On March 23, 2017 BioLineRx Ltd. (NASDAQ/TASE: BLRX), a clinical-stage biopharmaceutical company focused on oncology and immunology, reported that it has acquired Agalimmune Ltd., a private UK-based company with an innovative, anti-cancer immunotherapy platform. Acquisition consideration consisted of a $6 million upfront payment, of which $3 million is in cash and the remainder in BioLineRx shares (Press release, BioLineRx, MAR 23, 2017, View Source [SID1234518249]). Additional future payments may be made based on development and commercial milestones.

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Agalimmune’s lead compound is AGI-134, a synthetic alpha-Gal immunotherapy in development for solid tumors. AGI-134 harnesses the body’s pre-existing, highly abundant anti-alpha-Gal antibodies to induce a systemic, specific anti-tumor response to the patient’s own tumor neo-antigens. This response not only kills the tumor cells at the site of injection, but also brings about a durable, follow-on, anti-metastatic immune response.

AGI-134 has completed numerous pre-clinical studies, demonstrating robust protection against the development of secondary tumors in a model of melanoma with a single dose only. Synergy has also been demonstrated in additional pre-clinical studies when combined with a PD-1 immune checkpoint inhibitor, offering the potential to broaden the utility of such immunotherapies, and improve the rate and duration of responses in multiple cancer types. AGI-134 is in near-clinical development and is expected to commence a first-in-man study in patients with solid tumors in the first half of 2018.

Philip Serlin, Chief Executive Officer of BioLineRx, stated, "Immuno-oncology is one of the most promising approaches for the treatment of cancer. Although a number of current immunotherapies are receiving widespread attention, many solid tumors are still able to evade the immune system’s surveillance. Most immunotherapies work best in highly mutated tumors that are infiltrated with immune cells, known as ‘hot’ tumors. Unfortunately, the overwhelming majority of tumors are ‘cold’ tumors, and thus transforming a ‘cold’ tumor into a ‘hot’ tumor is a major objective in cancer treatment."

"In this regard, Agalimmune’s lead asset, AGI-134, harnesses naturally occurring, pre-existing antibodies to elicit a tumor-specific immune response that is unique to the treated individual and provides a universal, small-molecule approach to personalized immunotherapy. The subsequent stimulation and recruitment of T cells, which recognize the patient’s own neo-antigens, to the tumor site, has the potential of transforming ‘cold’ tumors into ‘hot’ ones. Through this important acquisition, we will also benefit from Agalimmune’s complementary immunology expertise and facilities in the UK, which support our strategic focus in this area. We are enthusiastic to incorporate into our pipeline this promising near-clinical asset, which substantially strengthens our position in the immuno-oncology space," added Mr. Serlin.

"We are very excited that we found an ideal partner for our promising therapeutic pipeline. We are extremely impressed by BioLineRx’s proven drug development capabilities, as well as their meaningful collaborations with global pharmaceutical companies," said Damian Marron, CEO of Agalimmune. "We strongly believe in the value of our unique platform and we look forward to its accelerated clinical development by BioLineRx."

About Agalimmune and AGI-134

Agalimmune Ltd. is a biopharmaceutical company with an innovative anti-cancer immunotherapy pipeline for generating a systemic, adaptive immune response to solid tumors. It was established in 2013 and is headquartered in London, England with laboratories in Sandwich, England and Boston, Massachusetts.

AGI-134, Agalimmune’s lead molecule is a synthetic alpha-Gal immunotherapy in development for solid tumors. AGI-134 harnesses the body’s pre-existing, highly abundant, anti-alpha-Gal antibodies to induce a systemic, specific anti-tumor response to the patient’s own tumor neo-antigens. This response not only kills the tumor cells at the site of injection, but also brings about a durable, follow-on anti-metastatic immune response. Alpha-Gal is a cell-surface carbohydrate antigen which is not expressed by humans, unlike virtually all other mammals and bacteria. Therefore, humans universally produce and maintain high levels of anti-Gal antibodies, due to exposure to alpha-Gal on bacteria in the digestive system.

AGI-134 is injected into the tumor, where it coats the tumor cell membranes, resulting in alpha-Gal being exposed on the tumor cell surface. Anti-Gal antibodies bind to the alpha-Gal part of AGI-134 to produce an initial immune response that activates complement-dependent and antibody-dependent cellular cytotoxicity (cell death). This cytotoxicity generates immune-tagged cells and cellular debris that trigger an uptake of tumor-associated antigens by antigen-presenting cells (APCs). These APCs induce a follow-on systemic immune response by the activation and clonal expansion of T cells (CD8+) to the patient’s own neo-antigens. This approach not only targets the primary injectable tumor, but has also demonstrated efficacy against existing distant secondary tumors. Furthermore, the mechanism of action suggests the potential of long-term protection against future metastases. The use of intratumoral alpha-Gal glycolipids to treat solid tumors was invented by Prof. Uri Galili, Ph.D., while at the University of Massachusetts, from where the intellectual property rights were licensed. The intellectual property rights relating to AGI-134 were in-licensed from KODE Biotech Ltd., the inventors of AGI-134.

On March 23, 2017 BioLineRx Ltd. (NASDAQ: BLRX, TASE: BLRX), a clinical-stage biopharmaceutical company focused on oncology and immunology,reported its financial results for the year ended December 31, 2016 (Press release, BioLineRx, MAR 23, 2017, View Source [SID1234518246]).

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Highlights and achievements in 2016 and to date:

Acquired Agalimmune Ltd., a UK-based biopharmaceutical company developing immunotherapeutic cancer treatments, thereby broadening and bolstering BioLineRx’s presence in immuno-oncology. Agalimmune’s novel lead compound, AGI-134, harnesses the body’s pre-existing, highly abundant, anti-alpha-Gal antibodies to drive a patient-specific, systemic, anti-tumor response for various cancer indications. AGI-134 may also bring about a long-lasting, protective, follow-on, anti-tumor immune response, and has exhibited synergies in combination with check-point inhibitor therapies;

Signed extensive immuno-oncology collaboration with Genentech, a member of the Roche Group, for several Phase 1b studies for BL-8040 in combination with Genentech’s Atezolizumab, in multiple solid tumor indications, including pancreatic cancer, gastric cancer and non-small cell lung cancer, as well as AML. The collaboration may also be expanded into additional indications;

Signed immuno-oncology collaboration with MSD (known as Merck in the US and Canada), and subsequently initiated a Phase 2a study in pancreatic cancer for BL-8040 in combination with Merck’s KEYTRUDA;

Initiated Phase 2b immuno-oncology collaboration with MD Anderson Cancer Center for additional BL-8040 and KEYTRUDA combination study in pancreatic cancer, as part of strategic clinical research immunotherapy collaboration between MSD and MD Anderson Cancer Center;

Reported partial results data on Phase 2 open label study for BL-8040 as novel stem cell mobilization treatment. Interim results support BL-8040 as a one-day dosing regimen for rapid mobilization of substantial amounts of stem cells, a significant improvement over the current standard of care which requires four-to-six daily injections of G-CSF.

In-licensed three new projects under strategic collaboration with Novartis, including two novel liver fibrosis/failure projects, and a novel anti-inflammatory treatment for dry eye syndrome;

Presented growing body of clinical evidence surrounding BL-8040 at leading medical and scientific conferences, including the American Society of Hematology (ASH) (Free ASH Whitepaper), Society of Hematologic Oncology (SOHO), and American Association for Cancer Research (AACR) (Free AACR Whitepaper);

Expanded geographic reach with new joint venture in China for development of novel drug candidates; and

Appointed Philip A. Serlin as CEO.
Expected upcoming significant milestones for 2017 and 2018:

Initiation of Phase 2/3 registrational study for BL-8040 in stem-cell mobilization for autologous transplantation expected in H2 2017;

Completion of Phase 2 study for BL-8040 in stem-cell mobilization for allogeneic transplantation, expected by year end;

Partial results from the immuno-oncology Phase 2a study for pancreatic cancer for BL-8040 in combination with Merck’s KEYTRUDA expected in H2 2017; top line results expected in H2 2018;

Initiation of Phase 1b immuno-oncology studies for BL-8040 in combination with Genentech’s Atezolizumab in multiple solid tumor indications and AML expected in H2 2017; partial results expected in H2 2018; and

Initiation of Phase 1 immuno-oncology study for AGI-134 in multiple solid tumor indications expected in H1 2018.
Philip A. Serlin, Chief Executive Officer of BioLineRx, remarked, "2016 demonstrated BioLineRx’s strengths, as we leveraged our BL-8040 oncology platform to initiate combination studies with industry leaders in the field of immuno-oncology, while steadily advancing our multiple other clinical studies. In addition, we continued to validate our asset discovery and development capabilities, with the addition of an immunology and fibrosis franchise following the in-licensing of three programs under our Novartis collaboration. As we enter 2017, we are pleased to have just announced our first acquisition, of Agalimmune Ltd., adding a unique oncology platform to our pipeline, which significantly expands and strengthens our immuno-oncology offering."

"We remain focused on building a robust clinical-stage oncology and immunology therapeutic pipeline offering us exciting potential business opportunities. We believe BioLineRx is at a very significant stage, with key milestones in the next 12-18 months," Mr. Serlin concluded.

Financial Results for the Year Ended December 31, 2016

Research and development expenses for the year ended December 31, 2016 were $11.2 million, a decrease of $0.3 million, or 2.6%, compared to $11.5 million for the year ended December 31, 2015. The decrease results primarily from a decrease in spending on BL-7010, partially offset by increased spending on new projects.

Sales and marketing expenses for the year ended December 31, 2016 were $1.4 million, an increase of $0.4 million, or 40.0%, compared to $1.0 million for the year ended December 31, 2015. The increase results primarily from consultancy services related to BL-8040 and new projects.

General and administrative expenses for the year ended December 31, 2016 were $4.0 million, an increase of $0.3 million or 8.1%, compared to $3.7 million for the year ended December 31, 2015. The increase results primarily from one-time salary-related payments and an increase in professional fees.

The Company’s operating loss for the year ended December 31, 2016 amounted to $16.5 million, compared with an operating loss of $16.2 million for the year ended December 31, 2015.

Net non-operating income of $0.2 million was recognized for the year ended December 31, 2016, a decrease of $1.2 million compared to net non-operating income of $1.4 million for the year ended December 31, 2015. Non-operating expenses and income for both periods primarily relate to fair-value adjustments of liabilities on account of warrants issued in the private and direct placements which we conducted in February 2012 and 2013. These fair-value adjustments were highly influenced by our share price at each period end.

Net financial income for the year ended December 31, 2016 was $0.5 million, compared to net financial income of $0.4 million for the year ended December 31, 2015. Net financial income for the two periods primarily relates to investment income earned on our bank deposits, as well as banking fees.

The Company’s net loss for the year ended December 31, 2016 amounted to $15.8 million, compared with a net loss of $14.4 million for the year ended December 31, 2015.

The Company held $35.6 million in cash, cash equivalents and short-term bank deposits as of December 31, 2016.

Net cash used in operating activities for the year ended December 31, 2016 was $14.5 million, compared to $14.2 million for the year ended December 31, 2015. The increase in net cash used in operating activities in 2016 was primarily the result of an increase in our operating loss.

Net cash provided by investing activities for the year ended December 31, 2016 was $9.3 million, compared to $15.6 million cash used in investing activities for the year ended December 31, 2015. The changes in cash flows from investing activities relate primarily to investments in, and maturities of, short-term bank deposits and other investments during the respective periods.

Net cash provided by financing activities for the year ended December 31, 2016 was $2.1 million, compared to $29.5 million for the year ended December 31, 2015. The cash flows in 2016 primarily reflect the funding under the share purchase agreement with LPC. The cash flows in 2015 primarily reflect the underwritten public offering of our ADSs in March 2015.

On March 23, 2017 Peregrine Pharmaceuticals, Inc. (NASDAQ:PPHM) (NASDAQ:PPHMP), a biopharmaceutical company committed to improving patient lives by manufacturing high quality products for biotechnology and pharmaceutical companies, and advancing its proprietary R&D pipeline, reported that four preclinical abstracts and one clinical abstract have been accepted for presentation at the Annual Meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper), to be held April 1 – 5, 2017 in Washington, D.C (Press release, Peregrine Pharmaceuticals, MAR 23, 2017, View Source [SID1234518245]).

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Peregrine scientists and collaborators will present positive findings from multiple studies of the company’s phosphatidylserine (PS)-targeting antibodies in combination with other anti-tumor agents, including results from two Memorial Sloan Kettering Cancer Center studies that evaluate the use of a bavituximab equivalent in combination with immune stimulating therapies. The following abstracts will be presented:
Abstract Number: 574
Session: PO.IM02.02 – Checkpoints 1
Presentation Title: Phosphatidylserine targeting antibody in combination with tumor radiation and immune checkpoint blockade promotes anti-tumor activity in mouse B16 melanoma
Presentation Day/Time: Sunday, April 2, 2017, 1:00 – 5:00 PM Eastern
Location: Section 25
Poster Board Number: 8
Author Institutions: Memorial Sloan Kettering Cancer Center, New York, NY; Peregrine Pharmaceuticals, Inc., Tustin, CA
Abstract Number: 1651
Session: PO.IM02.08 – Tumor Microenvironment and Checkpoints
Presentation Title: Targeting phosphatidylserine in combination with adoptive T cell transfer eliminates advanced tumors without off-target toxicities in a melanoma preclinical model
Presentation Day/Time: Monday, April 3, 2017, 8:00 – 12:00 PM Eastern
Location: Section 27
Poster Board Number: 29
Author Institutions: Memorial Sloan Kettering Cancer Center, New York, NY; Peregrine Pharmaceuticals, Inc., Tustin, CA
Abstract Number: CT159
Session: PO.CT02 – Phase III Clinical Trials and Phase II/III Clinical Trials in Progress
Presentation Title: IFN-γ analysis in blood and tissue as a potential prognostic and/or predictive biomarker
Presentation Day/Time: Monday, Apr 3, 2017 1:00 – 5:00 PM Eastern
Location: Section 33
Poster Board Number: 25
Author Institution: Peregrine Pharmaceuticals, Tustin, CA
Abstract Number: 3652
Session: PO.IM02.05 – BITES Bispecifics and Checkpoints
Presentation Title: Combinational activity of LAG3 and PD-1 targeted therapies is significantly enhanced by the addition of phosphatidylserine targeting antibodies and establishes an anti-tumor memory response in murine triple negative breast cancer
Presentation Day/Time: Tuesday, April 4, 2017, 8:00 – 12:00 PM Eastern
Location: Section 26
Poster Board Number: 25
Author Institution: Peregrine Pharmaceuticals, Tustin, CA
Abstract Number: 3657
Session: PO.IM02.05 – BITES Bispecifics and Checkpoints
Presentation Title: Phosphatidylserine-targeting antibodies enhance anti-tumor activity of a tumor vaccine in a HPV-induced tumor model
Presentation Day/Time: Tuesday, April 4, 2017, 8:00 – 12:00 PM Eastern
Location: Section 26
Poster Board Number: 30
Author Institutions: Immunovaccine, Inc., Halifax, NS, Canada; Peregrine Pharmaceuticals, Inc., Tustin, CA
Bavituximab is an investigational monoclonal antibody that targets PS. Signals from PS inhibit the ability of immune cells to recognize and fight tumors. Bavituximab is believed to override PS mediated immunosuppressive signaling by blocking the engagement of PS with its receptors as well as by sending an alternate immune activating signal. Previous studies demonstrated PS-targeting antibodies shift the functions of immune cells in tumors, resulting in multiple signs of immune activation and anti-tumor responses.
Peregrine’s clinical development strategy for bavituximab currently focuses on small, early-stage, proof-of-concept trials evaluating the drug in combination with other cancer treatments. As part of this approach the National Comprehensive Cancer Network (NCCN) has awarded grants to support three different clinical trials of bavituximab treatment combinations. These trials will evaluate novel bavituximab combinations in glioblastoma, head and neck cancer, and hepatocellular carcinoma including an immunotherapy combination. Additionally, Peregrine continues to advance its pre-clinical collaboration with Memorial Sloan Kettering Cancer Center with the goal of evaluating combinations of bavituximab with other checkpoint inhibitors and immune stimulatory agents. The intent behind this strategy is to focus our research and development spending to further validate bavituximab’s combination potential as we seek to advance the program though a pharmaceutical or biotechnology partner.

On March 23, 2017 Merrimack Pharmaceuticals, Inc. (NASDAQ: MACK) reported the enrollment of its first patient in a Phase 1 study of MM-310 in solid tumors (Press release, Merrimack, MAR 23, 2017, View Source [SID1234518244]). MM-310 is an antibody-directed nanotherapeutic (ADN) that encapsulates a novel taxane and targets the EphA2 receptor, a protein which surveys suggest is overexpressed in 50-100% of many major tumor types, including prostate, ovarian, bladder, gastric, pancreatic and lung cancers.

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"The initiation of this study is an important step in evaluating MM-310’s safety and preliminary activity in patients diagnosed with solid tumors," said Vasileios Askoxylakis, MD, PhD, Medical Director and MM-310 Project Leader at Merrimack. "MM-310 was designed to maximize targeted delivery and local activation of a newly engineered and proprietary prodrug of docetaxel, a broadly-used potent chemotherapy that is often associated with significant drug-related toxicities, with a goal of minimizing exposure to healthy tissue. In several preclinical models, MM-310 not only demonstrated superior antitumor activity when compared to free docetaxel, but also fewer hematologic toxicities. We look forward to continuing MM-310’s development via this study."

The Phase 1 open-label study will assess the safety, pharmacology and preliminary activity of MM-310 in three parts. In part one, MM-310 will be assessed as a monotherapy until a maximum tolerated dose (MTD) is established. After the MTD of MM-310 is established, the study will include two further concurrent parts consisting of an expansion cohort as a single agent and a dose-finding phase in combination with other therapies. Merrimack expects to report data from part one of the study in 2018.

Five sites are currently expected to participate in this study. The first patient was dosed at Honor Health in Scottsdale, AZ.

About MM-310

MM-310 is an antibody-directed nanotherapeutic (ADN) that encapsulates a novel prodrug of the highly potent chemotherapy docetaxel in an ephrin receptor A2 (EphA2)-targeted liposome. EphA2 receptors are shown to be overexpressed in several solid tumors, including prostate, ovarian, bladder, gastric, pancreatic and lung cancers. Moreover, EphA2 receptors are associated with poor outcomes in certain indications. Preclinical data on MM-310 were presented in an oral presentation and three poster sessions at the 2016 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting and further data will be presented at the 2017 AACR (Free AACR Whitepaper) Annual Meeting in April. For more information on the Phase 1 study in solid tumors, please visit www.clinicaltrials.gov (Identifier: NCT03076372).

On March 23, 2017 Advaxis, Inc. (NASDAQ:ADXS), a biotechnology company developing cancer immunotherapies, reported the European Medicines Agency (EMA) issued an advanced therapy medicinal product certificate for manufacturing quality and non-clinical data (Press release, Advaxis, MAR 23, 2017, View Source [SID1234518243]).

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The certification procedure involved a thorough scientific evaluation over several months of the quality (CMC) data and non-clinical data by the EMA’s Committee for Advanced Therapies (CAT). After a positive opinion from CAT, EMA issued a certificate confirming that the CMC and non-clinical data comply with the standards that apply for evaluating the Marketing Authorization Application (MAA) of axalimogene filolisbac for the treatment of metastatic cervical cancer. Advaxis is now positioned to file the complete MAA in the second half of 2017.

"EMA’s issuance of this certification is a major milestone for Advaxis," said Daniel J. O’Connor, President and CEO. "With a significant portion of the MAA now reviewed and certified, we are preparing to file the complete MAA as we work to bring this innovative immunotherapy to patients with metastatic cervical cancer who have limited treatment options."

About Axalimogene Filolisbac

Axalimogene filolisbac is a targeted Listeria monocytogenes (Lm)-based immunotherapy that attacks HPV-associated cancers by altering a live strain of Lm bacteria to generate cancer-fighting T cells against cancer antigens while neutralizing the tumor’s natural protections that guard the tumor microenvironment from immunologic attack. In a phase 2 trial evaluating axalimogene filolisbac for the treatment of persistent or recurrent metastatic (squamous or non-squamous cell) carcinoma of the cervix (PRmCC), the drug candidate showed a 12-month overall survival rate of 38 percent observed in 50 patients in the trial. This is a 52 percent improvement over the 12-month overall survival rate that was expected in the trial’s patient population based on prognostic factors.

Axalimogene filolisbac has received Fast Track designation for adjuvant therapy for high-risk locally advanced cervical cancer (HRLACC) and a Special Protocol Assessment for the Phase 3 AIM2CERV trial in HRLACC patients. The immunotherapy has also received orphan drug designation in three clinical indications.