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Aptose Biosciences (APTO)

Participants
Susan Pietropaolo SMP Communications
William Rice Chairman, President & CEO
Jotin Marango SVP & Chief Business Officer
Gregory Chow EVP, Corporate Secretary & CFO
Gregory Renza RBC Capital Markets
John Newman Canaccord Genuity Corp.
Kalpit Patel Oppenheimer
Naureen Quibria Maxim Group
Matthew Cross JonesTrading Institutional Services
Call transcript
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Operator

Good afternoon. My name is Jimmy, and I will be your conference operator today. I would like to welcome everyone to the Aptose Biosciences conference call for the third quarter ended September 30, 2019. [Operator Instructions].

As a reminder, this conference call may be recorded. to like now would introduce Ms. I Pietropaolo. Susan go Please ahead.

Susan Pietropaolo

XXXX. welcome you, financial Biosciences Aptose Aptose Good Biosciences. September and representative Pietropaolo, and Jimmy. afternoon, to XX, ended conference quarter results the the am for for Susan communications Thank operational third I call to discuss

Officer. Chairman, Jotin and Vice Joining Chief President the Rice, Financial are Marango, Mr. President CEO; Officer; Dr. today on and Business Gregory Dr. Senior and Chief Vice me William and call President Chow, Executive

we like call certain include meaning Before would statements made securities forward-looking the that I remind everyone Canadian proceed, to within and during will of laws. this U.S. statements

the could Forward-looking that involve may future risks, about in filings. and differ events these assumptions on learn statements stated performance of known and SEDAR regarding uncertainties and that performance, uncertainties, cause expressed. and expectations those it guarantees Aptose's actual SEC reflect Form but is and to are read To factors from performance results, differ actual annual unknown these and materially expectations. report risks most current materially from recent They not risk and set more possible XX-K achievement and please Aptose's forth results

law. speak forward-looking date of to Aptose this call, only All this or as are the after these by events circumstances or of during statements statements they these update undertakes the date made revise as obligation call made. no to required reflect except

call over Biosciences. turn Dr. the Aptose Dr. and will I of Chairman, now to Rice, President Rice? CEO

William Rice

XXXX. the everyone our for XX, quarter like third ended welcome to Thank September I'd to you, Susan. call

both development. which clinical drugs, of as in from made the are CG-XXX in we well drugs the these in as hematology from and small development. another quarter, are X Mechanistically, development on the I molecules our quite one X During other progress and Phase hematology market group of distinct APTO-XXX, significant

questions. developments, clinical other as today's On the well status you both on corporate up open review financials, the we and we'll date then our to of programs will bring your call, quarterly as to call

CG-XXX, inhibitor only wild-type CG-XXX, Let's highly just upon mutant not it no potently BTK drug first-in-class cells update which This and noncovalent rely signaling agent all oral, driver forms development. oncogenic kinases. of like XXX, and survival. other for is under start inhibits pathways with commercialized potent or BTK and our cancer or the and suppresses our of simultaneously FLTX multiple FLTX,

well particular mutation we XXX as to or that FLTX inhibitor rely the much compensatory For FLTX mutation-agnostic those kinases Rather you is refer XXX be inhibitor. of mutant a engaging of it's new Aptose, or just XXX because BTK treat just not directed forms on who the multiple typical designed of your than at only FLTX/BTK than driver may the as one mutation at to to more overall target, BTK. drivers, CXXS diseases of multiple pathways. is as ITD

related kinases, mutations and viewed They of known Importantly, class in with the typically represents render targets is of new establish of our truly occur the mutation-agnostic the clusters designed resistant This multicenter, recommended as avoids yet suppress that to clinical B-cell key our safety, of the XXX XXX that assess the dose. XXX cells with agents. Certainly, entirely II patient. quarter highlights and third responses a to agent and was trial drugs. and trial and of preliminary dose-escalation first cancers the of Phase pharmacokinetics targets CLL AML to other it continues initiation cells of open-label, tolerability, efficacy Phase dosing pharmacodynamic can I in the toxicity. such an be the precision that associated the

of XXX CLL, As heavily XXX pretreated lymphocytic or oral or with daily. patient BID leukemia starting in of dosing milligrams chronic dose initiated twice in we announced at July, we the

You to XXX which only milligrams each in testing levels. administer patient we may clinical unless necessitate unexpected required of XXX at were recall milligrams calls our those BID, effects to titration XXX dose protocol one and levels, accelerated additional side trial an the at for that first X

in We're pleased this program. to report significant progress

Our one on currently lowest one on considered moved to dosage, disease patient. level in and X, at XXX has dose, patient dose is the status. we CLL level the patient XX-day is Because to stable cycle in dose the milligrams X of also required dose first requires XXX, have improvement only who BID continuing placed treatment was completed complication, only XX-day cycle, ECOG shown then first was which dose fifth that the without is

to second pretreated was milligrams XXX increase X. increase the dose Most This in has and treatment of initial XX-day lymphocytosis, also their also patient CLL. BID, defined lymphocytes, observed cycle third completed cycle. patient cycle has an currently Our blood and continued in heavily continuing XX-day interesting, throughout the is cycle as first peripheral is has during

This sign active of progression, CLL because lymphocytosis tissue into lymphoid the promote is when from considered clinical CLL inhibitors hallmark an with cells generally a BTK of is disease BTK active bloodstream. lymphocytosis While inhibitor. is the treated in response of patients, the being peripheral exfiltration

observation the lymphocytosis very for this good patient. is So news of

FDG-PET/CT very observed X regions, key cycle the activity, abdomen or patient, we hypermetabolic In for said patient. in This tumor way, the this nodes, decreases the with good we in is Across news index an too another decreases this burden. addition, scan. at end particularly in pelvis and of performed

tumor formal reduction it we a burden. Although and response to see this patients, reach thrilled takes in CLL are for typically a to patient lymphocytosis months in the

on drug-related well model far. fifth tolerated adverse serious or And of So were for safety observed, with the that their their continuing SAEs, study XXXX patients been two to both patients patient are conducted patient and October first dosing XXX been observations has dosing on these of review currently end showed, third suppression observed. and at data the Two, and three, one, a thus cycle. currently cycle events, second the on far, tolerability thus toxicities no summarize no has

clinical lymphocytes, described blood tumor foci scan. hypermetabolic to increase burden or Regarding dose evidence and one, CLL a BTK; by second classically response patient new index of on observed, a a multiple across in in in inhibition no FDG-PET/CT the and two, assessed as scheduled nodes the reduction lymphocytosis, we peripheral the response level, of robust as first at

the Regarding state with the dose-related end properties week the observed such by XXX well-behaved the of was dosing. that X pharmacokinetic profile PK patients, we of first of steady and first achieved

dose-related serum We cohorts. higher-dose levels patients, these we as by achieved see are gratified to and the to hope in continued exposures dose-escalate exposure we

request to review protocol, the XX-day X milligrams CSRC, this dose cycle our before at data their we are next able to XXX to represents of dose. clinical cohort of from we their BID dose dose, Review patients patients made had dosage we have doses per can next X, a level, will XXX-milligram of Indeed, enrollment continue that After cohort. such clear currently tolerated or XX-day attending we need if and that may patients on on the Committee, successfully a trial of to are successfully dosing the of by XXX XXX the dose BID. and milligrams Now let's patient continues dose we move the and recommended to higher well milligrams been discussion to XXX drug dose-escalate Also, already BID, the of the the and this their increase to dose next milligrams. X Safety physicians third XXX so on and to complete the lower be eager now the and date. proceed unanimously At level. currently X are that This enrolling for the screening design, X Clinical first two patients

per ascending CLL with dose. XXX Once three three patients dose, and of with be patients including followed that been relapsed at or milligrams up select recommended expansion milligrams with cancers, XXX patients non-Hodgkin's their an refractory B-cell by the MTD recommended patients intent as All cohorts the XXX dose XXX, in each going enrolled XXX our -- for Phase selected II that well, Phase to safe to be BID will at at biologically may or II and has phase and active treatment lymphoma. dose

patients for board. with enrolling U.S. on to additional sites scheduled we open come the As and sites of have study today, XX screening for

the specific the malignancy enrolling more on information B-cell and sites patients, clinical please trial For visit clintrials.gov.

let's the AML CG-XXX. Now study with discuss proposed

to I also Aptose plans XXX FDA mentioned, include to allowance that a or seek from move separate into previously AML refractory relapsed As trial. the patient populations in Phase

and patients As would a relapsed we do dose refractory population and clinical a to that chose ill first to likely wish not initiate this with we benefit. Therefore, the dose therapeutic not acutely to able patients. safety of subtherapeutic are From have patients to provide we should the patient collect clinical reminder, immediately data. malignancy be that identify we and result B-cell such to in benefit a AML trial likelihood deliver and believe data, PK dose the AML

For in have patients high to the agents to other referred population medical and having refractory inhibitors target patients or Moreover, patients, to gatekeeper AML unmet to relapsed view with plan and that trial intended patients distinct tyrosine wild-type as planned XXX IDHX AML mutation from initially resistant mutations other kinase Indeed, genotypes. We focus patients domains FLTX a who on or FLTX have the having needs. include typically as that we having other or are AML status. within ITD molecule as FLTX. we the relevant patients, IDHX AML the include well wish mutations in as venetoclax FLTX-positive we FLTX of those to FLTX or

our trial. for are with well under We new this clinical preparation way protocol

AML Our to during the clin-ops the next protocol expect trial, to submit team the sites first we has FDA in the to of year. half busy for and the identifying been be position

trial. our can the rationale here for perhaps comment Joti, AML you on

Jotin Marango

Bill. in drug. AML. we on AML, of And nature all-comers as to types. new of of with study Thanks, FLTX highlight CG-XXX is the to remain well This track XXX a mutants is in FLTX novel Overall, initiate that class continue as we wild the

malignancy Although covers be very there. which of targeted able and out been tackle for it AML, to to efficiently, nature polyclonal continues is the in curse agents many has FLTX also the the it

from in for At on community is foundation loud so share there, clear the who that therapy expand a preclinical important genotypes. meeting, are we and therapy now the or and here. meeting patients FLTX-independent Portugal, continued And and AML of me leukemia. European AML on FLTX to been ESH focused Now We strong of who we let on patients with or from myeloid gilteritinib been acute message, the that frontline returned a specific it have trials in have specific our with on Haematology just Estoril, mutations third-line XXX. quizartinib School midostaurin second- KOLs heard very relapsing

of profile that suggests would mutation-agnostic genotypes as emerging FLTX-specific XXX. work be FLTX-independent mutations preclinical covered these Our these by therapeutically as well the

drugs unfortunately polyclonal We majority believe mutation-agnostic that and spectrum resistance difficult in when fail, receiving of exceptionally give As blockbuster example, portion XXX. venetoclax later of believe, rise polyclonal also will polyclonal fail relapsing capture is therapies they therapies, will as well are genotypes, them we XXX speaking sensitive majority with approved they in to to being AML, relapse as sooner in which a patient, with another to the when looking AML targeted inhibitor, AML to intervention. of More an as current generally, all patients hematology, tackle in be which, able kinase this the relapse, of the various be of recently or of or mutations each this at a AML. they a FLTX-specific single-target

in So and prospects overall, commercial our's, the couraged presentations, ESH, potential the we meeting derivative interactions value with many following conversations very well from and acute others' about clinical the returned as as XXX many KOLs our leukemias. of the at

and physician broad from that it in it XXX It in study disease our the firming disease XXXX XXX CLL physician study all our value ongoing view is of initiation early broad as and a and step and competitors, at differentiates hematology. excites malignancies, beyond. the lymphoid potentially this towards exactly applicability our colleagues Beyond this in of colleagues our excites of pivotal B-cell we Aptose AML myeloid us to and across in

you, to Back Bill.

William Rice

Joti. Thanks,

clinical and Meeting. leukemias event in during ASH. by for lymphomas. early potential preclinical Those during submitted X additional week. a collaborators, we'll Society We abstracts accepted corporate of MD team conference at optimistic comprehensive B-cell Center. presentation provide data American where us were at online Several plan patients Druker's have look and We And data ASH, Brian be month many clinical them OHSU; Dr. sharing available about formal poster update. reasons more our and team its abstracts cancer an Michael including this our and to Hematology XXX in the Andreeff's will of an Anderson preclinical to and Dr. We the hold cautiously Cancer update forward at next and be to to

me quickly pay our been call efforts this APTO-XXX, a to it second as the Those who know it's of our XXX you up beginning been off. but following let on Now status looks we to of like long candidate, are compound, date have bring Aptose for road it. you continued clinical or

To the MYC of inhibitor, a MYC driver cancer oncogene and a remind is cell you, XXX proliferation. is major

fact, it's In seeking drug many coveted of years. for the a targets researchers inhibitor and been cancer, safe most one MYC in have

these is But focus inhibitor, currently As application anti-cancer have is tumor may MYC XXX Ib indications. our AML MDS trial hematologic solid in for you among clinical broad on and a and XXX malignancies, patients, development indications. a many Phase and as know,

I being the in The relapsed ascending or high-risk then over with or designed AML study AML once expansion cohorts Phase refractory is to clinical is reached. tolerated administered dose XX-day in as cycle MDS and until appropriate XXX single-agent patients at MDS. to weekly our Per is protocol, doses maximum transition

pleased of is relapsed/refractory X includes trial far, XXX total: X dose clinical I'm in the our first and the we XX-day with Phase dosing with X relapsed/refractory patients Thus completed I well. which in have MDS. that report cohorts, patients X AML to progressing

mentioned X We have demonstrated from biomarker dose at our per of AML. recently by XX side square. this analyses reductions AML MDS among XXX, drug-related been any clean at no yet on XX initial completed that on third peripheral call of meter maintaining XXX is inhibition been we dosing A relapsed MYC effects, undesirable last patients drug both to downward to patients. researchers and per profile dose MYC All or that a trend have SAEs have of cohort a in may refractory milligram patients expression safety meter observed We each concern have milligrams patients our the will tolerated we blood with major meter in maximum date. dose begin for XXX ascend dose clear screening week. reached. is dose all X inhibition Dosing MYC level continue until dose squared, expression gene that the per their cohort now levels is in cells and continue and expect fourth patients next and Notably, shortly. expected to to of observe milligrams across The dose square

for of We and few clinical AML expect engaged sites the more for sites the have year. dosing X actively MDS and screening currently next in patients end we cohorts, the a to add by

plan We ASH. our will you update on XXX also during to event at

For more you visit specific specifics this and please about criteria, in those interested the -- enrollment learning clintrials.gov. of trial

in known the events, continues inhibit is oncogene, can observed no evidence no directly expression APTO-XXX recap, quickly only drug-related To including including the demonstrated it well now adverse myelosuppression. molecule to clinical-stage MYC of and tolerated be humans, of that

clinically our and activity highly what may participating AML patients venetoclax may received It dose, also clinical its of modest agent appropriate is that robust it a agents. how all all observe to a because and thank one We single-agent we note knows single at from XXX physicians best no from for it that to hits or to in eager an expect like effective pathway be have to that the use wish be wish more the of distinct other that truly -- we and effect XXX, the such inhibitor. as that learn We're combinations trials. MYC

joined in the Aptose Last to Officer. me you mode. operations us Marango. let Dr. He Chief we other quarter, Joti perspective, Business highlights. as corporate growth quickly mention From is now finally, a So an introduced

build APTO-XXX, we're With key continuing CG-XXX team. in interest forward. our to activities, and clinical our attracted for we our and right high-quality As talent the team we've assembling growing expand believe assets, are moving clinical we

more have to say weeks. the about those in We we'll have -- activities coming more

who Mr. will now call the I Executive Greg our in the will Chow, turn Financial President Officer, Chief and to over review quarter. results Vice

Gregory Chow

you, equivalents to XX. We in Thank compared million ended approximately cash everyone. $XX.X $XX.X June and cash with the and million afternoon, good investments at quarter and Bill,

Aspire along XXXX. with us balance cash used ATM cash thus our provides which well current runway have we Our with into far, and facility, not

activities During XXX of surrounding attributable operating XXX cash the quarter, in well purposes. we to utilized as approximately which activities as G&A million and $X.X increased were

to headcount the on for formulations We improving on no increased Moving $X.X to for EDGAR per on XXX for XXX our for XXX and revenues were quarter. for filings loss was More expenses be to statement. had the development our were can operations the the and increased million, and income the XXX or share. G&A clinical and the net development continuing $X.X in found quarter expenses development Research clinical and million $X.XX activities, and for information related trials. detailed to quarter prepare attributable and salaries GMP $X.X million XXX SEDAR. in quarter

back turn call now to will the Rice. I Dr. over Bill?

William Rice

now I first Greg. could, to would Operator, for introduce questions. call please open you, you Thank if question. the the like

Operator

[Operator Instructions].

comes question Gregory RBC Capital with Renza from first Our Markets.

Gregory Renza

add small but bit. I we any any -- can at be team, that Bill the could applications your perhaps, the little around be of -- on helpful. bit of the you the mention of in seeing a Congrats our and we progress. said around would least what sounds might appetites ASH a just recognize maybe certainly It -- at stage whetting touch or the could additional won't potentially just ASH. wanted anything ASH like clinical samples or the in set publications patient at the hear on response I to that little and you

William Rice

Thanks, right. Greg. All

So be to I want clear.

a or complete have We that patients. a with are response response representing those partial not we

of providing evidence regarding information we're patient. and today qualitative We have response, the

excuse quantitative me, in provided or not the tumor sizes tumor any burden. regarding in data have -- changes We

in lymphocytosis. of increase provided data terms any have qualitative in the We not the

by hope We to of some the to XXX on preclinical as and do Hopefully, patients first to to hope numbers some so cohort X those next samples of quantitative from to these as corporate of studies, all we hopefully the forward. it also analyses. qualitative on event well be that plan you going collect be to capture related them presented as But being able because least ASH the at hopefully pharmacokinetics as yes, the we both event. from We have at guarantee additional to and marker we'll and meet be the provide ASH. to Again, and dose able posters activities able during able with analyze update of those when we are well that at everyone providing an some that. XXX. as data the as well clinical we'll then, perform levels are X that we hold ASH be Can't the X to PD will the do enough on from

Gregory Renza

very of tackling aggressive helpful has to of to the on think reiterating That's great. one helpful and and touched on curious Bill, that curious I'm hear both this to But market. trial, helping your is to view last the how also become and AML -- more thinking and see informing escalation or developmentally secondarily very landscape to either you and but point, as just factors evolving just on that? you then things what your some last perhaps, that kind you start the you about on, extent one Joti just that establishing how Clearly, and that. but involved elaborate side inform

William Rice

Well, in. Joti All a information and I'll of out Greg. right. bit will perhaps jump Thanks, start

data. for, trial, been hoped what getting and B-cell data the the malignancy So current in of terms PK collecting we've exactly particularly data safety we're had we from

seeing pharmacokinetics. So X we're now dose-related first we've these gone dose levels, that through

period we're Again, gratified I of the you any the that we're at when there. cycles. exposure state, used say in we're very dosing seeing. happy X, see level lowest that X, over, patients. think with And effectively X we that these levels achieving terms the the the is we in time not that providing -- yes, we're steady steady-state quantitative the numbers extended during say, I word exposures But

factor that going with dose levels in next can certain are those we're the able X exposures FDA have a we most dose-related to that level, dose there make yes, confidence to levels the we we're achieve the we going that we We that the can and dose to to to able to be us sure confidence that when possibly are that target the just we've believe present seeing exposure the belt either to do gives under dose get That truly achieve levels believe those be able important But be already patients effective X, we we going to that's level. doses to AML want our be to used going patients. occur so to with AML going have the predict going is we population. we're pharmacokinetics or

don't turn Joti, why over to So it with the second that, I and address part? can he

Jotin Marango

Thank the question. you for

So landscape start is eyes. it with landscape, our let's CLL. regarding flux. therapeutic very This changing is before the in And

we're one, perfect stage therapies to of a the patients. left right? meet Number we're response seeing? two, that the we therapies relapsed/refractory seeing the venetoclax, are line, we're available their the targeted combinations needs of what combined achieving in about front future prospect being so the front excitement seeing are the Number Number line. over at of the ibrutinib seeing sufficient ibrutinib lot in So excitement to three, rates, specifically, with of not move

inhibitors the segment. would And for example, so like, expressed PIXK within KOLs they to alternatives that

So We there. that's right the let's in here to continue XX, X but points. XX of could list stop

nature the venetoclax overall, opportunity these ibrutinib earlier slowly in as importantly, refractory experienced the line. front in is there's line. they the or in some as in a need emerging on relapsed/refractory and that blockbuster the relapsed will an disease, the CLL we of to together Also all of segment patients widening and So think drugs front move change it

it mutants, from the different including So presentation clinical be genotypes, and years may a of XXXS now. a actually few the incidence

at as it population agent from about targeting, may of a for be emphasizes heterogeneous, more the relapsed/refractory years XXX need -- thinking likely in relapsed/refractory few key and the means population, wider, this it heterogeneous. covers which pathways it which holistic the kinases may be oncogenic demands it will right, way mutation-agnostic And in now, which BTK. with coming QX respect So a a agent meet several which will is entrance, So this other then to XXX, by cumulatively look right? is of addition,

something to very Now and switching a What that patient few few over would it is both that the AML have would academics we when things the genotype to and quite time years seen in relapse, -- we getting side, given able the a is physicians get interesting of because in the much we excited. in words and is frame, well shorter have last relapsed few seen a more there this characterize years is acute leukemia. be What the disease. last

has mutation very our look So ability and ITD relapsing let's mutation, measure, an are at FLTX at to a able we've venetoclax recently, on able disease. to "Okay. in say the look to -- and mutation." say, a let's and take up Now gone and It potentially right? as actually patient a to HMAs, disease -- hypothetical had example it the We're IDHX we has microscopically been a RAS which

is is that able are What we analysis. separate mutations now to the actually clones. in So look single-cell different showing that these are at clone,

is agents mutation the was target and refer all cannot ITD combinations the I the which And either so what to again, I when shows for we referring on. IDHX to a really a So and targeting very reality by And the way this of specific which relapsed to order the remarks treatment, of prepared has venetoclax disease has and after targeted You these another emerging that's mutations. clone relapse, right? one have of then clones, right? So the earlier mutation an the that AML. challenging on FLTX less clone, only kill polyclonal in now, need in different in challenging just only

repopulate is the mutation-agnostic that can there oncogenic it. step the comes and which clones believe the One we need And of up a other pathways, for marrow. and cover will XXX agent multiple

William Rice

And safe.

Jotin Marango

Exactly.

we are something is neglect, the myelosuppressed patients extremely of that absence their is myeloid the And by especially because myelotoxicity in cannot primary these disease. arena, key

have And is of important the so we myelotoxicity. very that observations today, observed we no reported it some

Operator

next question John comes And our from with Newman Canaccord.

John Newman

progress Congrats here. on question for both on data is My CG-XXX. programs the the on

the patient to what was remarks prepared if acalabrutinib? or curious with of know patient, just that CLL that evidence some ibrutinib the -- Just response, patient had BTK is in not status mentioned you exposure and mutational prior or the that either curious whether you any for

William Rice

Yes.

not this of genotyping major regional So not the typically the It's regional sites. us patient. the came -- they typically the from one get of where to patient they one the give institution, from full institutions at That's -- done major of the the site.

agents other out and there, So already this well the refused also drugs. as patient the targeted drugs have chemotherapeutic agents standard as had failed a the number of

terms mutational was that patients. So about. be get also plays this the status. of that we'll around into we'll and status of what these patient provide able more some talking color to failed in back go everything Joti on and But this Hopefully,

patients the people landscape, these with changing get molecules, is not the different toward mutation the just driving all anymore. So treated CXXXS

for mutations, variety relapse the there and you as that's and why patients polyclonal want -- can thanks a You're this anything of calling we But Was any again, AML CLL questions drug getting other well question. John, in as to a had? in, target -- patients. have that these asking

John Newman

the when about interval checked peripheral is that lymphocytes, don't as check scans maybe I a increase see to you The it or know often? was in little the curious only the -- I more blood question started how same often bit was checked at

William Rice

throughout especially blood cycle. XX-day the take we first samples, cycle So first --

It draws We able and patients. week, we've we meeting the cycle. in increase But literally, to And increase the multiple cycle. we by the this throughout continuing continued the me, see it end So the it's in lymphocytes XX-day take to cycle. blood second the the first a blood in are weekly blood of after a draw to beginning continued don't been get entire to see an also the in excuse we samples, weekly increase. weekly and first And cycle. patient, -- during first can necessarily get second

there's Typically, for actually everybody kind comparison. a standard publication that -- talks it so that of takes about the drug ibrutinib, that's uses

in I So any slow in X.X also demonstrate emerge. it's complete to about it ibrutinib somewhat patients response months Because takes to rather treatment chronic patients, again, about a a of these patients And then XX.X on on and months level. average is of response of average, the treatment. response for are these think patients

So the lymphocytosis first fact of seeing patients the within was the week news. really good that dosing we're

so with to And tumor scan show up the then and to foci, follow seeing these in index we're reductions that that -- burden.

thrilled well this the we very with So were tolerated. drug and

hope it I that Did sufficiently? answers it. answer it So

John Newman

does. that Yes,

Operator

Our from comes next Biegler with Oppenheimer. Matt question

Kalpit Patel

Kalpit on and is the on for This congrats progress. Mark,

impact? get of we'll assuming broader how molecule? of for shortly, of we this details on to understand data spectrum your the biomarker First, be that additional activity considering clinical assays in focusing And XXX should drug's types are what phospho-BTK view, important

William Rice

Good question.

measures to we show me heard BTK. months has for this think everyone now say or phospho-BTK. And that I years everyone think I that can important inhibit it's

foci. the targeting tumor are we lymphocytosis the that reductions proof best BTK the the and right fact, is now In in

We collecting measure phospho-BTK. samples measuring or are we're to

we're wonderful We total to other quantitation. able activated. that. necessarily will that lymphocytes CCLX CCLX. measuring all hope out parameters chemokines we're is when relative are the cells, the We released uses Those the there. assay, using to assay the samples most B BTK are collecting to show measuring and that. It's phospho-BTK over ELISA do We're pathway be from is the B-cell not serum and anyone the we're an But measure

measuring samples be we'll that. collecting and So the

total back can total bring so on to the from we're and put it to mRNAs cells. pathways the grow laboratory at see we we there cells patients, these collecting can collecting expression. and plasma, also in that the in anti-cancer an And gene We're enough have there's lab and inhibit various drug look so measure plasma we that these if in effect into

together. the want We the those all collect test present of to had and of but to some to we round at what be to all going those, be patients. we only doing collecting So we're to of able doing those, samples those -- X from data able is hopefully, be event. ASH quantitative patients. And hope next we're batch them We're some

Kalpit Patel

Got gears it. XXX switching for Okay. to And then AML.

potential of running like have possible a on other XXX issues plan the your with about you like you do safety comment think AML? which combination know -- XXX if arm I about agents in potent also Phase combinations can on thoughts to we venetoclax started venetoclax. with does not clean toxicity molecule was of And a wondering when combining I I venetoclax, with profile, very As a for team's

William Rice

Yes.

a there. couple of So points

D. dose. such patient. So think effectively as from Joti mentioned, every we be and started just it can They vitamin escalate as But mentioned, patients AML difficult venetoclax came meeting to impressive And you should it they dose-escalate is the Estoril. included -- in this it's to to back you referring at highest some molecule as an can also

tolerate to difficult can't. you sometimes. It's just them, of Some

placed It still get You agent. be a an which syndrome. tumor in combination. will it that is there lysis in drug very every for agent effective out AML is But

that. already We've done in placed our is drug we've in So This combination. vitro.

from got killing with CLL, combined we of Dr. was patient primary venetoclax. Brian and in who it when cell remarkable studies those did patients. AML, all variety of a other every And case, So MDS quite samples and Druker's group enhancement we

its effects. toxicity Venetoclax those. The does side good XXX with has look news have is does overlapping it toxic like

about to in as us submit -- venetoclax. agent to well to our the with trial. combination to the a AML with with When single So plan we combination we asked well a drug in request as a it our you positions test combine And protocol submit very venetoclax. FDA,

way. Do also of move add under further those get are we we to your second And as as want answers to we'll hypomethylating drugs with Hopefully, along, and sure I'm you look that a So forward. variety of other all test anything? agents question.

Kalpit Patel

No.

Operator

[Operator Instructions].

question McCarthy comes Jason Our next from Maxim from Group.

Naureen Quibria

Jason. actually This for Naureen on is

So can me? you hear

William Rice

Yes, absolutely.

Naureen Quibria

that already XXX, with at study apologize late, First, of consider of correspond hope see perhaps But looking you another in MYC. or the you clinical -- you put joined wondering -- are of what obviously reduction levels so to I reductions answered I And you're terms to what the you've way, this. benefit if in call you do or reduction levels tell that meaningful, seeing? in it would can

William Rice

to no No, really had it's because the ever question knows MYC well-tolerated, no that one one's a answer inhibitor. a because non-toxic good

model. is an one even no animal expected needed what knows is in what So or

The in So also now from the levels in MYC not reduction MYC the expression. AML, we peripheral have XX% a all dose, peripheral lowest we includes molecule the -- normal only blood of blood that even That's in includes patients. humans, cells. even the blast cells the at that measured a saw overall it --

say MYC point And really what reduction required. that measuring. XX% because of no is a, seeing that Or is we're in sufficient? underestimate is reduction, XX%? the normal The we're also So an in Is is or some the we cells knows expect XX% we what if XX% XX% and in samples so have to patients, blood sufficient? many is a say peripheral one

in used. MYC? looking going where trying where to is drug start when to levels levels safe that different past we're get said us perform can -- much required? other to provides best different precedent. the that's that hope Is is these understand there a And higher we Those tolerated can the studies is of are it during with we see inhibition we we we just the this patients how to well benefit. Is in because in be get MYC MYC that expect? forward versus versus to that MDS? So data, low to that truly and dose What no we're it's show to AML collecting it have We only How have do we this way the can drug begin the continue inhibition, that -- humans. correlations and

a it's don't yet. just So good fully we question, but to we say have know

Naureen Quibria

That's will sharing the evaluate just that typical ASH, was you'll other at to drug? obviously phospho-XX. And be biomarkers you're and wondering sharing using biomarkers, I you be Right. the the But helpful. MYC Sure.

William Rice

looking actually We're Yes. affected as at well variety many pXX as be both different itself, genes a downstream might here MYC genes. of that

data again, moving well. of all -- try is in We We is data kind today, yes, measuring ASH to the to the And completed we're along release, be early presentation our telling event. I'd the evidence is XXX here, we're early of But of people should this seen of fourth. dose to say of to like So going what able roll of some those cohorts, is So provide that also. out we're that, study those. "Yes, benefit unveiling response." additional patient in our three ASH kind this the the and actually XXX, we'll levels during quantitative we've and ASH

Naureen Quibria

the mutation curious drug. registration-directed if regulatory I in this population, just accelerated quickly avenues just with you was But start authorities engage -- about CXXX and to for in the ultimately engage mutational the can't on drug, offer XXX. responses patients the let's study? say at just you that to for potential perhaps you great. you any move would that's And status have forward terms of to see know do other thinking one in I'm a approval I color you have -- point. your more.

William Rice

is evolving -- field we're seeing what to does Joti so quickly. very Well, that, that alluded is

certain continue now many then with population, with line, the there ibrutinib the to to the are get moved there, of in not But venetoclax we're It up that have going and first fail patients number venetoclax CXXXS. CXXXS CXXXS. patients a incorporated to of CXXXS more being may that, especially much over line. these as the in start still is may years. see drugs the So couple that how We actually we actually all patients, other population combining going some complex begins It's population be that, be may We as see decrease. first next into patients. of line the that and to decreases second sure

have now those relapsed/refractory we're on what are focused other that drugs. failed patients So the who are

looking we're CDXX the rituximabs, the ibrutinib, patients venetoclax, inhibitors. cytotoxic So the who failed PIXK antibodies, have for agents,

who drugs addressed everything, cells cells are mutations with failed patient driving So feel the still can those essentially -- we patients having that have to those XXX. other be those

for So on agnostic. We than that we're -- remember drug the best trying this to after is population. mutation go relapsed/refractory said rather focus think that lane we was to it just

have to going be our drug is not. think effective they CXXXS whether we or So

decrease. so going of begin to don't with is years. to mutation the subpopulation after And what we not to population that couple CXXXS go best next because now in That we're even population think sure that strategy be the right just the is may

Naureen Quibria

for trial MDS AML Sure. is both the be me. engaging That's it in to trial your do study? and going like final well large And you for that to just XXX, be similar move Or are to sites as you helpful. your from one question with third XXX institutions Once community as your CLL? into going you

William Rice

I running. The well for will The available we up get they're X running. wonderful. up regional months easily them. have site engage clinical are It and take one to coming They long couple clinical can characterized get a the There also No, patients of a have these X institutional sites, that. time take and capabilities. more tend to to both. but to the These reasons sites it to can they exceptionally major trial, all sites, -- to patients mean are the on

especially can quickly, these those get You lower patients doses. on at more

sites. have So regional it's great to these

all on going may to allows just failed quickly. the to us genotypically those drugs, again, patients have They all but You patients characterized as not who well patients demonstrate who -- can genotype. are but failed the they we're the drugs, to patients have dose-escalate be a as large particular get on, other and that get after the other institution not

Naureen Quibria

on it That's and Great. progress. the for me, congrats

Operator

Matthew JonesTrading. our next from with comes question Cross And

Matthew Cross

from month. programs progress and me. on couple here of forward A looking event for questions both next to Great the the news

broader other month. and even I I'm inhibition, next goal, exposure First from comparison or total and frame the I'm competitors have you fair BTK do a able preclinical results and clinical work, assuming here? achieve If extrapolate touched which I to that's a inhibitory on given bit, expect profile we harping a specific therapeutic make be guess hoping speculate the level a to to to guess will the know apologize little a CG-XXX exposure, you've already, if off, get you bit concentration to bit what I on but be here I

vivo I range some assume in based on work. seen mind have responses you in you've where So in preclinical

was just a I to bit of there. little context So trying get

William Rice

So you are correct.

back with promoting We AML the the B-cell We've the models. the state preclinical AML available the more able [ph] than malignancies. different relate as pharmacokinetics anas activity in efficacy, to there that know in steady many models to the particularly well involved are Because have the levels. Cmax quantitated in nadir, as We been at models. are that AUCs

those us have parameters the setting to We not they because not information the really judgment with with ultimately, to whether or The not as out have go will FDA. would on to to our agree quantities That's go make all out. why to FDA will We're to public and quantitative numbers have that the fed we the of what parameters careful. AUC, required are that into know been I is those you the patients. like Cmax, have hear half-life, of the AML the very that. quantitative the

the patients. data, AML to those because yet case to that to we that So the we we to are make going can we it data into the haven't utilize go disclosed believe have have FDA present that

as try that to you as to get So can. we out haven't soon done we why that's We'll that.

provide data the levels. the ASH, X at PK hopefully, the least level. data event for at dose And at patients, third we'll have will PK We on dose

the for again, we're see, to steady not think going that active would And the out you roll able then Cmax, that's between we'll we because to tell and levels the to in is But be be exposure AML what You'll the us state. you. that FDA. required

to that? Okay. to Does else anybody want add

with everybody So saying that. is they're good

be we'll ASHD in of at terms So able PK. the as that's as present to much that

Matthew Cross

looking And bar what's event it. actually, about in discussing obviously, -- fair detail with across kind greater a as Fair your to that the point aisle of in enough. forward the context looking of

where BTK these perspective, from other this a inhibitors line ones So in that different falling it's with PK inhibitory profile. all they're there and given -- the and where is noncovalent a

William Rice

what I you heard PK with say we're I are not the think Matt, that is I levels. we the exposure say you And earlier, show seeing. But Yes. that will we unhappy will

see specifics. gives that that of -- can't we numbers, once gives do you the give the So understanding you a how broad We broad kind this. just a of you

Okay.

question. You another had

Matthew Cross

for understand. a nice is sense. agent, makes it dose only things to your was focusing is with mutationally know out I is CG-XXX, take get to although this to be the really element the acalabrutinib levels. guess and intolerance, be speaking factoring starting again, totally here. basing lose are even BTKs XXXX vetted the of market to are hoping second XXXX. theoretically of out just existing they're any I there. agnostic there on both. relapse question I given Yes, I'm a about see the ibrutinib, that first XXX. focused. think reversible on reversible or X the They a market folks assumptions But the for exclusivity ibrutinib their late-stage in BTKs on rates lesser emphasized this But And I may BTK extent, Zanubritinib or And and in -- is And of X I'm of lot where XXX may in other development. you

resistance uniform other about be know in secondly, view? CXXXS is mechanisms, this And these rates stated enroll planning expecting are alluding binders as just of that design? and an cohorts covalent BTK -- of any AML when this I you across First, just mutation, XXX, you into different Or indication. for with your a get we ibrutinib the should covalent slice inhibitor expansion in expect what than that your you to then similar within bigger all-comer's to for exposure fairly the in market to view should potential not patients we you're mutation should because

William Rice

I'll just BTK of don't what that. to address some care failed. But a moment that, ask we the covalent inhibitor Joti part in of first they

if the having lot And I -- will a get lot pathways Even just of think wild refractory have BTK portion those fail the CXXXS, a they where the the refractory other those you they without type, still are many patients operative. have just still because of because fail of a is disease that's will of but will but them disease. resistance.

from after So inhibitors. ibrutinib BTK have or covalent yes, not, they they've or come whether the we of other want patients CXXXS to the whether any those go

noncovalent go ultimately, failed even want inhibitors, stuff. venetoclax I after we BTK in patients think the have to who

add So now. to perhaps to Joti wants that

Jotin Marango

Thanks and the to that, responses treatment picture Yes. for data also because but the in said because right, in the the quite time flux -- agents The here some offers is and of of ibrutinib to afterwards. agents. the potential of also these that ibrutinib only for the as combination relapse relapse frame showing the the there And but move other question. example, landscape and is arrival the different, line line not of suggested before, from compared X of acalabrutinib outcomes covalent I of from is venetoclax there front the so in the front types patient of out clinical in

leads expansion point, a few trends XXX cohort. ahead and we'll follow us. path the to this reporting. the physicians will are then you heterogeneity question otherwise, challenge mentioned attentively. had watching -- we it just And in you trial, be potential this comes marks pool the We cohorts, with to And it are be quite which think will of we're put extension know patients, the about we'll At when pragmatic increased comes our observing to be what existing when So on there data you that a I our relapse then agents. by and the where the that meet

Operator

I Thank for over will turn you. And call I'm Dr. showing the closing questions. further Rice now no back remarks. to

William Rice

thank wonderful as keeping us to We this both we thank been They've support patients up so bye. investigators And appreciate afternoon. and well analysts. entire date, of to our hard, profiles important to participating by progress evening. have Both Thank our you dose the XXX. our research dosing programs, our worked for staff. And going do in clinical on the everyone, have want to demonstrated for shareholders, you, and really forward everyone Bye, of forward. our our so we We both date as like a and diligently. programs. escalate work. look our pleased in XXX we've to of thank the I'd joining the safety this We're progress to Well, right. All favorable able --

to of the been to as support we our Ladies really important both the and this XXX look up-to-date appreciate by conference. We analysts, Thank able we've to worked in of And forward shareholders, clinical dosing hard, today's of the keeping safety well our want the date, that progress work. going pleased demonstrated evening. XXX, as and We're investigators our gentlemen, dose so our you, and research progress you of They've entire We so concludes staff. -- Thank our and a patients diligently. programs, both have the programs. our both you. thank favorable and thank to escalate on Bye-bye. we do wonderful participating everyone, forward. our profile

a You may have wonderful all disconnect, day. and

Operator

that you. Ladies concludes gentlemen, conference. Thank today's and

wonderful may all You day. and a have disconnect