ArQule Presents Clinical & Preclinical Data for ARQ 751 at the 30th EORTC/AACR/NCI Symposium

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Three poster presentations demonstrate ARQ 751’s potential as both a
monotherapy and in combination with other anti-cancer agents
BURLINGTON, Mass.–(BUSINESS WIRE)–Nov. 16, 2018–
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

All posters presented by ArQule at the EORTC/AACR/NCI Symposium are
available on the company’s website at

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.

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Source: ArQule, Inc.
Corporate Contact:Marc Schegerin, M.D.Senior Vice
PresidentHead of Strategy, Finance and
Media Contact:Allison Blum, Ph.D.LifeSci Public
Relations (646)

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2018-11-17 05:42:50