On June 4, 2015 OPKO HEALTH, INC. (NYSE:OPK) and Bio-Reference Laboratories, Inc. (NASDAQ:BRLI) reported that the companies have signed a definitive merger agreement under which OPKO will acquire Bio-Reference Laboratories (Press release, Opko Health, JUN 4, 2015, View Source [SID:1234506549]). Bio-Reference Laboratories is the third largest full service clinical laboratory in the United States and is known for its innovative technological solutions and pioneering leadership in the areas of genomics and genetic sequencing. Under the terms of the agreement, which has been approved by the Boards of Directors of both companies, holders of BRLI common stock will receive 2.75 shares of OPKO common stock for each share of BRLI common stock. Based on a closing price of $19.12 per share of OPKO common stock on June 3, 2015, the transaction is valued at approximately $1.47 billion, or $52.58 per share of BRLI common stock. The Companies expect the transaction to be completed during the second half of 2015. Closing of the transaction is subject to approval of Bio-Reference Laboratories’ shareholders and other customary conditions.

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OPKO intends to leverage the national marketing, sales, and distribution resources of Bio-Reference Laboratories to enhance sales of its 4Kscore test, a blood test that provides a patient’s specific personalized risk score for aggressive prostate cancer as well as other OPKO diagnostic products under development.

Through GeneDx, Bio-Reference Laboratories’ genetic sequencing laboratory, and GenPath Diagnostics, its Oncology and Women’s Health business units, Bio-Reference Laboratories has accumulated a vast array of genetic and genomics data that OPKO will make available to industry and academic scientists to enhance their drug discovery and clinical trial programs.

"I have long admired Bio-Reference Laboratories which, for almost 30 years, has enjoyed an impressive record of organic growth through constant innovation and clinical awareness," commented Phillip Frost, M.D., OPKO’s Chairman and Chief Executive Officer. "Bio-Reference Laboratories is a true success story that has culminated in cutting edge diagnostic solutions accompanied by a worldwide franchise in the diagnosis of rare diseases. GeneDx was the first commercial laboratory to offer next generation sequencing for rare disorders and almost a quarter of a million patients have benefited from these services including almost 20,000 patients who have undergone exome analysis. Their newly introduced sequencing services for use in oncology are both innovative and impressive."

"Over the years we have learned that diagnostics are integral to drug discovery," commented Marc Grodman, M.D., Bio-Reference Laboratories’ Chairman, CEO and President. "This has never been more apparent than today when new sequencing technologies have afforded us the opportunity to understand the biological basis of disease in far greater depth. At Bio-Reference Laboratories we have prided ourselves in finding disruptive diagnostic solutions that are clinically relevant. Dr. Frost is a visionary in the pharmaceutical world who, during a legendary career, has demonstrated the foresight to see new clinical applications for therapeutics before others. I am thrilled that I will be working and learning from him in the coming years as we seek to leverage our outstanding capabilities to improve lives of patients. In addition to identifying a synergistic partner for the value we have built over the past three decades, we are pleased that our shareholders will be rewarded by being able to share in the upside of the combined company."

OPKO intends to allow laboratory operations to continue seamlessly but with enhancement from OPKO’s pipeline of diagnostic products. The current diagnostic services of OPKO will be merged with the Bio-Reference Laboratories operations throughout the country. Bio-Reference Laboratories’ national presence will add valuable distribution capability to OPKO’s diagnostic services. Bio-Reference Laboratories is a full service clinical laboratory that can provide key areas of opportunity for OPKO’s services. Moreover, the seasoned management team at Bio-Reference Laboratories will bring valuable market intelligence to the combined operations.

Dr. Grodman continued, "Bio-Reference Laboratories has been a pioneer in commercial laboratory use of next generation sequencing for diagnostic purposes. GeneDx believes it was the first commercial laboratory in the world to offer next generation genetic sequencing panels based on specific clinical symptoms; it has maintained its leadership position in offering advanced panels, sophisticated analysis, in-depth reporting, and by scaling these tools to a high-volume commercial environment. Bio-Reference Laboratories has accumulated a plethora of genetic and genomics data that will be invaluable to the drug discovery programs at OPKO and other drug developers. The Bio-Reference Laboratories data is diagnostic, or disease-related, and therefore provides an important connection between disease, treatment and cure."

On June 4, 2015, OPKO HEALTH and Bio-Reference Laboratories reported that the companies have signed a definitive merger agreement under which OPKO will acquire Bio-Reference Laboratories (Filing, 8-K, Opko Health, JUN 4, 2015, View Source [SID:1234505230]). Bio-Reference Laboratories is the third largest full service clinical laboratory in the United States and is known for its innovative technological solutions and pioneering leadership in the areas of genomics and genetic sequencing. Under the terms of the agreement, which has been approved by the Boards of Directors of both companies, holders of BRLI common stock will receive 2.75 shares of OPKO common stock for each share of BRLI common stock. Based on a closing price of $19.12 per share of OPKO common stock on June 3, 2015, the transaction is valued at approximately $1.47 billion, or $52.58 per share of BRLI common stock. The Companies expect the transaction to be completed during the second half of 2015. Closing of the transaction is subject to approval of Bio-Reference Laboratories’ shareholders and other customary conditions.

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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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OPKO intends to leverage the national marketing, sales, and distribution resources of Bio-Reference Laboratories to enhance sales of its 4Kscore test, a blood test that provides a patient’s specific personalized risk score for aggressive prostate cancer as well as other OPKO diagnostic products under development.

Through GeneDx, Bio-Reference Laboratories’ genetic sequencing laboratory, and GenPath Diagnostics, its Oncology and Women’s Health business units, Bio-Reference Laboratories has accumulated a vast array of genetic and genomics data that OPKO will make available to industry and academic scientists to enhance their drug discovery and clinical trial programs.

"I have long admired Bio-Reference Laboratories which, for almost 30 years, has enjoyed an impressive record of organic growth through constant innovation and clinical awareness, commented Phillip Frost M.D., OPKO’s Chairman and Chief Executive Officer. "Bio-Reference Laboratories is a true success story that has culminated in cutting edge diagnostic solutions accompanied by a worldwide franchise in the diagnosis of rare diseases. GeneDx was the first commercial laboratory to offer next generation sequencing for rare disorders and almost a quarter of a million patients have benefited from these services including almost 20,000 patients who have undergone exome analysis. Their newly introduced sequencing services for use in oncology are both innovative and impressive."

"Over the years we have learned that diagnostics are integral to drug discovery," commented Marc Grodman, M.D., Bio-Reference Laboratories’ Chairman, CEO and President. "This has never been more apparent than today when new sequencing technologies have afforded us the opportunity to understand the biological basis of disease in far greater depth. At Bio-Reference Laboratories we have prided ourselves in finding disruptive diagnostic solutions that are clinically relevant. Dr. Frost is a visionary in the pharmaceutical world who, during a legendary career, has demonstrated the foresight to see new clinical applications for therapeutics before others. I am thrilled that I will be working and learning from him in the coming years as we seek to leverage our outstanding capabilities to improve lives of patients. In addition to identifying a synergistic partner for the value we have built over the past three decades, we are pleased that our shareholders will be rewarded by being able to share in the upside of the combined company."

OPKO intends to allow laboratory operations to continue seamlessly but with enhancement from OPKO’s pipeline of diagnostic products. The current diagnostic services of OPKO will be merged with the Bio-Reference Laboratories operations throughout the country. Bio-Reference Laboratories’ national presence will add valuable distribution capability to OPKO’s diagnostic services. Bio-Reference Laboratories is a full service clinical laboratory that can provide key areas of opportunity for OPKO’s services. Moreover, the seasoned management team at Bio-Reference Laboratories will bring valuable market intelligence to the combined operations.

Dr. Grodman continued: "Bio-Reference Laboratories has been a pioneer in commercial laboratory use of next generation sequencing for diagnostic purposes. GeneDx believes it was the first commercial laboratory in the world to offer next generation genetic sequencing panels based on specific clinical symptoms; it has maintained its leadership position in offering advanced panels, sophisticated analysis, in-depth reporting, and by scaling these tools to a high-volume commercial environment. Bio-Reference Laboratories has accumulated a plethora of genetic and genomics data that will be invaluable to the drug discovery programs at OPKO and other drug developers. The Bio-Reference Laboratories data is diagnostic, or disease-related, and therefore provides an important connection between disease, treatment and cure."

J.P. Morgan acted as the financial advisor to OPKO Health. Allen & Company LLC acted as financial advisor to Bio-Reference Laboratories. Greenberg Traurig, P.A. acted as legal advisor to OPKO and Davis Polk & Wardwell LLP was Bio-Reference Laboratories’ legal advisor.

On June 4, 2014 Provectus Pharmaceuticals reported new findings on PV-10, an investigational intra-lesional therapy for melanoma, were presented during the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper)’s Annual Meeting on May 31, 2015, Chicago, Illinois, USA (Press release, Provectus Pharmaceuticals, JUN 4, 2015, View Source [SID:1234505231]). The presentation entitled "A Changing Topography: The Role of Intralesional Therapy in Melanoma" was presented by Dr. Sanjiv Agarwala, from St. Luke’s Cancer Center in Bethlehem and Temple University School of Medicine in Pennsylvania, USA.

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Melanoma is a cancer that has its origins in melanocytes, cells that produce the brown pigment called melanin which protects the deeper layers of the skin from the harmful effects of the sun. Melanoma is much less frequent than basal cell and squamous cell skin cancers, but it is far more dangerous. Like basal cell and squamous cell cancers, melanoma is almost always curable if detected earlier but has a higher probability to spread to other parts of the body if it is not detected early.

PV-10 is Provectus Biopharmaceuticals’ new experimental drug for cancer, and was designed to be injected into solid tumors i.e. intralesional administration, to reduce potential systemic adverse effects. The FDA has already granted an orphan drug designation for Provectus’ melanoma and hepatocellular carcinoma indications.

Dr. Sanjiv Agarwala established as mains goals of intra-lesional therapy local disease control (decreasing tumor size during a prolonged period), control of symptoms and palliation, decreased systemic effect (immune mediated), delay or prevention of systemic treatment and neo-adjuvant potential. The researcher showed results from the phase 3 trial from T-VEC, an HSV-1-derived oncolytic immunotherapy conceived to induce local and systemic effects. He also showed phase 2 findings for PV-10, showing the drug accumulated within cancer cells but not normal cells, inducing acute autophagy and exposing antigenic tumor fragments to antigenic presenting cells (APCs).

Dr. Agarwala stated that intralesional approaches may hold a promising value, since they act locally and do not have a systemic immune effect. Moreover the researcher concluded that combination therapies are probably the future of melanoma treatment and may be the best way to transition into clinical practice.

On June 4, 2015 Cellectis reported that pre-clinical data on its engineered allogeneic CAR T-cells will be featured in two oral presentations and one poster presentation at the European Hematology Association (EHA) (Free EHA Whitepaper) Annual Meeting (Press release, Cellectis, JUN 4, 2015, View Source [SID:1234505236]). The meeting will be held from June 11th to 14th, 2015, in Vienna, Austria.

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The selected presentations are as follow:

Allogeneic adoptive immunotherapy of acute myeloid leukemia (ALM) by targeting CD123 with CAR T-Cells
Oral Presentation

Session Title: Gene therapy, cellular immunotherapy & vaccination

Presentation Time: Saturday, June 13th, 2015, 12:15pm to 12:30pm

UCART19, an Allogeneic "Off-the-Shelf" Adoptive T-Cell Immunotherapy Against CD19+ B-Cell Leukemias
Oral Presentation

Session Title: Gene therapy, cellular immunotherapy & vaccination

Presentation Time: Saturday, June 13th, 2015, 12:30pm to 12:45pm

Adoptive immunotherapy of multiple myeloma (MM) with allogeneic CAR T-Cells targeting CS1: enhancement of CAR activity through CS1 gene inactivation in effector cells
Poster Presentation

Session Title: Gene therapy, cellular immunotherapy & vaccination Presentation Time: Saturday, June 13th, 2015, 5:15pm to 6:45pm

On June 3, 2015 Boehringer Ingelheim reported that following a review by the National Institute for Health and Care Excellence (NICE) in the UK, VARGATEF (nintedanib*) in combination with docetaxel has been recommended for use within the National Health Service (NHS) in England and Wales (Press release, Boehringer Ingelheim, JUN 3, 2015, View Source [SID:1234505215]).1 This is positive news for patients with locally advanced metastatic or locally recurrent non-small cell lung cancer (NSCLC) of adenocarcinoma histology who have had limited treatment options that have been shown to extend survival after first-line chemotherapy.

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Dr Mehdi Shahidi, Medical Head, Solid Tumour Oncology, Boehringer Ingelheim commented: "We are delighted with this announcement from NICE which represents an important milestone in the effort to extend survival for patients with adenocarcinoma of the lung following initial treatment with chemotherapy. The survival advantage demonstrated by VARGATEF, in combination with docetaxel, has been shown with a predictable and generally manageable safety profile."

NICE has issued a Final Appraisal Determination (FAD) for VARGATEF and, subject to any appeal by consultees, the FAD may be used as the basis for the institute’s guidance on the use of the appraised technology in the NHS in England and Wales.1 Nintedanib, in combination with docetaxel, is the first and only triple angiokinase inhibitor available for EU patients with advanced NSCLC of adenocarcinoma histology after first-line chemotherapy.

Since the launch of VARGATEF in January 2015 it has also been:

accepted for use without restriction within NHS Scotland, as per its licensed indication2

accepted by the Swedish Dental and Pharmaceutical Benefits Agency to be subsidised as a treatment of advanced lung cancer patients with adenocarcinoma in combination with docetaxel after first-line chemotherapy3

assessed by the German IQWiG who indicated an added benefit for the treatment of advanced lung cancer patients with adenocarcinoma in combination with docetaxel after first-line chemotherapy without brain metastases4

These announcements are based on the outcomes of the LUME-Lung 1 study which demonstrated:5

nintedanib, plus docetaxel, significantly prolonged progression-free survival compared to docetaxel alone for patients with
adenocarcinoma (PFS: primary endpoint; 4.0 vs 2.8 months)

nintedanib, plus docetaxel, significantly extended overall survival to beyond one year for patients with adenocarcinoma, compared to docetaxel alone (OS: key secondary endpoint; 12.6 vs 10.3 months)

nintedanib, plus docetaxel, enabled 1 in 4 patients with adenocarcinoma to live for at least two years after first-line chemotherapy

Nintedanib in combination with docetaxel demonstrated a generally manageable side-effect profile without further compromising patients’ overall, health-related, quality of life compared to chemotherapy alone. The most common adverse events for patients taking docetaxel vs nintedanib plus docetaxel included: nausea 18% vs 24%; vomiting 9% vs 17%; diarrhoea 22% vs 42% and elevated liver enzymes 8% vs 29%.5

Adenocarcinoma is the most common type of lung cancer and the majority of patients are diagnosed in an advanced stage.6 Most patients will experience disease progression during or after first-line chemotherapy and there is a significant need for new, effective second-line treatments.5

VARGATEF was granted EU marketing authorisation in November 2014 and in combination with docetaxel is indicated for use in adult patients with locally advanced, metastatic or locally recurrent non-small cell lung cancer (NSCLC) of adenocarcinoma tumour histology, after first-line chemotherapy.