CD28

Reported $456.3 million in cash resources as of December 31, 2023, which when combined with certain anticipated regulatory milestone payments provides projected cash runway into 2H 2027 Initiation of rolling biologics license application (BLA) filing with the FDA for zanidatamab as second-line treatment for biliary tract cancers (BTC) in the United States (US) with anticipated completion of regulatory submission in 1H 2024 by our partner, Jazz Pharmaceuticals Initiation of Phase 3 confirmatory trial for zanidatamab as first-line treatment in BTC by our partner Jazz Pharmaceuticals Expected submission of BLA for zanidatamab with the National Medical Products Administration (NMPA) in China for treatment of HER2-amplified inoperable and advanced or metastatic BTC in 2H 2024 by our partner BeiGene Targeting HERIZON-GEA-01 pivotal Phase 3 readout in late 2024 and increased enrollment of patients to improve the statistical power for overall survival (OS) endpoint Two planned investigational new drug (IND) submissions or foreign equivalents in 2024 for ZW191 and ZW171 Acceptance of five abstracts to be presented at American Association for Cancer Research (AACR) in April 2024 to highlight R&D pipeline Will host conference call with management today at 4:30 p.m. Eastern Time (ET) VANCOUVER, British Columbia, March 06, 2024 (GLOBE NEWSWIRE) -- Zymeworks, Inc. (Nasdaq: ZYME), a clinical-stage biotechnology company developing a diverse pipeline of novel, multifunctional biotherapeutics to improve the standard of care for difficult-to-treat diseases, today reported financial results for the fourth quarter and year ended December 31, 2023, and provided a summary of recent business highlights. “We begin 2024 in a very strong position, with the initiation of the rolling BLA submission for zanidatamab in second-line BTC in the United States, and a projected cash runway to support the development of our expanded portfolio of clinical and preclinical product candidates into the second half of 2027,” said Kenneth Galbraith, Chair and Chief Executive Officer of Zymeworks. “We look ahead to a potentially transformative year for Zymeworks; both through potential upcoming regulatory approvals, and more broadly through executing on our development strategy for our early-stage product pipeline of antibody-drug conjugates and multispecific antibodies.” Galbraith continued, “We remain on track with our goal of completing two IND submissions this year, with multiple data catalysts highlighting the innovation within our pipeline. These IND submissions, along with additional planned submissions over the next two years, provide multiple opportunities for business development and collaborations. We remain committed to executing on our development strategy for our pipeline of unencumbered product candidates, all of which have the potential to improve the standard of care for patients in disease areas with high unmet need, and commercially attractive targets.” Recent Highlights and Current Developments Zanidatamab Continues to Advance with Multiple Catalysts In November 2023, our partner Jazz Pharmaceuticals plc (“Jazz”) and The University of Texas MD Anderson Cancer Center announced a five-year strategic research collaboration agreement to evaluate zanidatamab, an investigational human epidermal growth factor receptor 2 (HER2)-targeted bispecific antibody, in multiple HER2-expressing cancers. In December 2023, response rates in the HERIZON-BTC-01 Asian subgroup cohort were presented at the European Society of Medical Oncology Asia Conference, highlighting consistency across subgroups with durable tumor responses (overall response rate of 42% [95% CI: 28, 57], median duration of response 7.4 [3.9- Not Estimable] months) and a tolerable safety profile (no patients in the Asia subgroup experienced grade 4 or 5 treatment related adverse events). In December 2023, progression free survival (PFS) for zanidatamab in combination as chemotherapy-free regime was presented at the San Antonio Breast Cancer Symposium. Data from 51 patients with heavily pretreated HER2+/HR+ metastatic breast cancer who were treated with zanidatamab plus palbociclib and fulvestrant demonstrated a PFS at six months of 67% (n=34) [95% CI: 52, 79]. Secondary endpoint findings included a median PFS of 12 months [95% CI: 8, 15] and a confirmed objective response rate of 35% [95% CI: 21, 50] with a median duration of response of 15 months. The combination regimen was well tolerated with a manageable safety profile. In January 2024 at the American Society of Clinical Oncology Gastrointestinal (GI) Symposium, Patient-Reported Outcomes from HERIZON-BTC-01 demonstrate patients who responded to zanidatamab had less pain and pain interference compared to their baseline levels. In January 2024, our partner Jazz highlighted that for the HERIZON-GEA-01 trial, enrollment will be increased from 714 to 918 patients to improve the statistical power, for the OS endpoint only. This update allows Jazz to maintain the previously guided top-line readout, targeted for late 2024, which will continue to be based on the original enrollment numbers. Discussions with FDA and other regulatory agencies were held in advance of the decision to increase enrollment for the OS endpoint analysis. Jazz also announced that the rolling submission of the BLA submission for zanidatamab in second-line BTC has been initiated, with the intention of completing the BLA submission in the first half of 2024. In February 2024, our partner Jazz disclosed that they have initiated a Phase 3 confirmatory trial to evaluate zanidatamab as first-line treatment for patients with metastatic BTC. In February 2024, our partner BeiGene updated guidance on the expected timing of the BLA filing for zanidatamab with the NMPA for treatment of HER2-amplified inoperable and advanced or metastatic BTC in China during the second half of 2024. Progression of Research & Development Programs In February 2024, we published a manuscript in the American Association for Cancer Research Molecular Cancer Therapeutics Journal on the screening and selection process for our novel topoisomerase-1 inhibitor (“TOPO1i”) payload known as ZD06519. Our novel camptothecin analogue ZD06519 was selected based on its favorable properties as a free molecule and as an antibody conjugate, which include moderate free payload potency (~1 nM), low hydrophobicity, strong bystander activity, robust plasma stability, and high-monomeric antibody-drug conjugate (ADC) content. When conjugated to different antibodies using a clinically validated MC-GGFG-based linker, ZD06519 demonstrated impressive efficacy in multiple CDX models and noteworthy tolerability in healthy mice, rats, and non-human primates. Five abstracts accepted for presentation at the AACR Annual Meeting taking place April 5-10 in San Diego, CA. Abstracts accepted include two presentations from our multispecific antibody therapeutics (MSAT) program: DLL3 TriTCE Co-Stim: A next generation trispecific T-cell engager with integrated CD28 costimulation for the treatment of DLL3-expressing cancers (Abstract #6716) TriTCE Co-Stim: A next generation trispecific T-cell engager platform with integrated CD28 costimulation, engineered to improve responses in the treatment of solid tumors (Abstract #6719) and three presentations from our ADC program: ZW191 – a FRα-targeting antibody drug conjugate with strong preclinical activity across multiple FRα-expressing indications (Abstract #1862) Screening novel format antibodies to design bispecific ADCs that address target heterogeneity (Abstract #2052) Development of three-dimensional cancer cell line spheroid models for the in vitro functional characterization of cytotoxic antibody-drug conjugates (Abstract #3127) Zanidatamab zovodotin (ZW49) remains ready for a Phase 2 clinical trial, in combination with pembrolizumab, with the recommended Phase 2 dose of 2.5 mg/kg every three weeks. However, the initiation of the planned Phase 2 study has been deprioritized, pending more clarity from the evolving clinical landscape. We continue to explore potential development and commercial collaborations for zanidatamab zovodotin. On track to submit two IND or foreign equivalent submissions for ZW191 and ZW171 in 2024. “We have significantly accelerated the development timeline for our early stage ‘5 by 5’ programs, with four of the five IND candidates now nominated, the most recent being ZW251, our GPC3 targeting ADC being developed for the treatment of hepatocellular carcinomas,” stated Paul Moore, Ph.D., Chief Scientific Officer at Zymeworks. “We remain on track to accomplish our goal of submitting IND or foreign equivalent submissions in 2024 for both ZW191 and ZW171, in 2025 for ZW220 and ZW251, and to nominate our fifth IND candidate during 2024, with a planned IND filing in 1H 2026. We are also working on the next generation of ADC and MSATs beyond the ‘5 by 5’ portfolio, which we look forward to talking about in more detail later this year.” Business Updates & Corporate Developments Addition to the Nasdaq Biotechnology Index (Nasdaq: NBI) effective prior to the market open on Monday, December 18, 2023. Completion of a securities purchase agreement with funds affiliated with EcoR1 Capital, LLC (“EcoR1 Capital”), for the sale of an aggregate of 5,086,521 pre-funded warrants to purchase 5,086,521 shares of common stock at an exercise price of $0.0001 per share. The aggregate gross proceeds from the offering were approximately $50 million. The purchase price of $9.8299 for each pre-funded warrant was based on the closing price of $9.83 per share of Company’s common stock on Nasdaq on December 22, 2023. Significant additions to Zymeworks leadership team, including eight new Vice Presidents. These additions to the leadership team highlight Zymeworks’ commitment to nurturing and advancing internal talent to key leadership roles while strengthening the capabilities and experience of the organization. Appointment of Dr. Alessandra Cesano to the board of directors effective February 8, 2024. Dr. Cesano succeeds Dr. Kenneth Hillan, who stepped down effective February 8, 2024 after a successful seven-year tenure as a director of Zymeworks. Appointment of Mr. Scott Platshon to the board of directors effective February 22, 2024. Scott Platshon is a Partner at EcoR1 Capital. Financial Results for the Year Ended December 31, 2023 Revenue was $76.0 million in 2023 compared to $412.5 million in 2022. Revenue for 2023 included $71.5 million for development support and drug supply revenue from Jazz and $4.5 million from our other partners for research support and other payments. Revenue for 2022 included $375.0 million in upfront fees from Jazz, $24.3 million development support payments from Jazz, and a $5.0 million upfront fee from Atreca as well as $8.2 million in research support and other payments from our other partners. Research and development expense was $143.6 million in 2023 compared to $208.6 million in 2022. In 2023, research and development expense included a non-cash stock-based compensation expense of $2.4 million comprised of a $2.1 million expense from equity classified awards (2022 – $3.2 million expense) and a $0.3 million expense from the non-cash mark-to-market revaluation of certain historical liability classified awards (2022 - $0.8 million recovery). Excluding stock-based compensation and 2022 restructuring expense, research and development expense decreased on a non-GAAP basis by $59.3 million in 2023 compared to 2022. The decrease in research and development expense was primarily due to a decrease in expenses for zanidatamab as a result of transfer of this program to Jazz per our transfer agreement and amended and restated collaboration agreement with Jazz. This decrease, compared to 2022, was partially offset by an increase in preclinical expenses, primarily with respect to preclinical product candidates ZW171 and ZW191, and in higher zanidatamab zovodotin program costs, as a result of amendments to clinical development program agreements in 2022. In addition, salaries and benefits expenses decreased compared to the same period in 2022, due to lower headcount in 2023 and lower non-recurring severance expenses. General and administrative expense was $70.4 million in 2023 compared to $73.4 million in 2022. In 2023, general and administrative expense included a non-cash stock-based compensation expense of $5.3 million comprised of a $6.6 million expense from equity-classified awards (2022 – $4.1 million expense) and a $1.3 million recovery from the non-cash mark-to-market revaluation of certain historical liability-classified awards (2022 – $2.9 million recovery). Excluding stock-based compensation and 2022 restructuring expense, general and administrative expense decreased on a non-GAAP basis by $3.8 million in 2023 compared to 2022. The decrease in general and administrative expense was primarily due to a decrease in salaries and benefits expenses due to lower headcount and due to lower non-recurring severance expenses in 2023, as well as due to a decrease in expenses for professional services. This was partially offset by an increase in other expenses related to higher depreciation on facilities and higher technology spend in 2023. Other income, net increased by $14.1 million in 2023 compared to 2022. Other income, net for 2023 included $19.7 million of interest income partially offset by a $0.9 million in other expenses which includes foreign exchange losses partially offset by other miscellaneous income. Higher interest income in 2023 was due to income earned on higher cash resources and at higher rates of return in 2023. Other income, net for 2022 included $3.6 million of interest income and a net foreign exchange gain of $1.2 million primarily due to the revaluation of Canadian denominated items. Income tax expense decreased by $11.5 million in 2023 compared to 2022, primarily due to a reduction in U.S. taxes under the global intangible low-taxed income rules, in 2023. In 2023 we incurred a net loss compared to a net income in 2022, primarily due to the Jazz partnership. Net loss was $118.7 million in 2023 compared to net income of $124.3 million in 2022. Net loss in 2023 as opposed to net income in 2022 was primarily due to non-recurring upfront fee revenue from our collaboration agreement with Jazz in 2022, which was partially offset by higher collaboration revenue, lower operating expenses, higher interest income and lower income tax expenses in 2023. “We are happy to report a continued reduction of our operating cash burn and operating losses during 2023 compared to 2022,” said Chris Astle, Ph.D., Senior Vice President and Chief Financial Officer of Zymeworks. “Our strategy of re-focusing the business and building a diverse clinical-stage product pipeline of ADCs and multispecific antibody therapeutics continues to provide a strong foundation, helping to achieve our long-term goal of identifying additional product candidates and seeking valuable partnership options, while also maintaining our cash runway.” As of December 31, 2023, we had $456.3 million of cash resources consisting of cash, cash equivalents and marketable securities, comprised of $157.6 million in cash and cash equivalents and $298.7 million in marketable securities. For 2023, our cash used in operations was negatively impacted by working capital movements, primarily due to lower levels of payables as of December 31, 2023 compared to 2022. Based on current operating plans and receipt of certain anticipated regulatory milestones, we expect our existing cash resources as of December 31, 2023, when combined with certain anticipated regulatory milestone payments, will enable us to fund planned operations into the second half of 2027. Non-GAAP Financial Information In addition to reporting financial information in accordance with U.S. generally accepted accounting principles (“GAAP”) in this press release, we have elected to present selected non-GAAP, or adjusted, financial measures. Reconciliations between historical GAAP and non-GAAP information are contained at the end of this press release following the accompanying financial data. About Zymeworks Inc. Zymeworks is a global biotechnology company committed to the discovery, development, and commercialization of novel, multifunctional biotherapeutics. Zymeworks’ mission is to make a meaningful difference in the lives of people impacted by difficult-to-treat cancers and other diseases. The Company’s complementary therapeutic platforms and fully integrated drug development engine provide the flexibility and compatibility to precisely engineer and develop highly differentiated antibody-based therapeutic candidates. Zymeworks engineered and developed zanidatamab, a HER2-targeted bispecific antibody using the Company’s proprietary Azymetric™ technology. Zymeworks has entered into separate agreements with BeiGene, Ltd. (BeiGene) and Jazz Pharmaceuticals Ireland Limited (Jazz), granting each exclusive rights to develop and commercialize zanidatamab in different territories. Zanidatamab is currently being evaluated in multiple global clinical trials as a potential best-in-class treatment for patients with HER2-expressing cancers. Zymeworks is rapidly advancing a deep pipeline of product candidates based on its experience and capabilities in both antibody drug conjugates and multispecific antibody therapeutics across multiple novel targets in indications that represent areas of significant unmet medical need. In addition to Zymeworks’ wholly owned pipeline, its therapeutic platforms have been further leveraged through strategic partnerships with global biopharmaceutical companies. For information about Zymeworks, visit and follow @ZymeworksInc on X. Cautionary Note Regarding Forward-Looking Statements This press release includes “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 press release include, but are not limited to, statements that relate to Zymeworks’ expectations regarding implementation of its strategic priorities; the anticipated benefits of the collaboration agreement with Jazz, including Zymeworks’ ability to receive any future milestone payments and royalties thereunder; the potential addressable market of zanidatamab; the timing of and results of interactions with regulators; Zymeworks’ clinical development of its product candidates and enrollment in its clinical trials; anticipated preclinical and clinical data presentations; expectations regarding future regulatory filings and approvals and the timing thereof; the timing of and results of interactions with regulators; potential safety pro therapeutic effects of zanidatamab and Zymeworks’ other product candidates; expected financial performance and future financial position; the commercial potential of technology platforms and product candidates; our 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’ preclinical pipeline; anticipated sufficiency of existing cash resources and certain anticipated regulatory milestone payments to fund Zymeworks’ planned operations into the second half of 2027; and Zymeworks’ ability to execute new collaborations and partnerships and other information that is not historical information. When used herein, words such as “plan”, “believe”, “expect”, “may”, “continue”, “anticipate”, “potential”, “will”, “progress”, and similar expressions 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. 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: 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 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; 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; clinical trials may not demonstrate safety and efficacy of any of Zymeworks’ or its collaborators’ product candidates; Zymeworks’ assumptions and estimates regarding its financial condition, future financial performance and estimated cash runway may be incorrect; inability 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, including its Annual Report on Form 10-K for its year ended December 31, 2023 (a copy of which may be obtained at and ). 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. ZYMEWORKS INC. Consolidated Statements of Income (Loss) and Comprehensive Income (Expressed in thousands of U.S. dollars except share and per share data) Three Months Ended December 31, Year Ended December 31, 2023 2022 2023 2022 (unaudited) (unaudited) Revenue Research and development collaborations $ 16,926 $ 402,493 $ 76,012 $ 412,482 Operating expenses: Research and development 25,524 52,967 143,619 208,596 General and administrative 14,823 30,131 70,446 73,358 Total operating expenses 40,347 83,098 214,065 281,954 (Loss) income from operations (23,421 ) 319,395 (138,053 ) 130,528 Other income, net 4,217 1,041 18,811 4,706 (Loss) income before income taxes (19,204 ) 320,436 (119,242 ) 135,234 Income tax recovery (expense), net 4,722 (11,005 ) 568 (10,893 ) Net (loss) income $ (14,482 ) $ 309,431 $ (118,674 ) $ 124,341 Other comprehensive income: Unrealized income on available for sale securities, net of tax of nil 1,695 — 56 — Total other comprehensive income 1,695 — 56 — Comprehensive (loss) income $ (12,787 ) $ 309,431 $ (118,618 ) $ 124,341 Net (loss) income per common share: Basic $ (0.20 ) $ 4.65 $ (1.72 ) $ 1.91 Diluted $ (0.20 ) $ 4.65 $ (1.72 ) $ 1.90 Weighted-average common stock outstanding: Basic 70,829,828 66,510,825 68,863,010 65,194,775 Diluted 70,829,828 66,565,937 68,863,010 65,249,184 ZYMEWORKS INC. Selected Consolidated Balance Sheet Data (Expressed in thousands of U.S. dollars) December 31, 2023 December 31, 2022 Cash, cash equivalents and investments $ 456,257 $ 492,232 Working capital 357,163 449,081 Total assets 580,880 648,725 Accumulated deficit (677,437 ) (558,763 ) Total stockholders’ equity 464,806 492,956 NON-GAAP FINANCIAL MEASURES In addition to reporting financial information in accordance with GAAP in this press release, Zymeworks is also reporting selected non-GAAP, or adjusted, financial measures, including adjusted research and development expenses, adjusted general and administrative expenses, adjusted net loss per share (basic and diluted) and net operating cash burn. These non-GAAP financial measures are not defined by GAAP and should not be considered as alternatives to net loss, net loss per share or any other indicator of Zymeworks’ performance required to be reported under GAAP. In addition, other companies, including companies in our industry, may calculate similarly titled non-GAAP or adjusted measures differently or may use other measures to evaluate their performance, all of which could reduce the usefulness of our adjusted measures as tools for comparison. Investors and others are encouraged to review Zymeworks’ financial information in its entirety and not rely on a single financial measure. As defined by Zymeworks, adjusted expenses represent total research and development expenses and general and administrative expenses adjusted for non-cash stock-based compensation expenses for equity and liability classified equity instruments as well as expenses incurred in relation to the restructuring program completed in 2022. As defined by Zymeworks, adjusted net loss per share – Basic represents net loss per share – Basic adjusted for non-cash stock-based compensation expenses for equity and liability classified equity instruments on a per share basis as well as restructuring expenses incurred in relation to the restructuring program completed in 2022 on a per share basis, and adjusted net loss per share – Diluted represents net loss per share – Diluted adjusted for non-cash stock-based compensation expenses for equity and liability classified equity instruments on a per share basis as well as restructuring expenses incurred in relation to the restructuring program implemented in 2022 on a per share basis. As defined by Zymeworks, net operating cash burn represents net operating loss less cash used in the acquisition of property, equipment and intangible assets. Adjusted expenses and adjusted net loss per share (basic and diluted) are non-GAAP measures that Zymeworks believes may be helpful to investors because they provide consistency and comparability with past financial performance. Net operating cash burn is a non-GAAP measure that Zymeworks believes has been helpful to investors because it provided information about the cash resources used in funding our operations. As previously announced in our August 2023 earnings release, we are focused on our long-term cash resource plan to fund our operations, and due to available GAAP measures that convey similar information, we intend that the disclosure of our non-GAAP net operating cash burn included in this press release will be our last time reporting this information and will discontinue reporting of our non-GAAP net operating cash burn beginning with our results for the first quarter of 2024. GAAP to Non-GAAP Reconciliations (Expressed in thousands of U.S. dollars except per share data) (unaudited) Three Months Ended December 31, Year Ended December 31, 2023 2022 2023 2022 Research and development expenses $ 25,524 $ 52,967 $ 143,619 $ 208,596 Stock-based compensation expense for equity classified instruments (*) (1,428 ) (1,724 ) (2,112 ) (3,174 ) Stock-based compensation (expense) / recovery for liability classified instruments (*) (299 ) 9 (292 ) 781 Restructuring (expense) / recovery — 482 — (5,659 ) Adjusted research and development expenses (Non-GAAP basis) $ 23,797 $ 51,734 $ 141,215 $ 200,544 General and administrative expenses $ 14,823 $ 30,131 $ 70,446 $ 73,358 Stock-based compensation expense for equity classified instruments (*) (1,686 ) (2,580 ) (6,621 ) (4,102 ) Stock-based compensation (expense) / recovery for liability classified instruments (*) 160 (117 ) 1,305 2,893 Restructuring expense — (476 ) — (3,265 ) Adjusted general and administrative expenses (Non-GAAP basis) $ 13,297 $ 26,958 $ 65,130 $ 68,884 Three Months Ended December 31, Year Ended December 31, 2023 2022 2023 2022 Net income (loss) per common share – Basic $ (0.20 ) $ 4.65 $ (1.72 ) $ 1.91 Stock-based compensation expense per common share 0.04 0.06 0.12 0.05 Restructuring expenses per common share — — — 0.14 Adjusted net income (loss) per common share – Basic (Non-GAAP basis) $ (0.16 ) $ 4.71 $ (1.60 ) $ 2.10 Net income (loss) per common share – Diluted $ (0.20 ) $ 4.65 $ (1.72 ) $ 1.90 Stock-based compensation expense per common share 0.04 0.06 0.12 0.05 Restructuring expenses per common share — — — 0.14 Adjusted net income (loss) per common share – Diluted (Non-GAAP basis) $ (0.16 ) $ 4.71 $ (1.60 ) $ 2.09 (*): Research and development expenses and general and administrative expenses include $nil stock-based compensation expense related to the 2022 restructuring for the year ended December 31, 2023 (recovery of $5,516 and $4,865, respectively, for the year ended December 31, 2022, in research and development expenses and general and administrative expenses, respectively). Three Months Ended December 31, Year Ended December 31, 2023 2022 2023 2022 Net income (loss) $ (14,482 ) $ 309,431 $ (118,674 ) $ 124,341 Acquisition of property, equipment and intangible assets (1,754 ) (883 ) (4,077 ) (13,125 ) Net operating cash burn (Non-GAAP basis) $ (16,236 ) $ 308,548 $ (122,751 ) $ 111,216 Contacts: Investor Inquiries: Shrinal Inamdar  Director, Investor Relations (604) 678-1388  ir@zymeworks.com Media Inquiries: Diana Papove Senior Director, Corporate Communications (604) 678-1388  media@zymeworks.com

Five abstracts accepted for poster presentation highlight company’s differentiated antibody-drug conjugate and multispecific antibody clinical product candidatesStrong preclinical activity across multiple FRα-expressing indications for ZW191, a FRα-targeting antibody-drug conjugateNext generation trispecific T cell engager platforms with integrated CD28 costimulation demonstrate durable anti-tumor activity VANCOUVER, British Columbia, March 05, 2024 (GLOBE NEWSWIRE) -- Zymeworks Inc. (Nasdaq: ZYME), a clinical-stage biotechnology company developing a diverse pipeline of novel, multifunctional biotherapeutics to improve the standard of care for difficult-to-treat diseases, today announced acceptance of five abstracts for poster presentations at the upcoming American Association for Cancer Research (AACR) Annual Meeting taking place at the San Diego Convention Center in San Diego, CA from April 5-10, 2024. “Our team is especially excited to participate in AACR this year to highlight some recent advancements in the development of our next generation antibody-drug conjugate and multispecific antibody therapeutics,” said Paul Moore, Ph.D., Chief Scientific Officer at Zymeworks. “Five abstracts being accepted underscores the strong progress we continue to make in advancing multiple development programs based on our proprietary engineering platforms and integrated technologies.” Presentation Details Antibody-Drug Conjugates Title: ZW191 - a FRα-targeting antibody drug conjugate with strong preclinical activity across multiple FRα-expressing indicationsAbstract: 1862Session Category: Experimental and Molecular TherapeuticsSession Title: Antibody-Based Technologies and New Inhibitors Title: Screening novel format antibodies to design bispecific ADCs that address target heterogeneityAbstract: 2052Session Category: Experimental and Molecular TherapeuticsSession Title: New Technologies Title: Development of three-dimensional cancer cell line spheroid models for the in vitro functional characterization of cytotoxic antibody-drug conjugatesAbstract: 3127Session Category: Experimental and Molecular TherapeuticsSession Title: Antibody-Drug Conjugates Multispecific Antibody Therapeutics Title: DLL3 TriTCE Co-Stim: A next generation trispecific T cell engager with integrated CD28 costimulation for the treatment of DLL3-expressing cancersAbstract: 6716Session Category: ImmunologySession Title: Targeted ICEs Title: TriTCE Co-Stim: A next generation trispecific T cell engager platform with integrated CD28 costimulation, engineered to improve responses in the treatment of solid tumors Abstract: 6719Session Category: ImmunologySession Title: Targeted ICEs About Zymeworks Inc.Zymeworks is a global biotechnology company committed to the discovery, development, and commercialization of novel, multifunctional biotherapeutics. Zymeworks’ mission is to make a meaningful difference in the lives of people impacted by difficult-to-treat cancers and other diseases. The Company’s complementary therapeutic platforms and fully integrated drug development engine provide the flexibility and compatibility to precisely engineer and develop highly differentiated antibody-based therapeutic candidates. Zymeworks engineered and developed zanidatamab, a HER2-targeted bispecific antibody using the Company’s proprietary Azymetric™ technology. Zymeworks has entered into separate agreements with BeiGene, Ltd. (BeiGene) and Jazz Pharmaceuticals Ireland Limited (Jazz), granting each exclusive rights to develop and commercialize zanidatamab in different territories. Zanidatamab is currently being evaluated in multiple global clinical trials as a potential best-in-class treatment for patients with HER2-expressing cancers. Zymeworks is rapidly advancing a deep pipeline of product candidates based on its experience and capabilities in both antibody drug conjugates and multispecific antibody therapeutics across multiple novel targets in indications that represent areas of significant unmet medical need. In addition to Zymeworks’ wholly owned pipeline, its therapeutic platforms have been further leveraged through strategic partnerships with global biopharmaceutical companies. For information about Zymeworks, visit www.zymeworks.com and follow @ZymeworksInc on X. Cautionary Note Regarding Forward-Looking Statements This press release includes “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 press release include, but are not limited to, statements that relate to anticipated preclinical and clinical data presentations; Zymeworks’ preclinical pipeline; potential therapeutic effects and commercial potential of zanidatamab and Zymeworks’ other product candidates; Zymeworks’ clinical development of its product candidates and enrollment in its clinical trials; the ability to advance product candidates into later stages of development; and other information that is not historical information. When used herein, words such as “plan”, “believe”, “expect”, “may”, “continue”, “anticipate”, “potential”, “will”, “progress”, and similar expressions 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. 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: clinical trials may not demonstrate safety and efficacy of any of Zymeworks’ or its collaborators’ product candidates; 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; regulatory agencies may impose additional requirements or delay the initiation of clinical trials; the impact of new or changing laws and regulations; market conditions; and the factors described under “Risk Factors” in Zymeworks’ quarterly and annual reports filed with the Securities and Exchange Commission from time to time (copies of which may be obtained at www.sec.gov and www.sedar.com). 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. Investor inquiries:Shrinal InamdarDirector, Investor Relations(604) 678-1388ir@zymeworks.com Media inquiries:Diana PapoveSenior Director, Corporate Communications(604) 678-1388media@zymeworks.com

-- Clinical development focus on high-potential XmAb® T cell engagers and selective dual checkpoint inhibitor, vudalimab -- -- Vudalimab (PD-1 x CTLA-4) monotherapy generally well tolerated with encouraging clinical benefit for patients with high-risk mCRPC who have advanced beyond standard of care therapy -- -- Management to Host Conference Call at 4:30 p.m. ET Today -- PASADENA, Calif.--(BUSINESS WIRE)-- Xencor Inc. (NASDAQ:XNCR), a clinical-stage biopharmaceutical company developing engineered antibodies for the treatment of cancer and other serious diseases, today reported financial results for the fourth quarter and full year ended December 31, 2023 and provided a review of recent business and clinical highlights. The Company also presented encouraging early clinical data from its Phase 2 study of vudalimab monotherapy for patients with clinically defined high-risk metastatic castration-resistant prostate cancer (mCRPC). “We begin 2024 with a focus on advancing our high-potential XmAb CD3 and CD28 T-cell engagers for the treatment of patients with solid tumors and the evaluation of our PD-1 x CTLA-4 dual checkpoint inhibitor, vudalimab, in patients with metastatic castration-resistant prostate cancer and front-line non-small cell lung cancer,” said Bassil Dahiyat, Ph.D., president and chief executive officer of Xencor. “This focused pipeline is supported by our strong financial foundation. In 2023, we significantly strengthened our balance sheet with our partial royalty monetization and milestone payments and royalties from our partners, for which we received more than $325 million in proceeds. “The growing validation of T-cell engagers in solid tumors has encouraged us to build a range of new XmAb bispecific T-cell engager candidates, and we plan to select our next candidate for clinical development this year.” Vudalimab (PD-1 x CTLA-4) Monotherapy in Patients with High-Risk mCRPC Xencor is advancing vudalimab, a selective dual checkpoint inhibitor, in multiple clinical studies, including a Phase 2 monotherapy study (Study XmAb717-05) in patients with clinically defined high-risk metastatic castration-resistant prostate cancer (mCRPC). Early data from the study indicates that vudalimab has been generally well tolerated and associated with response to treatment in multiple patients who have visceral or lymph node metastases. At the February 7, 2024 data cut off, 14 patients with clinically defined high-risk mCRPC had been treated with vudalimab every three weeks at a flat dose of 1000 mg, or 1200 mg for patients greater than 80 kg. Patients were a median of 72 years old and were heavily pretreated, having a median of four lines of prior therapy. 79% (11/14) of patients had metastatic disease at diagnosis; all patients had measurable disease. The efficacy-evaluable population included 12 patients who had baseline and at least one post-baseline RECIST assessment. The objective response rate was 33% (4/12). Three patients had a confirmed partial response per RECIST 1.1 guidelines, and one additional patient had an unconfirmed partial response. An additional two patients experienced a best overall response of stable disease. Prostate-specific antigen (PSA) reductions of more than 90% from baseline (PSA90) were observed in 25% (3/12) of evaluable patients. The safety analysis included all 14 patients. The most common immune-related adverse events of any grade were rash (29%) and alanine transaminase (ALT) increases (21%). Treatment-emergent adverse events led to treatment discontinuation for two patients (14%). One Grade 5 adverse event of autoimmune hepatitis was deemed treatment related; there have been no known additional cases of Grade 5 autoimmune hepatitis among three clinical studies with more than 240 patients treated with vudalimab. Additional Vudalimab Clinical Studies and 2024 Priorities Enrollment of patients with mCRPC in the study of vudalimab in combination with chemotherapy (Study XmAb717-04) is ongoing; revised chemotherapy dosing regimens are being evaluated, as previously disclosed. In the fourth quarter of 2023, the Company dosed the first patient in a Phase 1b/2 study (Study XmAb717-06) evaluating vudalimab as a first-line treatment in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). Xencor plans to: Continue enrollment and provide a data update and decision whether to advance vudalimab as a monotherapy for patients with mCRPC in the first half of 2025. Continue enrollment and provide a data update and decision whether to advance vudalimab in combination with chemotherapy for patients with mCRPC in the first half of 2025. Continue to enroll the Phase 1b part of a study of vudalimab in front-line metastatic NSCLC. Additional Program Highlights and 2024 Priorities XmAb819 (ENPP3 x CD3): XmAb819 is a bispecific antibody in Phase 1 clinical development for patients with advanced clear-cell renal cell carcinoma (ccRCC). XmAb819 is designed to engage the immune system, activating T cells for highly potent and targeted killing of tumor cells expressing ENPP3, an antigen highly expressed on kidney cancers. Xencor’s XmAb 2+1 multivalent format used in XmAb819 enables greater selectivity of ENPP3-expressing tumor cells compared to normal cells, which express lower levels of ENPP3. During 2024, Xencor plans to advance the ongoing Phase 1 dose-escalation study toward target dose levels. XmAb808 (B7-H3 x CD28): XmAb808 is a tumor-selective, co-stimulatory CD28 bispecific antibody in Phase 1 clinical development. XmAb808 binds to the broadly expressed tumor antigen B7-H3 and is constructed with the XmAb 2+1 format. Co-stimulation is required for T cells to achieve full activation, and targeted CD28 bispecific antibodies may provide conditional co-stimulation of T cells when the antibodies are bound to tumor cells. During 2024, Xencor plans to advance the ongoing Phase 1 dose-escalation study toward target dose levels. XmAb541 (CLDN6 x CD3): XmAb541 is a bispecific antibody being developed for patients with advanced ovarian cancer and other solid tumor types. XmAb541 is designed to engage the immune system, activating T cells for highly potent and targeted killing of tumor cells expressing Claudin-6 (CLDN6), a tumor-associated antigen. Xencor’s XmAb 2+1 multivalent format used in XmAb541 enables greater selectivity for cells expressing CLDN6 over similarly structured Claudin family members, which may be expressed on normal tissue. During the first half of 2024, Xencor plans to dose the first patient in a Phase 1 dose-escalation study. Engineered Cytokines: Xencor has been conducting Phase 1 studies evaluating engineered cytokines XmAb564 (IL2-Fc in autoimmune disease) and XmAb662 (IL12-Fc in solid tumors). In the first half of 2024, Xencor plans to conclude studies of XmAb564 and XmAb662, complete internal data packages, and pause further development of both programs until after assessments of future data from competitor programs in this class and safety and biomarker data from Xencor’s studies. Recent Partnership Developments Janssen Biotech, Inc., a Johnson & Johnson Company: JNJ-9401 (PSMA x CD28) and JNJ-1493 (CD20 x CD28) are clinical-stage XmAb bispecific antibodies that J&J is developing for patients with prostate cancer and B-cell malignancies, respectively. Both programs entered Phase 1 clinical development during the fourth quarter of 2023, and Xencor received $20 million in development milestones. J&J also selected two B-cell targeting CD28 bispecific antibody candidates for further development, and Xencor received an additional $7.5 million in research milestones. In the fourth quarter of 2023, Xencor completed enrollment in subcutaneous dose-escalation cohorts of a Phase 1 study evaluating plamotamab. Corporate Update: In January 2024, Xencor reduced its workforce to align resources with the company’s clinical development focus on high potential T cell engaging bispecific antibodies and a more narrowly defined clinical program to evaluate vudalimab. The workforce reductions affected approximately 10% of positions at the Company. Financial Guidance: Based on current operating plans, Xencor expects to end 2024 with between $475 million and $525 million in cash, cash equivalents and marketable debt securities, and to have cash to fund research and development programs and operations into 2027. Financial Results for the Fourth Quarter and Full Year Ended December 31, 2023 Cash, cash equivalents, and marketable debt securities totaled $697.4 million as of December 31, 2023, compared to $584.5 million on December 31, 2022. Total revenue for the fourth quarter ended December 31, 2023 was $44.7 million compared to $21.6 million for the same period in 2022. Revenues earned in the fourth quarter of 2023 were primarily from the research and milestone revenue from the two J&J collaboration agreements, and royalty revenue from Alexion and MorphoSys, compared to the same period in 2022, which were primarily royalty revenue from the Alexion and Vir agreements and research collaboration revenue from the second J&J collaboration. Revenues for the full year 2023 were $168.3 million compared to $164.6 million for the same period in 2022. Revenues for the full year 2023 were primarily milestone revenue from Alexion, Gilead, J&J, Omeros and Zenas and collaboration revenue from the second J&J collaboration, compared to the same period in 2022, which were earned primarily royalties from Alexion, MorphoSys and Vir, milestone revenue from Astellas and collaboration revenue from the second J&J collaboration. Research and development (R&D) expenses for the fourth quarter ended December 31, 2023 were $63.0 million compared to the same period in 2022 which were $51.5 million. R&D expenses for the year ended December 31, 2023 were $253.6 million compared to $199.6 million for the same period in 2022. Increased R&D spending for fourth quarter and full year 2023, compared to amounts for the same periods in 2022, reflects additional spending on XmAb bispecific antibody programs including XmAb541, vudalimab and early-stage research programs. General and administrative (G&A) expenses for the fourth quarter ended December 31, 2023 were $15.3 million compared to $12.8 million for the same period in 2022. G&A expenses for the full year ended December 31, 2023 were $53.4 million compared to $47.5 million for the same period in 2022. Increased G&A spending for the fourth quarter and full year 2023, compared to amounts for the same periods in 2022, reflects additional compensation costs on general and administrative staffing and spending on professional fees. Other income for the fourth quarter ended December 31, 2023 was $20.2 million compared to $30.1 million in the same period in 2022. Other income for both periods represents unrealized gain from the change in fair value of equity securities and interest income earned on investments. Other income for the full year ended December 31, 2023 was $18.2 million, compared to $28.0 million in the same period in 2022, which reflects a net decrease in unrealized gain from equity securities, partially offset by an increase in interest income in 2023. Non-cash, stock-based compensation expense for the full year ended December 31, 2023 was $53.8 million compared to $48.9 million for the same period in 2022. Net loss for the fourth quarter ended December 31, 2023 was $19.1 million or $(0.31) on a fully diluted per share basis, compared to net loss of $12.0 million or $(0.20) on a fully diluted per share basis, for the same period in 2022. For the full year ended December 31, 2023 net loss was $126.1 million or $(2.08) on a fully diluted per share basis, compared to net loss of $55.2 million or $(0.93) on a fully diluted per share basis, for the same period in 2022. Greater net loss reported for the fourth quarter ended December 31, 2023, compared to the same period in 2022, is primarily due to increased R&D spending. Greater net loss for the full year 2023, compared to the same period in 2022, is primarily due to increased R&D spending, a decrease in other income and an increase in tax expense in 2023. The total shares outstanding were 60,998,191 as of December 31, 2023, compared to 59,997,713 as of December 31, 2022. Conference Call and Webcast Xencor will host a conference call and webcast today at 4:30 p.m. ET (1:30 p.m. PT) to discuss the financial results, provide a corporate update and review the clinical update of vudalimab monotherapy in mCRPC. The live webcast may be accessed through “Events & Presentations” in the Investors section of the Company’s website, located at investors.xencor.com. Telephone participants may register to receive a dial-in number and unique passcode that can be used to access the call. A recording will be available for at least 30 days. About Xencor Xencor is a clinical-stage biopharmaceutical company developing engineered antibodies for the treatment of patients with cancer and other serious diseases. More than 20 candidates engineered with Xencor's XmAb® technology are in clinical development, and three XmAb medicines are marketed by partners. Xencor's XmAb engineering technology enables small changes to a proteins structure that result in new mechanisms of therapeutic action. For more information, please visit . Forward-Looking Statements Certain statements contained in this press release may constitute forward-looking statements within the meaning of applicable securities laws. Forward-looking statements include statements that are not purely statements of historical fact, and can generally be identified by the use of words such as “potential,” “can,” “will,” “plan,” “may,” “could,” “would,” “expect,” “anticipate,” “seek,” “look forward,” “believe,” “committed,” “investigational,” and similar terms, or by express or implied discussions relating to Xencor’s business, including, but not limited to, statements regarding planned presentations of clinical data, planned clinical trials, projected financial resources, the quotations from Xencor's president and chief executive officer, and other statements that are not purely statements of historical fact. Such statements are made on the basis of the current beliefs, expectations, and assumptions of the management of Xencor and are subject to significant known and unknown risks, uncertainties and other factors that may cause actual results, performance or achievements and the timing of events to be materially different from those implied by such statements, and therefore these statements should not be read as guarantees of future performance or results. Such risks include, without limitation, the risks associated with the process of discovering, developing, manufacturing and commercializing drugs that are safe and effective for use as human therapeutics and other risks, including the ability of publicly disclosed preliminary clinical trial data to support continued clinical development and regulatory approval for specific treatments, in each case as described in Xencor's public securities filings. For a discussion of these and other factors, please refer to Xencor's annual report on Form 10-K for the year ended December 31, 2023 as well as Xencor's subsequent filings with the Securities and Exchange Commission. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. This caution is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, as amended to date. All forward-looking statements are qualified in their entirety by this cautionary statement and Xencor undertakes no obligation to revise or update this press release to reflect events or circumstances after the date hereof, except as required by law. Xencor, Inc. Selected Consolidated Balance Sheets Data (in thousands, except share and per share data) December 31, 2023 2022 Cash, cash equivalents and marketable debt securities - current $ 551,515 $ 580,631 Other current assets 71,645 94,711 Marketable debt securities - long term 145,892 3,826 Other long-term assets 183,640 167,098 Total assets $ 952,692 $ 846,266 Total current liabilities 84,709 63,844 Deferred income - long term 125,183 — Other long term liabilities 73,667 54,926 Total liabilities 283,559 118,770 Total stockholders' equity 669,133 727,496 Total liabilities and stockholders’ equity $ 952,692 $ 846,266 Xencor, Inc. Consolidated Statements of Loss (in thousands, except share and per share data) Three months Ended December 31, Year ended December 31, 2023 2022 2023 2022 (Unaudited) Revenue $ 44,689 $ 21,610 $ 168,338 $ 164,579 Operating expenses Research and development 63,046 51,452 253,598 199,563 General and administrative 15,272 12,751 53,379 47,489 Total operating expenses 78,318 64,203 306,977 247,052 Loss from operations (33,629) (42,593) (138,639) (82,473) Other income, net 20,177 30,136 18,200 27,965 Loss before income tax (13,452) (12,457) (120,439) (54,508) Income tax expense 5,811 (415) 5,811 673 Net loss (19,263) (12,042) (126,250) (55,181) Net loss attributable to non-controlling interest (163) — (163) — Net loss attributable to Xencor, Inc. (19,100) (12,042) (126,087) (55,181) Other comprehensive income (loss): Net unrealized gain (loss) on marketable debt securities available-for-sale 1,999 2,924 8,243 (5,442) Comprehensive loss attributable to Xencor, Inc. $ (17,101) $ (9,118) $ (117,844) $ (60,623) Net loss per common share attributable to Xencor, Inc.: Basic and Diluted $ (0.31) $ (0.20) $ (2.08) $ (0.93) Weighted average common shares used to compute net loss per share attributable to Xencor, Inc. Basic and Diluted 60,847,854 59,912,038 60,503,283 59,652,461