FOLR1 x CD3

VANCOUVER, British Columbia, April 08, 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 five presentations including new data from its preclinical development-stage programs at the 2024 American Association for Cancer Research (AACR) Annual Meeting being held in San Diego, California April 5-10, 2024. “Our team is looking forward to share new data from our strong portfolio of multispecific antibody therapeutics and antibody-drug conjugates including ZW191, an anticipated 2024 IND candidate,” said Paul Moore, Ph.D., Chief Scientific Officer at Zymeworks. “These data provide important new insights highlighting the potential of our candidates to represent major advances in the treatment of cancer while also demonstrating the potential to develop a new generation of novel antibody-drug conjugates and multispecific antibody therapeutics.” Presentation Highlights ZW191 - a FRα-targeting antibody-drug conjugate with strong preclinical activity across multiple FRα-expressing indications Abstract: 1862 Session Category: Experimental and Molecular Therapeutics Session Title: Antibody-Based Technologies and New Inhibitors ZW191 is a FRα-targeting antibody-drug conjugate (ADC) differentiated by its novel antibody and novel topoisomerase I inhibitor payload. The compelling preclinical activity pro ZW191 development across multiple tumor types, including FRα-high/mid/low ovarian cancers and other FRα-expressing indications, including non-small cell lung cancer, endometrial cancer, and triple-negative breast cancer. An investigational new drug (IND) submission or foreign equivalent is planned for 2024. Key Results: Superior internalization, payload delivery, and spheroid penetration to other FRα-targeted multi-specific antibodies. Bystander active payload drives activity in settings with heterogeneous FRα expression. Well-tolerated, with a highest non-severely toxic dose of 60 mg/kg in non-human primates. Screening novel format antibodies to design bispecific ADCs that address target heterogeneity Abstract: 2052 Session Category: Experimental and Molecular Therapeutics Session Title: New Technologies Inter-patient and intra-tumoral target expression heterogeneity is an obstacle in the design of ADCs that target a single tumor associated antigen (TAA). While bystander active payloads mitigate intra-tumoral target heterogeneity, bispecific ADCs that target two different TAAs independently provide an additional approach to overcome limitations associated with the expression pro any single target antigen. Critical to this bispecific ADC approach however is identification of the optimal bispecific antibody format suited for payload delivery to two independent tumor antigens. To address this challenge a novel design and screening approach of bispecific ADCs was employed, using FRα and NaPi2b as an exemplary target pair, independently expressed across various cancer types. Key Results: Leveraging Azymetric™, bioconjugation, analytical mass spectrometry, and high throughput functional screening, a workflow for the rapid generation and characterization of bispecific ADCs was established to identify optimal format, paratope, and valency. A library of 48 bispecific ADC molecules co-targeting FRα and NaPi2b was rapidly generated covering multiple paratopes, antibody formats, and valency bins (1+1, 2+1, 2+2). Functional screening of the library across multiple cancer cell lines expressing FRα and/or NaPi2b revealed ranges in binding, internalization, and cytotoxicity that were dependent on epitope, valency, and format geometry. Development of three-dimensional cancer cell line spheroid models for the in vitro functional characterization of cytotoxic antibody-drug conjugates Abstract: 3127 Session Category: Experimental and Molecular Therapeutics Session Title: Antibody-Drug Conjugates Antibody-drug conjugates are an effective class of cancer therapeutics comprised of a linker-payload conjugated to a monoclonal antibody targeting a TAA, to enable the delivery of the cytotoxic payload to cancer cells. Current standard in vitro monolayer models do not sufficiently reflect in vivo tumor tissue complexity, particularly in consideration of the interaction between protein-based therapeutics such as antibodies in a three-dimensional (3D) environment. To address this, methodology to yield in vitro 3D spheroid models from cancer cell lines in a rapid, robust, and uniform manner was developed. Subsequently methods were integrated to evaluate the tissue penetration capability and cytotoxic activity of structurally distinct antibodies or ADCs bearing various payload classes targeting multiple TAAs. Key Results: A readily implementable method for the rapid generation of cancer cell line spheroids was established and applied to over 50 distinct immortalized cancer cell lines derived from more than 10 tissue types, demonstrating varying morphological features with a success rate of >95%. In vitro assays were developed to evaluate the spheroid penetration capability and 3D cytotoxic activity of multispecific antibodies and ADCs, enabling the interrogation of various antibody formats and payload classes. These 3D models and assays serve as valuable functional tools that provide improved translation between in vitro and in vivo activity, supporting the characterization of therapeutic ADC candidates and their pipeline advancement. 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 Session Category: Immunology Session Title: Targeted ICEs Low T cell infiltration and T cell anergy are challenges associated with the treatment of solid tumors with conventional CD3-engaging bispecific T cell engagers (TCEs)1. By optimizing “Signal 1” (CD3) and “Signal 2” (CD28) within the context of a single molecule, co-stimulatory trispecific TCEs (TriTCE Co-Stim) have the potential to increase therapeutic responses beyond that achievable by conventional CD3-based TCEs by stimulating T cell proliferation in patients with poorly infiltrated tumors and providing more durable anti-tumor control by enhancing T cell activation. Key Results: Relative to comparator bispecific TCEs, the lead CLDN18.2 TriTCE Co-Stim molecule mediates enhanced T cell-mediated killing of tumor cells at low E:T ratios, exhibits sustained T cell mediated activity in serial challenge assays and supports superior antitumor activity in humanized models of gastric cancer. TriTCE Co-stim design facilitates obligate cis T cell binding and activation of CD28 that requires co-engagement of CD3 with no detectable cytokine levels observed upon incubation with human peripheral blood mononuclear cells in the absence of tumor target engagement. CLDN18.2 TriTCE Co-stim was well tolerated in non-human primates upon repeat dosing, with minimal peripheral cytokine elevations and no on-target histopathological changes observed. DLL3 TriTCE Co-Stim: A next generation trispecific T cell engager with integrated CD28 costimulation for the treatment of DLL3-expressing cancers Abstract: 6716 Session Category: Immunology Session Title: Targeted ICEs Small cell lung cancer (SCLC) is an aggressive neuroendocrine cancer with a poor prognosis and high unmet medical need2. DLL3 is a therapeutic target that is selectively expressed in SCLC and other neuroendocrine tumors. Bispecific TCEs targeting DLL3 have entered the clinic and demonstrated encouraging anti-tumor activity in SCLC patients3,4; however, SCLC is frequently characterized by an immunosuppressive microenvironment and poor T cell infiltration, which may limit clinical activity of CD3 engagers5. DLL3 TriTCE Co-Stim is a TriTCE designed to optimally engage CD3 and CD28 to redirect and enhance cytotoxic T cell responses to DLL3-expressing tumor cells while maintaining a desired safety profile. This approach has the potential to improve outcomes for patients, especially those with poorly infiltrated tumors, by increasing the depth and durability of response. Using Zymeworks’ TriTCE Co-stim platform in combination with our Azymetric™️ and EFECT™️ technologies, we generated a panel of DLL3 TriTCE Co-Stim antibody formats and evaluated multiple formats, geometries, and paratope affinities, which allowed for optimization of selectivity and activity to promote a widened therapeutic index with enhanced anti-tumor activity. Key Results: Induces greater in vitro cytotoxicity and improves T cell proliferation and survival compared to bispecific TCEs. Displays no cross-linking of T cells and exhibits obligate cis T cell binding of CD28, requiring co-engagement of CD3. Mediates improved in vivo tumor regression in an established SCLC humanized xenograft model relative to a clinical benchmark TCE. Posters will be available at the time of presentation at the conference on the Company's website located at . 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. A Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) seeking accelerated approval for the HER2-targeted bispecific antibody zanidatamab as a treatment for previously treated, unresectable, locally advanced, or metastatic HER2-positive biliary tract cancer (BTC) has been submitted. If approved, zanidatamab would be the first HER2-targeted treatment specifically approved for BTC in the U.S. 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 the anticipated data presentations; Zymeworks’ preclinical pipeline; the potential therapeutic effects of zanidatamab and Zymeworks’ other product candidates; anticipated regulatory submissions and the timing thereof; 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”, “anticipate”, “potential”, “will”, “continues”, 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: future clinical trials may not demonstrate safety and efficacy of any of Zymeworks’ or its collaborators’ product candidates; 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; 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 from time to time (copies 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. 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 ___________________ 1 Arvedson T., et al. 2022. Targeting Solid Tumors with Bispecific T Cell Engager Immune Therapy (Vol. 6, pp.17-34). 2 Saltos, A. et al. 2020. Update in the biology, management, and treatment of Small Cell Lung Cancer (SCLC). Front. Oncol. 10, 1074 3 Eastland, J. DLL3 market opportunity and KOL discussion of HPN328. Harpoon Therapeutics. Corporate slide deck Sept 15 2023. 4 Paz-Ares. et al. 2023. Tarlatamab, a first-in-class DLL3-targeted bispecific T-cell engager, in recurrent small-cell lung cancer: an open-label, phase I study. J. Clin. Oncol. 41:2898-2903 5 Tian, Y. et al. 2019. Potential immune escape mechanisms underlying the distinct clinical outcome of immune checkpoint blockades in small cell lung cancer. J Hematol Oncol. 12:67

— Complete data from Phase 1A clinical trial of SL-172154 as monotherapy in platinum-resistant ovarian cancer (PROC) to be presented at the 2023 American Society of Clinical Oncology (ASCO) annual meeting in June – — Dosed first patients in Phase 1B clinical trial of SL-172154 in combination with mirvetuximab soravtansine in PROC, initial data expected in the second half of 2023 – — Enrollment in dose-escalation portion of the Phase 1A/B clinical trial of SL-172154 in acute myeloid leukemia (AML) and higher-risk myelodysplastic syndromes (HR-MDS) expected to be complete in the second quarter; complete dose escalation and initial frontline expansion cohort data expected in the second half of 2023 – — Initial data from the Phase 1B clinical trial of SL-172154 in combination with liposomal doxorubicin in PROC expected midyear 2023 – AUSTIN, TX and DURHAM, NC, May 09, 2023 (GLOBE NEWSWIRE) -- Shattuck Labs, Inc. (Shattuck) (NASDAQ: STTK), a clinical-stage biotechnology company pioneering the development of bi-functional fusion proteins as a new class of biologic medicine for the treatment of patients with cancer and autoimmune disease, today reported financial results for the quarter ended March 31, 2023, and provided recent business highlights. “As a result of steady clinical progress through the first quarter of 2023, key efficacy readouts from our ongoing clinical trials for SL-172154 in PROC and AML/HR-MDS are expected midyear and in the second half of 2023, respectively. Additionally, our poster presentation at ASCO next month will provide further context for our selection of 3 mg/kg which we believe to be the optimal dose to move into combination trials with liposomal doxorubicin in patients with PROC. We are further encouraged by ImmunoGen’s positive Phase 3 confirmatory MIRASOL trial last week, and our clinical trial of SL-172154 in combination with mirvetuximab soravtansine is also proceeding nicely,” commented Taylor Schreiber, M.D., Ph.D., Chief Executive Officer of Shattuck. “I am also pleased to report that the dose-escalation portion of our Phase 1 trial in AML/HR-MDS has enrolled very well, and we expect to complete enrollment in that portion of the study in the second quarter. We then plan to proceed immediately to the frontline expansion cohorts in HR-MDS and TP53 mutant AML and to share initial data from those cohorts in the second half of the year. We expect that the data both from the dose-escalation and expansion portions of this trial will help inform what benefit SL-172154 may provide beyond azacitidine alone.” Anticipated Milestones ARC Platform SL-172154 (SIRPα-Fc-CD40L) Complete data from Phase 1A dose-escalation clinical trial of SL-172154 as monotherapy in PROC to be presented at the 2023 ASCO annual meetingInitial data from Phase 1B clinical trial of SL-172154 in combination with liposomal doxorubicin in PROC expected midyear 2023Complete dose-escalation data, as monotherapy and in combination with azacitidine, for Phase 1A/B clinical trial of SL-172154 in AML and HR-MDS and initial dose-expansion cohort data of SL-172154 in combination with azacitidine in frontline TP53 mutant AML or HR-MDS cohorts expected in the second half of 2023Initial data from Phase 1B clinical trial of SL-172154 in combination with mirvetuximab soravtansine in PROC expected in the second half of 2023 GADLEN Platform GADLEN Preclinical Compounds Additional clinical development detail and further program guidance regarding the advancement of potential product candidates from the GADLEN platform expected in 2023 First Quarter 2023 Recent Business Highlights and Other Recent Developments ARC Clinical-Stage Pipeline SL-172154 (SIRPα-Fc-CD40L) Presenting Complete Dose-Escalation Data from Phase 1A Monotherapy Clinical Trial of SL-172154 in PROC at 2023 ASCO Annual Meeting: This open-label, multi-center, dose-escalation clinical trial evaluated the safety, tolerability, pharmacokinetics, anti-tumor activity, and pharmacodynamic effects of SL-172154 administered intravenously in patients with PROC. Dose escalation reached a maximum administered dose of 10 mg/kg.Enrollment Progressing in Ongoing Phase 1A/B Clinical Trial in AML and HR-MDS: This trial is evaluating the safety, tolerability, pharmacokinetics, anti-tumor activity, and pharmacodynamic effects of SL-172154 as both monotherapy and in combination. In the dose-escalation portion of this trial, enrollment is complete in the monotherapy cohorts through 6 mg/kg, and in the combination cohorts, in combination with azacitidine, through 3 mg/kg. To date, SL-172154, both alone and in combination, has an acceptable safety profile. The final dose-escalation cohort of SL-172154 at 6 mg/kg in combination with azacitidine is expected to complete enrollment in the second quarter. The trial will then evaluate SL-172154 in combination with azacitidine in an expansion cohort in frontline HR-MDS patients and a second expansion cohort in frontline TP53 mutant AML patients. Both expansion cohorts are expected to begin enrollment in the third quarter of 2023, and we now expect to complete enrollment in both expansion cohorts during the second half of 2023. We expect to share full dose-escalation data and initial data from the frontline expansion cohorts in the second half of 2023. Enrollment Progressing in Phase 1B Clinical Trial of SL-172154 in Combination with Liposomal Doxorubicin in PROC: Enrollment is continuing in this trial, which is evaluating the safety, tolerability, pharmacokinetics, anti-tumor activity, and pharmacodynamic effects of SL-172154, using the selected dose of 3 mg/kg, in combination with liposomal doxorubicin in patients with PROC. We expect to present initial data from the trial midyear 2023.Dosed First Patients in Phase 1B Clinical Trial of SL-172154 in Combination with Mirvetuximab Soravtansine in PROC. This trial is evaluating the safety, pharmacokinetics, pharmacodynamic effects, and preliminary anti-tumor activity of SL-172154 administered in combination with mirvetuximab soravtansine in patients with PROC. Mirvetuximab soravtansine is an antibody-drug conjugate targeting folate receptor alpha (FRα), which provides for both direct tumor cell killing as well as enhanced macrophage phagocytosis through binding with Fc gamma receptors and has received accelerated approval for PROC patients whose tumors are shown to be FRα positive, defined as ≥75%, as determined by the VENTANA FOLR1 (FOLR1-2.1) RxDx Assay. Preclinical studies have shown that both of these killing mechanisms are complementary to the mechanism of SL-172154 by enhancing the activity of macrophages to phagocytose FRα- expressing ovarian cancer cells, and that SL-172154 may broaden the activity of mirvetuximab, particularly in patients with tumors that express lower levels of FRα. We intend to enroll patients with broader FRα expression, including those with “high” (greater than ≥75%), “medium” (≥50% to <75%), and “low” (≥25% to <50%) expression of FRα, as determined by the VENTANA FOLR1 (FOLR1-2.1). We expect to present initial data from the trial in the second half of 2023. Gamma Delta T Cell Engager (GADLEN) Preclinical Pipeline Preclinical Pipeline Development We presented preclinical data from our GADLEN platform at the American Association for Cancer Research (AACR) annual meeting in April 2023 that demonstrated that the CD20-targeted GADLEN efficiently directs small numbers of human Vγ9Vδ2 T cells to serially kill greater than 99% of human B cells in a humanized mouse model. These results led to the first study of a GADLEN compound in non-human primates, where once again treatment with a CD20-targeted GADLEN directed low frequencies of endogenous Vγ9Vδ2 T cells to eliminate CD20 positive B cells with a rapid kinetic. The GADLEN compound was well tolerated in non-human primates up to the highest administered dose of 25 mg/kg, without evidence of cytokine release syndrome or other toxicities, potentially providing differentiation from CD3-directed T cell engagers. First-Quarter 2023 Financial Results Cash and Cash Equivalents and Investments: As of March 31, 2023, cash and cash equivalents and investments were $135.5 million, as compared to $239.2 million as of March 31, 2022. Research and Development (R&D) Expenses: R&D expenses were $16.7 million for the quarter ended March 31, 2023, as compared to $19.2 million for the quarter ended March 31, 2022. This decrease was primarily driven by a decrease in expense associated with the manufacture of clinical trial materials to support our ongoing clinical trials. General and Administrative (G&A) Expenses: G&A expenses were $5.1 million for the quarter ended March 31, 2023, as compared to $5.0 million for the quarter ended March 31, 2022. Net Loss: Net loss was $20.7 million for the quarter ended March 31, 2023, or $0.49 per basic and diluted share, as compared to a net loss of $24.5 million for the quarter ended March 31, 2022, or $0.58 per basic and diluted share. 2023 Financial GuidanceShattuck believes its cash and cash equivalents and investments will be sufficient to fund its operations through year-end 2024, beyond results from its Phase 1 clinical trials of SL-172154. This cash runway guidance is based on the Company’s current operational plans and excludes any additional capital that may be received, proceeds from business development transactions, and/or additional costs associated with clinical development activities that may be undertaken. About SL-172154SL-172154 (SIRPα-Fc-CD40L) is an investigational ARC® fusion protein designed to simultaneously inhibit the CD47/SIRPα checkpoint interaction and activate the CD40 costimulatory receptor to bolster an anti-tumor immune response in patients with advanced cancer. Multiple Phase 1 clinical trials are ongoing for patients with PROC (NCT04406623, NCT05483933) and patients with AML and HR-MDS (NCT05275439). About Shattuck Labs, Inc.Shattuck Labs, Inc. (NASDAQ: STTK) is a clinical-stage biotechnology company pioneering the development of bi-functional fusion proteins as a new class of biologic medicine for the treatment of patients with cancer and autoimmune disease. Compounds derived from Shattuck’s proprietary Agonist Redirected Checkpoint, ARC®, platform simultaneously inhibit checkpoint molecules and activate costimulatory molecules with a single therapeutic. The company’s lead SL-172154 (SIRPα-Fc-CD40L) program, which is designed to block the CD47 immune checkpoint and simultaneously agonize the CD40 pathway, is being evaluated in multiple Phase 1 trials. Additionally, the company is advancing a proprietary Gamma Delta T Cell Engager, GADLEN™, platform, which is designed to bridge gamma delta T cells to tumor antigens for the treatment of patients with cancer. Shattuck has offices in both Austin, Texas and Durham, North Carolina. For more information, please visit: www.ShattuckLabs.com. Forward-Looking StatementsCertain statements in this press release may constitute “forward-looking statements” within the meaning of the federal securities laws, including, but not limited to, our expectations regarding plans for our preclinical studies, clinical trials and research and development programs, plans for clinical trial design, the anticipated timing of the results from our preclinical studies and clinical trials, anticipated timing for preclinical development updates, potential clinical benefit of our product candidates, and expectations regarding the time period over which our capital resources will be sufficient to fund our anticipated operations. Words such as “may,” “might,” “will,” “objective,” “intend,” “should,” “could,” “can,” “would,” “expect,” “believe,” “design,” “estimate,” “predict,” “potential,” “develop,” “plan” or the negative of these terms, and similar expressions, or statements regarding intent, belief, or current expectations, are forward-looking statements. While we believe these forward-looking statements are reasonable, undue reliance should not be placed on any such forward-looking statements, which are based on information available to us on the date of this release. These forward-looking statements are based upon current estimates and assumptions and are subject to various risks and uncertainties (including, without limitation, those set forth in our filings with the U.S. Securities and Exchange Commission (the “SEC”)), many of which are beyond our control and subject to change. Actual results could be materially different. Risks and uncertainties include: global macroeconomic conditions and related volatility, expectations regarding the initiation, progress, and expected results of our preclinical studies, clinical trials and research and development programs; expectations regarding the timing, completion and outcome of our clinical trials; the unpredictable relationship between preclinical study results and clinical study results; the timing or likelihood of regulatory filings and approvals; liquidity and capital resources; and other risks and uncertainties identified in our Annual Report on Form 10-K for the year ended December 31, 2022, and subsequent disclosure documents filed with the SEC. We claim the protection of the Safe Harbor contained in the Private Securities Litigation Reform Act of 1995 for forward-looking statements. We expressly disclaim any obligation to update or alter any statements whether as a result of new information, future events or otherwise, except as required by law. The Company intends to use the investor relations portion of its website as a means of disclosing material non-public information and for complying with disclosure obligations under Regulation FD. Investor & Media Contact: Conor RichardsonVice President of Investor RelationsShattuck Labs, Inc.InvestorRelations@shattucklabs.com PART I - FINANCIAL INFORMATIONItem 1. Financial Statements SHATTUCK LABS, INC. CONDENSED BALANCE SHEETS(In thousands) March 31, 2023December 31, (unaudited)2022Assets Current assets: Cash and cash equivalents$66,043 $47,379 Investments 69,452 113,901 Prepaid expenses and other current assets 22,342 23,304 Total current assets 157,837 184,584 Property and equipment, net 16,887 17,671 Other assets 2,953 3,069 Total assets$177,677 $205,324 Liabilities and Stockholders’ Equity Current liabilities: Accounts payable$5,128 $7,170 Accrued expenses and other current liabilities 10,881 17,795 Total current liabilities 16,009 24,965 Non-current operating lease liabilities 4,014 4,202 Total liabilities 20,023 29,167 Stockholders’ equity: Common stock 5 5 Additional paid-in capital 397,724 396,041 Accumulated other comprehensive loss (339) (877)Accumulated deficit (239,736) (219,012)Total stockholders’ equity 157,654 176,157 Total liabilities and stockholders’ equity$177,677 $205,324 SHATTUCK LABS, INC. CONDENSED STATEMENTS OF OPERATIONS AND COMPREHENSIVE LOSS (Unaudited) (In thousands, except share and per share amounts) Three Months Ended March 31, 2023 2022 Collaboration revenue$57 $— Operating expenses: Research and development 16,667 19,187 General and administrative 5,051 4,979 Expense from operations 21,718 24,166 Loss from operations (21,661) (24,166) Other income (expense) 937 (362)Net loss$(20,724) $(24,528)Unrealized gain on investments 538 33 Comprehensive loss$(20,186) $(24,495) Net loss per share – basic and diluted$(0.49) $(0.58)Weighted-average shares outstanding – basic and diluted 42,439,204 42,357,625

Program beginning today at 8:30 AM Eastern Standard Time (EST) to feature updates and perspectives from Zymeworks senior leadership and scientific experts Progress in early-stage research designed to support Company goal to to five new Investigational New Drug (IND) applications in the next five years Live webcast to be available on the Investors & Media section of Zymeworks’ website at VANCOUVER, British Columbia--(BUSINESS WIRE)-- Zymeworks Inc. (“Zymeworks” or the “Company”) (NYSE: ZYME), a clinical-stage biopharmaceutical company developing multifunctional biotherapeutics, today announced the highlights from its early R&D Day reviewing the Company’s progress and plans for the development of its novel pipeline assets and applications of its proprietary next-generation technology platforms. “This event is an important opportunity for us to provide an update on our progress in developing the next generation of innovative therapeutics based on our proprietary engineering platforms and integrated technologies,” said Kenneth Galbraith, Chair and CEO of Zymeworks. “During the program we will review recent data related to our antibody drug conjugates (ADC) and multi-specific antibody therapeutics (MSAT). Our goal at Zymeworks is to submit five Investigational Drug Applications in the next five years, and we believe today’s early R&D Day will demonstrate that we have the momentum, expertise, and resources in place to be successful in developing the next wave of potential best-in-class therapeutics.” The event will include presentations on ADC and MSAT research programs and emerging pipeline candidates that expand the Company’s focus on cancer indications with significant unmet patient needs. Similarly, the event will highlight the future development path and strategy that we believe will help drive the next advances in antibody-based therapeutics. Presenters will include: Paul Moore, Ph.D., Chief Scientific Officer Stuart Barnscher, Director, Preclinical Programs, ADC Therapeutics Development Jamie Rich, Ph.D., Director, Technology, ADC Therapeutic Development Thomas Spreter Von Kreudenstein, Ph.D., Director, Protein Engineering Nina Weisser, Ph.D., Director, Multispecific Antibody Therapeutics “Our team is excited to have the opportunity to share these important updates and provide insight into the future in antibody-based therapeutics we are pursuing at Zymeworks,” said Paul Moore, Ph.D., Chief Scientific Officer of Zymeworks. “The use of our advanced technology platforms and continued scientific advancements in both protein engineering and antibody conjugation brings us further towards our goal of addressing difficult to treat cancers with traditionally poor patient prognosis.” Zymeworks Early R&D Day Program Highlights Update on the Company’s ADC programs, including: Topoisomerase 1 inhibitor (TOPO1i) payload ZW191– a Folate Receptor-alpha targeted topoisomerase-1 ADC ZW251 – a Glypican-3 targeted topoisomerase-1 ADC ZW220 – a NaPi2b targeted topoisomerase-1 ADC Review of progress in MSAT development, including: ZW171– a Mesothelin x CD3 targeted 2+1 format bispecific antibody Tri-specific T-cell Engagers incorporating co-stimulation (TriTCE-costim) Tri-specific T-cell Engagers incorporating checkpoint inhibition (TriTCE-CPI) Early R&D Day Webcast Information A live webcast of the Company’s Early R&D Day event will be available on the Investors & Media section of Zymeworks’ website, . A replay of the webcast will be available following the presentation. About Zymeworks Inc. Zymeworks is a clinical-stage biopharmaceutical company dedicated to the discovery, development and commercialization of next-generation multifunctional biotherapeutics. Zymeworks’ suite of therapeutic platforms and its fully integrated drug development engine enable precise engineering of highly differentiated product candidates. Zymeworks’ lead clinical candidate, zanidatamab, is a novel Azymetric™ HER2-targeted bispecific antibody currently being evaluated in multiple Phase 1, Phase 2, and pivotal clinical trials globally as a targeted treatment option for patients with solid tumors that express HER2. Zymeworks’ second clinical candidate, zanidatamab zovodotin (ZW49), is a novel bispecific HER2 ‑targeted antibody-drug conjugate currently in Phase 1 clinical development and combines the unique design and antibody framework of zanidatamab with Zymeworks’ proprietary ZymeLink™ linker and cytotoxin. Zymeworks is also advancing a deep preclinical pipeline in oncology (including immuno-oncology agents) and other therapeutic areas. In addition, its therapeutic platforms are being leveraged through strategic partnerships with global biopharmaceutical companies. For more information on our ongoing clinical trials visit . For additional information about Zymeworks, visit 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’ preclinical pipeline, Zymeworks’ development of potential product candidates, expectations regarding future regulatory filings and the timing thereof, the commercial potential of technology platforms and product candidates, Zymeworks’ ability to identify additional development candidates and successfully advance such candidates through clinical development, Zymeworks’ ability to develop best-in-class therapeutics and other information that is not historical information. When used herein, words such as “plan”, “hope”, “believe”, “expect”, “may”, “continue”, “anticipate”, “potential”, “will”, “progress”, “look forward”, 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: preclinical studies may not support continued development of potential product candidates; future 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 the COVID-19 pandemic 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, may be more severe and more prolonged than currently anticipated; the impact of new or changing laws and regulations; market conditions; Zymeworks’ assumptions regarding its financial condition, future cash needs or future financial performance 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 the Quarterly Report on Form 10-Q filed by Zymeworks BC Inc. for its quarter ended June 30, 2022 (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.