- Active drug with multiple confirmed responses and stable
disease observed in several tumor types
- Differentiated safety profile with the majority of adverse
events being grade 1 or 2
- Expansion cohorts open and enrolling patients at 2.5 mg/kg once
every three weeks
- Maximum tolerated dose not established, dose escalation
continues in parallel
Zymeworks Inc. (NYSE: ZYME), a clinical-stage biopharmaceutical
company developing multifunctional biotherapeutics, announced today
that the Company has begun enrolling patients into the expansion
cohort portion of the ongoing Phase 1 clinical trial for ZW49, its
novel HER2-targeted antibody-drug conjugate (ADC). Supporting data
from the Phase 1 dose escalation portion were highlighted today via
a webcast and conference call and are summarized below.
Phase 1 Dose Escalation Study Design
The dose escalation portion of the study employed a standard 3 +
3 design to evaluate escalating doses within different dosing
regimens including once every two week (Q2W) and once every three
week (Q3W) schedules with the objective of selecting a dose and
schedule to advance into the expansion cohorts.
To date patients from sites across the US and Canada with a
variety of heavily pretreated HER2‑positive cancer types have been
enrolled, including breast cancer, gastroesophageal adenocarcinoma,
gynecologic cancers, non-small cell lung cancer, anal cancer, and
colorectal cancer.
ZW49 Safety and Tolerability
In the 35 patients who have received ZW49 across all dosing
regimens, there have been no dose limiting toxicities, no
treatment-related hematologic toxicities including neutropenia or
thrombocytopenia, no treatment-related pulmonary toxicity including
interstitial lung disease or pneumonitis, and no treatment-related
liver toxicity. There have been no treatment-related deaths.
Over 90% of treatment-related adverse events have been mild or
moderate (Grade 1 or 2) in severity, with the most common being
keratitis, fatigue, and diarrhea, which have been reversible and
manageable in an outpatient setting. There have been no
discontinuations due to treatment-related adverse events, and the
maximum-tolerated dose has not yet been established.
ZW49 Interim Antitumor Activity
ZW49 has demonstrated antitumor activity across all regimens and
dose levels evaluated to date, including at the starting dose of 1
mg/kg Q2W. Partial responses and stable disease per RECIST 1.1 have
been observed in both Q2W and Q3W dosing regimens, with the Q3W
regimen starting to demonstrate a dose-response relationship.
Beginning at the initial dose of 2.0 mg/kg Q3W, several patients
experienced stable disease including some with disease control
greater than four months. At the highest doses tested in the Q3W of
2.5 or 3.0 mg/kg there were six response-evaluable patients with
centrally confirmed HER2‑positive disease spanning several
different tumor types. The antitumor activity in these six patients
consisted of two patients with confirmed partial responses and two
patients with stable disease, three of which are still active on
study. This regimen is currently enrolling patients at the 3 mg/kg
dose with the potential to add new escalation cohorts.
“We are encouraged by the antitumor activity we are seeing so
far with ZW49 and look forward to accelerating development by
expanding our dataset in disease-specific cohorts,” said Diana
Hausman, M.D., Chief Medical Officer of Zymeworks. “In addition,
the differentiated safety profile allows us to continue in dose
escalation, with the opportunity to fully realize the therapeutic
potential for ZW49.”
Expansion Cohort Phase
Based on the antitumor activity demonstrated by ZW49, three
indication-specific expansion cohorts utilizing the 2.5 mg/kg Q3W
regimen are open and enrolling patients. These include
HER2-positive breast cancer, HER2-positive gastroesophageal
adenocarcinoma, and a basket cohort of other HER2-positive cancers.
The expansion cohorts are actively enrolling at sites in U.S. and
Canada, and are expected to open soon at additional sites in South
Korea and Australia in collaboration with our partner, BeiGene.
“I believe ZW49 is on track for becoming the HER2 ADC that
delivers efficacy without compromising safety,” said Ali Tehrani,
Ph.D., President and CEO of Zymeworks. “These data highlight that
ZW49 can potentially provide physicians and their patients with a
differentiated alternative to currently-approved HER2 ADCs. We look
forward to presenting additional data at a medical conference later
this year.”
About ZW49
ZW49, Zymeworks’ second product candidate, is a novel bispecific
HER2-targeted ADC developed using Zymeworks’ proprietary Azymetric™
and ZymeLink™ platforms. ZW49 combines the unique design of
zanidatamab with a proprietary cytotoxin and cleavable linker
resulting in enhanced internalization and tumor cell killing. ZW49
is currently in a Phase 1 clinical trial and is being developed for
several indications characterized by HER2 expression, especially
for patients whose tumors have progressed or are refractory to
HER2-targeted agents and those that express lower levels of HER2
and are ineligible for treatment with existing HER2-targeted
therapies.
About ZymeLink™ Antibody-Drug Conjugates
The ZymeLink ADC platform is a modular suite of proprietary
cytotoxins (cell-killing drugs), customizable linkers, and
conjugation technologies designed for targeted delivery of
cytotoxins to diseased cells with optimal safety and efficacy. The
ZymeLink platform can be combined with a diverse array of targeted
therapies, including traditional antibodies and Azymetric™
bispecific antibodies, to deliver cell-killing compounds to
diseased target cells. These modular technologies are designed to
develop next-generation ADCs with broad therapeutic windows.
About Zymeworks Inc.
Zymeworks is a clinical-stage biopharmaceutical company
dedicated to the development 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 (ZW25), is a novel Azymetric™
bispecific antibody which has been granted Breakthrough Therapy
designation by the FDA and is currently enrolling in a pivotal
clinical trial for refractory HER2-amplified biliary tract cancer
(HERIZON-BTC-01) as well as several Phase 2 clinical trials for
HER2-expressing gastroesophageal and breast cancers. Zymeworks’
second clinical candidate, ZW49, is a novel bispecific
HER2-targeting 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 nine
biopharmaceutical companies. For additional information about
Zymeworks, visit www.zymeworks.com and follow @ZymeworksInc on
Twitter.
Zymeworks 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 Zymeworks’ expectations regarding the
enrollment of patients into the expansion cohort portion of the
ongoing Phase 1 clinical trial for ZW49, dose escalation of ZW49,
the therapeutic potential of ZW49, and other information that is
not historical information. When used herein, words and phrases
such as “continue”, “believe”, “starting to”, “look forward to”,
“expected to”, “potential to”, 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, including assumptions regarding anticipated reporting
of additional clinical and preclinical data, the efficacy of
zanidatamab, ZW49, and Zymeworks’ therapeutic platforms, and
Zymeworks’ ability to maintain its partnership arrangements.
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, 2020
(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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version on businesswire.com: https://www.businesswire.com/news/home/20210127005991/en/
Investor Inquiries: Ryan Dercho, Ph.D. (604) 678-1388
ir@zymeworks.com Tiffany Tolmie (604) 678-1388 ir@zymeworks.com
Media Inquiries: Mary Klem (604) 678-1388 media@zymeworks.com
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