Mirati Therapeutics (MRTX) 5 May 222022 Q1 Earnings call transcript

Good afternoon, and welcome to the Mirati Therapeutics First Quarter 2022 Earnings Call. My name is Kevin, and I will be the operator for today's call. [Operator Instructions] It is my pleasure to introduce Ryan Asay, Vice President of Corporate Affairs at Mirati. Ryan, you may begin the call.

Thank you, Kevin. afternoon's this to everyone, call. Welcome,

Founder the available Joining Mirati's Officer, Christensen, of Dr. Mirati's from Research Chief President, couple Chief Commercial Scientific Vickie Officer. today locations me Chuck Development; are Reed, Jamie Mirati's Officer; Accounting on Chief different Executive David a Chief Ben of Mirati's and call Meek, Dr. Head and Officer; Baum, and conference for Mirati's Hickey, Please is will the and portion to differ will also those the may with Because call. this us many materially results of with and in statements. note forward-looking forward-looking be that deal future call and include the risks statements are statements. Actual from Q&A such uncertainties. events subject

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

and an for on And to quarter, significant and to goals provide on Thank your will for the Jamie XXXX this remarks share portfolio progress taking afternoon's to our we us provide first quarter turning to you, call, clinical preclinical programs first comment initial questions. Ryan. year joining we update a will afternoon, for financial Mirati. and critical thank few to a Chuck on I our results. concluding Good the ourselves. development made you today. On our remarks ambitious then Vickie summarize before I established in is before transformational

patients doing. there across company The all the work portfolio, be areas well are to continues our impact we for making the we with are and continue and We the having cancer. of execute life-changing to living on progress across we significant enthusiasm are

is new review treated is as mutation who pembrolizumab of previously is our includes results. under are as and we review both pilot for that presented beyond tumors the and lines cell a fully broad a single Without of the for potential agent the earlier KRAS previously advancing also doing FDA's and cell harbor we pancreatic help of with believe beginning solid are NDA cell launch-ready program. lung NDA under a full with first the in across cancer The in are just non-small where our non-small We We have Securing a cancers, can compelling approvability is the we priority colorectal pleased cancer aggressive, the product company, for accelerated commercial early in cell This FDA. work cancer drug in adagrasib combination of setting non-small therapies in treated patients. including number other tumors. second-line therapy of reviewing patients with investigational and of other plan U.S. the previously will for a first-line development and third broad non-small adagrasib a lung this where FDA in such application combination oncology treatment lung confident key the the with in approval real-time and is approval of the remain a in we but a a range executing it quarter. launch cancer lung be GXXC

pipeline. our expand to broad addition adagrasib, target continue we In to advance oncology and

quarter for trial with Phase of overall events XXXX. X an reach needed the positive, to enrollment number a recently and we completed trigger analysis would opportunity in fourth commercial be of expect synergistic a sitravatinib, highly the If SAPPHIRE adagrasib. interim For registration survival sitravatinib to in

these XXX,XXX following or are a checkpoint and there our Europe, with with is NTA patients MRTXXXXX, inhibitor prior U.S. second are of data patients X/X PRMTX in benefit treatment clinical the third-line the of year. non-squamous ongoing reminder, a cancer trial patients non-small XX,XXX in and with As enrolling clinical approximately over next who cell derive histology. program expected proof-of-concept an clinical Phase lung cooperative

new MRTXXXXX, oncology target second of in the inhibitor our SOSX and advance including toward earlier-stage Our continue our GXX half MRTXXXXX, XXXX. investigational KRAS to drug inhibitor pipeline, applications

tremendously as to that put position us We productive unique to and the commercial points the as call advance mechanisms synergistic months. in-house in in discovery terms clinical capability have future yet next clinical development a of many five have novel a execution in in continues XX discover programs and and

We this across later adagrasib strong launch FDA success for potential continue which financial position and pending execute a strategy, pipeline our the target to approval to our flexibility in year. on a with for us and in provides preparation successful to invest be oncology

As we enable are we continuing better call objectives. that, turn strengthen to our our I'll to our capabilities over grow advance to With the Chuck. to and achieve pipeline, us

Thank you, David. I'll begin with adagrasib update.

to FDA application our new review work they the based with on breakthrough review designation. our oncology drug We as therapy and real-time continue

complete We possible. the quickly review closely continue as the to to work with FDA as

with the quarter will and we in Medicines of application to of In are year. XXXX. progressing validation accelerated States States, of the this the complete ASCO. review beginning with approval is remain marketing confident and United significant XXXX, progress pleased clinical an the Agency how for updates a the our number are in in expect Outside program, the second report making European authorization we submission We to United and the adagrasib

by abstracts accepted We to two for have ASCO oral are pleased presentation.

of patients results non-small the for tumors the registration-enabling Phase whose study adagrasib the CRYSTAL treated cohort cancer KRAS presentation X first of mutation. lung The cell harbor previously is GXXD in the I evaluating with

STKXX as presentation metastases. treated nervous PD-LX well like or In mutations will status, as important previously several central patient system, genomically based patients including addition, across populations, with subgroups patient CNS, data co-occurring the defined include stable on

including highlight presentation active KRAS first inhibitor the patients will approximately cell is of inhibitor. non-small single full CDKX/X CNS SOSX, and we clinical dual present our where cancer with pembrolizumab, to adagrasib with a in as reinforce of data mutated in development non-small the with presentation the patients a lung development MEK/RAF program activity and care. be second to metastases. the tumors will pathway these with an GXXC activity cancer untreated with with of Together, SHPX, molecular are CNS frequency a up broad standard The profile and patients a CNS showing adagrasib's combination, cell adagrasib these increases approach metastases important untreated activity and lung of over KRAS CNS combinations cetuximab, time with in underscore attribute XX% GXXC metastasis. because with agent mutations advancing presentations pursuing current and commitment This unique

of We additional are wide generating data with actively range that enrolling are patients patients worldwide adagrasib clinical in a in cancers. studies

Our X%. patients non-small GXXC patients as non-small underserved XX in previously adagrasib well are which Phase to randomized as X in to GXXC adagrasib confirmatory GXXC patients than with certain cell mutated worldwide. scores TPS STKXX patients continues KRAS cell and study less monotherapy known continue cancer, lung docetaxel patients as or well of cancer to lung COMI CRYSTAL first-line harboring subpopulations, treated KRAS with in mutation KRAS including a In enroll explore we

pembrolizumab and plan combination from a X for later interest as share Cristal on year to stratified this and analysis trial approval accelerated We update to XK provide we regulatory is cell in combination pembrolizumab potential patients additional well cohorts as subpopulations study VII initial We these pembrolizumab, from cancer evaluating non-small in plus in by full cancer with study well data of a the on which combination, patients dose are first-line expect VII, combination both pathway focus which these score. physicians. TPS with year, XXXX. year. first-line XXX-milligram pembrolizumab. cell to plan combination using in This on this Phase of Based in include adagrasib sharing patients lung Cristal this patients, aggressively adagrasib this Also initiate strong will an non-small the clarity Phase from lung the an enrolling BID of the in results dose with exploring from we adagrasib a trials with is adagrasib

in advancing cancer, in Beyond cetuximab an X line and in population. colorectal second-line The with continues patients opportunity ongoing the patient well lung with potentially this combination we colorectal to and second-line Phase both in cancer, cancer in the enroll to first late settings. enrollment market to registration-enabling with are study be us provides in

mutations GXXC explore subpopulations. these including with approval tumors cancer, patients gastrointestinal solid enroll accelerated to continue in to and others, patients other in pathways will regulatory continue and pancreatic, potential We biliary

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

Now sitravatinib. to move to on

or X enrollment cancer we David SAPPHIRE treatment non-small being in trial, which with prior Phase inhibitor. mentioned, completed is As derived checkpoint second- cell with who conducted third-line following clinical have benefit recently a lung the in patients

track overall positive, be and full the of If filings year. for could trigger of submitted the the for both survival on in in quarter approval in are next number analysis by Europe with analysis the to the events We interim of regulatory U.S. needed an reach the being XXXX. to fourth markets interim middle basis

of MTAP study MTA our deletion, Phase dose tumors make X whose dose are to enrolling in XX% escalation program, a solid tumor MRTX-XXXX, patients. expansion we cooperative For harbor and up which PRMTX patients

will tumor basket lung, including and and nerve We a nonclinical mesothelioma, explore several as other studies single types. sheath tumor agent in translational across through rational MTAP-deleted malignant peripheral types, identified strategies a MRTXXXXX of accommodation cohort tumor pancreatic,

let And share and it of have initial data discuss to expect the dose Jamie selected XXXX this that, preclinical for concept. after programs. demonstrate to clinical to sufficient hand our proof to with clinical a We in data off we generated me program

known other binds of activity inhibitor KRAS KRAS address the Chuck. reinforcing enhances to that pathway. These XXXX high irrespective address platform preclinical SOSX antitumor GXXD affinity data in preclinical on which presented pipeline GXXD. KRAS towards and of the insight our KRAS to broad mutation the XXXX At provided preclinical Association KRAS pipeline state to Meeting, for in cancers, our selective mutated combined shared a broad complement and into potential for combination to our with by At and recently a selective to additional the currently This majority resistance KRAS and This XXXX are we activity on within noncovalent is models. Thanks, adagrasib. next-generation of to acquired AACR. inactivated activity in inhibitor GXXC with selective regression active is the the selective MAP state and Annual kinase XXXX inactivation also Spectrum briefly Research and inhibitor target IND-enabling of its the include additional pocket complete XXXX track AACR, GXXD pathway KRAS and the American SOSX studies, data, also of XXXX target either as the in adagrasib. additional pancreatic to and is IND filing in its exert Mirati inhibitors. we preclinical touch inactive mutations. XXXX of KRAS the market also impact MRTXXXXX in with chemical the we KRAS mutations KRAS We along XXXX. anticipated the an switch intrinsic has or type. reactivation programs. XXXX and feedback augment MRTX-XXXX, with putting AACR, inhibitor, I'll on combinatorial agent opportunities is cancer disclosed is and kinase MAP inhibitors. to combination Cancer anticipated profile agents additional shifts to strategies to in of XXXX. This models presentation also our potent including of at antitumor KRAS of structure

focus pursue We and track strategies, long-acting strategies IND in filing including formulation XXXX XXXX. of focus to the Stealth with IND on continue to injectable Liposomal on development continue

ratios candidates, these continue KRAS which our mutations. targeting of multiple versus with of we pursue KRAS targeting potential potency to approach, Additionally, of meat could to development various selected different targeting mutation wild type inhibitor and a KRAS and profiles KRAS for yield platform variance mutations selectivity program. spectrum-selective additional is This

We have potential development will XXXX. a goal candidates turn I for of to Vickie. this it in With that, identifying program over

same research facilities with quarter compensation and first in the and with for due of to the the David, business ongoing professional the diluted per and the of share and expenses additional share-based details and press compared the programs, same to and $XX see to including due first associated results. costs of per hand IT as including cash and I'll first same about Please the $XX.X million first were XXXX 'XX. our Net million back million and costs basic as cash, and compared administrative to diluted for development investments. basic early was afternoon XXXX. release for XXXX. and quarter a our you. related $XXX.X and sitravatinib our to to this Research The million earlier for over salaries or equivalents in loss growth first of XXXX in The sent period employee-related $XXX to ended were We salaries advancement is expenses quarter net period for Jamie. or quarter $X.XX in to period billion financial million activities, for compared discovery $XXX.X an and expense. was in increase the employee-related you, 'XX in expenses for increase as preclinical share-based $XXX.X $X.X approximately adagrasib growth services, for continue million well expenses, expenses, we $X.XX in XXXX the development short-term loss of increase prepare our Thank quarter of compensation clinical primarily commercialization. General share

Thank Vickie. you,

excited team, from potential Mirati. the is to lie lot in about in both progress We're we've you the short us. made before a the there long-term opportunity about can As and hear the of happening

not long-term products term the sustainable need to only and we to drive capabilities, in short have the We growth. but capital, people execute also

synergies tremendous portfolio. is operational targeted across multiple a to tumors targets commercial Our and strong value the us platform creation significant and oncology broad, spanning and pipeline support and gives

become we stage Vickie company. invest also and expansion enable preclinical to our to As prudently appropriately resources to have the and in of and the continue us advancement a indicated, financial and to clinical in commercial portfolio preparing

subject to We a commercial prepare and continued launch preparations approval. we to successful strategy advance adagrasib as FDA have our for execute commercial on our

be grateful we launch GXXC drive our but ready portfolio. we and that, member further to with to at asking lot the priority develop assets in to meet continue lives the talented, innovative take impressed strive passionate the the oncology optimizing growth sustainable and continue objective not at we they and by have expectations every our exceed to tremendous and Mirati, team, a inhibitor, committed also of KRAS questions. remains potential critical market-leading we're this Our team while of to improve and the product as With to only of a patients. full important exciting other invest target I

[Operator Instructions] first Salveen from question Goldman And the comes Richter of Sachs.

is Tommy later being many - This talked how is on for Salveen. isn't And the how like question the about patients are as in progress showing up in files diagnosed that patient our Andrew status they to necessarily KRAS about with has KRAS line.

a are you what take ensure so can facilitate with identification to So or patients Thanks patient that actions and being treated much. KRAS steps inhibitor.

got Great question, Tommy. Officer. We've Bob. our Thanks, Commercial Dan Chief here,

at with as looking team. he's been So closely his

turn I'll Dan. over So it to

a real in patients all, would identification a number Yes. being it of cancer the is and the issue these of are to the say, patient I lung treated in for first question. community. Thanks regards

within really the and in lot the itself. we've community But a time, from patients mature understand believe a study And it's become all, over spent is that still as to ensuring we that patient. I community frontline, commercially as and of time, the that of secondarily as other patients they flagging will present that ensuring particularly patient in EMR networks a time we're of would flow And cancer actually more tested second market our a recording then included of immature over first So patients as one. patients lung some And get had taking time. will the that ready, spending line. with GXXC fully lot become available say we market those time,

Cowen. next question from comes Our Tyler of Buren Van

the of potential data do on should dataset for the taking the median mets Friday the you when more its ask PFS CNS questions. about I Phase treat how presentation think to to impact to duration to upon the bar Congrats the comparing sotorasib lung And we could X or thanks Should ability progress. and prior on DOR improve be and Or the think sitravatinib. set want world recent AACR about adagrasib and - ASCO. at response for it?

being data to going Yes, all, that best Tyler, be ASCO, at the be ASCO. it's data. reserve of at data see think first conversation presented share - going I regarding that that's excited the to the released certainly We're we were until all to that's we

think I we have ASCO. So conversation can that on

next Our Burnett of Ben question Stifel. from comes

Carnahan Neil is This for Ben. on

dose you profile XXX-milligram you the any doses are combo, forward? able evaluated BID BID below - if doses, safety pulling to for characterize you're could you say now adagrasib Thank and pembrolizumab the that XXX-milligram On you. then any also the the

question have we'll Chuck Yes, team. the for answer that Sure.

Okay.

- we've that's looked patient full enrolling of were not there present So the because in now. pembrolizumab. on population an dose. talked with in doses we we're the going our the - go-forward tolerability the good. And then at the yes, that's indicated, XXX we've emphasis the XXX-milligram we data to our that's BID those as as - half second we're XXX milligrams the the study But have the year, fully planning we and as previously, patients we switched about for - that to milligrams started was that were with dose, to had

the of year. XXX the us which And go/no-go intend make patients the make end we'll a position at second to of we milligrams number the put of to on will So in decision that X, half full this pembro in year. BID have by Phase treated substantial the dose a in

good XXX So, things far, so the at milligrams. are looking

patients we're to patients, the pleased But in those said, I well thus the results follow the continue talked far. we'll of a we fulsome those with new about and last present and half, more we data the as X in as second So all way. as year.

comes from next Barclays. Gena from Wang Our question

follow the safety I up first-line regarding just also data. data, pembro combo

one on you unique based better agree you months regarding think then drug Pembro data do data for question update show seen plus And dosing ASCO the the forward? compound. to versus think live Lumacrost, Chuck, a another BID path do differentiation Or a is so live full to effect? Or class CRYSTAL X do is think it's is do DOR. you XXX-milligram So you've specific i.e., definitive that two to tox to you you the expect PFS far, or the the specific

the forward going good for we happy So We're we'll a with question, patients X the time. are first that give have what dose lot the which at dose. should the entire be. should of accruing We're what and trial be of the Phase next the patients at of all with BID will range, us and GPS step a XXX-milligram design this sense

that of is as and planned quite all well. continues So growing

So we're encouraged by that.

not the we the In that I really is specific. terms competitors. sort haven't that challenge data that, can full But class toxicity, of think part of liver seen from be necessarily of compound specific,

haven't heard we we've seen it, it. - it's about really So but

terms would point, So this clarity I'm hoping around that I and more of tox. our results of nature a for concern the as data we is. present - But we'll of not liver present not more say program have at more those level is in that this they we're that high year, what data

to add to Mike, a here. Chuck just comments Yes. few

adagrasib the there of molecules regard distinct different are and think, penetration, at trough I entity to all, asset different steady new PK first with to ratios chemical small physiochemical properties. perspective properties, that different with tissue state from peak the

they GXXC, modifying mechanism molecules. to being are share distinct small able although the irreversibly KRAS So they

split rest pembrolizumab when their field tavazetabbot like it's the example, have for as to effective think to or at then shared immune and in sitravatinib, checkpoint same for TKIs, and - combination. to example, inhibitors whatever contrast these be looking kind were with set for molecules drugs to also date, that with [indiscernible] the kinase combine was and of other but targets quite GTK, our own note ability deemed checkpoint noncombinable you look combinable fair reason, sunitinib, immune at the of I inhibitors, in

couple class a So regard historically a there's, of I different within with drugs examples think, of that differentiate tolerability. to target their

so as regard anything what last I to is think to deemed might be just point with penotoxicity. a seen make liver that we've far function and the

test those So Grade X as seen a Grade and fraction we have We've X. of elevations. a X seen monotherapy, function small being Grade liver

toxicity respect combination, to We In XXX seen seek highs due have hepatotoxicity. Chuck so or But to I think to seen we've level. not not X dose to with function patient mentioned, to X liver including discontinue to test we We've add dose-limiting patients BID or with we're respect signal do seen no with abnormalities thing law respect what is mg toxicity, path appetite happy underlying with fairly as adagrasib cases a dose that monotherapy. to be see discontinuation. that intensity to

to I date all So think fairly positive with look of combination. signals our pembrolizumab the respect to

Jonathan from Miller Evercore.

how guess I question. to ask combination move the rapidly want looking Obviously, just like to I little combo here. the safety a could profile more here comfortable this that Xs. on strategy bit year. does Phase to But up you in data forward It seem getting with and you're larger following later also PD-X

we pivotal starts are and expect what this that the what trial factors should happen? point at So to gating on

to couple implications just over a as you. to I move team. going a say was Yes. then Chuck, Yes, start jump and of folks,

I haven't what the we think points we're – getting we're discussed advancing program – are. advancing those

data, we'll discuss are. with certainly year the we those the year. of we're as start for we as Phase share later X say, evolves, a some did this think gains as preparing I But

Markets. Evan from BMO Capital Next Seigerman of question

may the of But theoretically are of actually we're around the or drug I where the kind target tick discussed ahead Reneuron heard the not engagement. van the I've whether brain the not Ataata, drug. what or you talk drug thoughts actually on you Looking giving your reports about just to seeing can the excelled that - know in be penetrability and

any color the on of on thoughts And X helpful. You confirmatory. would Phase the be so want any enrollment - that

this has with at Point satiategrassiv Sure. at preclinically a the the CNS enter we've regard drugs. has other clinically. X I of to favorable brain into Yes, have hetograsib, get would properties think, first tissue polar appropriate principle and would looked any log, with unique to area the drug regard tissue. penetrants that relative penetrants. it that and And say to number is surface both distribution physiochemical actually And I to with lipophilicity is, CNS of

second levels, of eFlex drug say, coefficient bought the with The are or up partition like that its tissue KPU when at to that the a out mouse that And a CNS. it's we to PGP are levels the dose and looked X.X to inhibitor, a CNS substrate. preclinically achieved free human, of that associated PGP or achieving is and adagrasib fraction relative plasma that clinical thus, what's unique see a transaction we've clinically, own X.X. dose you related the [indiscernible] But let's protein a is we also it people true is and is actually that at concentrations inhibits ePlex we between

mg at evidence would say the comparable KPU see just dose is CSF response CNS when is into depending So X.X of meaning and levels we It's patients the to that that getting dose are extensive their we've X.X around drug we've with intercranial are in of that intracranial meaning examples penetrants extensively adagrasib, than and seen level, we tissue our XXX response rates an distribution. cited. what lower get of inhibitors seeing study we're X.XX, in consistent is which additional there. of with measured their Alectinib - [indiscernible] CNS KPU clinically we are with a example and measured CNS on the into uptake rates Osimertinib BID again, a ALK activity. the generally achieved has

dropped one. is think elite drug state of half-life two, that XX%. of is with disease has you associated the We never are remind the around as XX around able well The a trough pizza to target. that's relevant adagrasib for to believe administering at effective metastases. in And the about at BID. you and XX-hour peripheral of we here just ebb I steady being half-life hours as Point only both point concentrations the inhibit that's that XX% the variation our that flow mentioned and well as So to below study state

the course, talking at far, good there. of So, so we'll intracranial about ASCO. actual here so And be upcoming response

second pivotal think I I going was is take. David believe, question, The to the and study,

confirmatory, X the our CRYSTAL pleased So that's quickly the regarding study. XX enrollment. with We're Phase

As said, we're you our Europe. drive U.S. rolling also the know, in enrollment. China Also and will in partner help

So we're be the enrollment XXXX. this of rate seeing study the pleased in the at we're of first enrolled with time, half fully should and

of The comes Schmidt Michael Guggenheim. next from question

is Paul This Michael. on for

X upcoming later plus see expect quick on clinically met patients with patients another this sort data your year. color many on response the of that any we the Just rate there could then at CNS conversations you on data adagrasib adagrasib ASCO in in positions with to is combo pembro based brain physicians, And a how find just meaningful? secondly,

talk would well as research that the as physicians the range. think with be about centers. community we've well the let's it's in the what the conversations CNS, had first XX% in activity to So expect. XX% That's We physicians academic accepted. and

continue say would I on to program. the Yes. build we'll

that, know think a We our rate respect of drug is lot we CNS strategy what apply to additional the should with into that to therapies to enhance able ability with monotherapy. I evolves being as in the our get to anticipate targeted well. adagrasib around combination combination response combining

the would in So program. advance rate internal ability the we as our to I response augment expect

Stanley. Ulz of question Morgan The Michael from comes next

updates a on the just so Maybe here. get ASCO of month some in X or another we'll

patient? maybe status. You - mentioned some in subgroup X analysis in the KX study that TPS less and than clarify Can is and on PD-X it you in particular, based specifically

Sure.

A We will be presenting goes into data at ASCO subtypes. Cohort that molecular on

be a different draw both and number related TPS data have to status able or a PD-LX strata set that conclusions present of will response includes whether patients will that continuously that to say about we categorically would this So significant adagrasib. to to

Secondly, and subtype. common also like SDK, things looking about but we've mutation like by before we'll CDKNXA. mutations includes talked TPXX That be

those. able be on will all we to So provide perspective

are STKXX example. we know, non-small to cell an strategies for pursuing less also you as the cancer molecular than, lung example, subtype think for related I first-line in

Just in what chemoimmunotherapy ASCO with first-line And just all be continuing But data and creating be part are presenting are in they're when nonresponsive that, we pleased say, particularly to in enrollment thus subtypes those line are setting. presentation. seen remind I you to to that general, those development an KRAS subpopulations the that of will continue the that as by bottom mutation. those is of we we potential particular X path would for accelerated They particular opportunity of see studies.

helpful. Got you. a X what's bar than you Maybe X. on just What stratification, less monotherapy - think than follow-up there. greater TPS based That's adagrasib for and the do

at would institutions to less than rate PD-LX just know, TPS KEYNOTE-XXX, have have you have - XX% otherwise subset chemo response particular that work was score anticipate if major there. what's analysis, on the impact Notably subset We not a the medical here But that immunotherapy. out I X a look do those subset. or around response the with out would that major on a KRAS would to X, KEYNOTE-XXX response of same lesson based patients poor for do the of analysis say we growing TPS inhibitors.

the these at response look STKXX, you or that XX%. is treatment-naïve in Note again, at KEYNOTE-XXX institutions, medical patients. major either If here the rate are

to never chemoimmunotherapy. chemoimmunotherapy, this seen have they is their and So response

medical data for. seen if that able to to even KRAS believe continues that to way, to bar adagrasib reason in monotherapy, our us And inhibitor as a So we hold a for response those be need rates in exceed the up populations. or a creates should unmet for shoot

of Nochomovitz Yigal to go Citi. can We

Carly is for This Yigal. on

pembro. later inhibitor CRYSTAL a this you [indiscernible] would follow combo from I X. up with adagrasib study Can designing the of preliminary early Just prior the helpful. on on X be know stop will on year, combo share clinicaltrials.gov, thoughts any how on ALSX notice depend on with you're different potential the thoughts you but the the And of it thinking then options Phase some questions on boring table the any to data on did recruiting.

well. that for reason be if give more So could as would you on color any helpful the that,

and it could will then Chuck into Phase over start, - I'll into X evolve evolve turn study, CRYSTAL trial. Sure. the And what regarding a X. I'll a to Yes. combination

more half registration we're thinking you year. some really of point, for at Chuck? a it's high trial, give we'll second the share we'll preliminary, but of reminder, this this Just data a maybe in where but level

we with Yes. still obviously, us I think opportunity than XX% for early, of that those Yes. patients versus optimal we're where but XXX less conversation TPS be in score the a It's regimen. initially thinking had might would the have previously

We're that. yet, that's now. ignoring we're greater right population. XX% the also not on working thoughts we're So the - It's than not solidified but

have We but more study data there. trial. that, be continue to we'll larger and that a longer and would

that's the doable terms in be in to we as doing enter in could the noted, we trial and probably And think than the did a clinic favorable BI potentially us we own properties. of has a you of year. that study. get priority, this So our approval also X that's faster, we of Yes, it the TPS discontinue, second then half first the have think And less going would more of score. first-line [indiscernible] to you sort XX% mentioned

And our focus so going where we're that's going forward. to efforts

file I to add is was about basis we adagrasib adverse one mentioned, events. start the Chuck enthusiastic comment remain quite the there's we to to any related our And the related we toxicities end for well this Chuck's that thing which patients program, by of year own as not think enrolling hope IND. stopping study or as after to

Andrew comes next of Securities. The from Berens question SVB

but some you what some color didn't know priority get additional assume concern may to review does if investors process wondering help happened? more us you more I think you you some with be concern seem think dialogue since reluctant, I I continue since do I be review it you a that the comfortable can breakthrough it would questions with give the was to the reason of despite outcome having get about. still a lingering feel designation. about on I there's and had FDA

PDUFA approved standard in I with the So application we the our it's a we productive, mentioned QX. good have we very therapy think FDA, do review, There's I'll And pilot be our going dialogue have fully as designation confident breakthrough in we new remain drug adagrasib. the - real-time approvability launch-ready opening program of We're to oncology and review active of many and in leveraging the Chuck both comments, in while date the a we before examples been well. have. progressing we're and there's where drugs working

So and progressing, that's remain where optimistic. we are review. with It's NDA the we

from of question comes Jay next The Olson Oppenheimer.

plan forward to about maybe inhibitor. the and the lessons and for can picture KRAS tumor are a is required talk FDA-approved you development What of tumor learned noncolorectal agnostic path first appreciate it. adagrasib that GXXD some apply have types? do for big XXXX just you non-lung and adagrasib of And to then I you from a question. what the Can

Sure, on with that. start we'll Jamie

we've we've I regulatory mean the are be the with of think compelling approval. seen of what you familiar tumors, rates what We inhibitors Yes. I with and know patients regarding response as adagrasib with GI that then call at shown [indiscernible], I with also early other that pancreatic MSI-high. with would the solid looking immune cancers type associated and were would Sure. signs precedent durability checkpoint here tumor-agnostic in that

know inhibitors. this as inhibitors NTRK also to of BRAF as well We respect with

a that there's than the both do we other well precedent mutation lung we've So anticipate CXC so many to to tumors activity infrequency so colon. that get show the that tumor-agnostic different the path take trial anticipate large and but it we approval, on that would would would patients be that KRS have there, as tumors on a the with for of wouldn't as a the that having valuable and number tumor drug based the seen types respond enrolled to far drug. regulatory of the a We as diversity due it we us believe can of to do

remain a So that, for think that's path going us. optimistic to be I we

Regarding read-through the GXXC. from GXXD

colon be is encouraged the have been durability with inhibitor of suffice talking the read-through will we cancer duration with by setting that line cancer of third adagrasib been pretreated combination in GXXD to heavily evaluating plus cancer. So we cetuximab patients have the And able in our and and pancreatic from response models colon see see this activity, over particularly and colon year, and about up XX%. response there say later response we the with so hold then what to far. in but And rates just that are activity we we in rates

that we've On cancer XX% with response to XXXX response With in what around in that out a setting. the about KRAS pancreatic see of seeing the like starts the just then rate very regarding seems seen is XX% with the preclinically with the up being to What seen supportive pancreatic that. XXXX, the XX%, monotherapy response consistent colon we've in driver we the we've cetuximab, seen of monotherapy compound far but a rate in to around X rate so we're a side, durability with When cancer pancreatic clinically GXXC. And models models. XX combine XX%, of responses. cancer go models, we

over So with with adagrasib we've response therapy. XX%, rates model what an seen probably consistent

be pancreatic our in or We antibodies to preclinical setting also with monoclonal know inhibitors a approach the based seems on EGFR that combining data. promising

dose confident molecule we that and is So therapeutic a really can the level that I'm covers XXXX advance that we forward. that question. to be do target would to that strategies with on if driver into we a KRAS are last the blanking we at clinic, advance come the up able believe your

is hit can program. transitioned development. that the adagrasib add certainly, The program That team just adagrasib lessons XXXX discovery program the to very through there's apply pretty here was Mirati in more much lessons I team it. would the into for is learned from the that you comforting from I think us. from we late learned and GXXD

are have development and synergies portfolio types expands There synergies the as well So will study the the we some tumor the we so of we in as academic on. help think organization that center talked significant and sites about earlier.

about we're So excited that.

Yes. guess last hit just state. I competitive question, your to on

GrowthXXD program. So pulse directly to to be of we'll would We inhibitor patent course, say, aspire would at and whether entry indicate on haven't shouldn't we literature And really and But that. that the probably following hope the a can't answer on publications. clinic our there that the continue approved. been out the inhibitor we question advance to we've that GrowthX And just as seen keep is imminent. much that another into of we first

JMP question Tuerkcan next comes from The Securities. Silvan of

Could already Congrats clinic. direct contrast or us just neighbors KRAS the inhibitors you that stage they ACR quarter. on tell compare the obviously also In KRAS the emergence inhibitors. to Pan opinion, are [indiscernible] in the potential I as and about of such seem my would were that yours progress much in earlier how KRAS

Sure.

remain we I think that interested to as space well. note that first in

program program. have our that there target to We as GXXD program our the learned are own We've as in active KRAS inhibitor spectrum-selective that ways legitimate well state.

that of at our continue With kind we So GXXC. for respect to programs. to to look with regard read-through the

respect target that and One balance the for So in an we you cycling as plasma significantly GXXC does KRAS we full state, remain has interval. that GXXC. it's although GDP know, meaning mutations dose is the irreversibly adagrasib adagrasib is think rapidly state. between most of its And confirmation above the with among bind for inactive in GDP concentrations inactive advantage that binds KRAS, it shifts

finally, probably to is to looking Really, kind And active lot state. it predominate active we're to is QXX right able at asked some with able by kind to the setting. you due we something we're able buy desirable or state And has believe the present. the engage go stick protect state and even the may Boehringer-Ingelheim and There state. effectively to to kinetics of about active inactive Revolution of we after based to the that that, are now that state. regard our regardless to is state GXX accomplish Med we're to a mutations Medicines GXXC the is the competition other pan-KRAS has aware know the target that actually from still Bongerheim of the So that the What inhibitors for and be of GXXC level achieve that we cyclophilin active machinery. of with or that strategies which an them Also we though active Rev there, strategies cycles, believe to least program. And that. those about active kind lot state to mutations engage note are targeting of the the inhibition do of about And whether pipeline. it's at talked is so that talked mutations like with a

So bottom target line a state can of is think with we the differentiated active action. we mechanism

Raycroft Jefferies. Maury Next question of from comes

are wondering patient suggest you of the of the KRAS X, could patients in are can arm GXXC And general lastly, these than you in confirmatory what that then from Phase was expecting or I for population what better to remind proportion docetaxel. PFS on do kind there docetaxel patients is adagrasib coming China? the worse your And anything patients? in

Sure. take I that. can

at around or metal analysis where subset. those months So data studies like conglomerate. at X.X studies as a the falls a if done is for controlled from of you meta-analysis all that a looked look the our KRAS docetaxel we've was conclusions And published generally, the

on bit historical what are around look based X% data. at from numbers little So expect generally, landing at the population. would you than a worse overall we When survival overall the again

bit a So than less suggests population. the data again, the little overall

player I to suggests are is and and note a caveat But present immunotherapy is the that poor are immunotherapy and subpopulation. studies older. a chemo those that the preponderance X of KRAS-mutated think evidence KRAS

the that. question, is take David China I think going to Regarding

XX year. Europe. come enrolling later U.S. in trial yet China has this CRYSTAL the is iPERVATORE trial come the on and Regarding The online. not will trial. currently It online

So study U.S. next to in of that relatively total and half a have finishing of contributed amount primarily by patients will Europe small first China the the be enrollment, the year,

from comes Jason of question Bank next America. of The Gerberry

one Thanks from and me, our on on Two one for taking This SHPX is for monotherapy on Jason. questions. combination. [indiscernible]

rate and the safety looks milligram to the therapeutic of PD profile and with with with you the the compared with pembro, So at on I'm patients, explore with milligram looking combined XXX response cyclin combination if curious better PDX. from BID. lung XXX-milligram getting monotherapy BID dose the monotherapy, how like sort window the XXX It specifically you're

I understanding the monotherapy of secondarily, of and think So, because do there the requirement. same [indiscernible] based on a think the quite lot players of And combination, excitement a for some question haven't optimists, body and number since clinical the there initially rationale you to across work adagrasib on industry. the is bit on limited your seen of mechanistic then then, then project of quite patients, was an shift from data and a we data timeline of preliminary push also of but

speak So to they what ship Mirati you X with opportunity at Thank cannot to combination. Phase right now - but perspective, regarding but lately, Novartis the indicated are a starting you. the companies with are Obviously, combination. a where you other from rational SHPX

things. say yes, a would Optimis. XXX-milligram BID confident approvability we're And is mentioned Number few the I So in X of project part dose highly our had the you package. as of submission

is as the the the we're continue And importance continue commitment, we're with this to front. So noting the agency, going BID with post-approval monotherapy. anticipate a collaboration XXX at looking question mg a XXX-milligram optimists. BID. to of of And project on the agency of the do and work then does We agency reinforce your that kind dose to part as that about

XXX Again, PK/PD inhibiting mg short, near concentrations exposure of kind it quartiles target consistent is biopsies derived have the look to appears the and at accomplish we're our a that KRAS are the in data target. KRAS dose, it would response plasma anticipated mg the modifying clinically and inhibiting that be We, as our level dose and to XXX that covering noting response clinic. exposure at a and we from And X.X also on of we response remain fairly various target I completely and at One are the observed. looking the rates across above that is at near for the own level that note. those dose continue models, data are things of successing we at KRAS target confident that is is full the and preclinical XXX-milligram to completely that looking the from concentration that. repeat per both dose look think XXX the ml. to ability covers analysis. that micrograms several of that our course, interval So suggesting based rates we is In derived at concentration dose That

confident adagrasib in related with combination ship in see intensity exploration think to we dose we're our especially with have as X. of program. last and dose combination development part in I as SHPX in XXX plans We your our then the So continue overall And inhibitors increased in pembrolizumab. was combination general, to question of do

now that David remarks. like additional concludes gentlemen, the question-answer any for for or would session and over closing today's Mike conference. hand Ladies to to I

weeks about have in relentless joining our closing, In Well, therapies and confident and Ulta Mirati we in this and to forward novel care, of with look sharing afternoon. on we're additional successfully see innovative execute. you coming excited us thanks to path many blazing translating updates I'll the with the And for ASCO. and science we're we ability speaking months Take reinforce bring everybody. at patients. We're in the you that focus

today's concludes That call.

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