ArQule Announces Preclinical Data Demonstrating Potential of Miransertib (ARQ 092) to Treat PIK3CA-Driven Vascular Malformati...
October 21 2019 - 7:00AM
Business Wire
Treatment with miransertib prevents formation
of new PIK3CA-driven vascular malformations and leads to regression
of existing PIK3CA-driven vascular malformations in experimental
mouse model
ArQule, Inc. (Nasdaq: ARQL), today announced preclinical data
demonstrating the potential for miransertib (ARQ 092), it’s pan-AKT
inhibitor, to treat PIK3CA driven vascular malformations (VMs) in a
poster at the 2019 American Society of Human Genetics Annual
Meeting. Studies conducted in an experimental mouse model show that
miransertib prevents the formation of PIK3CA-driven VMs and shows
high efficacy in regressing vascular growth in already developed
VMs.
“We are encouraged by these data generated by our collaborators
at the Vascular Signaling Laboratory in Barcelona, as they further
strengthen the therapeutic profile of miransertib in treating
conditions characterized by overactive PIK3CA signaling,” said Dr.
Brian Schwartz, Chief Medical Officer of ArQule. “We are looking
forward to continuing to examine the potential of miransertib to
help patients with mutations in the PIK3CA/AKT pathway while at the
same time focusing on enrolling our registrational MOSAIC
(Miransertib in Overgrowth Syndromes
in Adults and Children) trial of miransertib for the treatment
of Proteus syndrome and PIK3CA-related Overgrowth Spectrum
disorders, also known as PROS.”
The poster presented today at ASHG details findings from studies
of miransertib in an experimental mouse model that develops
PIK3CA-driven VMs resembling those found in humans. Data show that
miransertib prevents the formation of PIK3CA-driven VMs by
suppressing vascular growth and endothelial cell proliferation.
Treatment with miransertib was also found to lead to a regression
in growth of already developed VMs, as measured by a significant
reduction in retinal vascularity and endothelial cell number and
proliferation.
VMs are painful, disfiguring lesions that can be present in any
tissue and can lead to bleeding and obstruction of organs. The
condition has an overall incidence of 1 in 5000, and no approved
pharmacological options currently exist. Most VMs are caused by
mutations in the PIK3CA or TEK gene, both of which lead to
increased PIK3CA signaling through the PI3K/AKT pathway.
Miransertib works by inhibiting AKT, thereby reducing the abnormal
cell growth which results from increased PIK3CA signaling.
A copy of poster can be accessed by visiting the Publications
& Presentations section of the ArQule website.
About MOSAIC
The MOSAIC (Miransertib in
Overgrowth Syndromes in Adults
and Children) trial is an
international, multi-center, open-label study that will evaluate
the objective response to miransertib in patients with Proteus
syndrome (PS) and PIK3CA-related Overgrowth Spectrum disorders
(PROS). The study will enroll approximately 30-35 patients with
documented somatic mutations in the AKT1 or PIK3CA genes in the
registrational cohorts for PS and PROS. Thirty to 35 additional
patients will be enrolled in two other cohorts for patients under
compassionate use or those ineligible to enter the registrational
cohorts.
About Miransertib
Miransertib (ARQ 092) is an orally available, selective, pan-AKT
(protein kinase B) inhibitor that potently inhibits AKT 1, 2 and 3
isoforms and binds both the active and inactive forms of AKT which
directly inhibits and prevents membrane localization, respectively.
Dysregulation of AKT has been implicated in a variety of rare
overgrowth diseases and cancers; however, there are currently no
approved inhibitors of AKT. AKT inhibitors, either as a single
agent or in combination therapy, show significant promise in
molecularly defined patient populations. Miransertib has been
granted Rare Pediatric Disease Designation for Proteus syndrome by
the U.S. Food and Drug Administration (FDA) as well as Orphan Drug
Designation by both the FDA and European Medicines Agency. Fast
Track Designation has been granted by the FDA for PROS.
About Proteus syndrome
Proteus syndrome is an ultra-rare condition characterized by the
aberrant overgrowth of multiple tissues of the body. Patients with
Proteus syndrome experience changes in the shapes of certain body
structures over time, including abnormal, often asymmetric, massive
growth (overgrowth) of the skeleton, skin, adipose tissue and
central nervous system out of proportion to the rest of the body.
Although patients may have minimal or no manifestations at birth,
the disease develops and becomes apparent in early childhood (6-18
months) and rapidly progresses with intense growth in the first 10
years of life. The worldwide incidence is believed to be
approximately one in a million. There are currently no approved
medicinal treatments for Proteus syndrome, leaving patients with
minimal treatment options to manage the disease and a mortality of
25% by age 22.
About PROS
PROS is a term used to refer to a spectrum of rare diseases
identified by somatic mutations in the PIK3CA gene, that result in
excess growth in certain areas of the body. While the individual
diseases that fall within the overgrowth spectrum have similar
symptoms, each disease is defined by unique clinical
characteristics. The implementation of genetic sequencing has led
to the identification of the underlying genetic mutations that
drive these overgrowth disorders, allowing for the development of
medicines that target the specific causes of disease.
About ArQule
ArQule is a biopharmaceutical company engaged in the research
and development of targeted therapeutics to treat cancers and rare
diseases. ArQule’s mission is to discover, develop and
commercialize novel small molecule drugs in areas of high unmet
need that will dramatically extend and improve the lives of our
patients. Our clinical-stage pipeline consists of four drug
candidates, all of which are in targeted, biomarker-defined patient
populations, making ArQule a leader among companies our size in
precision medicine. ArQule’s pipeline includes: ARQ 531, an orally
bioavailable, potent and reversible dual inhibitor of both wild
type and C481S-mutant BTK, in phase 1/2 for patients with B-cell
malignancies refractory to other therapeutic options; miransertib
(ARQ 092), a potent and selective inhibitor of the AKT
serine/threonine kinase, in a registrational trial with cohorts in
Proteus syndrome and PROS; ARQ 751, a next generation highly potent
and selective AKT inhibitor, in phase 1 for patients with solid
tumors with AKT1 and PI3K mutations; and derazantinib, a
multi-kinase inhibitor designed to preferentially inhibit the
fibroblast growth factor receptor (FGFR) family, in a
registrational trial for iCCA in collaboration with Basilea and
Sinovant. ArQule’s current discovery efforts are focused on the
identification and development of novel kinase inhibitors,
leveraging the Company’s proprietary library of compounds.
Forward Looking Statements
This press release contains forward-looking statements,
including without limitation those regarding possibly pursuing VM
and other indications driven by mutations in the PIK3CA pathway and
the ongoing MOSAIC registrational study in Proteus syndrome and
PROS. These statements are based on the Company’s current beliefs
and expectations and are subject to risks and uncertainties that
could cause actual results to differ materially from those set
forth in this press release. Positive information about preclinical
or early stage clinical trial results does not ensure that later
stage or larger scale clinical trials will be successful. For
example, miransertib may not demonstrate adequate therapeutic
effect; in addition, it may not demonstrate an appropriate safety
profile in current or later stage or larger scale clinical trials
as a result of known or as yet unanticipated side effects. The
results achieved in current or later stage trials may not be
sufficient to meet applicable regulatory standards or to justify
further development. Problems or delays may arise prior to the
initiation of planned clinical trials, during clinical trials or in
the course of developing, testing or manufacturing that could lead
the Company to discontinue development. Even if later stage
clinical trials are successful, unexpected concerns may arise from
subsequent analysis of data or from additional data. Obstacles may
arise or issues may be identified in connection with review of
clinical data with regulatory authorities. Regulatory authorities
may disagree with the Company’s or its collaborators’ view of data
or require additional data or information or additional studies. In
addition, the planned timing of completion of clinical trials is
subject to the ability of the Company and, in certain cases, its
collaborators to enroll patients, enter into agreements with
clinical trial sites and investigators, and overcome technical
hurdles and other issues related to the conduct of the trials for
which each of them is responsible. There is a risk that these
issues may not be successfully resolved. Only a small number of
research and development programs result in the commercialization
of a product. Furthermore, the Company may not have the financial
or human resources to successfully pursue drug discovery in the
future. For more detailed information on the risks and
uncertainties associated with the Company's drug development,
financial condition and other activities, see the Company's
periodic reports filed with the Securities and Exchange Commission.
The Company does not undertake any obligation to publicly update
any forward-looking statements.
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version on businesswire.com: https://www.businesswire.com/news/home/20191021005188/en/
Corporate: Kathleen Farren Investor Relations &
Executive Assistant to the CFO ir@arqule.com
Media: Cait Williamson, Ph.D. LifeSci Public Relations
(646) 751-4366 cait@lifescipublicrelations.com
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