On June 4, 2015 Navidea Biopharmaceuticals reported that four presentations of Manocept data from Kaposi’s Sarcoma (KS) studies are scheduled at the 18th International Workshop on Kaposi’s Sarcoma Herpesvirus (KSHV) and Related Agents in Hollywood, Florida from June 30 – July 3, 2015 (Press release, Navidea Biopharmaceuticals, JUN 4, 2015, View Source;p=RssLanding&cat=news&id=2056585 [SID:1234505429]). This research highlights a very likely new approach to the origin of KS supported by preclinical and clinical imaging studies. In addition, data will be presented demonstrating the therapeutic potential for Manocept therapeutic conjugates. MT1001 is a proprietary agent designed to target cells expressing the mannose receptor (CD206) and destroy the cell and its contents. Data will be presented demonstrating MT1001’s ability to target KS and KS tumor-associated macrophages by selectively binding to CD206. Details of the presentations are listed below.

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Poster Session:

Date: July 1, 2015
Title: In Vivo Localization and Potential for Therapeutic Targeting of Kaposi’s Sarcoma (KS) With A Novel CD206 Localizing Agent
Authors: M McGratha,b*, J Zhanga, T Maurera, S Behra, B Abbruzzesec, J Sandersc, P Braccia,b, FO Copec (*Presenter)

aUniv of California-San Francisco; bAIDS & Cancer Specimen Resource, SFGH c Navidea/Macrophage Therapeutics

Poster Session:

Date: July 1, 2015

Title: Imaging and Therapeutic Potential for Kaposi’s Sarcoma (KS) In Non-Cutaneous Foci with a Novel CD206 Localizing Agent

Authors: B Abbruzzesea*, FO Copea, J Zhangb, T Maurerb, S Behrb, J Sandersa, P Braccib,c, M McGrathb,c (*Presenter)

aNavidea/Macrophage Therapeutics; bUniv of California-San Francisco; cAIDS & Cancer Specimen Resource, SFGH

Poster Session:

Date: July 1, 2015

Title: Kaposi’s Sarcoma (KS) is a Macrophage (MO) Tumor Resulting from a Fusion CD206+MOs and Lymphatic Endothelium

Authors: FO Copea*, J Zhangb, T Maurerb, B Abbruzzesea, J Sandersa, S Behrb, P Braccib,c, M McGrathb,c (*Presenter)

aNavidea/Macrophage Therapeutics; bUniv of California-San Francisco; cAIDS & Cancer Specimen Resource, SFGH

Oral Session: Translational Studies. KSHV Malignancies Associated with HIV/AIDS

Date: July 2, 2015
Title: Manocept, a Novel CD206 Targeting Agent for Potential Use in Treatment of Kaposi’s Sarcoma

Authors: Rongzhen Zhanga, Frederick O. Copeb, Joshua Walkerc, Ken Williamsc, Ekaterina Maidjia, Cheryl Stoddarta, Paige M. Braccia, Michael S. McGratha* (*Presenter)

aUniversity of California San Francisco; bNavidea/Macrophage Therapeutics; cBoston College

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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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 3, 2015 Celgene International Sàrl, a wholly-owned subsidiary of Celgene Corporation (NASDAQ:CELG), reported that data from 11 abstracts (two oral presentations, six poster presentations and three published in The Abstract Book) evaluating Celgene investigational and marketed products will be presented at the European League Against Rheumatism (EULAR) Annual Congress in Rome, Italy, June 10 – 13, 2015 (Press release, Celgene, JUN 3, 2015, View Source [SID:1234512521]). The data will include the latest research findings on Otezla (apremilast), the Company’s oral, selective inhibitor of phosphodiesterase 4 (PDE4), in psoriatic arthritis and plaque psoriasis, as well as CC-220, an investigational immunomodulatory compound for systemic lupus erythematosus (lupus).

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Among the data presented will be long-term (104-week) results from Celgene’s PALACE program, including pooled results of three phase III trials (PALACE 1, 2 and 3) assessing the effects of OTEZLA on two distinct manifestations of psoriatic arthritis – enthesitis (inflammation at sites where tendons or ligaments insert into bone) and dactylitis (inflammation of an entire digit). Additional analyses of PALACE trials will evaluate long-term safety and efficacy of OTEZLA in patients with active psoriatic arthritis, as well as the impact of OTEZLA on work productivity and physical function in these patients.

Data will also be presented on the effect of CC-220 on blood cell levels of Ikaros and Aiolos – transcription factors that, when mutated, are associated with an increased risk of systemic lupus erythematosus. The presentation will include phase I data on the impact of CC-220 on the immune response in healthy volunteers. Additional preclinical studies on CC-220 in lupus will be presented.

"We are excited about the presentation of these new long-term data of OTEZLA in psoriatic arthritis at EULAR. Additionally, data presented on our investigational compound CC-220 provide one example of the depth of Celgene’s clinical trial programs in other serious inflammatory diseases with high unmet medical need, including lupus," said Scott Smith, President, Celgene Inflammation & Immunology. "We remain committed to further developing our new and existing therapies to provide innovative treatment options for patients living with painful, debilitating chronic immune conditions."

Celgene will also host a variety of educational programs during the Congress on the unmet needs of patients with psoriatic arthritis, including a symposium for healthcare professionals as well as programs for patient/professional advocacy organizations and media.

The following abstracts will be presented at EULAR as an exchange of scientific and clinical information (all times, CEST):

OTEZLA (apremilast) Abstracts at a Glance

Oral Presentation 3594; Friday, June 12, 10:30 AM – 12:00 PM
Apremilast, an Oral Phosphodiesterase 4 Inhibitor, is Associated with Long-Term (104-Week) Improvements in Enthesitis and Dactylitis in Patients with Psoriatic Arthritis: Pooled Results from Three Phase III Randomized, Controlled Trials; Dafna Gladman, MD
Location: Hall 3, 10:45 AM – 10:55 AM

Poster Number 1113; Poster Tour Presentation Thursday, June 11, 12:05 PM – 1:45 PM
Apremilast, an Oral Phosphodiesterase 4 Inhibitor: Improvements in Nail and Scalp Psoriasis and Psoriasis Area and Severity Index in Patients with Moderate to Severe Plaque Psoriasis (ESTEEM 1 and 2); Kim Papp, MD
Poster Tour Presentation location and time: Hall 5, 12:05 PM

Poster Number 2907; Poster Display Thursday, June 11, 8:00 AM – 5:30 PM
Long-Term (104-Week) Efficacy and Safety Profile of Apremilast, an Oral Phosphodiesterase 4 Inhibitor, in Patients with Psoriatic Arthritis: Results from a Phase III, Randomised, Controlled Trial and Open-Label Extension (PALACE 1); Arthur Kavanaugh, MD
Poster Tour Presentation location and time: Hall 5, 12:00 PM – 1:45 PM

Poster Number 2889; Poster Tour Presentation Thursday, June 11, 12:05 PM – 1:45 PM
Disease Activity and Safety During Long-Term (104-Week) Treatment with Apremilast, an Oral Phosphodiesterase 4 Inhibitor, in Patients with Psoriatic Arthritis: Results from a Phase III, Randomized, Controlled Trial and Open-Label Extension (PALACE 3); Christopher Edwards, MD
Poster Tour Presentation location and time: Hall 5, 12:05 PM

Poster Number 2986; Poster Tour Presentation Saturday, June 13, 10:20 AM – 12:00 PM
Long-Term (104-Week) Efficacy and Safety of Apremilast Monotherapy in DMARD-Naïve Patients with Psoriatic Arthritis: A Phase III, Randomized, Controlled Trial and Open-Label Extension (PALACE 4); Alvin Wells, MD
Poster Tour Presentation location and time: Hall 5, 11:20 AM

Poster Number 3582; Poster Display Thursday, June 11, 8:00 AM – 5:30 PM
Long-Term (104-Week) Safety Profile of Apremilast, an Oral Phosphodiesterase 4 Inhibitor, in Patients with Psoriatic Arthritis: Pooled Safety Analysis of Three Phase III, Randomized, Controlled Trials; Philip Mease, MD
Poster Tour Presentation location and time: Hall 5, 12:00 PM – 1:45 PM

Poster Number 3590; Poster Display Saturday, June 13, 8:15 AM – 2:00 PM
Long-Term Work Productivity Improvement Associated with Apremilast, an Oral Phosphodiesterase 4 Inhibitor, in Patients with Psoriatic Arthritis: Pooled Analysis of Three Phase III Studies; Frank Zhang, MD
Poster Tour Presentation location and time: Hall 5, 10:15 AM – 12:00 PM

Publication Number 4114
Long-Term Impact of Apremilast on Physical Function in Patients with Psoriatic Arthritis Using the HAQ-DI Assessment; Frank Zhang, MD

CC-220 Abstracts at a Glance
Oral Presentation 3498; Thursday, June 11, 10:30 AM – 12:00 PM
The CRL4CRBN E3 Ubiquitin Ligase Modulator CC-220 Induces Degradation of the Transcription Factors Aiolos and Ikaros: Immunomodulation in Healthy Volunteers and Relevance to Systemic Lupus Erythematosus; Peter Schafer, Ph.D.
Oral Presentation location and time: Hall 8 – Room 8A, 11:35 AM (preliminary)

Publication Number 3187
B-Cell Proliferation and Plasmablast Generation from Naïve and Memory B Cells are Differentially Regulated by Baff, Il-21, and Cd40l and Inhibited by the Systemic Lupus Erythematosus Drug Candidate CC-220; Yumi Nakayama, MD

Publication Number 3487
Effects of CC-220, a CRL4CRBN E3 Ubiquitin Ligase Modulator, on Immune Responses; Ying Ye, Ph.D.