Earnings call transcript Q1 2023

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Operator

Good day and welcome to Revolution Medicine's First Quarter 2023 Earnings Conference Call. [Operator Instructions] As a reminder, today's conference is being recorded.

I would now like to turn the conference over to your host, Erin Graves, Senior Director of Corporate Communications and Investor Relations. Erin, please go ahead.

Erin Graves

Thank you and welcome, everyone, to the first quarter 2023 earnings call.

call today's on me are Dr. Joining Revolution Goldsmith, Medicine's Chairman Dr. Officer; Executive Chief and Mark President and of Chief our Kelsey, Steve R&D; Financial Jack Officer. our Anders, us of Peg the our Chief Officer, also Horn, Operating Q&A call. today's join portion will for

materially are slide other to the As Act. constitute our will from to we and company's and revise of concerning the forward-looking or the subject beliefs our required review release the statements I include that to These respect as obligation any of the current presentation company SEC the within these begin, update with may and of like to Private by statements. regarding corporate our well the number note forward-looking presentation law, Reform these of assumptions, statements would press Actual of as uncertainties. I all or statements encourage filings differ earnings Securities no to disclaimer Litigation company as statements business the legal a undertakes meaning with matters. you that except the risks results

call, which this our posted will During prior few to website this was to call. to corporate our be slides from a we presentation referring

over to Chairman that, will the Mark turn With Chief Goldsmith, Revolution I Medicine's Executive Dr. call and Mark? Officer.

Mark Goldsmith

we It's will for progress, before financial company few and Jack earnings. today's our progress call, On will of good this provide open afternoon a on XXXX questions. quarter the update of highlights our and Kelsey with on highlights Erin. to Thanks, you R&D cover update I'll be first to Anders line provide results our our an Dr. brief a provide

quarter. we the this a X year to important first steps strong shared that with We're start in off

harboring Phase GXXV. First, activity, tumors encouraging we RASMULTI(ON) with communicated range which mutations, particularly and and inhibitor findings our KRAS of showed GXXD first-in-class KRAS advanced KRAS-GXXX safety tolerability antitumor solid the a patients distinct I/Ib study for RMC-XXXX, from of early

small and size, the important positive update inhibitors. portfolio relatively action it validation RMC-XXXX sample a provided clinical pioneering across implications this and deep carried an and potential of as While covering of of of RAS(ON) initial utility mechanism our was novel also

near-term March first wave A RAS(ON) successful inhibitors and million consider reinforced senior development second staff. capital organization our position. to to proceeds the The $XXX offering gross of the our additional in and of important was long-term and is further raised through prepare allowing and strong public which equity investments additional strengthen to a of financial advancement leaders of step clinical for RMC-XXXX our hiring of additional us

to from Dr. several We'll now and highlights clinical turn Steve Steve? quarter. review Kelsey to the preclinical

Steve Kelsey

you, Mark. Thank

RMC-XXXXXXX on the with additional beginning Let provide in comments updates RMC-XXXX, RAS(ON) development our trial. stage of our RASMULTI(ON) a me inhibitor drug on wave of few escalation dose candidates, first

RECIST by day of milligrams on an First, metastatic am update this corporate XX a treated pleased previously partial cycle I CT of the deck cycle with report highlighted this KRAS reduction we X shown The response at day on response at confirmed an are subsequently tumor with the XX and X pancreatic Slide harboring that unconfirmed on mutation. measurements continues X We case in GXXD patient partial RMC-XXXX scans on on daily. The patient XX% had was in an patient treatment. reported X. February to a cancer

now through daily and XXX-milligram the XXX backfill milligrams XXX the Second, to are also levels. evaluating while daily XXX- dose we dose have level escalated and milligrams continuing

clinical antitumor continue to we well that at tolerated. activity for be accumulate encouraged are evidence that appear We doses RMC-XXXX of to

combination will presentations clinical in at updates meetings the corporate on year. this plan to a be beginning scientific QX. currently program and We updates of multiple These provide disclosures additional via

connection in provide a to these updates earnings release. our with be expect We able detailed of QX to more schedule

We'll from our AACR disclosure first the data selected This is Meeting, provided we inhibitor. new drug preclinical chemical exemplifies bring candidate favorable drug how bioavailability, the KRAS candidate. of the macrocyclic RAS(ON) pioneering a able GXXC(ON) recent and of including next and discuss the collection. RMC-XXXX to to Beyond Annual are presented first structure RMC-XXXX Rule our we inhibitor drug-like selectivity mutant potency, At disclosure of this compounds. of these X structure oral properties,

dose. exposures. be II in dose a twice not yet RMC-XXXX tolerated track to RMC-XXXXXXX the and to well on maximum dose daily remain the focused or we Phase continuous the a escalate continues selected continuing year. provide now to half in second of reached on recommended are maximize dosing are to study We schedule and have update We drug this tolerated an

KRAS inhibitor, wave RMC-XXXX, shortly goal GXXD(ON) groundbreaking of covalent clinical under on first selective the our in this oral evaluation. X inhibitors support in mid-XXXX. evaluation of track of of we'll remains have entire beginning and compound clinical our RAS(ON) Hence, mutant

of in RAS(ON) nervous cases X activity system visceral first intracranial the demonstrating propensity define Today, emerge. important system. of may it metastasize to the to important the nervous have inhibitors. As inhibitors brain, involving potential systemical if This epithelial to central in we RAS(ON) studies a these highlight tumors antitumor mutant activity the particularly have into improvements treatment against disease wave more to tumors is by many central preclinical allow the RAS of become that each tumors metastasized

the As we of the mutation, the in shown quantitation of a model cell of an which carrying corporate tumor embedded cancer xenograft LUXX non-small enables deck, human used well-validated intracranial KRAS gene Slide noninvasive size. XX GXXC lung luciferase model on

in twice intensity it shows of animals validation a adjacent group The daily milligrams per the to kilogram on signal of of at treated for XXX with adagrasib the graph day a as showed the published cancer last reduction. far and roughly signal the consistent display lower important reported slide tumors untreated by animals This lung GXXC that and XXx those left preclinical since activity metastases results. Mirati to model representing an brain patients was in results with with KRAS point against significant match year adagrasib antitumor bioluminescent tumor

a treatment pancreatic versus essentially shows by tumors identical of indicating to regimen, a at antitumor greater an orange showing the XXX per reduced to be in analogous a KRAS implanted for model intracranial observed. milligrams brain next from that group of grove is which a in cancer the significant selected GXXD daily, antitumor in kilogram is adagrasib daily antitumor where right RMC-XXXX an twice signal as well. indistinguishable this is on effect finally, next study was with milligrams of compound carrying effect per showing profoundly And signal control treated RMC-XXXX the And blue, mice with at treated impact dose RMC-XXXX XX in The the encouraging adagrasib. kilogram

system a models, limitations a clinical trials. results property RAS(ON) the inhibitors shared orthotopic these by penetrate preclinical agents. This central Collectively, metastasis, X of these cancer Despite all favorable into potentially in define of shared nervous other not will property be subsequent to evaluated

to stage status X our clinical update companion I'd a like brief on inhibitors. Finally, RAS provide

The with of First, out inhibitor, track patients fully sotorasib half Phase second our lung cancer cell enrolled XX KRASGXXC line for SHPX RMC-XXXX year. and II RMC-XXXX who RMC-XXXX. in the is read this in to results we on non-small global top combination trial, evaluating remain

associated as Second, with our of combination patients monotherapy in studies mutations continues RMC-XXXX, RAS(ON) mTORCX-selective carrying advancing goal tumors evaluation in the its signaling into select with hyperactivation inhibitors with inhibitor, of mTORCX patients. with

after doses, treated optimization a inhibitors. week side effect dose were common the is we dose-limiting with mTORC X X higher at observing in milligrams on range in to Previously, mucositis patients that a focused

X on escalation Since prophylaxis has above then, of a severity revised successfully scientific We allowed to second the and dose year. of have diminish at we a RMC-XXXX both appears to update piloted meeting plan provide week. milligrams the half clinical mucositis that in strategy and a this frequency per

Mark. you, to Back

Mark Goldsmith

momentum new we've our to continued organization Thank late-stage RMC-XXXX. with especially our at a our and emphasis records who you, efforts. several RevMed on as further of the building Steve. capabilities assets described In particular the bring I'm conjunction with leadership and substantial track have pleased enhancing support announce joined to executives to group today experience such also progression above, clinical

Wei significant us Kelsey's addition Medical Dr. and Genentech, experience, and leadership R&D at a oncologist Wei joined Harvard affairs and Dr. training to he organization. Center, completing during an academic strategy Cancer Lin, medical led and School early-stage programs has cancer at clinical development Anderson and oversees Medicines. now Chief Revolution and drug MD Officer, at with medical Erasca as career a Nektar Medical industry the late-stage After

commercial Alicia joined variety her a Vice Vice have and Rogers Vice as planning. of Commercial. has In of of leadership Naganathan for Controls. management, Development; also Regulatory and oncology Sriram and Chemistry, and Nisha Gardner Senior welcomed its Zane strategy Alicia President Commercial President as Genentech, Vice including President we of And as Affairs; Brown President Manufacturing as launch cycle career life held across hematology franchises roles at

recent turn to highlights update. Jack our and these a provide progress, to With Anders, I'll organizational of and Jack? our now financial CFO R&D

Jack Anders

Thank you, Mark.

investments planned financing, is offering now March XX, which cash as ending the sheet million deducting During the and commissions of $XXX $XXX.X approximately proceeds balance first with and were underwriting estimated fund common was stock, $XXX upsized Net of balance raising Including expenses. million gross quarter, to discounts, million. proceeds of the after public XXXX. XXXX, our we operations expected strengthened our offering into

the Revenue over XXXX by year collaboration expenses an as advancement due expenses expenses trials to RMC-XXXX quarter operating first Sanofi were the to operating of the period. The million, from XXXX. was million headcount. additional as to first of in $XX.X XX% in related prior our and RMC-XXXX of increase increase with well quarter clinical related agreement Total $X.X for R&D an expenses in personnel-related into was increase largely the

or XXXX Net was of $XX.X the $X.XX quarter million loss for per first share.

compensation XXXX loss and between loss of our We commercial expense leaders include stock-based financial inhibitors GAAP updating is our increase are supply increased strengthen of clinical in noncash $XXX of XXXX full a and senior first advancement estimated additional net which to of $XX late-stage and development, now planning The million. million wave and expanded GAAP and for manufacturing $XXX expected $XX including clinical be million across year net support investments guidance expect to result RMC-XXXX. RAS(ON) to million for

Mark. And with back that, over I'll call now turn to the

Mark Goldsmith

Thank you, Jack.

year by forward wave further and We and our this updates far are so We look this momentum. the the year. continue on with RAS of inhibitors RAS(ON) ambitious inhibitors pipeline first plans half of exciting amplifying clinical in organizational companion highly second progress sharing the to energized to

clinical to and shareholders and investigators, our support outsmart the the RevMed our scientific appreciate of patients, our business RAS-addicted deeply of in and pursuit advisers collaborators, tireless employees of efforts cancers. We mission

turn our operator for remarks now I'll call concludes today the to prepared Q&A session. over This the and the for

Operator

with [Operator Instructions] Cowen. comes Our Marc from question TD Frahm first

Marc Frahm

Congrats you of data that progress and the on dropped little Steve, in there. update, the bit

patients expect GXXD And just given updates. out patient for the of histologies? to part now, focused context the you these some follow-up updates the start data in forward looking has been really kind see next of get to the the of in Maybe most POC XXXX kind Or very give then mutations on Right is epidemiology GXXD? to Just and we other in staying additional can just off, broadened probably there. I'll numbers? from Should epidemiology. have a to this the

Mark Goldsmith

think still following been patients a Thanks, your question. give Obviously, Mark, right more that around accumulating for now. don't who we have lot you study. can We're we're still on color really I data.

are We dose. doses cohorts escalation backfilling below and then escalation into at enrolling the we're

we'll hand. have So certainly larger a

think study. that's broadly seeing that are is mutation know, seeing large the we represented you GXXD But the As genotypes. the that epidemiology common what a in additional KRAS population and we're patient most degree, we the is which to

continue of as lung but patients cancer most and terms pancreatic tumor we are cell see there cancer non-small clearly, types others the well. in some In histology, to

closer are point. hard get that we So where it's we'll we from disclosure today, to better say know to as

Marc Frahm

are through of then, and And you of work that the over kind to a kind start? in of helpful. obviously, those what's expansion looking trials the walk -- significant GXXC here is kind the loss remainder the some implies That's just year. priority Okay. combo guidance And that but getting of monotherapy growth maybe of is there. net the expenses priorities Can you're what really underway? or the multi-RAS the the Is for that

Mark Goldsmith

announcing studies. Yes, think necessarily we're I new today don't

personnel, of along justified increase more it's And think because of -- that up already we've progress. it plans of both which supply feel the the has our that as the probability support on. next for there I year commitment to the is those well, as we providing do studies had the into this leadership well supply lines that into that to we plans, and as about talked but course, extend and expanding gone so year continue senior will

development broader a to a run combination point it's I in update to specific disclosing around you plan can we're start So, the that continuing to and parallel expect really that. there today for monotherapy and today no priority studies as think us expanding certainly RMC-XXXX don't the get into well but but specifically that is on

think to sort into after and coming unveiled I projections later get appropriate data, be as that what's year then we've more next. with the it about think I more of we clinical will combine

Operator

And question from comes Eric our of next Joseph line JPMorgan. with the

Eric Joseph

escalation there's now now the you what the in escalate? update think where if guess with talk dose -- you a I that right bit XXX headroom mg currently dose on saw little are XXX further comfortable Can tolerability Just mg. to you do terms and widening at of at you're dose interval perhaps about you

Mark Goldsmith

comment Steve will that. think I on

Steve Kelsey

last the consider of our have in tolerability favorable. The profile RMC-XXXX no tolerability changes continues Sure. profile we be what since qualitative been update. RMC-XXXX There of to

is feel expect toxicity on laboriously went GI remains most we frequent and that basis it dose would And back to toxicity the believe February, frequent ultimately studies become the in is as ultimately, what studies But had so that now, most to become limiting. previously would though we maybe dose to somewhat in is of dose rash We And as difficult not predict toxicity limiting. articulated, continuing we toxicity, going that's happening. through I even comfortable escalate. nonclinical the -- really mechanistic

that this. may we're do continuing program to than continues honestly you we're predict give if difficult I escalate. the And going stop to to, color cannot on dose Other extremely I with so even could. Eric, where very It's well. that, to I

Eric Joseph

with out medical third a from of visibility difference meaningful medical quarter. in scope midyear -- the Okay. a investors of you have if difference guess, you meeting a data I conference from expect having expectation meaningful don't I just but of know the on might sort at this sort program. reading being in the should highlighted what of the present at this

Mark Goldsmith

corporate think Well, of we're think starts midyear that communicating, be in set don't next But QX. to is going a we're scientific having by presentations I an our meeting an week, that and I update including in will updates, Eric, what be update begin followed update that QX. multiple series

I are think those begin of in that the same QX. will part series all

Operator

And we have Michael Schmidt from Guggenheim.

Michael Schmidt

comparable. what be I relative follow-up from looking differentiation, other are BID a inhibitors switch on guess, efficacy I in Question few it more of the others for data dosing. clinical program? either safety, the that are for or on look clinic question the at to now seen you what for then, a at rather XXXX AACR. minimum, we've on which And the GXXC sets degree guess to you looking a your

twice little understand the bit schedule. to more what that from once-daily planned only daily Just a drove into move dosing help decision us

Mark Goldsmith

there's of it Yes, can if those Michael. to to just I might both add. take and add anything Steve

the RMC-XXXX shorter that, dosing. XX-hour we've a now that really We impact that see with dosing we reported is the preclinically. PK adverse saw turns the of be to it that in fact half-life coverage consistent out animals seen question from the what really the than preclinically, BID is And much of daily we full preclinically. than of in have -- and nothing So type saw impact drove and -- that of specific and of dosing, other people, daily didn't

all almost were fact, we dosing. In data of from the reported daily preclinical

differentiation reported that But daily that we here. opportunity to in humans, And be we so successful nonetheless, the dosing. to every preclinical have supported by want was

that, at for on not going we'd and comes have really a more -- continuous that Twice will benefit patients. there's coverage like there's that us behalf dosing staying daily give from a of dosing. argument if to daily to And good

that really there's decision. from that's there else question the is So the -- was? first your nothing all clinic drove that And

Michael Schmidt

far? differentiation I for you're was inhibitors other of comparable clinic in to just fairly which asking about of there so the relative the look degree looking GXXC out sort the

Mark Goldsmith

that sort entire expected in to to the point I drug but so. relatively pool inhibitor of much pool leg off-state of of that reserve And to do look -- Yes. chasing is similar. a that's on we we've the Well, they RAS that's the always without that's inhibiting the up of going ability think based trying the biology candidates, RAS(OFF) get be and what key you're biological the

we greater or response be manifested durability greater all incorporate rates ultimately, to Those So greater and seen us going tolerability. preclinically give clinical sure that of any RMC-XXXX higher talked humans. like that those and/or regimens past, response we've And in could as in we're we've to benefit. not in be that's the all features exactly are or about whether

think as do pretty monotherapy. monotherapy to asking, because RMC-XXXX before of plan it explicitly that can since combination quickly need we've puck though, as I studies in focus long-term we to our you're I the how and multiple past has to that the times see studies start strategy combination much into around move our we is combinations moved already we on think indicated

play future And going where we're the behalf trying the puck be patients. is to in so to of on

relative know. And to need the is because it know answer about the much not as and concerned we to as qualitatively studies too we differentiated. going get in that benchmarks how define going can prepared of to you benchmarks. for combination differentiated, answer and not to really -- we're profile monotherapy that. see compare an we basic we to we be to the to sort We And superiority need to just it we're and differentiation or is mechanistically move quickly into that to those we We're don't

of patients. number So in up relatively what about hyped too exactly we're see small a not we

one the those be might are relatively Phase a small to in a we escalation think pathway combination If I superior that from from a continue ballpark that don't if anticipate draw So vastly allow us such I study, going the dose we're a really but into conclusions way studies. we monotherapy down could we'll of that benchmarks, study. in

Operator

Sachs. Chris Shibutani from us Goldman joins

Unidentified Analyst

This [ph] seeing point. to RAS(ON) we're across for It's this is that the Charlie on activity see the Chris. platform at CNS nice

so advance just wanted proceed to the the get as the activity in seeing clinic. to So in that I that human you of your out into of intracranial take might that would translate translatability intracranial and into there we subjects tri-complex mouse terms in for Is call potential models particular further action mechanism that you're anything about influence the that of the activity far?

Steve Kelsey

think I so. don't

the penetrating is extent by a CNS I to are these of patient be impact mets think in to very into being large which going population determined drugs the tested.

ultimately, metastases. So control to be you highly therapy technology With will then that unmet of into getting that's or medical and of to the need the metastases per caused as for selective get see the in effectively, implanted They're these to so have regards more RAS. earlier as are speak, CNS the the se, mutant translatability, mutant increasingly selective we compounds opportunity the part regressions we going large visceral into the think I when of disease to lines brain particularly impact compounds which tumors. tri-complex an these

into So in there's the penetrating any translation to any unlikely CNS. toxicity from be impact CNS-based normal

good -- how really compounds We handle don't CNS. of how have these much into of a gets honestly normal much the very on

that And the to like in to growing message evaluations I the All that's central are at been within date the we nervous would moment. system. tumors the convey that have of done think specifically

Unidentified Analyst

with a one you be are this thus particular a the or at the partners on maybe leaving are then -- maybe just That's with relatively combination partners particular to a all combination in at on there you time? Great. this profile likely anything terms XXXX Is of still that combination profile less really And that's potential far partner seeing emerging. seeing in that's table that's quick Or more combinable point? tolerable XXXX helpful.

Mark Goldsmith

normal I other with wild-type in with degree, suppressing mean suppress open. tissues, at that RAS tissues. normal principle or this I is in there some Obviously, normal Yes. inhibitor overlap everything RAS also think to be point, would inhibitors in RASMULTI suppressing is that the signaling

RMC-XXXX be about combination more that's of inhibitor that about SHPX but An combinable a you nonoverlapping for be worry effect. selective combining mechanistic may PD-X. would not So a example, has would or that may they something might and you example be than and with they highly

we've targeting, impact So XXXX, and more of PD-X can principle, can models. might in the be and preclinical lot see And targeting mechanistically a combined imagine things not mechanistically in you RAS combinable. preclinically, those

think just some it's hard guidance just what I I've predict So best. those sort priorities of some about might will have think priorities. work But you and how out given about you exactly to do today we

Operator

us America. of from Alec Bank Stranahan joins

Unidentified Analyst

is [ph] for John This on Alex.

quick on data preclinical Just one XXXX. Obviously, saw a AACR. we some at

characteristics dosed you dose can tumor into getting the the in of your we types monotherapy what's in for as clinic of expect? first patient you the the are terms go to study, patient In kind going study. escalation like And what baseline

that? you shed If could some on light

Steve Kelsey

now, that right to and RNC-XXXX right ourselves right that is plan for convince constituents the we II dose Well, there identify other out the and obviously dose. Phase possible as persuade expediently have dose that's as recommended a the

think compound. in colorectal that much to that's And say an about predominantly types patients the experience from types RMC-XXXX to now of the mutation, handle you're a mutations harboring we of a obvious GXXD see patients escalation, with Phase plan this with lot to now. XXXX cancer They're apart with on which the can cancer, the don't tumors going study. predominate. the pretty cancer. in a I know lung unusual Phase patients have So is And going frankly. I KRAS X all we're KRASGXXD I of we going and histo There be get enough We from to for get dose difference right think pancreatic restriction nothing

Mark Goldsmith

hundreds And worth estimate studies XX,XXX across we asked sometimes underlying to access of -- talking don't cases about have most you're with from about. going be any RMC-XXXX. patients. U.S. we of any from given competition of It companies either each that a -- to be the versus patients might GXXD is access about I that dozens competition don't it which others or multiple new know, there's slightly question KRAS plenty are might time, to same think There the that was impact get year. GXXD I at XX,XXX adding KRAS tumors. extent to of cancers there even at be underway patients We'll

Unidentified Analyst

follow-up that. to quick a And Okay.

likely CRC be one to that the mentioned You of going of type recruited. is patients

given mutations? So to in of colorectal screening the the of screening complexity cancer than other suppressant GXXD, KRAS you KRAS going for absence general, are also of be other for

Mark Goldsmith

I just Phase comments, a Well, the later the compound wants that's might where Steve's after prioritize. to a on think time good of That build which comes not have you first behaves typically thing apply to how to bunch a a it is sense seen escalation you've at do and dose with of one whole and I restrictions.

up that sort will a of few think conventional other Steve be other the don't mentioned genetic So but any KRAS genetic -- relatively think other and than putting I restrictions. then there exclusion be I criteria we'll mutation restrictions GXXD significantly inclusion is

Operator

Stifel. Burnett Ben Our next from question comes with

Benjamin Burnett

I just an off build want to earlier question.

Just the agnostic to get for mutation I label? for show many sort variants of have about but a regulatory days need you of early you a to sense data how do broad of RASMULTI genetic RMC-XXXX. realize different KRAS the sort its on path

Mark Goldsmith

people when on we that activity decision. that with Ben, then who on depend It no, will a we there much the mature and data don't make depend conversation how set is have will more just know. ultimately

Operator

joins Olson Oppenheimer. us Jay And from

Jay Olson

from following progress. Can property about a AACR? And by received you also, brain for is activity? on penetrant the reason all is physicians your any CNS talk feedback of particular high you there Congrats X molecules Or the design? the

Mark Goldsmith

first was but So thinking I you -- sort second again? me it was about question what say remind the your -- could of the first question

Jay Olson

Any feedback following from AACR? physicians

Mark Goldsmith

you on our are are AACR. about about Or are the programs? you -- feedback about things other Jay, you asking Could And asking just at feedback asking you on clarify?

Jay Olson

presented. data the on you Feedback

Mark Goldsmith

the think generally, be continues feedback very I positive. to

are investigators enthusiastic. that previously. We've Our said quite

like patients able able available demand to make available. investigators escalation waiting there's slots and compound to the active. receive many constrained high we'd paradigm just as that, We to the we make And sort investigational tolerated are far, and not appears They're as feedback of be by so waiting. continue study to well be and and to

And the I excitement so a question. then about second of And lot forgot RMC-XXXX. quite there's now

Jay Olson

Was it by design?

Mark Goldsmith

It on Oh, who ask. was it by you Yes. depends design.

I how compounds have and also, physicochemical out think are the to properties at that determined in properties have most and a incorporate these more molecules. those figured create certain chemists those sense, importantly, into there RevMed drug-like

So is orally somebody have the all through universally this of all X it as think, was this, I accepted that X of notable, who's history that not which these property lived bioavailable are and properties as a set on of these now into chemical endowed assumptions been and pretty through they large backbones. based going these RAS(ON) macrocyclic directed the efforts. inhibitors discovery development with have of But

Whether specifically support into more maybe probably, or get of by we the So, question I CNS able them design not aiming else. them was philosophical chemistry do that. with they many others anything think to than should acknowledge that team the a medicinal to

questions, don't yes. answer I to have philosophical So

Jay Olson

data on from what talk investors you'll XXXX. learn if to update have about And great. Can I follow-up Okay, could, of that? expect maybe sort what the and should next and data you one just

Mark Goldsmith

sure. Well,

on noted, patient we've As who drug. we're any following stays

following continue We them.

and we'll and where the tolerability when scale they're are and of dose later how, we'll So data data deeper a a get durability drug patients, of of if then, course much we at the shows who sense course, Phase on that II better been we get for have remain those sense recommended get candidates a better to sense on have the reach or us of escalation going patients backfill on. from what a are We're who durability are treatment and might are from be. already not recommended tolerability And talked as epidemiology have are of patients, they a as for sense those those what The to a Phase enrolled and deeper and II of with in about tumor going game. backfill the antitumor mutations much them from activity earlier, be, a sense they the to types dose. dictate we level the

will And total so today. large of number genotypes, what's the set that hard those just in depending of how each absolute is, the of each say to those on histotypes determine too

you are than looking we'll the shown So, described to to to Phase couple scaling in we what broader. comes there next. they our language degree what think more support differences. larger are beyond trends that degree, definitely if definitely we set continue, it. about clarity Ib where activities looking investors to support that. sort have earlier, data more our up the for what we've information we And I already dose compound data degree when the see what given go and of of all are what and But a escalation. we'll should about be this to that's We've deeper whether thinking hope there to of that before needs kind are with we And differences, We're body with detail that

Operator

Ami joins from Fadia us Needham.

Ami Fadia

a ask after And me able dose the With how there the the to RMC-XXXX, in really ORRs in you in the see you reach pause to maybe order is that. now. it regards the preclinical dose let to XXX-milligram question where I'll models? the achieve you were to next dose that comparable And preclinical discuss tested is can relative important to that studies.

Mark Goldsmith

Ami, appreciate Okay. the questions. I

big how increase data data the the and the with window, the then called. all meeting the how at XXX. to the determine you a There's PK. committee remind that tolerability look activity a and They to RevMed, much we've safety escalation review they increase is of package in input is cleared Just which They of made. proceed a before selection XXX-milligram they DLT at and a determine, up they if is made they received dose and investigators. all And look selection versus dose that. to They course, from the

to and how arrive everybody blood milligrams, will just obtained the and to be make at So determined With patients we sure understands samples know we dose what exposure what those level dose at XXX -- numbers. after their regard we'll PK.

our We know. can't we So don't priority. know

projections have -- projections we We that around are but projections. but

today. answer question I So that can't

or your then, third? And second

Ami Fadia

How important going is [indiscernible] keep up?

Mark Goldsmith

the be more That I of most not mean in better. for but we've is said antitumor these case for most always drugs. ways, compounds, I Yes. to just think ours seems various

the We're high you're out, of as your we'd optimist like much is question for right also see project difficult is and up now because which safety and that equally that question to enough. as is Steve optimist bounds in get asking to So asking pointed can And tolerability. as not of we tolerability. answer to realm it's an good how within sort continuing project we're

mg. dose mice. believe the what level equivalent in -- the through levels active which of at in XXX per up the the is exposure we had to So that even we've mouse there have much there exposures an exposure side in level some will other seen worrying not where we're -- and And we be the milligrams kilogram above so we're or pleased it's dose just effects. But hard than zone won't about side It's the significant effects be But effects we're pretty more point, to with side even be conceive in was XX at mice far. very we've it.

And at been so it exactly is XXX bit. that. above above say. -- hard we where we're are well but for to We've mg And a

Ami Fadia

the time then set? I least to you. call, that guess that just my you data what shared time at you in maybe support the of data relative that to to you do follow-up perhaps will improve do saw drug, terms frame drug clinical expect could what set the preclinical is responses uplift? beyond in last in RAS(OFF) that you to at other superiority respond data that earnings do patient's KRAS(OFF) if you think the point sort question of At the And

Mark Goldsmith

Okay.

think over as on drug. stay was, improve rates we time to second follow-up do patients there I response question expect your

how that's heard I question. think that I

Ami Fadia

Yes. Sure.

Mark Goldsmith

set, of Well, evidence made we'll as time firmer a answer at report assertion it that made stand activity answer dose previously. clinical point. preliminary February. of we'll have we did we that a and over And that by we the statement as out, to we the see We that end by data holds Yes. back we to accumulate And when we that opposed but assertion. whether continuing We're with the at escalate. stand assert antitumor

because against clinic genotypes. it's test the far its in active in So that about in to ON best is OFF compound is any not in unique know probably that's many profile as the clinic place ON RMC-XXXX so it the the versus versus yes, we different as OFF, or for to be

And of stands its has own it it's own. and with its on sort -- it so class sort of a defines to stand

so histologies. it And in each will of be to compared care more of the standard

at standard line differentiation KRAS RMC-XXXX ultimately, a from standard GXXC(OFF) where, I the must care targeted inhibitor. of in is of one show second care, now and regimen least think includes treatment

we have RMC-XXXX combination So the ultimately conveyed to be to it's combination like for ON together large KRAS the is best is the context. think -- a additive but RAS combinations, of likely in That's in a we'd best because come be that to that is And to is the us kind put part whatever strategies. vision there mechanism. our that GXXC from the play very of RMC-XXXX inhibitor is what will of we've inhibitor and in tested its when Phase candidate form program. II in But

Operator

by it And from of SVB with our Jonathan question. last Securities. Stand line Chang comes the for

Jonathan Chang

one see do the Just RMC-XXXX? What for you me. competition as for

Mark Goldsmith

that's a good question. Jonathan,

of the up against. That's going what most is we're indications, competition the care. of standard For

any compounds other aside or of For for today. other example, GXXB from there the C, GXXX in mutations the aren't clinic

are the there obviously, GXXD, For compounds have other that entered some clinic.

compound about a for genotype. judgment And so not which superior. the of that are in my those KRAS-GXXB principle, competitive statement population, That's is

or compounds be just competition. clinic You on those considered to to about in know would be the to the list. have are clinic, what's in And that the those want

Operator

would Goldsmith, turn back Chief Officer, I like our Mark to it remarks. Dr. for that Chairman Executive And now to closing concludes Q&A. and

Mark Goldsmith

you thank your operator support you, Medicines. for today everyone Revolution participating and thank of and for to continued Well,

Operator

your Thank does the participation. program. you This conclude for

disconnect. now may You

Revolution Medicines (RVMD) 8 May 232023 Q1 Earnings call transcript