BL-8040

BL-8040, a 14-amino acid synthetic cyclic peptide, is a novel, best in class, high-affinity CXCR4 antagonist with long receptor occupancy (>48 hours) and extended CXCR4 inhibition. BL-8040 is developed for the treatment of solid tumors, hematological malignancies and indications requiring hematopoietic stem cell transplantation.

BL-8040 pipeline is based on the vital roles of CXCR4-CXCL12 (SDF-1) interactions in oncologic processes (growth, invasion, survival, angiogenesis and metastasis) in various cancer types and in the maintenance of hematopoietic stem cells, immune cells and hematopoietic cancer cells in their protective niche.

BL-8040

Without BL-8040

Limited availability ofimmune cells

Immune cells circulate in periphery and tumor

Poor immune cell infiltration

Fibroblastic cells at tumor edge produce CXCL12, which isolates effector immune cells at the tumor edge

Immunosuppressive TME

CXCL12 secreted by the tumor creates immunosuppression

With BL-8040

Immunostimulant

Increased numbers of immune cells (NK, B and T cells) circulate in periphery and tumor

Potentiator

Effector immune cells no longer held at tumor edge & traffic into tumor

Microenvironment modifier

Blockade of CXCR4 on immuno-suppressor cells reduces their attraction & infiltration into the tumor, relieving immunosuppression and possibly acting synergistically with checkpoint inhibitor agents

Solid tumors

In January 2016, BioLineRx entered into a collaboration with MSD, known as Merck in the U.S. and Canada, in the field of cancer immunotherapy. Based on this collaboration, in September 2016 BioLineRx initiated a Phase 2a study, known as the COMBAT study, focusing on evaluation of the safety and efficacy of BL-8040 in combination with KEYTRUDA® (pembrolizumab), MSD's anti-PD-1 therapy, in patients with metastatic pancreatic adenocarcinoma. Partial results were presented at the 2018 ASCO Gastrointestinal Cancers Symposium (ASCO GI) and ASCO-SITC in January 2018, with top-line results expected in the second half of 2018.

In August 2016, in the framework of an agreement with MD Anderson Cancer Center, BioLineRx entered into an additional collaboration for the investigation of BL-8040 in combination with KEYTRUDA® in pancreatic cancer. BioLineRx is supplying BL-8040 for this Phase 2b study, which commenced in January 2017. This study was presented at the 2018 ASCO GI in January 2018.

In September 2016, BioLineRx entered into a collaboration with Genentech, Inc., a member of the Roche Group, in the framework of which both companies would carry out Phase 1b/2 studies investigating BL-8040 in combination with atezolizumab (TECENTRIQ®), Genentech's anti-PDL1 cancer immunotherapy, in various solid tumors and hematologic malignancies. Genentech commenced a Phase 1b/2 study for the treatment of pancreatic cancer in July 2017, as well as a Phase 1b/2 study in gastric cancer in October 2017. Genentech expects to commence an additional Phase 1b/2 study in lung cancer by early 2018. In September 2017, BioLineRx initiated a Phase 1b/2 study under this collaboration in acute myeloid leukemia (AML). These studies will evaluate the clinical response, safety and tolerability of the combination of these therapies, as well as multiple pharmacodynamic parameters.

Investigator Initiated Studies

BioLineRx is currently conducting several investigator-initiated studies in a variety of indications to support the interest of the scientific and medical communities in exploring additional uses for BL-8040. These studies serve to further support current indications and broaden BL-8040 mechanism of action.