Company Presentation. February 2016

Transcription

1 Company Presentation February 2016

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 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. 2

3 BioLineRx Snapshot Drug development company focused on oncology & immunology 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 Lead program is BL-8040 oncology platform For multiple cancer and hematological indications Significant collaborations with global pharma companies Strategic collaboration with Novartis for screening and early-stage clinical development of Israeli-sourced assets Immuno-oncology collaboration with Merck in pancreatic cancer (BL-8040 & Keytruda) Out-licensing of European rights for BL-5010 to Omega Pharma (now Perrigo) 3

4 Main Pipeline Assets * * BL-1040 for the prevention of ventricular remodeling post AMI is currently sub-licensed to Bellerophon, pending decision on future development in light of negative results from CE mark registration study recently reported 4

5 Long Term Relationships with Israeli Institutions Technion Rambam Medical Center Academic Institutes Tel Aviv University Hebrew University Weizmann Institute Tel-Aviv Haifa Rehovot Jerusalem Be er Sheva Sheba Medical Center Hadassah Medical Center Medical Centers Ben-Gurion University Bar-Ilan University Sourasky Medical Center Extensive in-licensing track record with majority of academic & research centers in Israel 5

6 SELECTED PROGRAMS 6

7 BL-8040: BEST-IN-CLASS CXCR4 ANTAGONIST FOR TREATMENT OF MULTIPLE CANCER AND HEMATOLOGICAL INDICATIONS 7

8 BL-8040 Highlights Platform Molecule: Multiple cancer and hematological indications Received Orphan Designation from FDA for AML & SCM Mode of Action: Inhibits CXCR4 (a cell surface protein) CXCR4 overexpressed in >70% of tumors; correlates with severity; well validated Sensitizes cancer cells to treatment by mobilizing the cells from bone marrow to blood circulation Induces cancer cell death (apoptosis) Multiple clinical studies ongoing or in final planning stages Includes entrance into immuno-therapy field through collaborations 8

9 BL-8040 is Best-in-Class vs. Competitors BL-8040 Mozobil Affinity for CXCR4 1-2 nm 84 nm 5nM BMS (MDX1338) Inhibition Inverse agonist Antagonist (partial agonist) Antagonist CXCR4 Binding site Extracellular domains in the CXCR4 receptor Trans-membrane regions in the CXCR4 receptor Extracellular domains in the CXCR4 receptor Plasma half-life hr ~3-5 hr More than 24hr Receptor occupancy More than 24 hr ~2 hr Not published Cancer Cell Death Induces apoptosis in preclinical models. Evidence of remarkable apoptosis in samples from patients administrated with 0.75 and 1 mg/kg (phase 2). None Demonstrated apoptosis in preclinical models, modest effect in patients (ASH 2013) Mobilization 6-8 fold increase (phase 2a study in r/r AML, ASH 2014) 2.5 fold (phase 1/2 study, Blood 2012) 2.1-fold increase (phase 2 study, ASH 2013) Other remarks of BL-8040: Synergizes with Rituximab and Bendamustine to stimulate Lymphoma cell death in vitro. Synergizes with Bortezomib (Velcade) to stimulate multiple myeloma 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). Synergizes with AC220 to minimize residual disease in FLT3+ AML (in vivo) Superior Comparable Inferior 9

10 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 (MDX-1338) * Study was conducted by scientists from BMS * Kuhne MR, Clinical Cancer Research,

11 BL-8040 Clinical Program ONGOING PLANNED COMPLETED PROTOCOL INDICATION Pre-Clinical Phase I Phase II Phase III ACUTE MYELOID LEUKEMIA (AML) BL BL BL R/R AML AML Consolidation (BLAST) AML FLT3-ITD Ph2a - Ongoing Ph2b - Ongoing Ph2a Planned to initiate Q1/2016 IMMUNOTHERAPY COMBINATION BL Pancreatic Cancer (Keytruda) Ph2a (collab with Merck) Planned to initiate mid-2016 BONE MARROW FAILURE INDICATIONS BL hmds and Aplastic Anemia Ph1/2 Ongoing STEM CELL MOBILIZATION BL BKTSC001 BL SCM as Single Agent (Allogeneic) SCM with G-CSF (Myeloma) SCM as Single Agent Ph2a Planned to initiate Q1/2016 Ph1/2 - Completed Ph1 Completed 11

12 Phase 2a - Treatment of r/r AML patients Study Design Dose escalation phase Expansion phase: expand safe, efficacious dose group Efficacy endpoints: 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) BM biopsy Day BL-8040 Ara-C Screening Treatment Follow up

13 Results from Dose Escalation Stage No BL-8040 related SAEs and no AEs were considered DLTs Remission rate (CR + CRi) was 38% in subjects receiving only one cycle of BL-8040 at doses of 1 mg/kg and higher (n=16) Robust leukemic blast mobilization was observed (above 40- fold increase) BL-8040 monotherapy decreased amount of leukemic cells in BM by median of ~60% BL-8040 monotherapy achieved >three-fold increase in AML cell apoptosis BL-8040 induced leukemia progenitor cells towards differentiation Top-line results from study are expected in Q

14 Stem Cell Mobilization for Transplantation G-CSF is current standard for stem cell mobilization 4-6 daily injections of G-CSF, plus 1-4 apheresis sessions required G-CSF is associated with bone pain and other side effects Number of injections & apheresis sessions represent significant cost to payers and hospitals BL-8040 value proposition Shorten treatment time significantly One administration of BL-8040 and one apheresis session Lower overall costs for complete procedure 14

15 Top Line Results in Stem-Cell Phase 1 Study All safety and efficacy endpoints were met BL-8040 as single agent was safe and well-tolerated at all doses Resulted in efficient stem cell mobilization and collection in all study participants Only one collection (apheresis) session was required for all study participants Results support BL-8040 as one-day, single-dose collection regimen After single administration, BL-8040 enabled collection of a yield of stem cells that exceeds the number required to support a transplant in all treated participants Type B meeting with FDA held in October 2015; Phase 2 study in allogeneic transplantation expected to commence in Q Regulatory submission made in December 2015 Study will be under collaboration with Washington University School of Medicine, Division of Hematology and Oncology 15

16 Two Additional Studies Initiated in 2015 AML Consolidation (Phase 2b) Collaboration with German Study Alliance Leukemia Group Double-blind, placebo-controlled, repeated administrations, multiple treatment cycles ~200 patients; sites in Germany Topline results expected in 2018 Myelodysplastic Syndrome & Aplastic Anemia (Phase 1/2) Collaboration with MD Anderson Cancer Center Open-label, repeated administrations, single treatment cycle Interim results expected by Q4 2016; topline results expected by Q

17 Three New Studies Planned to Initiate in 2016 SC Mobilization for Allogeneic Transplantation (Phase 2) Collaboration with Washington University Open label; 24 donor/recipient pairs will be recruited to study Interim results expected by Q416; topline results expected by Q417 Metastatic Pancreatic Cancer (Phase 2a) Cancer immunotherapy collaboration with Merck (combination treatment with Keytruda) Open-label, multicenter, single-arm study in up to 30 patients Partial results expected by mid-2017; topline results by mid-2018 AML FLT3-ITD (Phase 1/2) Collaboration with MD Anderson Cancer Center Open-label, two parts: (i) part 1 - dose selection, Sorafinib in combination with BL- 8040; (ii) part 2 - combination in different FLT3-ITD patient populations Interim results expected in 2017; topline results in

18 BL-8040 Potential in Cancer Immunotherapy Immunostimulant - BL-8040 is powerful mobilizer of immune cells (T-cells, B-cells, immature Dendritic-cells and NK cells) from bone marrow and lymph nodes Potentiator - BL-8040 increases infiltration of immune cells into tumors - exhibiting synergistic effect with anti PD1/PD-L1 immune checkpoint inhibitors Chemo-attractant - BL-8040 induces expression of chemokines by tumor cells, thereby increasing trafficking of immune cells toward tumors Microenvironment modifier - BL-8040 affects suppressive tumor microenvironment by decreasing CXCR4 mediated migration of immune suppressor cells

19 Highlights of Immunotherapy Collaboration with Merck for Phase 2a Study in Pancreatic Cancer Study highlights: Combination of BL-8040 with Merck s anti-pd-1 immune checkpoint inhibitor Pembrolizumab (Keytruda) Patients with metastatic pancreatic adenocarcinoma Open-label, multicenter, single-arm trial Up to 30 patients will be enrolled Study will evaluate clinical response, safety and tolerability, and multiple pharmacodynamic parameters, including ability to improve infiltration of T cells into the tumor and their reactivity Treatment cycles will be repeated until progression or until intolerable toxicity Study will commence in mid-2016

20 BL-8040 Summary CXCR4 is a validated target BL-8040 has demonstrated signs of efficacy in multiple clinical studies BL-8040 s MOU has been clinically validated BL-8040 is a platform for a wide range of oncology and hematology indications Including immuno-oncology collaboration with Merck for pancreatic cancer 20

21 BL-7010: NOVEL GLIADIN BINDING POLYMER FOR CELIAC DISEASE 21

22 BL-7010: Polymeric Binder for Celiac Disease Indication: Celiac disease and gluten sensitivity Mode of Action: Non-absorbable polymer with high affinity to gliadins (immunogenic peptides contained in gluten) Status: Phase 1/2 completed Product Highlights Prevents pathological damage to small intestine Non-absorbable Non-toxic 22

23 Celiac/Gluten Sensitivity 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) ~30% of celiac patients are symptomatic even with GFD ~10% of world s population is gluten sensitive 23

24 BL-7010 Prevents Formation of Gliadin s Immunogenic Peptides Gluten Gliadin Gluten BL-7010 Copolymer of sodium styrene sulfonate (SS) and 2-hydroxyethyl methacrylate (HEMA) 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 Inflammatory Cytokines The polymer and gliadin are excreted in feces APC Prevention of intestinal damage Lymphocytes 24

25 BL-7010 Maintains Normal Structure of GI Model: HLA-DQ8/HCD4 transgenic male mice sensitized to gliadin non-sensitized mice Gluten-sensitized mice Gluten-sensitized mice + BL-7010 Villus-to-crypt ratio 5.96 ± ± ±

26 BL-7010 Clinical Program Overview Phase 1/2 study in celiac patients completed Consisted of 2 parts: Single ascending dose Safety endpoints No efficacy endpoints Assessment of systemic exposure 14 days repeated administration 3 times per day Safety w/o efficacy endpoints Assessment of systemic exposure Positive top-line results from study Safe and well tolerated; no serious or dose-limiting side effects Optimal dose identified: 1 gram x 3 per day Confirmed no systemic absorption; supports medical device classification in Europe (significantly accelerates potential approval) 26

27 BL-7010 Summary Significant unmet medical need BL-7010 has unique and simple MOA Successful Phase 1/2 pilot study Well tolerated, no systemic exposure BL-7010 recently classified as Class IIb medical device in Europe Next study expected to begin in 2016 Evaluation of food pathway continuing in parallel Significantly shorter time to market Huge population with unmet medical need 27

28 BL-5010: A NOVEL FORMULATION AND APPLICATOR FOR NON-SURGICAL REMOVAL OF SKIN LESIONS (TOPICAL USE) 28

29 BL-5010 Highlights Novel formulation/applicator for non-surgical removal of skin lesions Status: CE mark registration process for OTC indications Product Highlights: Medical device classification in EU Outstanding clinical data ~97% removal rate; 94% good/excellent cosmetic results State-of-the-art applicator developed for streamlined application Short time to market (sales expected in 2016) 29

30 BL-5010 Roadmap Partnered with Omega Pharma (now Perrigo) in December 2014 Licensed rights for OTC indications in Europe, Australia and other territories Omega/Perrigo obligated to bring two OTC products to market Recently conducted study to support marketing in EU Application for CE Mark submitted in Q315; first sales expected in 2016 BLRX retains OTC rights to US and rest of world, as well as worldwide non-otc rights BLRX has full access to all clinical, R&D and manufacturing data generated by Omega/Perrigo 30

31 CORPORATE 31

32 Strategic Collaboration with Novartis Novartis selected BioLineRx as its leading partner for identification and early development of Israeli-sourced drug candidates Exclusive first look at all Israeli-based projects scouted by BioLineRx Co-develop selected projects through clinical proof-of-concept (POC) Provides lasting shareholder value and key insights Builds pipeline in conjunction with global leader, gaining Big Pharma perspective Financial highlights: Upfront $10 million equity investment in BLRX Upon selection of project, BioLineRx will receive: $5 million option fee (non-dilutive) 50% of remaining R&D expenses up to POC (in equity at a premium to market) Novartis receives right of first negotiation for full out-license upon clinical POC 32

33 Financial and Corporate Summary Cash position ~$51 million as of September 30, 2015 Funds operational capital into 2018 Capital structure Traded on NASDAQ and TASE (Symbol: BLRX) 54 million shares outstanding; 62 million fully diluted US shareholders represent ~70% of investor base, including key lifesciences investors Other Novartis holds ~9% of Company 55 employees, approximately 2/3 with advanced degrees Covered by several analysts: JMP Securities, Roth Capital, Maxim Group, Edison Investment Research 33

34 Major Achievements in last ~12 Months Business development (signed agreements) December strategic collaboration agreement with Novartis December 2014 out-licensing agreement with Omega Pharma (Perrigo) January immuno-oncology collaboration agreement with Merck (MSD) Scientific/Regulatory BL r/r AML study partial results BL Device designation in EU BL-5010 Completion of marketing study for EU and final preparations for product launch (including CE mark package submission) 34

35 Major Development Milestones 2016 and 2017 BL-7010 regulatory pathway determination BL-8040 (FLT-3) phase 1/2 initiation BL-7010 (Celiac) CE pivotal study initiation BL-8040 (Pancreatic Cancer) phase 2 initiation 2016 BL-8040 (Pancreatic Cancer) IO agmt with Merck BL-8040 (AML) phase 2 completion BL-8040 (SC Mobilization) phase 2 initiation BL-5010 (Skin Lesions) CE Mark approval BL-8040 (AML) discussions with agencies BL-5010 selection of second OTC indication BL-8040 (hmds & AA) phase 1/2 interim results BL-5010 (Skin Lesions) product launch BL-8040 (SC Mobilization) phase 2 interim results BL-8040 (Consolidation) LPI BL-8040 (Pancreatic Cancer) phase 2 partial results BL-8040 (FLT-3) interim results 2017 BL-8040 (hmds & AA) study completion BL-8040 (SC Mobilization) study completion 35

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