Company Presentation
November 2014
Forward Looking Statements
This presentation contains "forward-looking statements."
These statements include words like "may," "expects,"
"believes," “plans,” “scheduled," 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.
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BioLineRx - General
• Founded in 2003 by Teva and other key players in Israeli Life
Sciences industry
• Bridge “development gap” for Israeli assets
– Leverage carefully selected early-stage technology, primarily at academia level,
following proof of concept in animals (at a minimum)
– Invest 3-6 years in asset through to major catalyst
– Partner the asset (depending on the stage)
• For commercialization
• For late-stage clinical development
• For early and mid-stage co-development
• Current pipeline of 10 assets, 6 in clinical development
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BioLineRx Value Proposition
Extensive deal-flow funnel
• Outstanding access to early assets via expert in-licensing team
constantly monitoring life science innovations in Israel and abroad
• In-licensing efforts guided by open dialogue with R&D and BD divisions
Expedited development
• Multidisciplinary team with extensive drug development experience
• Emphasis on regulatory strategy to assure optimal route to approval
• 3 pharma assets on device regulatory pathway
Strong financials
• ~$30 million cash – sufficient to fund operations for over two years
• Several value accreting milestones in 2014-2015
• Traded on both NASDAQ and TASE (symbol: BLRX)
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Long Term Relationships with Israeli Institutions
Rambam Medical Center
Haifa
Tel Aviv University
Tel-Aviv
Hebrew University
Sheba Medical Center
Rehovot
Jerusalem
Be’er Sheva
Hadassah Medical Center
Weizmann Institute
Ben-Gurion University
Medical Centers
Academic Institutes
Technion
Sourasky Medical Center
Extensive in-licensing track record with majority of
academic & research centers in Israel
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Main Pipeline Assets
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LEAD DEVELOPMENT PROGRAMS
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BL-8040:
BEST-IN-CLASS CXCR4
ANTAGONIST FOR
TREATMENT OF
HEMATOLOGICAL
CANCERS
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BL-8040 Highlights
• Indications: Acute myeloid leukemia (AML) & other hematological cancers
– Orphan designation received from FDA for both AML and stem-cell mobilization
• Mode of Action: CXCR4 antagonism
– CXCR4 over-expressed in >70% of tumors, and correlates with disease severity.
• Status: Phase II trial ongoing
• Product Highlights:
– Induces apoptosis in cancer cells
– Mobilizes cancer cells from bone marrow to peripheral blood
– Sensitizes cancer cells to chemo- and bio-based anti-cancer therapy
– Safety and mobilization activity demonstrated in Phase I/II study in myeloma patients
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AML – Treatment and Unmet Medical Need
• AML is most common acute leukemia in adults
– Over 60,000 new cases recorded worldwide in 2010, growing to 130,000 by 2020
– 14,000 cases of AML diagnosed in the US in 2012
– Majority of AML patients relapse and require repeated treatment cycles
• AML has poor prognosis – less than 25% five-year survival
– Over 10,000 fatalities from AML in the US in 2012
• AML treatment regimens have changed little in past 30 years
– Treatment of AML is based largely on use of older chemotherapeutic drugs
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BL-8040 Mechanism Of Action
• Binds CXCR4 with high affinity (1-2 nM)
• Maintains extended inhibition of CXCR4 through long receptor occupancy (>24 hours)
• Works as inverse agonist of CXCR4
• Induces apoptosis of tumor cells dependent on CXCR4 for survival
• Increases sensitivity to anti-cancer agents by mobilizing tumor cells from protective
microenvironment
BL-8040
induces
tumor cells
mobilization
BL8040
BL-8040
directly
induces
apoptosis
BL-8040
BL-8040
sensitizes
tumor cells to
other drugs
BL-8040 +
SoC
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BL-8040 Superiority to Mozobil
Mobilization
Number of Neutrophils
BL-8040 12 mg/kg
Mozobil 3.2 mg/kg
Time post BL-8040/Mozobil injection
Cell Death
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Other Evidence of BL-8040’s Superior
Anti-Cancer Effect
BL-8040 (formerly BKT140) inhibits proliferation of Ramos cells compared
with Mozobil (AMD3100) and BMS-936564 (MDX-1338)
*
Study was conducted by scientists from BMS
* Kuhne MR, Clinical Cancer Research, 2012
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Summary of BL-8040 vs. Competitors
BL-8040
(BKT-140)
Mozobil
(Plerixafor/AMD3100)
BMS-936564
(MDX1338)
Affinity with CXCR4
1-2 nM
84 nM
5nM
MOA
Inverse agonist
Antagonist (partial agonist)
Antagonist
Binding site
Extracellular domains in the
CXCR4 receptor
Trans-membrane regions in
the CXCR4 receptor
Extracellular domains in the CXCR4
receptor
PK (T1/2 in human)
0.3 – 0.7 hr
~3-5 hr
More than 24hr
Receptor occupancy
More than 24 hr
~2 hr
Not published
Inducing apoptosis in
tumor cells
Induces apoptosis in preclinical
models. Evidence of remarkable
apoptosis in samples from
patients administrated with 0.75
and 1 mg/kg (phase II).
None
Demonstrated apoptosis in
preclinical models, modest effect in
patients (ASH 2013)
Mobilization of
Leukemic blasts
6-8 fold increase
(6/8 patients, phase IIa)
2.5 fold
(A phase I/II study, Blood
2012)
2.1-fold increase
(14/24 patients in phase II study,
ASH 2013)
Other remarks of BL-8040:
•
•
•
•
BL-8040 synergizes with Rituximab and Bendamustine to stimulate Lymphoma cell death in vitro.
BL-8040 synergize with Bortezomib (Velcade) to stimulate MM cell death in vitro.
Combination of BL-8040 with Imatinib in CML cells overcomes the protective effect of stroma in vitro.
BL-8040 alone is highly efficient in eliminating lymphoma cells in the bone marrow and combined with Rituximab significantly
reduces tumor load (in vivo).
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Phase IIa - Treatment of r/r AML patients
A phase IIa, multicenter, open-label study designed to evaluate safety and efficacy
profile of repeated escalating doses of BL-8040 in adult subjects with relapsed or
refractory acute myeloid leukemia
Study design:
– Dose escalation phase – 3+3 design, up to 5 escalating doses (0.5-1.5 mg/kg)
– Expansion phase: expand safe, efficacious dose group
Treatment:
– 2 consecutive days of BL-8040 monotherapy
– 5 days of BL-8040 + chemotherapy
Endpoints:
– To assess the safety and tolerability of escalating repeated doses of BL-8040 as monotherapy and when
combined with high-dose Ara-C in AML adult subjects with relapsed or refractory disease
– To assess the clinical efficacy (response rates) of escalating repeated doses of BL-8040
– To assess the apoptotic effect of BL-8040 on leukemic blasts
– To assess the effect of BL-8040 on mobilization of AML blasts to peripheral blood (PB)
– To assess the single and multiple dose pharmacokinetic profile of BL-8040
Screening
BM biopsy
Day
Treatment
1
2
3
4
5
Follow up
6
7 ------------------------------------------------------------------------------ 30
BL-8040
Ara-C
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Partial Results in AML Phase II Study
• Safe at all doses tested to date (0.5, 0.75, 1.0 and 1.25 mg/kg)
• Substantial mobilization of cancer cells from BM to peripheral blood
• Evidence for robust effect of cancer cell death
Peripheral blood
sample apoptosis
assay
• Completion of dose escalation stage in early 2015; top-line results
expected in H2 2015
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BL-8040 Summary
• CXCR4 is a validated target
• BL-8040 has robust mobilization activity and apoptosis
– Validated in preliminary data from Phase II study in AML, and Phase I/II study in multiple
myeloma
– BL-8040 has very favorable profile in comparison with leading CXCR4 antagonists
• BL-8040 is an inverse agonist
– Blocks the auto-signaling of CXCR4
• BL-8040 is a platform for a number of hematological indications
– Additional study stem-cell mobilization commenced
– Additional investigator-initiated studies will be performed
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BL-7010:
NOVEL GLIADIN
BINDING POLYMER
FOR
CELIAC DISEASE
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BL-7010: Polymeric Binder for Celiac Disease
• Indication: Celiac disease
• Mode of Action: Non-absorbable polymer with high affinity to gliadins
(immunogenic peptides contained in gluten)
• Status: Phase I/II completed
• Product Highlights
– Prevents pathological damage to small intestine
– Non-absorbable
– Non-toxic
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Celiac Disease – Large Unmet Medical Need
• 1% of world’s population suffers from celiac disease
– Number underestimated due to lack of awareness/diagnostic tools
• Market projected to reach $8 billion by 2019
• No current pharmacological agents approved for celiac
– Only treatment option is life-long, strict gluten-free diet (GFD)
– ~20% of celiac patients are symptomatic even with GFD
• Major interest shown by Big Pharma
– AbbVie recently acquired rights to phase II asset from Alvine for $70 million upfront
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BL-7010 Prevents Formation of Gliadin’s
Immunogenic Peptides
Gluten
Gluten
BL-7010
Copolymer of sodium
styrene sulfonate (SS)
and 2-hydroxyethyl
methacrylate (HEMA)
Gliadin
Enterocytes
BL-7010 demonstrates
distinguished specificity
towards gliadin
Small intestinal damage with loss of
absorptive villi and hyperplasia of the
crypts, typically leading to malabsorption
The polymer and
gliadin are excreted
in feces
Inflammatory Cytokines
APC
Prevention of intestinal damage
Lymphocytes
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BL-7010 Maintains Normal Structure of GI
Model: HLA-DQ8/HCD4 transgenic male mice sensitized to gliadin
non-sensitized
mice
Villus-to-crypt ratio
5.96 ± 1.23
Gluten-sensitized
mice
Gluten-sensitized
mice + BL-7010
2.58 ± 0.43
4.89 ± 1.51
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BL-7010 Clinical Program Overview
• Phase I/II study in celiac patients
– Consists of 2 parts:
– Single ascending dose
– 14 days repeated administration
– Safety endpoints
– 3 times per day
– No efficacy endpoints
– Safety w/o efficacy endpoints
– Assessment of systemic exposure
– Assessment of systemic exposure
- Top-line results were presented in early November
-
The compound is safe and well tolerated; transient GI side-effects were noted
in some of the patients, both in the active and placebo groups, none of which
were considered serious or dose-limiting
-
Optimal dose selected at 1 gram x 3 per day
-
No systemic absorption; supports medical device classification in Europe
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BL-7010 Clinical Program Overview (cont.)
• Pivotal study for EU in celiac patients expected to begin in 2015
– 6-week repeated oral administration
– Efficacy endpoints (primary and secondary) and safety endpoints
• A pre-IND meeting with FDA is expected to take place in H1
2015
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BL-7010 Summary
• Celiac disease is a huge unmet medical need
– There are only a handful of clinical-stage programs in development
• BL-7010 has a unique MOA
– High-molecular-weight polymers
– High affinity to gluten
– Secreted through feces
• Phase 1/2 pilot study completed
– Compound is well tolerated
– No systemic exposure
– Will likely be classified as medical device in Europe
• Pivotal study for EU expected to begin in 2015
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BL-1040:
FIRST-IN-CLASS
MYOCARDIAL IMPLANT
FOR PREVENTION OF
VENTRICULAR REMODELING
FOLLOWING AMI
Out-licensed to Bellerophon
(f/k/a Ikaria) and being
developed as Bioabsorbable
Cardiac Matrix (BCM)
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BL-1040 Highlights
• Indication: Cardiac remodeling post-AMI
• Mode of Action: Provides support to ischemic tissue during healing
• Status: CE Mark registration trial – completion expected in mid-2015
• Device designation (including FDA)
• Partnered with Bellerophon BCM (f/k/a Ikaria)
– Total deal structure $282.5 million; $17 million already received; 11-15% royalties
– All program costs funded by Bellerophon BCM
• Market Opportunity: > Billion dollar market*
*Based on a customized survey and report prepared for BioLineRx by Defined Health
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Unmet Medical Need
Vessel occlusion
Tissue damage
Successfully treated
with PCI and stents
No sufficiently effective
treatment for myocardial
damage
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How Does BL-1040 Work?
Arterial injection deposits
material into infarcted tissue
Turns from liquid to gel on
contact with infarcted tissue
Porcine AMI model, day 60
Untreated
L
V
BL-1040
L
V
Gel-like scaffold provides
mechanical support to damaged
tissue
Transitions to liquid and exits
the body within 6 weeks
• Dilated left ventricle
• Thin LV wall
• Normal size left
ventricle
• Normal LV wall
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Promising Results from Pilot Study
• Designated as device by regulatory authorities
(including FDA)
• Pilot study in Europe – completed January 2010
– 27 patients, safety and preliminary efficacy in patients with
primary MI at high risk for LV remodeling
• 9 sites: 6 in Germany, 3 in Belgium
• Trial results show
– No treatment related complications, arrhythmias, elevations in
cardiac enzymes or occlusions
– Comparison to historical data suggests superior efficacy
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BL-1040 Pivotal Clinical Development Program
Pivotal CE Mark Registration trial progressing at full steam
• Placebo controlled, total enrollment ~300 patients, six-month followup
• ~80 sites currently active in nine countries (including 16 sites in US)
• >280 patients enrolled to date
• Endpoints: End diastolic volume, QLQ, six-minute walk test
• Trial to be completed by mid-2015
US pivotal trial in planning stages
• Final discussions with FDA
• Placebo controlled, >1,000 patients, 12-month follow-up
BL-1040 Summary
• Huge unmet medical need
– >$1 billion market
• Designated as device in both US and Europe
• Pilot study successfully completed
– No safety or tolerability issues after six months of follow-up
– Promising efficacy in comparison to historical data
• CE mark registration study approaching completion of enrollment
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CORPORATE
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Financial and Corporate Summary
Strong cash position
• $29.6 million as of June 30, 2014
• Funds operational capital through end of 2016
• Expect to reach several value inflection points during this time
Capital structure
• Traded on NASDAQ and TASE (Symbol: BLRX)
• 34 million shares outstanding; 40 million fully diluted (based on ADSs)
• US shareholders represent ~60% of investor base
Other
• 46 employees, approximately 2/3 with advanced degrees
• Covered by several analysts: Aegis Capital, Roth Capital, Maxim
Group, Edison Investment Research
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Major Development Milestones – 2014 and 2015
√
BL-9020 (Type 1 Diabetes) collaboration with JHL
√
BL-7010 (Celiac Disease) phase 1/2 study update*
2014
BL-7010 (Celiac Disease) phase 1/2 completion
BL-8040 (SC Mobilization) phase 1 initiation
√
√
BL-8040 (AML) announcement of next steps
BL-1040 (AMI) complete CE mark study enrollment
BL-8040 (SC Mobilization) phase 1 completion
BL-8040 (AML) phase 2 partial results*
BL-8040 platform - initiation of 2 new clinical trials
BL-8040 (SC Mobilization) phase 1 apheresis data
BL-7010 (Celiac Disease) pre-IND mtg with FDA
2015
BL-1040 (AMI) CE mark study completion
BL-8040 (AML) phase 2 completion
BL-7010 (Celiac Disease) CE pivotal study initiation
BL-7010 (Celiac Disease) US study initiation
* End of dose escalation phase
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