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

Therapeutic areas

Therapeutic areas

Stem cell mobilization
Hematological malignances
Solid tumors

Mode of action

Mode of action

CXCR4 antagonism

Stage of development

Stage of development

Active clinical development with multiple Phase 2 and Phase 3 studies

Main Indications

Stem cell mobilization

Stem cell mobilization

Acute Myeloid Leukemia (AML)

Acute Myeloid Leukemia (AML)

Solid tumors

Solid tumors

Development

BL-8040 (formerly known as BKT140 and developed by Biokine Therapeutics Ltd.) is a novel selective inhibitor of the CXCR4 chemokine receptor that is currently being developed for several indications including mobilization of hematopoietic stem cells (HSCs) for autologous and allogeneic transplantations and treatment of solid tumors and hematological malignancies.

A Phase 3 study is currently carried out to evaluate the efficacy of BL-8040 on top of G-CSF for mobilization of HSCs for autologous transplantation in multiple myeloma patients. This study was based on earlier clinical studies demonstrating the superior capability of BL-8040 to mobilize HSCs from multiple myeloma patients and from healthy volunteers 1-2.

BL-8040 is also developed for the treatment of acute myeloid leukemia (AML). BL-8040 is being tested in combination with high-dose cytarabine as a consolidation AML therapy in a phase 2 study. It is also tested in combination with Atezolizumab (anti PD-L1; Tecentriq) as maintenance AML therapy in a Phase 1/2a study, as part of a collaboration with Genentech. Aside from its ability to mobilize AML blasts, BL-8040 demonstrated direct apoptotic effects on AML blasts. These observations were strengthened by findings from a phase 2a relapsed/refractory (r/r) AML study in which BL-8040 in combination with HiDAC significantly improved overall survival of relapsed/refractory AML patients, compared with historical data.

The immune-mediated effects of BL-8040 are being explored in combination with PD-1/PD-L1 immune checkpoint inhibitors (i.e. Pembrolizumab/Keytruda and Atezolizumab) in several clinical studies in solid tumors (pancreatic, gastric and non-small cell lung cancer) in collaboration with Merck and Genentech.

  1. Peled et al. The High-Affinity CXCR4 Antagonist BKT140 Is Safe and Induces a Robust Mobilization of Human CD34+ Cells in Patients with Multiple Myeloma. Clin Cancer Res 20; 469-79 (2013).
  2. Abraham et al. Single Dose of the CXCR4 Antagonist BL-8040 Induces Rapid Mobilization for the Collection of Human CD34 Cells in Healthy Volunteers. Clin Cancer Res 23; 1-12 (2017).