Motixafortide (BL-8040)

Motixafortide targets CXCR4, a chemokine receptor and a well validated therapeutic target that is over-expressed in many human cancers including PDAC. CXCR4 plays a key role in tumor growth, invasion, angiogenesis, metastasis and therapeutic resistance, and CXCR4 overexpression has been shown to be correlated with poor prognosis.

Motixafortide is a short synthetic peptide used as a platform for cancer immunotherapy with unique features allowing it to function as a best-in-class antagonist of CXCR4. It shows high-affinity, long receptor occupancy and acts as an inverse agonist.

In a number of clinical and preclinical studies, motixafortide has been shown to affect multiple modes of action in “cold” tumors, including immune cell trafficking, tumor infiltration by immune effector T cells, and reduction in immunosuppressive cells (such as MDSCs) within the tumor niche, turning “cold” tumors, such as pancreatic cancer, “hot” (i.e., sensitizing them to immune checkpoint inhibitors and chemotherapy).

Motixafortide (BL-8040)

CXCL12 in bone marrow stromal cells retain leukemic cells in the protective bone marrow niche

BL-8040 blocks the interaction between CXCL12 and CXCR4 by binding to CXCR4

As a result, leukemic cells are mobilized from their protective niche into peripheral blood; in addition, CXCR4 inhibition can induce direct apoptosis of the leukemic cells

Mobilized leukemic cells detached from their niche are sensitized to chemotherapy as well as to direct and indirect BL-8040-mediated apoptosis

AML

During 2016, we completed and reported on a Phase 2a proof-of-concept trial for the treatment of relapsed or refractory acute myeloid leukemia, or r/r AML, which was conducted on 42 patients at six world-leading cancer research centers in the United States and at five premier sites in Israel. The study included both a dose-escalation and a dose-expansion phase. Results from the trial showed detailed, positive safety and response rate data for subjects treated with a combination of motixafortide and high-dose cytarabine (Ara-C), or HiDAC. At the annual meeting of the European Hematology Association, or EHA, in June 2018, we presented positive overall survival data from the long-term follow-up part of this study. A 39% CR (CR+CRi) was demonstrated, as compared to historical data of 19% for patients treated with Ara-C alone and, in terms of survival, a median OS of 10.7 months was seen, as compared to historical data of 5.8-6.1 months for patients treated with Ara-C alone.