* Pursuant to the terms of the licensing agreement between Zymeworks and

    BeiGene, Zymeworks is entitled to receive an $8 million milestone payment
    from BeiGene and remains eligible to receive up to $164 million based on
    additional milestones plus royalties on product sales
  * A Biologics License Application (BLA) to the U.S. Food and Drug
    Administration (FDA) for zanidatamab as a treatment for previously-treated,
    unresectable, locally advanced, or metastatic HER2-positive biliary tract
    cancer (BTC) has also been recently accepted for Priority Review by the FDA
    with target action date of November 29, 2024

VANCOUVER, British Columbia, June 10, 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 that the Center for Drug
Evaluation (CDE) of the National Medical Products Administration (NMPA) in China
has accepted the BLA for zanidatamab for second-line treatment of HER2-positive
BTC. Under the terms of Zymeworks' Asia Pacific license and collaboration
agreement with BeiGene for the development and commercialization of zanidatamab,
Zymeworks is entitled to receive an $8 million milestone payment. Zymeworks also
remains eligible to receive up to $164 million based on additional milestones
plus royalties on product sales in the Asia Pacific region.
This BLA is based on the data from the HERIZON-BTC-01 (NCT04466891
(https://clinicaltrials.gov/search?term=NCT04466891), CTR20202607) clinical
trial, which was published in Lancet Oncology
(https://www.thelancet.com/article/S1470-2045(23)00242-5/fulltext) in June
2023(1). The trial is an open-label phase 2b study that evaluated the efficacy
and safety of zanidatamab in previously treated patients with unresectable,
locally advanced, or metastatic HER2-positive BTC. Zanidatamab demonstrated
clinically meaningful anticancer activity and durable responses in subjects with
previously treated HER2-positive BTC. As of October 10, 2022, the objective
response rate (ORR), median duration of response (DOR), and median progression-
free survival (PFS) assessed by independent central review (ICR) were 41.3% (95%
CI: 30.4-52.8), 12.9 months (95% CI: 6.0-not estimable), and 5.5 months (95% CI:
3.7-7.2), respectively.
"Acceptance of this BLA in China represents a significant milestone in the
global effort to bring effective, targeted treatment options to those affected
by locally advanced or metastatic HER2-positive BTC," said Kenneth Galbraith,
Chair and Chief Executive Officer of Zymeworks. "We are grateful to all of the
stakeholders who have worked tirelessly to help us reach this milestone,
including our dedicated teams in manufacturing, quality control, regulatory
affairs, and clinical research at Zymeworks, and our collaboration partner in
Asia Pacific, BeiGene, as well as the study investigators, patients, and
families who have supported this development program for zanidatamab. We remain
confident about zanidatamab's potential as a new treatment option for multiple
HER2-expressing cancers, with ongoing Phase 3 trials in first-line advanced or
metastatic HER2-positive BTC (HERIZON-BTC-302) and first-line HER2-positive
gastroesophageal adenocarcinoma (HERIZON-GEA-01
(https://clinicaltrials.gov/study/NCT05152147?term=HERIZON-GEA-01&rank=1))."
"We further our mission by collaborating with other innovative companies to
advance the development and delivery of impactful cancer medicines to more
patients around the world," said Clare Fisher, Senior Vice President of Business
Development at BeiGene. "We thank our partners at Zymeworks for their dedication
and contributions toward achievement of this important milestone for
zanidatamab. We look forward to continued partnership as we work to reach more
patients in the Asia-Pacific region."
Under the terms of its collaboration with BeiGene regarding zanidatamab,
Zymeworks has received $53 million in upfront and milestone payments as well as
certain co-development funding for zanidatamab clinical studies, not including
the $8 million milestone payment Zymeworks is eligible to receive in connection
with the NMPA's acceptance of the BLA for zanidatamab for second-line treatment
of HER2-positive BTC. Through our collaboration with BeiGene on zanidatamab, we
remain eligible to receive up to $164 million in additional development and
commercial milestones together with tiered royalties of up to 19.5% of net sales
in BeiGene territories.
About Zanidatamab
Zanidatamab is an investigational HER2-targeted bispecific antibody that can
simultaneously bind two non-overlapping epitopes of the HER2 receptor, known as
biparatopic binding. This unique design and increased binding results in
multiple mechanisms of action, including dual HER2 signal blockade, removal of
HER2 protein from the cell surface, and immune-mediated cytotoxicity leading to
encouraging antitumor activity in patients. Zanidatamab is being developed in
multiple clinical trials as a targeted treatment option for patients with solid
tumors that express HER2. Zanidatamab is being developed by Jazz Pharmaceuticals
and BeiGene under license agreements from Zymeworks, which first developed the
molecule.
The U.S. Food and Drug Administration (FDA) has accepted and granted Priority
Review of the Biologics License Application (BLA) for zanidatamab with a
Prescription Drug User Fee Act (PDUFA) action date of November 29, 2024.
Zanidatamab was also granted Breakthrough Therapy designation in patients with
previously treated HER2 gene-amplified BTC, and given two Fast Track
designations: one as a single agent for refractory BTC and one in combination
with standard of care chemotherapy for first-line gastroesophageal
adenocarcinoma (GEA). Additionally, zanidatamab has received Orphan Drug
designations from FDA for the treatment of BTC and GEA, as well as Orphan Drug
designation from the European Medicines Agency for the treatment of BTC and
gastric cancer. Zanidatamab was also granted Breakthrough Therapy designation
from the Center for Drug Evaluation (CDE) in China.
About HERIZON-BTC-01
HERIZON-BTC-01 (NCT04466891, CTR20202607) is a global, multicenter, open-label,
single-arm phase 2b trial to evaluate the efficacy and safety of zanidatamab in
patients with previously treated advanced or metastatic HER2-amplified BTC. The
primary endpoint was objective response rate (ORR) assessed by independent
central review (ICR) in HER2-positive patients. Secondary endpoints included
ICR-assessed duration of response (DOR), progression-free survival (PFS), and
overall survival (OS).
About Biliary Tract Cancer
Biliary tract cancer (BTC), including gallbladder cancer and intrahepatic and
extrahepatic cholangiocarcinoma, account for 65%)
are diagnosed with tumors that cannot be removed surgically.
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(TM) 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 zanidatamab as a treatment for previously-treated,
unresectable, locally advanced, or metastatic HER2-positive biliary tract cancer
(BTC) has been accepted and granted Priority Review. A BLA has also been
accepted for review by the Center for Drug Evaluation (CDE) of the National
Medical Products Administration (NMPA) in China. If approved, zanidatamab would
be the first HER2-targeted treatment specifically approved for BTC in the U.S.
and China. 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
(https://www.zymeworks.com/) and follow @ZymeworksInc
(https://twitter.com/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 licensing agreement with BeiGene and agreements with
other partners, 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; the timing and status of ongoing and future studies and the
related data; expectations regarding future regulatory filings and approvals;
the timing of and results of interactions with regulators; potential safety
profile and therapeutic effects of zanidatamab and Zymeworks' other product
candidates; the commercial potential of technology platforms and product
candidates 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 (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.
Contacts:
Investor Inquiries:
Shrinal Inamdar
Director, Investor Relations
(604) 678-1388
ir@zymeworks.com (mailto:ir@zymeworks.com)??
Media Inquiries:
Diana Papove
Senior Director, Corporate Communications
(604) 678-1388
media@zymeworks.com (mailto:media@zymeworks.com)
--------------------------------------------------------------------------------
(1) Harding JJ, Fan J, Oh D-Y, et al. Zanidatamab for HER2-amplified,
unresectable, locally advanced or metastatic biliary tract cancer (HERIZON-BTC-
01): a multicentre, single-arm, phase 2b study. Lancet Oncol.
2023;24(7):772-782.
(2) Valle JW, et al. Lancet 2021; 397:428-44
(3) Siegel RL, et al. CA Cancer J Clin 2022; 72;7-33
(4) BTC overall diagnosed patients as per SEER 22;
(5) Assumes anatomic subsites intrahepatic CCA, extrahepatic CCA, gallbladder
cancer, and BTC unspecified;
(6) Assumes HER2 positivity rates per anatomical subsite from: Galdy, S.,
Lamarca, A., McNamara, M.G. et al. Cancer Metastasis Rev 36, 141-157 (2017),
Nobuyoshi Hiraoka, et al. Human Pathology, Volume 105, 2020, Pages 9-19
(7) Major markets: U.K, France, Germany, Spain, Italy. Note: HER2+ BTC patients
in Jazz-controlled commercial territories, which includes Japan, and excludes
other certain Asia Pacific countries licensed to BeiGene, Ltd
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