Mirati Therapeutics (MRTX) 1 Mar 222021 Q4 Earnings call transcript

Good afternoon, and welcome to the Mirati Therapeutics Fourth Quarter 2021 Earnings Call. My name is Sarah, and I will be the operator for today's call. All lines have been placed on mute to prevent any background noise. After the conclusion of the speakers' prepared remarks, there will be a question-and-answer session. [Operator Instructions] It is my pleasure to introduce Ryan Asay, Vice President of Corporate Affairs at Mirati. the begin may you call. Ryan,

call. Scientific of Research Welcome, Thank Because participate and to Baum, Development, Vickie note be call With Dr. not conference Reed, to materially afternoon's this Mirati's with such future a Chief statements. call. Mirati's Head will in events Chuck subject Chief able Unfortunately, will minute this statements. to today you, uncertainties, Jamie Commercial are and from and due and may Mirati's and Officer; last risks Sarah. Dr. actual me Please deal Executive David afternoon's forward-looking differ this in Chief that those are acute forward-looking Mirati's Hickey, flu, Founder, include many Officer. everyone, President, Meek, results Officer; Ben Officer; to Accounting Christensen, statements Chief the Mirati's stomach

please report U.S. over that, recent that turn For and results of these December quarter our discussion risks and updates. for uncertainties, Exchange and Securities filed annual With This review at is the we is to This Commission. David. a of released our XXXX available on afternoon mirati.com. financial section XX, XX-K release Form with full on press call the ended the Investors website the corporate I'll

questions. mutated I'll are concluding for XXXX update to and few to many provide of an non-small call, of the strong adagrasib's There preparedness cohort them previously submission announced We of cell for breakthrough positive and our this Thank your GXXC KRYSTAL-X treated for commercial lung and data encouraging execution provide you, new adagrasib few lung highlight II topline share Ryan. data results. program. to was Good taking team highly our cancer some the previously asking achievements in the growth, our afternoon, treated both comment I you year financial a received of for and summarize KRAS programs. non-small designation therapy for drug Phase and pilot for monotherapy then before progress FDA's patients in a just a I cancer. adagrasib will Ben, will afternoon's We study an We treatment Jamie Mirati. accomplished, our here. adagrasib important remarks everyone, registrational the us. in On oncology the with of real-time clinical under and remarks Vickie joining on completed thank initial colorectal presented review combination patients. development late-line single-agent application before cancer with cetuximab cell on as

without non-small colorectal a the studies provided combination cell We lung continued cancer prioritization including in also registrational adagrasib lung initiated second-line pembrolizumab cetuximab strong share several of in preliminary subpopulations We well first-line single-agent which additional results as with in and potentially support first-line certain and for cell of combination. from our as combination this as cancer. of cancer, adagrasib, non-small

and application oncology submission including Beyond for our later capital this to potential position continue success appropriately to invest offering which secondary increased a financial our and across commercial launch strength gives U.S. with a us public pipeline for preparation flexibility year. in we for an investigational In November, MRTXXXXX, our to we that broad advance drug expand and MTA pipeline, inhibitor. adagrasib, completing increasingly new the of PRMTX our cooperative targeted continue bolstered

with where end-to-end through strong continue discovery from build strong functions. foundational corporate early commercial development and our a We enabling company expertise to capabilities drug with

of ahead excited the transformational We about us. are year incredibly

to our adagrasib lung commercial and resources rapidly first prepared our well and other for approval patients product We cancers. priority. to patients We blockbuster make potential pancreatic in Important agenda. confident have and to adagrasib include a bold gaining remain top the FDA has lung, are profile the achieve our milestones difference Adagrasib's that cancer U.S., which meaningful potential. XXXX launching with potential colorectal, has remains the in for with

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clinical the We high large programs now with value are areas of three opportunity other broader aggressively have moving a unmet drivers forward in meaningful commercial our important portfolio. and We each in need. development,

interim Phase events needed second We submit SOSX our I inhibitor and the on of study the and reach the MRTXXXXX, MTA for We III of initiated MRTXXXXX, to of for cooperative study are the a program clinical readout second Phase our PRMTX our sitravatinib to track XXXX. of to at INDs inhibitor MRTXXXXX, in half number half trigger SAPPHIRE XXXX. expect KRASGXXD

of ambitious lives to see momentum cancer. I of a our have company established I'll on ourselves this goals Jamie. the transform am proud the excited about to areas company With of year. are we and building. continue execute it enthusiasm we significant We priorities passion as with of all to and over for patients We the and drive with that, urgency across turn sense results these

inhibitor. Chuck's I will touch sitravatinib absence today, on Adagrasib, development. In our MRTXXXXX, MTA and in our clinical David. cooperative three Thanks, programs PRMTX

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cancer filing designation to NDA review patients collaborative process. of brain patients in as from our set of untreated had primary clinical KRYSTAL-X the metastases expect status and active the well cohort the cohort and from study, a separate lung basis continue as the KRYSTAL-X registrational Phase non-small to which We NDA activity have therapy data study brain who FDA in cell and initial look positive was the breakthrough with the have metastases. through with full forward presenting from We II the to interactions

We data and both this expect targeting as present are potential of medical year. ASCO these a venue meeting sets the to at

include TPS adagrasib we than of single-agent as and and enroll We in additional are first-line patients harboring clinical data explore STKXX underserved generating X%. non-small with to less of continue in co-mutations In subpopulations. studies range cancer, as cancers. to in scores as KRAS patients with GXXC wide adagrasib cell patients lung a mutated certain well These patients a continue

pembrolizumab, approval monotherapy non-small enroll from in these BID priority patients XXX-milligram second as pathway at as well where XXXX. studied of in combination of with year in We a expect study patients the in of half adagrasib to plan is II the we the highest provide KRYSTAL-X ongoing cancer, including this We sharing this is additional these initial potential continue lung the accelerated TPS score. adagrasib adagrasib in systemic an patients stratified dose of by study. share from Phase clarity on update trials. cell advanced naive the being in a KRYSTAL-X combination to The Also therapy cohorts and to analysis for year, as most data

ongoing year. III a later results evaluating planning This actively from the subject the study. pembrolizumab to in KX to treatment-naive and adagrasib trial is combination Phase start We also this are patients

late-line both colorectal in enroll We with also a single-agent continue with to as cancer, patients in cetuximab. combination and CRC

We registration-enabling enroll second-line III are in the in study to with also CRC continuing Phase cetuximab combination patients.

Cancer ASCO Symposium GI results pleased the we at We recently in favorable are and cancer the presented with cancers. also other gastrointestinal pancreatic

other tumors regulatory KRAS are We patients and in approval solid populations. potential continuing and to to enroll explore these continue will mutations with patient pathways accelerated

pathway provide We steps approval well adagrasib CRC in as sharing to solid including cancer on for of this late-line as a in expect additional other tumors, accelerated year. clarity pancreatic potential next

adagrasib development beyond inhibitor include pursue cetuximab. a X/X a pembrolizumab SOSX combinations inhibitors pathway mechanism as with continue MEK/RAF well the and combination VS-XXXX, combinations unique We of These a broad CDK with with action. to or for SHPX, as program

we've data additional in proof-of-concept to expect generated of We some data. initial have combination studies XXXX for these after readouts

will of combination are explore beyond we the options additional potential We currently evaluating. to continue novel those

moving to on sitravatinib. Now

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or second-generation PRMTX to this cooperative MRTXXXXX. Again, the Now inhibitor. moving on next-generation MTA is

cancers. of to with complex. cells. of into human program MTA and target to principle another This first-generation is are to MTAP-deleted synthetic on predicted First, cancer deletions, available non-tumor PRMTX in MTAP ability to spare the of we XXXX selectively XXXX observed to through PRMTX elevated lethality from of bind PRMTX designed advanced is all In MTAP-deleted sparing uniquely very orally are toxicities the XXXX leverages MTA while found abnormally PRMTX is first-generation pleased development. in present MTA targeting selectively based nearly to inhibitors, XX% XXXX a contrast have which cancers. clinical healthy complex targets patients the its cells inhibitors. levels is unique

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to continue preparations our financial launch I'll as are year. our to to a will we strategy enable launch Jamie. several on us subject anticipation We years of to a we of execute ago, of adagrasib. staged quarter in touch approval that early believe Thanks, treatment competitive. successful pillars on approach launch third launch for FDA and as a the highly this be There initiated our two efforts briefly

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top ongoing centers engagement across medical XXXX, customer-facing capability, have unique oncology of experience a to expanded our in products. with networks of industry's because both initiation and in in has built has oncology program. profile launching seen our and have adagrasib's field and enabled a medical. some targeted top extensive an in investment because oncology access academic affairs community success outstanding We culture in roles, incredible commercialization of us we pipeline. significant of and This as This team and Beginning the an demonstrated interest including recruit the resulted

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lung The excited enthusiastic cancer patients With important are about We physicians are this turn and to very this who that, treat with over who Vickie. being deliver it of to for are potential I'll cancer. able treatment to new launch and type this their living also option options with patients to patients. treat waiting

in full-year including to development quarter with billion fourth increases development costs, were in increase growth fourth compensation ended XXXX. employee-related for scale-up additional quarter batches. XXXX fourth you. manufacturing was expense afternoon and General to or of the includes approximately primarily we short-term a expense, salaries expenses Please in and release and $XX.X other business. our period is costs, as increase is share-based of Net other results. the well loss $XXX.X to early sitravatinib, $X.XX with is for of million share-based financial in and fourth Ben. in costs share increase $XXX.X expense, XXXX. associated other same to activities, as to and or and the loss in it cash, and $X.XX includes registrational the Research million $XX.X compared quarter due million $XXX associated about expenses net research to and proceeds and XXXX. with and and adagrasib from period in primarily million discovery for the quarter same this in approximately our related basic development diluted period net our hand associated which and quarter of We research compared professional earlier XXXX costs growth and capital you, an raise investments, related David, basic salaries over expenses XXXX I'll back a November the equivalents the the of due preclinical fourth which includes The share XXXX. Thank services in administrative million costs, same one-time with other secondary $XXX.X development were for compensation cash commercial $XX.X XXXX the see completed for compared per million of $X.X for which expenses million to press from for diluted which details of per The

exciting is reinforcing what Thanks, for by conclude time Vickie. I'll it Mirati.

targeted and significant We portfolio. and commercial tumors our synergies have long-term operational pipeline value in sustainable multiple and and across see a the broad across targets oncology

for We long-term have the financial to resources invest continue success. to

of to important We invest to the are a adagrasib development blockbuster optimize well broad as continuing enable product. is readiness launch in in U.S. to potential us plan this

develop is market-leading to Our objective a further launch and KRASGXXC inhibitor.

of drive and to pipeline rapid We across innovative beyond are ensure our investing breadth target adagrasib. oncology progression sustainable the growth

accelerating In fourth agreements. two built, the we addition to through our the In internal collaboration capabilities non-exclusive progress have partnerships. we announced we are enhancing clinical quarter, and selective

The first inhibitor. with SHPX of Sanofi's evaluate is combination investigational with Sanofi adagrasib the to

The investigational the adagrasib inhibitor. second Verastem's is evaluate with to RAF/MEK Oncology with of combination Verastem

partnerships. active We opportunities our pursuing expect to and in continue to through pipeline be accelerate expand to

incredible improving have we be energy We continue Mirati. thank to milestones the have as have are With to for are patients I incredibly continued important transform the cancer. for I the pleased their focus progress the of forward made questions. we we passion an and at take to work the with them look the with They we and lives efforts and lives team are impressed ready to patients. that, approaching. many by we of

Thank Cowen Instructions] will & We question our Company. Van you. Tyler [Operator take with Biren from first

thank questions. see the progress, Hey, I have and two. to guys. all Great you for taking the

for recent the FDA question And have the earlier look visits if regulatory than RTOR related as site with on expected data. is ASCO. audits that First, response And be occurring anything might elaborate been and conducted there disclosed that positive the data this conversations previously, could based look to CNS that could process? by We'll full else should other confirm the been your results is the the II Is you to disclosed second data Or on to site at but differentiating? have consultants? Phase be than of that or part obviously release primarily we that? met

couple of A Tyler, it's David. things.

Regarding part think having pilot a review. review, adagrasib, certainly sign without is business. site are I on real-time FDA a of start gives audits the the it's the certainly the being of We it standard take – for as the the engaged, agency the that program occurring oncology it that already some good head

slide happen, to I happening that have the now the ongoing interactions happened, more not think So on are discuss but as some they will that. right sign we're the FDA, it going but take with a positive we with

at the Regarding be a full at so data that A we the ASCO. trial having we set time. that going expect first the We're time to same ASCO, to data well we're will presented data present the published at announcing data. for registrational intend for [Brady as We data for ASCO. data be to Med's] stay released the cohort as the announce of at the tuned set presenting We're that

you. Thank

you. Thank

And next, on we'll Gena to Barclays. you. Thank move with Wang

good evening. you Hi, okay? Can This for Gena. on is hear Rashida me

Yes.

Thank you.

a clarification, data I that have STKXX these monotherapy First, I low, in I just and be sets XXXX? both a question. follow-up XL sometime will first-line correctly the set had hear then for presented data and TPS quick Did

is Yes. or Jamie. two cohorts That be our these are would just note separate goal. This And that studies. to

and them KRAS is STKXX of One co-mutation. mutation with

KRAS with on planning than year. yes, in presenting would that other score And we one next The TPS be X%. less is mutation

for the patients assume the to can it you point, XX three for time have Thank the Great. least enroll minimum quarters PD-X the XXX-milligram set of in at follow-up that at XX-patient in second to had other be Okay. the that fair to Then range is you. cohort, combo I least that is the half number given data patients?

to elaborate. Jamie on David. I'll that it's ask and So jump

BID that announced now encouraged we is trial actively ongoing protocol when we're in fall what a milligrams The recruitment. we're We're going full So switch with the dose enrolling. as is to to we pembrolizumab. XXX the plus right enrolling trial do

So a decision patients. it into preparing into couple for scans Phase III Phase it And else? a inform double-digit number and to and of well can that to patient use be to will of a we're you already us patients data what combination, tolerability to think Rashida? we're That the going but meaningful maybe to anything going the we're have as the a helps, III start, We this, at of we'll We Okay. do get safety meaningful is data by will population. of actively and set. the we'll to look make be that Phase going that range jump for That will know, Jamie, III. that program. number

that's No, much. so you helpful. Thank

Sure.

Thank you.

we'll Next, Gavin move on with to JPMorgan. Scott

Hi. Thanks for taking the question.

while on PD-X follow-up a underpinnings I that the just [Lumata] chemo. or PD-X molecular any better patients that there combo. patients with trial treated the a in I'm has your guess around would PD-X highlighted suggest asking had in response you've context guess are there, I XX%. previously registrational Just XX% that

So just curious your on thoughts.

Yes. This again. is Jamie,

unmet premise the around that X% see standard that less it's us we date developing setting suggesting activity to say sure agency would data subpopulation. need enhanced X% at OS we today of STKXX follow looking the course, rest We're unmet rate there the logical than to with PFS patients. If to fairly are in as point response unmet we at have and, discussion strong population that making for of a need. partially it therapies. also to immunotherapy the prior be of the need the we're think chemo going after of would drug this of That's medical both least with TPS the relates as data the TPS there. on that wouldn't continue with the the and that the suspect therapy response medical answer no Amgen's Would fully than of there, good as and less rates, would medical low is subset be believe co-mutated hard I kind population based to that there's out the just we in a STKXX as reminder there a KEAPX information hand, question say especially co-mutations, the and reason

say an preclinical that on response patient that data, could effort we citing And as do immune as us based again, tumors reawaken cold, I mentioned inhibitor So for somewhat a maybe believe, monotherapy. populations earlier. that would immune that that KRAS those I the remains the just in

like one as fact, please monotherapies. than with So STKXX, believe these therapies we'll and me both well the I populations treatment pursuing answer do subject didn't in less would know. combination And if KEAPX And both question, be TPS as that that angles be there. let your to

you. helpful. That was very Thank

you. Thank will move on Umer ISI. next to And Evercore Raffat we with

on Eric is for This Umer. Hi.

Just questions. quick two

the first on The PRMTX.

agents? submitted, profile details of expected can what With sort trial versus safety the you PD the And share IND design? what's competitive or on the

Sure. Yes.

regarding trial First, the design.

XXXX therapies And development essentially settings are designed in on the subsets targeting guidance studies multiple allow are around agency's utilizing these patients. and We of rapid multi-cohort for that studies. to are essentially targeted

So this we and with one where a to toxicology in approaching as us Phase way, we study of the pleased be doses, into a an studies patients tolerability establish or an which would would different would perhaps be objectives. as Ib well Number dose high reasonably understanding multiple antitumor the escalation allow monotherapy with a that study studies II will we with We're any for of study. start with MTAP enhanced first evaluating outcome patient Army be our activity Once deletion dose be Swiss dose-dependent, in gene also will part pursuing the the recommended Phase to therapeutic of concentrations. dose a get first activity. is the breaking we studies, be knife in of

that malignancies. I the we squamous Phase well as as cell all cell moving of a activity catch then And with the doesn't mesothelioma a two ductal adeno four non-small including sets of cancer, those would finally, kind pancreatic both looking be mentioned, And dose, II expansion we'll different primary expanded a sheath peripheral and soon had would cohorts. the nerve adenocarcinoma, indications, recommended they're monotherapy. we're Phase be four as opening patient Anybody more lung As in confident tumors. all. as these essentially niche in one cancer II cohorts one additional at have And malignant be first forward which and of who cohort,

I pointed but So go to say PRMTX say interesting setting I studies two substrate couple that in combinations. as are we be that's not will co-dependencies to have a one. soon into in recommended detail much with that going ongoing to inhibition of would I'm combinations preclinical is the part Part interested today, as would II identify the Phase rational we a dose. the start

interesting So that one would to also be I think inhibitors. Then [histones] as with And gene potentially inhibitor molecular mechanism be of regulate part which the the of associated to how molecular with thing works to last near is PRMTX dose studies dimethylarginine, marker the of was maximally relationship, this come first-in-human effective expression. is separate aspects pursue that the action marker aggressively study study. has your relative completely a question particular and PRMTX that or our the inhibiting suggesting symmetrical in through first-generation depending preclinical pharmacodynamic could on a also really primary or related out PK/PD and

second complete dose we inhibition the differentiated first the to SDMA inhibitors that or do And near is complete the critical. going complete – essentially inhibition. key is factor for second-generation do believe near be So of full versus view that to circle achieve ability with

proposition inhibition going the this to is limited somewhat monotherapy think, They're they're be analyzed, thrombocytopenia, by critical measure, good to the are First-generation value full inhibitors achieve our and pretty premise SDMA of able anemia inhibition. activity. I to class drugs. and although it's for of development drive In neutropenia,

hit the I points. think all Did I miss anything? I key

dynamics the timeline all. any that's change And no, plans Are there readiness updates given one review just longer question. No, or commercial follow-up competitive to in the any there?

David. Hi. Sure. It's

tell field. preparedness, so this the – commercial we've year. I being We medical that excited got already affairs And a a come did far. launch-ready plan you, we've organization where Regarding we're QX by really the launch about on in

value have team and access in the We field.

launch. successful management sales even a time the have gives rapid for and timeline to highly field. This more prepare We us in

rapid add we're right launch ready approach we'll So Ben, that's the there want that? be to a for forward and and launch building to really, the taking to planning, you blockbuster. and a look anything go really to

No.

big get understand confident. pretty little interactions more. more a you’ve No a and few well. our of got think changes. We'd We've customers very going sharpen on, the and dynamics I really with framed we to some things feel

time can sharpen So that I bit little we think further. things a more even means hopefully

Great. Thank you.

we'll Goldman to And Salveen move on you. Thank Richter next, with Sachs.

This Andrea taking for please. the questions question. for is Salveen. Thanks on Two for us,

The to ASCO. as prior CNS first, you're expecting on maybe the the question follow-up a data at that

Just frame expectations will this you differentiation read into think meaningful wondering about could if you help Lumakras? you how when think and to this demonstrating be against

Sure. Yes, Lumakras presented we the and course, data. look closely formerly aware properties are of drug our we and of of at

what's called the relative the level is of time at KPU approaching about studied adagrasib, we concentrations commented think CNS. I free point. which previously values a which drug few preclinically comparable plasma clinically, into cerebrospinal X.X, key So And fraction to the of value, and essentially on points we've seen is adjusted both a KPU get in fluid we've the a the ability the And to drug meaningful.

inhibitors. strong and activity is agents with of of different brain values or are of that have very ALK kind osimertinib relative invents pretty to penetrants couple patients brain than X.X and, bars an first-generation in example CNS of a greater X is has inhibitor and in value Just metastases. with alectinib, metastases a robust the drug very about that that, have drugs of a The that again, activity differentiated KPU two space, against and KPU lorlatinib demonstrated

crizotinib rates response with the around rate in inhibitor then in And is of lung the So again, intracranial space, space, in with XX% a EGFR a inhibitor. penetrant and gefitinib non-brain XX% no, let's about agents note are and that metastases cancer patients. an erlotinib agent ALK response

consistent agents have You that fairly rates that intracranial disease. osimertinib with may demonstrated activity their alectinib be peripheral in aware are all lorlatinib, response

suggesting the drug there. that if essentially into the So can and can differentiated robust get be demonstrate CNS activity it

or note meeting patients brain substantial As have essentially open believe will there, we would about we ASCO I metastases or the brain talk in with the wherever number untreated mentioned we we've had a to the cohort active that land and of metastases. call, at

of also analysis which have that from We least talk drug metastases. talking setting. I We'll treated [indiscernible] will be the preliminary about essentially in patients be to meaningful about talking will appraise that patients, this the our we'll of to about And think number at that. be activity subset again, controlled have or brain the

then for Ben. question, a it. for And Got second maybe

and than with Lumakras fourth diagnosis patient had Just being robust. lighter some quarter expected, despite the being sales identification pretty

for physician your can what slowing the here? anything is you drive when And is curious Thanks uptake additional do is is so much. there what on adagrasib sense Just market? utilization to

Sure. the Thanks for question.

think I the novel testing does class of a occur line. bear, front almost XX% to that most reminder, to the it with be in as just coming have reminded a of people

regimen, still patients those for these into months now actually So with benefit beyond or therapy. the XXX of XX to come second patients XX the line it's taking to

take does while that a understanding in work it the also dynamics the And time. a some So the understanding take done does to EMR. secondarily, local about we've identified patients and for lot of be that

on it. actual be So action physicians to to able and to see mutation an that take it's

physicians be and mature. take the So little line hopefully, becoming those expect as for that I that mature KRASGXXC this available a to we year, patients it to market, continuing we market And will later inhibitor. looking come preferred second and the while in to We will see beyond. think

second being been in to already not its its market. not And sometimes the have focused the some sometimes so case, something not – this much we testing it best, are advantages. has have date. of to completed, that's having foundational work we always that on the It's but been So

lot going that that, of behind add physicians and this as by shaping I of then KRASGXXC building doing profile our on benefit testing. to think And the for educating were the patients. clinical inhibitor a and time we're us, efforts those the we by of – to on Yes. certainly, the Lumakras GXXC will communicating market a would their we be can approved adagrasib focus we

much. so Thanks

Thank you.

Capital our we'll BMO Evan with Markets. Next, next question take Seigerman from

Thank my Hi, so you for guys. much questions. taking

updates. the Just a for you few guys with

frontline I regulators the bar what STKXX looking on the conversations with co-mutation. setting here. And in TPS to less patients And can the had So the the in for if of then follow-up than expand and X with two you have kind as monotherapy they're you both questions? for

Sure.

KEYNOTE-XXX to it of first TPS as your question, noting, score. first Regarding relates all,

may you hypothesis And with a had did that overall around the the TPS essentially, rate upon recall, rate X% and that whole scores patients the analysis, then less of for XX%. to XX%. bogey our improve as of response than was KEYNOTE-XXX, response And So the co-mutations. when represents KRAS they subset

XX%. that has mostly the analyses subset, to XX% major coming rate is also going the about Secondly, be think that defined response by there numbers patients STKXX at there And KRAS centers. been co-mutation are have that bogey the for academic I cancer the to KRAS a STKXX out is

So essentially improve we upon. again, to that's what need

Now I think sets the when prior or in a to you a for look shoot bit drug at a precedent approvals setting, also bar for. us first-line of that

first-line the with perhaps drug approvals XX% response over setting, of over been And some in in so cases. rates there have XX%,

so populations. a parts And clear how the those patient be XX% a XX% you those of take or give differentiation expect response to able in you particular hit if standard-of-care to from equation rate performs two higher to would would together,

We ongoing need to quote those patient think exceed. present review range duration particular they submit we with responses for a will, I they or issue. us we would response But data agency number compelling rate have of should particular in the call that ranges had with that course, of sets. if never the in generally a target reasonable to encouraged that provide we discussions They be

really that's stand we today. where So

our our All are preliminary data-driven. rest is with now agency program discussions of the the considered and of

a when kind study about That's expand you talk may planning for of for waiting can and III what when PD-LX combo, like then Phase you're And And you actually here? on also quite that the touch helpful. what start means?

to patients setting be in inhibitor first and launched the available and GXXC we population. start, approved of want want protocol. it's And and significant preparation realize aggressive, the we in and fast. move want and So We let over to David, to that the is, We be that frontline for regarding first that the time. is to opportunity me to for patient studied Phase all, ultimately be the III combination

why that's plus planning XXX So for pembro. success milligrams BID we're with

things do as can. to parallel like like and fast here. do we don't we as sequentially to So move We things in

over part I'll Jamie first So question. it that that's the of turn to to...

we certainly mean than greater success note months. let's here. And an is study for Phase a need I equation nine agree. I III poised be opening Yes, to that planning and its of globally

statistical open perform able control essentially, know is, patients. hypothesis, that is and of think So regard how would to we a that I KRAS-mutated be what equation the to planning as study. regimen that actively KEYNOTE-XXX in we part With are to

respect ongoing pembrolizumab assumptions essentially basing of initially we're our how to as trial will know, the adagrasib clinical So design and with dose additional least we have be And to help perform you that. study we KRYSTAL-X make around intensity then with some inform on response to to data, assumptions with design. able rate. otherwise, trial initial also the tolerability, at some that clinical but regard And would and

this we've small encouraged what mg are So the and seen that's along. really where understand we We've looking from number the better comes as stand patients of been point. that to BID at with year XXX

All right. Thanks Appreciate much it. so guys.

you. next, with And move to Michael on we'll Schmidt Thank Guggenheim.

you questions. for my taking Thank

in approval an question accelerated you. Thank earlier the enrolled then Or cohorts. you setting cohorts. in follow-up I first a about monotherapy, perhaps and on any cancer we have was two potentially? preliminary strategy size pancreatic your consider cohorts, are the to these potential the patients line should to PDAC? other in targeted Just move a plans And the cancer many about really two with your those had there are discussions the in either of how sample into opportunities guess third-line be conversations FDA,

Sure. Yes.

cohorts. Regarding the two

no response response. again, PD-LX we would rate would hypothesis the So a the it in what know of somewhere beat X, for with facto essentially XX% to subpopulation response the be XX% meaningful duration XX% around lesson it STKXX range, the meaningful of duration for a with

the give agency, in the be we we approval response what a or they with will unreasonable. in number but targets, prior experience other approval us if of settings. essentially, regard the noted therapies have to duration as these of targeted response, not number use rate get monotherapies the wouldn't necessary As of patients those discussions as we need with with do to to accomplish And

We safety additional as a significant all that work other the also we're database we doing. recognize have monotherapy a from

So cancer a enrollment in non-small I for can't other really give you cell the accelerated that a targeted approvable in range number approvals set of data therapies monotherapies today, of believe be kind could setting. but lung we of or the the essentially

on question I the think your earlier of you're GI at pancreatic this presented For aware cancer, data we ASCO year.

duration So line. even when progression-free of and first response a months you is meaningful of just care, to seven north six XX% standard look survival know, to of rate for at response or maintaining a actually

Now patients. it program would in start to for be development us a challenging treatment-naive

So third-line we'll continue patients. to focus on and second

we'll holds get data, durability along along we for more a of help ongoing in would if inform we've path. those that generated generation the more with other types and really, possibility understanding of that further that settings. and a better of one up, mature data that approval database that will otherwise, As either safety think accelerated And the And be the of an response. wait we of cancer to with again, data

it. And Got clarify… just Okay. to

frontline as with that that patients non-small patient say with first-line the cell patient the represents well cancer X%, aggressively mutation. already just just me less cancer the lung population Mike, XX% on the lung score the because we're with let STKXX than about Sorry, very of of GXXC in and some TPS co-mutation the moving

need So great Back opportunity in Mike. the the is that patient and to is high unmet you population.

make sense. That

cohort in non-small or are certain patients.? something cell lower a in than we Just that to clarify, XXX that, cancer patients have other line you already data given first thinking per just amount of

mean, in remains undefined. issue review spirit a and is this that response please I take it Again, my the Right.

XX% So in statistical hypotheses. of in of would convincing response you to X ultimately, XX% of depending XX% to agency. beyond that to hypotheses purely hypotheses. the targeting a developed or those look would higher the out, shakes a assuming STKXX to less the essentially if and number determine just a that on XX% way, Again, be present data assuming or this probably the number hypotheses rates argument, say, the statistical how at were no statistical those XXX. And the as our the we've are under patients assumptions argument But than would in and TPS XX% necessary

Stifel. Burnett Thank you. Ben And next, we'll move on with to

you Thank very the just much. quick I had a on Excellent. question data. CNS

label? be that is at potentially this drug timing Just in something given adagrasib the ASCO, might included the

try we'll much as put going guarantees. the and the question, dialogue no in to certainly to emerges, possible. We'll that Ben. possible, data with to get label, certainly the Yes. that We're moving as clinical data as with agency both Great as the fast adagrasib data preclinical We're have agency. have approved have as

guidelines, listing, be So in I'd say as with catch the able in to a we're will if a the up available to label, like pathways go label. minimum, clinical data would until compendia not the the it's listing for published certainly we

just level GXXC kind of is if equally That's of in Understood. as on are were what tumors we And just KRASGXXD addicted – I having. could pancreatic helpful. I tumors Okay. guess discussion evidence piggyback the pancreatic as that cancer.

inhibitor get a this Just GXXD Any adagrasib And sense good thoughts what here. predictive data if the in a for from to be to there? might somewhat trying expect setting?

And that GXXD. I a well. that's versus Yes, and think been as think there question. some GXXC interesting commonalities I mutations really We've are at looking between [PDAC]

a intraepithelial appear which by is pancreatic think of genetic kind at XX in I that, adenocarcinoma observations that of genetic ductal neoplasia, those those very from cancers class lesion, founding one of mutations. of looking going KRAS of years move be this the now caused sequence of is events these kind are back to event early pancreatic the kind

to GXXD of not up a tried mutation. number The off So if look late to a tumor not to certainly size stacks we Number would and at both decreasing And models at disease possible pancreatic topically GXXC with get regard least, to tumor We've and pretty is implantation. KRAS we hands at that when looked models. looking the our of XX% of have be very genetic two going every them, the have the on or XX%. expect all heterogeneous acquisition vast well. greater a cells, are to least adenocarcinoma majority preclinically, orthotopically modeling data ductal majority we at those than the in model, the of founder at are mutation It's demonstrate event. of going

DepMap functional responded lines. than likely a in of tumor So certainly pancreatic and that if Project systemic tumor kind of if strongest regression knockdown paper for pancreatic of genomic of different across goes including X,XXX over will mining. enrichment we the higher those often at over – It's of at the ductal of closely then hundreds, that. DepMap not cell studies adenocarcinoma lines you shortly, dependencies looking a looked the the at MRTXXXXX you strongest least by again, these pops found at if XX%, of eight DepMap both the XX look data be kind have studies, hits, adenocarcinoma models models and And it out lot accepted and of that large up as Drive have for in one GXXD those here look finally, ductal genes,

triangulate, is is do a that and GXXD in some PDAC and likely there kind pieces believe those very take of of read-through that for we you three adagrasib. driver strong So information

is the GXXD is population significantly And patient mutations is patient pancreatic patients. than prevalence of significantly it longer for GXXC significantly – larger, the greater of population

on the build going comment, Yes, ductal have adenocarcinoma David's a patients to are mutation believe is around GXXD pancreatic XX% overall to just prevalence I of U.S. XX,XXX.

are medical those strong a unmet of need. All

That's color. you. Thank it. great Okay. appreciate I

Thank Maurice with you. We'll move Jefferies. on Raycroft to

Strang for taking Kevin is on This questions. Maury. my for Thanks

on listed you'd prior PDUFA? you be than have confident able how Could how the is more plan the XXX III. right you you enrollment any this to not Phase and whether sites going then any are the the on you color December first enroll to Just And that open give into now? to or

of cell too, in jump in trial can cancer. Jamie couple David, It's and A non-small second-line the confirmatory things. for lung adagrasib for Yes.

For trial. that, It's we've With time. in the we're expanded global this trial increase really a enrollment. encouraged by at the that,

Asia. partner added U.S. – sites me, us in Zai excuse our we've sites helping of So a European number is

is recruitment the well. going So

clarity, for that approval. be an regulations. Just per to That's to prior fully enrolled trial does not need FDA

recruited underway be we be later will and well we very However, time are we'll this year. Jamie? think well by approved should adagrasib be the underway well and

trial [indiscernible] and that's mass global The I with that in major would a is opening uptick of certainly really the we now, opening globally, for enrollment only sites thing opening and see the now associated catalyst add with are can trial. up too an the

Does that answer your question, Kevin?

couple Yes, on just in PDAC. – cell small of ct.gov on cetuximab one quick And a for you. it you've does. combinations new a opened and Thank then study your arms for KRYSTAL

for You've and Can about rationale you your about talk spoken just pursuing before shown indications? – combination these you've data that for in CRC.

to and link it that's well. among EGFR that believe cancer, remain also KRAS. important in EGFR first pancreatic EGFR demonstrated we biology cancers be turned a Sure. very to very lung family but colorectal to as out in Certainly, and observed have strong is and top been combinations we've preclinically

us down success are for that essentially, we in that as look covering the and both able to up of want opened double CRC, And some those to cetuximab So due well. make other certainly the it to to to options sure at malignancies of and be of block all interest we pathways.

really of that's us that. So the basis looking at

you. Thank Great.

Ulz Thank And we'll Morgan Mike you. next, take Stanley. with

thanks for the taking question. Hey guys,

are of dose mentioned Or if us you'd one for the well? considering that I'm me as XXX adagrasib PD-X you adagrasib terms quick XXX-milligram there? curious combination you providing using strategy But beyond of can you're in one using on dose? remind cetuximab, Is the year. it next what data Just just of and your some

started XXX then escalation, looks can dose if go up we're we with that we starting promising, when from and XXX. Generally,

would combination to XXX. with combination trials escalated ongoing have XXX we have we So some and up that I right the now dose, have studies say

to just constantly is of response the the of highly clinical BID And to So as confident you exposures exposure say like quite regard well. analysis generated, are mg imagine, we've sets done we're things essentially any looking covering some at the that dose and we analysis target can both. at and in XXX – we've data XXX with look PK that that

it milligram or response, pembrolizumab forward level. move we that combination at XXX data be overall any level, promising look the dose whether dose quite otherwise, So in exposure that PK a with

Thank you.

Yes. Sarah time Mike. have one question. Thanks last looks like we for

Thank Nochomovitz last Citi. Yigal from We'll take one question you. with

on Yigal. Great. question. for for Thanks so Hi. This Carly much our taking is

We have questions. two

First, begun launch. affairs that I in the medical think mentioned activities you you've preparation for

properties, the context there CNS So stand any helpful. program? of with the certain We get that PK then we're or question the work be else, on whether long hoping where second adagrasib just could something half-life most penetrants just were physicians, resonating additional you. believe would curious GXXD. an if are you is are aspects you differentiation just formulation there provide update on to you for with Thank And it's that

will answer this. Jamie David, So and Ben

Regarding affairs been the in field medical medical since affairs, has XXXX.

of approaching that The rates, well physicians to unique that that has response very the rapidly in our adagrasib they’re adagrasib profile. trial. XX-hour is have time on as very the a and KRASGXXC been rate for the we in the appreciative target two part So reading registration inhibitor. marketplace, molecular have the response excited as the very half-life, the years XX% preparing market through overall about story appealing the And find physicians

activity also is the we to and well. very Also, and very that's spoke profile unique CNS over appealing Jamie mets going regarding the have about So molecular physicians. earlier brain there

impact they're you add. Organization, And of comments Medical the couple So regarding having. there's a other Affairs would data Ben, points

in magnificent are back consistently profile Yes. the seen U.S. we and about then and across forward the what brain They one, that ask the the the believe and I presentation. seeing they data data tumors. enthused doing enthused XX-hour studies. would the and from, on folks why more data part hear looking to of that clinical certainly and half is a mets by forward a that's but around of And data, us they're some preclinical just obviously, we've rates the molecular enrollment from are response both the consistent results lightening. upcoming lot to on driving that From job focused we in add EU a they have and story do looking

satisfied And communicated. the GXXD I Okay. of respect think initially potency, checks lot low. GXXD on activity. the necessary a intrinsic developing duration we've X.XX with front, the this to a to Yes. is and really as of oral And fairly so boxes formulation, metabolic previously we but stability, the as target But coverage weren't IV with viability solubility monotherapy drive otherwise. standard just started

and range, associated example our shifted of absorption be approach. been, evaluated then up formulation as long-acting that And make there us cycle long-acting that of enhance the with drug a well. as duration a achieving think is oral think, at as if clinically advancing at to well. we set And we we exploratory progress long-acting of the injectables. I a to encouraged gears we in the And some liposome-based that is we've that have Those addition bioavailability So long-acting a in by injectable the a could with do going coverage. also I for a other us it's life in week that I'd way that more IV there somewhere the can forward other that this if longer IND are that point, can to date. clinically, where had once target oral we've that in that And develop or feasible process. ongoing, We or to deliver of it's drug. injectables half-life possible those but properties with to finally, One maybe formulation. we've ways we're move formulations essentially And see in extending preclinical can strategy the far, are we've PK injectable seen looking track species say, preclinical we've into we there, data where discovered the we're eventually towards that strongly XXXX are differentiated thus

very Great. you everyone, for Jamie. Thank thank much you, And for your questions. today. us Thank you, joining also

exciting you leading and from ones. the their and and of oncology therapies future innovative Mirati. therapies science updates on intangible relentless our on sharing patients the really look focus translating that bring deliver design of biotech There's our way in loved target creating novel and transform about you with with cancer hope lives of patients, told Mirati we company to one forward continue a get we're a many mission to speaking of portfolios team, most As at with We're we the toward to biopharma. as the excited to additional discover, progress and to well breakthrough to

does appreciate do And teleconference. conclude you. that Thank today's We participation. your

now may You disconnect.