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 announced the publication of a manuscript in the
journal Science titled: “Kinase Impaired BTK Mutations Are
Susceptible to Clinical Stage BTK and IKZF1/3 Degrader NX-2127”
that elucidates a previously unappreciated oncogenic scaffold
function of BTK responsible for clinical resistance to enzymatic
inhibitors and shows that NX-2127, a potent targeted protein
degrader with differentiated activity against BTK and IKZF1/3, can
overcome this resistance across a broad range of acquired
mutations.
“While BTK inhibitors have positively changed clinical outcomes
for patients with B-cell malignancies, the emergence of acquired
resistance to these medicines is a growing clinical problem,” said
Alexey Danilov, M.D., Ph.D. Professor and Co-Director, Toni
Stephenson Lymphoma Center, City of Hope National Medical Center.
“Identification of the different types of mutations has important
implications for the therapeutic sequencing of currently used
targeted BTK inhibitors and reinforces the need for the development
of novel agents, such as Nurix’s NX-2127 and NX-5948, that have the
potential to provide improved mutation-agnostic treatment options
for patients.”
The article describes studies designed to investigate and
characterize acquired BTK mutations that confer resistance to BTK
inhibitors commonly used in the treatment of B-cell malignancies.
The research identified a new class of kinase impaired mutants that
render BTK enzymatically inactive and revealed that these mutations
create novel protein-protein interactions that can propagate
biochemical signaling through a process known as scaffolding, a
nonenzymatic function of the BTK protein that sustains B-cell
receptor (BCR) signaling and promotes the growth of malignant
B-cells. Importantly, the authors report data demonstrating
efficient proteasomal degradation of BTK in the blood of all
NX-2127-treated patients with chronic lymphocytic leukemia (CLL),
resulting in reduction of BTK enzymatic activity and suppression of
BCR signaling regardless of mutational status. The work was carried
out by Nurix in collaboration with scientists and clinicians at
several prominent cancer research centers, including Sylvester
Comprehensive Cancer Center at the University of Miami Miller
School of Medicine and the Sloan Kettering Institute at Memorial
Sloan Kettering Cancer Center.
A Drug Annotation manuscript published contemporaneously in The
Journal of Medicinal Chemistry entitled “Discovery and Preclinical
Pharmacology of NX-2127, an Orally Bioavailable Degrader of
Bruton’s Tyrosine Kinase with Immunomodulatory Activity for the
Treatment of Patients with B Cell Malignancies” reports data
detailing the discovery and optimization of NX-2127, including
characterization of NX-2127’s activity in preclinical tumor models,
cross-species pharmacokinetics and in vitro safety which supported
the advancement of this molecule into clinical testing.
“These publications represent the first compendium of
biochemical, cellular, and clinical evidence that NX-2127 degrades
both previously described and newly discovered BTK inhibitor
resistance mutations, a novel mechanism of action in the treatment
of B-cell malignancies that is associated with meaningful clinical
responses,” said Gwenn M. Hansen, Ph.D., chief scientific officer
of Nurix. “The data described in this publication in Science
reinforce the broad utility of the targeted protein degradation
mechanism compared to inhibition approaches to more completely
block BTK function and potentially other important enzymatic
disease targets where development of acquired resistance is an
issue.”
“The first-in-human trial of NX-2127 is ongoing in patients with
relapsed and refractory B-cell malignancies, including CLL. Based
on our clinic data, which were recently presented at the 2023 ASH
Annual Meeting, we have also initiated expansion cohorts in
patients with diffuse large B cell lymphoma (DLBCL) and mantle cell
lymphoma (MCL),” said Paula O’Connor, M.D., senior vice president
of clinical development at Nurix. “With the ability to target BTK
inhibitor resistance mutations and achieve clinical responses, we
believe that BTK degraders have the potential to become the next
dominant class of agents in the significant BTK-targeted therapy
field. We look forward to presenting additional clinical data from
this program, and from our NX-5948 BTK degrader program, which is
also being evaluated in patients with CLL, at future medical
meetings.”
About NX-2127NX-2127 is a novel bifunctional,
orally bioavailable, investigational new drug that degrades BTK and
cereblon neosubstrates Ikaros (IKZF1) and Aiolos (IKZF3). NX-2127
is currently being evaluated in a Phase 1 clinical trial in
patients with relapsed or refractory B cell malignancies.
Additional information on the ongoing clinical trial can be
accessed at www.clinicaltrials.gov (NCT04830137).
About NX-5948NX-5948 is an investigational,
orally bioavailable, small molecule degrader of BTK that, unlike
NX-2127, has been designed to lack cereblon immunomodulatory
activity. NX-5948 is currently being evaluated in a Phase 1
clinical trial in patients with relapsed or refractory B cell
malignancies. Additional information on the ongoing clinical trial
can be accessed at clinicaltrials.gov (NCT05131022).
About Nurix Therapeutics, Inc.Nurix
Therapeutics is a clinical stage biopharmaceutical company focused
on the discovery, development and commercialization of innovative
medicines 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 Statements
This 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 strategies for NX-2127 and
NX-5948; the therapeutic potential and other advantages of Nurix’s
BTK degraders, including the potential of NX-2127 and NX-5948 to
address a range of acquired mutations; the planned timing for the
provision of updates and findings from the NX-2127 and NX-5948
clinical trials; and the extent to which targeted protein
degradation may potentially address a broad range of diseases.
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 clinical trials for its drug candidates and
receive results on its expected timelines, or, at all;
(ii) the unexpected emergence of adverse events or other
undesirable side effects during clinical development; (iii) whether
Nurix will be able to successfully complete clinical development
for its drug candidates (iv) whether regulatory authorities will be
satisfied with the results from Nurix’s clinical studies; (v)
whether Nurix will be able to obtain regulatory approval of and
ultimately commercialize its drug candidates; (vi) whether Nurix
will be able to fund development activities and achieve development
goals; (vii) the impact of macroeconomic conditions and global
events on Nurix’s clinical trials and operations; and (vii) other
risks and uncertainties described under the heading “Risk Factors”
in Nurix’s Quarterly Report on Form 10-Q for the fiscal quarter
ended August 31, 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:
InvestorsSilinda NeouNurix
Therapeuticsir@nurixtx.com
Elizabeth Wolffe, Ph.D.Wheelhouse Life Science
Advisorslwolffe@wheelhouselsa.com
MediaAljanae ReynoldsWheelhouse Life Science
Advisorsareynolds@wheelhouselsa.com
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