. the And, different well in we to actually has National quite And reimbursement that potential of respect course, scheme. with consequences that Medicare

plaque we like, around little I accelerated of look asking the continues bit, to think maybe of was and approval the lecanemab. and accelerated the other the the measured basis approval question approval Phase you that were the a fact based really by X reduction and on data, as amyloid the encouraged PET. that were what there was particular basis on of approval kind that pathway of that by of course, In

our we're which a way. think path can thinking which of that the an but with forward a broadest clinic is the approval provided appropriately key the time, that's same that accelerated elements and and holistic end-to-end, and need. through on enter ambitious, remains data molecule package most So We're pathway, pathway, way open meet the from our it it's program the looking at the do a the about that same potential We PRXXXX. we think continues that perspective, But at medical time, you disease unmet commercial provides in that we market. serious in us at to move accelerated how this for

that think we from we're about do an end-to-end So, -- perspective.

you Tran, But published and further field. kind that comment I yesterday decision see the of the can to how you CMS maybe bit little ask on a

I mean, the know the fact data, there clearly on is you that they I build just to Yeah. said that Phase meaning was the how what more I it letter read we pointed to think, understood X is, data.

they registry a Association And will they at what the out to that do the upon broaden I for that that is, have review, full NCD What they They communicated CED broadened they There a work they've has. said is put existing broader basically within to look get work registry. this and didn't Alzheimer's to in that. a they that the mention expeditiously there. that order think during they coverage wanted patients, approval.

even real that how that this period, they after a of data is least at approval, then potentially At after see at and of look we'll registry. review collected, than to the They're review would broadening Phase world coverage take something data, details then a hey, X saying, so, we'll go changing they But the broader that that. And potentially get it. and back the you'll through full And between of broader in review -- what data. are are. point,

of I so, working is, was, what start we it'll And new a a do kind were think from NCD which with through registry. nine XX take they broadening to okay, for versus zero, months process a

with potential make the of So, work But again, our talk There prodromal very of understand regulators feel to CMS approval as they I so And decision forward to after is build as a on FDA speak. us review we regulators ultimately that's accelerated years about patients approve, saying of to based stage is as covered, do. happens, hundred on do mild then approval again, of also we again, will are we can it need but to job was to with the need and that. that we estimates -- underpenetrated Gene to marketing, And they year do Gene do to market, there's know, patients. FDA's the think millions for that that the what to you think path and need. then again lecanemab. And paths that thousand e data just what see see they to that about we in But three to encouraging. that according and or working in we once disease. an And size, a even of patients on unmet

when and there that so And hard work we figure and are. come our we'll happens. to update all will to what out an you be will back you. And Thank path patients unmet need

to Abrahams next Brian go Capital at RBC Markets. We'll

afternoon. you dosing sort paradigm the will of with you or a might with for for to Do I'm envisioning your Good are guys the antibodies? dosing I'm maintenance? for robust think amyloid taking my progress. guess XXX on checks, congrats dosing there. Thanks. enabling most future Alzheimer's development be some potential the beta this curious I set question all finite curious, and And Hi, how that safety approval. accelerated amyloid data how shape regards induction strategy chronic Thanks potentially

Brian. Thanks Yeah.

different right. exactly are and slightly a you're There species paradigms talking that out dosing different think are differently. target the couple slightly monoclonals I beta amyloid about yeah, So, of there

of it from think, or in we about its is the dysregulated a misfolded treatment pervasive paradigm. in perspective, the as amyloid I form state, So, chronic most brain, think targeting our

biomarkers I So to where were actually ASI and we're X aligned from where starting that think the revert back they've done, they that many with, showed to gap during some the you data for the of that, of their Phase that year weren't hear particularly analysis that in set at folks had key they from the a time. some patients example, dosing and things of worsening

period has sense a reduced. are I'll that in in substantially where to or actually in term the to And CNS. time of And well. after that treatments. other But target context I maybe, stop profile. be particular not at lead not ask material species less there a eliminated it beta of all And be treating been true the may think translational better make long as subspecies of or a least that out there treatment of to that on may may it post modification I under may that think conditions, approaches that there Wagner may comment amyloid those

Abeta that's across come sets after we'll ways. target I particularly out longer, compounds have something multiple that longitudinal slightly in and that, long that think compounds -- multiple find beta different in

Our is amyloid of key it is in in key chronic insult as Not disease. a such own, does current toxic CNS on leads only but of it its treatment the likely cause to the Alzheimer's proteins view tau. The of beta that context needed. dysregulation is the other problems data

that about beta reasons One PRXXXX because that we we pathways. do targeting of are as agents believe on talk tau key amyloid the those a target biologies is dual

know, So, do beta which example, regulation, to lead tau can can neuronal directly we amyloid that for dysregulation. lead

So, part insult treatment a needs modification. we unchecked, disease a toxic to it's provide as and of to Abeta think left it do foundational will be about continue we therefore ultimately that think if

to maybe So science? want on expand you some of Wagner, that do

Yeah.

the of is. echo what what what Just to the I is determines think likely you mechanism period said Gene, -- treatment just the

very you can of If the because of a aggregates. doesn't position more we've completely that that's a when plaque morphous the more accelerate can removed scan, the you you solid binds are mean be forms that around do an from have -- forms antibiotic likely most to quickly be chronically Even multitude compact in toxic small it if and to small need aggregates, patients. toxic OID, amyloid that those PET you and the forms delivered formed you of brain although all of solid a even antibody you very have make visualize the what that material don't

all If that chronic we you're pathogenic those forms, as the forms, binding a antibody see all treatment.

initial to of and a the lag is, antibodies if time pathogenic is material, that of form. that Now a then of once you between formation translation the there post requires course, modification rid got happen a to the binding new

antibody around target. if probably So, sense don't have it the wouldn't make you have to an

all lecanemab, it that sense forms treatment. So, it mechanism chronic think on and terminal as of a depends antibody to again, perfect end the like to action PRXXXX. all like of the position antibody makes pathogenic that binds We

going the what clearly, and -- on is, follow data saying build and here. Wagner we're we'll was to Gene to Just

translational Abeta, I X of Clarity excited what that Phase pathogenic, data could to species in look post of think trial what amyloid know dose the hitting Wagner in, results all X we the design And trailblazer the Phase from stop. the about maybe that terms be have, Phase from said at that AD, the given we'll modification, X pyroglutamate and just where the We're just in that to they see donanemab. trial Clarity. they X data not negative terms

how going be learning us to it'll a see forward. clinical registrational and affects design we'll tell endpoints, all that great So, that'll think our I trials how because

Jason JMP Securities. And next Butler we'll from move to our question at

taking thanks question. Hi, for the

Just had PRXXXX. one on

taken mentioned XXX comments from that this CSF, you're to you results how Thanks. and some you're include about you of how looking about year. MAD if guess forward from how think away you going specifically in SAD biomarkers Just give and in target tau thinking engagement the program? and it how the terms the you've as take you what could about I later what wondering results

Yeah. Thanks Jason. question. Good

protein, little in variants. has I got were, those It of a splice variants, first, mean, we -- the we six right? complex a over tau about amino XXX MTBR just to how region. bit So, We is some acids

negative was, when to to of it target associated how quite important. some understanding ameliorate so the becomes dysregulated it order that's And biology that protein with in

the looking think up within gave and MTBR under at antibodies. this great effects. that job did protein. targeting robust a us region, direction how region really that team antibodies, being really And targeting immunoterminus, key you consistent was target biological something I Wagner's very Really that exploring determinist, in the ended carbo it

and when then in some to work these containing on And fragments. start started the the really MTBR see field, were region we MTBR so, we encouraged to focus in compelling

So, important critically for Mark example, in MTBR fragments the work suggesting Diamond's are dysregulated transmission of these tau. cell that

dementia call, only And patients in with potential we U, containing disease. in fragments MTBR with CSF, also also suggesting as not Alzheimer's PET, they of much but these that the evaluate when the Randy tau at in Wash you work Bateman's really track mentioned with better level

were So, we encouraged that. by

I again, that multiple remiss are that, interested study, at didn't of in MTBR the say, tolerability. objective safety and CSF dose But study definitely question looking fragments. the correct Hideki you if specifically is would me target interested particular in engagements. I'd in we your say To as be these We're in primary

of fragments I nervous effect we'll like CSF. Wagner, Hideki compartments nature the in you kind in the want that or the And if don't system to of pharmacodynamic context potential know, of speak here, the a to central the be evaluating

Yeah. just ahead go first. Wagner, I'll you Go reiterate.

full fragments Wash detail of fragments we'll the the a opportunity reported for on great by fragments track certainly the us. with but so, they're well progression that it's different not the example. identity, provide U, Maybe from looking as what we for are disease for, And

we what that good is of target the very this a the reach of full understanding to antibodies. potential for have engagement We want

activity So, using, confirmation review we brain that we details to And as data the about assumptions our once we'll that a the use going and for data, assays be well. and in set. the the are of as that dose selection we have the

the measure same to sensitivity. It an can of empirical in I why it developed of was point and being time, we MTBR the that mention just is field that are is all tau want extremely other via was at screening. a Not MTBR fragments impactful are, domain long today mystery ago in we why was the but we question that CSF, not a a MTBR the determination, to CSF. lucky the found the present it

studies has that your one of, availability for we which more become bigger, or one in legion us just allows it we directly the containing antibody we not to make now position that if we sites multiple that making, element And that, that read believe or of a designed intracellular pathology. the for recommendations in what that to there But to to these And out. helps have decision activity where can with all can is are confirm tau I'm track MTBR So, that to in the antibody the a the have binds the MTBR fragments. of phase we basically is also as to CNS. you also assay another going PET elements best anti add us in that use

So, all I'll about point, the Hideki is but of talk let of part it. that is,

patients. engagement. as as not show CSF engagement a Wagner have far in results we'll from that have substantial we're with is data, Alzheimer's the wanted we I And indicates the and that safe, CSS which mentioned, will SAD that Yeah. reiterate MTBR the target MAD very announced we tolerable, the data to we're pleased penetration, particular CSF the but and pleased have terms only we really safety, earlier of very extremely data with because as just X.X% in

end So that's all we data of the by year. expect

Kinney turn closing further back I call for remarks. And at are to will over the no time, Gene questions. there this

on And thank our us all to call your the you and updates all. interest over coming further programs. operator. I on in today. you We want the to Prothena, thanks Thank we forward appreciate months for Well, joining look sharing

participation. does Thank your conclude you for today's conference call. That

now disconnect. may You