Full Press Release Details
Zymeworks Presents New Data from Multiple Preclinical and Clinical Development Programs at the 2023
American Association for Cancer Research Annual Meeting
Vancouver, British Columbia (April 18, 2023) Zymeworks Inc. (Nasdaq: ZYME), a clinical-stage biotechnology company developing novel,
multifunctional biotherapeutics, today announced 11 presentations including new data from its clinical and preclinical development-stage programs at the 2023 American Association for Cancer Research (AACR) Annual Meeting being held in Orlando,
We are very excited to showcase new data from our portfolio of antibody-drug conjugates and multispecific antibody therapeutics including
our anticipated 2024 IND candidates, ZW191 and ZW171, said Paul Moore, Ph.D., Chief Scientific Officer at Zymeworks. These findings provide many new and exciting insights about the potential of our therapies to represent significant
advances in the treatment of cancer and other diseases, while also highlighting our cohesive strategy and path forward in developing a broad portfolio of novel antibody-drug conjugates and multispecific antibody therapeutics. The significant number
of presented abstracts is a reflection of the power and breadth of our protein engineering platforms, and our capabilities and experience to engineer potentially differentiated and novel medicines. We look forward to advancing at least five novel
medicines into clinical studies by 2027 under our previously-announced ZYME 5 x 5 R&D objectives.
Presentation Highlights
ZW191, a novel FR -targeting antibody-drug conjugate bearing a topoisomerase 1 inhibitor payload
Session Category: Experimental and Molecular
Session Title: Antibody Technologies
folate receptor alpha (FR ) is a glycosyl-phosphatidylinositol-linked membrane protein. Expression of FR is rare in normal tissue, but frequently elevated in several solid tumour types including epithelial ovarian cancer, endometrial
cancer and lung adenocarcinoma. ZW191 is an antibody-drug conjugate (ADC) targeting FR comprised of a novel fully humanized IgG1 antibody covalently conjugated to a novel topoisomerase 1 inhibitor ZD06519, a camptothecin derivative, via
endogenous interchain cysteines with a drug to antibody ratio (DAR) of eight. The linker in ZW191 consists of a maleimidocaproyl anchor and a glycyl glycyl phenylalanyl glycine-aminomethyl protease-cleavable sequence. Upon target binding and
receptor-mediated internalization of ZW191, intracellular release of bystander-active ZD06519 induces cell death of FR positive cells and FR negative cells through bystander-mediated killing.
ZW171, a T cell-engaging, bispecific antibody for the treatment of mesothelin-expressing solid tumors
Session Category: Immunology
Session Title: Therapeutic Antibodies 2
is a glycosylphosphatidylinositol-linked membrane glycoprotein that is overexpressed in many cancer indications, including pancreatic, mesothelioma, and ovarian1, for which there is a high unmet
medical need. While MSLN-targeting agents have shown early signs of clinical activity, there remains a need for therapies with improved safety and efficacy2. T cell engager (TCE) therapies have
exhibited clinical utility against hematological malignancies but have shown limited success against solid tumors due to dose-limiting toxicities associated with risk of cytokine release syndrome (CRS) and
on-target off-tumor effects3.
To improve the therapeutic intervention of MSLN-expressing tumors, Zymeworks utilized proprietary technologies based on the company s Azymetric and EFECT platforms as well as focused engineering strategies to generate a panel of MSLN-targeting TCEs with a variety of formats,
geometries, and paratope affinities. ZW171 was selected for development from this panel based on its enhanced anti-tumor activity and safety.
glypican-3-targeting antibody-drug conjugate bearing a topoisomerase 1 inhibitor payload
Session Category: Experimental and Molecular
Session Title: Antibody Technologies
Glypican-3 (GPC3) is a membrane-associated proteoglycan that is specifically up-regulated in a substantial proportion of patients with hepatocellular carcinoma (HCC)4, the most common type of liver cancer. Liver cancer is a major cause of death in many countries, and the number of people diagnosed with liver cancer is expected to rise5. ZW251 is an ADC consisting of a topoisomerase 1 inhibitor payload conjugated to an antibody targeting GPC3. Topoisomerase 1 inhibiting ADCs have demonstrated wide clinical benefit in solid tumors
and ZW251 aims to apply this against a target expressed in hepatocellular carcinoma (HCC), a disease with high unmet need and limited treatment options.
Additional ADC Program Presentations
Revisiting the dogma of antibody-drug conjugates (ADCs): Emerging data challenge the benefit of linker stability and the primacy of payload
Experimental and Molecular Therapeutics
Session Title: Antibody Drug Conjugates
ZW220, a novel NaPi2b-targeting antibody-drug conjugate bearing a topoisomerase 1 inhibitor payload
Session Category: Experimental and Molecular
Session Title: Antibody Drug Conjugates
Additional Multispecific Antibody Therapeutics Program Presentations
TriTCE Co-stim, next generation costimulatory trispecific T cell engagers for the treatment of solid tumors
Session Category: Immunology
Session Title: Combination Immunotherapies 2
TriTCE CPI, next generation trispecific T cell engagers with integrated checkpoint inhibition (CPI)
for the treatment of solid tumors
Session Category: Immunology
Session Title: Therapeutic
PROTECT , a novel trispecific antibody masking platform with integrated
immune modulation displays unique activity and differentiated modes of action
Session Category: Immunology
Session Title: Therapeutic
ZW270, a conditionally masked IL-12 cytokine fusion protein displaying potent anti-tumor
activity absent systemic toxicity
Session Category: Immunology
Session Title: Therapeutic
Clinical Product Candidate Presentations
ERBB2 amplification detected in ctDNA as a surrogate for tumor tissue FISH analysis of HER2 status in a phase 1 study with zanidatamab for the treatment of
locally advanced or metastatic HER2 expressing cancers
Session Category: Clinical Trials Posters
Session Title: Phase I
Zanidatamab zovodotin (ZW49) induces hallmarks of immunogenic cell death and is active in patient-derived xenograft models of
Experimental and Molecular Therapeutics
Session Title: Antibody Technologies
Conference Call and Webcast Information:
Zymeworks management will host a conference call and webcast for investors and analysts on April 18, 2023, at 6:30 pm EDT. The event will be
webcast live with dial-in details and webcast replays available on Zymeworks website
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 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; anticipated preclinical and clinical data presentations; 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 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; 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, 2022 (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.
Director, Investor Relations
Director, Corporate Communications