BioLineRx (NASDAQ: BLRX)(TASE: BLRX), a clinical-stage biopharmaceutical
company dedicated to identifying, in-licensing and developing promising
therapeutic candidates, announced today that Prof. Arnon Nagler,
Director of the Hematology Division and Bone Marrow Transplantation
Center at Sheba Medical Center, Israel, has received final regulatory
approval to evaluate BioLineRx’s BL-8040 as a treatment for chronic
myeloid leukemia (CML) in a Phase 1/2 clinical study. BioLineRx is
currently developing BL-8040 in a Phase 2 study for treating acute
myeloid leukemia (AML), and in a Phase 1 study for stem cell
mobilization, as a pre-treatment for stem cell transplantation. The
Company has received orphan drug designation for both these indications.
Dr. Kinneret Savitsky, Chief Executive Officer of BioLineRx, stated, "We
are extremely pleased that our promising and versatile therapeutic
candidate is ready to commence a Phase 1/2 clinical trial for a third
indication, namely CML. Prof. Nagler’s decision to pursue BL-8040 for
CML in an independent clinical study is a testament to the potential he
sees in our molecule for treating hematologic cancers. Each of these
indications stands to benefit from the two main characteristics of
BL-8040 - its ability to mobilize cells from the bone marrow into the
peripheral blood system, and its ability to induce cancer cell death
directly."
CML is a cancer of white blood cells that is driven by a constitutively
active oncogenic tyrosine kinase. The main treatment today is with
tyrosine kinase inhibitors, such as Imatinib (Gleevec), but about 15% of
patients do not have an optimal response to the drug, and 40% eventually
develop resistance to the drug. In addition, treatment with Gleevec does
not always prevent recurrence of the disease, presumably due to the
survival of dormant, tumorigenic stem cells in the bone marrow.
The study is designed as a Phase 1/2, randomized, dose-escalation study
to assess the combination of BL-8040 with standard-of-care Imatinib for
improving the response of CML patients in the first chronic phase of the
disease who have achieved a less than optimal response with Imatinib
alone. Primary endpoints of the study are the safety and tolerability of
BL-8040 in combination with Imatinib, and the secondary endpoints
include assessing the efficacy of the combination therapy in achieving
improved cytogenetic and molecular response in CML patients. The study
will be performed at the Sheba Medical Center, and will include up to 40
patients.
“The bone marrow has a protective effect on CML stem cells, and enables
them to evade eradication by existing drugs. Preclinical data have shown
that BL-8040 efficiently synergizes with Imatinib in-vitro1
and in-vivo, overcoming the protective effect of the bone marrow,
and we therefore hope that the combination of these two drugs will
override drug resistance and suppress residual disease," stated Prof.
Nagler. "It is conceivable that adding BL-8040 to Imatinib therapy in
CML patients who have not achieved optimal cytogenetic or molecular
responses may improve their response to Imatinib by directly inducing
apoptosis of the tumor cells and by mobilizing leukemic stem cells from
the bone marrow’s protective niches and sensitizing them to
Imatinib-induced cell death.”
About BL-8040
BL-8040 is a clinical-stage drug candidate for
the treatment of acute myeloid leukemia, as well as other hematological
indications. It is a short peptide that functions as a high-affinity
antagonist for CXCR4, a chemokine receptor that is directly involved in
tumor progression, angiogenesis (growth of new blood vessels in the
tumor), metastasis (spread of the disease to other organs or organ
parts) and cell survival. CXCR4 is over-expressed in more than 70% of
human cancers and its expression often correlates with disease severity.
BL-8040 mobilizes cancer cells from the bone marrow and may therefore
sensitize these cells to chemo- and bio-based anti-cancer therapy.
Importantly, BL-8040 has also demonstrated a direct anti-cancer effect
by inducing apoptosis (cell death). Pre-clinical studies show that
BL-8040 is efficient, both alone and in combination with anti-cancer
drugs such as Rituximab, Imatinib and Bortezomib in lymphoma, CML and
multiple myeloma models (respectively).
BL-8040 also mobilizes stem cells from the bone marrow to the peripheral
blood, enabling their collection for subsequent autologous or allogeneic
transplantation in cancer patients. In a Phase 1/2, open-label, dose
escalation, safety and efficacy clinical trial in 18 multiple myeloma
patients, BL-8040 demonstrated an excellent safety profile at all doses
tested and was highly effective in combination with G-CSF in the
mobilization of hematopoietic stem cells and white blood cells from the
bone marrow to the peripheral blood. BL-8040 was licensed by BioLineRx
from Biokine Therapeutics and was previously developed under the name
BKT-140.
About CML
Chronic myeloid leukemia (CML) is a cancer of
white blood cells that is driven by a constitutively active oncogenic
tyrosine kinase. Tyrosine kinase inhibitors, such as Imatinib (Gleevec),
revolutionized the treatment of CML and remain a major therapeutic
strategy for CML patients. However, dormant leukemic stem cells that are
resistant to tyrosine kinase inhibitors and may be responsible for CML
resistance and recurrence, are protected from therapy-induced cell death
by the bone marrow microenvironment and in particular, by bone marrow
stromal cells. Therefore, novel drugs are needed that can target
leukemic stem cells in the bone marrow.
About BioLineRx
BioLineRx is a publicly-traded,
clinical-stage biopharmaceutical company dedicated to identifying,
in-licensing and developing promising therapeutic candidates. The
Company in-licenses novel compounds primarily from academic institutions
and biotech companies based in Israel, develops them through
pre-clinical and/or clinical stages, and then partners with
pharmaceutical companies for advanced clinical development and/or
commercialization.
BioLineRx’s current portfolio consists of a variety of clinical and
pre-clinical projects, including: BL-1040 for prevention of pathological
cardiac remodeling following a myocardial infarction, which has been
out-licensed to Bellerophon BCM (f/k/a Ikaria) and is in the midst of a
pivotal CE-Mark registration trial; BL-8040 for treating acute myeloid
leukemia (AML) and other hematological indications, which is in the
midst of a Phase 2 study; BL-7010 for celiac disease, which is in the
midst of a Phase 1/2 study; and BL-5010 for non-surgical removal of skin
lesions, which is expected to commence a pivotal CE-mark registration
trial in the first half of 2014.
For more information on BioLineRx, please visit www.biolinerx.com
or download the investor relations mobile device app, which allows users
access to the Company’s ‘SEC documents, press releases, and events.
BioLineRx’s’ IR app is available on the iTunes App Store as well as the
Google Play Store.
Various statements in this release concerning BioLineRx’s future
expectations, including specifically those related to the development
and commercialization of BL-8040, constitute “forward-looking
statements” within the meaning of the Private Securities Litigation
Reform Act of 1995. These statements include words such as “may,”
“expects,” “anticipates,” “believes,” and “intends,” and describe
opinions about future events. These forward-looking statements involve
known and unknown risks and uncertainties that may cause the actual
results, performance or achievements of BioLineRx to be materially
different from any future results, performance or achievements expressed
or implied by such forward-looking statements. Some of these risks are:
changes in relationships with collaborators; the impact of competitive
products and technological changes; risks relating to the development of
new products; and the ability to implement technological improvements.
These and other factors are more fully discussed in the “Risk Factors”
section of BioLineRx’s most recent annual report on Form 20-F filed with
the Securities and Exchange Commission on March 17, 2014. In addition,
any forward-looking statements represent BioLineRx’s views only as of
the date of this release and should not be relied upon as representing
its views as of any subsequent date. BioLineRx does not assume any
obligation to update any forward-looking statements unless required by
law.
1 Combination
of Imatinib with CXCR4 antagonist BKT140 overcomes the protective effect
of stroma and targets CML in vitro and in vivo.
Beider K,
Darash-Yahana M, Blaier O, Koren-Michowitz M, Abraham M, Wald H, Wald O,
Galun E, Eizenberg O, Peled A, Nagler A.
Mol Cancer Ther. 2014 Feb
6. [Epub ahead of print]
Copyright Business Wire 2014