Trial will enroll patients with Overgrowth
Diseases driven by the PI3K/AKT1 pathway
ArQule, Inc. (Nasdaq: ARQL) today announced that the first
patient has been dosed in a company sponsored phase 1/2 trial with
its AKT inhibitor, ARQ 092, in patients with Overgrowth Diseases
driven by genetic alterations of the PI3K/AKT1 pathway. ARQ 092 is
an orally available, selective pan-AKT inhibitor.
The phase 1/2 trial will be open to patients ages six and older
and be conducted at sites in the U.S. and E.U. The trial will
recruit patients with Overgrowth Diseases such as PROS
(PIK3CA-Related Overgrowth Spectrum), which includes orphan
diseases such as CLOVES (Congenital Lipomatous Overgrowth, Vascular
malformations, Epidermal nevi, Spinal/skeletal anomalies and/or
scoliosis) and Fibroadipose hyperplasia, as well as Proteus
syndrome.
ArQule plans to enroll six patients in a dose escalation cohort
as part of the phase 1 portion of the trial. An additional 10
patients will be enrolled in an expansion cohort as part of the
phase 2 portion of the trial. The objective of this study is to
determine a clinically meaningful endpoint to pursue in a
registrational trial. ArQule has been granted Orphan Disease
Designation in the U.S. and has applied for a Rare Pediatric
Disease Priority Review Voucher in Proteus syndrome.
In parallel with the company sponsored phase 1/2 trial, ArQule
will continue to provide ARQ 092 on a named patient basis to those
patients unable to travel to a clinical trial site due to severe
disease, as well as support the phase 1 study in Proteus syndrome
being conducted by the National Institutes of Health (NIH).
“There are a spectrum of Overgrowth Diseases that are rare, are
known to be driven by PI3K or AKT1 mutations, and have no approved
therapeutic options,” said Dr. Brian Schwartz, M.D., Head of
Research and Development and Chief Medical Officer at ArQule.
“These diseases begin showing symptoms in infancy and generally
result in patients undergoing multiple surgeries in their childhood
and sometimes into adulthood. With this trial, we are increasing
our efforts to determine an appropriate dose as well as a clinical
endpoint for a registrational clinical trial with the hope of
providing a therapeutic option for these patients.”
About the AKT Pathway and ARQ 092
ARQ 092 is an orally bioavailable, selective small molecule
inhibitor of the AKT kinase. The AKT pathway when abnormally
activated is implicated in multiple oncogenic processes such as
cell proliferation and apoptosis. This pathway has emerged as a
target of potential therapeutic relevance for compounds that
inhibit its activity, which has been linked to a variety of cancers
as well as to select non-oncology indications.
Dysregulation of AKT is also a driver of certain rare
proliferative disorders. For example, the E17K mutation of AKT1
causes Proteus syndrome, a rare non-cancerous segmental overgrowth
disorder, and the analogous PIK3CA-Related Overgrowth Spectrum
(PROS) is caused by genetic alterations in the PI3K pathway. ARQ
092 has been shown preclinically and clinically to inhibit AKT and
PI3K cell signaling and therefore may provide the potential for
much-needed treatment options for patients with these diseases.
ARQ 092, the lead compound in ArQule’s AKT program, has
completed phase 1a clinical testing and has advanced into phase 1b
expansion testing in cohorts of patients with endometrial cancer,
lymphomas and tumors harboring either AKT or PI3K mutations. A
company sponsored phase 1/2 trial is being conducted in the U.S.
and E.U. for Overgrowth Diseases, including PROS and Proteus
syndrome. ARQ 092 is also in a phase 1 trial being conducted by the
NIH for Proteus syndrome. Collaborators are exploring in
preclinical testing other indications for ARQ 092, including sickle
cell disease.
About Overgrowth Disease
Overgrowth Disease is a term used to refer to a spectrum of rare
diseases identified by somatic mutations, often of the PI3K or AKT1
pathway, 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
characteristics. Diseases that are part of the overgrowth spectrum
include PROS diseases (PIK3CA Rare Overgrowth Spectrum) and Proteus
syndrome. Each disease on its own is rare, sometimes ultra-rare,
often only impacting an estimated one in a million people
worldwide.
As an example, CLOVES (Congenital Lipomatous Overgrowth,
Vascular malformations, Epidermal nevi, Spinal/skeletal anomalies
and/or scoliosis) is a disease that is part of the PROS family of
diseases. According to the CLOVES Foundation
(www.clovesfoundation.org), CLOVES is an extremely rare progressive
overgrowth disorder, affecting approximately 200 people
worldwide. The symptoms vary from mild soft tissue tumors to
Vascular Malformations encompassing the spine or internal
organs. CLOVES is closely linked to other overgrowth disorders
like M-CM (Macrocephaly-Capillary Malformation) Syndrome,
Klippel-Trénaunay-Weber syndrome, and Proteus syndrome.
About Proteus Syndrome
According to the patient advocacy and support group, the Proteus
syndrome Foundation (http://www.proteus-syndrome.org/), the
condition was named for Proteus, the Greek god who could transform
his shape. Patients 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, which may appear normal. 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 ten years of life. It is primarily
a childhood-onset disease.
Proteus syndrome is a rare condition with an incidence of less
than one in one million people worldwide. Only a few hundred
individuals have been reported in the medical literature. At this
time, there are more than 120 documented cases worldwide, but
because not all cases are documented, it is not known how many
people have this disease. The incidence of Proteus syndrome
classifies it as a rare disorder, defined by the National
Organization of Rare Diseases (NORD) as any disease affecting fewer
than 200,000 Americans.
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 five 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 proprietary pipeline includes: ARQ
087, a multi-kinase inhibitor designed to preferentially inhibit
the fibroblast growth factor receptor (FGFR) family, in phase 2 for
iCCA and in phase 1b for multiple oncology indications; ARQ 092, a
selective inhibitor of the AKT serine/threonine kinase, in a phase
1/2 company sponsored study for Overgrowth Diseases, in a phase 1
study for ultra-rare Proteus syndrome conducted by the National
Institutes of Health (NIH), as well as in multiple oncology
indications; ARQ 751, a next generation AKT inhibitor, in phase 1
for patients with AKT1 and PI3K mutations; and ARQ 761, a
β-lapachone analog being evaluated as a promoter of NQO1-mediated
programmed cancer cell necrosis, in phase 1/2 in multiple oncology
indications in partnership with the University of Texas
Southwestern Medical Center. In addition, we have advanced ARQ 531,
an investigational, orally bioavailable, potent and reversible
inhibitor of both wild type and C481S-mutant BTK, through
toxicology testing and plan to initiate a phase 1 trial by the
third quarter of 2017. ArQule’s current discovery efforts are
focused on the identification and development of novel kinase
inhibitors, leveraging the Company’s proprietary library of
compounds. You can follow us on Twitter and LinkedIn.
Forward Looking Statements
This press release contains forward-looking statements regarding
the Company’s clinical trials with ARQ 092. 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. Positive information about pre-clinical, and
early stage clinical trial results, including in Overgrowth
Diseases, Proteus syndrome and sickle cell disease, does not ensure
that later stage or larger scale clinical trials will be
successful. For example, ARQ 092 may not demonstrate promising
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 later stage trials may not be
sufficient to meet applicable regulatory standards or to justify
further development. Problems or delays may arise during clinical
trials or in the course of developing, testing or manufacturing the
compound that could lead the Company or its partners, including the
National Institutes of Health, 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 view of the data or
require additional data or information or additional studies. Drug
development involves a high degree of risk. Only a small number of
research and development programs result in the commercialization
of a product. Furthermore, ArQule 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 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: http://www.businesswire.com/news/home/20170607005254/en/
ArQule, Inc.Dawn Schottlandt, 781-994-0300Vice President,
Investor Relations/Corp. Communicationswww.arqule.com
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