Kura Oncology Identifies Farnesylated Proteins Associated with CXCL12 Expression, Potential Biomarker of Clinical Benefit fr...
April 02 2019 - 3:04PM
– Tipifarnib is a farnesyl transferase inhibitor
that downregulates CXCL12 –
Kura Oncology, Inc. (Nasdaq: KURA), a clinical-stage
biopharmaceutical company focused on the development of precision
medicines for oncology, reported new findings regarding the
mechanism of action of the Company’s lead drug candidate tipifarnib
and its potential clinical applications. These findings are being
presented today at the American Association for Cancer Research
(AACR) Annual Meeting 2019 in Atlanta. A copy of the poster is
available on Kura's website at www.kuraoncology.com.
Tipifarnib is a potent and selective farnesyl transferase
inhibitor currently in a registration-directed clinical trial in
patients with head and neck squamous cell carcinoma (HNSCC) that
carry mutations in HRAS, an exclusively farnesylated oncogene.
Tipifarnib has also been shown to downregulate production of the
chemokine CXCL12 in tumor models and cancer patients. New findings,
presented today, suggest that gene expression of the exclusively
farnesylated proteins RHOE (RND3) and PRICKLE2 is strongly
associated with CXCL12 expression in bone marrow stroma, which may
provide a mechanistic rationale for why the CXCL12 pathway is a
therapeutic target of tipifarnib and other farnesyl transferase
inhibitors.
In addition, an analysis of a subset of patients from a
previously conducted Phase 2 trial of tipifarnib in patients with
relapsed and refractory lymphomas identified pre-treatment tumor
CXCL12 expression as a potential biomarker of clinical benefit in
patients with diffuse large B-cell lymphoma (DLBCL) and mycosis
fungoides, the most common form of cutaneous T-cell lymphoma
(CTCL). This observation is consistent with similar findings from
Kura in other indications such as peripheral T-cell lymphoma
(PTCL), acute myeloid leukemia (AML) and pancreatic cancer. CXCL12
and its receptors, CXCR4 and CXCR7, have been implicated in cancer
progression and poor prognosis across a large spectrum of solid
tumor and hematologic
indications. “The
target of farnesyl transferase inhibitors has been elusive for
several decades. These findings provide key evidence supporting the
inhibition of the CXCL12 pathway as a mechanism of action mediating
the activity of tipifarnib in the clinic,” said Antonio Gualberto,
M.D., Ph.D., Head of Development and Chief Medical Officer of Kura
Oncology. “CXCL12-expressing cancers represent a major unmet
medical need, and we believe that CXCL12 pathway biomarkers could
enable registrational strategies for tipifarnib in multiple
hematologic and solid tumor indications.”
In December 2018, Kura reported activity from an ongoing Phase 2
trial of tipifarnib in patients with relapsed or refractory PTCL,
including a significant association between CXCL12 expression and
clinical benefit, as well as proof-of-concept in angioimmunoblastic
T-cell lymphoma (AITL), an aggressive form of PTCL often
characterized by high levels of CXCL12 expression. The Company
anticipates providing an update on this trial, including duration
of response data from the AITL cohort and additional data from the
CXCL12-high PTCL cohort, in mid-2019.
About Tipifarnib
Kura Oncology’s lead drug candidate, tipifarnib, is a potent and
highly selective inhibitor of farnesylation, a key cell signaling
process implicated in cancer initiation and development. Tipifarnib
was previously studied in more than 5,000 cancer patients and
showed compelling and durable anti-cancer activity in certain
patient subsets, however no molecular mechanism of action had
previously been determined that could explain its activity across a
range of diverse clinical indications, including squamous tumors
that carry mutant HRAS, as well as in lymphoid, myeloid and solid
tumors that do not carry HRAS mutations. Leveraging advances in
next-generation sequencing as well as emerging information about
cancer genetics and tumor biology, Kura is seeking to identify
those patients most likely to benefit from tipifarnib.
About Kura Oncology
Kura Oncology is a clinical-stage biopharmaceutical company
committed to realizing the promise of precision medicines for the
treatment of cancer. The Company’s pipeline consists of small
molecule drug candidates that target cancer signaling pathways
where there is a strong scientific and clinical rationale to
improve outcomes by identifying those patients most likely to
benefit from treatment. Kura’s lead drug candidate is tipifarnib, a
farnesyl transferase inhibitor, for which the Company has initiated
a registration-directed trial of tipifarnib in recurrent or
metastatic patients with HRAS mutant HNSCC. In addition, tipifarnib
is being evaluated in multiple other Phase 2 clinical trials in
solid tumor and hematologic indications. Kura’s pipeline also
includes KO-947, an ERK inhibitor, currently in a Phase 1
dose-escalation trial, and KO-539, a menin-MLL inhibitor, which is
anticipated to enter into a Phase 1 clinical trial in the second
quarter of 2019. For additional information about Kura, please
visit the Company’s website at www.kuraoncology.com.
Forward-Looking Statements
This news release contains certain forward-looking statements
that involve risks and uncertainties that could cause actual
results to be materially different from historical results or from
any future results expressed or implied by such forward-looking
statements. Such forward-looking statements include statements
regarding, among other things, the efficacy, safety and therapeutic
potential of tipifarnib, the conduct, results and timing of
clinical trials of tipifarnib, including Kura Oncology’s Phase 2
clinical trial of tipifarnib in patients with PTCL, plans regarding
future clinical trials and development and commercial activities,
the regulatory approval path for tipifarnib and expectations
regarding biomarkers related to tipifarnib. Factors that may cause
actual results to differ materially include the risk that compounds
that appeared promising in early research or clinical trials do not
demonstrate safety and/or efficacy in later preclinical studies or
clinical trials, the risk that Kura Oncology may not obtain
approval to market its product candidates, uncertainties associated
with performing clinical trials, regulatory filings and
applications, risks associated with reliance on third parties to
successfully conduct clinical trials, the risks associated with
reliance on outside financing to meet capital requirements, and
other risks associated with the process of discovering, developing
and commercializing drugs that are safe and effective for use as
human therapeutics, and in the endeavor of building a business
around such drugs. You are urged to consider statements that
include the words “may,” “will,” “would,” “could,” “should,”
“believes,” “estimates,” “projects,” “promise,” “potential,”
“expects,” “plans,” “anticipated,” “intends,” “continues,”
“designed,” “goal,” or the negative of those words or other
comparable words to be uncertain and forward-looking. For a further
list and description of the risks and uncertainties the Company
faces, please refer to the Company’s periodic and other filings
with the Securities and Exchange Commission, which are available at
www.sec.gov. Such forward-looking statements are current only as of
the date they are made, and Kura Oncology assumes no obligation to
update any forward-looking statements, whether as a result of new
information, future events or otherwise.
Contacts
Company:Pete De SpainVice President, Investor Relations
&Corporate Communications(858)
500-8803pete@kuraoncology.com
Investors:Robert H. UhlManaging DirectorWestwicke Partners,
LLC(858) 356-5932robert.uhl@westwicke.com
Media:Jason SparkManaging DirectorCanale Communications(619)
849-6005jason@canalecomm.com
Kura Oncology (NASDAQ:KURA)
Historical Stock Chart
From Mar 2024 to Apr 2024
Kura Oncology (NASDAQ:KURA)
Historical Stock Chart
From Apr 2023 to Apr 2024