ZYME - Earnings call transcript Q2 2024

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Operator

Thank you for standing by. This is the conference operator. Welcome to Zymeworks Second Quarter 2024 Results Conference Call and Webcast. [Operator Instructions] The conference is being recorded. [Operator Instructions] I would now like to turn the conference over to Shrinal Inamdar, Director of Investor Relations. ahead. go please Shrinal,

Shrinal Inamdar

Good XXXX thank results operator. our for second quarter conference afternoon, you, you and joining Thank call.

during number Before to we identified commentary. forward-looking in a accompanying and forward-looking remind like including, statements of oral you that our limitation, begin, we'll be statements I those this call, would the without slides making

at and various our our subject to are statements based are and in development. on Forward-looking of companies usual stage our uncertainties risks assumptions industry with current and expectations and associated the

of a updates, Strategy, refer to as over moment, For will who with our as and you a to these recent hand and results financial our and discussion risks found Bijal second be discussing uncertainties, Desai, our for filed website along filings SEC. In the will we with our the latest corporate quarter VP SEC I Finance on XXXX. of

for our Development of Pranshul Following the application At Galbraith, this, key the and our our Chauhan, about Moore, ZWXXX Ken well be and and Medical for second FDA. Scientific of Q&A CEO, Bijal, talk will will Associate by investigation Chief Officer, Dr. for ZWXXX Director Paul, Paul end the available quarter, new ZWXXX. including highlights as clearances call, for for the Chair as Early-Stage drug

website the today. I Bijal. will slides a also the from Zymeworks over and on audio to the later As be now reminder, this call available will call turn

Bijal Desai

we review BTC programs global milestones Similarly, everyone, BTC regulatory BTC our as for European China. of License target key has with Application call. key Medicines financial of XX, zanidatamab XXXX. you, validated as the us zanidatamab an being the States zanidatamab, thank the tract earnings for treatment granted call development of reviews I biliary including regarding Application Biologics regulatory as second In second the the our for from and cancers Shrinal, remain priority November review late-stage a and today's XXXX action our second-line well for for BLA date achievements in in asset, quarter, second-line results. for Marketing begin achieved in Authorization or Thanks, joining or underway United today the our will of quarter overview with Agency zanidatamab in

pleased China. are received of with to USD license and million Zymeworks zanidatamab's payment Pacific the have July X terms We under BeiGene milestone a with acceptance in Asia in agreement BLA collaboration conjunction in of

Society with look track. States BTC HERIZON-GEA-XX zanidatamab for be enrollment partner, will our first-line Our and patients Jazz, Together pivotal patients Jazz initial based patients. safety to responses confirmed a or expected sustained promising with with potential of clinically the survival is on blinded findings of overall with to to estimates of remained partners, forward we we assessment treatment progression with previously zanidatamab's the subject our gastroesophageal events The data as all Oncology support opportunities in favorable in meaningful to treated ever of in and durable ongoing and meaningful Near track first survival partner, this of the in United the BTC Jazz. Results the includes benefit Jazz look American zanidatamab remains continue United zanidatamab BTC analysis. quarter continues and long-term enrolled that indicate by XXXX. Phase Based on from Meeting highlighting provide is to the the the tolerability clinical HERIZON-BTC-XX for IIb in zanidatamab term, zanidatamab further where can in This presented the trial quarter second zanidatamab. trial durable we HERX-positive to data Clinical presenting Annual evaluating analysis a XXXX. the approval, fourth time from in line Jazz for continued demonstrated manageable or support aiming PFS forward and on responses, initial launch GEA at assumptions. the approval trial has that for potential that antitumor protocol second-line the compared relative trial adenocarcinoma deep in to profile progression-free monotherapy top in the States second-line benefits and available events, line

into wholly-owned clinical In which addition, significant for Zymeworks early-stage progress to of report pleased X pipeline, candidates. our we are transitions programs

ZWXXX for remains zani coverage we where believe complementary as zo zo. cancer, -- and focus other applications XXXX. We I review following pipeline of applications with our This our filings to escalation zo half formally clinical We may and/or second and best-in-class conjugate, in or potential by Phase accelerating into in other ZWXXX HERX-targeted early-stage initiate the breast on which zani pipeline, first-in-human our promising planned clinical lung have a we permission these programs, the with jurisdictions mind, the on respective ZWXXX cancer half the be we ZWXX for partnering the for zani studies trials IND development actively decision non-U.S. United and well of a the and first-in-class studies clinical advancements XXXX XXXX. We made discussions By the therapeutics. dose the can of to to in a to wholly-owned focus continue provide commitment FDA of IND Phase aligns the also known and regulatory to progressing progression stage seeking of to ZWXXX the we of cell the for planned successfully and we in II-ready in non-small commence and our explore as are zovodotin, in cleared reallocating our ZWXXX States, with the believe have decision antibody-drug ZWXXX ZWXXX emerging development second as indications. of asset, to discontinue program zanidatamab resources, strategic ZWXXX

scientific to development processes zani in We patients. gratitude the rigor extends the deliver committed involved zo heartfelt and goal health of program. of team our to the the development with candidates Our professionals remain patients, families in greatest degree with to focusing benefit on highest to the potential care the

oncology a broader continues trial lung priority commence enrollment program in be to XXXX, development X Phase cancer. including cell non-small anticipated to with I of patients with Our

Turning which in the to June year an related was XXXX, a in This share to XXXX. loss for decrease second zanidatamab quarter position. our reported loss results XX, ended million XXXX in and Zymeworks a to in financial million Zymeworks' partially offset of $X.XX primarily the to same was or financial of compared months and net for expenses, net $XX.X charge period XXXX. lower per diluted recognized afternoon, for development X loss zovodotin. decrease net loss administrative due The general was by and and impairment revenue research the $XX.X

costs in and was expenses same offset the increase administrative months ZWXXX ended and candidates, included in support expenses partially for and for the million to in for period period million stock-based in decrease ZWXXX from and activities administrative $XXX Jazz, a payments for other partnership for partners payments. from offset by from zanidatamab $X expenses transfer X contractual and of compared The of in responsibility legal in same in of development for was fees by XX% facility for and was same due million support This million in the $XX.X in XXXX The product June benefits with relation ended million the million our due manufacturing offset for was NMPA compared by XXXX. of operating in operating of our primarily the decreased a and $XX.X June to was XXXX, XX, research XXXX. to expenses general period XXXX support to to other revenue general information insurance a IND amortization $X.X from CDE support well for a compared and second-line to decrease our expense were BTC, development external year-over-year. programs. Salaries same issued expenses by nonrecurring decrease and As expense. drug June supply reduction was the costs expense partially XXXX XXXX, in This technology, a for for for ended representing to Jazz partially consulting Overall, for in an overall XX, for drug expenses and an expenses from in to the research other million both research in of services, long-term a decrease result million lease revenue X was the for incurred in decrease to the due depreciation Seattle in included for Revenue same decrease decrease due and of Jazz. development by $XX.X the in XXXX. ZWXXX, reported, XXXX, compared period as to severance in our costs in advisory from $XX.X The to amendments million expenses programs, and in in and XXXX, months and XXXX. in in compensation to $X.X the Jazz, for partially preclinical resulted same for termination period respect research of the expense from XX, X and the acceptance decrease compared milestone HERX-positive increase decrease research $X.X XXXX, treatment $XXX the period revenue which to support BeiGene for to million development other other revenue expense program decrease support which and BLA a a expenses primarily zanidatamab this development offset a research million primarily BeiGene China to as as and supply for credit of payments. Revenue arrangement our partners the $XX months

$XX.X June the zovodotin the of X to as charge assets. decision ended XXXX, discontinue zanidatamab research noncash development a the recorded development program, of technology During in-process utilize company's represented which and months million the impairment clinical XX, a acquired we by result

common shares outstanding XXXX, prefunded shares warrants. XX, of common XX As approximately approximately issuable of we under had and July million X.X stock million of stock

of had compared cash of As we of securities XX, as XXXX, to XXXX. resources, cash, million million consisting and $XXX.X equivalents marketable XX, of as cash December $XXX.X June

available quarterly www.zymeworks.com. review and to encourage earnings you our other our and on website I details results, additional year-end as our For SEC at filings on release

second candidates achieve long-term product additional plans, seeking million $XXX.X potential the assist a foundation, half commercialization. Based XXXX, believe antibody-drug therapeutics resources payments clinical also operating we XXXX. milestone of June together runway building of antibody gives this We regulatory cash in and us provide may of will current a extend global as into business new of or R&D and diverse to an the fund may refocusing in our anticipated and with in expanded scope stage or of on choose certain expected an existing able goal where position valuable XX, collaborations, which BeiGene continues with of our strong connection help conjugates multispecific partnership through to pipeline to be product ADCs, partnerships form. financial runway and milestone options payments identifying or strategy to and to and which we Jazz with regulatory Our partnerships our solid development appropriate approval

payments XX.X% ZWXXX over annual pending to milestone on on like royalties and on details net XX% Scientific the Moore, and between clinic. provide commercial Dr. moving and I'd addition, XX% we to Paul. our on Officer, into approval, and pipeline In between wholly-owned XX% Chief tiered zanidatamab hand you, sales more Paul regulatory to ZWXXX and that, net Jazz's and annual are regarding of to will receive BeiGene's specifically who sales. With eligible Over based sales our

Paul Moore

Thank you, Bijal.

engagers ADC cell comprehensive broad cancer We of approach gynecological growing I'm the X balancing cancers, areas and our areas. about fundamental therapeutic unmet medical system, ensures cancers modality high and to talking pipeline, focus. today, focus lung delighted we across on these while oncology is both these So the need, built To targeted coverage X digestive which date, and currently therapeutic believe various pillars: this of have and diseases. area T of challenging be

years. outcome. assets, various on focus early-stage will believe both in forward, expertise leveraging we with areas the patient and of with of our pipeline driving continue development improve deep includes to aim be technical coming the our progress to combine and modality in our therapeutic Moving that the modalities our key as the and growth months we to adapt This expanding of

including the You will plans in expansion or our hear fifth trispecific that T on our for later and TriTCE. cell year, of growth engager candidate, a about the more nomination product

also treatments mesothelin folate of NaPiXb and standards that our and underscores level validated previous deliver meet Our that to designed as agents of and shown wholly-owned cell with strategic ADCs balance efficacy, of activity not commitment the targeting to optimize T targets and are have with the engagers monotherapy care, both innovative of selection benefit. ZWXXX starting antigens ZWXXX clinically receptor alpha, like with expression. highest already but in the combination only highest

ZWXXX enhance As geometry, T cell see and coverage helps that linker immune the offers are receptor cell something compared killing to relatively which cancer targets We levels antibody for agents, through NaPiXb in broad across and and effectively bind the enhanced non-small an offers cell cadherin-X, a to our crucial response engagers our robust potentially against folate and believe tumor receptor relatively unique for against comprehensive tumors regardless and X+X robust of providing can modality. By of Similarly, leveraging mesothelin, [ T in ovarian precise a of ] and ADCs mesothelin-expressing such eliminate in payload candidate you format a position expression ZWXXX cancer. effective higher folate lung competitive maximizing alpha-expressing therapeutic efficacy and here, the landscape. tumors. holds ovarian unique to expressed also cancer, high our therapy potential levels the leveraging cells helping a as to cancer, at other are

achieved have by we and ZWXXX development. into our stage in quarter, advancing This ZWXXX significant progressing milestones clinical pipeline both

these of cancer. ZWXXX patients INDs, standard and are to range the to with therapies, moderate strong opportunity care T the tumors of right mesothelin offer keep closer could the great in With these ovarian non-small to that improve potential landscapes. best-in-class providing cell therapeutics the and in our cell lung of clearance one expression particular, has endometrial potentially engagers with effective observed FDA with step cancer, we goal more patients for treatment pancreatic of cancer, cancer for

engager come targeting developing cell its cancers challenges. doesn't without the However, opportunity T for mesothelin-expressing

lines, of X our profile and to ovarian thoughtful including including mesothelioma. potentially cell tumor uses normal mesothelin to a and with on mesothelin tumor expression cancer, which with lines effects, believe the preclinical ovarian, shown mesothelin-dependent cells what mesothelin XX, minimizes mesothelial cancer minimizing binding For And -- lung reduces expression, across mesothelin colorectal avidity-dependent soluble lung, potentially demonstrates cystic significantly cell relatively relative paratopes an reducing high to or moderate of ZWXXX, taken target a cytotoxicity toxicity. On ZWXXX data design cell selective we representative to enable population. ZWXXX's look we ability approach for CRC in demonstrates have mesothelin and patient cytotoxic potent high the survival exhibit impact potency, here Slide off and tissues like lung cell cancer In lines, cancer and target would this tumor at approach, concentrations. low various

specifically control. cytotoxic mesothelin-expressing expression mesothelin-expressing these results, minimizing relative potential targets and in suggests potential -- negative previous across believe a We tissue, relatively off-target in ZWXXX activity therapeutic Importantly, improving cancers findings mesothelin and profiles. The helps in clinical the with this cell expression we cells, high that to to the preclinical mesothelin these healthy lines of efficacy showed safety that further shown tumors various reflective promising including on ZWXXX a minimal low ensure validate moderate similar for normal selective demonstrated broad setting. ZWXXX, to are effects tumor Based slide. as on preparing effects

patient across now clinicaltrials.gov study XXX evaluate in regions. Part open-label Phase will and and X year the non-small Part design metastatic of North participants this study mesothelin-expressing website first I global dose tolerability to study NCT and study X the cancer, cancer expect or evaluate study expected I cell cancers. and ovarian Asia Europe of of ZWXXX available multicenter America, lung includes Phase the tolerability. ZWXXX pathologically We the on The cancers The in to advanced ZWXXX the care under locally is other of our enroll the safety RECIST participants cancers standard according will Pacific is number, available XXXXXXXX. antitumor in treatment of metastatic first Inclusion future care the advanced no discussing calls. progress that and coming look standard available care of activity or standard of continuing criteria, We which evidence unresectable criteria and/or cancers while of safety to the cannot earning and the of evaluate the near forward treatment, in tolerate to refractory of is for to all are to reporting therapy. confirmed with disease, refuses dose while participant patient diagnosis evaluation with

expression high focus with as of described ZWXXX, highlights moving Now on continued to I earlier. levels our which antigens targeting

of portions over platinum-resistant endometrial a level folate cancer XX% strong XX% By defined and As in in attached adenocarcinoma, focusing been receptor X alpha these in receptor for cell and is develop tumors alpha positivity cell to -- which presents -- cancers, commonly alpha XX% scoring ovarian cancer folate frequently folate receptor of folate also a receptor cancer, In reported we improving non-small demonstrating on XX% not cell minimize patient example, by high. Endometrial off-target high. score ovarian illustrated outcomes. of XX% lung scoring portion alpha, are significant potentially tumor high aim non-small represent or that's non-small alpha that's XX% patients ovarian in IHC such the of folate therapeutic of have receptor also receptor that treatments is to cancer expressed greater to effects, efficacy receptor express only of antigens demonstrate but some as and opportunity positive notable with with with alpha lung lung cancer. as folate folate slide, than cancer Similarly, levels around TPS cancer, alpha expression over exhibit overexpressed cancer, equal plus. substantial

novel the ZWXXX. seeing working a in clinical our cleared We forward We're submission how and translates we're to for -- looking this setting. pleased to for unique are ADC design has payload FDA IND report that

more previously X. ADCs. the TOPOXi to we our ZDXXXXX that we activity. expect As was maximizing antibody designed potentially at have evidenced chemistry these efforts tolerability mg on a we clinically would antibody compared selected instability. to ] or primate novel observed developing attachment tolerability, potency focused has selecting on well-established with X with payload a inhibitor bystander efficacy kg allow known discussed on humans ZDXXXXX ADCs and the and high and properties [ a calls, as dose exemplified while strong ZDXXXXX as ADCs specifically ADCs approach topoisomerase designed drug In moderate by payloads, XXX the drive high of non-human ratio per of potent linker DXd implemented validated antibody of of superior with inhibitor TOPOX with as dose We balanced then studies, in

can the higher as of to with Slide toxicity highlighted an DXd here you bottom the or unexpected show As XX, we table, section stability platform. On in ADCs see in the higher compared antibody our we by AACR receptor presentations demonstrate ZWXXX's targeting to compared poster programs. earlier this relative the receptor encompassing folate folate monoclonal X ] other internalization alpha alpha antibodies ADC [ year,

humans. when pleased dosing expected action, cell than type to for ] traditional in its spheroid and T Chair, through year. I line mechanism being components in results Q&A activity of ZWXXX's our compelling factoring see, deliver is our mg per over STRO-XXX, monoclonal of efficacious models is the aids will This of internalization closing of non-severely all [indiscernible], potential primates before of the us in for the of trial this candidates. This from our can clinical antibody able compared to later antitumor gives presenting in in to PROXXXX. levels and toxic the our observation MORAb-XXX, a to Ken, have Phase initiate now in and dissection higher consistent non-human decision hand you in the [ models ZWXXX, antibodies and antibodies achieved confidence to X in these call. monoclonal in kg, ADC monoclonal dose XX highest payload pool a of enhanced are remarks care ability I vivo antibody profile of to for Further, we with internalization predictive model begin portion CEO larger designing more dark to demonstrated As the we our also replicate for blue in the from ZWXXX select ADC which of

Kenneth Galbraith

product update, and That's Financial for Vice the in XXXX, than our date effective in Leone upcoming line more top for biotech in of TriTCE be strategies Xst. as quarter catalyst, of data growth. Leone's record September term, our excited how is see therapy and great. be BTC patients. We're HERX, for and to well We're an readout finance, Phase remain ZWXXX data-driven financial breast the developing demonstrate Thank will our data for in our Patterson the GEA forward Phase announce public an and these we look our we that patients Chief Jazz, Officer, In Jazz, we're multiple for and designed zanidatamab business be and with readout we second successful the XXXX. partner, approach phases track for to studies, to pivotal also expansion PFS cancer zanidatamab with ZWXXX progression safety first III later which plan our meetings pleased validate to advancing a company of you, to after first-line HERX designing on our XX Officer zanidatamab's for President, submissions XX, in of years year. trial, Chief of to dedicated strategy, operations this period November Business executing partner an both by opportunity III on as PDUFA HERX-targeted respective forward efficacy guiding BeiGene, proven available second-line and treatment. with to line zanidatamab's Together expertise with On where XXXX, zanidatamab near in continue top ZWXXX standard has appointment who IND care chemotherapy peer-reviewed nominating brings there's transformative as evaluate Ms. -- into Phase Executive next ZWXXX also through combination our I translates growth experience study we the candidate of of Paul. can pleased another in to to as and data therapies and Patterson in planning key company. United EmpowHER and improve the of to year announce Jazz our further government initiated potential the look the will the where to looking efficacy important more forward filing we after this sharing medical the to estimate an partners, States. during We're

Before we Q&A, concurrent over with call turn financial talk the a was to release the program, to share like which press via report. I'd announced repurchase about our second quarter XXXX

press decision around disclosed of confidence expected strategic zani candidates future business, cash further repurchase allows to XXXX. is associated the share spending. in the believe in to program long-term the million of As providing optionality maintaining has and continue and clinical our to potential authorized the on our million share our This decision program the our purchase capital program to development repurchase release, our $XX We preclinical with our our bolstered half our program the us to a second $XX continue repurchases ample by pipeline. product our promptly the product strong Board us begin strategic while partnerships supported portfolio, development and of and capital R&D zo, enables of for by of the which candidate value outlook reflects reallocate during execute resources deprioritize portfolio that allocation. The advancing position share

second existing anticipated assuming in based the and purchase runway program milestone completion strategic and stock upcoming regulatory believe share on XXXX, expect currently $XX cash undervalued capital resources way in allocation assuming projected ahead as this and receipt in We of of our XXXX. also expected cash the buyback We is full ourselves of the million half to certain maintain catalysts our payments. a see XXXX through invest thoughtful to

cash enable Our to may manage share on repurchases, time, pursue I'd to they our that $XX will enables strategic question-and-answer the capital over shareholders can we and reserving capitalize arise. By execute for X the make opportunities million the for believe session. thank future. With growth future remaining our to balanced to both repurchases operator the flexibility compromising approach that to flexibility us conditions in and market allowing the everyone begin And without resources. repurchase plan that, call This additional thoughtful the over maintain us to listening. gives Operator? opportunities and decisions adapt allocation us us phases the now prudent to we as to in benefit I'll turn to like

Operator

[Operator at from line of question the first comes Instructions] Stephen Our Willey Stifel.

Stephen Willey

ZWXXX you're the IHC for I can I? for getting expression the folate wondering ZWXXX, Thanks at the on that was Yes. the levels are and Phase of What clinic. mesothelin alpha speak baseline just if requiring you to receptor And step dosing there cutoff you say cadence values that dose, about ZWXXX then the you're any requirements requiring for and the is using, you'll both? be that for anything might inpatient able any starting to be of up administration?

Kenneth Galbraith

wants Pranshul, Clinical maybe not Lead but some, Stephen? Global who for to answer Sure. Stephen. those all is He ZWXXX. ask questions, I'll Maybe Thank of the you,

Pranshul Chauhan

and I phases, we'll expression on our expression Initially, retrospectively. escalation Stephen, share start studies. the asked dose analyzing about in thank clinicaltrials.gov. you mesothelin question. levels levels To I alpha off, what's our with you in think receptor folate your can available you for be publicly of

as these So mesothelin, be for to for there's as of validated such, no some cutoff yet example. are

Your second something question dosing haven't is yet. that regarding available strategy, this we made publicly

However, explore piece was last in ZWXXX your intend question, next the formats clinic. what Sorry. and of your of we to -- various And dosing do Stephen?

Stephen Willey

step a dose, of any then requirements. administration starting any Just up dosing, question inpatient and

Pranshul Chauhan

our There a requirements starting regulatory inpatient dose during The in subset discussion the as bodies. in for patients escalation yet. something will with be is requirement dose publicly the by small shared of haven't this we regulatory phase, Yes. is mandated

will we different for where dosing However, work later in requirements strategies the hospitalization study. do we intend to at dosing explore with on

Stephen Willey

be that... expression tumor that or be to you of even folate retrospectively looking just I clarification mesothelin side the on on clear, just Can receptor that will Okay. So you'll IHC the levels side, a then is for types these you so via expression I and maybe alpha enriched enrolling -- of know guess I'm ask question? at each antigens be and target

Pranshul Chauhan

Exactly.

Stephen Willey

Okay.

Operator

Our from next question comes from Citi. Nochomovitz Yigal

Amin Makarem

had Amin on Yigal. a We is couple. This for

on the ZWXXX. First

ZWXXX Given ADC then think previously do ADCs, NaPiXb you the risk failures do molecules payload gives about using what from confidence investigated the Genentech? in in any ADC on same you differentiates your the programs? prior second strategy, you and one the general payload? And What for the this Mersana X by see

Kenneth Galbraith

No, you would to X of like questions? Paul, answer both questions. those great

Paul Moore

Sure. Sure.

design of selected our ZWXXX comes of against down first the think have others or to really the ADC I level in confidence being So all, to failed, the payload. NaPi successful antibody on that from ADCs our

So question your really believe was potency, the as what bystander time regards for aware, spent but we of balance may a second total carefully be right payload. the you activity of to picking payload, lot we

this efficacy antibody favorable. can all in the of the that payloads patients type potency target preclinical against that payload our profile for question about supports we ADCs. your that. that So our of efforts indication again is think that And from of And targets this a and we before, which important, We that feel use our with level with what overall of from benefit particularly previous programs, safety NaPi, through competitor programs tackle and the efficacy a there benchmark with of When then others balance from using larger feel those and disease and to the -- an select to both very X profile could very really targets. different there. payload, profile selected our we comfortable we've approach. And tried feel breadth prior within have regarding X across or we from not ADCs that what looks differentiates payload, options all ADC so we program of TOPO the is data across the

that our in clinic X So all with forward supports programs. the moving

Operator

the comes Tewari from Our question Akash Jefferies. next line of from

Unknown Analyst

number the prespecified not the events you enough related This for interim Jazz is events And PFS is accumulated that to slower be by analysis the anticipated analysis? to to it ] originally just of HERIZON-GEA-XX protocol? any QX announced Divy disclosed have for [ data preplanned than is accumulated interim on of that for Akash. PFS pushed was late from yesterday XXXX 'XX. progressing Does back that enrollment or from mean as getting

Kenneth Galbraith

very of in unblinded your study did events. And being to there's getting question, and is disclosure number is the currently after delay they now was no the in number second very first the estimates think of call that and earnings targeted required was were clear their unblinded which no, guidance our enrollment actual it, to the And events I question, study, I on because on to to their track Jazz XXXX. to your related Yes. clear as of answer QX listen

Operator

of Brian line Our comes question JPMorgan. at from Cheng next the

Unknown Analyst

This is Brian. ] for Sean [ on

you share? first Just that So follow-up. posted on saw you can insights target there's we the a on Phase effect if selected? preclinical doses evaluating? ZWXXX. side many was We clinicaltrials.gov. you And the And that quick think I how profile based curious the on thing any should How of are I additional have

Kenneth Galbraith

might seen? Paul, have want first mesothelin, the you what tolerability we to take do preclinical the about of question characterization,

Paul Moore

although it's -- very is cancer because expressed question, although that's there of highly a it expression types, some of good level that, is on normal a mesothelin. Yes, target

carefully about with you tumor target the have how to think so differentially avoiding the And you normal.

so has of of on tumors, primates. taken lot we of the and us molecules doesn't the time and much potent the represent that's better but molecules spent compromise antitumor that format mesothelin-positive that high-expressing. why evidence safety, preclinical a very a the get other to window, profile. seen tissue in that there, We've on And we toxicity. activity mesothelin, And that levels wouldn't models seen we have into We've low-expressing we've activity normal non-human give formats the trying where different evaluation our so preclinically haven't of done regarding

going come of we the design you're we'll so pay have that, clinic, to -- to really monitor tried dosing to be into with a we to that Pranshul far, that part attention That's asking. But up what we'll -- there. the Of we the evaluating. course, really have of exactly modes address strategies alluded to

Kenneth Galbraith

question second of the Phase And number levels planned study. I'll on the I dose the for about Pranshul for let

Pranshul Chauhan

Yes.

increase we is progression. -- profile. or gather or trial, they're as the as study, but to This tolerability remains DLT on there long I on continue to and participant data to the So is that and trial and safety X answers dose we toxicity plan levels. will on if decrease evaluate and days remain the based question. safety hope your evaluation may XX different tolerability for period

Kenneth Galbraith

And I had think you another question?

Unknown Analyst

clarification you [ quick modeling question. a ]. the for Thank have just Yes. I

that saw we So the impact R&D zo for near-term now cash changed, runway that model should the zani but there with hasn't expenses? discontinued, is we any

Kenneth Galbraith

been subsequent planned on continued related and zo a II decline of some for study. that zani would have Yes. There'll registration to the study Phase in spending to complete the obviously expenses prepare a be

decline -- share million program that's our was which from of period coincidentally time. will over will that the And again, approximately initial program. matches repurchase $XX repurchase that the next So allocated, that

that, released we'll to future expect would R&D and from repurchase to we expense, be reallocate be the will share time. that using over capital that So program

Operator

from at line Miller comes of the question next Jon Evercore. Our

Jonathan Miller

presence these if program. mesothelin at be there those Presumably slides that's mesothelin-negative mentioned start your bit of the and not in does Or you expectations looking -- some on mesothelin bind don't sop patients? on don't sink else would circulating what little of more And you in there. potency Do a you'll binding drive are a but the is be to in tissues, T maybe T a soluble I'll something I patients. there expression Yes. maintain tox note exhaustion on cells tumor I normal-expressing But mode? that. get the CRS you relatedly, have antigen activity? an see going cell you mesothelin? you of by to color the cytotoxicity separately, soluble Is sort retrospectively even expected have you to good the you the itself? of can know up I absence from absence guess, by in of know antigen helping love for that sufficient bispecific perspective I'd that or activity driven you the mesothelin,

Kenneth Galbraith

you for thanks, questions mesothelin? both address No, of Paul, those to Jon. want do

Paul Moore

Sure. Yes.

you most of it tumor question mean, would have I that the about patients going some limited. that mesothelin. first level of types be So we're maybe is into That on the wouldn't or have a possible. mesothelin target

through possible a -- but your ZWXXX, to theoretically think having consistent think well. So then negative engagers T you're could unlikely. about then potential low of and deleterious sure requires -- T cell it on on it's and we comprehensively engage question looked or that -- as probably it's And target the cell Part I leading design the effect. the exhaustion effects also would that then the you right, The But made pretty activation. And T with then gives that But got is happen. cell CDX you not that you at. we with activation. affinity, then molecule it co-engage you sites not very interaction first the binding to CDX get X a mesothelin we've mesothelin don't And set down really on population. that's other

So a that I'm about effect. not so being worried negative

to that to effect again The part think there, surface of launched impact I on mesothelin very tested vitro, or the need to and protein. opposed And that a to maximum we and any on killing to impact still activity, a about and that you get there's really other basically this and combined you is cellular levels the be we as partly fact get just that in soluble binding mesothelin avidity-driven the there you can soluble killing. have a limited with

speaks discuss but that So that that mechanism the with action. to to share -- that it further, happy Jon, and you more and of data supports detail on

Jonathan Miller

Makes sense. I a session One I love about given sense. said for but alpha things you guess, the here. effective. Q&A isn't intrinsically curious more that's there, support why detail I'm can the folate I you was on maybe in would the I of valuable, that talk on that the not itself ask the program? a prepared would payload And follow-up to FR were alpha receptor higher guess remarks in blocking looking that specifically a antibody Makes dose.

to benefit dose is a dose versus toxicity if lower the what's So aggregate giving similar? higher a payload

Paul Moore

question. Yes. Yes, good that's a

the that you've the you can to thinking target. I think get into got higher a that drug more the actually chance there's the patient, of dose partly getting is the

of So to you penetrance just got actually X% gets that aware be site. you've only may X% through doses, antibody lower tumor the the into to the

the the internalization, why chance because internalize dose why so well. efficiently. threshold more the it's antibody promote a got So important that higher does that this opportunity bring as front point gives also well. That's of us you you've want in as better very tumor get to also That's ADC the also into tumor. you've And the getting a on up also to antibody end got patient, of about of we the level what me at to having

moderate of get where then that the more similar a so to to thinking by And got on DXd, to higher that can better having patient get is. a that you've that potency that's payload dose allows our amount So design that or drug there into you tumor.

Jonathan Miller

I I'm given a through driving point is this use cash shareholders at X obviously, and very value in about active I sense. then a this to very -- clinic, on there expectations versus repo. And final guess of just programs clinical drug Makes return development? the discovery guess a capital excess share effort. really curious Is to capital, plus the one one for

Kenneth Galbraith

No, good question.

very now, funded. They're ZWXXX are current and ZWXXX, going look think at funded. ZWXXX schedule into are ZWXXX to fast operations obviously, well and the I if on go our year. are you clinic well next

that, and fifth well Beyond [ what's and right Paul's in indication behind portfolio call which is Advanced ] forward. the we now, that, moving funded

company. what certainly is allocation the Advanced in current outlook I will reasons convinced boost have that think again to coexist But and We've capital periodic we to catalyst a forward total and for that's is we valuation, right allocated we've be return adequately we're in to runway, a most seen with we've cash to the with front capital use the the long-term $XX think back it to with now. can the to and claw our outside the excess a utilize opportunity to make do decision we with us, a now, ourselves our XXXX that made we strength of And, for or our we some XXXX the to thoughtful front happens return. And the that had might have And catalysts million a need the to zo benefit of process positive funding in of which quite invest therefore, investments. Strategically, over study optimism about in to going to thoughtful the for shareholder all front for invest doesn't of think a so that's we in we being buybacks provide think in about we cash, And ourselves. allocation about in portfolio. the we're total of registration opportunities for that optimize ourselves, Paul's of of biotech we've strategy as and now hopefully, that's we in that committed while be which remaining portfolio, looked capital. zani outlined, the shareholder And we're shareholders, that little to. chosen to program uniquely complete going for So R&D the allocation we're happy XxX can opportunities Phase the and and level capital the all a think II to shareholder do. of cash that's are what R&D smart surely way some and prepare

Operator

next Burns [Operator the comes of Wainwright. Robert line from at H.C. Instructions] question Our

Robert Burns

go/no-go to achieve Congrats may. dose good cancer NSCLC? for ovarian me, in point demonstrated [indiscernible]. gavo-cel be signal With And to with are and us? [ X you ZWXXX, a from ] looking from in what reference in escalation, particular if cancer I the regards to would perspective ovarian regard a

Kenneth Galbraith

let decide what question. I'll to Pranshul looking answer for. Good question he that wants how we're

So...

Pranshul Chauhan

Yes. good question. Very

lot the we're to bringing thought of a to have our a want spent time in into the of structure. design strong group has -- time and I assess and we we of candidate think assets. Paul's of safety the feel that a initially, lot We clinic. tolerability

tolerability. So mesothelin-targeting that would be the a focus safety on and shows agent

study. core the I of the that's Phase So

these efficacy to safety gather such criteria on other focus to PFS study and on the But data be of RECIST our data, I these fundamental rate. We in OS data. using tumor Phase types, data the measured as be response will We'll gathering tolerability. measure and and will objective is

Operator

Shrinal closing Thank at this now you. would it I'm to I like showing time. no further back questions to for remarks. queue the in turn

Shrinal Inamdar

Ken for handed being closing That's Apologies. to remarks. over

Kenneth Galbraith

on great. and tuned, reporting please that's you throughout your remainder much milestones to against attention on thank course year. provide for very the progress of stay and time the Thank very the listening forward Yes, our questions. look And And progress some much to very today of Well, and XXXX. we'll for we updates much. you

Operator

Thank conclude the today's does This conference. participation your you for program. in

You may now disconnect.

Zymeworks 1 Aug 242024 Q2 Earnings call transcript