Nurix Presents the Discovery and Chemical Structure of First-in-Class CBL-B Inhibitor NX-1607 at the American Chemical Society (ACS) Meeting
20 Março 2024 - 10:40AM
Nurix Therapeutics, Inc. (Nasdaq: NRIX), a clinical stage
biopharmaceutical company developing targeted protein modulation
drugs designed to treat patients with cancer and inflammatory
diseases, today disclosed the discovery and structure of NX-1607 in
the First Time Disclosures session at the American Chemical Society
Spring 2024 meeting in New Orleans, LA. This is the first inhibitor
of CBL-B to advance into clinical studies and a prime example of
Nurix’s ability to target previously undruggable E3 ligases.
“Today’s presentation at the ACS meeting showcases Nurix’s
innovative combination of structure-based-drug-design and
industry-leading expertise in the biochemistry of E3 ligases,”
noted Gwenn Hansen, Ph.D., Nurix’s chief scientific officer. “Our
unique approach to drug discovery enables us to design novel drugs
that either inhibit E3 ligases, such as NX-1607, or harness E3
ligases for targeted protein degradation.”
In an oral presentation at the American Chemical Society Spring
meeting entitled NX-1607: a First-In-Class Inhibitor of Casitas
B-lineage Lymphoma B (CBL-B) for Immuno-Oncology, Nurix disclosed
the structure of NX-1607 and its discovery history. NX-1607 acts as
a specific intramolecular glue of the CBL-B protein, locking it in
a closed and inactive conformation that lowers the threshold for
T-cell activation. This mechanism of action is notable because
CBL-B lacks a classic enzymatic active site binding pocket,
preventing typical inhibitor design and thereby requiring a novel
drug discovery approach. A copy of the presentation is available on
the Posters and Presentations section of the scientific resources
page of Nurix’s website.
Nurix is testing NX-1607 in an ongoing, first-in-human,
multicenter, open-label, Phase 1a/1b dose-escalation/expansion
trial to evaluate the safety, tolerability,
pharmacokinetics/pharmacodynamics (PK/PD), and preliminary
anti-tumor activity of NX-1607 in patients with advanced
malignancies, including solid tumors and lymphoma. The trial
includes both a monotherapy and a combination cohort utilizing
paclitaxel. In 2024, Nurix expects to present data from the Phase
1a dose-escalation portion of the trial of NX-1607 and to define
dose(s) to enable Phase 1b cohort expansion. Additional information
on the clinical trial can be accessed at www.clinicaltrials.gov
(NCT05107674).
About CBL-BCBL-B is an E3 ubiquitin ligase
expressed in immune cells that regulates T-cell activation. CBL-B
inhibition reduces T-cell exhaustion and increases cytokine
production upon T cell receptor stimulation, overcoming suppressive
signals in the tumor microenvironment. Furthermore, lack of CBL-B
allows T-cell activation despite low target antigen expression on
tumor cells, potentially reversing the tumor escape mechanism of
resistance. Nurix is pursuing inhibition of CBL-B as a means to
increase anti-tumor immune responses and potentially improve
outcomes in patients with solid tumors and hematologic
malignancies.
About Nurix Therapeutics, Inc.Nurix
Therapeutics is a clinical stage biopharmaceutical company focused
on the discovery, development and commercialization of innovative
small molecules and antibody therapies based on the modulation of
cellular protein levels as a novel treatment approach for cancer,
inflammatory conditions, and other challenging diseases. Leveraging
extensive expertise in E3 ligases together with proprietary
DNA-encoded libraries, Nurix has built DELigase, an integrated
discovery platform, to identify and advance novel drug candidates
targeting E3 ligases, a broad class of enzymes that can modulate
proteins within the cell. Nurix’s drug discovery approach is to
either harness or inhibit the natural function of E3 ligases within
the ubiquitin-proteasome system to selectively decrease or increase
cellular protein levels. Nurix’s wholly owned, clinical stage
pipeline includes targeted protein degraders of Bruton’s tyrosine
kinase, a B-cell signaling protein, and inhibitors of Casitas
B-lineage lymphoma proto-oncogene B, an E3 ligase that regulates
activation of multiple immune cell types including T cell and NK
cells. Nurix is headquartered in San Francisco, California. For
additional information visit http://www.nurixtx.com.
Forward-Looking StatementsThis press release
contains statements that relate to future events and expectations
and as such constitute forward-looking statements within the
meaning of the Private Securities Litigation Reform Act of 1995.
When or if used in this press release, the words “anticipate,”
“believe,” “could,” “estimate,” “expect,” “intend,” “may,”
“outlook,” “plan,” “predict,” “should,” “will,” and similar
expressions and their variants, as they relate to Nurix, may
identify forward-looking statements. All statements that reflect
Nurix’s expectations, assumptions or projections about the future,
other than statements of historical fact, are forward-looking
statements, including, without limitation, statements regarding:
Nurix’s plans and expectations for its drug candidates, including
its plans to present data from the Phase 1a dose-escalation portion
of the trial of NX-1607 and its plan to define dose(s) to enable
Phase 1b cohort expansion; the extent to which Nurix’s drug
candidates, including NX-1607, may address a range of diseases; and
the potential advantages of Nurix’s scientific approach and
DELigase™ platform. Forward-looking statements reflect Nurix’s
current beliefs, expectations, and assumptions regarding the
future. Although Nurix believes the expectations and assumptions
reflected in such forward-looking statements are reasonable, Nurix
can give no assurance that they will prove to be correct.
Forward-looking statements are not guarantees of future performance
and are subject to risks, uncertainties and changes in
circumstances that are difficult to predict, which could cause
Nurix’s actual activities and results to differ materially from
those expressed in any forward-looking statement. Such risks and
uncertainties include, but are not limited to: (i) whether Nurix
will be able to successfully conduct and complete clinical
development and commercialization of any of its drug candidates,
including NX-1607; (ii) the risks inherent in the drug development
process, including the unexpected emergence of adverse events or
other undesirable side effects during clinical development; (iii)
whether Nurix will be able to fund development activities and
achieve development goals; (iv) risks and uncertainties relating to
the timing and results of clinical trials; and (v) other risks and
uncertainties described under the heading “Risk Factors” in Nurix’s
Annual Report on Form 10-K for the fiscal year ended November 30,
2023, and other SEC filings. Accordingly, readers are cautioned not
to place undue reliance on these forward-looking statements. The
statements in this press release speak only as of the date of this
press release, even if subsequently made available by Nurix on its
website or otherwise. Nurix disclaims any intention or obligation
to update publicly any forward-looking statements, whether in
response to new information, future events, or otherwise, except as
required by applicable law.
Contacts:
InvestorsJason Kantor, Ph.D.Nurix
Therapeuticsir@nurixtx.com
Elizabeth Wolffe, Ph.D.Wheelhouse Life Science
Advisorslwolffe@wheelhouselsa.com
MediaAljanae ReynoldsWheelhouse Life Science
Advisorsareynolds@wheelhouselsa.com
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