Biolinerx Ltd. · TASE:BLRX
Biolinerx — Investor Presentation (March 2014)
50 slides from Biolinerx's investor presentation, Mar 3, 2014
Slide 1: Company Presentation
Company Presentation February 2014
Slide 2: 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
Slide 3: Offering Summary
Issuer BioLineRx Ltd. Listing/Ticker NASDAQ: BLRX Offering Size Approximately $20 million Securities Offered Common Stock (ADSs) Expected Timing March 4, 2014 Use of Proceeds Continued clinical development of lead programs (BL- 8040 and BL-7010) and general corporate purposes Book-runner Roth Capita
Slide 4: BioLineRx - General
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 yea
Slide 5: BioLineRx's Value Proposition
BioLineRx’s Value Proposition • Multiple shots on goal • Several meaningful value inflection points in next 12 months • Two assets in pivotal studies during next 12 months • Two pharma assets regulated as devices • Strategic relationships and access to Israeli technology
Slide 6: Our Proven Business Model
Our Proven Business Model • Strong scientific basis • High chance of regulatory approval • Competitive advantage • Strong IP • Validate results of inventors • Resolve main concerns regarding toxicity, CMC, etc. • Accelerated development program • FDA/EMA standards • Continued clinical development, i
Slide 7: Efficient Project Development Infrastructure
BD In-licensing and Out-licensing Chemistry Team (Organic, Analytical, Bioanalytical, Formulation) Expert Project Managers Medical and Clinical Team Pre-Clinical Team Regulatory Affairs Team Intellectual Property Experts Multiple Projects Efficient Project Development Infrastructure
Slide 8: Pipeline
Pre-Cinical LEAD DEVELOPMENT PROGRAMS AML ‘Stem cell mobilization BL-8040 BL-7010 Celiac disease ADDITIONAL DEVELOPMENT PROGRAMS BL-5010 ‘Skin lesions BL-7040, Inflammatory bowel disease BL-9010 ‘Severe asthmalallergies PROGRAMS PARTNERED OF IN CO-DEVELOPMENT BL-1040 ‘Ventricular remodeling post-ANI
Slide 9: Lead Development Programs
LEAD DEVELOPMENT PROGRAMS
Slide 10: BL-8040: Best-in-Class CXCR4 Antagonist for Hematological Cancers
BL-8040: BEST-IN-CLASS CXCR4 ANTAGONIST FOR TREATMENT OF HEMATOLOGICAL CANCERS
Slide 11: BL-8040 Highlights
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: Pha
Slide 12: AML - Treatment and Unmet Medical Need
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 poo
Slide 13: BL-8040 Mechanism Of Action
BL- 8040 BL-8040 + SoC BL- 8040 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 • Increase
Slide 14: XIAP
XIAP Smac/DIABLO HSP32 Claspin BCL-2 BCL-X Reference spot Cytochrome C CTRL BL-8040 HSP70 HSP27 Treatment: HIF1α cIAP1 K562 cells (CML) were treated with BL-8040 (20 uM, 24h). Analyzed by WB. • Down regulation of Bcl-X and Bcl-2 leads to activation of BAX/BAK, and the activation of caspases. • Down
Slide 15: Current BL-8040 Phase II Study in AML
Current BL-8040 Phase II Study in AML • Study summary – Open-label study under IND carried out at multiple centers in the US and Israel – Relapsed or refractory AML patients (up to 50 patients) • Study design – Dose escalation phase - up to 5 escalating doses (0.5-1.5 mg/kg) – Expansion phase of saf
Slide 16: BL-8040 AML Study Design
BL-8040 AML Study Design Screening BL-8040 BL-8040 + Chemotherapy [ Cytarabine (ARA-C)] Evaluation of response 1 2 3 4 5 6 7 ------------------------------------------------------------ 30 Day: BM biopsy: BM biopsy • Completion of AML study expected end of 2014 / beginning of 2015
Slide 17: Partial Results in AML Study
Partial Results in AML Study • Safe at all doses tested to date (0.5, 0.75 and 1mg/kg) • Substantial mobilization of cancer cells from BM to peripheral blood • Evidence for robust effect of cancer cell death • Additional information on will be provided at end of dose escalation stage - expected by m
Slide 18: BL-8040 Superiority to Mozobil
BL-8040 Superiority to Mozobil Time post BL-8040/Mozobil injection BL-8040 12 mg/kg Mozobil 3.2 mg/kg CXCL12 serum levels Time post BL-8040/Mozobil injection BL-8040 0.11 BL-8040 0.167 BL-8040 0.22 Mozobil 0.11 Mozobil 0.167 Mozobil 0.22 Mobilization Cell Death
Slide 19: Superiority of BL-8040's Anti-Cancer Effect
Superiority of BL-8040’s Anti-Cancer Effect * * Kuhne MR, Clinical Cancer Research, 2012 BL-8040 (formerly BKT140) inhibits proliferation of Ramos cells compared with Mozobil (AMD3100) and BMS-936564 (MDX-1338)
Slide 20: BL-8040 is Effective on FLT3 Mutated AML Cells (in-vitro)
M. Abraham et al., Unpublished data BL-8040 is Effective on FLT3 Mutated AML Cells (in-vitro) * p<0.05 vs. control ** p<0.05 vs. BL8040 alone In-vitro effect of BL-8040 or AMD3100 -/+ ARA-C on viability of human AML cells with the FLT3 mutation
Slide 21: BL-8040 is Effective on FLT3 Mutated AML Cells (in-vivo)
BL-8040 is Effective on FLT3 Mutated AML Cells (in-vivo) Effect of BL-8040 in NSG mouse model with FLT3-mutated AML cells (MV4-11), in vivo • Results show: – Multiple BL-8040 injections reduced number of AML cells in blood and BM – Multiple BL-8040 injections induced apoptosis of AML cells in blood
Slide 22: BL-8040 vs AC220 (Quizartinib) in FLT3 Mutated AML
BL-8040 is Effective on FLT3 Mutated AML Cells in comparison with AC220 (Quizartinib, Ambit) • Results show: – Similar efficacy of BL-8040 and AC220 (FLT-3 targeted therapy) in FLT3-mutated AML model – Multiple BL-8040 injections reduced the number of AML cells in blood and BM Number of AML cells wi
Slide 23: BL-8040 vs Mozobil and BMS-936564 comparison
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 CXCR
Slide 24: Additional Study Planned in Stem-Cell Mobilization
Additional Study Planned in Stem-Cell Mobilization • Expected to start in H1 2014; results expected in H2 2014 In-vivo results show that BL-8040 has significantly better stem cell mobilization, as compared with G-CSF and Mozobil
Slide 25: BL-7010: Novel Gliadin Binding Polymer for Celiac Disease
BL-7010: NOVEL GLIADIN BINDING POLYMER FOR CELIAC DISEASE
Slide 26: BL-7010: Polymeric Binder for Celiac Disease
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 ongoing • Product Highlights – Prevents pathological damage to small intestine – Non-absor
Slide 27: Celiac Disease - Large Unmet Medical Need
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-lo
Slide 28: Small intestinal damage with loss of
Small intestinal damage with loss of absorptive villi and hyperplasia of the crypts, typically leading to malabsorption BL-7010 Gluten Gliadin Enterocytes Lymphocytes Inflammatory Cytokines APC Copolymer of sodium styrene sulfonate (SS) and 2-hydroxyethyl methacrylate (HEMA) Gluten BL-7010 demonstra
Slide 29: BL-7010 Maintains Normal Structure of GI
BL-7010 Maintains Normal Structure of GI non-sensitized mice Gluten-sensitized mice Gluten-sensitized mice + BL-7010 5.96 ± 1.23 Villus-to-crypt ratio 2.58 ± 0.43 4.89 ± 1.51 Model: HLA-DQ8/HCD4 transgenic male mice sensitized to gliadin
Slide 30: Preliminary ADME Shows BL-7010 is Excreted in Feces
Preliminary ADME Shows BL-7010 is Excreted in Feces • [ 3 H]-BL-7010 was given orally to SD rats (single dose and single dose after 21 days of dosing of non-labeled compound) • Total urine and feces were collected from 0 to 12, 12 to 24, 24 to 36, 36 to 48 and 48 to 72 h after administration • Blood
Slide 31: BL-7010 Clinical Program Overview
BL-7010 Clinical Program Overview Two studies in celiac disease patients are planned in 2014: • Phase I/II study in celiac patients (ongoing) – Single and repeated ascending dose study – Safety endpoints, no efficacy endpoints – Assessment of systemic exposure – Top-line results expected in mid-2014
Slide 32: BL-7010 Phase I/II Study in Celiac Patients
BL-7010 Phase I/II Study in Celiac Patients • Part 1: Single ascending administration phase (ongoing) – Two alternating cohorts; 8 patients each (6 on BL-7010 and 2 on placebo) – Up to 6 escalating administrations – Population - well controlled celiac patients = absence of gastrointestinal symptoms,
Slide 33: Additional Selected Programs
ADDITIONAL SELECTED PROGRAMS
Slide 34: BL-1040: First-in-Class Myocardial Implant
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)
Slide 35: BL-1040 Highlights
BL-1040 Highlights • Indication: Cardiac remodeling post-AMI • Mode of Action : Provides support to ischemic tissue during healing • Status: CE Mark registration trial - results expected in 2014 • Device designation (including FDA) • Partnered with Bellerophon BCM (f/k/a Ikaria) – Total deal structu
Slide 36: Unmet Medical Need
Unmet Medical Need Vessel occlusion Tissue damage
Slide 37: How Does BL-1040 Work?
How Does BL-1040 Work? Infarct related artery injection Deposits into infarcted tissue Upon contact with infarcted tissue, turns from liquid into gel Gel-like scaffold provides mechanical support to damaged tissue Transitions to liquid and exits the body within 6 weeks
Slide 38: BL-1040 Prevents Structural Changes
Normal size left ventricle Normal LV wall Dilated left ventricle Thin LV wall BL-1040 Prevents Structural Changes Untreated BL-1040 Porcine AMI model, day 60
Slide 39: Promising Results from Pilot Study
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
Slide 40: BL-1040 Pivotal Clinical Development Program
BL-1040 Pivotal Clinical Development Program • Pivotal CE Mark Registration trial progressing at full steam – ~75 sites currently active in nine countries (including 15 sites in US) – Placebo controlled, 306 patients, six-month follow-up – Endpoints: End diastolic volume, QLQ, six-minute walk test –
Slide 41: BL-5010: A Novel Formulation for Non-Surgical Removal of Skin Lesions
BL-5010: A NOVEL FORMULATION FOR NON-SURGICAL REMOVAL OF SKIN LESIONS, EMBEDDED WITHIN NEW APPLICATOR PEN (BL-5010P) - FOR TOPICAL USE
Slide 42: BL-5010 Highlights
BL-5010 Highlights • Novel formulation for non-surgical removal of skin lesions • Status: CE mark registration trial to commence in H1 2014 • Product Highlights: – Medical device classification in EU – Single application office-based treatment – Pilot study completed with outstanding results • ~97%
Slide 43: BL-5010 Roadmap
BL-5010 Roadmap • Pivotal CE Mark Registration study to commence in H1 2014 – Bridging study of BL-5010 pen-like applicator in seborrheic keratosis – Regulatory submissions have been completed – Study results are expected H2 2014 – Commence CE-mark registration process in H2 2014 • Clinical study in
Slide 44: Biologics Collaboration
BIOLOGICS COLLABORATION
Slide 45: Biologics Collaboration with JHL Biotech
Biologics Collaboration with JHL Biotech • Collaboration deal inked in January with JHL Biotech for BL-9020, monoclonal antibody for treatment of Type 1 diabetes – JHL responsible for manufacturing – BioLineRx responsible for pre-clinical activities – JHL receives commercialization rights in China &
Slide 46: Corporate
CORPORATE
Slide 47: Financial Summary
Financial Summary • Available cash as of December 31, 2013 - ~$18.2 million − Annual burn rate ~$12 million − Cash expected to last into mid-2015 • Number of employees - 45 − Approximately 2/3 with advanced degrees • Capital structure (on basis of ADSs) − 24.1 million outstanding - basic capital − 2
Slide 48: Analyst Coverage
Analyst Firm Robert Hazlett Roth Capital Partners, LLC Raghuram Selvaraju Aegis Capital Corp. Robin Davison; Jason Zhang Edison Investment Research Analyst Coverage BioLineRx Ltd. is followed by the analysts listed below: Please note that any opinions, estimates or forecasts regarding BioLineRx Ltd.
Slide 49: 2014 Major Milestones
2014 Major Milestones BL-5010 (Skin Lesions) pivotal EU study initiation BL-5010 (Skin Lesions) pivotal EU study results BL-7010 (Celiac Disease) phase 1/2 top line results BL-7010 (Celiac Disease) pivotal study initiation BL-1040 (AMI) pivotal CE mark study results BL-8040 (AML) phase 2 topline res
Slide 50: BIOLINEM ><
BIOLINEM ><