Zymeworks Presents New Preclinical Data on Antibody-Drug Conjugate
Programs at EORTC-NCI-AACR Conference
- Presentations highlight key
preclinical data that support investigational new drug application
(IND) submissions for ZW220 in 1H and ZW251 in 2H in 2025
VANCOUVER, British Columbia, Oct. 25, 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 new preclinical data
for Zymeworks’ antibody-drug conjugate (ADC) candidates ZW220 and
ZW251 in presentations at the European Organisation for Research
and Treatment of Cancer-National Cancer Institute-American
Association for Cancer Research (EORTC-NCI-AACR) Conference taking
place in Barcelona on October 23-25, 2024.
"We are thrilled to present preclinical data for ZW220 and ZW251
at the EORTC-NCI-AACR Conference," said Paul Moore, Ph.D., Chief
Scientific Officer at Zymeworks. "These innovatively designed
molecules, incorporating our proprietary payload, ZD06519, show
significant potential to address critical unmet needs in oncology.
The preclinical data presented this week supports our belief that
these programs could advance treatment options beyond current
standards of care, offering renewed hope for patients battling
challenging cancers where therapeutic progress has been
limited."
Oral Presentation Details
An oral presentation titled “ZW220, a NaPi2b-directed
topoisomerase I inhibitor Antibody-Drug Conjugate, demonstrates
compelling preclinical activity in NSCLC, ovarian and uterine
cancer models, with a favorable toxicology profile in non-human
primate” highlights preclinical data that continue to support
an IND submission in the first half of 2025.
Results demonstrate that ZW220 has the potential for improvement
over previous NaPi2b ADCs and on the basis of efficacy,
tolerability and payload mechanism. ZW220 features a novel,
moderate potency TOPO1i payload with strong bystander activity,
beneficial for tumors with low and heterogeneous NaPi2b expression.
We believe it offers a differentiated safety profile compared to
other ADCs currently in the clinic, demonstrating high tolerability
in animal studies with MTD ≥90 mg/kg in non-human primates (NHP)
and ≥200 mg/kg in rats, suggesting potential for high doses in
humans. The low drug-antibody ratio (DAR) and moderate stability of
the antibody-linker provide a good balance of stability,
tolerability, and anti-tumor activity, while potentially minimizing
antibody-driven toxicities. ZW220's strong internalizing antibody
enables efficient cellular trafficking and tissue penetration,
potentially improving anti-tumor activity even at lower NaPi2b
levels.
Poster Presentation Details
A poster titled “ZW251, a novel glypican-3-targeting
antibody-drug conjugate bearing a topoisomerase I inhibitor
payload, demonstrates compelling preclinical activity in
hepatocellular carcinoma models” highlights preclinical data
that continue to support an IND submission in the second half of
2025.
Results demonstrate that ZW251 shows promise as a new treatment
option for patients, potentially improving upon the current
standard of care (SOC). Demonstrating strong anti-tumor activity
across a wide range of hepatocellular carcinoma (HCC) models,
including those with lower and heterogenous GPC3 expression, ZW251
was designed with a DAR of four, striking a balance between
tolerability and broad anti-tumor effectiveness. In NHP
studies, ZW251 displayed significant tolerability at doses up to
120 mg/kg. As an ADC, ZW251 offers flexibility in treatment
strategies, potentially serving as either a standalone therapy or
in combination with existing SOC treatments.
About ZW220
ZW220 is an ADC that targets NaPi2b-expressing NSCLC and ovarian
cancers, and is built, like ZW191, using our proprietary TOPO1i-
payload technology. The NaPi2b-targeting monospecific antibody
incorporated in ZW220 was developed in-house and selected based on
a favorable binding profile and enhanced internalization properties
to enable targeting of both high- and low- NaPi2b-expressing
tumors. The antibody in ZW220 is Fc-silenced, containing mutations
in its Fc region which abolish FcγR (Fc gamma receptor) binding in
normal cells, with the goal of minimizing potential off-target
toxicities. A DAR of four and a moderate stability antibody-linker
were selected to balance tolerability and efficacy. NaPi2b is
reported to be expressed in approximately 96% of ovarian serous
adenocarcinoma and 87% of non-small cell lung cancer (NSCLC)
adenocarcinoma1, and ZW220 has demonstrated anti-tumor
activity in patient-derived xenograft models and robust growth
inhibition in 3D spheroid models of these cancers. The bystander
effect of the TOPO1i payload may help address NaPi2b heterogeneity
across these cancers. ZW220 is well-tolerated in non-human primates
(NHP) and rats, reaching maximum tolerated doses (MTDs) of ≥ 90
mg/kg and ≥ 200 mg/kg, respectively. We expect to submit an
investigational new drug application (IND) and non-U.S.
applications for ZW220 in the first half of 2025.
About ZW251
ZW251, a potential first-in-class ADC molecule designed for the
treatment of glypican 3 (GPC3)-expressing HCC, incorporates the
same Zymeworks proprietary bystander-active TOPO1i payload utilized
in ZW191 (anti-FRα) and ZW220 (anti-NaPi2b). A DAR of four and a
moderate stability antibody-linker were selected to balance
tolerability and efficacy. In preclinical studies, anti-tumor
activity for ZW251 was observed in multiple patient-derived
xenograft models of HCC reflecting a range of GPC3 over-expression.
GPC3, a glycosylphosphatidylinositol (GPI)-anchored cell surface
oncofetal antigen, is over-expressed in most HCC patients
(>75%2), and displays minimal normal adult tissue
expression, making it an appealing ADC target. In NHP studies,
ZW251 displayed significant tolerability at doses up to 120 mg/kg,
suggesting the possibility of high initial dosing in human trials.
We are encouraged by published research demonstrating the potential
of GPC3-targeting antibody in HCC patients as evidenced by tumor
localization of iodine radiolabeled condrituzumab, a prior
clinical-stage anti-GPC3 mAb, and believe that ADC-based targeting
of GPC3 could enable a novel and effective approach to treatment of
HCC. We expect to submit an IND and non-U.S. applications for ZW251
in the second half of 2025.
About Zymeworks Inc.
Zymeworks is a global clinical-stage 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™ 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
robust pipeline of wholly-owned product candidates, leveraging its
expertise in both antibody-drug conjugates and multispecific
antibody therapeutics targeting novel pathways in areas of
significant unmet medical need. Phase 1 studies for ZW171 and ZW191
are now actively recruiting. In addition to Zymeworks’ 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 X.
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
anticipated preclinical data presentations; the timing and status
of ongoing and future studies and the release of data; expectations
regarding future regulatory filings and approvals and the timing
thereof; the timing of and results of interactions with regulators;
Zymeworks’ preclinical pipeline; the anticipated benefits of the
collaboration agreements with Jazz and BeiGene; the commercial
potential of technology platforms and product candidates;
Zymeworks’ clinical development of its product candidates and
enrollment in its clinical trials; the potential addressable market
of zanidatamab; potential safety profile and therapeutic effects of
zanidatamab and Zymeworks’ other product candidates; 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: clinical trials and any future 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 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; 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 (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
Media Inquiries:
Diana Papove
Senior Director, Corporate Communications
(604) 678-1388
media@zymeworks.com
1Lin et al. 2015. Clin Cancer
Res
2Wang HL et al., Arch Pathol Lab Med 2008
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