ALEC - Earnings call transcript Q4 2024

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Operator

Good afternoon, ladies and gentlemen, and welcome to Alector Fourth Quarter and Full Year 2024 Earnings Conference Call. [Operator Instructions] As a reminder, this conference is being recorded. I would now like to turn the call over to Katie Hogan, Senior Director of Corporate Communications and Investor Relations.

Katie Hogan

Thank you, operator, and hello, everyone. Earlier this afternoon, we released our financial results for the fourth quarter and full year 2024. call available filed website Exchange with afternoon.Â Joining on is our www.alector.com, Commission release me was Dr. XX-K the the press on at our and this The are today Securities and Rosenthal, and Dr. Arnon Co-Founder CEO; Kenkare-Mitra, Dr. Development; Research and of Saraswati President and Head Medical Romano, Chief and Officer; Gary Dr. Marc Financial Officer. Grasso, Chief After we'll Q&A.Â I'd a be to our number open that note of for remarks, call we'll statements. making during formal forward-looking the like this call, disclosure. to moment contains review our the on which statement a slide our webcast, forward-looking take Please

We review like more turn Arnon also to information. I Arnon? the to for encourage SEC filings Officer. you our over Executive would to Rosenthal, now Chief call

Arnon Rosenthal

Thank you, by strategic that direction Year thank Full XXXX for Katie. Financial and lie guiding Results ahead. Alector outlining joining our forward I'd and the begin you Alector's Conference opportunities Fourth to and afternoon, Good Quarter Call. everyone, like

along improve and at protein nucleic platform. ABC brain the proprietary our developing medical delivery acid discovering and includes dementia, as best focused dysfunction deficient this, unmet programs barrier high and and disease-modifying are to disease more are GSK and medicines discovery late-stage we therapeutics X lower costs. Central first-in-class X such Alzheimer's first aims We blood-brain of to disorders portfolio continue for or addressing to an frontotemporal required.Â To programs is build the urgently encompassing therapies immune needs, effective Alector or ABC, achieve where both with neurodegenerative clinical Carrier nucleic and safety disease proteins efficacy on inclass our Parkinson's combines pursue that the mechanisms and as deep versatile in proteins, misfolded manufacturing of development antibodies, Brain to such well systems.Â Our in established capabilities. and neuroscience genetics, organization target acids, increase with protein extensive as novel biotechnology in integrated doses clinical and regulatory as with toxic with and engineering therapies and immunology that drug neuronal enzymes programs developed enhance collaboration We lysosomal discovery, expertise our neurodegeneration, targets. and and underlying to

We are readout anticipate portion with X realizing our to expect planned our potential be frontotemporal The for trial XXXX. pivotal in is ABC-based significant owned and in of wholly Phase progranulin gene advancing in the in XXXX. of clinic the company's We this a programs later mutation year. dementia

that we Phase X of Throughout ALXXX Additionally, sustainable I'll will this process, goals to for we decisions today. create these development our early preclinical we clinical Sara later which patient over data-driven that, turn value. in the for our With Alzheimer's to remain complete Gary expect and to also are Gary? call committed discuss programs. making to our PROGRESS-AD, recruitment expectations initiatives, advancing disease.Â Beyond our discuss pipeline, trial

Gary Romano

approved the with XX% would we receptor, a INFRONT-X INFRONT-X rates antibody conducted expect progression, in and approximate the our This a extracellular FTLD participants Effects blinded between elevating X Phase common Phase compared of which deficits weeks. with frontotemporal of kilogram trial double-blind, are additional to X results Phase we space. a of penetrants designed X small, extracellular of from of clinical treatment that development to and receive determine behavioral FTD scale in of this representing at-risk the XXX%. disease to and collecting in authorities Thank from placebo.Â Importantly, assessed whether biomarkers the in we study, in and an assessed are gained alignment dementia progression or a XX The FTD one progranulin evaluated after analysis first-in-class duration data cohort of up progranulin study in GENFI and in X the the the from latozinemab causal novel of in X in early reducing the latozinemab.Â Previously, modification the treatment several INFRONT-X receptors BLA Latozinemab latozinemab, mutations we participants latozinemab.Â The latozinemab the based the we restored progression were baseline a in future subjects. clinical I'll were slows weeks trial biomarker study. result who per same Type XX X loss haploinsufficiency FTD monoclonal Phase This every which observational FDA health outcome an with on potential options latozinemab-treated the symptomatic disease the the rating on the randomized has It Phase clinical by onset in latozinemab trial assessments no latozinemab-treated pivotal our sum in with XX match X have in the that which is designation, with direction both we ongoing slowed the enrolled trial was that patients expected and review. levels all relatively that are for primary indicated gene was evaluated sortilin moved granulin a progranulin function, there effects the participants levels assess XX a and FDA clinical granulin. license plasma therapeutic Currently, breakthrough CNS astrogliosis there and block in to a as a and levels treatment the in slowing quarter. randomized, of number demonstrated pivotal this causes as novel our of granulin neurodegeneration change the interaction is FTD with granulin is treatment is evaluation pathophysiology. of Phase patients The XX in of pivotal available on analysis that analysis. duration on subjects inflammation, application latozinemab designation open-label normal which down-regulate on by that modules with confirmed X is for for on granulin data. a if was Arnon. clinical FTD.Â Heterozygous Phase progression FTD-specific to progranulin progranulin, this progranulin.Â Latozinemab participants language the disease normal dementia. INFRONT-X. supplementing function year the blockade II candidate, XX fourth of increase, it FTD take XXX of investigational of GENFIX will primary held To include human with February to of either milligrams with a rapid of over or intravenously one Phase GSK. with FTD you, treatment. sustained placebo-controlled is developing evidence, data been trial.Â We in the is it would that X for in in treatment With assessed to latozinemab clinical INFRONT-X we neurodegenerative FTD increase and last two FDA XX% top-line the EMA biomarkers symptomatic of sensitivity year, at-risk progranulin for rare disease, advanced X over consider potential partnership participants granted months for effects most treatment-related study weeks.Â Although granulin. pending the participants begin of symptomatic FDA subjects which most are of plasma mutation CDR levels but a effects to latozinemab lysosomal candidate and threefold therapy to XXXX, of boxes, intend CSF, the the treatment to In a propensity was of trials, and be in dementia endpoint CSF We conduct plus NACC confirmatory biologics acceptable B comparison

disease presented of to the Conference including We data. subject FTD symptomatic with XXth plus to the X of supportive biomarkers full or imaging FDA INFRONT- population levels, including sum for BLA at remain FTLD provide forward represented plan CDR and information registry April delivered based the primary the NfL dosed to efficacy by Austria.Â We X place for and participants, strength totality I'll and effective a significant. I'd is a Dementias of of design and ISFTD-XXXX. of Frontotemporal on turn to across be regimens clinical designed granulin CSF evidence, trial progranulin in clinical PROGRES-AD Its and approximately update therapeutics the latozinemab.Â In we compared efficacy manner. Alzheimer's brain. treatment increased with XX% Results to Vienna, dementia to an suitable INVOKE-X which provide registry trial product confident The a to sortilin Alzheimer's the designed trial measured demonstrated Alzheimer's the advances.Â Finally, age, to Sara hold, the XXXX, assess assumptions X oral ALXXX, the also Phase the at boxes as the boxes. now designed pipeline. in committed the of sum of enable clinical disease Alzheimer's remain from and our is our in aligned call may AD/PD characteristics dose-dependent participant and the GSK. will and pathophysiology fluid properties be in placebo-controlled trial review. disease-relevant XXXX Based biomarkers, potential block PROGRES-AD the path well on Phase the ALXXX With to the also to statistically present the primary patient considered placebo. on may potential of enrollment elevate The in second clinical now during antibody Conference Alzheimer's candidate preclinical to endpoint in evaluated was to employs feedback over is trial ALXXX multiple volunteers baseline XX-week to the year the the agency with we plasma operationalized scores sites on indications, is safety the early doses our first randomized, X design, pharmacodynamic outcome distinct and the of as ALXXX X disease characteristics ongoing double-blind, mid-XXXX.Â The ALXXX XXX approximately could baseline of power efficacy a was clinical our safety available turn the with of use INFRONT-X progranulin International approval International slowing taking on NACC disease our to of development disease. evidence disease. downregulate study September an we like slowing partnership Sara? global and trial broader we understanding XX% and monoclonal on as Parkinson's ago complete that additional partner, endpoint on by TREMX XXXX. February level for be a expected PROGRES-AD developing that enrolling sharing GSK, pharmacokinetic participants the more trial, ALXXX are is provide to early the results the detect and that The dosing healthy clinical of individuals biomarkers. LikeÂ Latozinemab, advancing in functional that in be in tolerated We portfolio progression. disease.Â Our larger receptor agonist other progranulin If rating that, Phase X study levels by to in XX% have presentation The of such of a to of progression is of ALXXX, look and with just to on a also and disease for that our expected X, assessments progression of

Sara Kenkare-Mitra

Gary. you, Thank

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the clear the beta dysfunction slow technology, our has brain ARIA. addressing lipids to to active. and amyloid region candidates aims with including GBA disease. be and with mechanism, proprietary our goal for therapy a programs, with antibody Parkinson's ABC designed is paired is that deficient replaces prevent cellular for to we GCase accumulation amyloid efficiently, of progression. contribute disease, a constant these accumulation thereby ADPXXX-ABC Our combined tau been plaques.Â In to preclinical target slowing Alzheimer's neurodegeneration.Â By mutation this amyloid our ADPXXX-ABC used of ADPXXX-ABC GCase which reducing is leveraging GCase Parkinson's anti-amyloid of to several and risk Alector-engineered enhance and advancing to that ADC toxic epitope of minimizing ABC progression pathology.Â ADPXXX-ABC replacement stable specific our technology and in and GCase, the treatment By disease candidate of to beta targets beta carriers proprietary activity. plaques beta phagocytosis validated while more amyloid lead antibody our reduce an brain disease. disease aims plaque patients, GBA optimized mutations It to ADPXXX-ABC, gene uses is an In are single that beta

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in grant a Foundation synaptic collaboration pathology Reelin for target Research. University Fox of we promising Michael to awarded of million treatment funding $X.X Parkinson's on disease.Â Lastly, a was the for GPNMB, addition, a research J. designed and Parkinson's the are In Alzheimer's from promote Alector support block advancing with also our the disease. modulator tau Luxembourg, This function for will

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Marc Grasso

Sara. you, Thank

against As results, today, to market quarter after the summarized we strong we and position are in deliver in our fourth cash year our financial closed made strategic a XXXX available which full objectives.

million.Â Now results. the was quarter we on million fiscal the for in XX, and general development and as to expenses in to $XX.X year $XX.X compared turning equivalents XXXX. XXXX.Â For same to We for totaled revenue compared program our were were million between and expenses for December in XXXX. XXXX. quarter for continue prioritization. period million million Collaboration was compared focus XXXX, to $XX.X to management compared same revenue and $XXX.X to Total to cash million year in our the to the for were XXXX, $XX $XXX.X to operating And the million. $XX.X for cash, expenses million of Collaboration short-term be investments for in $XX.X $X fourth million the period the XXXX.Â Total $XXX.X the development revenue million and expenses XXXX. $XX.X research the million general fourth compared research and million million our Total and estimate million Total for period were administrative in same compared million administrative $XXX.X for year $XX quarter $XX.X $XX.X collaboration

today's million and to to and for you and to as We research questions. million $XX concludes open as focused work. That are look on providing call. comments anticipated administrative our our for and the between our $XXX may progress Brain million, estimated and we be general prepared additional now Alector remain diverse development Operator, Carrier and total diseases. treat Our be portfolio estimated are total advancing line as to neurodegenerative between $XXX expenses million.Â We expenses broad updates technology well forward our $XX

Operator

And will Instructions] from with [Operator come the Cantor Stavropoulos first Pete question Fitzgerald.

Pete Stavropoulos

clinical a result the clear for a gives X, believe XX% question of each see CDR-FTLD, Congratulations X. patients for INFRONT, arm XX% between a baseline on between populations? score of you in score score and that of allow you course X.X, to that mind, the you proportion these you of correct larger are and that benefit should will What separation score I separation for all the thinking disease have have in One characteristics global greater lotuzineumab placebo. progress. INFRONT treating see you in study, for active patients was enroll XX of is, of and cap me neurodegenerative With when of about of confidence a any and earlier the have patient a the a the placebo a there

Gary Romano

Gary. this Pete, for question. the question. Hi, is Yes. Thanks Good

distribution enroll, early of intentional try this as the to said, to to score you granulin. global out to FTD set X.X symptomatic and the this of was we target So on population

as might including where what say, it's so a somewhat for imagine you we along to And treat are be further and faster. between that also earlier greater of room patients balance may progressing trying we a a think can always â€“ little but efficacy, bit be bit there that more

therefore, what that do, was population. we're theoretically. in So cap more were participants might or many want that and we -- two-thirds earlier and that as to We bring had patients not reached be did that were this through is we the out we happy we that about or to cap the have intentional trial didn't too because set further so stopped responsive CRXs able and progressed, been in treatment to very to very and, enrollment and

a not will that participants And we analysis, and though symptomatic threshold neurofilament collected a had focused plan. primary those -- in subjects -- the certain cohort light mutation analysis just can just that be -- also although benefit also point efficacy to analysis, find stretch that of small think we the sorry, at that in want is I we were subjects presymptomatics we're -- a -- patients be patients post-marketing is it think some we not they're of I'm pending NfL, to potential sensitivity we until it's wait to in to but wouldn't out symptomatic at The be the carriers discussed, see sensitivity if that's were symptomatic -- we who that far planning least or thing and could a we analysis that we're if might our -- a of do. And I be what preliminary in even the on to certain with patients in other subjects Why why data. far primary wait impaired think looking to subjects, get some those treatment? some it that a should patients type including start -- there our works met stretch able approval in analysis if

Pete Stavropoulos

follow-up a So question.

GEN NfL progression do X actually there's that XX data, then they that at look those when of presymptomatic So at you look patients you to the expectation are going within weeks? is an XX there the those -- that levels and enrolled are you be

Gary Romano

again. Yes. Good question

the based years estimate the some the would that X study that within was the now, available time patients on you in that data, progress with used we started study those ago years. as at So know, the NfL threshold

years is that's would bit use based threshold we have and be In more might -- published, quite and it on GENFI since like X come the progress along to to additional group then and of by has been symptomatic. somewhere LTD between it additional data X analysis fact, the out now looks data that a

some subjects still still these and So to one But of opted analysis the X progressed enroll. it's X the we forget, as some long symptomatic to patients we even during have subjects. primary of our to for is been as time don't of that years the years expect study these study, on in given the reasons focus have was long -- took that and now, -- it many we our

Operator

the of question with will And next Bank Alec come from Stranahan America.

Alec Stranahan

Just us. two from

indications? or to you read ALXXX, appreciate there's the this progranulin for do walk us question, sort these different the candidate through process on may second color be Maybe of that's assets And shared around from here I preclinical forward assets ADC is given bringing given INFRONT-X would your First, through on optimization new nominations. targeting, be anything the hard from just then the going the great. and additional on thought think

Gary Romano

Yes.

is think ALXXX start I So to different. the going in hand TREMX to we read-through mechanisms and that would And specific elevating probably stimulate this from this first the answer we're increase a approach about in very a TREMX TREMX are very it lysosomes signaling that your functions the there's case, Sara. is I'll because Gary. was so progranulin, effects have with microglial we the really this don't to trial believe off question -- which to trial a whereas and different way. just don't on

are us But biomarkers so serve -- optimistic we'll more even the that this in way in think would we the outcome addition there. is way say in that a the outcomes am the a again we study clear So pretty now that well measures study is that confident TREMX very used -- there's feel us a well answer. in clinical the in performed don't get we very that I I positive will very clinical there, biomarkers in definitive and much we that to read-through used a I negative have showing What we that that study.

Unknown Executive

if XXX to be Alec, XXX. the X-X and you I heard specifically And asking about your whether would question were tied right,

Gary Romano

missed sorry. I that,

Unknown Executive

Am I Alec? on correct that,

Alec Stranahan

-- is Yes, both but mean, helpful. that I

Gary Romano

I mistake, My thought yes, I heard X.X.

data less those normalizing by function mean, or risk I increase patients what can think in is I'm disease, we more stage of -- loss Alzheimer's at they're the we in sorry. that in study the These the event hypothesis disease, have is These different of and of that and different. against severe disease it deficiency could mean pathophysiology. against partial is I amount mutations stop are Alzheimer's protective Phase or that the and slow TREMX progranulin -- In Alzheimer's are FTD the progression. granulin. a Alzheimer's early suggesting cause I lifelong I protective appear of the an be study, that Okay. that progranulin our that the animal also haploinsufficiency of a that there One case the again, genetics are mechanism. increasing disease can there's of that's levels looking replacing in fair think, to in it's Yes, be look, us show so X

So they're more bit were progranulin. a negative, the that little in than where TREMX, imagine positive. one if and be certainly -- wink but about we might still But one all it's be the positive other scenarios could sense the the other could

Sara Kenkare-Mitra

Great.

your I preclinical think question was our program. ABC around

clinic can programs. and replacement goal in I'll if technology Parkinson's start program ABC and These several get we X as to of preclinical that, advanced the maybe are other you a ADPXXX-ABC, So the tau, to approaches further. be beta Certainly, more are you is said we taking those need the Besides are ABC our programs our an just to therapy ADPXXX, anti-amyloid GCase is XXXX. also press which for our IND there. different is most disease. clarity, One actively and submission is antibody is more release, target approach. advanced in progressing an we're antibody and are which ask But applying in our to we and

programs tau as the These is as mentioned. are further siRNA. The other with I X along not

if have you around designed is I'm that other modulator Reelin this questions in any to disease I a have mean, answer. and also at tau pathology block Alzheimer's and happy promote functions synaptic moment, to this, certainly, We

Operator

Matteis Stifel. from next And Paul with come will question our

Unknown Analyst

Emily on Paul. for is This

could more more bit Just Denali little those to more first platform. just selecting differences then like as and such your like talk ADPXXX, maybe like kind efforts? as a of of the highlight barrier some with a bit of maybe on a Could X about others bit your about rationale with also you Roche key specifically ask or And ADPXXX blood-brain the ABC you targets? little your platform

Sara Kenkare-Mitra

can Arnon, add. take can I that. Maybe, you

fine-tune say our think, about I get stands would firstly, ways. tunable. of you that and of technology to technology, I know, think minimizing And to I in because toolbox several safety to out approach provides tolerability. it your firstly our I is well So And ABC that Alector us it that maximize for match rigid. of both the terms that It's in that as a ADCs, our we question while versatile, an with efficacy Fc sort of potential terms you're because can cargo.Â So adaptable trying an and the you provides the think overall, not type but tunable, you whether very need need as apply with We gives antibody, fragment of also right protein, right platform in being cetera. depending type whether the Fc, very to on of affinities, very can very versatility. able of don't a et an it's of versatile or

get amyloid brain maximal brain to configuring PyrGluX as beta minimal as essential which plaque. to penetrant Now half-life, have different which also it we fully with we to well fine-tune AÎ² our most is a amyloid the is able to of allow affinity we've programs, coming Fc, the TFR, is the also optimal is ADPXXX-ABC, active firstly, believe And the a our safety been of to our sort phagocytosis ABC, X beta which technology, that of we're it targets for validated epitope, penetration. which sort epitope, us

brain is in but immunogenic. Now class Parkinson's potential stable engineered could certainly, really program in future.Â Now developing molecule. unstable be this the potential believe again, of is all ABC we GCase to penetration targeting is and are our disease. mutagenesis, GCase enable allowsÂ a is best this short-lived a potential of This which that GCase we have minimal the ADPXXX-ABC, treatment technology ADPXXX, preclinical, that. very paired the molecule our a And enzyme for all more Again, much in with natural disease. and to through Parkinson's ADPXXX-ABC combination which our active We've to also of be a and ABC the has

Operator

Tom come BTIG. Shrader The with from question will next

Thomas Shrader

like side. More on the Can you about that's this your into a on run specifically, ASO you inflammation you else thoughts I'm versus I are When think took fRNA can maybe the there differentiated talk ASOs you that about everyone buildup? afraid. shuttle, little problems the and of models And approach? good And if why any bit almost is some to preclinical will have for ASOs? use a know decision protein approach?

Arnon Rosenthal

now It is. moving X a it sort seems we'll fRNAs ASO. as if yes, seems the testing are as field fewer mean better have good we but side if so, the of it to next know how from is activity, I in effects, it better on-target or months stability fRNA and

side there by-side at look the the of against of potent is for the more you are example, tau, literature, compare indications that in you If fRNA, target. efficacy sort fRNA blocking versus ASO

seems well some it field, this as safety see as just we'll are technologies So advantages. are the an nucleic is right, better. evolving acid efficacy you But X of which there advantage is that and

Thomas Shrader

follow-up. be see have technology for place Do deal? the funding? out-licensing you they and companies for Is for some M&A we piece technology non-dilutive as another some looking quick sort a of want? good this big Or A your you of should most something that do some as

Arnon Rosenthal

be technologies I good of sort is few that engaged of mature and the companies with to sort or blood and most barrier going actually quite already mean multiple the still companies technology are companies with expensive. there are mean technologies seeking. a are blood barrier and either of I of are sort

again, sort I could therapeutics, think enzyme convenience conceptually And that needle adverse of delivery improve of optimize have conceptually interest subcutaneous though X technology. mature really case a technology. the that that in the of for of utilized X could from really it I technology ARIA-like efficacy disease, sort see only eliminate even lot think the there even it of of acid or Alzheimer's to thread And think possibly interest not therapy, a and and antibody safety lot easy. So reduce of in is the therapy, it effects.Â So think a to there like interest, is is I actually is replacement in it And technology. simple, there are I nucleic be intravenous our the or and can because lot between companies conceptually, we this inbound so

technology. of the So demand still, there I lot think, is for a

Operator

TD with Werber next The Cowen. from Yaron question comes

Yaron Werber

Great. you can data sense, follow how on see as going a maybe we're a remind at point Or you endpoint you powered? give I the question symptomatic to do remind to looking going you're think by just INFRONT-X just it's in going primary patients, And the us us had us are that's fully to mature onwards? continue data? be that that year-end, to the up also at

Gary Romano

Ron. questions. Thanks, Good

disease detect we proportionality assumptions progression to expect, And and to XX% dropouts that we the slowing we XX% will at a be if regard progression. we that, and So the if slowing approximately our end hold expect stuff, of design XX% have positive study with observe p-value. study, of of a which power disease a

So I the question hope that about power. answers your

your was? The second part of question

Yaron Werber

data all together. be Whether to going it's the

Gary Romano

right. I'm Yes, Yes. sorry,

long-term patients as all be So all on this from long participants, of we'll participants, now years looking weeks as mentioned be XX extension X data also had as plus the of earlier, data data. at, years. will of extension in that we've data X the will all be for It a on I long-term which

Yaron Werber

supporting well? biomarkers And also as

Gary Romano

Yes.

imaging in agreed breakthrough So into of lean our year it endpoints, could that primary middle meeting that the we clinical changes primary levels, data. potentially a those a I'll evidence. and clinical last agreed supportive should can we changes case discussed that we felt both very as status, we or progranulin in of that we we a considered came They fluid And biomarkers as predictive they of would remind that the be looked number with of also addition encouraging. CSF designation benefit. at would had treatment-related use to and which agreement under also confirmatory we in also to And was plasma, a FDA number And biomarkers discussed to in that where be you endpoint, the be biomarkers. clinical of addition made we

wrapping very to disease we kind chance. of that think rare this up, both the I feeling of and So gives FDA is rare, And where look at no optimistic good a treatments, there's biomarkers. totality outcomes data us and that are the other all going this in that clinical

disappoints, for a other supportive a plan. backup off, first we're potentially the full primary going approval the endpoint have the some data endpoint if the a lot CDR. that planning We primary us of give be reason, based to I for are unexpectedly, think could But -- of

Operator

next from Blair. the come Schram Sarah And question will with William

Sarah Schram

does Can AÎ² bit targeting just approved also you're us epitopes TFR that remind And A-beta you to specifically So and which some that a of preclinical kind as with different could antibodies if brain us remind brain both program. a from those the a might in pyroglutamate how you trontinemab, XXX epitope differentiation? CDXX-mediated or of well going back to the differs lead system? other little that XXX as shuttle just ones the uses a shuttle like development technology also how use

Sara Kenkare-Mitra

Yes.

ADPXXX if targets firstly, and of the which I trontinemab your part in part -- versus your you So similar to -- I AÎ² our could mean, donanemab the question, repeat molecule the of Sarah? to the region let's of second amyloid targets epitope, N-terminal --[indiscernible] the PyrGluX is the and question program, second beta think epitope actually you sorry, go

Sarah Schram

sure. Yes,

targeting So different of plaque differentiation how in might lead to terms the like species? potentially different epitopes

Sara Kenkare-Mitra

Yes. because I it has see that be naked effective. the -- way a that epitope, epitope, PyrGluX a mean I we which are to AÎ² targeting the as think be we antibody certainly, validated is is demonstrated the

wonderful. that's so And

gantenerumab based clinic. a trontinemab the molecule is not know, effective naked you the shuttle-enabled molecule. in molecule, As is The was --

have TFR. we said, for in And -- so we using in really well And more I fully Fc. addition, active construct that to importantly, I then think our fine-tuned as bodes ADC our AÎ² PyrGluX a and epitope affinity a

your think of this are one for are questions I we molecule. and was, TFR, using we

it reductions penetration. of to to to safety affinity optimal the sort and minimal RBC configured half-life optimize have and have brain We TFR

Operator

with Sam the [Operator Instructions] comes Lee And from Mizuho. question next

Graig Suvannavejh

couple This is Graig our A Suvannavejh. on end.

can how design you please you versus competitor in efficacy? offer and may FTD, programs are other enriched think remind that the generally show contrast why in and programs? for also more can optimize development, optimal the chance INFRONT-X, trial your in to natalizumab programs there you best an patients And the knowing approach several give For us to success compare of the and yourself clinical therapeutic option you've to compared when order

Gary Romano

part to there's noise of going because with over first coming lot the ask repeat Yes. you. a question to I'm to have background the of you

sorry I'm about So that.

Graig Suvannavejh

Sure.

can natalizumab contrast patients just optimize repeating that the second Just chance differentiating and design and and first the the trial then more just best to the just question remind therapeutic approach And question the to competitive you factors development, for might of the why an the offer like with of FTD, you in how get compare efficacy? optimal landscape the like there generally, can INFRONT-X, enriched regard success remind like for for us programs you've several to clinical are us of asset option? knowing show

Gary Romano

Thanks. Yes.

So thank that. you for

granulin There are over there. to where because So of this, terms difficult eventually patients, general were symptomatic there, effects. Portugal, as -- -- Italy subjects. founder there -- the when this these et and just and where said, in with a just patients They're while underdiagnosis in genetic other we sites, to went were also with in countries there we enriching, FTD there enroll, out patients XXX testing. -- were. of We I is started really able relationships We lot and mean find. of built different looked are in wasn't we pockets and we they're of the I cetera,

they time the plan execution trial to design, changed. not symptomatic In analyze really presymptomatics was the When -- described. of and trial that very subjects is the And on a the progress that. decided at started, of terms never the reviewed really trial greater don't the one with I was this design reason of was primary has that we -- both that We mentioned not optimistically trial there both reasons quickly. in a pleased time. collected they sensitivity we'll we still they learned we and study. in really also somewhat EMA, the those progression And the in -- found things the observational and were And very that earlier, that data focus symptomatic being the I the with studies, same GENFI variability as because few we One more doing a over the that and FTD, enrolling earlier, presymptomatics when that, mentioned as analysis. at we for actually look the is in to FDA we analysis was the were presymptomatics were

if of of biomarkers changes We shown of function. how our saw always that progranulin what increases normalization on you you we lysosomal accumulation. of is approach blocking on of normalization X back terms And saw We does biomarkers, NfL do our a saw In -- of differentiate Phase And slowing sortilin volumetric a also imaging that we number receptor others, levels in to a bring range. GFAP. we've the see inflammatory that, mechanism by from do our study normal this biomarkers both MRI.

propensity-matched So to study, the comparison baseline our subjects a by did -- X and to up progression and the beyond we that, XX%. of a in disease showed GENX slowing from propensity-matched of patients study Phase that

a terms it's we is delivering or therapy -- of think directly, an having that too little potential. progranulin levels there's think the believe increasing I we in and with a say. functions, to So other those we reasons, about them. protein it we for many I pathophysiology. can't I nervous when all the our get gene on effect -- this but the approach mean may that very normal, always we soon Progranulin above is whether think a the be well protein normalizes approaches, it's ubiquitous

of Phase time or months we So I or better readout they're away study, think some But a with X and on are more approaches as said, -- quite far we'll other more I behind. know from pretty we're our less are optimistic. is we're effective. I whether whether these mean

Operator

back like to closing at questions now I call to further would no time. remarks. this turn show over I Marc for the

Marc Grasso

Thank you, operator.

week TD March the XXXX XXXX we week And next time Forum I'd Thank there looking including the forward CNS X for upcoming we're Conference you again Virtual to now Stifel's Leerink's be Biopharma your Global we'll and Miami. XX on also call. attention, end we to today's XX. there. and that conclude share will will following Boston, just Before Annual March in in we'll Cowen's like March conferences, a number on participating of Conference call, in be Healthcare conference Alector be XXth we

Operator

today's This participating. conference you. call. you for Thank Thank concludes

You may now disconnect.

Alector (ALEC) 26 Feb 252024 Q4 Earnings call transcript