Clinical Trials

* On November 3, 2016, BioLineRx disclosed  positive Phase 2a correlative data, as well as detailed mechanism-of-action data, for BL-8040, the Company's leading oncology platform, that will be presented at the 58th American Society of Hematology (ASH) Annual Meeting and Exhibition in San Diego, California, taking place December 3-6, 2016. In a poster titled, "The Selective Anti Leukemic Effect of BL-8040, a Peptidic CXCR4 Antagonist, is Mediated by Induction of Leukemic Blast Mobilization, Differentiation and Apoptosis: Results of Correlative Studies from a Ph2a Trial in Acute Myeloid Leukemia", BioLineRx reports the final correlative results from its Phase 2a trial in acute myeloid leukemia (AML). The trial consisted of 45 AML patients receiving BL-8040 monotherapy on days 1-2, followed by the same dose of BL-8040 plus chemotherapy (Cytarabine) on days 3-7. All patients had poor-risk disease and had been heavily pretreated, with 19% having relapsed after a short first remission (?12 months), 17% having 2 or more relapses, while 45% were refractory to 1-2 induction treatments. As previously reported, the composite complete remission rate, including both complete remission (CR) and complete remission with incomplete blood count recovery (CRi), was 38% in subjects receiving BL-8040 dose ?1.0 mg/kg (n=39). In the 1.5 mg/kg dose selected for the expansion phase of the study (n=22), the composite complete remission rate was 41%. These response rates are superior to the historical response rate of approximately 20% reported for high-risk AML patients treated with Cytarabine alone. The ongoing follow-up of responding patients (n=19) showed median Event Free Survival of 9.3 months (range of 4.3-12.8 months).

Results further show that BL-8040 monotherapy had a substantial therapeutic effect. Treatment with BL-8040 as a single agent triggered robust mobilization of AML blasts from the bone marrow to the peripheral blood stream, and the extent of mobilization was correlated with a positive response to treatment. The preferential mobilization of AML blasts over normal cells (4.7-fold vs. 1.4-fold, respectively) was further confirmed by FISH analysis in a subset of patients. In addition, BL-8040 monotherapy resulted in a 40% increase in AML blast apoptosis.

BioLineRx also reports detailed data on the mechanism-of-action by which BL-8040 directly induces apoptosis of AML cells. The data presented are from in vitro studies using human AML cell lines and human primary AML samples, as well as in vivo studies using human primary AML cells engrafted in NOD scid gamma (NSG) mice. The results of the pre-clinical studies show that BL-8040 treatment in vivo triggered mobilization of AML blasts from their protective bone marrow microenvironment and induced their terminal differentiation. In addition, the studies illustrate how BL-8040 increases the expression and activity of a special class of microRNA precursors termed miR-15a/16-1. These microRNA molecules have been previously linked to cancer, and shown to suppress the activity of several tumor-related pro-survival proteins. Therefore, by increasing the expression of miR-15a/16-1 microRNA molecules, BL-8040 decreases the expression of tumor-survival proteins and promotes tumor cell death. Importantly, in both in vitro and in vivo experiments, BL-8040 was found to synergize with a selective Bcl-2 inhibitor (Venetoclax) and an FLT3 inhibitor (Quizartinib, also known as AC220) in inducing AML cell death, pointing at potential drug combination treatments.

* On September 8, 2016, BioLineRx announced that the successful final results of BL-8040's Phase 2a clinical trial in relapsed or refractory acute myeloid leukemia (r/r AML) were presented  at the 4th Annual Meeting of the Society of Hematologic Oncology (SOHO), being held September 7-10, 2016, in Houston, Texas.The Phase 2a study assessed the efficacy of BL-8040, as a single agent and in combination with cytarabine (Ara-C), for the treatment of r/r AML. The reported data set includes 45 patients. The majority of patients in the study were heavily pretreated, with 45% of patients being refractory to one or two remission induction treatments, 19% of patients having relapsed after a short first remission of less than 12 months, and 17% of patients having undergone two or more relapses. In addition, the treated patient population included patients that had relapsed post allogeneic stem-cell transplantation (17%), as well as secondary AML patients (24%), both conditions which represent difficult-to-treat populations with poor prognoses.

Results show that treatment with BL-8040 in combination with Ara-C was safe and well tolerated at all doses tested up to and including the highest dose level of 2.0 mg/kg. Response to treatment was associated with efficient CXCR4 inhibition, resulting in high mobilization of blasts and induction of their differentiation. The composite complete remission rate, including both complete remission (CR) and complete remission with incomplete blood count recovery (CRi), was 38% in subjects receiving up to two cycles of BL-8040 treatment at doses of 1 mg/kg and higher (n=39). In the 1.5 mg/kg dose selected for the expansion phase of the study (n=22), the composite complete remission rate was 41%. These response rates are superior to the historical response rate of approximately 20% reported for high-risk AML patients treated with Ara-C alone.

In addition, the ongoing follow-up of patients participating in the study's expansion phase and responding to the combination treatment suggests long durability of the remissions achieved, with two-thirds of these patients still alive, based on a follow-up period to date of up to 12 months.

Philip Serlin, Chief Financial and Operating Officer of BioLineRx, commented, "The results from this study clearly confirm the anti-leukemic activity of BL-8040 and reinforce our interest in the AML space. The data demonstrate that sustained inhibition of the CXCR4-CXCL12 axis with BL-8040 is safe and well tolerated, and when given in combination with Ara-C, improves the response rate historically achieved with Ara-C alone. In addition, treatment with BL-8040 as a single agent rapidly and efficiently induces mobilization, differentiation and cell death of AML cells. This selective effect on chemotherapy-resistant cells may be translated into reduction of residual disease, thus pointing to incorporation of BL-8040 into earlier AML treatment lines." 

 * On March 29, 2016, BioLineRx announced positive top-line results from BL-8040's Phase 2 clinical trial in relapsed or refractory acute myeloid leukemia (r/r AML). Detailed results are planned to be presented at an upcoming scientific conference. Results of the Phase 2 clinical trial showed that BL-8040, as a single agent and in combination with Cytarabine (Ara-C), was safe and well tolerated at all doses tested up to and including the highest dose level of 2.0 mg/kg, with no major adverse events (n=45). The composite complete remission rate, including both complete remission (CR) and complete remission with incomplete blood count recovery (CRi), was 38% in subjects receiving up to two cycles of BL-8040 treatment at doses of 1 mg/kg and higher (n=39). Patients included in the study were patients that had undergone a significant number of prior treatments or that were refractory to induction treatment. The data include three compassionate-use patients treated at the study sites under the identical treatment protocol.

Importantly, the data suggest, for the first time, a correlation between improved clinical response and patients with a high disease burden in the bone marrow, along with a lower peripheral circulation of AML blasts at baseline (indicative of potential CXCR4 disease dependency). This finding may serve as a biomarker for patient selection in future BL-8040 AML studies.

In addition, treatment with BL-8040 continues to show a triple effect on the leukemic cells. First, BL-8040 monotherapy triggered robust mobilization of AML cells from the bone marrow to the peripheral blood, thereby sensitizing these cells to the Ara-C chemotherapy and improving its efficacy. Second, BL-8040 monotherapy showed a direct apoptotic effect on the leukemia cells in the bone marrow. Last, BL-8040 induced leukemia progenitor cells towards differentiation, as evidenced by a decrease in the number of leukemia progenitor cells, along with a three-fold increase in differentiated granulocytes, in the bone marrow biopsy conducted on day 3 of the treatment cycle prior to the Ara-C treatment, as compared to the biopsy performed at baseline.

* On November 5, 2015, BioLineRx  announced positive results from the dose escalation part of BL-8040’s Phase 2 clinical trial in relapsed or refractory acute myeloid leukemia (r/r AML). The results will be presented at the 57th American Society of Hematology (ASH) Annual Meeting, to be held December 5-8, 2015 in Orlando, Florida. Results showed that BL-8040, as a single agent and in combination with Cytarabine (Ara-C), was safe and well tolerated at all doses tested up to and including the highest dose level of 1.5 mg/kg, with no major adverse events. The composite complete remission rate, including both complete remission (CR) and complete remission with incomplete blood count recovery (CRi), was 38% in subjects receiving only one cycle of BL-8040 treatment at doses of 1 mg/kg and higher (n=16). Patients included in this part of the study were patients that had undergone a significant number of prior treatment cycles or that were refractory to induction treatment.

Treatment with BL-8040 had a triple effect on the leukemic cells. First, following only two days of monotherapy, BL-8040 triggered an average 40-fold mobilization of immature AML progenitor cells from the bone marrow to the peripheral blood, thereby sensitizing these cells to the Ara-C chemotherapy and improving its efficacy. Second, BL-8040 showed a direct and significant apoptotic effect on the immature leukemia progenitor cells in the bone marrow following the two days of monotherapy. Last, BL-8040 induced leukemia progenitor cells towards differentiation, as evidenced by a 58% median decrease in the number of bone marrow leukemia progenitor cells, along with a three-fold increase in differentiated granulocytes, in the bone marrow biopsy conducted on Day 3 of the treatment cycle prior to the Ara-C treatment, as compared to the biopsy performed at baseline. BioLineRx now looks  forward to discussions with the regulatory authorities regarding the future development plan for AML. The company anticipates reporting topline results from the full study by early next year.

* On May 4, 2015, BioLineRx announced successful completion of the dose escalation stage of its ongoing Phase 2 study of BL-8040, and commencement of the expansion stage at the optimal dose of this novel treatment for acute myeloid leukemia (AML). Top-line results from the study are anticipated in the fourth quarter of 2015. Results of the completed dose escalation stage, in which 22 patients participated, showed that all BL-8040 tested doses, up to 1.5 mg/kg, were found to be safe and well tolerated when administered in combination with Ara-C (Cytarabine). Building upon prior interim results, which included doses up to 1.25 mg/kg and were presented at the 2014 American Society for Hematology conference, the data indicate that BL-8040 exhibits robust single-agent activity, with a dramatic decrease in the amount of AML cells in the bone marrow and significant mobilization of these cells into the peripheral blood following two days of BL-8040 monotherapy, as well as direct induction of leukemia cell death. Based on the study’s pharmacodynamic data, 1.5 mg/kg was chosen as the dose for use in the expansion stage of the study. In parallel to initiation of the expansion stage, additional patients will be recruited to assess one higher dose level of BL-8040, in order to further expand the therapeutic window of the drug.

* On December 8, 2014, BioLineRx announced that data from the on-going Phase 2a clinical trial of BL-8040 for the treatment of patients with relapsed or refractory acute myeloid leukemia (AML) were reported at the American Society of Hematology (ASH) meeting, held on December 6-9, 2014, in San Francisco. Results reported to date in the dose-escalation stage of the Phase 2a study show that, even at the highest dose reached to date (1.25 mg/kg), there were no dose-limiting toxicity events or serious adverse events, nor early discontinuations attributable to BL-8040. Furthermore, BL-8040 triggered substantial mobilization of AML cancer cells from the bone marrow to the peripheral blood, with a median 6-fold increase of AML cells in the blood. This mobilization is crucial for exposing a higher ratio of AML cells to accompanying chemotherapy such as Ara-C. Additional results show that after only two days of BL-8040 monotherapy, there was a median decrease of approximately 70% in the amount of AML cells in the bone marrow, while the levels of normal progenitor cells remained stable. Furthermore, BL-8040 as a monotherapy showed a 3.5-fold increase in cell death (apoptosis) of AML cells, both in the bone marrow and in peripheral blood samples. The dose escalation stage, which is currently ongoing, is expected to be completed early next year and the full study is expected to be completed in the second half of 2015.”

* On November 3, 2014, BioLineRx announced that in light of encouraging pharmacodynamic and excellent safety data from the ongoing Phase 2 clinical trial of BL-8040 for the treatment of patients with relapsed or refractory acute myeloid leukemia (AML), the Company has filed with the FDA an amendment to the study protocol to test additional cohorts at higher doses in the current dose-escalation stage of the trial. The amendment will also include an increase in the total expected study enrollment, from up to 50 under the original protocol, to up to 70 patients. BL-8040 was found to be safe at all doses tested to date, with no serious adverse events related to BL-8040. Results from the trial to date continue to show substantial mobilization of leukemic cells from the bone marrow and robust induction of cancer cell apoptosis. The decision to add higher dosing cohorts, in order to determine the optimal dose to use in the upcoming expansion stage of the trial, was based on a unanimous recommendation from BL-8040’s Clinical Advisory Board (CAB). “Since we plan to increase the number of patients in the dose escalation stage, in order to maintain the adequate number of patients originally planned in the dose expansion stage, we have decided to increase the overall sample size of the study to 70 patients. This will enable treatment of at least 40 patients at the optimal dose. We now expect to complete the dose escalation stage of the study by early next year, and the full study, following the expansion stage, in the second half of 2015. BL-8040 is also in the midst of a Phase 1 stem cell mobilization study, with results expected by early 2015,” concluded Dr. Savitsky.

* On December 16, 2013,  BioLineRx, a clinical-stage biopharmaceutical company, has announced initial results for its BL-8040 drug candidate in a Phase 2 clinical trial for patients with relapsed or refractory acute myeloid leukemia. The early results show that BL-8040, as a stand-alone therapy and in combination with high-dose Cytarabine (Ara-C), is safe at all doses tested to date, and triggers substantial mobilization of cancer cells from the bone marrow to the peripheral blood, thereby increasing the vulnerability of the cells to chemotherapy treatment. In addition, signs of robust apoptosis of cancer cells were observed following administration of the higher doses tested to date. The study has not yet reached the highest planned doses, suggesting that a strengthening of BL-8040's effects may be observed in future dosing cohorts. Eight patients have already been enrolled in the study, out of a total expected enrollment of up to 50 patients at eight clinical sites in the U.S. and Israel. To date, there have been no serious adverse events related to BL-8040, while the primary adverse event has been a minor and transient reaction at the injection site. The BL-8040 dosing level of the current study cohort is 1 mg/kg, with the highest planned study dose being 1.5 mg/kg. The end of the dose escalation phase is expected during the second quarter of 2014, with final study results expected in the second half of 2014.

* On November 19, 2013, BioLineRx has announced  the publication of results showing that BL-8040 enables the efficient mobilization of stem cells from the bone marrow into the peripheral blood, thus facilitating autologous stem cell transplantation in multiple myeloma patients. The research was published in Clinical Cancer Research. The results, obtained in 2011 and currently published in Clinical Cancer Research, show that BL-8040 binds with a very high affinity to CXCR4, and more importantly, it dissociates from the receptor in a very slow fashion. As a result, BL-8040 has the unique ability, when compared to other CXCR4 inhibitors, to completely shut down the cell signaling process governing cell trafficking in the bone marrow. This exclusive activity of BL-8040 leads to a strong synergistic effect when combined with G-CSF, resulting in a rapid and robust stem cell mobilization therapy that is differentiated from the current standard of care.

This ability of BL-8040 was confirmed in patients in a phase 1/2 non-randomized, open-label, dose escalation, multi-center study in multiple myeloma patients who underwent stem cell mobilization and collection for autologous stem cell transplantation. Results of the clinical study show that BL-8040 was well tolerated at all concentrations, and that when combined with G-CSF, a single administration of BL-8040 at the highest dose (0.9 mg/kg) resulted in robust mobilization and collection of stem cells, which were then obtained through a single apheresis. Furthermore, all transplanted patients rapidly engrafted. At the highest dose, the median times to neutrophil and platelet recovery were 12 and 14 days, respectively. Dr. Kinneret Savitsky, Chief Executive Officer of BioLineRx, said, "We are very pleased with these promising results in stem cell mobilization, which are the basis for our decision to initiate an additional clinical trial for BL-8040 in this indication. In addition, we remain on track with BL-8040's on-going Phase 2 study for the treatment of relapsed and refractory acute myeloid leukemia patients, for which partial results are expected by the end of this year, with final results expected in the second half of 2014. Future development plans include additional clinical studies in stem cell mobilization and chronic myeloid leukemia, which are expected to commence during the first half of 2014."

* On June 6, 2013, BioLineRx has  announced enrollment of the first patient in a Phase 2 trial for BL-8040, for the treatment of acute myeloid leukemia (AML). The patient was enrolled at the MD Anderson Cancer Center in Houston, Texas. BioLineRx also announced that, in addition to receiving regulatory approval for commencing the trial in the U.S. this past April, it has also recently received regulatory approval from the Israeli Ministry of Health to conduct the trial in Israel. The activation of Israeli sites is anticipated during the next few weeks.

* On April 10, 2013, BioLineRx has announced that it has received all necessary regulatory approvals in the US to commence a Phase IIa trial for BL-8040, for the treatment of Acute Myeloid Leukemia (AML). The study is designed to evaluate the safety and efficacy profile of repeated escalating doses of BL-8040 in adult subjects with relapsed/refractory AML. It is also designed in a way that will enable the investigators to evaluate the capabilities of BL-8040 in mobilizing cancer cells from the bone marrow to the peripheral blood, and in inducing their cell death. The study is expected to be conducted in the U.S. and Israel, and will enroll up to 50 patients. Last September, BioLineRx has signed an exclusive, worldwide license agreement with Biokine Therapeutics for the development and commercialization of this drug candidate for the treatment of hematological cancers.