On August 17, 2015 BioLineRx Ltd. (NASDAQ: BLRX; TASE: BLRX), a clinical-stage biopharmaceutical company dedicated to identifying, in-licensing and developing promising therapeutic candidates, reported the initiation of a Phase 2b trial for BL-8040 as a novel consolidation treatment for acute myeloid leukemia (AML) (Filing, 6-K, BioLineRx, AUG 17, 2015, View Source [SID:1234507267]). The Phase 2b study will examine BL-8040 as part of a second stage treatment, termed consolidation therapy, to improve outcomes for AML patients who have achieved remission after the standard initial treatment regimen, known as induction therapy. The consolidation therapy is aimed at eliminating the minimal residual disease left in the bone marrow after induction therapy that can lead to relapse. This study is the first of three clinical studies in additional indications for BL-8040 which BioLineRx plans to commence during 2015, thus significantly expanding its unique BL-8040 oncology platform.

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Dr. Kinneret Savitsky, Chief Executive Officer of BioLineRx, stated, "The majority of high-risk AML patients achieving first complete remission relapse within one year, despite the current standard consolidation therapy. Patients with AML relapse have a poor prognosis despite further therapy, and less than 10% of these patients are cured by conventional therapy. Leukemic stem cells that are dormant in the bone marrow are presumed to be a major reason for AML relapse. Based on the pre-clinical and clinical data accumulated to date, BL-8040 is anticipated to boost the efficacy of consolidation therapy due to its dual mechanism of action. Firstly, BL-8040 induces mobilization of leukemic cells from the bone marrow, which enhances the cytotoxic effects of chemotherapy, and secondly, it possesses anti-leukemic pro-apoptotic properties that help eliminate AML cells directly. Based on positive results from our ongoing phase 2 clinical trial for BL-8040, which show substantial mobilization of AML cells from the bone marrow to the peripheral blood, as well as robust induction of AML cell apoptosis, we believe BL-8040 will be a promising addition to consolidation therapy for AML patients."

Dr. Savitsky added, "In addition to initiation of the Phase 2b AML consolidation study, we are eagerly looking forward to the top-line results from our ongoing Phase 2 study of BL-8040 for treating relapsed and refractory AML patients, which we expect in the fourth quarter of 2015. We also look forward to the next stages of development for BL-8040 as a novel stem cell mobilization treatment, after its recent successful completion of a Phase 1 trial. Finally, we are also excited about the anticipated initiation of clinical studies for BL-8040 in two additional indications over the next few months, thus further expanding and enhancing the potential of our oncology platform."

The Phase 2b trial, which is conducted in collaboration with the University of Halle as sponsor and with the participation of two large leukemia study groups in Germany, is a double-blind, placebo-controlled, randomized, multi-center study aimed at assessing the efficacy of BL-8040 in addition to standard consolidation therapy in AML patients. The primary endpoint of the study is to compare the relapse free survival (RFS) time in AML subjects in their first remission during a minimum follow-up time of 18 months after randomization. In addition, pharmacodynamic measurements will be conducted in order to assess the minimal residual disease, and biomarker analyses will be performed to identify predictors of BL-8040 response. The study will enroll up to 194 patients at up to 25 sites in Germany. AML patients between 18 and 75 years of age with documented first remission will be randomized in a 1:1 ratio to receive high dose Cytarabine, either with BL-8040 or with a matching placebo, as consolidation therapy.

About BL-8040
BL-8040 is a clinical-stage drug candidate for the treatment of acute myeloid leukemia, as well as other hematological indications. It 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. In a Phase 1/2, open-label, dose escalation, safety and efficacy clinical trial in 18 multiple myeloma patients, BL-8040, when combined with G-CSF, demonstrated an excellent safety profile at all doses tested and was highly effective in the mobilization of hematopoietic stem cells and white blood cells from the bone marrow to the peripheral blood. Additionally, in a Phase 1 stem-cell mobilization study in healthy volunteers, BL-8040 as a single agent was safe and well tolerated at all doses tested and resulted in efficient stem-cell mobilization and collection in all study participants. Importantly, the results of this study support the use of BL-8040 as one-day, single-dose collection regimen, which is a significant improvement upon the current standard of care.

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 inhibits the growth of various tumor types including multiple myeloma, non-Hodgkin’s lymphoma, leukemia, non-small cell lung carcinoma, neuroblastoma and melanoma. BL-8040 significantly and preferentially stimulated apoptotic cell death of malignant cells (multiple myeloma, non-Hodgkin’s lymphoma and leukemia). Significant synergistic and/or additive tumor cell killing activity has been observed in-vitro and in-vivo when tumor cells were treated with BL-8040 together with Rituximab, Bortezomib, Imatinib, Cytarabine and the FLT-3 inhibitor AC-220 (in NHL, MM, CML, AML, and AML-FLT3-ITD models, respectively). In addition, the current Phase 2 clinical trial in AML patients has demonstrated robust mobilization and apoptosis of cancer cells. BL-8040 was licensed by BioLineRx from Biokine Therapeutics and was previously developed under the name BKT-140.

About Acute Myeloid Leukemia (AML)
Acute myeloid leukemia (AML) is a cancer of the blood and bone marrow and is the most common type of acute leukemia in adults. According to the American Cancer Society, approximately 19,000 new cases of AML were diagnosed in the United States in 2014, and the median age of AML patients was 67 years old. The first treatment line for patients with AML includes a combination of chemotherapy drugs and is called induction treatment. The median survival for AML patients receiving induction chemotherapy is less than two years, with shorter survival for patients over the age of 60 or for those with certain gene or chromosome aberrations. Due to relapsed or refractory disease (where the disease is not responsive to standard treatments), the overall five-year survival rate for AML is between 10 and 40 percent.

On August 17, 2015 AVEO Oncology (NASDAQ:AVEO) reported an exclusive, worldwide license agreement with Novartis for the development and commercialization of AVEO’s first-in-class, potent, humanized inhibitory antibody targeting growth differentiation factor 15 (GDF15), AV-380, and related antibodies, including modified or derivative forms of any such antibody (the "Product") (Press release, AVEO, AUG 17, 2015, View Source;p=irol-newsArticle&ID=2079881 [SID:1234512505]).

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Under the terms of the agreement, AVEO will receive an upfront payment of $15 million and will be eligible to receive reimbursement, clinical, sales and regulatory-based milestone payments totaling $311 million assuming successful advancement of the Product. AVEO will also be eligible to receive tiered royalties on product sales ranging from high single digits to a low double-digit. Novartis will be responsible for all clinical development, manufacturing and commercialization activities and costs associated with the Product.

"AV-380 holds great promise as a potential treatment for cachexia secondary to multiple disease states, including cancer, chronic kidney disease, congestive heart failure and chronic obstructive pulmonary disease," said Michael Bailey, AVEO’s president and chief executive officer. "Novartis brings resources and expertise to bear on advancing this program, which we believe provides the optimal path forward toward realizing its full potential."

About Cachexia and GDF15

Cachexia is a complex metabolic syndrome associated with malnutrition and severe involuntary weight loss due to the loss of muscle and fat tissue, as well as the clinical manifestation of anemia, inflammation and suppression of immune functions. Cachexia is a serious and common complication in patients with advanced cancer and other chronic diseases. It affects some five million individuals in the United States¹.

GDF15 is a pro-inflammatory cytokine whose elevated circulating levels have been correlated with cachexia in cachectic cancer patients and several animal models of cancer cachexia. Current evidence suggests that a pro-inflammatory state may be responsible for many of the symptoms associated with cachexia. Preclinical data show that inhibition of GDF15 results in a switch from catabolism to anabolism, suggesting that GDF15 inhibition with AV-380 may reverse the effects of cachexia.

On August 17, 2015 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that in the large pivotal Phase II study, BIRCH, the investigational cancer immunotherapy atezolizumab (MPDL3280A; anti-PDL1) met its primary endpoint and shrank tumours (objective response rate; ORR) in people with locally advanced or metastatic non-small cell lung cancer (NSCLC) whose disease expressed PD-L1 (Programmed Death Ligand-1) (Press release, Hoffmann-La Roche , AUG 16, 2015, View Source [SID:1234507269]). The study showed the amount of PD-L1 expressed by a person’s cancer correlated with their response to the medicine. Adverse events were consistent with what has been previously observed for atezolizumab.

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"We are encouraged by the number of people who responded to atezolizumab and maintained their response during the study, which is particularly meaningful for people who had received several prior treatments," said Sandra Horning, M.D., Chief Medical Officer and head of Global Product Development. "We plan to present results at an upcoming medical meeting and will discuss these data as well as results from our other lung cancer studies with health authorities to bring this medicine to patients as quickly as possible.’’

Earlier this year, the FDA granted atezolizumab a Breakthrough Therapy Designation for the treatment of people whose NSCLC expresses PD-L1 and who progressed during or after standard treatments (e.g. platinum-based chemotherapy and appropriate targeted therapy for EGFR mutation-positive or ALK-positive disease). This designation is designed to expedite the development and review of medicines intended to treat serious diseases. Roche have seven Phase III studies evaluating atezolizumab alone or in combination with other medicines as a potential new treatment for people with early and advanced stages of lung cancer.

About the BIRCH Study
BIRCH is an open-label, multicentre, single-arm Phase II study that evaluated the safety and efficacy of atezolizumab in 667 people with locally advanced or metastatic NSCLC whose disease expressed PD-L1. PD-L1 expression was assessed on both tumour cells (TC) and tumour-infiltrating immune cells (IC) with an investigational immunohistochemistry test (IHC) being developed by Roche Diagnostics. Eligibility criteria included people whose tumours were determined to express PD-L1 with an IHC score of TC2/3 or IC2/3. People in the study received a 1200-milligram intravenous dose of atezolizumab every 3 weeks. The primary endpoint of the study was ORR. Secondary endpoints included duration of response (DoR), overall survival (OS), progression-free survival (PFS) and safety.

About non-small cell lung cancer
Lung cancer is the leading cause of cancer death globally. Each year, 1.59 million people die as a result of the disease, which means more than 4,350 deaths worldwide every day. Lung cancer can be broadly divided into two major types, NSCLC and small cell lung cancer. NSCLC is the most prevalent type, accounting for around 85% of all cases.

About Roche in lung cancer
Lung cancer is a major area of focus and investment for Roche, and we are committed to developing new approaches, medicines and tests that can help people with this deadly disease. Our goal is to provide an effective treatment option for every person diagnosed with lung cancer. We currently have three approved medicines to treat certain kinds of lung cancer and more than 10 medicines being developed to target the most common genetic drivers of lung cancer or to boost the immune system to combat the disease.

About atezolizumab
Atezolizumab (also known as MPDL3280A; anti-PDL1) is an investigational monoclonal antibody designed to interfere with a protein called PD-L1. Atezolizumab is designed to target PD-L1 expressed on tumour cells and tumour-infiltrating immune cells, preventing it from binding to PD-1 and B7.1 on the surface of T cells. By inhibiting PD-L1, atezolizumab may enable the activation of T cells.
All studies of atezolizumab include the evaluation of an investigational IHC test that uses the antibody SP142 to measure PD-L1 expression on both tumour cells and infiltrating immune cells. The goal of PD-L1 as a biomarker is to identify those people most likely to benefit when treated with atezolizumab alone, and to determine which people may benefit most from a combination of atezolizumab and another medicine. There are 11 ongoing or planned Phase III studies of atezolizumab across certain kinds of lung, kidney, breast and bladder cancer.

On August 16, 2015 Hospira Japan Co., Ltd. reported that two new generic oncology drugs have been approved by the Ministry of Health, Labour and Welfare (MHLW) in Japan (Press release, Hospira, AUG 16, 2015, View Source;p=RssLanding&cat=news&id=2079850 [SID:1234507271]).

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Gemcitabine I.V. lnfusion[Hospira] is the pre-mixed solution and the additional dosage form to Gemcitabine for I.V. lnfusion[Hospira] with freeze-dried formulation. It is expected to contribute to reducing the medical preparation time and the risks of exposure to cytotoxic agents.
Oxaliplatin I.V. lnfusion 200mg/40mL [Hospira] is the additional presentation to the current Oxaliplatin lineup – 50mg/10mL, 100mg/20mL.

We are committed to launching a broad portfolio of high-quality generics in Japan to meet medical needs of patients across the country.

About the Products
[Product name]
Gemcitabine I.V. lnfusion 200mg/5.3mL [Hospira]
Gemcitabine I.V. lnfusion 1g/26.3mL [Hospira]
[Therapeutic category]
Metabolic antagonist malignant tumour drug
[Indications]
Non-small cell lung cancer, pancreatic cancer, biliary tract cancer, uroepithelial cancer, inoperable or recurrent breast cancer, ovarian cancer progressing after chemotherapy, recurrence or refractory malignant lymphoma

[Product name]
Oxaliplatin I.V. lnfusion 200mg/40mL [Hospira]
[Therapeutic category]
Anticancer drug
[Indications]
Unresectable advanced/recurrent colorectal cancer, Supplementary postoperative chemotherapy for colon cancer, Inoperable pancreatic cancer

Hospira Japan has a partnership co-promoting oncology generic products with Mochida Pharmaceuticals in Japan.

On August 16, 2015 Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), reported that in the large pivotal Phase II study, BIRCH, the investigational cancer immunotherapy atezolizumab (MPDL3280A; anti-PDL1) met its primary endpoint and shrank tumors (objective response rate; ORR) in people with locally advanced or metastatic non-small cell lung cancer (NSCLC) whose disease expressed PD-L1 (Programmed Death Ligand-1) (Press release, Genentech, AUG 16, 2015, View Source [SID:1234507278]). The study showed the amount of PD-L1 expressed by a person’s cancer correlated with their response to the medicine. Adverse events were consistent with what has been previously observed for atezolizumab.

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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"We are encouraged by the number of people who responded to atezolizumab and maintained their response during the study, which is particularly meaningful for people who had received several prior treatments," said Sandra Horning, M.D., chief medical officer and head of Global Product Development. "We plan to present results at an upcoming medical meeting and will discuss these data as well as results from our other lung cancer studies with health authorities to bring this medicine to patients as quickly as possible."

Earlier this year, the FDA granted atezolizumab a Breakthrough Therapy Designation for the treatment of people whose NSCLC expresses PD-L1 and who progressed during or after standard treatments (e.g., platinum-based chemotherapy and appropriate targeted therapy for EGFR mutation-positive or ALK-positive disease). This designation is designed to expedite the development and review of medicines intended to treat serious diseases. We have seven Phase III studies evaluating atezolizumab alone or in combination with other medicines as a potential new treatment for people with early and advanced stages of lung cancer.

About the BIRCH Study

BIRCH is an open-label, multicenter, single-arm Phase II study that evaluated the safety and efficacy of atezolizumab in 667 people with locally advanced or metastatic NSCLC whose disease expressed PD-L1. PD-L1 expression was assessed on both tumor cells (TC) and tumor-infiltrating immune cells (IC) with an investigational immunohistochemistry test (IHC) being developed by Roche Diagnostics. Eligibility criteria included people whose tumors were determined to express PD-L1 with an IHC score of TC2/3 or IC2/3. People in the study received a 1200-milligram intravenous dose of atezolizumab every three weeks. The primary endpoint of the study was ORR. Secondary endpoints included duration of response (DoR), overall survival (OS), progression-free survival (PFS) and safety. Results from BIRCH will be presented at an upcoming medical meeting.

About Lung Cancer

According to the American Cancer Society, it is estimated that more than 221,000 Americans will be diagnosed with lung cancer in 2015, and NSCLC accounts for 85 percent of all lung cancers. It is estimated that approximately 60 percent of lung cancer diagnoses in the United States are made when the disease is in the advanced stages.

About atezolizumab

Atezolizumab (also known as MPDL3280A; anti-PDL1) is an investigational monoclonal antibody designed to interfere with a protein called PD-L1. Atezolizumab is designed to target PD-L1 expressed on tumor cells and tumor-infiltrating immune cells, preventing it from binding to PD-1 and B7.1 on the surface of T cells. By inhibiting PD-L1, atezolizumab may enable the activation of T cells.

All studies of atezolizumab include the evaluation of an investigational IHC test that uses the antibody SP142 to measure PD-L1 expression on both tumor cells and infiltrating immune cells. The goal of PD-L1 as a biomarker is to identify those people most likely to benefit when treated with atezolizumab alone, and to determine which people may benefit most from a combination of atezolizumab and another medicine. There are 11 ongoing or planned Phase III studies of atezolizumab across certain kinds of lung, kidney, breast and bladder cancer.