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Aptose Biosciences (APTO)

Participants
Susan Pietropaolo Communications Representative
William Rice Chairman, President and Chief Executive Officer
Rafael Bejar Senior Vice President and Chief Medical Officer
Jotin Marango Senior Vice President, Chief Financial Officer and Chief Business Officer
Ted Tenthoff Piper Sandler & Co.
John Newman Canaccord Genuity Corp.
Emily Bodnar Cantor Fitzgerald & Co.
Matthew Cross Alliance Global Partners
Matthew Biegler Oppenheimer & Co. Inc.
Call transcript
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Operator

Good afternoon. My name is Mary, and I will be your conference operator today. I would like to welcome everyone to Aptose Biosciences Conference Call for the Second Quarter ended June 30, 2021. At this time, all participants are in a listen-only mode. After the speakers' remarks, there will be a question-and-answer session. you. Thank Instructions] [Operator

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

Susan Pietropaolo

Biosciences [second] quarter Thank to June XX, financial afternoon, Good ended operational conference Aptose and the you, discuss call for and results XXXX. to Mary. the welcome

President Rice, Bejar, Business Senior Chief me Chief Vice and Joining G. Financial today's Senior Officer; CEO; and Officer, are call President on Chief and President, Rafael Dr. Dr. Vice William and Officer. Dr. Chairman, Jotin Medical Marango,

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

and Forward-looking stated by President I now Chairman, turn will statements of cause guarantees the that to performance during learn over of reflect except known expressed. annual SEDAR filings. Dr. made events the results or statements performance, update that and and SEC read expectations please report these and speak Dr. made. this circumstances and may Rice? expectations. achievement Rice, events uncertainties, and after undertakes they date law. and about in call, differ call to on as unknown only forth statements the forward-looking recent those revise that more future or are the actual All date risks, Form Aptose as of from required this are differ To most Aptose to Biosciences. the call Aptose's obligation of from materially XX-K no CEO to They actual risk reflect could not involve set results, these factors Aptose's uncertainties, it current regarding materially and performance, is assumptions and risks possible

William Rice

trials, XXXX. and or everyone quarter clinical Susan. to you, in progress our with with B-cell XX, cancers. in patients myeloid highlighted second the call leukemia luxeptinib AML, to acute quarter with of lux is by ended our June especially continued or welcome for the The like Thank patients I'd

Bejar, to early you have our that We engaged brisk a dose with Rafael sites in cohorts, will bring escalations pleased flow our Officer, both Dr. activity are patient our we to clinical we B-cell cancer our continue and highly through are in Because through and AML move the observed clinical cancer Chief and Medical moment. trials.

over continued Before in need the Bejar, these turn I cancers. like emphasize it to to for just therapies Dr. hematologic I'd

in most While and potent, lux it our under other is durable, BTK more the FLTX BTK oral, a relapse and Luxeptinib of and inhibitor development, active resistance. insufficiently inhibitor. remind the develop are there driver non-covalent of kinases highly are patients is is drugs you will and drug number often I on typical a that market FLTX will responses or or just no commercialized than like development. oral

failed in that therapies. are our point available both the I'll shown hematology only clinically AML, by or other market malignancies what safe treated found often that primary and sometimes target lux date. from B-cell been type TEC, trials cells with targets to other associated of patients of drugs avoids who are inhibits the FLTX on of a in sets to with that mutations patients development, what As kinases best and to it have also far, relapsed and you, CLL been remarkably and forms compelling. well-tolerated and lost, refractory that render related resistant agents, and Thus been FLTX, and has wild the BTK that and has mutant clusters remind the apart such in yet it This known as and AML gets and lux in already this targets, ErbBX BTK and of occur cells drivers precision and not is it set toxicities. makes it EGFR selectivity that selectively the suppresses including with

in clinical that progress of to lux our the therapies to observing of be of our will Rafael cancers. the ongoing prove these ask hematologic is hopeful Officer Chief overview activities. we trials and valuable that, in Medical encouraging, are to very populations in are So clinical I'll Dr. an difficult for Bejar, armamentum our Raf? we patient diversity With treat provide

Rafael Bejar

three two MYC myeloid MDS. inhibitor, NHL you, have lymphomas, failed more them, with drugs that to our options include one leukemia, who luxeptinib venetoclax repressor, has two start Indeed and Two received cancer are Bill. Aptose which clinical cancers, of or or acute investigational including established AML, kinase of with ibrutinib, I'll CLL in the with patients and previously of from agents. rituximab whom lines as in patients have failed B-cell or other regimens our and APTO-XXX, trial includes and B-cell the study. for This failure or and such to other AML intolerant chronic trial, with in leukemia had in trials. or Thank our lux, studies XX also available. or lymphocytic non-Hodgkins ongoing patients no treatment with may third or our other patients therapies,

lymphoma small drug, lymphocytic And luxeptinib malignancies. longer successfully dosing revealed levels of during phospho-BTK, with FDG even dose-escalation trial IgM evaluable in XXX dose-related and milligrams, as enrolled in currently and Phase duration Association, maybe disease patients type and tumor cycles. XXX been and to of June, milligrams well baseline, activity. Rice June and the aggressively treated with we've lymphoma, experienced multiple anti-tumor leading in malignancies, non-Hodgkin’s measurements XX% a size. we've Intermediate In levels XXX of reduction. activity, milligrams into had we times one patients cycles, cancers. BID lymphocytosis in X, clear demonstrated European encouraging EHA, daily including XXX that cohort our target with presenting mentioned has tumor reductions our leukemia, twice early follicular complete expect to macroglobulinemia, higher suggesting a aggressive cases dose-escalation for before, this treatment-related at aggressive reported clinical continuous on-target and event up are BID of luxeptinib. classic across of conjunction both of lymphoma in or treatment reductions Cycle Waldenstrom's CXXDX, on Since Dr. update, we've including target seven tumor As milligrams some including and different fully in our XXX recruitment delivered We've and milligrams, levels at the lesion or upon B-cell exposure in with luxeptinib milligrams B-cell milligram last size highlighting the the demonstrating dose picked described held lymphomas. observed completed of to observed growth in with call, all lux And by intra-patient reversal last with our relapsed reductions and these data corporate lesions Of we well chronic I activity, tolerated dose nicely and disease dose growing lymphocytic follicular four indolent levels, XXX of inhibition challenged scans activity lesion two-thirds yet X shrank is measurements at dose dose Hematology the with them indicators as engagements the compared we expanded by and luxeptinib patients our patient, we I after PET-CT Generally, Phase has that time. peak CLL, enrolled lesion level over compared when mentioned, extended XXX patients. at milligram of XXX dose-dependent the

escalations reminder, spotlight and continue may in the We this and It's during from and to of and the longer moving that EHA, patient relapsed as then higher this cancer to point successfully half to the trends the second has patients, of important B-cell to luxeptinib exposure also we to drug-related refractory year, luxeptinib generally safety case reported first disease. well-tolerated continued a half with out as refractory concerning of this in date. year expect relapsed no challenge been dose XX data

to intention, dose to milligram get higher the duration for population have is patients activity, an dose levels. it level as these as XXX to so further dose escalation possible as to many And dose presenting we refractory treatment dependent especially and anti-tumor continue our on increasingly begun tackle observe extended to

and For that sites specific enrolling clinicaltrials.gov. information visit the please the clinical patients, are more on trial

difficult turn let's has to AML. treat hematologic FLTX upon Now particularly a which because for lux been Aptose. always to in AML cancer and lux patients leukemia potently suppresses is AML rely or resistance. priority survival Acute signaling Treating AML myeloid pathways and drug for cancers oncogenic additional

as as trial all drugs. currently Bill available have gilteritinib, patients crenolanib, include the As FLTX in sorafenib, already as and venetoclax, failed well inhibitors, other which can therapeutics, treated have and the quizartinib our such best by and treatments mentioned, AML been midostaurin, investigational with been

population. XXX two we patient at tough FLTX luxeptinib, in multiple including for Event level. June, inhibitor XXX transplants, At is our EHA activity multiple prior patient activity data the cohort dose a relapsed stem had after anti-leukemic MRD-negative chemotherapy, the encouraging allogeneic dose complete this response date, to anti-leukemic BID, receiving So of deliver FLTX-ITD patients first a and milligram To in durable extremely an cell AML reported presented patients, Corporate lines on who in milligrams only promising treat therapy. have we

the and dose at completed the level, we on milligram milligram the XXX to treatment dose level complete level, and some enrolled currently milligram XXX dose with patients. also have with expect We patients milligram remaining XXX XXX

We tolerability trends is a we other reach continue signals that flow we prevent luxeptinib are vigorous This the of well-tolerated very to lux to further pleased diverse use dose doses, of because permit would allowing to agents. generally at future engaged the we it's and combination higher critical with have note patients. these that levels escalation. that find it and no that is us we date toxicity in will our with is sites dose then believe or to profile important are Also,

on escalations genotypes select programs. mention monotherapy data that therapy of observations to-date, our Finally, I explore dose studies to studies our our expansion and clinical guiding based are planning dose combination disease under the from will

strategy We around dose year-end. expect and to expansion select cohort AML an for

information on clinical visit are For the trial please that and sites recruiting more clinicaltrials.gov. patients, AML

Now, quickly for on and up clinical MDS. date currently the Xa/b in trials bring second AML Phase APTO-XXX, you to of me candidate let status our

MYC of you, cancer. MYC cancers. hematologic Some drug MYC oncogene and of poster these one coveted presented is at cell targets APTO-XXX is remind the major reported in a repressor including a cancer of proliferation, were EHA. is driver most data the To in

impeded has However, direct have substantial drug that there and development are undruggable in MYC considered challenges past. the targeted been

MYC transcription, APTO-XXX inhibitor this novel As for represents a direct pathway. a targeting oncogenic of approach

ongoing trial dosing findings Phase sustained far, XXX rapidly importantly, lymphoma B-cell patients per XX, more co-exists subsequent the note, meter are dose patients, on and mechanism to per a well-tolerated is we AML and of we the target we may days, escalations adverse patients provide of sixth enrolling Phase also patients. biology multiple XXX APTO-XXX MYC expanding The action, level in for further treated Thus treat peripheral APTO-XXX significantly Xa/b driven with MYC events, in square suggesting currently AML of current XXX and relapsed malignancies the are are level alter at at cells. study higher several other ongoing Currently, milligrams that iron been or with of relapsed/refractory the meter evidence support cancers. AML monomer and the is the Of over myelosuppression. patients dose tested the the milligrams square from dose continued in escalations dose the at other plan cycles. mechanistically anticipated. high-risk with of Our is MYC-driven on square. inhibitor that of no refractory XX, patients in conjugate and there In has evidence rearrangements. MDS milligrams with Burkitt’s patients study APTO-XXX sixth APTO-XXX. escalation the the study hematologic and MDS, Phase trial being to per active are and and pressure Collectively, of concentrations MYC meter to XX, Xa/b drug-related are our tumor In MDS Xa/b Based by gene blood XXX and dose the sustained no transforms include conjugate iron APTO-XXX of XXX and with

trials. the our tolerability of luxeptinib and APTO-XXX safety and We are programs at ongoing in across progress and dose the escalation all allowing drug are both by pleased candidates of our three clinical

quarter. our call and we Jotin Chief second who updates doses, Financial are As over at data we pharmacologic the to the treat more Business Dr. Marango, higher to year. this results for I'll review Chief provide pharmacokinetic that at adding ASH patients we Officer turn meetings hope financial Officer Jotin? the later now will further generally and

Jotin Marango

you, everyone. Rafael, and afternoon Thank good

We investments. turn ended quarterly to results. $XXX second quarter in the with now million and cash Let's the equivalents cash, approximately

$X.X Based to on first on in development surrounding hand we our to approximately fund which attributable During pipeline and activity XX, general as operating the well quarter, administrative with utilized purposes. all as million the including candidates cash research current resources activities, June XXXX. provides of into operations, at the sufficient operations, cash planned of and company half were

pipeline activities were $XX.X manufacturing $X.XX and loss EDGAR the and trials, million Moving the had SEDAR. detailed headcounts development on Rice. in quarter our our trial to million attributable continuing and trials, quarter. More million candidates found the call clinical over of net development the and including improving G&A quarter pipeline costs on studies. on our back income the were drug research per will the expenses candidates, statement. products and or filings now We manufacturing information for formulations Dr. our $X.X for can for Bill? and to be to revenues personnel $X.X was for quarter no costs Research turn our clinical expenses clinical for of for for share. supporting I

William Rice

Thank you, Jotin.

As Dr. questions, if the to Bejar we please open question Marango, to feel the introduce question. Dr. Operator, you the of any myself. please first call could us: or free for pose

Operator

first Your the Ted of Tenthoff from question Piper Instructions] from Sandler. comes [Operator line

open. Your line is

Ted Tenthoff

to beyond so CLL. lux And just wondering, I pursue start Thanks look to that you preclinical excited point very to that you data, toxicities was back upper the XXX, may really and much, or malignancies? that like dose-limiting you I'm ultimately to level to that and for? with Did see quick plans hear Thank AML saw if have And question, to excited follow-up the mechanism. I'm hematologic looking there anything at for guys. that about progress might towards much. data

William Rice

on. Ted Hi. thanks for so coming much

potential a if no did see feasible not it the out of in the in that's trend we both signal we’re but Let's luxeptinib any lux But event. toxicity all the doses, start talks, as question had in preclinical not on of both that to any our in We dosing, was with towards the is and It with toxicity we adverse, studies What be all decided can an until extraordinarily for count. what us the – studies very animal we the it in very anti-tumor to all or rodents, models, I maybe trial. maximum of dogs. had – after DLTs. but studies, with – the model that in look continue once-a-day we dogs. dose to mouse, well-tolerated great the in clinical and up GLP considered dogs gave not data there the so with are sufficient the what neutrophil that at those we'll the to whether first activity, drive listed highest this associated rodents were with and and twice-a-day point it to In going that, GLP a we is was the into the rodent therefore was days slight and preclinical models. and did reductions, be Even say any to observe, twice-a-day the some the associated neutrophil dose we talk in XX dosing trying lux on pointing saw and because seen went GLP talks the reduction species, effects the adverse

add he or XXX, wants to find I'll So also mentioned But APTO-XXX that. repressor. inhibit a It to to the can actually you moment, say ask in with MYC. Bejar, you. MYC agree to Dr. We that is if a exciting molecule

seen we have patients, not MYC We at toxicity. inhibition but over point, this any in have seen

did the malignancies, MDS. start Beyond heme escalate this, through dose to we we AML and with as continue

that also We to a to look like MYC some the the towards would may Dr. But just associated malignancies the malignancies pancreatic cancer, and want with tends of are that add are heme a that's rearrangements. MYC A awfully now even real go Bejar to solid And is humans. that shown And tumors. that in also moment. in we chemotherapy. been pancreatic tumors those will always beyond transient including example to good B-cell in studies classic it's of reductions the to non-human need in target in cancers your

of drug that like move some we'd able those which believe a And dose cancers of the we tumors. prolonged to the other into look consistent expression, be effect or pancreatic MYC solid tumors and drugs and show humans so combined combination to in possibly and once to transit chemotherapies get solid even of we of with for inhibition can studies we

I answer questions? that Bejar did to ask So And Dr. can your Ted? perhaps add.

Ted Tenthoff

quick one topic. just then And

So markers, dose if about see a you're for think good are we're not may that the how selection, not plateauing we in? of you look dose looking including that fact maybe would just for, in or a even or limiting we talks, that position do there

William Rice

on I'll to start and ask then that, on Dr. I'll So Bejar it. expand

of it back drug, dose ask the in cells the achieving then accepted continue the we to one way the further have for inhibit plasma look So the there And pathways pathways? to ERK, we PDGFR-alpha, that, dose some we after phospho-FLTX, it escalate. to targeted enough get on even exposure from cells, greater patients, the the as plasma XXX in key oncogenic get dose and is, is greater very the of you pathways with to that some the inhibition do we take SYK, of treating to The we dose nice laboratory, the did bring as the reporter way and hope and to we most as kinases. exposure to level, milligram things hammering drug common exposure AKT and of so have those levels the place to as escalate humans inhibit we CSFXR, escalate we are

terms for biomarkers. we So that's what of look in

on I'm to forward expand dose going tell that Bejar a And about thinking selecting so expansions. ask for and we're this to going also Dr. bit how to you

Rafael Bejar

Sure. Bill. Thanks,

see at assay And and dose. point that your just necessary, important. best we really to design certainly assay, the in the But that think of with I it’s study lowest But AML don't the see to about that if that's need that to a go phospho-FLTX inhibition you PIA level study. then as sufficient we the think described if not shows you're test right at but level in I higher. dose we in the inhibition I particular start think already is dose

seeing already. we're that So

permitting, I it's to well activity think before need fortunately, level. other think, dose and it's to toxicity observe able to that see right We we into these push necessary. to dose that. And said, I decide at I we're like as dose higher escalate the continue we're sufficient, not levels

patients, ultimately is be to not to the may escalate but Now that, mutations, profile sensitizing some resistant have applies we're we'll good have to a some dose do as of in have level and position, variability us that where may it one that you toxicity allowing given mentioned, may that. dose more to that mutations, continue AML the all-comers to explore

William Rice

Thank Raf. you, Perfect.

Ted Tenthoff

Excellent. Thank much. you very

William Rice

Ted. Okay. Thank you,

Operator

from from Next question Gregory comes RBC. Renza

open. is line Your

Unidentified Analyst

around was thinking Thank [indiscernible] I now. anti-tumor the taking the you latest my Greg, activity was is just for more dose provide XXX escalation what and in you. beyond you that your is release on dose level? if questions. thank And This press mg around dose-dependent that color could mentioned wondering Hi. for

William Rice

All right.

around Dr. start bit to a asked ask, as So for. more on Bejar again, color I'll you it provide I'll Then it.

induction escalate or especially of some dose doses, some indicators – and have some one we markers would in started a of patients, tumor So we start dose B-cell the continued dose levels particular, lymphocytosis and of to what we went inhibition, who tumor increase have greater the are as when malignancy as to would of But we lower we of we and on-target them levels, in inhibition. the patients, inhibition activity, – we level. dose see at levels to and often of seeing of the BTK, higher call the expand as seeing we higher then at out in or higher

Bejar about talk to at So I'll and point step seen Dr. ask what in that we've there.

Rafael Bejar

Yes.

you hope to those, gone dose example upon starts a where patient is the see level, see, the as higher lower your would kind Bill also then dose to exactly exposures. then see to, we've that improvements. And dose and at I to referring one begins we're activity higher of think have increasing levels, the does we've seen a not you

translate So into will we're that greater hopeful activity.

see to that have activity peak, whether tumor where the dose seen that some the of these in that phenomenon some baseline growth initial examples, escalate those initially meeting, actually a dose couple some And suggests tumor then or reduction seen have we at levels. and there of is and EHA as allowed were that come we in will higher to described in We it patients be growth. out get not, patients below study it we'll

for I in response. a exposure good dose see if of individuals it's we continuing greater get to can likelihood greater therefore and escalate and think motivator

William Rice

Yes.

the had asked increasing about off So level. that also XXX beyond play because possibly dose let milligram me she

XXX now. the at we're So

answer we question? continue in level. different to beyond four, we go your exposure that we pharmacokinetics well, get thereafter. to if some the PK If seek go hope we signals We that to see take us the dose XXX plans tolerated increased to safety it it’s the dose the dose be the direction. have tolerated to Did levels. We plateauing level exposures increase, well. that see milligram higher is to hope If also would XXX And increase continues a as that we we may milligram all

Unidentified Analyst

that translate needed does mutations, inhibit what's you. Thank was you. to levels? in just FLTX follow-up, with on And resistant may, quick of where I your if wondering, serum I will have and it dose PIA so the I terms that assay. far, on data based be expectation Yes, the a level Thank did. around the

William Rice

Dr. is data just And with FLTX, interesting What's AML. But FLTX diverse you some And clear in the to of essentially we've the at patients, looking are just activity, presented inhibiting PIA patients these only FLTX. what's ago, mentioned it a Bejar when is all with of micromolar, have in moment how assay tumors. the when you're is these particular, get of you the part FLTX-ITD. X.X driving the these the actually –

So the as FLTX the number you'll have as of tumors. other well

is essential we're it to to hit as can inhibiting that show for also many So as us we the to want possibly as FLTX as pathways activity. we get But possible. high

want you to it levels to typically pathways trying FLTX. So inhibit type the can. highest takes bit a [indiscernible] we in as achieve the that drug hit exposure tolerated to as the to you else, to And too. think humans much look type, are little as try of wild inhibition that are we wild what more seeing to But

have assay. PIA We a

we maybe wild effectively. of FLTX SYK that – the well as ORs the some the others. the surface PDGFR-alpha, the and at some and receptors the is as one CSFXR, does the other you two look very to do cell well is of ERKs inhibit sub and that company We again, at so need we've some also shown have as TRK But as the type, at internal kinases, the only already FLTX the we're cells, inhibit we different this. wild type think I And reporter we one micromolar levels, FLTX-ITD. of

will get drug need to that? always in you to want much We try add as tolerated. more Dr. more be So drug. as to Bejar, do to it want we

Rafael Bejar

like I in that of are but the And it Yes. I'll treatment arise relevant that that have resistance think call it asked those I description another things into for to to we And of inhibition about the so FLTX does setting other does, its you mutations, with specifically prior look example, and the take of agent. account. a an activity. to a inhibitor. is could accurate it out point tempting mean, it's many what lux drug at

are know very mutations One data effectively. tyrosine of arise very effective that mutations from occur don't preclinical those of in in inhibitors setting resistance resistance. that FLTX of targeting certainly out is mutations the that can at luxeptinib be We target kinase with that domain could there that those kinds the

that nanomolar preclinical as mutation data a mutation and other activity arise again suggests we also. low against gatekeeper that that can The FXXXL our have mutation

the to the that explore assay in-vitro had assay. concentrations opportunity do should type that above that the able are using believe that well PIA specifically we of we that We in that be haven't to

William Rice

Thank you, Dr. Bejar.

Unidentified Analyst

very Thank Great. you much.

Operator

the question Next Canaccord. from comes John Newman of from line

Your open. line is

John Newman

you bit you with Hi, cohort on this on guys. question you're at getting much patients as taking transplants. had just enrolling for might you're enrich to Thanks. the the a have if milligram FLTX you're if little the I'm study, a about XXXX? any you're follow-up reached or if taking prior of specifically my just XXX for I if talk that all successful patients. of can end And question. wondering Thanks luxeptinib curious type And looking I'm now AML here, the for also in we patients cohort. for how example,

William Rice

right. All

with we in against clearly type have FLTX FLTX-ITD able and We like FLTX-ITD wild it patient, have is say disease prove mutated FLTX. because mutations, that It patients, they to mutant to But a the type type in well, can because all types of the that, disease. other when have to disclosed have clear And multiple At of have absolutely you remind additional maybe type patients. shown again, you, almost have patients on FLTX gives activity we they've a be to So patients. wild represents the get overexpressed rise that the other definitively milligram again, XXX the patients. into and these different that wide of okay, FLTX, FLTX I study it activity time, that. that level. types which already of those are such wild coming diversity same is wild it we mutations against drugs to want on patients, I'll different maybe there both the different want everyone But been the the a that treated we patients not an dose have all-comer we

and wild want as that FLTX about we've well all we through. have balance We provide So to type to talked clearly the the want way as patients. mutated

the patients after transplants, In patient relapsed two we it's complete response, received highlight that after in particular, then several reported the the have one patient the response, which years terms that successful successful MRD-negative patient transplant successful of have in we had and transplant. complete

more to that coming. bit add So the data would talk a perhaps, Dr. and about to like Bejar

Rafael Bejar

Yes. other had and and We allow likely transplants patients wild criteria. type to We FLTX with selecting study to balance include they sites have to patients respond do more those met then that. cohorts us patients relapsed are that that believe mutant try to with several also have who in patients the subsequently do our help on prior

we about get into not as for trying follow-up type make how And by FLTX to you much are a go enrollment we clean about patients both limit they then mutant year-end. decisions to how want So any will and We in expansion. way. the asked picture wild we

the the for that in as mentioned, complete gauge how that we we from patients cohort we enrolled. the announced much dose will able be have study, it believe we'll from progress to milligram point. be that currently can time You we when with And escalation XXX AML have

John Newman

you. Thank Great.

William Rice

Yes.

you. Thank Okay.

question, Next please.

Operator

from line Fitzgerald. question from Alethia the of Next Young Cantor comes

open. line Your is

Emily Bodnar

you as Thanks Alethia. expansion XXX approaches you add cohort if for enroll fit on I'm taking Do if by I could combination your on combination you How Phase not, so, curious curious, you strategy the have would said the into agents consider? AML. that of portion questions. Emily dose expansion Thank for would And the maybe any then potentially if the mg the are have by is potential does dose updates thoughts And potentially plan for the you dose Do cohorts in end Or that? This I'm of you. what year? what that? to about think our you you year-end. also study? Hi. that

William Rice

Hi, right. All Emily.

tag start team. we'll again, one So This out. I'll

drug in or with drug we're this want a single monotherapy, in activity to combination agent. studies. as has approaches. specific perform genotypic But absolutely do We In combination a expansions that to that terms shown prove defined to the phenotypically a pursue either that. patients as combination of we parallel, pursuing is approaches, we single plan We've want agent

ones haven't yet. that going to pursue disclosed exactly which We we're

continue combinations will study, would to with of collect populations. remainder types patient in throughout the which data be the of year this We populations. And the particular see patient then the current appropriate

choose the And We're may then combinations we patient tolerated the it going the impact escalate. getting that exposure, decide the with in or And to milligram, at, is We well. XXX greater then will the That will dose timing XXX on that terms Well, more of how and milligram, does maybe then appropriately. dose possibly in we're XXX cohorts. level. into XXX, may the a if depending we we For relapsed I continue of to expansion the on higher move it drug fit again, refractory we’ll see into first-line. process? see what types look the that

follow provide what data, additional? always rational additional any you try which we will the Bejar, make information and decisions We then the some do, toward is year-end. with to Dr. and

Rafael Bejar

additional Nothing to comment XXX the milligram cohort. your about

we I regard be I been they want of bring a drug other the that's combine myeloma, hematologic think for other where like added With has to combination available, to accurate. of table. have the will that of in that have combinations, agents to multiple several be to one that keys therapeutic with malignancies, it able doesn't think we example. the is to for toxicity just as options because And the future think treatment to AML

necessarily for to the So cleanly be not to likely toxicity be push agent, doses the that and combine that able are exacerbate more able therapeutic both. you're another with to

William Rice

Yes. Great you, point. I Thank All should have right. brought that up. And Emily. thank you, Bejar. Dr.

Operator

of Next Alliance line the question Cross from Partners. Global comes from Matthew

Your open. line is

Matthew Cross

then Hope me. everyone of doing is a taking guys. Hey, and for couple thanks questions from well

trials, of we're I going seen curious due backfill now rationale a levels where or priority to exposure. XXX we've sounds was that think feel getting up to is to I of pretty it the in these much like. also substantial for of on dose how you either dose kind escalate it dosing you well laid XXX, out to and potentially the both higher

we're into believe the higher a if XXX next. So not twice formulation the as some end XXX the five been of potentially a moving giving curious, indication patients, to speak commentary in day. based up and QD pill setting if curious, kind dosages I about I transient differs you I a XXX were if and that And whether has from talking pills about part, problem day, will you of maybe we're really And dosage all talking on this preclinical for about work. was burden or was here. moving getting twice guess that? similarly, was could whether second I milligram to guess year, you're circumvent six about. way be I the into there the XXX then these BID. at if a to XXX there's we're probably

higher? you So I just Thanks. to are get curious insight was as some dosing there

William Rice

Thanks, right. All the somebody down Matt. on phone on looks me. have to That that great was

talking we escalate with start burden. me pill let about So as dose the

you mentioned but twice the we yes, we capsules we activity, XXX, six except day. five past, a to do that that be day pursue twice correct. will are haven't have At continue have it. we much XXX capsules said and development So formulation about a it, it really In

such the lux, are efforts Phase of commercialization. that II ways the formulation asked formulations So And do we we for then about There one that improve pill well development, most drugs, things high is to as with of as you for formulation potential can to does burden. often in continue would But given we're look move and new doses. as later as I require that the reduce we that couple a are that. of Phase the our administration towards stage doing

What have date. We're oral We we've it a advancement animal for preparation what with to actually clinic. absorption with models lux. formulation test what non-human formulation encouraging. for animal The very stability it successful date. – that to in significantly seen may been new been has It's in improve preparing to models manufacturing, of the developing multiple GMP new seeing. models I believe would we in happy say We're happy we're we're is

forward that we are a can properties. we regulatory stability, said, we it manufacturer, feel stage GMP like question. But show it remind I actually improved also no work that humans guarantees we bit. talk will moving appreciate actually the the you it's will getting the asking There this now but to about toward you manufacturing are remain. I that risks that in As still

may into looks and reduce humans, we it we're as we far, reduce that pill it to So everything not burden, we the the amount get can. we're of each give promising, may fingers it thus it the as good there yet, is and have crossed, to so to milligrams soon our but hope quite day humans keeping

good So question.

Okay.

So what was the follow-up?

Rafael Bejar

question. I can take I the Shall go? backfill

William Rice

do. Okay. Please Thanks.

Rafael Bejar

about You patients. mentioned and backfilling further escalating then dose

provides next a Patients the wait I us forward slots. think just advantages One frustrating escalations, it is dose limited patients backfilling in straight can necessarily study Phase a can't to there enroll dose several until open. that advantages. are fairly with of be to cohort number I

closed, us study and site with about a do able diversity is that by phenotypes safety welcomed during to at at continues patients from AML it's learn of explore what standpoint, it by we mechanism backfill often the efficacy But more our of in to ongoing having trying escalation. the a on drug, favor different and to patient the be we're study, then more dose when So dose a patients the escalation cohort opportunity engagement. sites a some or get might gives to put on genotypes and to otherwise putting to

about opportunity and So an more to patients get is the more agent it on. learn

for to sites understanding study, would patients pace It's dose it's it's on us Phase positive I like the positive study. escalation the frustrated for and the the think sometimes we get who So a are who for really with win-win. drug. It’s of positive

William Rice

Thank you, Dr. Operator? Bejar.

Operator

We from question, Oppenheimer. time one more for have Matt Biegler

line is open. Your

Matthew Biegler

bingo. hey trial. landscape on you. don't Phase I CLL multi-part Oh, the how guys I definitely Thanks a I'm demographics look I’ll I to ask to for and in evolving that's maybe question down look on in. your me affecting have only you. in treatment X'XX. up squeezing maybe

kind effectiveness any lux any show noticing you getting patients might some prior emerging And the wanted you and mechanisms BTK you to Thanks. to of think to Are thoughts follow-up class on whether Specifically, be here? non-covalent non-covalent a able are as the with your exposure? resistance uptick? whole, hear I to

William Rice

in. ask and right. All start Again, I'll then to we'll come Dr. Bejar

We're ask treated with CLL, and are treated seeing BTK that they have evolving in of patients then of terms every that with in effectively the failed seeing type there they particular, answer getting yes. inhibitors. been out those non-covalent patients come to the is and And landscape So you in us. we're if treatment

– that. rituximab, quite Most emerge of Bejar little we're Yes, but resistance the in and forward course, or So these many non-covalent it’s of that patients, actually of in are BTK, will patients patients. terms those have mutations are seeing the that the RAS see BTK, quickly, just of it of it's let about rare. a in can And them is now very mention to pathways. we're Venetoclax, these in coming that BPTX heavily But lot beginning a you more of very pretreated some get Dr. the me EIO. BTK covalent PIXK whether inhibitors, talk the bit inhibitors,

cannot achieve RAS for and studies sensitivity you maintain they getting you mutations, the studies, once see sufficient So we start is and don't that that actually drugs, BPTX RAS for you think bloodstream. activity, and levels those that's the most area [BPTX] or the Druker other had We've cells in an keen of just did lux. because Dr. various with activity exposure done us Brian mutations, lose you that

sensitivity fail patients. out experienced there Bejar, patients So array of other But you we're and towards to that Dr. these please hoping the drug. our that other types molecules, actually the cells would of very the as are driving molecules it's add. best again,

Rafael Bejar

Yes.

think that's correct. I

like other the we that exposure to They PLCgammaX be we prior just of of versus seeing I include itself, what BTK. ibrutinib patients for obviously entirely our had resistance on. think of pathways have that the in don't kind are and the are patterns some also sites. understand that so seen going but of resistance them, think the patterns enzyme of we've mutations aren't I

induce inhibitors drug. if activity but other mutations mutated, isn't regard the molecule the superior we'll me in So it’s have of may those cases explore to to will where BTK activity our unclear of themselves non-covalent having to that BTK they itself with

I yet. know think too it's early to

Matthew Biegler

Makes sense. Thanks guys.

William Rice

you, Thank Matt.

Operator

question. am I Rice further no I showing And turn call currently for closing will back Dr. to the over remarks. now

William Rice

joining everyone All for right. want Well, us thank this to I afternoon.

your would more possible at are patients importantly, also important with very our our a We be pursued who our by of the employees, stage And this without of We're are the to at analysts. and thank and keeping for We here forward And progress thank research half None have ending you of Aptose continued advance helping wonderful our work. want a development. I investigators look very the exciting we dedication of evening. year. to the you support. in shareholders all you appraised second

Operator

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

wonderful a You day. may and have all disconnect