Zymeworks BC, Inc.

4月2日，美国生物技术公司Zymeworks表示公司已经于3月31日罢免了首席财务官Christopher Astle，但是在美国证券交易委员会（SEC）的文件中没有提供罢免原因。Zymeworks首席执行官Kenneth Galbraith将担任公司临时首席财务官，直到找到接替者。“经过公司的深思熟虑，为了实现继续增长和成功的承诺，我们决定寻找一位拥有特定经验、专业知识和远见的新首席财务官，以有效地推动我们的业务战略向前发展，”Zymeworks的一位发言人对此表示。2023年公司财报显示，截止2023年12月31日，公司现金流为4.563亿美元，预计可以支持公司持续到2027年下半年。平台被大厂青睐Zymeworks成立于2003年，将蛋白质工程和药物化学领域行业领先的专业知识整合到其自身专有的多特异性抗体和ADC治疗模式中，并与疾病生物学相结合，开发主要用于治疗癌症以及自免疫性疾病和炎症性疾病的新一代抗体疗法。自2017年于纽交所上市后，Zymeworks就一直受到市场的关注，虽然没有产品获批上市，但是默沙东、辉瑞和GSK等大药企相继与其签订合作协议。大厂们看重的是Zymeworks的多抗和ADC技术平台。正所谓，单抗看靶点，双抗、ADC看平台。经过20多年的不断发展，该公司目前已经拥有四项专利技术平台：Azymetric、ZymeLink、EFECT和ProTECT。Azymetric平台可以将单特异性抗体，转化为双特异性抗体，同时结合同一目标上的多个不重叠表位，起到提高肿瘤特异性靶向和疗效，同时降低毒性和耐药性的可能性。与此同时，Azymetric 开发的双特异性抗体，还保留了单克隆抗体的理想药物样特性，包括长半衰期、稳定性和低免疫原性潜力。ZymeLink平台则是一套专有的细胞毒素、稳定的接头和偶联技术，有望提供增加递送效果，和减少脱靶效应等优势。凭借这一技术，Zymeworks获得2019年世界ADC奖最佳平台技术奖冠军。PROTECT平台能够在减少全身毒性的同时提高疗效，EFFECT平台主要作用是定制和优化免疫反应。且这几大平台可以相互搭配使用，例如，Azymetric与ZymeLink结合，可以开发双特异性ADC药物。好平台也需要好产品2017年上市之初，Zymeworks市值不到5亿，但随后市值不断攀升。2021年3月，在生物科技投资热潮顶峰时刻，公司市值一度达到36.4亿美金。但是由于一直没有产品获批上市，候选产品临床表现平平，在到达巅峰后，Zymeworks的股价就走了下坡路，如今市值6.51美元，和刚上市相差无几。Zymeworks最核心的产品是ZW25（Zanidatamab）和ZW49。Zanidatamab是一款通过Azymetric平台研发的新型靶向HER2双抗，可以同时靶向HER2胞外区域的亚基2和亚基4的两个不同表位，有可能带来更好的治疗效果。ZW49则是基于Zanidatamab开发的一款双靶点HER2 ADC，将 zanidatamab 的独特设计与专有的ZymeLink细胞毒素和可切割接头相结合。但是ZW49似乎没有想象中的那么好，2022年公布的ZW49治疗HER2+患者的一期临床数据显示，ZW49虽然起到了减毒的效果，不到10%患者产生3级以上副作用，但其疗效却未达到预期。29名接受2剂治疗的患者，ORR（客观缓解率）仅为28%。相比之下，DS8201各适应症ORR基本都超过50%。2018年，Zymeworks与百济就HER2双抗（ZW25）和HER2双抗ADC（ZW49）达成合作，Zymeworks授予百济在亚洲（不包括日本）、澳大利亚和新西兰进行ZW49的研究、开发和商业化的独家许可。可能是ZW49的临床数据差强人意，去年11月，百济神州退回ZW49的权利。除了百济神州，第一三共、BMS、强生、默沙东等公司也引进了Zymeworks的技术平台或产品。不过，2023年3月17日，Zymeworks子公司Zymeworks BC在一份提交给美国证券交易委员会（SEC）的文件中表示，第一三共已终止引进其双特异性抗体技术平台的许可协议。3月6日，Zymeworks在2023年财报中透露，由于临床情况仍在不断变化，在进一步明确之前，ZW49计划中的II期研究不再优先启动，公司将继续探索其潜在的开发和商业合作。小结再好的技术平台，没有足够硬的产品，依然不能说服市场，纵使很多大厂都钟意Zymeworks的抗体技术平台，但是其产品临床数据难以令人满意，不断走下坡路也在意料之中。参考来源：1.https://www.zymeworks.com/patients/#clinical-trials本周好文推荐如需转载请联系佰傲谷并在醒目位置注明出处···

DUBLIN--( BUSINESS WIRE )--The "Non-Small-Cell Lung cancer (NSCLC) - Pipeline Insight, 2024" clinical trials has been added to ResearchAndMarkets.com's offering. This report provides comprehensive insights about 100+ companies and 120+ pipeline drugs in Non-Small-Cell Lung cancer (NSCLC) pipeline landscape. It covers the pipeline drug profiles, including clinical and nonclinical stage products. It also covers the therapeutics assessment by product type, stage, route of administration, and molecule type. It further highlights the inactive pipeline products in this space. The reportoutlays comprehensive insights of present scenario and growth prospects across the indication. A detailed picture of the Non-Small-Cell Lung cancer (NSCLC) pipeline landscape is provided which includes the disease overview and Non-Small-Cell Lung cancer (NSCLC) treatment guidelines. The assessment part of the report embraces, in depth Non-Small-Cell Lung cancer (NSCLC) commercial assessment and clinical assessment of the pipeline products under development. In the report, detailed description of the drug is given which includes mechanism of action of the drug, clinical studies, NDA approvals (if any), and product development activities comprising the technology, Non-Small-Cell Lung cancer (NSCLC) collaborations, licensing, mergers and acquisition, funding, designations and other product related details. Report Highlights The companies and academics are working to assess challenges and seek opportunities that could influence Non-Small-Cell Lung cancer (NSCLC) R&D. The therapies under development are focused on novel approaches to treat/improve Non-Small-Cell Lung cancer (NSCLC) . Non-Small-Cell Lung cancer (NSCLC) Emerging Drugs Chapters This segment of the Non-Small-Cell Lung cancer (NSCLC) report encloses its detailed analysis of various drugs in different stages of clinical development, including phase II, I, preclinical and Discovery. It also helps to understand clinical trial details, expressive pharmacological action, agreements and collaborations, and the latest news and press releases. Non-Small-Cell Lung cancer (NSCLC) Emerging Drugs V940: Merck Sharp & Dohme LLC V940 is designed to stimulate an immune response by generating specific T cell responses based on the unique mutational signature of a patient's tumor. It is a novel investigational messenger ribonucleic acid (mRNA)-based personalized cancer vaccine consisting of a single synthetic mRNA coding for up to 34 neoantigens that is designed and produced based on the unique mutational signature of the DNA sequence of the patient's tumor. Upon administration into the body, the algorithmically derived and RNA-encoded neoantigen sequences are endogenously translated and undergo natural cellular antigen processing and presentation, a key step in adaptive immunity. The drug is in Phase III stage for the treatment of NSCLC. QL1706: Qilu Pharmaceutical Co., Ltd. QL1706 is an investigational bifunctional antibody with additional anti-cytotoxic T lymphocyte antigen 4 (CTLA-4) antibody could increase the anti-tumor effect of anti-programmed cell death 1 (PD-1) antibody. QL1706 is a novel dual immune checkpoint blockade containing a mixture of anti-PD-1 IgG4 and anti-CTLA4 IgG1 antibodies produced by a single cell line. The drug is in Phase III stage for the treatment of NSCLC. Zenocutuzumab (MCLA-128): Merus N.V. Zenocutuzumab (MCLA-128; Zeno) is a Biclonics antibody that overcomes HER3 mediated NRG1 (or NRG1 fusion) signaling in tumor cells. Zeno docks on HER2, then binds to and blocks the NRG1 fusion-HER3 interaction and HER3 heterodimerization with HER2. It has a dual mechanism against cancer, as it prevents NRG1 fusions from binding to the protein HER3 and it blocks the interaction of HER3 with HER2, which the cancer cells depend on to survive and multiply. Currently, the drug is in Phase II stage for the treatment of NSCLC. ZW49: Zymeworks BC Inc. ZW49 (zanidatamab zovodotin) is a bispecific anti-HER2 ADC that is based on the same antibody framework as ZW25 but armed with a cytotoxic payload. A biparatopic (targeting two different non-overlapping epitopes on ERBB2, on extracellular domains 2 (ECD2) and 4 (ECD4). ZW25 is an anti-HER2 biparatopic antibody which binds to the same domains as trastuzumab and pertuzumab. ZW25 simultaneously binds two distinct sites on HER2, a protein expressed on many types of cancer cells. This unique design results in multiple mechanisms of action, including dual HER2 signal blockade, increased antibody binding, receptor clustering, and removal of HER2 from the cell surface, and potent e?ector function. ZW49 is in Phase I of clinical trials for the treatment of non-small cell lung cancer. Non-Small-Cell Lung cancer (NSCLC): Pipeline Development Activities The report provides insights into different therapeutic candidates in phase II, I, preclinical and discovery stage. It also analyses Non-Small-Cell Lung cancer (NSCLC) therapeutic drugs key players involved in developing key drugs. Pipeline Development Activities The report covers the detailed information of collaborations, acquisition and merger, licensing along with a thorough therapeutic assessment of emerging Non-Small-Cell Lung cancer (NSCLC) drugs. Non-Small-Cell Lung cancer (NSCLC) : Therapeutic Assessment Major Players in Non-Small-Cell Lung cancer (NSCLC) There are approx. 100+ key companies which are developing the therapies for Non-Small-Cell Lung cancer (NSCLC). The companies which have their Non-Small-Cell Lung cancer (NSCLC) drug candidates in the most advanced stage, i.e. Phase III include, Merck Sharp & Dohme LLC. Phases Late stage products (Phase III) Mid-stage products (Phase II) Early-stage product (Phase I) along with the details of Pre-clinical and Discovery stage candidates Discontinued & Inactive candidates Route of Administration Products have been categorized under various ROAs such as Oral Intravenous Subcutaneous Parenteral Topical Molecule Type Products have been categorized under various Molecule types such as Recombinant fusion proteins Small molecule Monoclonal antibody Peptide Polymer Gene therapy Product Type Non-Small-Cell Lung cancer (NSCLC) Report Insights Non-Small-Cell Lung cancer (NSCLC) Pipeline Analysis Therapeutic Assessment Unmet Needs Impact of Drugs Non-Small-Cell Lung cancer (NSCLC) Report Assessment Pipeline Product Profiles Therapeutic Assessment Pipeline Assessment Inactive drugs assessment Unmet Needs Key Players Merck Sharp & Dohme LLC Suzhou Puhe Pharmaceutical Technology Co., LTD Merus N.V. Zymeworks BC Inc. Cytos Biotechnology Exelixis ProfoundBio US Co. Beijing Pearl Biotechnology Limited Liability Company Pfizer OncoResponse, Inc. Next Point Therapeutics, Inc. Light Chain Bioscience - Novimmune SA Medolution Ltd. Immunitas Therapeutics Shanghai Henlius Biotech Key Products V940 YK-029A Zenocutuzumab (MCLA-128) ZW49 CMP 001 XL092 PRO1184 PLB1001 PF-07257876 OR2805 NPX267 NI-1801 Keynatinib IMT-009 HLX301 For more information about this clinical trials report visit https://www.researchandmarkets.com/r/w14gce About ResearchAndMarkets.com ResearchAndMarkets.com is the world's leading source for international market research reports and market data. We provide you with the latest data on international and regional markets, key industries, the top companies, new products and the latest trends.

Net loss for the first nine months of 2023 decreased by 44% as compared to the same period in 2022Cash resources of $390.2 million as of September 30, 2023 expected to fund planned operations through at least the end of 2026, and potentially beyondUpdated clinical results from Phase 1b/2 study of zanidatamab plus chemotherapy and tislelizumab as first-line therapy for patients with advanced HER2-positive gastroesophageal adenocarcinoma (GEA) presented by our partner BeiGene at the European Society of Medical Oncology (ESMO) Annual CongressResults on quality of life outcomes from the Phase 2b HERIZON-BTC-01 study evaluating patients with zanidatamab-treated HER2-positive biliary tract cancer presented by our partner Jazz at the ESMO Annual CongressAnnounces next investigational new drug application (IND) candidate, ZW251, a glypican-3 (GPC3) targeted antibody drug conjugate (ADC), anticipated for IND filing in 2H-2025Will host conference call with management today at 4:30 p.m. Eastern Daylight Time (EDT) VANCOUVER, British Columbia, Nov. 07, 2023 (GLOBE NEWSWIRE) -- Zymeworks Inc. (Nasdaq: ZYME), a clinical-stage biotechnology company developing novel multifunctional biotherapeutics, today reported financial results for the three and nine months ended September 30, 2023 and provided a summary of recent business highlights. “We are pleased to have made key advancements to our product pipeline this year, along with the nomination of ZW251 as our latest IND candidate targeting GPC3. These advancements in our '5 by 5' strategy represent important steps in the development of our emerging product portfolio and provide us with wholly-owned opportunities for future growth,” said Kenneth Galbraith, Chair and Chief Executive Officer of Zymeworks. “We believe these are important steps, along with the upcoming anticipated regulatory filings, approval and subsequent product launches for zanidatamab, in our goal to generate value for stockholders by developing differentiated and improved treatment options for patients with difficult-to-treat cancers in areas of large unmet need. We look forward to updating the market on the progress and status of these product candidates.” “As we look forward, we expect to see IND submissions and commencement of clinical studies for ZW171 and ZW191 in 2024 followed by ZW220 and ZW251 in 2025, together with the top-line data readout from the zanidatamab Phase 3 GEA pivotal trial, HERIZON-GEA-01, expected in 2024.” Recent Highlights and Current Developments Zanidatamab Clinical Data Presented at the ESMO Annual Congress Our partners Jazz Pharmaceuticals ("Jazz") and BeiGene, Ltd. ("BeiGene"), presented abstracts for zanidatamab at the recent ESMO Annual Congress in Madrid: A poster presentation featuring updated results from a Phase 1b/2 study of zanidatamab plus chemotherapy in combination with tislelizumab, an anti-PD-1 monoclonal antibody, for the first-line treatment of human epidermal growth factor receptor 2 (HER2)-positive gastric/gastroesophageal junction adenocarcinoma (G/GEJC). The study, sponsored by BeiGene, showed zanidatamab plus chemotherapy and tislelizumab produced antitumor activity with a confirmed objective response rate (ORR) of 75.8%, a median duration of response (mDOR) of 22.8 months and a median progression-free survival (PFS) of 16.7 months. Safety data showed 22 patients (66.7%) experienced at least one grade ≥3 treatment-related adverse event. A Phase 3 trial (NCT05152147) evaluating this regimen is ongoing with top-line data from HERIZON-GEA-01 expected to be reported in 2024. A poster presentation featuring quality of life data from a Phase 2b study of zanidatamab for the second-line treatment of HER2-amplified biliary tract cancers (BTC), finding that patients with HER2-positive BTC who responded to zanidatamab reported improved health-related quality of life (HRQoL) compared with baseline. Overall, zanidatamab led to a meaningful clinical benefit, which may reduce disease burden and potentially result in improved patient HRQoL compared with baseline. We previously reported data from our Phase 2b study, where zanidatamab as monotherapy in this patient population had a confirmed ORR of 41.3% (51.6% in the IHC3+ patients) and a median PFS of 5.5 months. ZW251 Named as Next IND Candidate We anticipate filing an IND in the second half of 2025 for ZW251, a potential first-in-class ADC molecule designed for the treatment of GPC3-expressing hepatocellular carcinoma (HCC). Presentations on Clinical and Preclinical Programs at Multiple Medical and Scientific Conferences in Q4-2023 During the fourth quarter of 2023, we had the opportunity to present updated clinical and preclinical data at a number of medical and scientific conferences, including: 14th Annual World Bispecific Summit held in Boston, MA from October 2-4, 2023; AACR-EORTC-NCI held in Boston, MA from Oct 11-15, 2023; 14th Annual World ADC conference held in San Diego, CA from October 16-19, 2023; ESMO held in Madrid, Spain from October 20-24, 2023; and Society for Immunotherapy of Cancer (SITC) held in San Diego, CA from November 1-5, 2023. Presentation materials from these conferences are available on our website. Termination of Licensing Agreement for Zanidatamab Zovodotin with BeiGene Reacquiring BeiGene APAC territory rights for zanidatamab zovodotin marks a key step, granting us sole responsibility in steering its clinical development and exploring potential combination therapies in clinical trials. We are currently pursuing the initiation of a Phase 2 study of zanidatamab zovodotin in combination with a PD-1 inhibitor in subjects with locally advanced (unresectable) or metastatic HER2-overexpressing non-squamous non-small cell lung cancer (NSCLC). This study is expected to recruit patients in Asia, North America and Europe. Proposed Director Nominee We are delighted to nominate Dr. Nancy Davidson to join our Board of Directors. Dr. Davidson’s substantial expertise in the field of oncology and foundational work in advancing insights in cancer biology from the bench through clinical studies and into the patient community arrives at a crucial time as we prepare for multiple milestones in our product pipeline. She is a highly respected oncologist and researcher who is a top opinion leader in the field of breast cancer biology and treatment, with a particular interest in developing evidence-based clinical pathways in breast cancer treatment. Dr. Davidson is currently the Executive Vice President for Clinical Affairs and Professor, Fred Hutchinson Cancer Center (FHCC) and Professor, Department of Medicine, University of Washington based in Seattle. Prior to joining FHCC, she spent time at the National Cancer Institute, Johns Hopkins in Baltimore and the University of Pittsburgh. Dr. Davidson has previously served as both President of ASCO and President of AACR. Further Advancements to '5 by 5' Strategy with Nomination of Next IND Candidate “Today we are pleased to nominate ZW251, a potential first-in-class ADC designed for the treatment of GPC3-expressing HCC, as our next product candidate with an IND filing anticipated in the second half of 2025. HCC accounts for about 85%-90% of all primary liver cancers, the sixth most-commonly diagnosed cancer worldwide and third most common cause of cancer death, with little improvement in survival rates over the past 10 years. Annual cases and deaths from liver cancer are projected to rise by more than 55% by 2040. Currently approved therapies result in modest levels of efficacy and there are limited therapeutic options for later lines of treatment, making ZW251 an important potential treatment option for patients suffering from HCC both as monotherapy and in combination with other approved agents,” said Paul Moore, Ph.D., Chief Scientific Officer of Zymeworks. “The progression of ZW251 marks the next step in our '5 by 5' strategy, serving as the fourth novel medicine nominated for clinical development, joining ZW191 and ZW171, both expected for initiation of clinical studies in 2024, and ZW220, expected for initiation of clinical development in the first half of 2025.” GPC3, a GPI-anchored cell surface oncofetal antigen, is over-expressed in most HCC patients (>75%), and displays minimal normal adult tissue expression, making it an exciting ADC target. The GPC3-targeting antibody incorporated in ZW251 was selected based on key ADC attributes including its binding profile, efficient internalization and payload delivery across a range of GPC3-expressing models of HCC. ZW251 incorporates the same Zymeworks’ proprietary bystander-active topoisomerase 1 inhibitor payload utilized in two additional pipeline ADC programs, ZW191 (anti-FRa) and ZW220 (anti-NAPi2b). A drug-antibody-ratio (DAR) of four was selected to balance tolerability and efficacy, with ZW251 anti-tumor activity observed in multiple patient derived xenograft models of HCC reflecting a range of GPC3 over-expression. We are encouraged by published research demonstrating the potential of GPC3 antibody targeting in HCC patients as evidenced by tumor localization of iodine radiolabeled condrituzumab, a prior clinical stage anti-GPC3 mAb, and are confident that antibody drug conjugate-based targeting of GPC3 could enable a novel and effective approach to treatment of HCC. Financial Results for the Nine Months Ended September 30, 2023 Revenue for the nine months ended September 30, 2023 was $59.1 million compared to $10.0 million for the same period of 2022, representing a 491% increase. Revenue for the nine months ended September 30, 2023 included $56.3 million for development support and drug supply revenue from Jazz, and $2.8 million for research support and other payments from our other partners. Revenue for the same period in 2022 included a $5.0 million research license fee from our Atreca licensing agreement and $5.0 million in research support and other payments from our other partners. Research and development expense decreased by $37.5 million, or 24%, for the nine months ended September 30, 2023, compared to the same period in 2022. For the nine months ended September 30, 2023, research and development expense included non-cash stock-based compensation expense of $0.7 million, comprised of a $0.7 million expense from equity classified awards (nine months ended September 30, 2022 – $1.5 million expense) and a nominal expense related to the non-cash, mark-to-market revaluation of certain historical liability classified awards (nine months ended September 30, 2022 - $0.8 million recovery). Excluding stock-based compensation and 2022 restructuring expense, research and development expense decreased on a non-GAAP basis by $31.4 million in the nine months ended September 30, 2023 compared to the same period of 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 during the three months ended June 30, 2023 per the (i) transfer agreement by and between Zymeworks BC Inc., Zymeworks Zanidatamab Inc., and Jazz and (ii) and the amended and restated collaboration agreement by and between Zymeworks BC Inc. and Jazz Pharmaceuticals Ireland Limited. This decrease, compared to the same period in 2022, was partially offset by an increase in preclinical expenses, primarily with respect to preclinical product candidates of 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. General and administrative expense increased by $12.4 million, or 29%, for the nine months ended September 30, 2023 compared to the same period in 2022. For the nine months ended September 30, 2023, general and administrative expense included non-cash stock-based compensation expense of $3.8 million, comprised of a $4.9 million expense from equity-classified equity awards (nine months ended September 30, 2022 – $1.5 million expense) and a $1.1 million recovery related to the non-cash mark-to-market revaluation of certain historical liability-classified equity awards (nine months ended September 30, 2022 – $3.0 million recovery). Excluding stock-based compensation and 2022 restructuring expense, general and administrative expense increased on a non-GAAP basis by $9.9 million during the nine months ended September 30, 2023, compared to same period in 2022. This increase in general and administrative expense was primarily due to an increase in expenses for professional services and other expenses related to higher depreciation on facilities and higher technology spend in 2023 compared to the same period in 2022. This was partially offset by a decrease in salaries and benefits expenses due to lower headcount in 2023. Other income, net increased by $10.9 million for the nine months ended September 30, 2023 compared to the same period in 2022. Other income, net for 2023 included $14.7 million in interest income partially offset by a $0.1 million in net loss which includes foreign exchange loss and other miscellaneous income. Other income, net for the nine months ended September 30, 2022, included $1.9 million in interest income and a $1.8 million net foreign exchange gain and other miscellaneous amounts. This increase in interest income was due to an increase in interest income earned on higher cash resources and at higher rates of return. Net loss for the nine months ended September 30, 2023 was $104.2 million compared to $185.1 million for the same period of 2022, representing a 44% decrease in net loss. The decrease in net loss was primarily due to revenue from our collaboration agreement with Jazz and an increase in interest income as well as a decrease in research and development expense. This was partially offset by an increase in general and administrative expense and an increase in income tax expense. “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 for achieving our cash runway goals as well as achieving our long-term goal of identifying additional product candidates and seeking valuable partnership options.” As of September 30, 2023, Zymeworks had $390.2 million of cash, cash equivalents, and marketable securities, comprised of $94.3 million in cash and cash equivalents and $295.9 million in marketable securities. For the nine months ended September 30, 2023, our cash used in operations was negatively impacted by working capital movements, primarily due to higher levels of receivables, which we expect to partially reverse by the end of 2023. As of September 30, 2023, we have approximately $64.3 million in receivables from Jazz reflecting reimbursement for zanidatamab development costs. Based on current operating plans, we expect to have cash resources to fund planned operations through at least the end of 2026, and potentially beyond. 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 Inc. (Nasdaq: ZYME) is a global biotechnology company committed to the discovery, development, and commercialization of novel, multifunctional biotherapeutics. Zymeworks' mission is to make a meaningful difference for people impacted by difficult-to-treat cancers and other serious diseases. Zymeworks' 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 Zymeworks' proprietary Azymetric™ technology. Zymeworks has entered into separate agreements with BeiGene, Ltd. ("BeiGene") and Jazz Pharmaceuticals Ireland Limited ("Jazz"), granting each of BeiGene and Jazz with exclusive rights to develop and commercialize zanidatamab in different territories. Zanidatamab is currently being evaluated in global Phase 1, Phase 2, and Phase 3 clinical trials, including certain ongoing pivotal clinical trials as a treatment for patients with HER2-expressing cancers. Zymeworks' next clinical candidate, zanidatamab zovodotin (ZW49), is a HER2-targeted bispecific antibody-drug conjugate ("ADC") developed using Zymeworks' proprietary Azymetric™ and ZymeLink™ Auristatin technologies. Zanidatamab zovodotin is currently being evaluated in a Phase 1 clinical trial for patients with a variety of HER2-expressing, HER2-amplified or HER2-mutant cancers. Zymeworks is also advancing a deep pipeline of product candidates based on its experience and capabilities in both ADC and multispecific antibodies ("MSAT"). 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 Twitter. 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; potential 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; anticipated continued receipt of revenue from existing and future partners; Zymeworks’ preclinical pipeline; anticipated sufficiency of cash resources and other potential sources of cash to fund Zymeworks’ planned operations through at least the end of 2026, and potentially beyond; 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 Quarterly Report on Form 10-Q for its quarter ended September 30, 2023 (a copy 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. ZYMEWORKS INC. Condensed Interim Consolidated Statements of Loss and Comprehensive Loss (Expressed in thousands of U.S. dollars except share and per share data) (unaudited) Three Months Ended September 30, Nine Months Ended September 30, 2023 2022 2023 2022 Revenue Research and development collaborations$16,506 $2,631 $59,086 $9,989 Operating expenses: Research and development 32,775 37,097 118,095 155,629 General and administrative 16,968 15,892 55,623 43,227 Total operating expenses 49,743 52,989 173,718 198,856 Loss from operations (33,237) (50,358) (114,632) (188,867)Other income, net 5,660 2,483 14,594 3,665 Loss before income taxes (27,577) (47,875) (100,038) (185,202)Income tax (expense) recovery (1,110) 29 (4,154) 112 Net loss$(28,687) $(47,846) $(104,192) $(185,090)Other comprehensive loss: Unrealized loss on available for sale securities, net of tax of nil (485) — (1,639) — Total other comprehensive loss (485) — (1,639) — Comprehensive loss$(29,172) $(47,846) $(105,831) $(185,090) Net loss per common share: Basic$(0.41) $(0.72) $(1.53) $(2.86)Diluted$(0.41) $(0.72) $(1.53) $(2.86)Weighted-average common stock outstanding: Basic 70,575,773 66,477,016 68,212,756 64,751,271 Diluted 70,575,773 66,478,157 68,214,482 64,756,063 ZYMEWORKS INC.Selected Condensed Consolidated Balance Sheet Data(Expressed in thousands of U.S. dollars) September 30,2023 December 31,2022 (unaudited) Cash, cash equivalents and marketable securities$390,194 $492,232 Working capital 301,787 449,081 Total assets 556,366 648,725 Accumulated deficit (662,955) (558,763)Total stockholders’ equity 424,344 492,956 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 implemented 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 implemented 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 may be helpful to investors because it provides information about the cash resources used in funding our operations. GAAP to Non-GAAP Reconciliations (Expressed in thousands of U.S. dollars except per share data)(unaudited) Three Months Ended September 30, Nine Months Ended September 30, 2023 2022 2023 2022 Research and development expenses$32,775 $37,097 $118,095 $155,629 Stock-based compensation expense equity classified instruments (*) (1,324) (2,226) (684) (1,450)Stock-based compensation recovery / (expense) for liability classified instruments (*) 7 (2) 7 772 Restructuring recovery / (expense) — 108 — (6,141)Adjusted research and development expenses (Non-GAAP basis)$31,458 $34,977 $117,418 $148,810 General and administrative expenses$16,968 $15,892 $55,623 $43,227 Stock-based compensation expense equity classified instruments (*) (824) (2,473) (4,935) (1,522)Stock-based compensation recovery / (expense) for liability classified instruments (*) 177 (29) 1,145 3,010 Restructuring recovery / (expense) — 832 — (2,789)Adjusted general and administrative expenses (Non-GAAP basis)$16,321 $14,222 $51,833 $41,926 Three Months Ended September 30, Nine Months Ended September 30, 2023 2022 2023 2022 Net loss per common share – Basic$(0.41) $(0.72) $(1.53) $(2.86)Stock-based compensation expense (recovery) per common share 0.03 0.07 0.06 (0.01)Restructuring expenses per common share — (0.01) — 0.14 Adjusted net loss per common share – Basic (Non-GAAP basis)$(0.38) $(0.66) $(1.47) $(2.73) Net loss per common share – Diluted$(0.41) $(0.72) $(1.53) $(2.86)Stock-based compensation expense (recovery) per common share 0.03 0.07 0.06 (0.01)Restructuring expenses per common share — (0.01) — 0.14 Adjusted net loss per common share – Diluted (Non-GAAP basis)$(0.38) $(0.66) $(1.47) $(2.73) (*): Research and development expenses and general and administrative expenses include $nil stock-based compensation expense related to the 2022 restructuring for the three and nine months ended September 30, 2023 ($nil for the three months ended September 30, 2022; recovery of $5,516 and $4,865 for the nine months ended September 30, 2022, in research and development expenses and general and administrative expenses, respectively). Three Months Ended September 30, Nine Months Ended September 30, 2023 2022 2023 2022 Net loss$(28,687) $(47,846) $(104,192) $(185,090)Acquisition of property, equipment and intangible assets (1,135) (3,792) (2,323) (12,242)Net operating cash burn (Non-GAAP basis)$(29,822) $(51,638) $(106,515) $(197,332) Contacts: Investor Inquiries:Shrinal InamdarDirector, Investor Relations(604) 678-1388 ir@zymeworks.com Media Inquiries:Diana Papove  Director, Corporate Communications(604) 678-1388media@zymeworks.com