ArQule Presents Clinical and Preclinical Data for ARQ 751 at the 30th EORTC/AACR/NCI Symposium
November 16 2018 - 3:01PM
Business Wire
Three poster presentations demonstrate ARQ
751’s potential as both a monotherapy and in combination with other
anti-cancer agents
ArQule, Inc. (Nasdaq: ARQL) today announced the presentation of
clinical and preclinical data on ARQ 751 in three poster
presentations at the 30th EORTC/AACR/NCI Symposium held from
November 13 to 16, 2018 in Dublin, Ireland. The data presented
highlight clinical data from ARQ 751-101, a Phase 1 study in adult
patients with refractory and/or metastatic tumors that harbor AKT,
PI3K or PTEN genetic alterations, and preclinical data on ARQ 751
in combination with other agents.
Clinical data highlights and key conclusions include:
1. A Phase 1 Dose Escalation Study of ARQ 751 in Adult Patients
with Advanced Solid Tumors with AKT1, 2, 3 Genetic Alterations,
Activating PI3K Mutations, PTEN-null, or Other Known Actionable
PTEN Mutations
- ARQ 751 demonstrated manageable
toxicity at doses from 5 mg QD to 75 mg QD, and the recommended
Phase 2 dose was determined to be 75 mg QD
- Evidence of clinical activity was
observed with two partial responses in ER+/PR+/HER2- stage IV
breast cancer patients, one with PTEN C296fs*2 mutation, one with
PIK3CA H1047R mutation, 11 patients had stable disease
- The data support continued development
of ARQ 751 as a monotherapy or in combination with other
anti-cancer agents due to its manageable safety profile and
preliminary evidence of biological activity
“ARQ 751, as a highly specific allosteric AKT inhibitor, holds
great potential in treating patients with solid tumors harboring
mutations in the AKT/PI3K/PTEN pathways,” said Brian Schwartz,
M.D., Chief Medical Officer of ArQule. “The presented data are very
encouraging and demonstrate both preliminary signs of clinical
activity and a favorable safety profile while also determining the
recommended Phase 2 dose. At ArQule, we are committed to developing
genetically targeted cancer treatments to provide effective new
treatment options for patients, particularly those with advanced or
relapsed disease, and look forward to advancing the ARQ 751
clinical program.”
Preclinical data highlights include:
2. Combination of the AKT inhibitor ARQ 751 with Immune
Checkpoint Inhibitor and Other Therapeutic Agents
- In preclinical cellular models, ARQ 751
exerted greater anti-proliferative and biochemical effects when in
combination with multiple therapeutic agents including an ER
antagonist, aromatase inhibitor, androgen receptor antagonist and a
BTK inhibitor
- In an in vivo colon cancer animal
model, ARQ 751 in combination with an anti-PD-1 antibody exhibited
superior anti-tumor activity compared to single agents
3. Miransertib and ARQ 751 exhibit superior cell-death-inducing
properties compared to other AKT inhibitors and can overcome
resistance to other allosteric AKT inhibitors
- ArQule’s AKT inhibitors, miransertib
and ARQ 751 showed superior activity in comparison to other
allosteric and ATP-competitive AKT inhibitors currently in clinical
development
- Miransertib and ARQ 751 have the
potential to overcome some mechanisms of resistance to AKT
inhibitors
- Miransertib and ARQ 751 in combination
with ATM inhibition demonstrated synergistic effects
Dr. Shubham Pant, MD, Associate Professor in the Department of
Investigational Cancer Therapeutics at MD Anderson Cancer Center,
said “AKT inhibitors have significant potential to treat a broad
range of solid tumors in molecularly defined patient populations.
The presented data show that ARQ 751 exhibits unique properties
that differentiate it from other AKT inhibitors. It is our hope
that by combining ARQ 751 with a broad spectrum of therapeutic
agents, including hormonal agents, we could provide new
opportunities for combinatorial interventions in oncology.”
All posters presented by ArQule at the EORTC/AACR/NCI Symposium
are available on the company’s website at
https://www.arqule.com/publications-presentations/.
About ARQ 751ARQ 751 is an orally bioavailable, selective
small molecule inhibitor of the AKT serine/threonine 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.
ARQ 751 is currently in a Phase 1 study in adult patients with
refractory and/or metastatic tumors that harbor genetic alterations
along the AKT pathway.
About MiransertibMiransertib (ARQ 092) is an orally
bioavailable, selective, pan-AKT (protein kinase B) inhibitor that
potently inhibits AKT1, 2 and 3 isoforms. 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 single agent or combination therapy,
show significant promise in molecularly defined patient
populations. Miransertib is currently in a Phase 1/2
company-sponsored study for PIK3CA-Related Overgrowth Spectrum
(PROS), a Phase 1 study for ultra-rare Proteus syndrome conducted
by the National Institutes of Health (NIH/NHGRI), and a Phase 1b
study in combination with the hormonal therapy, anastrozole, in
patients with advanced endometrial cancer with AKT and PI3K
mutations. Miransertib has been granted Rare Pediatric Disease
Designation and Fast Track Designation by the U.S. Food and Drug
Administration (FDA), as well as Orphan Designation by the FDA and
European Medicines Agency in the rare overgrowth disease, Proteus
syndrome.
About ArQuleArQule 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 pipeline includes: ARQ 531, an orally
bioavailable, potent and reversible inhibitor of both wild type and
C481S-mutant BTK, in Phase 1 for patients with B-cell malignancies
refractory to other therapeutic options; Miransertib (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), and in Phase 1b in combination with the
hormonal therapy, anastrozole, in patients with advanced
endometrial cancer; ARQ 751, a next generation AKT inhibitor, in
Phase 1 for patients with AKT1 and PI3K mutations; Derazantinib, a
multi-kinase inhibitor designed to preferentially inhibit the
fibroblast growth factor receptor (FGFR) family, in a
registrational trial for iCCA; 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. 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 StatementsThis press release contains
forward-looking statements regarding the planned clinical
development of miransertib and ARQ 751, the Company’s AKT
inhibitors. 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 early clinical results does not ensure that
later-stage clinical trials will be successful. For example,
miransertib and ARQ 751 may not demonstrate sufficient therapeutic
effect in man; in addition, neither agent may not exhibit an
adequate safety profile in planned 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
miransertib 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
view of the data or require additional data or information or
additional studies. In addition, we are utilizing diagnostic tests
to identify patients in the trials with miransertib and ARQ 751 and
expect to utilize diagnostic tests in other clinical trials with
these agents. We or our collaborators may need to develop and
register these or other diagnostic tests as companion diagnostics
with the FDA. We or our collaborators may encounter
difficulties in developing and obtaining regulatory approval for
companion diagnostics, including issues relating to access to
certain technologies, selectivity/specificity, analytical
validation, reproducibility, or clinical validation. Any delay or
failure by our collaborators or us to develop or obtain regulatory
approval of companion diagnostics could delay or prevent approval
of our product candidates. Drug development involves a high
degree of risk. Only a small number of research and development
programs result in the commercialization of a product. 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.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20181116005501/en/
Corporate Contact:Marc Schegerin, M.D.Senior Vice
PresidentHead of Strategy, Finance and
Communicationir@arqule.com
Media Contact:Allison Blum, Ph.D.LifeSci Public Relations
(646) 627-8383Allison@lifescipublicrelations.comwww.ArQule.com
ArQule (NASDAQ:ARQL)
Historical Stock Chart
From Apr 2024 to May 2024
ArQule (NASDAQ:ARQL)
Historical Stock Chart
From May 2023 to May 2024