Clinical Trials

Date: 2015-06-15

Type of information: Presentation of results at a congress

phase: 1

Announcement: presentation of results at the 20th Annual Congress of the European Hematology Association (EHA) in Vienna, Austria

Company: BioLineRx (Israel)

Product: BL-8040

Action mechanism:

• peptide. BL-8040 is a short peptide that functions as a high-affinity antagonist for CXCR4, a chemokine receptor that is directly involved in tumor progression, angiogenesis (growth of new blood vessels in the tumor), metastasis (spread of the disease to other organs or organ parts) and cell survival. CXCR4 is over-expressed in more than 70% of human cancers and its expression often correlates with disease severity. BL-8040 mobilizes cancer cells from the bone marrow and may therefore sensitize these cells to chemo- and bio-based anti-cancer therapy. Importantly, BL-8040 has also demonstrated a direct anti-cancer effect by inducing apoptosis.
• BL-8040 also mobilizes cancer cells from the bone marrow and may therefore sensitize these cells to chemo- and bio-based anti-cancer therapy. Importantly, BL-8040 has also demonstrated a direct anti-cancer effect by inducing apoptosis. Pre-clinical studies show that BL-8040 is efficient, both alone and in combination with the anti-cancer drug Rituximab, in reducing bone marrow metastasis of lymphoma cells and stimulating lymphoma cell death.
• BL-8040 was licensed by BioLineRx from Biokine Therapeutics and was previously developed under the name BKT-140.

Disease: mobilization of stem cells from the bone marrow

Therapeutic area: Cancer - Oncology

Country: Israel

Trial details:

• The Phase 1 study consists of two parts. Part 1 is a randomized, double-blind, placebo-controlled dose escalation study exploring the safety and tolerability of escalating repeated doses of BL-8040 in healthy volunteers. Secondary objectives include assessment of the efficacy of BL-8040 in mobilizing stem cells as a stand-alone therapy, as well as monitoring the pharmacokinetic profile of the drug. This part will be performed in up to 4 cohorts, with 8 healthy volunteers in each cohort. Part 1 of the study will serve to select the optimal safe and efficacious dose of BL-8040 to be used as a stand-alone therapy in Part 2 of the study.
• Part 2 is an open-label study designed to assess BL-8040\'s stem cell mobilization capacity, as well as the yield of cells collected by leukapheresis. Secondary endpoints of the study include evaluation of the viability and biological activity of cells mobilized by BL-8040 and collected by leukapheresis. This part will be performed in a single cohort of 8 healthy volunteers who will receive the selected dose regimen of BL-8040 based on the data from Part 1.

Latest news:

• • On June 15, 2015, BioLineRx, a clinical-stage biopharmaceutical company dedicated to identifying, in-licensing and developing promising therapeutic candidates, announced the presentation of positive safety and efficacy results for its lead oncology candidate, BL-8040, as a novel approach for the collection of stem cells from the peripheral blood circulation. Treatment with BL-8040 as a single agent was found safe and well tolerated at all doses, and resulted in efficient stem-cell mobilization and collection in all study participants. Furthermore, the results support BL-8040 as a one-day, single-dose collection regimen, which is a significant improvement compared to the current standard of care. The full Phase 1 data set was presented in an oral presentation at the 20th Annual Congress of the European Hematology Association (EHA) in Vienna, Austria.
• Robust stem-cell mobilization was evident in all treated participants across the different doses tested, leading to a median 9.5-fold increase of stem cells in the peripheral blood following a single BL-8040 treatment. Two to four hours after a single administration, BL-8040 enabled collection of a stem-cell yield exceeding the number of cells required to support a transplant in all treated participants, following only one collection procedure. These results support a novel approach to stem-cell collection for transplantation purposes in patients with hematological malignancies or other indications. Importantly, the collection of CD34+ cells was accompanied by mobilization and collection of colony-forming cells, as well as T, B and NK cells.
• The collected human graft was further assessed for its viability and quality in vitro and in vivo. The cells collected from the subjects treated with BL-8040 showed excellent engraftment in irradiated mice, followed by a rapid reconstitution of normal hematopoiesis.
• The Phase 1 clinical trial was performed on healthy volunteers and consisted of two parts. The first part of the study was a randomized, double-blind, placebo-controlled, dose-escalation study in three cohorts of eight participants each, with each participant receiving two consecutive injections of BL-8040. Results show that BL-8040 is safe and well tolerated up to a dose of 1 mg/kg, and that dramatic mobilization of hematopoietic stem and progenitor cells (HSPCs) was observed across all doses tested. The robust mobilization supports the further use of a single injection of BL-8040 for HSPC collection.
• In the second part of the Phase 1 study, eight healthy participants received a single injection of BL-8040 at the highest dose of 1 mg/kg, and four hours later underwent a single, standard leukapheresis procedure. Robust and rapid stem-cell mobilization was evident in all treated participants, supporting a novel approach to stem-cell collection. The median level of collected stem cells was higher than 11 x 106 cells per kg, and the level of HPSCs in the peripheral blood circulation 24 hours after injection of BL-8040 enabled an additional apheresis on Day 2, if needed. These data support the use of BL-8040 as a single-agent, single-injection, one-day regimen for the collection of stem cells.
• “We are very happy to report these outstanding results supporting BL-8040 as an effective one-day monotherapy for collection of sufficient stem cells for hematopoietic cell transplantation. This is a major improvement over currently available procedures, which are lengthier and sometimes require the combination of several agents and multiple time-consuming apheresis sessions. Moreover, we see an improvement in composition of the collected cells, suggesting the potential of a better quality graft that may improve stem cell transplantation outcomes,” said Dr. Kinneret Savitsky, CEO of BioLineRx. “We intend to meet with the U.S. Food and Drug Administration (FDA) in order to discuss our next steps in the clinical development program for this indication, including the design of the planned follow-up Phase 2 study. In addition, we are looking forward to reporting top-line results from the on-going Phase 2 study of BL-8040 for treating relapsed and refractory acute myeloid leukemia patients, which we expect in the fourth quarter of 2015. We also look forward to initiating clinical studies for BL-8040 in three additional indications over the next few months, thus expanding and enhancing the potential of our oncology platform.”
• At the same conference, the Company also presented positive preclinical results for the treatment of acute myeloid leukemia (AML) at a poster session. The results show that BL-8040 rapidly and efficiently induces cell death of AML cells, and demonstrates for the first time that CXCR4 inhibition is associated with induction of terminal differentiation of AML cells.
• • On March 25, 2015, BioLineRx announced successful top-line results from the Phase 1 safety and efficacy study of its lead clinical candidate, BL-8040, as a novel approach for mobilization and collection of bone-marrow stem cells from the peripheral blood circulation. All safety and efficacy endpoints were met, showing that treatment with BL-8040 as a single agent was safe and well tolerated at all doses and resulted in efficient stem cell mobilization and collection in all study participants. Importantly, the results support BL-8040 as one-day, single-dose collection regimen, which is a significant improvement upon the current standard of care. Robust stem cell mobilization was evident in all treated participants, across the different doses tested, supporting a novel approach to stem cell collection. After a single administration, BL-8040 enabled collection of a yield of stem cells that exceeds the number required to support a transplant in all treated participants, following only one collection procedure. The Company intends to present the full set of study results at the European Hematology Association (EHA) Conference taking place in Vienna in June 2015.
• • On January 6, 2015, BioLineRx announced  that it has completed the dose escalation stage of a Phase 1 trial for its novel oncology platform, BL-8040, as a novel treatment for the mobilization of stem cells from the bone marrow to the peripheral blood circulation. All healthy volunteers completed the treatment phase and results are expected during the first quarter of 2015. BL-8040 is being developed along multiple tracks for the treatment of hematological malignancies and other hematological indications, with multiple clinical milestones expected in 2015.
• • On December 12, 2014, During an investor and analyst meeting hosted in New York, BioLineRx will disclose its multi-year development plan for BL-8040, a unique platform for the treatment of hematological cancers. The main development program for BL-8040 relates to acute myeloid leukemia (AML). A two-part Phase 1 study is currently ongoing, to explore the safety, tolerability, pharmacodynamic and pharmacokinetic effects of ascending doses of BL-8040 in healthy subjects. The results of this study are expected in the first quarter of 2015.
• • On September 3, 2014, BioLineRx announced dosing of the first patient in a Phase 1 trial for a second indication of its BL-8040 cancer therapy platform, as a novel treatment for the mobilization of stem cells from the bone marrow to the peripheral blood circulation, where they can be harvested for transplant supporting the treatment of hematological indications.
• • On June 16, 2014, BioLineRx announced that it has received approval from the Israeli Ministry of Health to commence a Phase 1 trial for BL-8040, a novel treatment for the mobilization of stem cells from the bone marrow to the peripheral blood circulation. The study is expected to commence during the third quarter of 2014 at Hadassah Medical Center in Jerusalem. Current treatment regimens involve daily injections for 4-6 days of G-CSF, with or without the addition of a mobilizing agent such as Plerixafor (Mozobil). BL-8040 given as a single injection was previously shown in a Phase 1/2 study in multiple myeloma patients to be highly effective in mobilizing stem cells in combination with G-CSF injections. The current trial aims to evaluate the mobilization capacity of one or two injections of BL-8040 as a stand-alone therapy, which could significantly shorten and reduce treatment costs. In parallel, BL-8040 is undergoing a Phase 2 study for relapsed and refractory acute myeloid leukemia patients, the results of which are expected in early 2015. The company also expects the commencement of an investigator-led Phase 1/2 study in chronic myeloid leukemia patients during 2014.
• • On January 13, 2014, BioLineRx has announced that it has filed the necessary regulatory submissions to commence a Phase 1 trial for BL-8040, a novel treatment for the mobilization of stem cells from the bone marrow to the peripheral blood circulation. The regulatory submissions were filed with the Hadassah Medical Center Institutional Review Board (IRB), and the study is expected to commence during the second quarter of 2014. Results of BL-8040\'s Phase 1/2 study in multiple myeloma patients, have been recently published in Clinical Cancer Research. These data show that a single injection of BL-8040 is highly effective in mobilizing stem cells in combination with G-CSF. This trial now aims to assess the mobilization efficacy of BL-8040 as a stand-alone therapy.
• BL-8040 is also currently in the midst of a Phase 2 study for acute myeloid leukemia patients, the results of which are expected in the second half of 2014.

Is general: Yes