BioLineRx (BLRX) announced that it has signed an exclusive, worldwide license agreement with Biokine Therapeutics, for the development and commercialization of Biokine's BKT140, a Phase II ready cancer drug candidate.
BioLine is a biopharmaceutical company with a wide-ranging portfolio of products in both clinical and pre-clinical development stages. BioLine's business model is based on in-licensing molecules from academic institutions and biotech companies, and advancing their development with partial funding from the Israeli Government's Office of the Chief Scientist. BioLine's goal is to partner with medium and large pharmaceutical companies for collaboration encompassing advanced clinical development and product commercialization.
What is BKT140?
BKT140, or as it will be named under BioLine's hands, BL-8040, is a highly selective and unique CXCR4 antagonist. CXCR4 is a chemokine receptor that is directly involved in tumor progression, angiogenesis, metastasis and cell survival. This receptor is over-expressed in more than 70% of tumor cells and its expression often correlates with disease severity.
The binding of BKT140 to CXCR4 on tumor cells blocks the receptor's availability to its ligand, CXCL12/SDF-1, for over 24 hours. According to experiments performed by Biokine, the antagonistic activity of BKT140 leads to several cancer therapy-associated mechanisms, including induction of tumor cells apoptosis and release of tumor cells from their microenvironment.
This proposed mechanism of action can be used in three different clinical approaches for treatment of hematological malignancies: (1) Direct administration, as monotherapy, to promote CXCR4-dependent selective tumor cell death by inhibiting AKT (PI3K/AKT/mTOR apoptosis pathway) and ERK signaling, (2) induction of healthy hematopoietic stem cells mobilization from the bone marrow into the peripheral blood, which can be utilized for their collection and subsequent autologous transplantation in patients, and (3) mobilization of cancer cells from the protective environment of the bone marrow and consequently elevating their exposure to chemotherapy and biological anti-cancer therapies.
To those of you who are familiar with leukemia and lymphoma treatment paradigms, the two latter clinical approaches detailed above may sound familiar. a CXCR4 antagonist called Mozobil (Plerixafor), developed by Genzyme (now a fully owned subsidiary of Sanofi (SNY)) is FDA approved for use in combination with granulocyte-colony stimulating factor (G-CSF) to mobilize hematopoietic stem cells to the blood for autologous transplantation in patients with non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM). Genzyme is currently conducting a phase 1 clinical study to evaluate the combination of Mozobil and chemotherapy in improving the response of relapsed/refractory acute leukemia patients to the chemotherapy.
So what news does BL-8040 bring to this therapeutic approach? Basically, this is a "second generation" CXCR4 antagonist, which has so far shown advantages over Mozobil, as detailed in the table below:
CXCR4 binding affinity
CXCR4 dissociation time
Over 24 hours
Reversible low affinity antagonist and weak partial agonist
Direct apoptosis of tumor cells
Importantly, both in preclinical models and following a phase 1/2a study, BL-8040 exhibited an excellent safety profile, as well as initial clues that its ability to mobilize bone marrow stem cells is greater than Mozobil's.
BioLine's approach to BL-8040's development
BioLine intends to initially develop BL-8040 for the treatment of acute myeloid leukemia (AML) a disease in which very low survival rates pose a real unmet medical need. Due to BL-8040's mechanism of action, the scope of clinical indications can probably be extended for additional oncology indications.
Another advantage associated to selecting AML as the target indication is the high probability of regulatory benefits, such as orphan and fast track status, which may reduce clinical development costs and duration. This can potentially advance an out-licensing deal faster than usual. Additionally, BL-8040's proposed mechanism of action, of enhancing the response to a wide variety of anti-cancer agents, could generate interest from multiple possible licensees, providing of course that result from future clinical trials will support beneficial safety and efficacy.
With this in-licensing agreement BioLine is entering the oncology field, which generates more deals than any other therapeutic field. The last time BioLine has in-licensed a technology in a "hot" area, Hep C treatment, its stock sky rocketed more than 70%. Since then we have seen a constant decline in BioLine's stock price reaching a 52 week low last Friday. The newest addition to BioLine's clinical pipeline should drive the company's stock back to an upward momentum.