Kezar Life Sciences, Inc. (Nasdaq), a clinical-stage
biotechnology company discovering and developing breakthrough
treatments for immune-mediated and oncologic disorders, today
presented preclinical data on the company’s novel protein secretion
program during two poster sessions at the American Association for
Cancer Research (AACR) 2021 Virtual Annual Meeting.
“The growing body of evidence generated by our team supports the
strong therapeutic potential of inhibiting Sec61 and the protein
secretion pathway as a way to generate novel therapies to treat
multiple tumor indications,” said Christopher Kirk, PhD, Kezar’s
President and Chief Scientific Officer. “These data provide a
robust scientific framework for identifying which tumor types might
be the most sensitive to inhibition of the Sec61 translocon and the
protein secretion pathway.”
Kezar examined the activity of KZR-261, a small molecule
inhibitor of the Sec 61 translocon, and a closely related
representative molecule in hundreds of tumor cell lines. The
objective was to compare drug activity and identify sensitivity to
gene mutations and impact on gene expression levels. No single gene
predicted the activity of KZR-261, consistent with the known impact
of KZR-261 on multiple targets. However, representative gene
modules identified through mechanism agnostic analysis were
associated with sensitivity in tumor cells and show high overlap
with key processes involved in protein secretion. Analyses of
primary tumor and tissue expression datasets predict that many
tumor types will be more sensitive than normal tissues and cells.
Data from these analyses will inform selection of tumor types for
study in future clinical trials.
Global proteomic profiling of protein secretion in tumor cells
and non-transformed cells was also conducted. KZR-261 and the
related molecules reduce expression of Sec61 clients, namely
secreted and transmembrane proteins. In tumor cells, these
compounds reduced expression of approximately 10% of Sec61 clients
by at least two-fold. However, in non-transformed cells, KZR-261
inhibited the expression of less than 5% of measured Sec61 clients,
many of which can be measured from clinical samples in future
clinical trials.
Pending successful completion of drug product manufacturing,
submission of an Investigational New Drug (IND) application is
anticipated in mid-2021. A first-in-human Phase 1 study to evaluate
the safety and anti-tumor activity of KZR-261 in patients with
solid tumors is expected to commence shortly thereafter.
Details on Kezar’s poster presentations at AACR are as
follows:
Title: Prioritizing tumor types for clinical study
of novel Sec61 inhibitors by searching for expression profiles of
sensitive cell lines in tumor sample databases Presenter/s:
Eric Lowe, R. Andrea Fan, Henry W. B. Johnson, Christopher J. Kirk,
Dustin McMinn, Yu Qian, Brian Tuch Session: Genomic
Profiling of Tumors – Abstract #2226 Date and time:
Available on demand [8:30AM ET, Saturday, April 10, 2021]
Title: Quantitative proteomic profiling of novel
anti-cancer small molecule inhibitors of Sec61: Mechanistic
investigation and biomarker discovery Presenter/s: Yu Qian,
Jennifer Whang, Janet Anderl, Andrea Fan, Henry W. B. Johnson,
Christopher J. Kirk, Eric Lowe, Dustin McMinn, Beatriz Millare,
Tony Muchamuel and Jinhai Wang; Kezar Life Sciences Session:
Proteomics and Biomarker Discovery – Abstract #2816 Date and
time: Available on demand [8:30AM ET, Saturday, April 10,
2021]
The posters are available in the “Our Science” section of
kezarlifesciences.com.
About KZR-261
KZR-261, a novel, first-in-class protein secretion inhibitor, is
the first clinical candidate to be nominated from Kezar’s research
and discovery efforts targeting protein secretion pathways. KZR-261
is a broad-spectrum anti-tumor agent that acts through direct
interaction and inhibition of Sec61 activity. The compound was
discovered by Kezar through a robust medicinal chemistry campaign
in which several scaffolds were progressed through the company’s
proprietary platform evaluating Sec61 modulation. As a result,
Kezar has established a broad library of protein secretion
inhibitors. KZR-261 has demonstrated several encouraging properties
that lead to its potential to be an anti-cancer agent for the
treatment of solid and hematologic malignancies. An IND submission
in solid tumors is expected to be filed in mid-2021.
About Kezar Life Sciences
Kezar Life Sciences is a clinical-stage biopharmaceutical
company bringing novel treatments to patients with rare autoimmune
diseases and cancer. The company is pioneering first-in-class,
small-molecule therapies that harness master regulators of cellular
function to inhibit multiple drivers of disease via single,
powerful targets. KZR-616, its lead development candidate, is a
selective immunoproteasome inhibitor being evaluated in Phase 2
clinical trials in lupus nephritis, dermatomyositis and
polymyositis. Additionally, an IND is planned in mid-2021 for
KZR-261, the first anti-cancer clinical candidate from the
company’s platform targeting the Sec61 translocon and the protein
secretion pathway. For more information, visit
kezarlifesciences.com.
Cautionary Note on Forward-looking Statements
This press release contains forward-looking statements within
the meaning of the Private Securities Litigation Reform Act of
1995. Words such as “may,” “will,” “should,” “could,” “expect,”
“believe” and similar expressions (as well as other words or
expressions referencing future events, conditions or circumstances)
are intended to identify forward-looking statements. These
forward-looking statements are based on Kezar’s expectations and
assumptions as of the date of this press release. Each of these
forward-looking statements involves risks and uncertainties that
could cause Kezar’s clinical development programs, future results
or performance to differ materially from those expressed or implied
by the forward-looking statements. Forward-looking statements
contained in this press release include, but are not limited to,
statements about the design, progress, timing, scope and results of
clinical trials, plans for initiating future clinical trials, the
likelihood data will support future development, the association of
data with treatment outcomes, and the discovery and development of
new product candidates. Many factors may cause differences between
current expectations and actual results, including the impacts of
the COVID-19 pandemic on the company’s business, clinical trials
and financial position, unexpected safety or efficacy data observed
during preclinical or clinical studies, changes in expected or
existing competition, changes in the regulatory environment, the
uncertainties and timing of the regulatory approval process, and
unexpected litigation or other disputes. Other factors that may
cause actual results to differ from those expressed or implied in
the forward-looking statements in this press release are discussed
in Kezar’s filings with the U.S. Securities and Exchange
Commission, including the “Risk Factors” contained therein. Except
as required by law, Kezar assumes no obligation to update any
forward-looking statements contained herein to reflect any change
in expectations, even as new information becomes available.
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version on businesswire.com: https://www.businesswire.com/news/home/20210410005029/en/
Celia Economides SVP, Strategy & External Affairs
ceconomides@kezarbio.com
Argot Partners (212)-600-1902 kezar@argotpartners.com
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