SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
FORM 6-K
REPORT OF FOREIGN PRIVATE ISSUER
PURSUANT TO RULE 13a-16 OR 15d-16 OF
THE SECURITIES EXCHANGE ACT OF 1934
For the month of June 2017
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BioLineRx Ltd.
(Translation of registrant's name into English)
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2 HaMa'ayan Street
Modi'in 7177871, Israel
(Address of Principal Executive Offices)
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Indicate by check mark whether the registrant files or will file annual reports under cover of Form 20-F or Form 40-F:
Form 20-F ☑ Form 40-F ☐
Indicate by check mark whether the registrant by furnishing the information contained in this form is also thereby furnishing the information to the Commission pursuant to Rule 12g3-2(b) under the Securities Exchange Act of 1934:
Yes ☐ No ☑
The registrant hereby files as Exhibit 1 to this Report on Form 6-K its new corporate presentation which contains, among other things, disclosures regarding the registrant's planned phase 3 registrational study for the use of BL-8040 in autologous stem cell mobilization.
This Form 6-K, including all exhibits hereto, is hereby incorporated by reference into all effective registration statements filed by the registrant under the Securities Act of 1933.
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned, thereunto duly authorized.
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BioLineRx Ltd. |
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By:
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/s/ Philip Serlin |
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Philip Serlin |
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Chief Executive Officer |
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Dated: June 12, 2017
Exhibit 1
Corporate PresentationJune 2017
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.
Drug development company focused on oncology & immunology:BL-8040 (CXCR4 antagonist) with robust clinical program in immuno-oncology, AML and bone marrow transplantationAGI-134 (alpha-Gal immunotherapy) activating a patient-specific, anti-tumor response to patient’s own cancer neo-antigensImmunology/fibrosis franchise under collaboration with Novartis PharmaSignificant collaborations with leading pharma companiesStrategic collaboration with Novartis for joint development of innovative assetsImmunotherapy collaboration with Genentech in multiple oncology indications (BL-8040 & Atezolizumab)Immunotherapy collaboration with Merck in pancreatic cancer (BL-8040 & Keytruda) BioLineRx Snapshot
OTHER Main Pipeline Assets PROJECT INDICATION PARTNERS PRE-CLINICAL PHASE 1 PHASE 2 PHASE 3 REGULATORY APPROVAL CANCER IMMUNOLOGY Consolidation AML Maintenance AML Gastric cancer Non-small cell lung cancer Pancreatic cancer Pancreatic cancer Stem-cell mobilization Type 1 diabetes NASH Liver failure diseasesDry eye syndrome BL-8040 BL-9020 BL-1210 BL-5010 Regional out-license to Perrigo Developed under strategic collaboration with Novartis Collaboration with JHL for China and Southeast Asia Immunotherapy collaboration with Merck (Pembrolizumab) Immunotherapy collaboration with Genentech (Atezolizumab) Skin Lesions Developed under strategic collaboration with Novartis BL-1220 BL-1230 Developed under strategic collaboration with Novartis AGI-134 Solid tumors
BL-8040 Best-in-class CXCR4 antagonist for multiple oncology indications
BL-8040 Highlights Best-in-class CXCR4 antagonistPlatform molecule with MOA relevant in multiple tumorsMost advanced compound targeting CXCR4Partnerships with leading companies and institutions (Genentech, Merck, MDACC)Multiple clinical studies ongoing or in final planning stagesMultiple studies under immunotherapy partnerships with Genentech and MerckData readouts in 2017 and 2018Large phase 2b study in AML consolidation treatment line running at full steamData readout in H2 2019; potential interim analysis in H2 2018Initiation of phase 3 registrational study in autologous SCM planned for H2 2017Received Orphan Designation from FDA for AML & SCMPotential for multiple phase 3 studies under immunotherapy partnerships
BL-8040 Clinical Development Program Pre-Clinical Phase 1 Phase 2 Phase 3 INDICATION STUDY ONGOING PLANNED AML Consolidation ACUTE MYELOID LEUKEMIA (AML) AML Maintenance (Atezolizumab) BLAST BATTLE H2/2017 initiation – Genentech collab Immunotherapy Combination Pancreatic (Pembrolizumab) COMBAT Merck collab MORPHEUS Pancreatic (Atezolizumab) H2/2017 initiation – Genentech collab MORPHEUS Gastric (Atezolizumab) H2/2017 initiation – Genentech collab MORPHEUS NSCLC (Atezolizumab) H2/2017 initiation – Genentech collab STEM CELL MOBILIZATION BL-8040.07 SCM as Single Agent (Allogeneic) GENESIS SCM (Autologous) H2/2017 initiation Pancreatic (Pembrolizumab) BL-8040.11 MDACC collab
BL-8040 in Immuno-Oncology
BL-8040’s MoA in Cancer Immunotherapy Immunostimulant - BL-8040 is a powerful mobilizer of immune cells from the bone marrow and lymph nodes (T-cells, B-cells, immature dendritic-cells and NK-cells)Potentiator - BL-8040 increases infiltration of immune cells into tumors (exhibiting a synergistic effect with anti PD1/PD-L1 immune checkpoint inhibitors)Microenvironment modifier - BL-8040 affects the tumor microenvironment by decreasing CXCR4-mediated migration of immune suppressor cells (i.e. MDSCs, Tregs) PD-L1/PD1 CXCR4 SDF1 Immunosuppressive cells Tregs CD8+ CTL BL-8040 PD1 Ab PD-L1 Ab PD1 or PD-L1 Ab. BL-8040
BL-8040 is a Powerful Mobilizer of Immune Cells(clinical data) BL-8040 CD56+/CD3- NK-cells CD3+ T-cells CD19+ B-cells Placebo Healthy volunteers were treated with BL-8040 or placeboSingle administration of BL-8040 triggered substantial mobilizationLong receptor occupancy results in prolonged effect (≥ 24 hours) Time post BL8040 (hr)
BL-8040 Increases T-Cell Infiltration into Tumors (mice model) Model: Orthotropic syngeneic tumors in pancreas of C57BL/6 male mice Treatment with BL-8040 for 10 consecutive days Treatment with BL-8040 induces accumulation of CD3+ T-cells in PDA tumors IHC: aCD3
BL-8040 Increases T-Cell Infiltration into Tumors (cont.) FACS analysis confirmed enrichment of immune cells within the tumor * Tumor sections were enzymatically digested and single cell suspensions were analyzed by FACS** Values in the table represent absolute cell count
BL-8040 Affects the Tumor Microenvironment(CXCR4/SDF-1 Immuno-Suppressive Role in Cancer) SDF-1 expression is an independent predictor of poor survival in cancer patientsCXCR4/SDF-1 axis is key pathway mediating the attraction of immuno-suppressive cells (MDSCs, Tregs, pDCs) to the tumor environment CXCR4 inhibition selectively reduces infiltration of Tregs into tumors and inhibits the migration of MDSCs to the tumor Righi E. et al., Cancer Res 2011;Zou W et al., Nature Medicine, 2001;Obermajer et al., Cancer Res, 2011 Ovarian epithelial carcinoma cells express functional SDF-1 CXCR4 inhibition High CXCR4 expression in cancer–isolated MDSCs MDSCs migration is inhibited by CXCR4 blockade
Immunotherapy Collaboration with Genentech Four phase 1b studies planned to investigate combination of BL-8040 with Genentech’s TecentriqTM (Atezolizumab - anti-PDL1 immune checkpoint inhibitor)Genentech to sponsor and conduct three phase 1b studies in multiple solid tumors BioLineRx to sponsor and conduct phase 1b study in (maintenance) AMLOpen-label, repeated administration studies in up to 60 patients eachStudy endpointsClinical response, safety and tolerabilityMultiple pharmacodynamic parametersStudies are expected to commence in H2 2017; top-lineresults expected in 2019
Immunotherapy Collaboration with Merck Phase 2a study to examine combination of BL-8040 with Merck’s Keytruda® (anti-PD1 immune checkpoint inhibitor)Up to 30 patients with metastatic pancreatic adenocarcinomaOpen-label, single-arm trial with sites in the US, Israel and South KoreaStudy endpointsClinical response, safety and tolerabilityMultiple pharmacodynamic parameters, including ability to improve infiltration of T cells into tumor and their reactivityStudy commenced at end of Q3 2016Partial results expected H2 2017Top-line results expected H2 2018
* BL-8040 Mechanism of Action in AML Binds CXCR4 with high affinity (1-10 nM)Maintains extended inhibition of CXCR4 through long receptor occupancy (>24 hours)BL-8040 induces apoptosis of AML blasts by down-regulation of survival factorsBone-marrow clearance - eliminates minimal residual disease BL-8040 directly induces apoptosis BL-8040 sensitizes tumor cells to other drugs BL-8040Induces terminal differentiation of tumor cells BL-8040induces tumor cells mobilization
BL-8040 Mechanism of Action in AML Binds CXCR4 with high affinity (1-10 nM)Maintains extended inhibition of CXCR4 through long receptor occupancy (>24 hours)BL-8040 induces apoptosis of AML blasts by down-regulation of survival factorsBone-marrow clearance - eliminates minimal residual disease BL-8040 directly induces apoptosis BL-8040 sensitizes tumor cells to other drugs BL-8040 BL-8040 BL-8040Induces terminal differentiation of tumor cells BL-8040 BL-8040 + SOC BL-8040induces tumor cells mobilization
* BL-8040 in AML – Background and Direction Company conducted successful proof-of-concept phase 2a study in relapsed/refractory AML (45 patients)Showed robust bone marrow clearance, induction of apoptosis and terminal differentiation of AML cells Excellent safety and tolerability
BL-8040 in AML – Background and Direction Company conducted successful proof-of-concept phase 2a study in relapsed/refractory AML (45 patients)Showed robust bone marrow clearance, induction of apoptosis and terminal differentiation of AML cells Excellent safety and tolerability
AML – Clinical Development Status Results support accelerated development in AML space with potential for elimination of minimal residual disease (MRD)Consolidation AML phase 2b study ongoing194 patients, double-blind, placebo controlled at ~25 sites in GermanyEnrollment ongoing: potential interim results in 2018; top-line results by end of 2019Maintenance AML phase 1b study (under Genentech collaboration) in late planning stagesCombination with Atezolizumab as maintenance therapy for high-risk, elderly AML patientsUp to 60 patients, open label study at multiple leading sites in the USExpected to commence in H2 2017
BL-8040 in SC Mobilization
Stem Cell Mobilization for Autologous Transplantation G-CSF is current standard for autologous stem cell mobilization4-6 daily injections of G-CSF, plus 1-4 apheresis sessions required50-70% of patients are poor mobilizersFor poor mobilizers, 1-4 daily injections of Mozobil on top of G-CSF are requiredFast route to registration in autologous SCMRegistrational study expected to commence in H2 2017 based on confirmatorymeeting with FDA held in April 2017:BL-8040 plus G-CSF will be compared to G-CSF plus placeboStudy expected to enroll ~200 patients in totalPrimary endpoint: proportion of patients who mobilize ≥6 million CD-34+ cells in up to 2 leukapheresis sessions in MM patientsPhase 2 allogeneic transplantation study ongoing as complementary indicationSuccessful partial results recently announcedSingle injection of BL-8040 mobilizes sufficient amounts of cells without need for G-CSFTopline results by end of 2017
BL-8040 is Powerful Mobilizer of CD34+ Cells Substantial HSC mobilization from BM to PB was recorded Consistent pattern of mobilization across all subjects treated with BL-8040 Time post BL-8040 (hr) BL-8040:
Single BL-8040 Administration Results in Robust Collection of Stem Cells Using Single Apheresis Subject # Whole blood processed (L) % CD34+ cells CD34+/KG (Donor weight) CD34+/KG (70kg recipient weight) 5001 9.8 0.75 4,091,848 5,091,429 5002 16.0 1.01 11,964,615 11,998,800 5003 16.6 0.85 13,667,866 14,917,500 5004 16.2 0.76 10,154,834 11,794,114 5005 16.6 0.78 11,366,255 15,230,781 5006 16.5 0.87 13,068,548 14,711,451 5007 17.5 0.64 11,076,197 9,652,114 5008 16.7 0.61 9,623,736 9,994,937 Median 16.5 ± 2.3 L 0.77 ± 0.13 % 11.2 x 106 (± 2.8 x 106) 11.9 x 106 (±3.5 x 106) Leukapheresis started 4 hrs post BL-8040 injection using the Spectra Optia® Apheresis SystemThe median amount of collected stem cells was higher than 11 x 106 per kg CD34+/µL ; WBC x 103/ µL Time post BL-8040 CD34+ PB levels 24 hr post BL-8040 are still high even after leukapheresis
CXCR4 Competitor Landscape Compound(Company) Dev. Stage Molecule Type Indications (under development) AML SCM IO BL-8040 (BioLineRx) Phase 2 Peptide (sc) Auto/Allo SCM; AML (r/r, consolidation, maintenance);Solid tumors (gastric, pancreatic, NSCLC) Ph 2 Ph 3 ready Ph 1/2 (+Pembro/+Atezo) Mozobil (Genzyme/Sanofi) Launched Small molecule (IV) Auto SCM;AML; Solid tumors (pancreatic, ovarian and colorectal cancers) Ph 1/2 Launched - LY-2510924(Eli Lilly) Phase 2 Peptide (IV) r/r AML; solid tumors Ph 1 - Ph 1 (+Durvalumab) Ulocuplumab(BMS) Phase 2 Ab(IV) AML Ph 1/2 - Terminated X4P-001(X4 Pharmaceuticals) Phase 2/3 Small molecule (oral) WHIM syndrome; RCC, melanoma; ovarian cancer - - Ph 1/2 (+Pembro/+Nivo)
BL-8040 Mozobil Ulocuplumab Affinity for CXCR4 1-10 nM 84 nM 5nM CXCR4 Binding site Extracellular domains in the CXCR4 receptor Trans-membrane regions in the CXCR4 receptor Extracellular domains in the CXCR4 receptor Molecule Type Peptide Small molecule Ab Plasma half-life 1-3 hr ~3-5 hr More than 24hr Receptor occupancy More than 24 hr ~2 hr Not published Cancer Cell Death Remarkable apoptosis in samples from clinical study patients (Phase 2 study rrAML) Has no effect on cancer cell apoptosis(Reum H et al., 2015) Apoptosis of AML cells. Modest effect in patients.(ASH 2013) Mobilization (fold increase leukocytes/ blast) 4/8 (Phase 2 in rrAML) 1.8/2.8(Uy G.L. et al., Blood 2017; Phase 1/2 in rrAML) 2/5 (Becker P.S. et al; Blood 2014; Phase1 in rrAML) T-Cell Infiltration into Tumors Infiltration was demonstrated in preclinical murine models Infiltration was demonstrated in preclinical murine models Not published Other remarks re BL-8040 (Abraham M et al., 2017):BL-8040 induces apoptosis of AML blasts by down-regulating ERK BCL-2, MCL-1 and cyclin-D1 BL-8040 synergizes with FLT3 and BCL-2 inhibitors to induce AML cell death Superior Neutral Inferior BL-8040 is Best-in-Class vs. Competitors
BL-8040 Summary Most advanced antagonist of CXCR4, an exciting and validated targetRobust platform for multiple oncology indicationsImmunotherapyAMLStem-cell mobilization/transplantationSignificant efficacy demonstrated in numerous clinical studiesPartnerships with Genentech and Merck in immuno-oncologyRegistrational study in autologous SCM expected to start in H2 2017
AGI-134 Alpha-Gal immunotherapy, activating anti-tumor response to patient’s own neoantigens
AGI-134 Highlights Unique mechanism harnessing naturally occurring immune machineryPromotes systemic anti-tumor response against patient’s own tumor antigensApplicable for large array of tumorsTargets primary tumor, as well as existing and potential future metastasesReduces immuno-suppressive nature of tumor microenvironmentNear-clinical stage (following pre-IND meeting)Phase 1 in solid tumors expected to initiate in H1 2018; final preparations underwayProposed initial indications: melanoma, liver, head and neck, colorectal, breast cancer, lymphomaStudies to include substantial biomarker identification
AGI-134 Mechanism of ActionTransforming cold into hot tumors, targeting patient’s own neoantigens Coating of tumor cells by AGI-134 Tumor destruction Intra-tumoral injection of AGI-134 Binding of anti - a Gal antibodies Initial cell death Spillage of tumor-associated antigens Alteration of tumormicroenvironment Increased uptake by antigen presenting cells Stimulation & recruitment of T cells Antigen presenting cell Tumor cell AGI-134 NK cell C3a / C5a Neoantigens T cell C1q anti - a Gal
AGI-134: Key Efficacy Findings In vitro and in vivo studies have validated the underlying steps of the MOASingle dose of AGI-134 demonstrated systemic effect by protecting mice from secondary tumor development for over 90 days Combination of AGI-134 with immune checkpoint inhibitor (PD-1) gave increased efficacy over either agent alone
AGI-134: Unique MOA Among Intratumoral Agents Oncolytic viruses PAMPs AGI-134 Injected tumor cells identified by naturally occurring pre-existing antibodies Antibody-bound tumor cells destroyed by activated complement and ADCC Tumor neoantigens release by spilling Antibody-activated complement system creates pro-inflammatory milieu in the tumor microenvironment Complement chemo-attractants recruit immune cells to the tumor Activation of antigen presenting cells and increased (APCs) uptake of tumor antigens APCs induce a follow-on systemic immune response by the stimulation and clonal expansion of T cells
AGI-134 Summary Novel and demonstrated mechanism of action Technology potential Addresses wide range of poorly treated solid tumorsTransforms “cold” into “hot” tumorsTargets patient’s neoantigensStrong pre-clinical data, clear development pathway discussed with MHRA and FDANear-clinical stage, with first-in-man study expected to initiate H1 2018Phase 1/2 development plan designed to include comprehensive biomarker strategyDemonstrated synergy with immune checkpoint inhibitorsAcquisition of Agalimmune provides BioLineRx with several earlier-stage projects, as well additional capabilities to augment focus on immunology and oncology
BioLineRx Management Philip A. Serlin, CPA, MBA – Chief Executive OfficerServed as the Company’s CFO and COO from 2009 to 2016. Previously CFO and COO of Kayote Networks and CFO of Tescom Software Systems Testing. Background includes senior positions at Chiaro Networks and at Deloitte in Tel Aviv, and at the SEC in Washington, D.C.Mali Zeevi, CPA – Chief Financial OfficerServed as the Company’s Senior Director of Finance and Reporting 2009-2016. Previously Vice President Finance at Tescom Software Systems Testing and manager at PriceWaterhouseCoopers.David Malek, MBA – Chief Business OfficerJoined the Company in 2011 as Vice President of Business Development. Previously in various management positions at Sanofi-Aventis, including Director of Oncology - New Products and Business Development.Ella Sorani, PhD – VP DevelopmentJoined the Company in January 2017. Previous 16 years served in a number of management positions in the global R&D division at Teva Pharmaceutical Industries. In most recent position, led global development of one of Teva’s leading innovative late stage compounds. Abi Vainstein, MD – VP Clinical and Medical AffairsServed as the Company’s Senior Medical Director from 2014 to 2016. Previously Director and Clinical Program Leader for COPAXONE®, and several other senior medical positions at Teva Pharmaceutical Industries.
Strategic Collaboration with Novartis Novartis selected BLRX as its partner for asset identification and early developmentExclusive first look at all Israeli-based projects scouted by BioLineRxCo-develop selected projects through clinical proof-of-concept (POC)Unique collaboration provides lasting shareholder value and key insights3 projects brought under collaboration so far, in areas of fibrosis and inflammationFinancial highlights:Upfront $10 million equity investment in BLRXUpon selection of clinical project (or when a project reaches IND), BioLineRx receives:$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
Cash position$55 million as of April 30, 2017Existing financial resources fund operational requirements into 2019Capital structureTraded on NASDAQ and TASE (Symbol: BLRX)96 million shares outstanding; 104 million fully dilutedUS shareholders represent ~70% of investor base, including key life-sciences investorsOther~50 employees, approximately 2/3 with advanced degreesAnalyst coverage: JMP Securities, HC Wainwright, Maxim Group Financial Summary
Principal Expected Development Milestones in 2017/2018 2018 2017 BL-8040 (Autologous SCM) phase 3 initiation BL-8040 (Pancreatic Cancer) phase 2 partial results BL-8040 (Allogeneic SCM) phase 2 top-line results BL-8040 (AML Maintenance) phase 1b initiation BL-8040 (Multiple Solid Tumors) phase 1b initiation BL-8040 (Pancreatic Cancer) phase 2 top-line results BL-8040 (AML Consolidation) phase 2b interim analysis Does not include milestones expected from newly in-licensed programs BL-8040 (AML Maintenance) phase 1b partial results BL-8040 (Multiple Solid Tumors) phase 1b partial results AGI-134 (Multiple Solid Tumors) phase 1/2 initiation BL-8040 (Allogeneic SCM) phase 2 partial results √
Takeaways…… Focus on oncology and immunology (mainly immuno-oncology)9 clinical studies ongoing or planned for next 12-18 monthsRead-out from 3-4 phase 2 studies over next 12-18 monthsInitiation of phase 3 registrational study expected in H2 2017Significant collaborations with 3 of the leading global pharma companiesAnticipated new clinical/advanced pre-clinical compounds to enter pipelineContinued execution of strategic transactions as opportunities arise