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Zymeworks Presents Safety and Anti-Tumor Activity Data from the Ongoing Phase 1 Study of ZW25 at the American Society of Clinical Oncology Annual Meeting (ASCO 2017)


Zymeworks Inc. ("Zymeworks"), a clinical-stage biopharmaceutical company
dedicated to the discovery, development and commercialization of
next-generation multifunctional biotherapeutics, today announced results
from the dose escalation portion of the first-in-human study of ZW25, a
novel Azymetric™ bispecific antibody targeting two distinct domains of
the HER2 receptor.

ZW25 was well-tolerated at all dose levels evaluated with single agent
anti-tumor activity in patients with advanced HER2-expressing cancers
that had progressed after multiple lines of therapy, including
HER2-targeted agents. These results provide the framework for further
advancement of ZW25 across multiple cancer indications.

A total of 16 patients were enrolled in the study, including 8 with
breast cancer, 6 with gastric, gastroesophageal junction, or esophageal
(GE) cancer, and 2 with other HER2-expressing cancers. All patients were
heavily pretreated having received a median of 4 prior systemic regimens
for metastatic disease, which included trastuzumab. Breast cancer
patients were also treated with T-DM1 (n=8); pertuzumab (n=6), and
lapatinib (n=6) and had a median of 6 prior HER2-targeted regimens for
metastatic disease.

"Despite the benefits provided by currently-available HER2-targeted
therapies, significant medical need remains," said Dr. Diana Hausman,
Chief Medical Officer of Zymeworks. "We are very encouraged by the
safety profile and single agent anti-tumor activity of ZW25 in patients
with advanced breast or GE cancer that has progressed after prior
HER2-targeted therapies. These results will guide further development in
the expansion cohort portion of this study."

Patients were treated with weekly ZW25 at 5 mg/kg (n=3), 10 mg/kg (n=6),
or 15 mg/kg (n=7) in cycles of 4 weeks each. ZW25 was well-tolerated at
all dose levels, with no dose-limiting toxicities. The majority of
adverse events (AEs) were Grade 1 or 2, with no treatment-related
serious AEs and no changes in cardiac function. The most common AEs were
diarrhea and infusion reactions, reported in 7/16 patients each.
Treatment-related Grade 3 AEs occurred in a single patient and included
hypophosphatemia, fatigue, and arthralgia. Eight patients had anti-drug
antibodies (ADA) prior to initiating treatment with ZW25; there was no
evidence of increases from baseline levels and no patients developed new

Durable single-agent anti-tumor activity was seen with patients having
received up to 8 cycles of treatment at the time of data cut-off. In 14
response-evaluable patients (defined as undergoing at least one tumor
restaging), best overall response (BOR) was 2 partial response (PR), 4
stable disease (SD), and 8 progressive disease (PD). The majority of
patients with measurable disease had a decrease in the size of target
lesions. BOR in 8 breast cancer patients was 2 PR, 3 SD (> 6 months in
one patient), and 3 PD, for an overall disease control rate (CR, PR, or
SD) of 63%. Three of the breast cancer patients developed PD due to
brain metastases but maintained systemic disease control at the time of
progression. BOR in 4 response-evaluable patients with GE cancers
included SD > 4 cycles in 1 patient, and 3 PD. Four patients remain
active on study.

"We will continue to rapidly advance development across multiple cancer
indications, with the goal of establishing ZW25 as the HER2-targeted
therapy of choice for physicians and their patients," said Dr. Ali
Tehrani, President and CEO of Zymeworks. "These results also highlight
the value of Zymeworks' Azymetric bispecific platform and support the
accelerated development of additional multifunctional therapeutics in
our candidate pipeline."

ZW25 Phase 1 Clinical Trial Details

The dose escalation portion of the study enrolled patients with
HER2-expressing cancers (either HER2 IHC 1+, 2+ or 3+, or FISH-positive)
whose cancer had progressed after treatment with all therapies known to
confer clinical benefit. HER2 status was assessed in archived or fresh
biopsies locally and at a central laboratory. Patients with HER2-high
breast cancer (HER2 IHC 3+ or IHC2+ and FISH-positive) had to have
received previous treatment with trastuzumab, pertuzumab, and T-DM1.
Patients with HER2-high gastric or gastroesophageal cancers had to have
been previously treated with trastuzumab. Patients could have measurable
or non-measurable tumor lesions per RECIST 1.1. Patients with known
active brain metastases were excluded from the study. Patients were
assessed during treatment for safety, including changes in cardiac
function, tumor response per RECIST 1.1 every 8 weeks, ZW25 drug levels,
and potential development of anti-drug antibodies.

About ZW25

ZW25 is Zymeworks' lead product candidate currently being evaluated in a
Phase 1 clinical trial in the United States, based on Zymeworks'
Azymetric™ platform. It is a bispecific antibody that can simultaneously
bind two non-overlapping epitopes of HER2, known as biparatopic binding,
resulting in dual HER2 signal blockade, increased binding and removal of
HER2 protein from the cell surface, and potent effector function. These
combined mechanisms of action have led to significant anti-tumor
activity in preclinical models of HER2-expressing cancer. Zymeworks is
developing ZW25 as a best-in-class HER2-targeting antibody intended as a
treatment option for patients with any solid tumor that expresses HER2.

About Zymeworks Inc.

Zymeworks is a clinical-stage biopharmaceutical company dedicated to the
discovery, development and commercialization of next-generation
multifunctional biotherapeutics, initially focused on the treatment of
cancer. Zymeworks' suite of complementary therapeutic platforms and its
fully-integrated drug development engine provide the flexibility and
compatibility to precisely engineer and develop highly-differentiated
product candidates. Zymeworks' lead product candidate, ZW25, is a novel
bispecific antibody currently being evaluated in a Phase 1 clinical
trial. Zymeworks is also advancing a deep pipeline of preclinical
product candidates and discovery-stage programs in immuno-oncology and
other therapeutic areas. In addition to Zymeworks' wholly-owned
pipeline, its therapeutic platforms have been further leveraged through
multiple strategic partnerships with global biopharmaceutical companies.

Forward Looking Statements

This press release includes "forward-looking statements" within the
meaning of the U.S. Private Securities Litigation Reform Act of 1995 and
"forward-looking information" within the meaning of Canadian securities
laws, or collectively, forward-looking statements. Forward-looking
statements include statements that relate to Zymeworks' Phase 1 clinical
trial, ASCO presentation and other information that is not historical
information. 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 our current expectations and various
assumptions. We believe there is a reasonable basis for our expectations
and beliefs, but they are inherently uncertain. We may not realize our
expectations, and our 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, market conditions and the factors described under
"Risk Factors" in our registration statement on Form F-1 and in our
supplemented PREP prospectus dated April 27, 2017 filed in connection
with our initial public offering on May 3, 2017 (copies of which filings
may be obtained at
Consequently, forward-looking statements should be regarded solely as
our current plans, estimates and beliefs. You should not place undue
reliance on forward-looking statements. We cannot guarantee future
results, events, levels of activity, performance or achievements. We do
not undertake and specifically decline any 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, except as may be required by law.

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