TEL AVIV, Israel, November 3, 2016 /PRNewswire/ --
BioLineRx Ltd. (NASDAQ/TASE: BLRX), a clinical-stage
biopharmaceutical company dedicated to identifying, in-licensing
and developing promising therapeutic candidates, disclosed today
positive Phase 2a correlative data, as well as detailed
mechanism-of-action data, for BL-8040, the Company's leading
oncology platform, that will be presented at the 58th American
Society of Hematology (ASH) Annual Meeting and Exhibition in
San Diego, California, taking
place December 3-6, 2016.
In a poster titled, "The Selective Anti Leukemic Effect of
BL-8040, a Peptidic CXCR4 Antagonist, is Mediated by Induction of
Leukemic Blast Mobilization, Differentiation and Apoptosis: Results
of Correlative Studies from a Ph2a Trial in Acute Myeloid
Leukemia", BioLineRx reports the final correlative results from its
Phase 2a trial in acute myeloid leukemia (AML). The trial consisted
of 45 AML patients receiving BL-8040 monotherapy on days 1-2,
followed by the same dose of BL-8040 plus chemotherapy (Cytarabine)
on days 3-7. All patients had poor-risk disease and had been
heavily pretreated, with 19% having relapsed after a short first
remission (≤12 months), 17% having 2 or more relapses, while 45%
were refractory to 1-2 induction treatments.
As previously reported, the composite complete remission rate,
including both complete remission (CR) and complete remission with
incomplete blood count recovery (CRi), was 38% in subjects
receiving BL-8040 dose ≥1.0 mg/kg (n=39). In the 1.5 mg/kg dose
selected for the expansion phase of the study (n=22), the composite
complete remission rate was 41%. These response rates are superior
to the historical response rate of approximately 20% reported for
high-risk AML patients treated with Cytarabine alone. The ongoing
follow-up of responding patients (n=19) showed median Event Free
Survival of 9.3 months (range of 4.3-12.8 months).
Results further show that BL-8040 monotherapy had a substantial
therapeutic effect. Treatment with BL-8040 as a single agent
triggered robust mobilization of AML blasts from the bone marrow to
the peripheral blood stream, and the extent of mobilization was
correlated with a positive response to treatment. The preferential
mobilization of AML blasts over normal cells (4.7-fold vs.
1.4-fold, respectively) was further confirmed by FISH analysis in a
subset of patients. In addition, BL-8040 monotherapy resulted in a
40% increase in AML blast apoptosis.
In an oral presentation at ASH, entitled "The High Affinity
CXCR4 Inhibitor, BL-8040, Induces Apoptosis of AML Blasts and their
Terminal Differentiation by Blocking AKT/ERK Survival Signals and
Downregulating BCL-2, MCL-1 and Cyclin-D1 through Regulation of
miR-15a/16-1 Expression", delivered by Prof. Amnon Peled from the Hadassah Medical Center and
Biokine Therapeutics, BioLineRx reports detailed data on the
mechanism-of-action by which BL-8040 directly induces apoptosis of
AML cells. The data presented are from in vitro
studies using human AML cell lines and human primary AML samples,
as well as in vivo studies using human primary AML
cells engrafted in NOD scid gamma (NSG) mice.
The results of the pre-clinical studies show that BL-8040
treatment in vivo triggered mobilization of AML
blasts from their protective bone marrow microenvironment and
induced their terminal differentiation, further supporting the data
presented by BioLineRx at the American Association for Cancer
Research annual conference earlier this year.
In addition, the studies illustrate how BL-8040 increases the
expression and activity of a special class of microRNA precursors
termed miR-15a/16-1. These microRNA molecules have been previously
linked to cancer, and shown to suppress the activity of several
tumor-related pro-survival proteins. Therefore, by increasing the
expression of miR-15a/16-1 microRNA molecules, BL-8040 decreases
the expression of tumor-survival proteins and promotes tumor cell
death. Importantly, in both in vitro and in
vivo experiments, BL-8040 was found to synergize with a
selective Bcl-2 inhibitor (Venetoclax) and an FLT3 inhibitor
(Quizartinib, also known as AC220) in inducing AML cell death,
pointing at potential drug combination treatments.
Philip Serlin, CEO of BioLineRx,
commented, "We are pleased to be presenting additional positive
results about BL-8040, our lead oncology platform. In particular,
clinical studies show that BL-8040 acts selectively on
chemotherapy-resistant cells, which may be beneficial in reduction
of residual disease and supports the incorporation of BL-8040 in
front-line treatment settings such as AML consolidation. Such
studies are currently ongoing. We are also encouraged to see, in
pre-clinical models, a synergistic effect between BL-8040 and
Venetoclax, and between BL-8040 and Quizartinib, drugs which are
also being investigated as AML treatments. Given the high
percentage of patients experiencing a relapse or that are
refractory to available treatments, we anticipate that BL-8040, in
combination with a growing repertoire of drugs, will be able to
offer hope to AML patients around the world."
About BL-8040
BL-8040 is a short peptide for the treatment of acute myeloid
leukemia, solid tumors, and certain hematological indications. It
functions as a high-affinity antagonist for CXCR4, a chemokine
receptor that is directly involved in tumor progression,
angiogenesis, metastasis and cell survival. CXCR4 is over-expressed
in more than 70% of human cancers and its expression often
correlates with disease severity. In a number of clinical and
pre-clinical studies, BL-8040 has shown robust mobilization of
cancer cells from the bone marrow, thereby sensitizing these cells
to chemo- and bio-based anti-cancer therapy, as well as a direct
anti-cancer effect by inducing apoptosis. In addition, BL-8040 has
also demonstrated robust stem-cell mobilization, including the
mobilization of colony-forming cells, and T, B and NK cells.
Furthermore, scientific findings in the field of immuno-oncology
suggest that CXCR4 antagonists may be effective in inducing the
infiltration of anti-tumor T cells into the tumor. Therefore, when
combined with immune checkpoint inhibitors, BL-8040 has the
potential to enable activated T cells to better reach tumor cells.
BL-8040 was licensed by BioLineRx from Biokine Therapeutics and was
previously developed under the name BKT-140.
About BioLineRx
BioLineRx is a 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 leading therapeutic candidates are: BL-8040, a
cancer therapy platform, which has successfully completed a Phase
2a study for relapsed/refractory AML, is in the midst of a Phase 2b
study as an AML consolidation treatment, and has recently initiated
a Phase 2 study in stem cell mobilization for allogeneic
transplantation; and BL-7010 for celiac disease and gluten
sensitivity, which has successfully completed a Phase 1/2 study. In
addition, BioLineRx has a strategic collaboration with Novartis for
the co-development of selected Israeli-sourced novel drug
candidates; a collaboration agreement with MSD (known as Merck in
the US and Canada) to run a Phase
2a study in pancreatic cancer using the combination of BL-8040 and
Merck's KEYTRUDA®; and has recently signed a collaboration
agreement with Genentech, a member of the Roche Group, to
investigate the combination of BL-8040 and Genentech's Atezolizumab
in several Phase 1b studies for multiple solid tumor indications
and AML.
For additional information on BioLineRx, please visit the
Company's website at http://www.biolinerx.com, where you can review
the Company's SEC filings, press releases, announcements and
events. BioLineRx industry updates are also regularly updated on
Facebook, Twitter, and LinkedIn.
Various statements in this
release concerning BioLineRx's future
expectations 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
10, 2016. 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.
Contacts:
PCG Advisory
Vivian Cervantes
Investor Relations
+1-212-554-5482
vivian@pcgadvisory.com
or
Tsipi Haitovsky
Public Relations
+972-52-989892
tsipihai5@gmail.com
SOURCE BioLineRx Ltd.