ArQule Announces Preclinical Data Demonstrating Potential of Miransertib (ARQ 092) to Treat PIK3CA-Driven Vascular Malformations at 2019 ASHG Annual Meeting
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
“We are encouraged by these data generated by our collaborators at the
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
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.
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
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.
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.
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
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LifeSci Public Relations