Karyopharm Publishes Preclinical Data in Nature Demonstrating Selinexor’s Potential in KRAS-Mutant Non-Small Cell Lung Canc...
September 29 2016 - 7:30AM
- Nuclear Transport Machinery Identified as a
Necessary and Universal Driver of KRAS-mutant Cell Survival
-
Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a clinical-stage
pharmaceutical company, today announced that preclinical data
describing XPO1 inhibition with selinexor (KPT-330), the Company’s
lead, oral Selective Inhibitor of Nuclear Export / SINE™ compound,
in a KRAS-mutant non-small cell lung cancer (NSCLC) model, were
published online in Nature. The paper, titled, “XPO1
Dependent Nuclear Export is a Druggable Vulnerability in
KRAS-mutant Lung Cancer,” discusses preclinical results supporting
selinexor’s potential as a new therapeutic strategy for patients
with highly aggressive and difficult to treat KRAS-mutant NSCLC.
In the manuscript, scientists from the
University of Texas Southwestern Medical Center and Karyopharm
demonstrated that KRAS-mutant NSCLC cells are addicted to Exportin
1 (XPO1) and that inhibition with selinexor induced robust cellular
apoptosis of these malignant cells, both in vitro and in vivo.
“We are honored to collaborate with Dr. Michael
White at UT Southwestern Medical Center on this important research.
The KRAS gene is known to play an important role in cell division,
differentiation and apoptosis,” said Sharon Shacham, PhD, MBA,
President and Chief Scientific Officer of Karyopharm. “This
research provides an improved understanding of the role of XPO1
nuclear transport in KRAS-mutant NSCLC and recognizes the potential
for therapeutic intervention utilizing an XPO1 inhibitor such as
selinexor in certain patient sub-types that can be identified
through genomic screening. Beyond NSCLC, these findings could
have implications in other KRAS-driven malignancies, including in
patients with KRAS mutant colorectal cancer.”
“Many of the most lethal human cancers harbor
oncogenic mutant KRAS proteins, and this observation, combined with
new detection methods to identify somatic KRAS mutant alleles in
patient samples, has led to intensive efforts to develop drugs that
inhibit KRAS activity,” said Erkan Baloglu, PhD, Senior Director,
Discovery and Early Development Program Lead at Karyopharm, and
co-author of the paper. “However, advances have been hindered
by several factors, including druggability of key pathway members
and the swift development of acquired-drug resistance to otherwise
effective targeted therapies. These data show the dependence
of KRAS-mutant NSCLC cells on XPO1-mediated nuclear export,
suggesting that XPO1 inhibition could provide a promising new
therapeutic strategy for a considerable cohort of patients with
lung cancer when coupled with genomics-guided patient selection and
observation.”
“Very importantly, this study also reveals
potential predictive markers of response to selinexor and XPO1
inhibition,” said Yosef Landesman, PhD, Senior Director, Head of
Scientific Affairs at Karyopharm and co-lead author of the
paper. “Those markers are genes from two central cellular
pathways: The NFκB pathway that controls inflammation and
tumorigenesis, along with the Hippo signaling pathway that controls
organ size, cell proliferation and apoptosis.”
As a result of this research, Karyopharm
Therapeutics is evaluating the potential for a clinical trial of
selinexor in patients with KRAS mutant NSCLC.
About Selinexor
Selinexor (KPT-330) is a first-in-class, oral
Selective Inhibitor of Nuclear Export / SINE™ compound. Selinexor
functions by binding with and inhibiting the nuclear export protein
XPO1 (also called CRM1), leading to the accumulation of tumor
suppressor proteins in the cell nucleus. This reinitiates and
amplifies their tumor suppressor function and is believed to lead
to the selective induction of apoptosis in cancer cells, while
largely sparing normal cells. To date, over 1,700 patients have
been treated with selinexor and it is currently being evaluated in
several mid- and later-phase clinical trials across multiple cancer
indications, including in multiple myeloma in combination with
low-dose dexamethasone (STORM) and backbone therapies (STOMP), and
in acute myeloid leukemia (SOPRA), diffuse large B-cell lymphoma
(SADAL), and liposarcoma (SEAL), among others. Karyopharm
plans to initiate a pivotal randomized Phase 3 study of selinexor
in combination with bortezomib (Velcade®) and low-dose
dexamethasone (BOSTON) in patients with multiple myeloma in early
2017. Additional Phase 1, Phase 2 and Phase 3
studies are ongoing or currently planned, including multiple
studies in combination with one or more approved therapies in a
variety of tumor types to further inform the Company's clinical
development priorities for selinexor. The latest clinical trial
information for selinexor is available
at www.clinicaltrials.gov.
About Karyopharm Therapeutics
Karyopharm Therapeutics Inc. (Nasdaq:KPTI) is a
clinical-stage pharmaceutical company focused on the discovery and
development of novel first-in-class drugs directed against nuclear
transport and related targets for the treatment of cancer and other
major diseases. Karyopharm's SINE™ compounds function by binding
with and inhibiting the nuclear export protein XPO1 (or CRM1).
In addition to single-agent and combination activity against
a variety of human cancers, SINE™ compounds have also shown
biological activity in models of neurodegeneration, inflammation,
autoimmune disease, certain viruses and wound-healing.
Karyopharm, which was founded by Dr. Sharon Shacham,
currently has several investigational programs in clinical or
preclinical development. For more information, please visit
www.karyopharm.com.
Forward-Looking Statements
This press release contains forward-looking
statements within the meaning of The Private Securities Litigation
Reform Act of 1995. Such forward-looking statements include those
regarding the therapeutic potential of and potential clinical
development plans for Karyopharm's drug candidates, including the
timing of initiation of certain trials and of the reporting of data
from such trials. Such statements are subject to numerous important
factors, risks and uncertainties that may cause actual events or
results to differ materially from the Company's current
expectations. For example, there can be no guarantee that any of
Karyopharm's SINE™ compounds, including selinexor (KPT-330), will
successfully complete necessary preclinical and clinical
development phases or that development of any of Karyopharm's drug
candidates will continue. Further, there can be no guarantee that
any positive developments in Karyopharm's drug candidate portfolio
will result in stock price appreciation. Management's expectations
and, therefore, any forward-looking statements in this press
release could also be affected by risks and uncertainties relating
to a number of other factors, including the following: Karyopharm's
results of clinical trials and preclinical studies, including
subsequent analysis of existing data and new data received from
ongoing and future studies; the content and timing of decisions
made by the U.S. Food and Drug Administration and other regulatory
authorities, investigational review boards at clinical trial sites
and publication review bodies, including with respect to the need
for additional clinical studies; Karyopharm's ability to obtain and
maintain requisite regulatory approvals and to enroll patients in
its clinical trials; unplanned cash requirements and expenditures;
development of drug candidates by Karyopharm's competitors for
diseases in which Karyopharm is currently developing its drug
candidates; and Karyopharm's ability to obtain, maintain and
enforce patent and other intellectual property protection for any
drug candidates it is developing. These and other risks are
described under the caption "Risk Factors" in Karyopharm's
Quarterly Report on Form 10-Q for the quarter ended June 30, 2016,
which was filed with the Securities and Exchange Commission (SEC)
on August 4, 2016, and in other filings that Karyopharm may make
with the SEC in the future. Any forward-looking statements
contained in this press release speak only as of the date hereof,
and Karyopharm expressly disclaims any obligation to update any
forward-looking statements, whether as a result of new information,
future events or otherwise.
Velcade® is a registered trademark of Takeda
Pharmaceutical Company Limited
Contact:
Justin Renz
(617) 658-0574
jrenz@karyopharm.com
Gina Nugent
(617) 460-3579
nugentcomm@aol.com
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