BL-8040 Best-in-class CXCR4 antagonist for treatment of multiple oncology indications

BL-8040 Highlights Platform Molecule: Multiple cancer and hematological indicationsReceived Orphan Designation from FDA for AML & SCMMode of Action: Inhibits CXCR4 (a cell surface protein)CXCR4 overexpressed in >70% of tumors; correlates with severity; well validatedIncreases sensitivity to anti-cancer agents by affecting tumor microenvironmentSignificant clinical superiority in immune cell mobilization Potential synergy with multiple immuno-oncology platformsInduces cancer cell death (apoptosis)Multiple clinical studies ongoing or in final planning stagesIncluding immunotherapy collaborations with Genentech and Merck for multiple cancer indications

BL-8040 MoA in Immuno-Oncology

BL-8040 Potential 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) Healthy volunteers treated with BL-8040 or placebo (clinical trial BL-8040.02)Single administration of BL-8040 (1 mg/kg) triggered substantial increase in T-cells, B-cells , NK-cells and Dendritic-cells in the bloodLong receptor occupancy results in prolonged effect (≥ 24 hours) T cells BL-8040 Placebo Blood levels Fold change from time 0 B cells NK cells

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 as single agent for 10 consecutive days CD3 IHC Treatment with BL-8040 induces accumulation of CD3+ T-cells in PDA tumors

The immuno-suppressive role of CXCR4 in the tumor microenviroment CXCL12 expression is an independent predictor of poor survivalCXCR4-CXCL12 axis is the key pathway mediating the attraction of immuno-suppressive cells (MDSCs, T-regs, pDCs) to the tumor microenvironment preventing local T-cell activationCXCR4 inhibition selectively reduces intratumoral Tregs-cell infiltrationCXCR4 inhibition selectively inhibits the migration of MDSCs to the tumor Ovarian epithelial carcinoma cells express functional SDF-1 CXCR4 inhibition Righi E. et al., Cancer Res 2011; Zou W et al., Nature Medicine, 2001; Obermajer et al., Cancer Res, 2011 High CXCR4 expression in cancer–isolated MDSCs MDSCs migration is inhibited by CXCR4 blockade

BL-8040 Clinical Development Program

BL-8040 Clinical Development Program Pre-Clinical Phase I Phase II Phase III INDICATION PROTOCOL BL-8040.07 SCM as Single Agent (Allogeneic) AML Consolidation ACUTE MYELOID LEUKEMIA (AML) STEM CELL MOBILIZATION Immunotherapy Combination Pancreatic (Pembrolizumab) COMBAT AML Maintenance (Atezolizumab) BLAST BATTLE MORPHEUS Pancreatic (Atezolizumab) MORPHEUS Gastric (Atezolizumab) MORPHEUS NSCLC (Atezolizumab) ONGOING PLANNED Planned to initiate H1/2017 Planned to initiate Q3/2016 Planned to initiate H1/2017 Planned to initiate H1/2017 Planned to initiate H2/2017

AML – Background and Direction Company conducted successful proof-of-concept phase 2a study in relapsed/refractory AML38% composite remission rate versus 20% historical benchmarkShowed longer than expected durability of remissionsExcellent safety and tolerabilityShowed direct triple anti-leukemic activity: robust mobilization, induction of apoptosis and terminal differentiation of AML cells Results support accelerated development in AML spaceBL-8040’s high response rate indicates selective effect on chemotherapy resistant cellsBL-8040 showed direct anti-leukemic activity and bone marrow clearance by mediated robust mobilization suggesting potential elimination of minimal residual diseaseResults encourage accelerated development of two specific AML treatment lines: (i) consolidation and (ii) maintenance

AML – Clinical Development Status Consolidation AML phase 2b study ongoing194 patients, double-blind, placebo controlled at ~25 sites in GermanyEnrollment ongoingInterim results expected in 2018Maintenance AML phase 1b study (in collaboration with Genentech)Combination study with Atezolizumab as maintenance therapy for high-risk elderly AML patients following induction treatmentUp to 60 patients, open label study at multiple leading sites in the USIn late planning stages, expected to commence in first half of 2017

Phase IIb - Consolidation Treatment for AML Patients A Phase II, double- blind, placebo controlled, randomized, multicenter study to assess the efficacy of BL-8040 in AML patients in first complete remissionStudy DesignDouble blind, placebo controlled, repeated administrations, multiple treatment cycles. TreatmentTwo or three cycles (age based) of consolidation with high-dose Ara-C together with either BL-8040 or Placebo. Ara-C 1 g/m2 per dose for patients older than 60 years and 3 g/m2 for patients younger than 60 years. Ara-C is administered IV twice a day (10 am and 10 pm) over 3 hours on day 1, 3 and 5. Placebo or BL-8040 is administered SC at 8 a.m. on days 1, 2, 3, 4 and 5 of each consolidation cycle. EndpointsTo compare the Relapse Free Survival (RFS) 3, 6, 9, 12 and 18 months after randomizationTo assess the toxicity, safety and tolerability of BL-8040 in combination with high-dose Ara-CTo assess MRD (by FACS/PCR) at time of enrollment and during the follow up period (3, 6, 9, 12 and 18 months)To assess overall survival (OS) as an open label extension SCREENING TREATMENT PERIOD FOLLOW-UP AGE <60 BM Biopsy Cycle 1 Cycle 2 Cycle 3 Day 1 2 3 4 5 28 1 2 3 4 5 28 1 2 3 4 5 28 EOT 6M 9M 12M 18M BL-8040 Ara-C

Phase Ib - Combination with Immunotherapy as Maintenance Treatment for AML Patients A Phase Ib, Multicenter, Single Arm, Open-label study, to Evaluate the Safety and Efficacy of BL-8040 and Atezolizumab combination for maintenance treatment in AML elderly High Risk patientsStudy DesignOpen label, repeated administrations, multiple treatment cycles. High risk AML patients unfit/not planned for transplant; Maintenance after consolidation for patients in CR1TreatmentBL-8040 is administered SC on days 1-3 of each 21-day cycle Atezolizumab is administered IV on day 2 of each 21-day cycleEndpointsTo assess Relapse Free survival assessed from the day of CR1 until relapseTo assess the toxicity, safety and tolerability of BL-8040 in combination with AtezolizumabTo assess MRD (by FACS) at time of enrollment and on treatmentTo assess overall survival (OS) SCREENING BL-8040 + ATEZOLIZUMAB REPEATED CYCLES UNTIL PROGRESSION BL-8040 Atezolizumab Cycle 1 Cycle 2 1 21 1 21 Bone marrow Aspiration Bone marrow Aspiration will be done at Baseline, Month 1, 2, 3, 6, 9,12 and then every 6 months till discontinuation

Immunotherapy Collaboration with Genentech Several phase 1b studies to investigate combination of BL-8040 with Genentech’s TecentriqTM, (anti-PDL1 immune checkpoint inhibitor) in multiple cancer indicationsGenentech to sponsor and conduct several phase 1b studies in multiple solid cancer indications (gastric, NSCLC, pancreatic)BioLineRx to sponsor and conduct phase 1b study in (maintenance) AMLOpen-label, multicenter, repeated administrations studiesStudy endpointsClinical response, safety and tolerabilityMultiple pharmacodynamic parametersStudies are expected to commence H1 2017

Phase Ib - Combination with Tecentriq for Solid tumors SCREENING BL-8040 + ATEZOLIZUMAB REPEATED CYCLES UNTIL PROGRESSION BL-8040MONOTHERAPY BL-8040 Cycle 1 Cycle 2 1 5 8 29 1 21 A basket phase Ib, multicenter, open-label study to Assess the Safety and Efficacy of BL-8040 in Combination with Atezolizumab in Patients with NSCLC, Gastric and Pancreatic CancerStudy DesignOpen label, repeated administrations, multiple treatment cycles until progressionTreatmentDaily SC BL-8040 injection as monotherapy for five consecutive days Combination part - On day 8 start combination therapy consisting of SC BL-8040 TIW and IV of Atezolizumab E3W The combination therapy will continue for up to two years, or until progression, clinical deterioration or early termination, whichever comes firstEndpointsTo assess Objective Response Rate (ORR) according to RECIST 1.1 criteria.Progression-free and Overall survivalSafety and tolerability of the combinationMultiple pharmacodynamic parameters Atezolizumab

Immunotherapy Collaboration with Merck Phase 2a study to examine combination of BL-8040 with Merck’s Keytruda® (anti-PD1 immune checkpoint inhibitor) in pancreatic cancerUp to 30 patients with metastatic pancreatic adenocarcinomaOpen-label, multicenter, single-arm trialSites 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 reactivity.Study will commence by end Q3 2016All regulatory submissions were completedPartial results expected H2 2017Top-line results expected H2 2018

Phase IIa - Combination with Keytruda for PDAC A phase IIa, multicenter, open-label study to Assess the Safety and Efficacy of BL-8040 in Combination with Pembrolizumab in Patients with Advanced Pancreatic CancerStudy DesignOpen label, repeated administrations, multiple treatment cycles until progressionTreatmentDaily SC BL-8040 injection as monotherapy for five consecutive days Combination part - On day 8 start combination therapy consisting of SC BL-8040 TIW and IV of Pembrolizumab E3W The combination therapy will continue for up to two years, or until progression, clinical deterioration or early termination, whichever comes firstEndpointsTo assess Objective Response Rate (ORR) according to RECIST 1.1 criteria.Progression-free and Overall survivalSafety and tolerability of the combinationMultiple pharmacodynamics parameters SCREENING BL-8040 + PEMBROLIZUMAB REPEATED 21 DAY CYCLES UNTIL PROGRESSION BL-8040MONOTHERAPY BL-8040 Pembrolizumab Cycle 1 Cycle 2 1 5 1 21 Biopsy 1 21 1 5 1 21 1 21 Imaging (1-15 pt) (16-30 pt)

BL-8040 Development and Commercialization Strategy in SCM

Stem Cell Mobilization for Transplantation G-CSF is current standard for stem cell mobilization4-6 daily injections of G-CSF, plus 1-4 apheresis sessions requiredG-CSF is associated with bone pain and other side effectsG-CSF is not approved for allogeneic transplantationNo agents are approved for allogeneic transplantationPhase 1 results support BL-8040 as single agent one day collection regimen Type B meeting with the FDA held in October 2015Phase 2 study allogeneic transplantation ongoingCollaboration with Washington University School of Medicine, Division of Hematology and OncologyPartial results by end of 2016; topline results by end of 2017

BL-8040 Long Term Clinical Development Plan Development of BL-8040 for SCM for allogeneic stem cell transplantation The overall goal is to demonstrate that BL-8040 produces a similar quality of allograft as that produced by G-CSFStudies will likely demonstrate advantages:Shorter duration of treatment prior to leukapheresis – single BL-8040 injection versus 4-5 injections of G-CSF with or without off label treatment with Plerixafor.Reduction in the number of leukapheresis collections in order to obtain an adequate amount of cells for bone marrow transplant.Overall donor treatment duration of 1-2 days.Development plan toward registration:Single pivotal studyTotal of 370 treated volunteersLong-term follow up of healthy donors could be done in a post marketing settingCompany considers taking all the way toward commercialization, either with a partner or by itself

BL-8040 Long Term Clinical Development Strategy 2016 2017 2018 2019 2020 2021 2022 SCM Allogeneic Ongoing Ph2a Long term follow up Drug registration (NDA) Commercialization Prep for Ph3 Phase 3 AMLConsolidation Ongoing Ph2b BLAST study Drug registration (NDA) Prep for Ph3 Potential Ph3 conducted by BioLineRx and/or partner Immuno-Oncology MSD Ph2a PDAC COMBAT study Out licensing deal and/or Ph3 conducted by partner Ph2a PDAC MDACC study GENE Ph2a AML BATTLE study Out licensing deal and/or Ph3 conducted by partner Ph2a solid tumors MORPHEUS study Phase 3 ready positionInitial input from open label immuno-oncology studiesAML consolidation interim results during 2018 Late stage SCM Phase 3 – NDA for SCM Final data from immuno-oncology studiesAdvanced stage of development for AML consolidation Multiple value generating events in coming months with strong potential for partnership deal early in 2018

BL-8040 Summary BL-8040 is platform for multiple solid and liquid oncology indicationsFocus on immunotherapy, AML and allogeneic stem-cell transplantationBL-8040 has demonstrated efficacy in several clinical studiesBL-8040’s MoA has been clinically validatedCXCR4 is a validated targetCollaborations with leading global pharma companies provide significant additional validation of program potential

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