ARVN - Earnings call transcript Q4 2024

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Operator

Good day, and thank you for standing by. Welcome to the Arvinas Fourth Quarter 2024 Earnings Conference Call. [Operator Instructions] Please be advised that today's conference is being recorded. I would now like to turn the conference over to your speaker for today, Jeff Boyle. Please go ahead.

Jeff Boyle

Good morning, everyone, and thank you for joining us. of a XXXX with available financial Investors Media issued and fourth on we arvinas.com. and year at full results, section today, press our release quarter the Earlier website the which is

Joining the Arvinas' Officer, our Medical and President Chief Chief Chief John Scientific Noah our Andrew Angela Chief Financial Saik, Berkowitz, our Executive Chairperson; Officer; today call are Houston, Cacace, Officer; and Officer.

uncertainties statements and I'll remind These you today's that begin involve are we read. forward-looking risks, the company's uncertainties press the call, and the recent Before today's filings which Commission, you release assumptions. I Exchange in discussion risks to that in with contains outlined and urge Securities and

call. And our turn John now over to Our President CEO, call I'll what results actual differ today's materially the Houston, may Chairperson. from John? and on is discussed

John Houston

cusp you quarter Thanks, joining we're time us and data results here for at very this top neurodegenerative expected that line Phase us from data III first-in-human this the some Jeff. everyone, disease. as exciting Good PROTAC It's a include targeting our first for of later morning, Arvinas our first and major accomplishments thank morning. on

of to We and across robust programs a portfolio the potential diseases. development neurodegenerative continue broad have range transform progressing that landscape treatment cancers the exciting a of

overview Noah provide overview or program, from and of neuro Phase III update ARV-XXX, our I'll program organization. with will vepdegestrant PROTAC your an of earlier-stage provide Today, the overview our first BCLX LRRKX And to financials then KRAS vepdeg discovery clinical morning novel open for full this VERITAC-X been company, the ARV-XXX platform an year XXXX of pipeline. finally, provide of programs, including backbone class important to we update our our begin provide fourth an our update always Arvinas, approach reviewing an degrader. discovering, has GXXD our before our questions. our provide Andrew and clinical Our trial we're an developing Angela degrader. our call with including and brief a update and of quarter new commercializing an our also at medicines will degrader, on on the a for up time and such pleased an and the will

of significant Over lives the year, the mission on of improve and course have patients life-threatening debilitating with last the we made to diseases. progress our

Our designed system proteins. disease-causing pipeline chimeras and protein remove been the targeting and disposal to degrade of body's PROTAC to proteolysis protein or natural have degraders selectively harness efficiently

us that goal breakthroughs and include pipeline, a cancer. Together treatment we trials Vepdeg monotherapy, PROTAC with orally create innovative protein platform degraders drug-like degradation. making deep are enabled to while a significant bioavailable breakthroughs has Our in properties targeted designing These is plan when ongoing development monotherapy to needed, to III most advanced in program blood-brain additional the Phase cross able And our pipeline. backbone X includes for addition the first our and the first current our trial, a in are best-in-class therapy specifically the of breast combination with settings Phase multiple oral to degrade second as line III the combination ER+/HERX- across estrogen with with vepdeg degrader protein is becoming metastatic an designed of and receptor PROTAC patients Pfizer, breast target in strategies. cancer. with the developing ER-targeting then barrier. Vepdeg

trial. trial an overview results call. of first these will we trial support will in this in and Arvinas, quarter. expect important our milestone will our III Data from company. Noah first-ever commercial drug soon, an the from hand VERITAC-X, stage forward And and to be have If our clinical this positive, data to application III sharing later new transition to later we Phase mark the look potential Phase top for results line a provide

first answering expect line, first we that questions Q&A the and in progress the updates III trials emerging intend XXXX. portion CDKX vepdeg and a initiate Last be we close we second-line we our are on or for with Pfizer's we data how inhibitor, the during plus additional to with guidance offering Now call. given we about development III XXXX, this to trial combination to CDKX/X month, Phase our feedback. In Phase we novel announced authority announced expectations a settings, evaluating that trial combination clinical the in to vepdeg in health will plan pending trial investigational initiate not of for atirmociclib. to which In inhibitor, also announced vepdeg initiate we line, VERITAC-X disclosure, a plans second

data-rich there to believe we highlight neuroscience. In for vepdeg, to from and data which opportunities April, exciting the we LRRKX first-in-human will across the plan our we offer patients a Beyond we our have are year PROTAC believe can present ahead, value ARV-XXX, neurodegenerative degrader, PROTAC oncology diseases. degraders potential and with

trial I call KRAS Noah degrader Additionally, ARV-XXX our to application this programs. year. I'll lymphomas. finally, we from an BCLX over vepdeg are degrader data drug to non-Hodgkin preliminary of turn GXXD with patients an with in overview we on for XXXX, track now plan our in for file our And new ARV-XXX, Noah? to Phase investigational and share the the

Noah Berkowitz

together program. year, and vepdeg morning, John, with Thanks, Pfizer, good progress everyone. we with our great Last made

III and top intend line new year. initiate As later quarter, this results this in to settings trials from second-line we in addition sharing mentioned, later the John combination Phase X to VERITAC-X first

has ER-targeting and vepdeg best-in-class believe tolerability demonstrate become by to their and potential to physicians superior a the therapy efficacy preferred and patients. backbone continue We

events made a with in much prior agent first-ever receiving regulatory degrader. Recall, CDKX/X the could of who metastatic been received won't a progressed only median successful, ESRX ITT in Given application has time potential metastatic the with managed patients to in progressed the if a few an with with and to months treatment advanced CDKX/X submission who PROTAC approved in ago result for the yet a mutations trial VERITAC-X VERITAC-X and the efficacy with the treatment. An vepdegestrant trial. and X.X need primary medical need response, extend years evaluating clinical activity, previously of inhibitors has and PFS highlights subpopulation. The quality in endpoints. ongoing cancer of unmet few PFS the discussing patients a new secondary benefit vepdeg population have assessed fulvestrant Important has and of or worth approval opportunity of mutation VERITAC-X the PFS is for proximity This the data improvement for with of I X intention-to-treat drug breast also advanced assessments. to breast cancer of therapy. the ESRX upcoming the measures inhibitor, endocrine overall a patients oral too including line cancer central that months. treatment and there clinical safety among determining And duration there response are life blinded is of VERITAC-X compared the by ER+/HERX- objective in be after safety noting the patients top outcome review. include progress course, readout, rate. which, trial, study is will independent survival, in PFS on antitumor It that and have breast combination spend and

to also XXXX, top host present announce in we to release QX We a where congress full a at intend press VERITAC-X in investor to an line the and expect of in medical call. outcome results

vepdeg to on in advance evidence the for is novel data We trials addition in and based represents plus vepdeg the in In as progressing investigational the trial inhibitor, plus shifting combinations. in plan vepdeg evaluating initiate TACTIVE-K potential evidence emerging a first-line registration setting. the potential and feedback. be Pfizer's plus setting are trials palbociclib. This atirmociclib Later treatment our a authority excited plans addition early CDKX trial are late-line the vepdeg evaluating setting to to first-line option by treatment pending decision first-line anticipating with in atirmociclib breast plus atirmociclib, setting. vepdeg to in advanced new combination year, VERITAC-X confidence is from a new gives that ongoing results, of the Phase pleased this this paradigms the atirmociclib vepdeg option the combination of we treatment initiate this to Ib/II Pfizer The health combination and cancer we best and for to combination us to our evaluating Phase prioritize III totality

with from include the consistent rate Breast the of XX% trial been rate December in shared have at XX demonstrated clinical of trial XXXX, plus inhibitor. data vepdeg of CDKX/X vepdeg clinical vepdeg emerging and the inhibitor Our and efficacy in abemaciclib a presented for an in Compelling the second-line Safety plans agents. In the pending in preliminary response Cancer combination combination with signals was initiating more both with feedback. overall previously plus Phase XX% profile than patients generally with abemaciclib Symposium. combination III combination and with XXXX, we nearly data setting. San Ib and treated Phase also or in benefit health a combination authority palbociclib encouraging previously of patients of demonstrated activity Antonio the tolerability CDKX/X This of second-line

cancer options. generated data this to demonstrated going second-line in patients had by regulatory as -- vepdeg, and vepdeg and potential totality, of Importantly, later meaningful supported both our metastatic pharmacology continue vepdeg data new abemaciclib therapy. clinical combination the DDI vepdeg for belief I'm emerging to to with development not the no and effect combinability III now our significant the have support which turn is The to were also tolerability, has breast vepdeg no clinical look of ongoing provide monotherapy clinically We program. combination interactions treatment concern potential trial that observed ER feedback. In year, on a drug neuroscience that initiating we backbone a drug forward as I pending trial need efficacy superior to exposure. a was a and for Phase who of Phase the

an of scaffolding initiated single target address on peripheral kinase that Phase healthy or nervous neurodegenerative the is and genetically cross studies. In ARV-XXX in in Our we XXXX, I by blood-brain progressive of safety from to presented high from the in establish LRRKX from PROTAC designed sharing. measure I'm to potential with pleased trial improved blood The and and biomarkers disorders from Preclinically, This AD/PD palsy Disease movement first-in-human nonhuman need barrier exposure strive the and CSF a ascending diseases. disease-relevant oral ARV-XXX forward neurodegenerative primates. neuroscience confirm be that large repeat ARV-XXX, in share look degrade barrier will We've advanced Parkinson's fluid disclose severe or cohort And in the cross that primarily in medical valuable we X at intend and shown establish PROTAC, orally dysregulation. the most data a ARV-XXX disease. but and the ongoing the barrier of of Phase is to humans. These to of showing lysosomal dose to the degradation volunteers. of linked inhibitors observed a trial and Phase brain are exciting penetration LRRKX of data central we trial in degradation and designed also will region of will Conference, CSF. At implicated Disease/Parkinson's initial April. dose-dependent will an oral healthy in ability clinical cerebrospinal in explore penetrant leucine-rich I dysfunction dosing it supranuclear we LRRKX. LRRKX in system of brain ARV-XXX, the degradation novel that in ARV-XXX blood-brain differentiation in this to kinase multi-domain in milestone blood-brain volunteers, the the effects We AD/PD we the LRRKX to to the the session Alzheimer's I incredibly deep the be that patients trial periphery was unmet or ARV-XXX Conference preclinical as LRRKX CSF bioavailable in have achieves learnings also and X to data the crosses is

ARV-XXX in complete cohort we this It later is palsy enrollment disease with ascending this been dose the from the recently to I which Parkinson's LRRKX pathology. We of disease ascending disease. also progressive and expect strongly to progressing study initial data which later first disease and patients has year. contribute trial Phase with with be Parkinson's noted The shown mutations second in a plan present dose should initiated linked supranuclear to a And patients in initiate LRRKX in is faster to are this disease, year. Parkinson's that multiple

BCLX our Now KRAS turn Angela, to going it degrader ARV-XXX, will to Angela? over who I'm about GXXD our and talk degrader.

Angela Cacace

and good has protein morning, designed oral Thanks, positive. of to preclinical everyone. ARV-XXX, The Noah, B-cell degrade lymphoma PROTAC profile highly or been our BCLX X

non-Hodgkin protein BCLX which a and patient-derived and repressor transcriptional lymphomas. data ARV-XXX vivo in rate Cancer degrades B-cell critical proliferation is to Research facilitates activity and presenting as lymphoma. through B-cell a a DNA April. terminal overcoming preclinical non-Hodgkin the several the on and BCLX. significant in the a has of demonstrated of ARV-XXX ARV-XXX of gene antitumor models American the has models. These vivo sustaining rapid It types is angioimmunoblastic plan potently preclinical the which cycle lymphomas. PROTAC-mediated in data activity. major promise repression checkpoints, Association in profile. and becomes undruggable BCLX for We T-cell dysregulated ARV-XXX Conference show at of protein, preclinical BCLX rapidly has apoptosis resynthesis lymphoma background, in monotherapy numerous driver overcome cell BCLX's somatic tolerance in of degradation of damage For The nature rapid of the recombination response, historically to potential differentiation, differentiated antitumor

ARV-XXX with care and in vivo will standard of DLBCL molecule in agents inhibitors we high-grade biologic models. show combination in small aggressive Additionally, and

progress We with significant clinical to initial of and have lymphoma data year. in Phase in non-Hodgkin's made patients look sharing enrolling I trial this ARV-XXX a forward

final several to care. GXXD, poor major this for dose year that responsive molecule KRAS and standards As our track KRAS activity cancers, on is types and our a driver colorectal with mutated including potent highly Preclinically, we KRAS drug in GXXD pancreatic investigational selective an resistance note, of demonstrates leading degradation antitumor degrader robust cancers. is to degrader. KRAS tumor in and of new to a is remain oncogene application file GXXD associated prognosis and a

PROTAC-induced rather forms Our ternary elimination both states complex event GXXD. a in the and the KRAS GXXD. inhibition This inactive of active with binding the KRAS results degrader than of

and the vitro Andrew. potent call inhibitor Arvinas the In currently addition, an at our discovery in GXXD our I months. With look are that, on forward more coming in XX-fold KRAS that over degraders updating in KRAS degrader to promising is turn with progress you at least to the than other in clinic. I'll Andrew?

Andrew Saik

morning, and XX, December financial ended I'm and good Angela, year XXXX. Thanks, share the to the quarter for fourth pleased everyone. highlights full

reminder, As issued release the and press detailed are this morning. quarter the a financial fourth included we results year-end in for

move into on had are marketable billion financial the cash cash, into billion a on position At equivalents hand strong cash operations with sufficient sheet, in compared the the we quarter, As just we XXXX. XXXX. XXXX, end and the end securities in we at $X fourth support $X.X of to of over balance with

launch sheet balance all us strong advance key portfolio which first will program, our of include promising Our clinical our of preparing allow for objectives, to developing earlier-stage strategic commercial degraders. progressing the vepdeg and our PROTAC

turn quarter the year full and me Let now financial XXXX fourth to highlights.

decrease year due $XXX.X $XX.X million the revenue which negative in quarter, to the the revenue primarily same fourth changes compared of the million estimates, we made The year. General expenses administrative a $XXX.X in of the revenue, the period for million were was to recorded contract and in The for revenue resulted $XX.X million of $XX.X compared to compared During period $XX.X fourth XXXX in increase of quarter, revenue in in to for in of were related and prior XXXX. in adjustments to in $XX.X XXXX. fourth negative was out-licensing $X.X of million of in $XX recorded driven of million The We related the quarter were XXXX. by $X.X same $X.X million million from expenses for million, million. compared same to in year. $XXX.X Research of $XX.X our a million external commercial of million million $XX.X the the XXXX. G&A year, primarily primarily $X.X increase to $XXX.X million expenses million prior development fees for was ARV-XXX. expenses due the infrastructure professional quarter, net $X.X and of the to in period of personnel developing compared and decrease million costs to the operations million

the XXXX, XX, were to year December $XXX.X for year. R&D million million prior For compared the ended $XXX.X expenses

an with quarter first results potential with expected later exciting III for We the line into are XXXX move top we capitalized for year, beginning VERITAC-X. milestone-rich well Phase as this our

milestone is trial study. the first share another multiple dose in this single ascending the of For portion expect the same targeting the year, we the data company. data Phase first-in-human and initiate disease in with patients important presentation degrader ARV-XXX, April dose our from I for Parkinson's our ascending to cohort disease, neurological of Later in

forward KRAS look I'll that, GXXD sharing study over also call John? ARV-XXX for back application the to We data our Phase closing the from I turn remarks. submitting in non-Hodgkin's of degrader, patients IND BCLX with our John for and to degrader. With an lymphoma

John Houston

Andrew. Thanks,

us and have trial pipeline of a Phase ahead clinical protein trial III We readout for year our our of key expect from to a as promising prepare degraders. we data-rich advance VERITAC-X

to support could our begin not now to call want life-threatening we the gratitude for portion As this thank as potential for achieved want Jeff? ever have multiple first Phase diseases. With I'll the new want our our to over possible work patients my I the who together for physicians benefit express the data Arvinas Q&A also I dedicated team of our call. patients thank here none tirelessly promise a as first without protein of that, collective turn to trials. to III sincere our for are Jeff we I our we success bring at across But PROTAC, palpable. them working encouragement and is it prepare enthusiastically to efforts. today the to and participating continued of degraders your excitement shareholders clinical bring readout, the to would to medicine in their without patients. be and to

Jeff Boyle

John. Thanks,

of related questions on to our providing data Before will the VERITAC-X be the remind for to progress operator, the time. over this call expectation I'll we guidance or status at answering trial or I the not turn additional you,

the that, open please with up operator, you will queue? So

Operator

will question first from the line Derek come Archila today Our of Wells Fargo. of Instructions] [Operator

Derek Archila

about Just different cadence second-line combo? the data waiting the CDKX/X meetings? one reading that across out in this to for of of terms you'll really cohorts are on think medical ultimately, decide be year, that you just TACTIVE-U that the data And

John Houston

he Thanks, Noah, and Derek. answer I'll over to can directly hand that.

Noah Berkowitz

Thanks, Derek.

TACTIVE-U, as vepdeg agents. So evaluating other is in know, is you combination that study some knowledge, a with for everyone's is

CDKX those abemaciclib. also and include inhibitor, agents a So ribociclib

to data we've combination. data So shared abemaciclib the continue Those about mature.

haven't We yet. information the other X shared for

mature, is guidance offered haven't updates share of more. the we We hope sharing But data will about specific can when the as be that these. we

question CDKX/X inhibitor determine this this to with combined at whether of with that's will We established combines the As we've about very or vepdeg and choice point, nicely not palbo the with abemaciclib. vepdeg. think combines that

So what we best the of be will overall, what the drug the likely in setting. with to combine second-line combine determinant is

So I few on don't but want that we give more to months. now, right the go can that detail updates in next into hope we

Derek Archila

if And on squeeze LRRKX. I Understood. can X more

guess, Just the to you for degradation plan therapeutic level in what to setting? human of how that to terms will kind of in I the of you be what preclinical And the SAD, do share translate find setting?

John Houston

to you that Yes. want Angela, do answer question?

Angela Cacace

the Certainly. question, for Thanks Derek.

preclinical showing on of as others published that protein well the alpha-synucleinopathies, XX% tauopathies. is certain many of reduction in by data including context, been context based So that's in the as disease-modifying

those are published. data So

there's expression confirmed brain, microglia. recently And particular, expression Parkinson's in been in iPSC-derived cell relate that that genetics patients, studies In in LRRKX where us in to of disease. idiopathic overexpression LRRKX cells omics the guide this addition, has -- show from on LRRKX there's Parkinson's human that disease microglia on in more in levels elevation twofold in single

brain, the that's in reducing that and the central believe best to hypothesis aim LRRKX the show stand we of we chance testing what the LRRKX by XX% in we compartment. So

Operator

Evercore. be coming Jonathan And of will from our line of question the next Miller

Jonathan Miller

and second-line the make TACTIVE-K you've much CDK data on you I the trial for in Phase need you the to on III trial Do design guess the need here atirmo question started? we I'll the Obviously, FDA assumptions? gating combo combo a getting What's study line. CDKX. just the design How those to can that III? gating do you the factor before the X-months already chosen go the Phase with factors, first since data ask had with to at

John Houston

Noah? question. great Yes,

Noah Berkowitz

question, for thanks So, the Jon.

atirmo in and So combined that were our overall, line of have first first-line with shared, as combine on back overall, the recognizing in line. on in These what to plan that the -- is combination in later we're data we based settings, at setting. could where the of reflecting part shift evidence also of the we and And we palbociclib, but X in with with we atirmociclib did there. use vepdeg now in in the being assessed totality see XXX looking And expansion we've which there's atirmociclib also in we of opportunity we've this the palbociclib were vepdeg looking how in earlier future. how different which and much are do an set from we doses is CDKX/X line a great for a less, much, first is the used and in atirmo

The As to that a for have data nicely. need is we've months we we -- feel data. to look not have It to news authority good is the what's continue not do health health some least we we at shared, of with to authorities. -- continue need conversation at this there mature data is gating, that discussion, X as to have and the

Jonathan Miller

questions And not X talk a what your can there preparations commercial of to could to squeeze what I launch? for maybe couple ready VERITAC-X, prep assume is we if do more. going be be -- going? in answering readout a How I to wonderful ramp you commercial beyond you're does know you be a about think And needs to but weeks?

John Houston

the Yes. on commercial runway organization. been focused a building for initial Clearly, we've

in as getting of components We a launch other place well. have that different place. All in the aspects for the are

Pfizer, U.S. we'll with be we'll know, lead. launching the be you and As

So related of planning to amount that. a significant

the good and very made getting shape. in I'm team, we're progress yes, So the pleased by with

Operator

Watsek be question of And of the line our will Li next from Cantor. coming

Li Wang Watsek

trials be of design it this read-through if impacted to I Phase on by elements year? trial wonder if that III Any the any initiate comment the the might you can has results? X plan VERITAC-X, just you to maybe

John Houston

talk that least you at do want Noah, to the part of initial about influence?

Noah Berkowitz

we I preparation and would the read-through into scope for guess our if health to second-line be that. of just We the anything, in setting, through the like I activity discussion to line. see it see in authority monotherapy setting. line. process more Yes, the second any maturity read-through, second-line go having the understanding probably and of the details We're data can't the also in going first continuing more the evaluate of don't in

Li Wang Watsek

Understood. a into And pipeline you've perspective, got clinic. guess the from additional X I just programs that forward you're moving

what So Parkinson's guys looking I guess for level especially that indications of larger make, are to you investment the disease? like

John Houston

or progress of getting whether to how find the we're Yes program of compound interesting made the very year. future to Yes. situation well the into. are of last in question. a significant We'll compound areas milestone. for to seeing stage That's now, a we program there's excited and on Great And that first and internally about our neuroscience, an the see partner. Clearly, and is, Right disease, the forward PSP us. moving it we're ahead And a with forward. the very very Parkinson's development. us has pleased neurodegenerative progress focused that very not degrader where take to moving we portfolio strategic move LRRKX all through placed significant ideal

Operator

come Tewari will question from of Akash line of our Jefferies. the And next

Akash Tewari

and percent your part with that not saw should we but mind, we what to not, in has rate (sic) in timing know now. second-line progressors? requirement line decision [ what data? dose? And And then Will fast of that the are can right if on response to first you give X-month a the do an So in take follow-up that have ET combo you isn't upcoming we're mentioned think be CSF]? be go-forward that remove what to an the decision. With expect We for sufficient VERITAC-X, study concerned previously a Lilly? efficacy-based would to combo prior frame ET a for progressors vepdeg enough your going expectations versus Pfizer early CFS you first-line progress question, on is do fast on setting both this how you And CDKX

John Houston

we that So be again, questions we the said beginning, answering as second of the any to won't question, VERITAC-X. half at related

First of question... the half

Noah Berkowitz

is the In efficacy factor. safety be safety know I we've established first terms going that into much you There's we'll we've -- decisions as And setting looking in I we'll of it's overall and driven. data just at, Phase second-line are well, the drug, how activity of about deciding but from line at think your mostly also be programs to want already efficacy the dominant the safety run. looking which plus the

whether the So we at be to mostly or the and look acceptable discussions authorities with unfolds. now, to it's we just those continue the not discussing maturity that is dose anything recommend just to going as health to -- of have data see if

Operator

the Ahmad of Tazeen from Bank coming be America. line of will question next of The

Tazeen Ahmad

Okay.

me. that's think I

have I questions. couple a of maybe So

metastatic The breast on is one cancer. first

think a And then palbo, confidence with show a example? what they CDK inhibitors had to you have have on that atirmo, like So the lot to follow-up. ribo experience just need give data will for do that considering KOLs of historically, to and more profile the I other you'll

John Houston

Noah?

Noah Berkowitz

for thank Yes, question. you the

today line, the of the prepared other so or I that's the we the design, that focused have years We think feedback generic. plan. terms, have see? what something in -- that's we if than from X when is know months, to improvement of want against we're more palbo substantially they months the that up if to on We're targeted, ratio question the see expect statistical PFS features But a general to -- being get is not exact go investigators X median in first even all to few different, hazard into would is generic study competition

range, first-line that between And you'd CDKX/X that AI XX plus delivering X something combination so in you want see to of know to the something and as special. XX-months X, if better median PFS, have months you view somewhere

Tazeen Ahmad

competitive. it. this could degrader given ask it how And Got be you you pretty Okay. then space think if on degrader. might KRAS talk GXX I your is Can a differentiated about that question

companies see it Astellas other forward? would And order in to what like got you to the You've in move want clinic.

John Houston

And our excited answer We're to KRAS do Yes. you program. Angela, very want about that?

Angela Cacace

Yes, sure.

doses, inhibitors the due think, we've very public, that with Astellas than on We vitro in molecule. It the based that the inactivated profiles competitive, discontinued to So to and do based for catalytic know complex, that respect XX-fold competitive at the terms in that We the know in we're some terms than on cell feel potent we're of we degrader higher efficacy so proliferation We very a space vivo degrader potent inducing more bind that we've generated. we're was, we to and activated We GXXD to the both that I in issues our the very more that show know of details is the did the different action. Astellas we're death. compared and mechanism in are an encouraging cell of we in Astellas inhibiting both. And believe that profile The that but states inhibitor. data binds safety. have degrader. ternary

producing compelling And the mechanisms beyond not. terms can that that, scaffolding disrupt GXXD. for functions we're do known are know the some data profiles of and that have and of that GXXD potential neoantigen for some we we distinct KRAS, that also the have We we impact resistance we very with in inhibitors non-overlapping

Noah Berkowitz

first this So ultimately, compound some important because -- it, and Angela, -- Difficulty] dose point, [Technical may Astellas but think you touched on in line that abnormalities an did some that add becomes and I demonstrate created the limitation. patients the just potency first-generation issue have to to

into maybe So have with come we the do address efficacy before play. to opportunity ours those

Operator

the coming And Devarakonda the the will line coming from line next of next the Truist. from be of be -- of question will question

Srikripa Devarakonda

My about any follow-up. there's status whether patients? And Can a fit talk first profile might or you this subset enrollment on the for is on with of particular And do think and you program little targets question this into I where a BTK ARV-XXX. BCLX? bit other like of focus target, landscape the a given the NHL have

John Houston

Thanks, great That's a question. Srikripa. Noah?

Noah Berkowitz

it into Srikripa, break areas. a We're let's pretty question. down this and excited about few compound Yes, different great

little later than year. started expected, patients going last In we backlog nice its enrollment It terms and but a of initially making progress. so things study far, of very enrollment nicely, was the

first may sense in there drug no in -- are BCLX degrader this has and probably There that similar stage of how differentiated a it's inhibitors development, of of out are is the approved. differentiate really the much at development it's shared. in there, another itself clinic all, terms been In well, that's not or that

of We attention want shared, which we've where AACR, your are there's some direct satisfied data, to with is lot which an you coming, we very going towards of combination would and combinations to that to there activity. the of can view to door what potential orthogonal update. We for opportunity a up approach an this be you -- open anti-lymphoma is the more see

what expression One you degree out be to these to us single necessary mono, of that inhibitor, with the bispecifics. for drug really there agents working -- suggest you expression that do is tox pathway if studies, opportunities an or hasn't that for mentioned, of antibody real talking this we're isn't toxicity are is agent. the of how targeted whether BCLX BTKi combinability, in with effectively we're it's demonstrated it's to combine need our any the -- The about whether it's therapy, preclinically anti-CDXX things or nicely fact ] [ much this whether and evidence hematopoietic that therapy

about So moving then And combinability. dose we lots generating of step, tolerated follow. is and first a data on paths maximum the to can obviously,

Srikripa Devarakonda

We'll keep out AACR. an eye for

year and commercial Commercial about got or a key so a Just We rollout. question. a concerns inbounds follow-up before potentially before around readout little about investor you Officer some help this? right leaving potential talk alleviate it a bit Chief the Can and

John Houston

of and Yes, Chief Luckily can't our been John in he get into also which for the through into. Interim breach planning, had to unfortunately, line we reasons, our absolutely Commercial to Officer, has personal absolutely. because a us Commercial Chief Santini, great leave, highly and I Northcott, Alex experienced step had executive, superb. who Yes, he's as able Officer, second

the continued that game haven't was can a plan Alex is So we out the by honestly laid say I missed team has progressing John really well. and beat.

had the able terms team really quite depth we easily. in unfortunate, such to there, So but we'll move of it a was because leadership great on be

Operator

of will the question Mukherjee BTIG. line next be our of And Jeet from coming

Jeet Mukherjee

later functional year? translate a for you this to can more follow-up. bit there ARV-XXX hoping have the what would expect we any on patients? And was a could update I Parkinson's improvements elaborate for in patients be And that from looking you'd these are I biomarkers

John Houston

to Thank with Angela? you you. or Noah, I'll to go start

Noah Berkowitz

Jeet. Thanks, Yes.

So just demonstrated share we've to healthy volunteers. to put or us first the step on like in the same page, the immediate -- to what is what demonstrate

properties PD. PK/PD, understanding how drug in the central course, then, virtue tracked we in nervous also can what of of the to what system in be see And there's PK periphery, the by And involves dosing understanding so this but of CSF. leads of so our

So what's periphery CSF. again, in importantly, more happening to and in the the LRRKX,

hope we we at year. update can move share to multiple we glimpse patients, recognize at schedule, first started the and in be point data Conference data and would at with And can disease we is shared, have patients. reasons about data this also have ascending begun Vienna Disease dosing, to April. those SAD, next dose. off, disease progress can't as dosing this when the early in we'll hope shared, the of in nicely that would by the Alzheimer's in much later conference then how we we now, ascending dose going guidance appropriate depending on be accumulate right we it's expect conference so offer of this, but -- we would Parkinson's least we've we and for so SAD so But And will Disease/Parkinson's Parkinson's some on the MAD exactly see those very we that but regulatory And can a single patients. Unfortunately,

Angela Cacace

we've continue conduct saying, J. with studies, Fox are that And primate from to effort able been Noah least just Foundation. based respect in driven was on we LRRKX at discovery around what a to Parkinson's initiative Michael the to think biomarkers progression nonclinical disease published

endpoints, by that data we as encouraged move can as that our endpoints. we're suggests well nonclinical lysosome function neuroinflammation So

it's So promising.

getting assess disease this. to towards await studies the Parkinson's MAD of portion we so And

Jeet Mukherjee

maybe And a helpful. That's Understood. VERITAC-X mind. question, wouldn't if you just

rules you could line said conference. as a abstract the part release? full embargo medical at what any top potentially present say press You you of limit Would results

John Houston

Yes, I there would think be.

more get we'll and information past that that we stage. as on get -- next So

Operator

from question next of line coming of Canino be Brad the Stifel. will our And

Bradley Canino

from trials should plan? Listening kicking CDKX/X earnings, pertain the inhibitors in to around this and frontline your with we these expect That's off about How studies as the pharma Roche vep they will to Arvinas Phase the be CDKX. large SERD right the will think results combination and oral frontline frontline year. III AstraZeneca of the time Pfizer you

John Houston

we're Thanks, be data going about very say want to interested Noah, both do in the Obviously, Canino. that? companies. to anything those from coming Brad sets you to additional

Noah Berkowitz

of this going question impact can I this the care? is that's standard than enroll, it's going have not on have to it's likely operational will Sure. with And guess that launch and the less take the any impact not to a in the feeling of be, study Thanks, years of couple to feasibility the Brad. on our way. to study -- year --

there some anything, it results. just, creates positive guess, if if excitement area So the some I this -- are of kind in

targeted different of end at of We PROTACs are SERDs day also the than because degradation. our the very recognize that

from be that something we can would So see a we -- see, can expectation we stronger and our PROTAC. whatever hope

creates looking recognize So that just it with but we're anticipation, opportunity.

Operator

from be coming of the our question of will line And Stephens. next Sudan Loganathan

Sudan Loganathan

one be combination first plan will regards vepdeg. atirmociclib in that on to first-line my you with And

view, CDKX, probably like metabolism palbociclib neutropenia for increase or the the potentially. think I CDKX in which selectivity like up curious with glucose fourfold toxicities I and have atirmociclib But is how out hematologic helps component than to with other showed ribociclib any safety or that CDKX/X for by makes out any how the profile? there? may uniquely the And a you what inhibitors over just believe play view XX-fold CDKX that very characterized that I And in even may palbociclib, follow-up. on and a your view broad your involvement better that in of just have atirmociclib in

John Houston

Noah? Sudan. Thanks,

Noah Berkowitz

specifically neutropenia. so Sudan, So, you the had mentioned

liability. a some neutropenia just there a palbo observation, was since And a probably shared -- give abema signal vepdeg an as a observed don't of glimpse or which So general we've as is was very don't really enough combination we data liability view neutropenia that strong view having we with and increased was neutropenia, combination no really in this. then, anything palbo. of safety like for There to

comes So that to palbo's we is been whole concept and when fading particular away, to DDIs, -- toxicity. may have that it

has atirmo note III what of should a in combined terms announced. to is In first with already expect line, that AIs Pfizer we that Phase well, study

that listed reviewed that it's that authorities, -- can That that by on a trial clinicaltrials.gov. willingness been let and go health forward. presumably there's to see you been So means it's

profile profile authorities. safety of tolerability the and to was was the health that chosen So that dose of acceptable

now glimpse been and vepdeg seeing a Pfizer. So and with dosing really we've collaboration atirmo case, in in fine. efficacy attractive our been We've with look early of patients safety

hurdles then, of just as us health So don't shared, the significant course, schedule, dosing bar. Hyperglycemia reach about authority the of and a high we're agreement health now, design. trial updated. which with you is And those are just to planning we'll authorities think on we to not just have update for concern we'll But a is keep we've you discussions. ours right

Sudan Loganathan

to the PROTAC evolved And technology I with believe, degrader? is the provided you I Could my employs degradation share the ARV-XXX. to and this Squibb's one of on if appreciate in potential And efficacy there. second in which the B-cell has No, your ligand-directed the comparison perspective Bristol-Myers utilization to for to preliminary regards insight BMS-XXXXXX, in degrader BMS your point data response changed or up has malignancies. any strategy their BCLX that

John Houston

of Yes, obviously question. BMS Nice the Yes. we're aware degrader.

way haven't of from the in that We much company. data seen

program that using is our will our technology insights, Our and belief our a better. technology, be our designed so belief our is significantly have we degrader

to data anything have to the BMS difficult But seen way the of see looks how going there. degrader mention we We forward. because that about in much haven't

taking own to stage. next on our focused forward very we're that and So and moving the program that

Operator

And Sandler. our Ted be of Tenthoff coming next of will Piper question line the from

Edward Tenthoff

changing question all treatment data earlier paradigm second-line are the changing, second Similar treatment are of how is -- about for line. VERITAC-X With How monotherapy you the ahead paradigm the data? frontline seeing year. excited upfront with line? how data I'm guys this you seeing of and sort asked like vepdeg to in the but of SERDs first in kind the a the to CDKX/X those

John Houston

over Thanks, straight Noah. question. Ted. to I'll hand Great

Noah Berkowitz

the So, thanks for question.

ribo being in setting, So more setting that's somewhat than adjuvant palbo's in in is the certainly, And abema, in more stating first-line used the landscape. trend now use that so is and changes treatment and there are more the there. even and bigger the and is

much second-line data would still So aren't be data question of you second-line would what and outside palbo with happens? there the some. of think vepdeg, palbo There's use limited. CDKX/X? the that our out But setting. CDKX/X use for there there great there It's experience and less in ribo in Is the the is after combining of setting,

part So of physicians some their that about CDKX/X there's palbo combination using the limit inhibitors. probably using on interest in after or other

what accumulating in So targeting we impact. we're is that of data do for recognize addition those trends the some use drugs are pathway. And but there having to -- the general that's PIXK

for are the seen III Phase program obviously data we KATX setting. kicked second-line off and there You've that's know some in been exciting

and -- fulvestrant. fulvestrant. is with combined combined that's this atirmo with So is There that's

oral work and will So drugs vepdeg with it how with to hope probably in there support the demonstrate end, of have support end various drugs are to combined be make. in or that they agent whether whatever And the some just fulvestrant, we the to they will can setting. be fulvestrant data to to that do up an being bunch use want will they'd those And this physicians -- practice-informing settings. are combined will be a using types in wanting decision in be of

Edward Tenthoff

helpful. Okay. That's really

Looking too. rest the of from the for data pipeline

Operator

from coming of UBS. Ellie next be the the question And of line will Merle

Eliana Merle

then vepdeg, frontline on follow-up. of oral for thinking might more for about I latest an responsive a patients develop be to have in the might mutation. enrichment potential are thinking which strategies you your what of setting SERD And an terms the are Just who predictors and how ESRX patients

Noah Berkowitz

jump in. I'll Sorry,

John Houston

please. Yes,

Noah Berkowitz

Ellie, comers are so be in our line, likely first yes, all taking So, to we in the not study.

fulvestrant. be So patients exposed been in there And standard patients setting adjuvant now obviously have AIs. that care rapidly these in inhibitor they've plus would when the are to a CDKX/X some of progressed

to are those included not likely So be design. study in our

as other ESRX strategies, as here well a ESRX we enrichment drug for that believe have we wild mutant. As type degrades

well in something population. ESRX have patients may wild should first-line, therefore, type. range a in of so that in And very broad XX% work

So enrichment of there's there. no thought molecular

study because because ESRX well. first-line is can clones the work prevent the of the as reasons we of better by that maybe even evolution would mutant -- that develop may that degrade effectively suppressing clone One we the any

So in going to the into I don't think study ESRX design. play mutant selection way any is

We're happy to Beyond add discuss that, some if not you clinically. offline good ideas. much more to that you have with some

Eliana Merle

target broader whether how that follow-up, target have say, There's just on the so aren't a in development a strategic just on question. latest a platform And what's perspective focus like on just maybe PROTAC expertise say, your protein to a [ there targets been target for STATX selecting as ] lot But then would And degraders. space? making you a of many immunology in the a take candidate? it degraders. companies to your a perspective, or, obviously, focus making expand from, might long from a What's

John Houston

of been over has immunology brought focus elements as There's our been Clearly, Ellie, has years, as that last know, of oncology neuroscience. immuno-oncology and in Yes. you elements the several well.

always drive aware we're So of we could believe that potential a targets differentiation. degrader

and oncology, to look that, has at it do So future. like that things But we're been continue we focus not to and for major that. and blind our foreseeable the be neuro will

fairly our the you point, to against of of target in that To move what need design starting get though, it's terms good points the very forward we ligands a to on to dependent rapidly. approach are. starting the In points forward, terms have PROTAC Clearly, moving target. abilities

fast you So interest? then a ligand of the to that a and program because Do a to that we move have is you quality have determinants the of of big the or speed. high know how insight of when good binds technology. our can target apply forward one relatively quality And that,

important to generic early that? anything to answer, is fairly you add ligand want piece discovery this an it's on. Angela, a to So but

Angela Cacace

that learn where over that I add pharmacokinetic, to through the pharmacodynamic technologies have wanted molecules have to our we the add wanted and from rapid learnings movement been just into platform had past built we've -- we properties lead Yes, pipeline. some to years that I our more in our of it's some the great, XX that iteratively just John. of designs accelerated

So point the with targets. And assets we're about in of defined, building these some John just looking to course, some some at are under to ligand the we out then constraints our of our that immunology of immune focused course, drugged core indications, of just indication. is where now capabilities a tackle

and in role disorder. like a innate play may disorders immune BCLX So other MS

we're evaluating. preclinically, So

seeing there bowel on studies. we're its move, role Parkinson's biomarkers as that keeping an so at and as we're some that extended And least in may in preclinical LRRKX disease the open based and well be of eye disease irritable

So lot opportunity I our of in of and a think pipeline. a there's lot potential

Operator

question GS. next be coming of line will from the And the Choi Paul of

Kyuwon Choi

who initial what that I just clinical had or Any initial fragile comment EHA traditionally are Phase confirm post to think ones would coming the can data great. later this if quick such maybe as or I of just too ASH? of clarity for elderly R-CHOP? be like to you be that's care such into about your couple a as in And on Can standard see will either second, there sub-populations be year population you'd other at data you up just cell ARV-XXX. expansion stem from maybe potential on patients

Noah Berkowitz

Noah Okay. Paul. here. Thanks,

it's a So in we're to I. and off also bit still we this far giving we're enrolling -- when while Phase presenting we're obviously, not patients as still guidance this,

back, you that? Can of did go say trying cell? terms to repeat something you just In about stem

John Houston

Stem cell?

Kyuwon Choi

R-CHOP? modulation, too or Post-transplant yes for traditionally Yes. elderly fragile who are populations

Noah Berkowitz

Yes.

study So these gets and design issues the opportunity. -- into that that -- gets what's into

there R-CHOP in sorry, B-cell upfront. B-cell So large that in we patients for recognize we are may cure There large -- lymphoma that R-CHOP I'm are of lymphoma limitations opportunities. recognize XX%

preferred And so it's a treatment.

with Polivy check this in see being increasingly. also You population used

with Yet more become patients a those there addressed with standard are -- of that's options. So that be of care. can't treatment

preclinical think to a thought We're combination we data good with And so post-transplant guess how patients. we'd bring of It's we I the a forward. But looking your this for it. in inroads anti-CDXX question, showing would referred that be make we and That therapy. is, population. possible. be you at can of And then -- overall,

or with I guess to you're I On autologous And comment or hand, no talking CAR-T. think one that's as with challenging or have also first medical populations. doubt So and severe that's it's it's bispecifics at patients are progressors need, to look where premature very there's transplant an your the significant unmet rapid but indication. most whether a those disease on population those it's

whether late-line study. So it's a bispecific a to it I agents, XXX line these But and inevitability combining our to with to then our other hopefully or that as depends Phase some an and second other on combinability anti-CDXX combinations continue in accumulate even advanced the think data to I there's in in or line. agents settings first start therapy, moving obviously we

Angela Cacace

look are we specifically. lines that, a just assess key have then that opinion ARV-XXX And add leaders refractory taking preclinically if just who could post to are collected performs I there in at setting how that CAR-T to

So I to come. think more

Operator

question is the line of of Schmidt Guggenheim. the from And next coming Michael

Michael Schmidt

trying this postMONARCH and can A of study? subset Phase to as the efficacy of couple design more for data in relative data from the assumption case from data last year? of contextualize arm PFS what the to present in palbo any EMBER-X VERITAC-X, your are ESRX the And there any in December, III for learnings lead-in on fulvestrant is to with mutant base perhaps we are Lilly's terms experience then vepdegestrant. from Are ITT planning to you VERITAC-X control be atirmociclib? And the ASCO, that perhaps that with study planned for applied that

John Houston

atirmociclib relation our moved guided. we've We'll some sharing the of SLI, Clearly, the in in point choice Thanks, to that Yes, data. point, Michael. to first-line be we where setting. our haven't partner is at combination

data it atirmo, we've that we've the the entirety in the through probably terms SLI with the of in of got of plus decision-making. we decision combo. terms decision, vepdeg Clearly, seen informed the So in data terms the how the lower was of made ranking we

that data will once data we next But really we're at about So set. people related decision-making. sets any happy I data answered. not get be to come scenario the beginning, past on talking out, questions with to point, big to But including out questions, understand you will frustrating all the we're close some when and VERITAC, potentially answering question the very for at related next set, be we'll SLI. Again, that know comes and call. so the as And we this that's said VERITAC very once data a that we're set this

Operator

Q&A back for John closing This over I today. to session does call would remarks. now Please conclude Houston for to the go the like ahead. turn

John Houston

Well, thank for to you, us great the operator, and everyone questions. all thanks joining and

we're As we in a pleased can execution progress very exciting XXXX. to our really expect, you with look and and 'XX, forward

morning, So thank and you a day. your great for this time have

Operator

Thank call. conference today's you joining all for

now disconnect. may You

Arvinas (ARVN) 11 Feb 252024 Q4 Earnings call transcript