ArQule Announces First Patient Dosed in Company Sponsored Phase 1/2 Trial of AKT Inhibitor, ARQ 092, for Rare Overgrowth Diseases
Trial will enroll patients with Overgrowth Diseases driven by the PI3K/AKT1 pathway
The phase 1/2 trial will be open to patients ages six and older and be
conducted at sites in the
In parallel with the company sponsored phase 1/2 trial,
"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.
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
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
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
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
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