Basilea Announces Collaboration to Study Derazantinib & Atezolizumab (Tecentriq®) in Urothelial Cancer

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BURLINGTON, Mass.–(BUSINESS WIRE)–Jan. 24, 2019–
ArQule, Inc.’s (Nasdaq: ARQL) partner, Basilea Pharmaceutica Ltd. (SIX:
BSLN), announced today that it entered into a collaboration with Roche
(SIX: RO, ROG) to explore a combination of derazantinib (BAL087) and
Roche’s PD-L1-blocking immune-checkpoint inhibitor, atezolizumab
(Tecentriq®), in patients with urothelial cancer. Basilea
expects to start a biomarker-driven multi-cohort phase 1/2 study in
mid-2019.

The planned study will assess the safety, tolerability and efficacy of
the derazantinib-atezolizumab combination in patients with advanced
urothelial cancer and confirmed FGFR genomic aberrations. Basilea will
be the sponsor of the study, and Roche will provide clinical supply of
atezolizumab.

http://www.basilea.com/Investor-Relations/News-and-Media/
Peter Lawrence, President and Chief Operating Officer of ArQule, said,
“This new combination trial with Tecentriq represents an important step
in the development of derazantinib (BAL087, formerly ARQ087) and has the
potential to expand meaningfully its therapeutic utility. We look
forward to further progress and updates from Basilea.”

Derazantinib was licensed to Basilea Pharmaceutica in April 2018 in the
US, EU, Japan and the rest of world excluding Greater China. Under the
terms of the license agreement, ArQule is eligible to receive up to $326
million in regulatory and commercial milestone payments.

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.

About derazantinibDerazantinib (BAL087, formerly ARQ 087)
is an investigational orally administered small molecule inhibitor of
the FGFR family of kinases with strong activity against FGFR1, 2, and 3.
Therefore, it is called a panFGFR kinase inhibitor. FGFR kinases are key
drivers of cell proliferation, differentiation and migration. FGFR
alterations, e.g. gene fusions, overexpression or mutations, have been
identified as potentially important therapeutic targets for various
cancers, including intrahepatic cholangiocarcinoma (iCCA), urothelial
(bladder), breast, gastric and lung cancers.1 Current
scientific literature suggests that FGFR alterations exist in a range of
5% to 30% in these cancers.2 In addition, derazantinib
inhibits the colony-stimulating-factor-1-receptor kinase (CSF1R).
CSF1R-mediated signaling is important for the maintenance of
tumor-promoting macrophages and therefore has been identified as a
potential target for anti-cancer drugs.3 Moreover,
pre-clinical data has shown that tumor macrophage depletion through
CSF1R blockade renders tumors more responsive to T-cell checkpoint
immunotherapy, including approaches targeting PD-L1/PD-1.3, 4, 5
Basilea in-licensed derazantinib from ArQule Inc. in April 2018. The
drug candidate has demonstrated favorable clinical data in previous
clinical studies, including a biomarker-driven Phase 1/2 study in iCCA
patients.6 Derazantinib has U.S. and EU orphan drug
designation for this disease.

About urothelial cancerUrothelial cancer is the sixth most
common cancer in the U.S. These cancers start in the urothelial cells
that line the inside of the bladder. 80,000 new cases of bladder cancer
have been estimated in the U.S. for 2017. Up to 20 percent of patients
will have muscle-invasive disease and present with or will later develop
metastases.7 For patients with metastatic disease, outcomes
can be poor due to the often rapid progression of the tumor and the lack
of efficacious treatments, especially in relapsed or refractory disease.

About BasileaBasilea Pharmaceutica Ltd. is a commercial
stage biopharmaceutical company, focused on the development of products
that address the medical challenges in the therapeutic areas of oncology
and anti-infectives. With two commercialized drugs, the company is
committed to discovering, developing and commercializing innovative
pharmaceutical products to meet the medical needs of patients with
serious and life-threatening conditions. Basilea Pharmaceutica Ltd. is
headquartered in Basel, Switzerland and listed on the SIX Swiss Exchange
(SIX: BSLN). Additional information can be found at Basilea’s website www.basilea.com.

Forward Looking StatementsThis press release contains
forward-looking statements regarding clinical trials with derazantinib
as well as the potential for future milestone and royalty payments under
the Company’s exclusive license agreement with Basilea. 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 does not ensure that later stage or larger
scale clinical trials will be successful. For example, derazantinib may
not demonstrate promising therapeutic effect. In addition, derazantinib
may not demonstrate an acceptable 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
derazantinib that could lead the Company or Basilea to discontinue its
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 Basilea’s view
of the data or require additional data or information or additional
studies. In addition, we or Basilea plan to develop and use a companion
diagnostic to identify patients with FGFR2 fusions and possibly other
fusions for our future derazantinib clinical trials. We or Basilea
intend to outsource the development of such companion diagnostics to one
or more third party collaborators. Such collaborators may encounter
difficulties in developing and obtaining approval for such companion
diagnostics, including issues relating to selectivity/specificity,
analytical validation, reproducibility, concordance or clinical
validation. Any delay or failure to develop or obtain regulatory
approval of such companion diagnostics could delay or prevent approval
of derazantinib.Moreover, Basilea has only a limited track
record of drug development in oncology. If derazantinib is not
successfully developed and as a result of any of the foregoing or other
issues, risks or uncertainties, ArQule may not receive any future
milestones or royalties under the license agreement with Basilea.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.

References

1

 

R. Porta, R. Borea, A. Coelho et al. FGFR a promising druggable
target in cancer: Molecular biology and new drugs. Critical Reviews
in Oncology/Hematology 2017 (113), 256-267

2

T. Helsten, S. Elkin, E. Arthur et al. The FGFR landscape in cancer:
Analysis of 4,853 tumors by next-generation sequencing. Clinical
Cancer Research 2016 (22), 259-267

3

M. A. Cannarile, M. Weisser, W. Jacob et al. Colony-stimulating
factor 1 receptor (CSF1R) inhibitors in cancer therapy. Journal for
ImmunoTherapy of Cancer 2017, 5:53

4

Y. Zhu, B. L. Knolhoff, M. A. Meyer et al. CSF1/CSF1R Blockade
reprograms tumor-infiltrating macrophages and improves response to T
cell checkpoint immunotherapy in pancreatic cancer models. Cancer
Research 2014 (74), 5057-5069

5

E. Peranzoni, J. Lemoine, L. Vimeux et al. Macrophages impede CD8 T
cells from reaching tumor cells and limit the efficacy of anti–PD-1
treatment. Proceedings of the National Academy of Science of the
United States of America 2018 (115), E-4041-E4050

6

V. Mazzaferro, B. F. El-Rayes, M. Droz dit Busset et al.
Derazantinib (ARQ 087) in advanced or inoperable FGFR2 gene
fusion-positive intrahepatic cholangiocarcinoma. British Journal
of Cancer. Published online on November 13, 2018. https://doi.org/10.1038/s41416-018-0334-05

7

B. Dietrich, S. Srinivas. Urothelial carcinoma: the evolving
landscape of immunotherapy for patients with advanced disease.
Research and reports in urology 2018 (10), 7-16

View source version on businesswire.com: https://www.businesswire.com/news/home/20190124005082/en/
Source: ArQule, Inc.
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.com
www.ArQule.com

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