Transforming science into medicine

Transcription

1 Transforming science into medicine

2 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.

3 We are committed to developing novel compounds in oncology and immunology that will deliver life-changing innovations for patients. Philip Serlin, CEO

4 4 Who are we? NASDAQ: BLRX Oncology and immunology focus Lead assets: BL-8040 AGI-134 Significant pharma collaborations Attractive investment case Strong balance sheet $44 million (end Q1 2018) Significant upcoming milestones: Top line combination results from phase 2 COMBAT study in pancreatic cancer Results from initial lead-in period of phase 3 GENESIS study in SCM Interim analysis from phase 2b BLAST study in consolidation AML

5 5 Management team PHILIP A. SERLIN Chief Executive Officer MALI ZEEVI Chief Financial Officer HILLIT MANNOR SHACHAR Vice President Business Development ABI VAINSTEIN- HARAS, MD Vice President Clinical & Medical Affairs ELLA SORANI, PhD Vice President Research & Development

6 6 Main pipeline assets PROJECT INDICATION PRE-CLINICAL PHASE 1 PHASE 2 PHASE 3 REGULATORY APPROVAL CANCER BL-8040 Stem-cell mobilization Consolidation AML Maintenance AML Gastric cancer Non-small cell lung cancer Pancreatic cancer Pancreatic cancer AGI-134 Solid tumors IMMUNOLOGY BL-1230 Dry eye syndrome OTHER BL-5010 Skin lesions

7 BL-8040 Best-In-Class CXCR4 Antagonist for Multiple Oncology and Hematology Indications For treatment of solid tumors, AML and indications requiring hematopoietic stem cell transplantation

8 8 BL-8040 a best-in-class CXCR4 antagonist targeted at multiple indications BL-8040 is a 14-amino acid synthetic cyclic peptide, high-affinity CXCR4 antagonist with long receptor occupancy (>48 hours) and extended CXCR4 inhibition

9 9 Stem-cell mobilization for patients with hematological malignancies undergoing bone-marrow transplantation Patients with hematological malignancies often require HSC transplant after treatment to restore immune system Significant unmet medical need in SCM Multiple apheresis sessions required 50-70% of patients are poor mobilizers For poor mobilizers, 1-4 daily injections of Mozobil on top of G-CSF are required BL-8040 potentially offers a more effective and convenient mobilization option for patients

10 10 Role of BL-8040 in stem-cell mobilization

11 11 BKTS001 Phase 1/2a study: Stem-cell mobilization in multiple myeloma patients NCT (N=16) Multiple myeloma patients were treated with increasing doses of BL-8040 on top of standard-of-care to assess mobilization of HSCs BL-8040 increases HSC mobilization in a dose-dependent manner Conclusion: BL-8040 increased mobilization of HSCs when added to standard-of-care, enabling collection of sufficient HSCs in single apheresis session

12 12 GENESIS Phase 3 study: Mobilization of HSCs for autologous transplant in multiple myeloma patients Initiated Q Phase 3 randomized, placebo-controlled, safety and efficacy study (n=177): NCT Study design Part 1: Lead-in period - dose confirmation in up to 30 multiple myeloma patients Part 2: Randomized placebo-controlled study in combination with G-CSF in 177 multiple myeloma patients Primary endpoint Proportion of subjects mobilizing 6.0 x 10 6 CD34 + cells/kg with up to 2 apheresis sessions in preparation for auto-hct after a single administration of BL-8040 or placebo + G-CSF BL-8040 potentially offers patients: Robust HSC mobilization Single administration on top of SOC No more than two apheresis sessions

13 13 BL-8040 s potential role in AML treatment pathway increasing leukemic cell exposure to anti-cancer therapies Malignant cells are harbored within protected niche of bone marrow (minimal residual disease), which impacts remission and survival rates BL-8040 mobilizes AML cells to the peripheral blood where they are exposed to anti-cancer therapies, including checkpoint inhibitors

14 14 Role of BL-8040 in AML 1. Bensinger W et al. Bone Marrow Transplant 2009;43:

15 15 BL Phase 1/2a study: Encouraging results in patients with relapsed/refractory AML Phase 1/2a dose escalation/expansion study (n=42): NCT Study design Dose escalation (0.5 to 2.0 mg/kg) with expansion cohort at 1.5mg/kg Safety MTD was not reached, mild/moderate (grade 2/3) transient AEs Efficacy 1. Composite CR for dose selected for expansion (1.5 mg/kg) = 39% 2. Median OS for dose selected for expansion (1.5 mg/kg) of 9.2 months, as compared to historical data of 6.1 months for patients treated only with high-dose Ara-C Comparison of the composite response rate (CR + CRi) of BL high-dose Ara-C, versus high-dose Ara-C alone BL CR, complete response; CRi, complete response with incomplete hematological recovery

16 16 BLAST Phase 2b study: Consolidation therapy for AML patients in first remission Phase 2b double-blind, multi-center placebo controlled study (n=194): NCT Treatment: Two or three cycles (age-based) of high-dose Ara-C in combination with either BL-8040 or placebo Endpoints Relapse free survival (RFS) Toxicity, safety and tolerability of BL-8040 in combination with high-dose Ara-C Minimal residual disease (MRD) Overall survival (OS) BL-8040 potentially offers AML patients prolonged remission and increased overall survival

17 17 BATTLE Phase 1b/2 study: Combination of BL-8040 and atezolizumab in AML patients with high risk of relapse Phase 1b/2 single arm, multi-center open-label study (n=60): NCT To evaluate the safety and efficacy of BL-8040 in combination with atezolizumab for maintenance treatment in AML patients 60 years or older Endpoints Relapse free survival (RFS) Toxicity, safety and tolerability of BL-8040 in combination with atezolizumab Minimal residual disease (MRD) Overall survival (OS) BL atezolizumab potentially offers prolonged remission and better overall survival for elderly AML patients not eligible for transplant

18 18 BL-8040 addressing unmet needs in cancer immunotherapy Despite significant advances in cancer immunotherapy, material needs remain: Improving efficacy of immunotherapy in cold tumors, such as pancreatic cancer Increasing rates and durability of response to existing therapies such as anti-pd1 and anti-pdl1 antibodies BL-8040 may address these needs by: Mobilization of immune cells to peripheral blood circulation Increasing immune cell infiltration into tumors Reducing immunosuppression in tumor microenvironment

19 19 Role of BL-8040 in solid tumors

20 20 Data supporting role of BL-8040 in immunotherapy Robust mobilization Healthy volunteers were treated with BL-8040 or placebo Single administration of BL-8040 triggered substantial mobilization Long receptor occupancy results in prolonged effect ( 24 hours) Tumor infiltration 1 Pre-treatment Microenvironment modification CXCR4 antagonism selectively inhibits the migration of immunosuppressive cells Day 5 BL-8040 monotherapy % specific migration of MDSCs p< MDSCs migration is inhibited by CXCR4 blockade 2 1. Hidalgo, Manuel M., et al. "Evaluation of pharmacodynamic (PD) biomarkers in patients with metastatic pancreatic cancer treated with BL-8040, a novel CXCR4 antagonist." (2018): Obermajer et al. Cancer Res 2011;71:

21 21 BL-8040 ongoing collaborations with global pharma companies NCT , NCT , NCT , NCT COMBAT Phase 2a study of BL pembrolizumab (Keytruda ) Study in metastatic pancreatic cancer Open-label multi-center single arm study Commenced September 2016 Top-line results expected H Four phase 1/2 studies planned of BL atezolizumab (Tecentriq TM ) 3 studies in solid tumors (pancreatic, gastric, NSCLC) 1 study in AML Open-label multi-center single arm studies Pancreatic and gastric studies commenced H2 2017

22 22 COMBAT Phase 2a study: Advanced pancreatic cancer Phase 2a open-label, multi-center study in combination with pembrolizumab (n=30): NCT To assess the safety and efficacy of BL-8040 in combination with pembrolizumab (Keytruda) in patients with advanced pancreatic cancer Endpoints Objective response rate according to RECIST 1.1 criteria Disease control rate Progression-free and overall survival Safety and tolerability of the combination Multiple pharmacodynamic parameters Intermediate monotherapy results BL-8040 increased absolute number of immune cells in the blood BL-8040 had long CXCR4 receptor occupancy on lymphocytes BL-8040 caused a reduction of Tregs in peripheral blood BL-8040 increased T-cell tumor infiltration in 75% of patients

23 23 MORPHEUS Phase 1b/2 study: Pancreatic, gastric and NSCLC Phase 1b/2 open-label, multi-center, randomized study in combination with atezolizumab : NCT , NCT Umbrella study to evaluate efficacy and safety of multiple immunotherapy-based treatment combinations in patients with locally advanced unresectable or metastatic pancreatic, gastric and NSCLC cancers Endpoints Objective response rate (ORR) according to RECIST 1.1 criteria Progression-free and overall survival Safety and tolerability of the combination Multiple pharmacodynamics parameters

24 AGI-134 Cancer Immunotherapy Small molecule inducing hyper-acute, multi-arm immune response targeting tumor-specific neoantigens

25 25 AGI-134 harnessing pre-existing immunity to deliver a patient-specific anti-tumor response Tumors vary from patient to patient in their neoantigen load and identity AGI-134 is a universal drug that evokes a vaccine effect via a unique, hyper-acute, multi-arm mechanism that targets patientspecific neoantigens

26 26 alpha-gal and anti-gal The alpha-gal epitope is abundantly synthesized on glycolipids of non-primates Due to constant exposure to this antigen (expressed by gut flora) humans develop and maintain high levels of anti-gal Abs Xenotransplantation experiments in the 1980 s-90 s found that, when introduced to humans, the alpha-gal-positive tissue was bound by pre-existing human anti-gal antibodies, which were the main cause of the rejection of porcine heart valves AGI-134 is a fully synthetic alpha- Gal glycolipid molecule for intratumoral injection into solid tumors, to induce an immune response against a patient s own neoantigens

27 27 AGI-134 MoA

28 28 Compelling pre-clinical data supports Phase 1 study expected to initiate in mid-2018 Intratumoral administration of AGI-134 induced regression of established melanoma primary tumors in GT KO mice Days post inoculation ASCO-SITC 2018 Abstract 68 / poster E4

29 29 AGI-134 exerts a potent durable abscopal effect and demonstrated synergy with anti-pd1 Single dose of AGI-134 into primary tumor protected mice from secondary tumor development for more than 90 days Combination of AGI-134 with immune checkpoint inhibitor (anti-pd-1) resulted in increased efficacy over monotherapy effect of either agent Inoculate melanoma cells into right flank (1 tumor) and left flank (2 tumor) Treat 1 tumor with PBS or AGI-134 Monitor the appearance of 2 tumors * * *** *** PBS (n=7) AGI-134 (n=8) PBS (n=13) AGI-134 (n=16) anti-pd1 (n=11) AGI anti-pd1 (n=16) ASCO-SITC 2018 Abstract 68 / poster E4 AACR 2016 poster 4862 AACR 2017 poster 616 ASCO 2016 poster 3083

30 Looking ahead

31 31 Principal Milestones for 2018 BL-8040 (Auto SCM) Lead-in results BL-8040 (Pancreatic Cancer) Phase 1/2 top-line results (Merck) 2018 BL-8040 (Allo SCM) Phase 2 top-line results BL-8040 (Multiple Solid Tumors) Phase 1/2 partial results (Genentech) BL-8040 (Pancreatic Cancer) Phase 1/2 partial results (Merck) BL-8040 (r/r AML) Overall survival data BL-8040 (AML Consolidation) Phase 2b interim results AGI-134 (Solid tumors) Phase 1/2a initiation

32 32 Takeaways Focus on oncology and immunology (specifically immuno-oncology) 9 clinical studies ongoing or planned for the next 12 months Read-out from 3-4 Phase 2 studies over the next 12 months Phase 3 registrational study ongoing; read-out from lead-in period mid-2018 Significant collaborations with 3 of the leading global pharma companies