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Making a meaningful differenceA royalty-driven organization differentiated by in-house R&D capabilities developing novel medicines for patients with difficult-to-treat diseases JANUARY 2026
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This presentation and any accompanying oral commentary include “forward-looking statements” or information within the meaning of the applicable securities legislation, including Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. Forward-looking statements in this presentation and the accompanying oral commentary include, but are not limited to, statements that relate to Zymeworks’ expectations regarding implementation of its strategic priorities and the anticipated benefits thereof, including shareholder returns and the anticipated manner of such returns; anticipated capital allocation strategy; the anticipated benefits of its collaboration agreements, including Zymeworks’ ability to receive any future milestone payments and royalties thereunder; statements relating to potential milestone payments upon regulatory approvals of Ziihera in GEA; industry opportunities for acquisition of new revenue streams or collaborations; statements that relate to Zymeworks’ ability to execute the share repurchase plan, in whole or in part; expected timing and amount of repurchases; Zymeworks’ ability to pursue its business objectives following repurchases under the share repurchase plan; expectations regarding future regulatory filings and approvals and the timing thereof; the timing of and results of interactions with regulators; the timing and status of ongoing and future studies and the related data; clinical development of product candidates and enrollment in clinical trials; anticipated preclinical and clinical data presentations; the potential addressable market of zanidatamab and other product candidates; potential safety profile and therapeutic effects of zanidatamab and other product candidates; the commercial potential of technology platforms and zanidatamab and other product candidates; extrapolations or comparisons of results derived from independent studies instead of head-to-head studies are subject to misinterpretation, assumptions or caveats of each study, and may be different from head-to-head comparisons; Zymeworks’ early-stage pipeline; evolution of Zymeworks’ business strategy related to anticipated and potential future royalty streams and existing and potential new partnerships; Zymeworks’ ability to execute new collaborations and partnerships; the anticipated benefits of its collaboration agreements with Jazz, BeOne and other partners; Zymeworks’ ability to receive any future milestone payments and royalties thereunder; anticipated sufficiency of existing cash resources, when assuming full execution of the share repurchase plan and combined with the assumed receipt of certain anticipated regulatory milestones, to fund Zymeworks’ planned operations beyond 2028; Zymeworks’ ability to satisfy potential regulatory and commercial milestones with existing and future partners; the timing and status of ongoing and future studies and the release of data; anticipated continued receipt of revenue from existing and future partners; Zymeworks’ early stage pipeline; Zymeworks’ strategic priorities; preclinical development progress and expectations for future investigational new drug and foreign equivalent application submissions; and other information that is not historical information. When used herein, words such as “plan”, “believe”, “expect”, “may”, “continue”, “anticipate”, “potential”, “will”, “progress”, “on track”, and similar expressions, or any discussion of strategy, are intended to identify forward-looking statements. In addition, any statements or information that refer to expectations, beliefs, plans, projections, objectives, performance or other characterizations of future events or circumstances, including any underlying assumptions, are forward-looking. All forward-looking statements are based upon Zymeworks’ current expectations and various assumptions, including, without limitation, Zymeworks’ examination of historical operating trends. Zymeworks believes there is a reasonable basis for its expectations and beliefs, but they are inherently uncertain. Zymeworks may not realize its expectations, and its beliefs may not prove correct. Actual results could differ materially from those described or implied by such forward-looking statements as a result of various factors, including, without limitation: Zymeworks’ assumptions and estimates regarding its financial condition, future financial performance and estimated cash runway may be incorrect; any of Zymeworks’ or its partners’ product candidates may fail in development, may not receive required regulatory approvals, or may be delayed to a point where they are not commercially viable; Zymeworks may not be able to execute the share repurchase plan, in whole or in part; the anticipated benefits of the share repurchase plan may not be realized; Zymeworks may not achieve milestones or receive additional payments under its collaborations; regulatory agencies may impose additional requirements or delay the initiation of clinical trials; the impact of new or changing laws and regulations; market conditions, including the impact of tariffs; potential negative impacts of FDA regulatory delays and uncertainty around recent policy developments, changes in the leadership of federal agencies such as the FDA, staff layoffs, budget cuts to agency programs and research, and changes in drug pricing controls; the impact of pandemics and other health crises on Zymeworks’ business, research and clinical development plans and timelines and results of operations, including impact on its clinical trial sites, collaborators, and contractors who act for or on Zymeworks’ behalf; zanidatamab may not be successfully commercialized; Zymeworks’ evolution of its business strategy related to anticipated and potential future milestones and royalty streams and existing and potential new partnerships may not be successfully implemented; ongoing and any future clinical trials clinical trials may not demonstrate safety and efficacy of any of Zymeworks’ or its collaborators’ product candidates; Zymeworks’ evolution of its business strategy may not deliver meaningful shareholder returns; Zymeworks may be unsuccessful in actively managing and/or aggregating revenue-generating assets alongside its active R&D operations; Zymeworks may be unable to maintain or enter into new partnerships or strategic collaborations; and the factors described under “Risk Factors” in Zymeworks’ quarterly and annual reports filed with the Securities and Exchange Commission (copies of which may be obtained at www.sec.gov and www.sedarplus.ca). Although Zymeworks believes that such forward-looking statements are reasonable, there can be no assurance they will prove to be correct. Investors should not place undue reliance on forward-looking statements.The above assumptions, risks and uncertainties are not exhaustive. Forward-looking statements are made as of the date hereof and, except as may be required by law, Zymeworks undertakes no obligation to update, republish, or revise any forward-looking statements to reflect new information, future events or circumstances, or to reflect the occurrences of unanticipated events. Legal disclaimer 2
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Recognized revenue of $25.0M development milestone payment from J&J HERIZON-GEA-01 Topline Data Readout 3 Executing on an established model, positioned for scalable growthShareholder returnsOperational progress Jazz and BeOne to file sBLA for zanidatamab for the treatment of HER2+ GEA FDA approves Ziihera® for the treatment of HER2+ (IHC 3+) BTC resulting in $25.0M regulatory milestone payment from Jazz Completion of initial $30.0M of share repurchase program First patient dosed in the Phase 1 trials of ZW191 and ZW171Decision to discontinue development of ZW171 Expansion of Board and management team focused on strategic BD Recognized revenue of $25.2M in partnership milestone payments* NMPA conditional approval of Ziihera® for BTC resulting in $20.0M milestone payment from BeOne Recognized revenue of $2.5M research milestone payment from GSK Completion of $30.0M of share repurchase programAnnounced $125.0M share repurchase program Initial clinical data from the Phase 1 trial of ZW191 showcasing best-in-class potential First patient dosed in the Phase 1 trial of ZW251 2H 20241H 20252H 20251H 2026 PARTNERSHIP PROGRESSPIPELINE PROGRESS
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4 Evolving our value proposition We are transforming from a traditional biotech to a revenue-generating organization differentiated by in-house R&D capabilities Return and compound existing valuable royalty streams in a tax-efficient manner We are pivoting to this novel strategy to: Enable internal R&Dto focus on its strengths – delivering highly innovative medicines with early proof of differentiation – while avoiding costly and binary late-stage development Deploy capital with a focus on best possible risk-adjusted returnto shareholders
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5 Pathways to return and compound valuefor shareholdersCOMPOUND VALUE ALTERNATIVESInternal ProgramsAcquired ProgramsAcquired Royalties RETURN VALUE ALTERNATIVESShare RepurchasesSpecial Dividends CASH FLOW FROM PARTNERS We seek to allocate capital based on which path we believe will provide the highest return for shareholders
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6 Ziihera Peak Sales Estimate Over TimeEvolution of Wall Street Consensus | 2023 vs. Now | ($ Millions) $1,197.0 $2,326.8 Fe b-2023 Cu rrent 94% Change Feb-2023 Current $1, 197.0 $2,326.8 94% change
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7 Differentiation of partner focused R&D Partner driven clinical developmentR&D operations self-funded through partnerships and milestones, without dependencyon royalty cash flow Preclinical and early clinical stage development focusMinimize costly, lengthy, binarylate-stage development programs Ability to leverage internal discoveryand external BDEnables diverse scientific platforms and multiple areas of expertise Success metrics: partnerships, royalty and milestone generation
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8 Well-positioned with R&D and asset aggregation synergiesAcquire existing royalties Create synthetic royaltiesUnlock trapped royaltiesEstablish platform collaborationsPartner internal programsPartner acquired programs TRADITIONAL ROYALTY BUYERSTRADITIONAL BIOTECH
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9 Differentiated pipeline of multifunctional therapeuticsProgramTechnologyTargetIndicationDiscoveryPreclinicalPhase 1Phase 2Phase 3Solid Tumor Oncology: Antibody-Drug Conjugates (ADC)ZW191Topo1i ADC | DAR 8 | Fc WTZD06519 PayloadFRα GynecologicalThoracicZW251Topo1i ADC | DAR 4 | Fc WTZD06519 PayloadGPC3Digestive System (HCC)ZW220Topo1i ADC | DAR 4 | Fc MutZD06519 PayloadNaPi2bGynecologicalThoracicZW327Topo1i ADC | DAR 8 | Fc MutZD06519 PayloadLy6EMultiple indicationsSolid Tumor Oncology: Multispecific Antibody Therapeutics (MSAT)ZanidatamabBispecificAzymetric™ HER2Multiple indicationsZW209Trispecific TCE | Tri-TCE CostimAzymetric™, Novel anti-CD3Conditional CD28DLL3 x CD3 x CD28ThoracicZW239Trispecific TCE | Tri-TCE CostimAzymetric™, Novel anti-CD3Conditional CD28CLDN18.2x CD3 x CD28Digestive System Autoimmune & Inflammatory Diseases ZW1528Dual Cytokine BlockerAzymetric™Hetero-Fab | YTEIL4Rα x IL-33ZW1572Dual Cytokine BlockerAzymetric™Hetero-Fab | YTEIL4Rα x IL-31 NCT06555744NCT07164313 Development partners: Jazz Pharmaceuticals and BeOneAnticipated IND in 2026 Anticipated regulatory submission in 2026
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10 Partnering is central to Zymeworks' history and futureLeverage partnerships to extend the reach of Zymeworks’ best-in-class platforms and capabilitiesPLATFORM AND DISCOVERY PARTNERSHIPS TOPO1i Platform Engineered Cytokines ZymeLink™ AuristatinHemiasterlin Novel Payloads T cell engagers EFECT™ Azymetric™ ASSET-BASED /PIPELINE PARTNERSHIPS zanidatamab Commercial Partners FUTURE PARTNERSHIP OPTIONALITY FOR OUR WHOLLY-OWNED PIPELINE ZW191ZW327 ZW251ZW220 ZW209ZW239 ZW1528ZW1572 Antibody-Drug ConjugatesT-cell EngagersBispecificsAIID programsOncology programs
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11 Proven execution and financial foundation with Ziihera® UP TO $440M Anticipated near-term milestones for globalGEA approvals1 $400MUpfront and milestone payments received to date* $81MUpfront and milestone paymentsreceived to date $1.3BFuture potentialregulatory and commercial milestones*** $2.0B+Peak sales potential provided by jazz210-20% tiered royalties $144MFuture potentialregulatory andcommercial milestones 19.5%High single-digitroyalties fromBeOne sales¹
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12 Diverse potential revenue streams fromexisting platform partnershipsPartner & PhasePotential Future Milestone PaymentsRoyalty Rate Phase 3Up to Tiered worldwide royalties in themid-single digit percentages Phase 1Up to $1.1BTiered worldwide royalties in the low to mid-single digit percentages Phase 1Up to $313MTiered worldwide royalties on sales PreclinicalUp to $230MTiered worldwide royalties from low single digit percentages up to 10% PreclinicalUp to $1.1BTiered worldwide royalties in the low single digit percentages PreclinicalUp to $921.8MTiered worldwide royalties on sales $434m1 PROMISING UPDATES FROM PASRITAMIG First Phase 3 initiated in September 2025 (NCT07164443): pasritamig vs placebo in castration-resistant prostate cancerPhase 3 scheduled for 2026 (NCT07225946): pasritamig with docetaxel vs docetaxel for metastatic castration-resistant prostate cancerJ&J guidance of $1-5B in sales2 Encouraging Phase 1 clinical data presentedat ASCO 2025* ALT OPTION
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13 Partnerships that benefit both Zymeworks and our partners Partner Benefits Zymeworks Benefits Access to proven team with deep scientific and engineering expertise PEOPLE Builds reputation as partner of choice and knowledge leader across modalities Unique combination of biology and engineering enables development of complex therapeutics PLATFORM Extends the reach of Zymeworks’ novel and differentiated technologies Flexible model enables partners to tailor collaborations to their strategic priorities PARTNER Non-dilutive capital to enable further scientific innovation and builds royalty pipeline
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14 Operating from a strong financial position +$270MCash resources1 provides a runway beyond 20282 $125MShare repurchaseplan announced in November 2025 $103MRevenues reportedfor 20253 +$440MFrom potential cumulative globalGEA approvals UP TO Cash runway expected to fund operations beyond 20282 with accessto non-dilutive potentially lower cost of capital financing
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15 Pushing the boundaries of antibody-based therapeutics through multispecifics and optimized drug conjugates MULTISPECIFIC ANTIBODIESUnlocking new biology and therapeutic possibilities through optimal design and formatANTIBODY-DRUG CONJUGATES Utilizing antibodies to more effectively deliver small molecules through optimal linker-payload design and antibody format
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ZW191ADC Designed to TargetFRα-Expressing Tumors Phase 1 trial ongoingin 2H 2024 (NCT06555744) Optimized design1ADC targeting FRα-expressing tumors including ovarian cancer, other gynecological cancers, and NSCLCComprised of a humanized IgG1 antibody conjugated to a novel camptothecin-based topoisomerase 1 inhibitor payload technology, ZD06519Drug-to-antibody ratio ~8Validated peptide cleavable linker sequence Differentiated profileDifferentiated anti-tumor activity in preclinical tumor models with a breadth of FRαexpression1 Phase 1 trial preliminary efficacy data, shows 64% overall response rate in gynecological cancers at doses ≥6.4mg/kg and a manageable safety profile, with low rates of dose modifications, dose delays, and Grade ≥3 treatment-related adverse events2 Opportunity to treat broader range of FRα-expressing cancers Significant patient need FRαis found in ~75% of high-grade serous ovarian carcinomas3 and ~70% of lung adenocarcinomas4 16
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17 ZW191 demonstrates a favorable clinical safety profile TRAE, n (%)Data cutoff:September 10, 2025ZW1911.6 mg/kg (n=3)ZW1913.2 mg/kg (n=3)ZW1914.8 mg/kg (n=4)ZW1916.4 mg/kg (n=10)ZW1918.0 mg/kg (n=11)ZW1919.6 mg/kg (n=8)ZW19111.2 mg/kg (n=2)Total(n=41) Any TRAE1 (33)3 (100)3 (75)8 (80)10 (91)6 (75)2 (100)33 (80)Grade ≥3 TRAE01 (33)01 (10)4 (36)1 (13)07 (17)TRAE leading to dose interruption02 (67)001 (9)003 (7)TRAE leading to dose reduction0001 (10)1 (9)002 (5)DLT eventa 0001 (20)0001 (4) Presented at 2025 AACR-NCI-EORTC Conference on Molecular Targets and Cancer Therapeutics No serious TRAEs, discontinuations due to AEs, or deaths reported
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18 ZWI-ZW191-101| preliminary clinical results Best percent change in target lesion size from baseline (n=27) Presented at 2025 AACR-NCI-EORTC Conference on Molecular Targets and Cancer Therapeutics Data cutoff: September 10, 2025 Preliminary efficacy for response-evaluable participants with gynecological cancer Data cutoff: September 10, 2025BestresponseZW1911.6 mg/kg (n=3) ZW1913.2 mg/kg (n=3) ZW1914.8 mg/kg (n=4) ZW1916.4 mg/kg (n=7) ZW1918.0 mg/kg (n=4) ZW1919.6 mg/kg (n=3) ZW191 6.4-9.6 mg/kg(n=14) Total(n=24) PR, n (%)a02 (67)1 (25)4 (57)2 (50)3 (100)9 (64)12 (50) cPR, n (%)02 (67)1 (25)3 (43)1 (25)04 (29)7 (29) SD, n (%)1 (33)1 (33)2 (50)3 (43)2 (50)05 (36)9 (38) PD, n (%)2 (67)01 (25)00003 (13)
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19 ZW191 | Next steps Data-driven developmentBuilding confidence in our ADC platform through safety, pharmacokinetics, and efficacy with emerging clinical data Optimization & differentiation11.2 mg/kg dose definedas MTD since this data-cutRandomized dose optimization began in 4Q-2025 in platinum resistant ovarian cancer at 9.6 and 6.4 mg/kg doses (~30 pts/cohort)Early data supportsbest-in-class potential Strategic growth potentialEmerging data will inform registration and combination strategies, includingearlier-line opportunitiesIn parallel, partnership discussions are underway to further refine andaccelerate development
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ZW251ADC Designed to Target Glypican 3-Expressing Hepatocellular Carcinoma (HCC) Phase 1 clinical trial underway(NCT07164313) Optimized designPotential first-in-class ADC designed to treat GPC3-expressing HCC with a new MOAComposed of a humanized IgG1 antibody conjugated to a novel camptothecin-based topoisomerase 1 inhibitor, ZD06519Intermediate drug-to-antibody ratio ~4Validated peptide cleavable linker sequence Differentiated profileStrong preclinical activity in models with a breadth of GPC3 expression1 High tolerability in repeat dose nonhuman primate studies of up to 120mg/kg Preclinical tolerability profile enables high first in human dose of 3.2 mg/kg Significant patient need GPC3 is expressed in 76% of HCC, with highexpression observed in ~55% of HCC2 HCC is the most common type of primary liver cancer and the third leading cause of cancer deaths globally1 20
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21 Hepatocellular carcinoma epidemiology and current treatment https://seer.cancer.gov/statfacts/ HCC BURDEN1Globally 6thmost common cancer and third most common cause of death from cancer STANDARD OF CARE FOR SYSTEMIC HCC2In the US, most patients receive IO-VEGF or IO-IO combinations in 1L; multi-targeted TKIs are a 2L option 3.5% 8.2% 15.6% 3131.0% 34.1% 21.6% 25.4% 65.0% 90.7% 97.1% Liver Lung Colon Breast Prostate5-Year Relative Survival, US (2013-2019) All StagesDistant Disease0 25 50 75 100 02 4 6 8 ORR (%) mPFS (months) Standard of Care, ORR & PFS atezolizumab + bevacizumab1L, IMbrave150durvalumab + tremelimumab1L, HIMALAYA sorafenib or lenvatinib2L retrospective As a first-in-class TOPO1-based ADC for HCC, ZW251 offersthe potential of anew MOA for patients,and an opportunity to improve upon the current standard of care
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22 ZW251 | potential utility in hepatocellular carcinoma ZW251 0.00010.0010.010.11101001,000 0 20 40 60 Concentration (nM) % Cytotoxicity Robust ADC internalization and cytotoxicityZW251 internalized in HCC cell line Internalization visualized after 24-hour treatment Tumor spheroid cytotoxicity in HCC cell line Cytotoxicity assessed by cell line spheroids (treatment over 4 days) Differentiated modality demonstrates anti-tumor activityAnti-tumor activity of ZW251 against hepatocellular carcinoma patient derived xenografts expressing high and low GPC3 0 10 20 300 500 1000 1500 2000 Days a+er dosing Tumour Volume (mm3, Mean ± SEM) 0 10 20 300 1000 2000 3000 Days a*er dosing Tumour Volume (mm3, Mean ± SEM) Vehicle ZW251, 8 mg/kg HCC PDXGPC3 H-Score: 288HCC PDXGPC3 H-Score: 84 Impressive tolerability and dose-proportional PK in NHPNon-GLP toxicology study in non-human primates dosed 3 times every 3 weeksDoseMTDT1/2 (day)20 mg/kg≥ 120 mg/kg4.660 mg/kg4.8120 mg/kg5.4 Total IgG in NHP serum
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ZW220ADC Designed to TargetNaPi2b-Expressing Ovarian Cancer and NSCLC IND-ready candidate Optimized design1ADC targeting NaPi2b-expressing solid tumorsComprised of a humanized IgG1 antibody conjugated to a moderate potency topoisomerase 1 inhibitor payload technology with bystander activity, ZD06519Intermediate drug-to-antibody ratio ~4Validated peptide cleavable linker sequenceFcγR silenced to potentially minimize toxicities driven by target mediated cellular uptake via FcγR Differentiated profileStrong preclinical activity in models with a breadth of NaPi2b expression2 Encouraging tolerability in repeat dose NHP toxicology studies1 Desirable PK and is well tolerated at high dosesFirst-in-class ADC potential for NaPi2b-expressing solid tumors Significant patient need NaPi2b is found in ~83% of ovarian serous adenocarcinomas2 and ~77% of NSCLC adenocarcinomas2 23
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ZW209Trispecific T cell engager (TriTCE) Designed to T arget DLL3-expressing Solid Tumors On track for IND submission in 2026 Optimized designPotential first-in-class TriTCE Co-Stim targeting eradication of DLL3-expressing tumor cells through simultaneous engagement of CD3 and CD28 on T cellsOptimized DLL3, CD3, CD28 binding affinities and coordinated binding geometry usingAzymetric™ and EFECT™ platformsLeverages obligate cis-T cell binding and conditional CD28 engagement to prevent unintended T cell activation and T cell fratricide, while enabling tumor-targeted cytotoxicity Differentiated profileSuperior in vitro and in vivo pharmacology profile relative to DLL3 x CD3 bispecifics including TarlatamabIntegrated co-stimulation increases target-dependentT cell proliferation, survival and anti-tumor activityNo T cell activation or cytokine activation in absence of DLL3 target cells, no T cell fratricideWell tolerated at high dose in nonhuman primates displaying antibody like pharmacokinetics Significant patient need DLL3 is expressed on the surface of SCLC and other neuroendocrine tumors but rarely on the surface of normal cellsSCLC accounts for about 15% of all lung cancer diagnoses in the U.S. each year1 24
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ZW1528Bispecific Designed to Address Respiratory Inflammation On track for IND submission in 2026 Optimized designIL-4Rαx IL-33 bispecific molecule that inhibits multiple pathways within complex pathophysiology of inflammation in diseases such as mixed-type COPDIn-house antibody discovery of novel anti-IL4Rαand IL-33 paratopesNative IgG-like geometry Differentiated profilePotently blocks two complementary pathways of respiratory inflammation: IL-4Rα and IL-33Targets three cytokines in a single biologicOffers a unique approach that leverages clinically validated targetsDemonstrates high manufacturability and incorporates half-life extending Fc modificationsAligns with requirements for successful AIID therapeutics Significant patient need Mixed-type COPD patients are hospitalized 2-3.6 times more often than those with other COPD phenotypes1 Anti-IL4Rα Anti-IL-33 IgG4 YTE 25
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26 Meaningful catalyst events anticipatedthroughout 2026 2026Presentedpractice changingand clinically meaningful mPFSand mOSin Phase 3clinical trial of zanidatamabin 1LGEAwith our partners Jazz and BeOneat ASCO GIZanidatamabPhase 3 data in 1L GEA submitted for inclusionin the National Comprehensive Cancer Network Guidelinesby our partner Jazz Ongoing royalty revenue for Ziihera® from by Jazz and BeOne Additionaldata from the Phase 1 trial of ZW191 isanticipatedto be presented at a major medical meeting in 2026 Cash2runway forecast beyond 2028 when combined with receipt of certain anticipated regulatory milestone payments3 Jazz expects to submit sBLA in the U.S. in 1H-2026 to support Ziihera as a 1L treatment for patients with HER2-positive GEA with potential approval and launch in 1L GEA in late 2026Zymeworkshas the potential to receive substantial near-term milestone payments related to futureanticipatedregulatory approvals in GEA including $250.0 million in the U.S. as early as 2026 Expected IND submission for ZW209(DLL3) in 2026Expected regulatory submission for ZW1528 (IL4R x IL-33) in2026 Execution of strategic initiative to compound existing royalties through strategic transactions including partnerships and acquisitions. Potential to opportunistically execute on share repurchase programprovidingthe ability to repurchase up to $125.0million in common stock
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27 Company contactsINVESTOR RELATIONSShrinal InamdarVice President, Investor Relationsir@zymeworks.com+1 604 678 1388MEDIA RELATIONSDiana PapoveVice President, Corporate Communicationsmedia@zymeworks.com+1 604 678 1388