- ZW25 Active and Well Tolerated Across
Multiple HER2-expressing Tumor Types
- Durable Anti-Tumor Activity with
Confirmed Partial Responses and Median Progression-Free Survival
> Six Months
- 82 Percent of Heavily Pretreated
Patients Experienced Disease Control
Zymeworks Inc. (NYSE/TSX: ZYME), a clinical-stage
biopharmaceutical company developing multifunctional therapeutics,
announced today the plenary presentation of updated ZW25 clinical
data by Murali Beeram, MD, a clinical investigator at the START
Center for Cancer Care, San Antonio, Texas. Data from Zymeworks’
ongoing multi-center Phase 1 study showed single agent ZW25, a
bispecific antibody, induced anti-tumor activity and was well
tolerated in heavily pretreated patients with a variety of
HER2-expressing cancers.
“Today we report, for the first time, the durability of ZW25’s
anti-tumor activity,” said Ali Tehrani, Ph.D., President and CEO of
Zymeworks. “With a median of over six months of progression-free
survival in these heavily pretreated patients, these data further
support our previously-communicated clinical strategy which
includes registration-enabling studies for single-agent ZW25 in
gastrointestinal-related cancers where the unmet need is so great
worldwide.”
ZW25 Clinical Results Presented Today
The plenary presentation includes all 24 gastroesophageal and
other cancer patients treated at the Phase 2 recommended dose, of
which 17 were response-evaluable (defined as having measurable
disease and at least one tumor restaging) at the time of data
cut-off. Of these 17 patients, eight had gastroesophageal cancers,
four had colorectal cancer and five had other HER2-expressing
cancers including gall bladder, cholangiocarcinoma, cervical,
fallopian tube and salivary gland. The participants in the study
were heavily pretreated with a median of three prior cancer
treatments.
The overall disease control rate (DCR), which includes patients
with partial responses and stable disease was 82%. There were seven
partial responses (41%), seven stable disease (41%) and three
progressive disease (18%). The median progression-free survival
(mPFS) in all 24 patients was 6.21 months (95% CI 1.94-9.33).
“To observe this level of activity across so many different
tumor types is quite compelling,” said Murali Beeram, MD. “These
were heavily pretreated patients who had essentially run out of
therapeutic options, so for them to respond so favorably is indeed
encouraging.”
In the eight gastroesophageal cancer patients, who had a median
of four prior systemic treatments, the response rate was 50%. In
the four colorectal and five other HER2-expressing cancer patients
the response rate was 33%. Anti-tumor activity was assessed per
RECIST every eight weeks.
In the study, ZW25 was well tolerated. All treatment-related
adverse events were Grade 1 or 2 with the exception of one patient
with Grade 3 fatigue, and no treatment-related serious adverse
events were seen. There were no Grade 4 or 5 adverse events. The
most common adverse events (25% or greater) were diarrhea, infusion
reaction and nausea.
“The favorable tolerability we have seen with ZW25 supports its
use as both a single agent and in combination with approved
anti-cancer agents,” said Diana Hausman, MD, Zymeworks’ Chief
Medical Officer. “We are excited to be advancing ZW25’s development
and have plans to explore its efficacy in a number of tumor types,
including gastroesophageal and breast cancer.”
Plenary Presentation Details
The presentation is part of the Symposium on Molecular Targets
and Cancer Therapeutics sponsored by the European Organization for
Research and Treatment of Cancer (EORTC), the National Cancer
Institute (NCI) and the American Association for Cancer Research
(AACR).
Title: “Single Agent Activity of ZW25, a HER2-Targeted
Bispecific Antibody, in HER2-Expressing Gastroesophageal and Other
Cancers”
Session: Proffered papers, Plenary Session 2, Abstract 6
Time: Wednesday November 14, 3:45 pm GMT
Location: Auditorium
About the Trial
Zymeworks’ adaptive Phase 1 study has three parts. Enrollment in
the first portion of the study (the dose-escalation phase) has been
completed. The recommended single-agent dose was determined to be
20 mg/kg once every two weeks or 10 mg/kg weekly. In the second
part of the study (the cohort expansion phase), additional patients
are being enrolled to further assess ZW25’s single-agent
tolerability and anti-tumor activity against a variety of cancer
types in different settings. The third part of the study (the
combination phase) is underway and is evaluating ZW25 in
combination with selected chemotherapy agents in gastroesophageal
and breast cancer patients with HER2 high or lower HER2 expression
levels.
About ZW25
ZW25 is a bispecific antibody, based on Zymeworks’ Azymetric™
platform, that can simultaneously bind two non-overlapping epitopes
of HER2, known as biparatopic binding. This unique design results
in multiple mechanisms of action including dual HER2 signal
blockade, increased binding and removal of HER2 protein from the
cell surface, and potent effector function and has led to
encouraging anti-tumor activity in patients. Zymeworks is
developing ZW25 as a HER2-targeted treatment option for patients
with any solid tumor that expresses HER2. The FDA has granted
Orphan Drug Designation to ZW25 for the treatment of both gastric
and ovarian cancers.
About the Azymetric™ Platform
The Azymetric platform enables the transformation of
monospecific antibodies into bispecific antibodies, giving them the
ability to simultaneously bind two different targets. Azymetric
bispecific technology enables the development of multifunctional
biotherapeutics that can block multiple signaling pathways, recruit
immune cells to tumors, enhance receptor clustering and
degradation, and increase tumor-specific targeting. These features
are intended to enhance efficacy while reducing toxicities and the
potential for drug-resistance. Azymetric bispecifics have been
engineered to retain the desirable drug-like qualities of naturally
occurring antibodies, including low immunogenicity, long half-life,
and high stability. In addition, they are compatible with standard
manufacturing processes with high yields and purity with the
potential to significantly reduce drug development costs and
timelines.
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 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 an adaptive Phase
1 clinical trial. The company’s second product candidate, ZW49,
capitalizes on the unique design and antibody framework of ZW25 and
is a bispecific antibody-drug conjugate, or ADC, armed with the
company’s proprietary ZymeLink™ cytotoxic payload. 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.
Cautionary Note Regarding Zymeworks’ 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 in this news release include
statements that relate to ZW25 and its potential as an anti-cancer
treatment, Zymeworks’ clinical plans and future results, Zymeworks’
technology platform, and other information that is not historical
information. When used herein, words such as “believe”, “may”,
“plan”, “will”, “estimate”, “continue”, “anticipate”, “intend”,
“expect”, 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, market
conditions and the factors described under “Risk Factors” in
Zymeworks’ Quarterly Report on Form 10-Q for its fiscal quarter
ended September 30, 2018 (a copy of which may be obtained at
www.sec.gov and www.sedar.com). Consequently, forward-looking
statements should be regarded solely as Zymeworks’ current plans,
estimates and beliefs. You should not place undue reliance on
forward-looking statements. Zymeworks cannot guarantee future
results, events, levels of activity, performance, or achievements.
Zymeworks does not undertake and specifically declines 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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Investor Inquiries:Ryan Dercho, Ph.D.(604)
678-1388ir@zymeworks.comMedia Inquiries:Angela Bitting(925)
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