ALEC - Earnings call transcript Q2 2024

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Operator

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

Katie Hogan

Thank you, operator, and hello, everyone. Earlier this afternoon, we released our financial results for the second quarter 2024. available filed website Exchange with afternoon. is our www.alector.com, Commission release was XX-Q the press on at our and this The Securities and

we'll that me and of a remarks, call a of Research Arnon this Development; Dr. webcast, Arnon Arnon? our to statements. moment turn for statement are during Dr. encourage Joining formal forward-looking to Chief our Executive filings we'll Chief Kenkare-Mitra, Grasso, and call information. I for the Rosenthal, Medical Chief Romano, like SEC also and disclosure Officer. After Officer; more Sara Head contains to the be Co-Founder the on to you would number Marc call making our like Q&A. CEO; Dr. Officer. Please to and and President Gary the we on Dr. open note over review take Rosenthal, call, our I'd which review today forward-looking slide Financial now

Arnon Rosenthal

Katie. Good by highlighting Thank stage start you half the our initiatives during to invite conference key of discuss I'll afternoon, first our programs. Gary appreciate you, later Then today. Alector's I'll call everyone. clinical We XXXX. joining

progress Brain we will blood-brain we share achieved with update have on Alector an provide will Sara technology platform. Next, and results Carrier, outlook. milestone the versatile proprietary Mark our believe barrier Afterwards, our financial

the a we of for XXXX, pipeline to setting advancing are committed half remain first the During period stage ahead. maturing and transformative our

the a enhance current the brain in July. neurodegenerative TREMX INVOKE-X protect play that INVOKE-X Specifically, approach International agonist of for in to our with immuno-neurology Alzheimer's in of multiple and and Alzheimer's clinical Today, compared we the that confirm the an activate potentially QX. reported beneficial will role TREMX readout from ALXXX offering in the disease, ALXXX enables Phase Association healthy continue target patient to Alzheimer's an add-on a leverages trial therapy advantage diseases. This efficacy prepare candidate Conference expected microglia of microglia with characteristics setting effect characteristics mechanisms activating the healthy of II early anti-amyloids. trial data to to advanced most against baseline for the aims in and potential signaling ALXXX the at development disease. monotherapy representative is therapies or proteins. ALXXX worldwide study testing population we TREMX the These individual as discuss misfolded that

We study, and imaging to design our will INVOKE-X also all into readouts extension trial trial, close and for analysis. clinical which our trial long-term of were common disease [indiscernible] delve statistical the the the designed multiple biomarkers and strengthen

Additionally, latozinemab to our February FTD readout GRN what Gary share for granted In XXXX, data like. FDA limitation. the treatment breakthrough will the with the look successful therapy potential on thoughts of designation

to a of is a breakthrough that level The this the recall provided You may on antibody support potential our latozinemab immune may that has increased designation key additional clarity for regulatory by with we submission. on how monoclonal the the protein interactions progranulin path have FDA biomarkers now And program. opportunity elevates sortilin. regulatory blocking the

We will call. feedback this details FDA today's provide on during more

dementia costs in trial the all we combining penetration reducing all indications. Furthermore, turn call past. At with to delivery implicated of agents year. in strive progranulin PROGRESS-AD to ahead, suitable relic are latozinemab, diseases. To June, indications. XXXX delivery goal we represents disease in for therapeutic where offers dosing the early ABC time, temporal The with candidates for ALXXX these introduced Gary. for pharmacodynamic broader other initiated drug Carrier, diseases of summarize, of first-in-class III our Phase a address specifics Alzheimer's share to in trial the efficacy By late the are with disorders targeting to in patient with level, distinct and the and capabilities Like technology of and of doses Looking science the this we Phase ABC, outcomes. for technology, readouts genetic our from of innovative Enrollment disease, a global degenerative continue but data platform. Brain II XXXX, brain blood-brain believe on ALXXX greater genetically over front soon. track Alzheimer's degenerative Alector significant we that pathways for and in continues INFRONT-X challenges pharmacokinetics pivotal and of early improving we proprietary best-in-class drug plan this more lower ABC we advancement world introduction emerging and degenerative early I'll at advancing a a barrier profile and clinical validated elevates enhances continue

Gary Romano

I'm begin with ALXXX. provide our stage insights Thank later further our pleased you, and I'll into Arnon. focusing to on ALXXX advancements portfolio, clinical progranulin our with programs.

randomized, to robust our up evaluating with reminder, common a XXXX ALXXX, of Association with increased double-blind, As This or a trial, was study, ongoing AAIC fully II XX XXX characteristics Conference, baseline September doses close INVOKE-X is which the enrolled ALXXX Alector which trial International for treatment in X includes placebo-controlled, in Alzheimer's microglial participants target I Phase early weeks signaling presented Alzheimer's and disease. participant study. At in engagement INVOKE-X. demonstrated of our last Phase week,

testing cohorts. TREMX milestone participants impairment dementia early clinical diagnosis confirm disease clinical our baseline of The for intended which aims important II Phase population and due As trial, assessments aligning Alzheimer's XXX.X an Alzheimer's while global centaloid in first-in-class Alzheimer's and was safety enrollment to amyloid XX% to with may of evaluate the mild efficacy enrollment the Alzheimer's of XX% of This due participants ALXXX for the and mean with disease progression for a level participants. Notably, early baseline disease. disease slow mild of expectations Arnon that with this participants the disease. Alzheimer's to mentioned, assessments of marks the cognitive data hypothesis of agonist demonstrated

the the our statistical long-term outcome INVOKE-X readout The data our CDR XXXX. Today, like approach, the in is for trial's the to of measures, track Sum quarter extension expected study on are of outcomes. trial Boxes. outcome fourth primary analysis and the We describe clinical I'd

robust are also assessments, effects ADCS-ADL-MCI or will also target package, treatment biomarker outcome and levels We XX from soluble effects treatment trial will deliver the the derive engagement, Rating be including measuring effects by secondary iADRS. which clinical This and TREMX. integrated treatment Alzheimer's a ADAS-Cog engagement Scale, and assessing on of on pathophysiology. Target we on Alzheimer's effects on CSF microglia functional will collecting assessed treatment

highest reductions on be microglial that phagocytotic RN, changes at SPPX recall IL-X of assessed and measuring study volunteer levels CSF Treatment signaling soluble will following saw of doses, and activity healthy our from doses. including by in effects You reflects proliferation, will survival we I exceeding XX% dose-dependent microglia. our in TREMX, Phase which single CSFXR, baseline

reported, on each we treatment pathways previously Phase saw of after study. these in As single effects doses I our

on exploring of and be plasma Treatment microglial as in TAU both as pathophysiology A-beta effects Alzheimer's [indiscernible] assessments with We changes assessed Tau-PET. CSF and amyloid-PET well subtypes. treatment-related also are will biomarkers, with and

will last proportional continue they to the weeks a weeks to data we will weeks. Efficacy We invited enables be all include astrogliosis, This closed neuroinflammation, of use of the health XX statistical us average design had until we have MMRM, up by size. have treatment provided power, and treatment will study data enrolled out across If treatment. will have biomarkers the for analysis the participants join effect. of significance from trial. completes anti-amyloid this or at -- weeks approach use potentially in in design drug to and XX common trial extension participants enabling calculated before also neurodegeneration. The who all synaptic may We remain of INVOKE-X in data which have participants effects intend participant This visits. observed which study Phase a as utilizes a disease in our follow-up double-blind the double-blind Earlier effect effect long-term reach proportional include progression common our served additional means the the of to II post-baseline also treatment antibodies, approach study. to treatment XX comparable us multiple for XX are participants a collected a increases slows specifically maximum closed a to significant to smaller

participants the the have who long-term in data. INVOKE-X or dose lower treatment at LTE LTE XX% collection imaging This enrolled who assessing amyloid-related abnormalities placebo MRI to than will of starting active resembling on assignment, eligible LTE currently a the of also have meaningful treatment-emergent from the trial titration the also will to dose findings, remains effects intended participants LTE study. In ARIA. from titration MRI ongoing this Thus in slower roll and lower an study, dose safety titration extension over a is titration using biomarker clinical of Participants initial a resemble for used findings the ongoing treatment far, blinded severity of of the approximately allowing treatment that study and the was study is in period. Our dose trial a underway for INVOKE-X in effects treatment-related completed the observed explore we are double-blind and begin schedule. This ARIA. double-blind modified slower on to at the

and started dose dosing the per weeks trial. months milligrams in every X during double-blind kilogram the first INVOKE-X context, the escalation XX at occurred For trial, of X

additive maintenance amyloid-targeted readouts. With of its tolerance. Thus, against mechanism disease reduce functional restoration Our restoration that neurodegenerative with our used to complementary of to will This trial and signaling, ALXXX disease the as biomarker therapeutic may and the the action, demonstrated treatment as or clearance a for INVOKE-X increase will therapy also we but such demonstrate misfolded and broad combination and that proteins, slowing support functions as of standalone repair of amyloid, ALXXX such vulnerability TREMX Alzheimer's microglial demonstrate barrier with that expect and and will is be of effects of brain's ALXXX hypothesis to leading by includes disease. ALXXX to effects on healthy the oligodendrocyte the a that protect when clinical, microglial expect synaptic the and vasculature treatment-related in function immune of microglia neurodegenerative amplify also as brain effective of therapeutics. we combination astrocyte beneficial regulation is progression maintenance trial by broader synergistic of and blood INVOKE-X expectation of connections, function, the brain the of

antibodies. have of also anti-amyloid We may that manifest in differently seen we benefits trials the treatment from believe ALXXX what of

with necessary biomarker threshold, may to regard efficacy signal clearance. action relevant condition cerebral antibodies goes appears ] [ to to example, be to for which of for responses, the anti-amyloid beyond XX amyloid not lowering be mechanism amyloid-PET For centoid this clinical that a

Alzheimer's preclinical for to thus, healthy dementia. or stages of pathophysiological microglia through And ranging to Additionally, potential TAU, to may disease intervention may specific disease. we be therapeutics effects limited broader. not beneficial do benefit expect have patients disease Unlike from stages the targeting optimal advanced of amyloid be ALXXX

Turning would FDA for now clinical BLA interaction we the indicated In on to with the levels license feedback GSK our evidence, cerebrospinal recent latozinemab. a programs. on has of consider potential confirmatory FDA, and future that The and it the Type potential as progranulin B application latozinemab, progranulin effects plasma supplementing review. effects fluid the of latozinemab received pending biologics

path clinical neurodegeneration approval confident that provide also be disease-relevant agency considered aligned also and review. with evidence the as latozinemab. for of atrophy. Based supportive biomarkers a could primary imaging potential remain and subject include feedback, the may the on that evidence, biomarkers biomarkers endpoint astrocyte and on These efficacy, We the function, fluid we to clinical of FDA brain including BLA totality to of

to We prevalent believe pivotal late XXXX these productive II XXXX. In more III disease. potential Alzheimer's interactions are clinical of supporting the for our strategy in spectrum, progranulin across GSK Alzheimer's genetic providing readout enrollment data the Alzheimer's between AAIC, parallel, Phase that [indiscernible] as in evidence data Alzheimer's on potential ALXXX be the an of Parkinson's treatment for continues early increases disease. neurodegenerative Following may levels demonstrate increased and co-developing we FDA, PROGRESS-AD early disease Phase consistent or trial progranulin for and These risk partner findings GSK presented compelling the therapeutic increasing a hypothesis track disease levels with disease. At poster for progranulin of the ALXXX gene levels diseases, INFRONT-X Alzheimer's treat are the reduced we for including a progranulin effective Global disease. therapeutic treatment highlighting and associations causal

for therapies dedicated and over our this these updates time, programs, forward remain clinical Sara I'll we Brain harnessing with advance transformative Alector expertise diseases. At turn our to progress Carrier. drive As scientific the to for neurodegenerative it on to we

Sara Kenkare-Mitra

proprietary dedicated you, versatile we event Alector developing have Thank In ABC. barrier we virtual several Gary. Brain June, Alector, At Carrier, technology Alector highlighting a technology known platform. R&D to held Brain years our as blood-brain our Carrier

in drug improving doses as protein our We pipeline tool preclinical pipeline lower are enables our requiring distribution, novel leveraging the include and requiring brain to to ABC diseases antibody pipeline delivery. expand replacement. enhances subcutaneous enzyme vital us neurodegenerative or development. ABC novel and our enabling It platform potentially a by

to development focused Additionally, CDXX system. transferrin proteins we Having antigrowth cargoes. validated targets, the complexes brain of known as has safety. surface. Both targets and endolysosomal delivers on and its technology X to targets enabled effective across target in heavy are transport with tailor of system, well-known efficacy the iron antibodies our receptors receptor cargoes, multiple ABC transport also to second-generation been us TfR pipeline amino drugs the swiftly delivery to the cargo Notably, TfR, chain we leveraging our endothelial receptor validated optimizing within therapeutic and targets. allows cargo acid while towards transporting key multiple CDXX cells including nervous heavy receptor a functional and chain. uptake primarily ABC central cell

with its versatility, distinguished is approach Our tunability ABC translatability. by and

to while Our our application neurodegenerative cargoes, across and ABC receptors technology with ensuring to diverse different a diseases. of core efficacy utilizing is Tunability to varying barrier technology, accommodate precisely of can therapeutic safety. affinities cargoes antibodies from panel wide enhancing nucleic range to thus acids, optimizing binders a its match is versatile blood-brain

to clinical translatability for advancing ultimately the can to ABC's at in of in the Additionally, innovative to our trials, commitment diseases brain, is be neurodegenerative delivery preclinical clinical key underscore to from drug efficient capabilities to feature path delivery challenges by Alector's and neurodegenerative of us disease overcoming positioning therapies accelerating treatments enabling important species drug a patients. development. forefront

our updates reinforcing as they Looking programs frontiers dedication health. brain ahead, pioneering to we on progress, to provide will in continue ABC new our

update milestone the on and I'll outlook. over financial results for call Marc an Now turn to our

Marc Grasso

quarter Thank XXXX in today. you, results market second release press financial that the Sara. closed We made after summarized we our the available

we our of a remain $XXX.X position First, with second I'll We that objectives. to the ended highlight strategic cash XXXX execute well quarter of million. funded strong

readout Phase the cash runway including II robust future financial for Our preparedness of ALXXX data with the extends readout. Phase the runway strength approximately readout financial data year XXXX, and INVOKE-X INFRONT-X coverage the key growth latozinemab, for through the completion INFRONT-X through III demonstrating beyond milestones, extending and a pivotal

financial XXXX guidance. Turning now to

and We between to collaboration revenue million. continue $XX to be anticipate million $XX

guidance $XXX We have tightened million. million to and between our total $XXX research and be development

our total general administrative reiterated have $XX $XX to million. guidance between be and and We million

look our We are well for may capitalized stage open portfolio. line for the robust cash position concludes and today's additional remain progress and focused later We for on Operator, comments the prepared we now updates call. to work. That our providing you advancing forward questions. as ABC our

Operator

question [Operator comes from Paul with first Instructions] Matteis our Stifel. And

Julian Pino

Julian is for This on Paul.

the also weeks the participants in you on this do mind absence latozinemab, predicting CSF from to long-term can me. mean what proportion extension exactly couple evidence and does TREMX, seems group just to me, clinical a study? And homozygotes it's And weeks unusual consider confirmatory were do in a for biomarker in PGRN XX what benefit. also reminding of readout? placebo that would be you your rolling plasma over it clarify the expect XX to that data So little benefit of confirmatory? then data. guess just Usually, APOEX from On as everybody I on in and upcoming you to clinical of FDA a out clinical between -- somewhere biomarkers and plan as you it

there. color would be additional helpful any So really

Gary Romano

is that. I can This Gary. take

first different have the your at the do was patients time how is question points. around think I -- So we what TREMX, many

assignment, blinded so safety, to be later, patients which will later, XX we biomarkers outcomes, fact XXX, remind on treatment that X of weeks expect our remains XX years on be the have collect and X minimum patients, will around and and treatment. And be we'll And those, all we'll then data able of all months is which about but treatment. still of on up LTE original X clinical weeks of complete also given treatment to half of the XX means to and -- just data. want of I have about blindedness a weeks then you have weeks we'll XX completers, -- X/X So have will all months that we'll data of the to meaningful that the and that

was the -- discontinued homozygotes. is second placebo study question which changes stopped saw the of I anymore. and not we about we we the rollover MRI homozygotes. Your at population -- because group, the homozygotes were the about think, LTE, are rolling the in does ARIA APOEX study APOEX more like study APOE them rest early over which of include in current No, enrollment the They resembling severe

which -- that the is -- region of discussed biomarkers what we if clinical some means the these were this last And on confirmatory volumetric the with CDR confirmatory we FTLD in result -- be measure. that mean the of about think was your would would CDR positive that say, benefit. they the that modules behavior you what the it for not outcome biomarkers that about a clinical evidence FTD in FTD the clinical be clinically should -- does clinical -- measure. It they NFL -- -- measure, -- a added CDR surrogates language if So additional It effects -- is to for latozinemab, that of clinical effect does and clinical have. primary on mean context have rolling see specifics use, biomarkers X it's outcome be the volumetric not on evidence that outcome LTE. And and I be would we are it over we the it MRI, biomarkers, a be difficulties, that basically -- patients including which NAC, means GFAP question would interest to in some would and imaging they would fluid and the

said, based I some predominantly. FTD we see these and also in to FDA, mean with that on accelerated that similarities. this prognostic NFL here tofersen based was drugs study, those fully the likewise, in a biomarkers And approved discussion biomarkers, are are that there similarities However, are of same approval on about had many cognizant we like an this we

we was don't some if that Phase be -- saw a data, so did the were and expect effects, approach. I on promising, we an very could backup if outcome, strategy directional reason, which if if but approval we we And are expect but this, especially II our by accelerated for disappointed think we based that we -- mean, clinical

We have that yet, not we by but biomarkers FDA their encouraged discussed we're that suggested. of think with that endorsement -- the I their

Operator

next And Alec Stranahan our with from comes Bank of question America.

Unknown Analyst

we This in be is question How INVOKE-X. a about on a of ] I efficacy? [ thinking Alec. should study long-term had for INVOKE-X in patients and Susan extension for about terms enrolling tolerability

Gary Romano

Thank Yes. Susan. you,

how in and pleased to very patients to we eligible and LTT over safety? so and Well, tell efficacy up that's XX% the of have of enrolling been the by So most have fact point, patients patients now first, decided we're that by that far, do are around have I LTE. the to in do you that about think this to roll

be have -- we we completed know. actually terms LTE. efficacy, don't in will of Some the And

looked we and at efficacy. haven't blinded, still are We

up detail. the data. With that some at to later in -- that analysis year and the of the really as the signal the be any described been lot have with is when small which have we've time in regard will antibody. reactions, And signals data significant lock our to database LTE the We to will time unexpected number resembles haven't infusion ARIA, which sensitivity a collected of look safety also there this monoclonal not a include we a be been beyond MRI of safety, that

Operator

Hung Our next with from Jeffrey Stanley. question comes Morgan

Michael Riad

on Michael Riad Hung. is Jeff This for

INVOKE to the Going back baseline data.

capture around cognitive X/X But mild you had and that you like also saw between impairment baseline. whether XXX dementia. able So to mild differed of Are PET centroids X/X mean had say cognitive a amyloid Is something of a it's that resolved? terms dementia? in versus impairment populations also of And population. get And the a trial full X total have will that the I not follow-up.

Gary Romano

Yes.

the levels. down mild we tell So -- We don't I by [indiscernible] that. regarding the -- you broken don't I have I the AD don't data have just MCI and can't looked we me asking. question? didn't other capture. the aggregate did question -- follow catch what miss your the see, I full let at didn't you're And [indiscernible] levels. I about quite I

Michael Riad

meant PET just in XXX? just be amyloid baseline was it the Sorry I whole is something -- and captured like patients, trial low enrolled about would the I mid-XXXs had like that -- like more or mean the thought that. like through the population like

Gary Romano

Yes.

So at baseline is this characteristics. the --

the what that therefore, on of was patients -- scan. this baseline and So used a for PET inclusion amyloid the was we was had patients reported PET amyloid out had number where that

that which So had we that everyorne everyone point for would Yes. up because include to -- that which enrolled. fully with data

the question. hope this -- answers I that's your So

Michael Riad

-- Yes. Like for sort reduction follow-up. is think you expectations the No, a of that's would quick INVOKE? what in And [indiscernible] as very What helpful. just then follow-on.

Gary Romano

Yes, good that's question. a

since be we MRI to amyloid. resembles finding We prolong that surprised wouldn't this see in manner. ARIA every So

And ALXXX by during after are are antibodies. misfolded clearing tagged also they we wouldn't -- fact anti-amyloid also is involved amyloid given restore microglia conditions in and involved this and amyloid removal under in function. in compacting know believe a that be we We microglial regular that that proteins that will get and -- also of the other surprised

doesn't So would see it we us surprise that that.

anti-amyloid see And downstream know and than In our brain the mechanism would microglia presentation, as microglial by different don't is we I it you I very has we this is We a looked. think we tell preserve important But truly health. by really expectation, restoring terms in mechanisms many restoring -- which antibodies. are -- -- point. we -- -- different we're described yet yet of haven't a don't is this function, this that we

XX us. agent. Therefore, not if necessary an level reach amyloid, do a do that amyloid-lowering the So the we clinical not intended we because going centoid to this to be -- really not or to condition for going antibodies, be based mechanism. just that seems is don't make really clearance, amyloid we're anti-amyloid decision goes bother for this that's efficacy the to this on not And beyond a

Operator

question with Cantor And from our comes next Fitzgerald. Stavropoulos Pete

Unknown Analyst

This Samantha on the is [ Pete. for ] line

protocol you idea us regarding outline to safe the program an have into assume be and observations first expect release later-stage moving quarter? to for observations? And a this been regarding see driven? you bar it finally, give could any is of can study? REO-like TREMX, theoretical clear the safety CDXX? tissues Or biomarker that what efficacy? Has CDXX you it the data be been What's a new any describe minimized ABC expressed And feedback to do next forward associated where targeting on or types cell technology, to the driving need for is Firstly, risks due Will for what signal these the with of clinical changes? there KOL monitoring, might

Gary Romano

Thanks, Samantha. questions. Good Thanks. Okay.

expect safety, biomarkers. release but So what what in press outcomes clinical We're will press in what also to we'll a the terms of going -- terms and not expect data to the release data typical top report. line you we're primary include, include have going and that of relevant only to -- do to on going we're

a combination making and we readouts is based of this As biomarkers. and I of functional biomarker said, on clinical, a have we were -- lots decision

right? we are decision, we that those top at consistency of seeing the out out to that be what the a the report physiology disease press with -- -- -- and that's included. making we're the biomarkers to will line. And release, slowing there out just the of some bar and just same to the advance? at relevant biomarker to showing outcomes intend what clinical Alzheimer's all on combination are reporting that that's it, I on those of do. particularly is across It's of because not -- be those day, all We'll -- progression end said So

measure slowing -- going about effects see we do progression directional of biomarker just the excited if see compound. And a don't, directional outcome consistent if clinical -- So win. very that's be us, effects p-value advance it's be disease not to or hitting that's there, that's we we'll for a on that and that showing with to

We You we it MRI at the Well, MRI -- surveillance, said, know. the APOEX, also we our also the see before severity ARIA. anti-amyloid dose titration dropped as our it amyloid know antibody it's slowly the under as the actually, often they X we know every after low weeks And do that they do but I we incidents, they doing sure, each we've that it think we're that and doing Is months we observed in can come trials what to as go? And was you then -- added we when about first then it less were I asked surveillance. -- for minimized? is the tell X the after which it extension, long-term is likely akin I current titrating could of going signal. the of ARIA, don't the been severity added increased know Is III you're us that find ARIA program amount for of what that. ARIA. Lilly, way, and We ARIA that X saw weeks when a that that looking to more ARIA. radiographic of you're ARIA is increases exploring in things Phase in found they've incidence and the for ARIA don't lower that study is can whether their one dose the because every reduced. reported starting in reduce -- addition, the that also for surveillance, surveillance, donanemab actually XX% down higher in ARIA saw Also Meaning date by they they more minimized? at population. more has that,

I -- We're to the of what says, learn amyloid mechanism. I'm think this study. And -- to be mechanism -- well this the we what hope does last -- question conservative. that related the as yes. talking extension to does our show about about I'm That mechanism, was very So to long-term has what we clearance. well, Everyone that in was this kind sorry,

wait but for I till a CDXX I And that's I'll a the good question think see data, there's Sara. I bet. So think

Arnon Rosenthal

Yes, I --

Sara Kenkare-Mitra

Yes. Thank you.

Arnon Rosenthal

to Yes, to and the human little tissues plus the pancreas, skin. genitalia CDXX protein according of -- kidney, the bit sort a the in in in as in the in express endocrine

expressed will cells, in In if neurons So using tissue. of levels astrocyte and the looking any which is in lower -- be endothelial in blood-and-barrier adverse yes, supporter transport. brain, outside enable this and microglia the there's in effects a we CDXX it higher as

Operator

TD Werber question Yaron with comes next Cowen. from Our

Brendan Smith

Actually, when quick was is to just on one to QX on you and out would This AbbVie if do the expect that in the a what -- maybe Brendan opt-in -- QX? kind then potential comes data is programs And And to just that at you just book happen? there? expect after good, maybe book the expect you timing II Phase that. in might deeper first, of know payment. Can let enter for us factors remind potentially data think the there might which obviously, Are report would when wondering that the [indiscernible] us looking just you clinics pipeline, how other you gating the you Yaron. just

Gary Romano

the Yes. questions, Brendan. Thanks for

the recall, option you of the that's as option, So end as it their to payment million relates II. the $XXX at AbbVie, at with Phase

of advanced. we're early package have XX the payment QX with to would the opting And is package year. and so of decide earlier the the they're that second which aligned that then package acceptance end with of is the of QX, concept they most programs study which So our the that our be both question sharing portfolio we days, them in, of year, towards will to currently. And be around put their your in expectation this at plan this them around QX if advancing end and

of and number you as a year years. forward have undisclosed We around we providing number a disclosed programs the and in next progresses of to programs look that coming updates portfolio

this made specifically for one to haven't is as us. a at advancing We time statement which

Operator

question next from comes Barclays. Carter our And Gould with

Carter L. Gould

this, sounds it in to the of Type want is endpoint, primary of a that of clear I that of sounds off, equivocal regulatory Is this on guess data I on that of affirmation INVOKE-X, first strategy characterization? in guess, a your what like message of meeting. sort coming then potentially path be forward. And represent out and contingency way, program? And B any fair there'll strategy confidence out just on a primary. follow evolution data like context being separation I an It's be but appreciating of on to the does a in it the coming exactly up your

we their AbbVie read-through as And I guess, think to a moving I you of of necessarily that, expect deprioritize we again, XXX? sort did if fair A-beta or there's And recently sort get about decision discontinue and view they is forward that the program. their commitment process, So products alongside any guess do shouldn't the we when characterization How that? data. any that on

Marc Grasso

the question. take Maybe latter Gary, the you I'll first take X.

Gary Romano

Yes, yes, is sure. No, your Thanks this really a for question. not strategy. contingency

biomarkers. that committed approval and outcomes we full outcomes, and optimistic the the can we're get a are We secondary primary on based

the one were biomarkers? effects, are with. we these see could begin can were to if these at. We biomarkers that really to the -- that we biomarkers we that look felt were There's questions biomarkers lot are ones are of proposed a prognostic that Our

So symptoms, if changes MRI you see or before you GFAP volumetric in see changes symptoms. there even are even before in NFL

single So rare know a in clinical prognostic advance but see whether outcome. it's study. This trajectories you would even should these a changes changes the of symptoms is surrogate it support that yet biomarker. If that because these we disease. biomarkers don't a in clinical of is It's the marker, a we imagine

So XXX study. it's small patients. a It's relatively

good looking biomarkers And this whatever, of best maybe enough were full a we have or important thought are And to way committed questions these but we show devise didn't in SAP, relevant totality benefit. that think If we're is that so they thinking these ask. statistical to or to by about drug can are the then would approval the analysis plan based encouraged for are how our on about always a providing and We we our really information. very differently the data.

Marc Grasso

we're question program, decision, think to the that. asking That next, answering forward programs Carter, not looking that would advancing obviously, was but so I component, to AbbVie's be second the opt-in I prior TREMX. pipeline question, And referring earlier about analyst on advance subject related Yes. were we the would -- think your a -- which the to

be in, that the that III. they the we We expect would as remind opt a and If and the be profits next in they also XX-XX me on Carter? stage III taking would share Phase And Phase advances. cost program third your question,

Carter L. Gould

AbbVie's types level, around see And narrowing A-beta read-through interest sort program some their you or do XXX? deprioritize on you all from any that's in their say could discontinue portfolio? read-through then any Again, their decision of to

Marc Grasso

Maybe see we program Yes. didn't to speculate activation they us looking role Yes. A-beta Again, that mechanism else can microglia is that they there. really the broader hard the remind with were complementary It's play. differentiation for of for the and there. what out to relative

don't I II we're AbbVie, study we there, mentioned, highlighted, we read-through with has package around, very as a data Gary our readout aligned What speculation. with say in that's and that. necessarily the see is that's Phase So concept including as but can associated the

Operator

from question BTIG. And Shrader Tom our comes with next

Thomas Shrader

They're on seen of see level, derisk you're obviously signal to here, the Have but at to if MRI you if the the us progress some AD, program you XXX. you characteristic see going update seen you've some are doesn't ARIA? It's ARIA? or entire it did interesting with if trial progranulin going --

Gary Romano

Tom, a that's Yes, question, good as always.

we involves of tell any because think, the have days derisk would Would look mean with in I it that it's the We far, we -- you study mechanism built study, haven't program? can microglia, we into the somehow... to involved, MRI study. ARIA. sense that -- seen don't we have You early signals -- see we we if that such have and action it well, any thus surveillance this have

Thomas Shrader

what Say, supposed extracellular [indiscernible] to. does it's

Gary Romano

ways, I I make that we we that about signal a miss we safety about biological anything mean, the -- seen be, Yes, far, in yet. think would so. don't suppose to I just But way I haven't looking think it on. an we're ALXXX it in encouraging eye But we sure think as I in yes, so -- same just activity. mostly some we need keep mean, to

Thomas Shrader

increasing to It a step that as is based almost sold increasing are characterization? levels progranulin an that backwards biology everything. that high that everything the fair a than fixing on broad guys lysosome rather quick, into, hoping TREMX? follows and else seems And the effect Is like is you're you real as forces TREMX

Gary Romano

to to want or I'm Arnon, you you do want happy to answer speak -- it? if do to -- you that,

Arnon Rosenthal

range of for of progranulin different also is lysosomal of but It in a a which Yes, very of component types activity. fighting but survival neurons. factor has multiple activities. activity, as chaperone, you is mechanism, It sort critical also enhances broad misfolded a enhances normal a it sort it is said, lysosomal a it's protein,

is disease think broad are multiple that less large think that different we to testing such we a these sort the for antibody, pathologies. unmet don't sufficiently it's progranulin We need, multiple to think So because -- sort that, and is we of is is or broad address now generation worth mechanisms programming example, yes, that think is mechanisms. anti-beta similar of

Operator

with William Our Blair next & comes from question Myles Company. Minter

Unknown Analyst

for You've progress. the on [ ] on Myles. got Congrats Sarah

tested those pool to dose AD patients in as how So to of the severity, be second, doses you these would the other of whether treated to And a to from now those biomarkers? patients? arm separate trials long disease decline powering do enough consider your you are relates just individually? And be And view, all including to entire measurable compare seen range function will in treated patients XX think weeks see group dosing, therapeutic baseline and in stage placebo those regarding potentially do enrolled you potentially we've seen INVOKE-X we've assumptions, that expecting in the it each your can therapeutic? remind or us characteristics

Gary Romano

great are you. Thank they questions. Well,

our therapeutic? doses greater in yes, reductions saw saw X XX%, highest where soluble we think Well, engagement, doses do low robust that. and but the dose study, in we Phase were testing TREMX. still we're in were because They than target So are lower than the they so even I all top we in that

I So that that, based it that is on be would therapeutic. -- think

pathways, -- increased increased signaling saw we saw IL-X also microglial We multiple across RN.

doses. those and we mentioned CSFXR this all think SCPX at I the call in in

those So are yes, think we that therapeutic. do potentially

dose in terms In be look And also versus placebo, doses so we overlapping their the are data. the of in fact, analysis, top but X will at PK. we will each pooling considerably

down that donanemab, we our a higher for definitely do the say. the definitely. And bit anti-amyloid at I we -- middle, but compare size saw that analysis would will on down a bit really distribution How centoid right level than it's is what part thing right pre-specified the had, the a we'll lower same patients that's Really the clinical I of so looking other to data be looked in it based in than mean, of [indiscernible], little the middle. they the the And diagnosis. antibodies?

So question we was the range of entire right. pleased right, I last that. And think were very with does dose the

that treatment this the expect clearing astrocytes restoring duration of This about supporting and -- and those the if here at synapses, is be for the by restoring barrier, right there mean blood-brain oligodendrocytes will effects design reasons one there's time, take we was would close microglial take that I happen you're common maintenance tolerance, earlier. could XX necessarily in weeks we function temporal If might the all enough. -- a could and asking is the on can't same dynamics the mechanism. So the of vasculature, of of right? I And think amyloid those expect are effects effects in potentially the longer. immune novel functions

XX should we So we XX we hope to weeks. do think that -- at weeks, something see

blinded the XX. one data double AbbVie -- after be so and reasons the study We will to -- long-term double-blind. have the to that's invest even meaningful extension assignment the of we'll out data get in that to we the really could to wanted even to double-blind, And we treatment have in after

have we'll able be see have that weeks to that. to we XX. out out that study if in those even But to be think could we to data [indiscernible] early, full possible -- and to capture it's may it's XX those the this design we'll will those that see that. of take some we -- mechanism Hopefully, the think I but of it to longer that emerging, So get effect

Operator

And question comes from Ghosh Ananda our H.C. & Wainwright next with Company.

Ananda Ghosh

a couple of have I questions.

Type one D of the is, meeting. first The course, on

you So if or open they surrogate FDA the consider itself how look program which sulfate the syndrome, surrogate takeaway, as just the going PRN be Hunter in some you where [ the like hyperfine ALS, ] encouraging consider curious, at biomarkers mentioned, example, your to FDA's might what stand forward? has biomarker, the like like Procradunin given as for been a might of tofersen biomarker

Gary Romano

a a And of been certainly, you. been how -- Thank agree and comes We're considering Yes. -- to I expect we which with are what some good more think especially to in as see see. if we have still even seem -- still -- we're rare with going that. That approval outcome that enough to have there's a more and the doesn't -- examples. gave somehow here, they approach. we they said, are when or That that good disappointed to we it biomarkers we to you you really backup diseases biomarker flexibility. changes that the there's if we be very lot clinical for a supportive measure with an but regulatory shot by I to we -- good feel full approval flexibility in so at more plan think encouraged traditional be some

it for flexibility, that for debatable. by us think patients, could if us be not full approval. encouraged but full would for So like get is we're I we better a it's It's a approval better

Ananda Ghosh

it. coming Got now pointed NFL from before tofersen, kind lot is European than A SODX-mutant actually ALS drop that case follow-up and benefit a of Conference, it's in the much in see program patients. the of well clinical see of established on the you question tofersen KOLs the at you out

a is behind in the markets you some lags have progranulin biomarkers there for benefits track are kind program, kind -- that about see of the of to the the also drop thought the key So like to thought way way you where or of your -- bar clinical progressing?

Gary Romano

Yes. you. same Yes, in true agree we And the FTD. is I with --

and but that they many we also out progression to the a levels. We and and knew data we -- them analysis. elevated fewer we before analysis, a had because our who EMA, but function were signs asymptomatic, and we it but risk because in originally to in they were why as primary loss a on variability that NFL and You proposed see find symptoms. because primary the study, in went we lot our clinical patients we -- will analyze started of the had see they FDA progranulin in focus changes include we had NFL year, including rates, at they you still last originally to That's of analysis, of and plan patients mutation the sensitivity had to they're hard to symptomatic presymptomatic for we're patients

that. So in work about -- and early patients. better in presymptomatic excited very symptomatic may work it's We even the patients we're patients, think if going the it to in

data we of -- and look clinical -- may So we whether dynamics on the at outcomes. our those changes see the in versus biomarkers when see effects NFL we'll temporal we precede that yes,

Ananda Ghosh

Got it. I the X questions TREMX. just have And on

and high The one like their Biogen TAU, both trials. first Lilly analysis TAU the has this, AD obviously is done low for

titration schedule population? a how analysis where on is ramp-up of TAU And do looking low be are So your of like and to of you have out or later ALXXX what might this TAU subgroup second kind -- in kind figure you what to do -- the at ALXXX? impacts the kind have fast you the plans for how for high in --

Gary Romano

Yes.

So -- okay.

to question the use of about Yes, -- at We're our prespecified every going we that's So TXXX every in will we TAU have patient. -- really -- definitely TAU terciles. analysis. part about

PXXX it in plasma-p-TAU doing smaller a we'll do have based also can on We've we levels. it PET TAU mostly So be markers. subset, by but

would -- with of this work a don't that whether We an disease to in of window there's some give or low-TAU us best. differential at really you us we differences more -- patients. much -- course, tell seeing the expect of the antibody, defined going see may we a with terciles. That, are we these or are look high-TAU of those will spectrum where said, seeing mid-TAU with anti-amyloid effects than would That mechanism pathophysiology across as indication to the are

second the about ramp-up. The is question

So to We're in the that was at that earlier, to could ARIA. titration roll whether increase putting and a for when -- as MRI mitigating starting titration, every was we surveillance. want in slowing we a the we that went we study, mentioned patients -- weeks lower the LTE be X the because our dose it we down in over learn And were why that I in dose. that's in

Operator

with Mizuho next Our from Graig Securities. question Suvannavejh is

Graig Suvannavejh

as Could you on that trial. your I the think have an hoping about analytical methodology taken speak approach view Earlier you're to who powering be analyzed not had may the innovative will congrats others that to apply compare the to with wanted methodology. how progress. your of with here I in someone in to It methodology their you've you how prepared increase And does seem if trial? the differences as you study, the that particular might that well-versed Alzheimer's disease. just but in INVOKE-X remarks, ask the Alzheimer's between mentioned And others

Gary Romano

Yes. Yes.

common before method we really remember in been Alzheimer's look was. as studies data, it II is we're us possibly also, the that -- treatment close all design as Phase that are used one the it in a This allows to a with I have one patients trials has analysis of MMRM, proportional allows to of outlined. it's don't you which really I we ASI, DIAN in at of used believe this it helpful and it used. study their but mentioned, that it I can and different and So sensitivity was And -- where proportional use that as particularly I method, novel using durations

it the the common I that years a should different would design and study, be of really have AbbVie make of lot started. would best study around types some we a this and it's design the readouts. -- -- is I agreed thought close We this ago So before really say to but thought explored that we it. we think for -- novel, this us, Yes, trying given have biomarker-rich others given were

sensitivity approaches, but mean, more outcome. also is primary So with our yes, this I analysis traditional we'll other do

Operator

then question from next Our Johnson comes [ Goldman ] with Sachs. Corinne

Corinne Jenkins

related amyloid Maybe the could the don't just it talk bit you -- of runway comments going but to to platform more have bit containing could understand, same I centoid is the you if but just you've a particularly the ABC reduction could little maybe clearance, you are around to guidance, expand to square on clinical degree to get mechanism, see the time little made with think around I going you a that respect effect. And activities cash within embedded frame. which then be that

Gary Romano

Yes.

So Corinne. I'll first question. Thanks. take Yes. Good one, the

think that the I neurodegenerative hypothesis pathways aging of is so is increasing of of is microglia. a number what was we have increased referring to signaling this know that And of function -- triggers population survival. disease, proliferation that with allow signaling for shift our that So microglia, TREMX and that you senescence other to microglia. We and with a going

microglia we'll active and beneficial functional and those healthy I from -- come microglia, more that amyloid including to But clearance interesting on with all microglia and the shifting it's effects by have misfolded Alzheimer's come So won't clearance that the of there's potential proteins. And usually lots that of seen comorbidities signal. are the disease. of amyloid way, ARIA-like because by focused we're repeat not that

they clear the are and amyloid, they microglia TDP-XX for would not like. clear would So selective other and alpha-synuclein

excited the so we're XX need I say centoid it, about mechanism. When why it is doesn't this think this we to So reach level.

that's amyloid. curve. data like looks now lowers think an It what antibody, plenty -- showing it does. of that I anti-amyloid for there's It where lots

show to the seeing an that studies one in benefit. I were to one seen robust. have of You've you the aducanumab, the graphs, get there. get clinical, start is mean didn't gantenerumab study there, clinical less a certain the need example data didn't you before didn't that I'm And sure quite get we of level clinical

centoid if get of mechanism but XX we mechanisms play. So have we it using. all downstream beyond mechanism are that this might amyloid level think goes looks down have these like you're This that's at you clearance, that. Yes, your to to

the of the mechanism clearance did just the see. question? amyloid of that hope this judge or we help that did amyloid that to amount I clearance, on answer going not action based we're so And --

Corinne Jenkins

really was That helpful. Yes.

Arnon Rosenthal

in A-beta the -- between A-beta can data this contain add basically can to nerve in it. the this little surrounding are even they the TREMX-dependent to manner injure neurons longer Maybe -- A-beta human I a and and the barrier a microglia can plus make I no A-beta without They form bit. that plus There removing add can a the neurons.

the you said, damasynaptic even get be damaged. the are you replacement Alzheimer's addition, abnormal. is up as There removal for A-beta can in disease, is They [ responsible So synopsis ]. ] replacement damage of XX% responsible transmission functional direct yes, [ microglia. And if to benefit mile without of are of disease. [ damaged microglia recruit can Alzheimer's neural Gary without connections neural responsible therapeutic A-beta in of for significant ] on transmission in They microglia, for miling the

translate there that activities should benefit to of pathology. a clinical lot So independent other are A-beta of

Marc Grasso

Corinne. just guidance, cash runway the on And

and X TREMX XXXX full that reiterated expected milestones this end full or of or beyond any years doesn't a our AbbVie assume opt-in Phase next year through business end of year III from FTD the we readout that's and expected readout So beyond and runway data year development. a is other

pretty -- progresses to those we portfolio. healthy going Carrier more progress. think that's it as program provide to Brain that as and We're a a strong programs relates the Alector updates So as runway position

advance what be through specifically INDs on said that programs But expect would those that would could haven't through. We that programs. you

Operator

session. for the his I now back like closing question-and-answer it remarks. this And turn concludes to to would Marc

Marc Grasso

everyone, questions. the Thanks, thoughtful for

September conferences, to York; you XXth attention the the in Global Healthcare New just Conference on Xth Thank New in H.C. number Wainwright's Xth, York. share, like Cantor's Global September Annual time York; upcoming for will participating we in of Healthcare end Conference, Conference New September we be a on today. Investment your and again including and call, Before Stanley Morgan Global I'd in

Operator

the for today's This participation conference. conclude program. you thank And your in does

You disconnect. may now

Alector (ALEC) 7 Aug 242024 Q2 Earnings call transcript