On July 20, 2015 Radius reported that Debasish Roychowdhury, M.D., who previously served as Seragon’s Acting Chief Medical Officer, has been elected to the company’s Board of Directors. Dr. Roychowdhury is a leader in the pharmaceutical industry with a strong background in oncology research and development, and regulatory and commercial operations, having previously served in key senior leadership roles at Sanofi, GlaxoSmithKline and Eli Lilly (Press release, Radius, JUL 20, 2015, View Source [SID:1234506529]). Debasish played a key role in the development and advancement of Seragon’s selective estrogen receptor degraders (SERDs) platform for breast cancer and other hormone-driven cancers.

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Radius Health also announced today that it has formed an Oncology Clinical Advisory Board (OCAB) comprised initially of two renowned leaders in the field of oncology: Professor Mitch Dowsett, FMedSci, PhD, and Professor George W. Sledge Jr.

"We are delighted to have attracted someone with Debasish’s experience and leadership in the field of oncology to join our Board of Directors. In addition, we are honored to have the esteemed counsel of two of the leading authorities in the field of breast cancer research, Professor Dowsett and Professor Sledge, join our newly formed OCAB," said Radius Health CEO, Robert E. Ward. "We are excited about the value these accomplished individuals are expected to bring to Radius as we seek to accelerate the development of RAD1901 in breast cancer."

Debasish has a distinguished track record in the field of oncology having been involved in the approval of nine oncology drugs, including Almita, Tykerb and Jevtana. Currently, he is President of Nirvan Consultants, LLC and in this capacity he serves in senior advisory roles for biotechnology companies to help advance their pipeline of therapeutics. Debasish also serves as a member of the Board of Directors for Lytix Biopharma AS.

Prior to the acquisition of Seragon by Roche, Debasish was one of the founding members of the Seragon Clinical and Scientific Advisory Board and served as Seragon’s Acting Chief Medical Officer. Previously, Debasish was the Senior Vice President of Global Oncology and Head of the Global Oncology Division at Sanofi until November 2013. Prior to that, he served as the Vice President for Clinical Development at GlaxoSmithKline and directed the oncology global regulatory group at Eli Lilly and Company. In his academic career, Debasish served as a faculty member at the University of Cincinnati. He trained at the All India Institute of Medical Sciences and University of California, San Francisco.

Oncology Clinical Advisory Board (OCAB)

Radius is pleased to announce the formation of the OCAB with its first two members, both of whom are world renowned scientific and clinical authorities in the field of oncology: Professor Mitch Dowsett, and Professor George Sledge.

Professor Mitch Dowsett, FMedSci, PhD, is Head of the Academic Department of Biochemistry and Head of the Centre for Molecular Pathology at the Royal Marsden Hospital in London, UK. He is also Professor of Biochemical Endocrinology at the Institute of Cancer Research, Professor of Translational Research in the Breakthrough Breast Cancer Centre, Team Leader for Breast Cancer Research for the Biomedical Research Centre for Cancer and Leader of the Endocrinology Team at the Breakthrough Breast Cancer Centre. Dr. Dowsett’s main scientific interests have been related to the endocrine basis of the majority of breast cancers, and his studies to understand the mechanisms of response and resistance to estrogen deprivation in the treatment of breast cancer. His studies led to the development of aromatase inhibitors.

Dr. Sledge is Professor and Chief of Medical Oncology at Stanford University Medical Center, and specializes in the study and treatment of breast cancer. Dr. Sledge directed the first large, nationwide study on the use of paclitaxel to treat advanced breast cancer. His recent research focuses on novel biologic treatments for breast cancer. He has published over 300 articles in medical journals about breast cancer and chaired several clinical trials involving new breast cancer treatments. Dr. Sledge serves as Editor-in-Chief of the journal Clinical Breast Cancer and is past President of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper). He served as Chairman of the Breast Committee of the Eastern Cooperative Oncology Group from 2002 to 2009 where he played an important role in the development of several nationwide clinical trials. He has also served as Chair of ASCO (Free ASCO Whitepaper)’s Education Committee, member of the Department of Defense Breast Cancer Research Program’s Integration Panel, member of the Food and Drug Administration’s Oncology Drug Advisory Committee (ODAC) and is currently a member of the External Advisory Committee for the Cancer Genome Atlas (TCGA) project.

About the Investigational Drug RAD1901

Radius is developing the investigational drug RAD1901 as a potential treatment for estrogen-receptor-positive (ER+) breast cancer. The drug also has potential as a treatment for other ER+ cancers, such as ovarian or endometrial cancer. The National Cancer Institute estimates that approximately 70% of breast cancers are ER+ and may grow in response to exposure to estrogen. Endocrine therapy is intended to block the estrogen signal or reduce the production of estrogen. More information about breast cancer and endocrine therapy may be found on the National Cancer Institute website View Source

RAD1901 is an investigational, non-steroidal small molecule that is designed to selectively bind and degrade the estrogen receptor. RAD1901 has demonstrated potent anti-tumor activity in xenograft models of ER+ breast cancer in preclinical testing and complete suppression of the FES-PET signal after six days of dosing in a maximum tolerated dose clinical study. In preclinical models thus far, RAD1901 has shown good tissue selectivity, does not appear to stimulate the uterine endometrium, and appears to protect against bone loss in an ovariectomy-induced osteopenia rat model. In addition, we believe that RAD1901 also has the ability to cross the blood-brain barrier. Radius recently reported preclinical activity of RAD1901 in combination with either mTOR or CDK inhibitors, the results demonstrated potent tumor shrinkage in a patient-derived tumor explant animal model.

Radius has begun a Phase 1 multicenter, open-label, two-part, dose-escalation study of the investigational drug RAD1901 in postmenopausal women with advanced estrogen receptor positive and HER2-negative breast cancer. The study is designed to determine the recommended Phase 2 dose of RAD1901, and includes a preliminary evaluation of the potential anti-tumor effects. The incidence of dose limiting toxicities will be assessed during the first 28 days. Tumor response will be evaluated in patients with measurable or evaluable disease, using RECISTv1.1 guidelines every 8 weeks until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 12 months of treatment. Plasma concentrations of RAD1901 will be assessed every 28 days for up to 12 months of treatment. The details of the Phase 1 study of RAD1901 are posted on www.clinicaltrials.gov.

Radius is also developing RAD1901 at lower doses as a Selective Estrogen Receptor Modulator for the potential treatment of vasomotor symptoms. Historically, hormone replacement therapy ("HRT") with estrogen or progesterone was considered the most efficacious approach to relieving menopausal symptoms such as hot flashes. However, because of the concerns about the potential long‑term risks and contraindications associated with HRT, Radius believes a significant need exists for new therapeutic treatment options to treat vasomotor symptoms. In a Phase 2 proof of concept study, RAD1901 at lower doses demonstrated a reduction in the frequency and severity of moderate and severe hot flashes. Radius intends to commence a Phase 2b trial in vasomotor symptoms in the second half of 2015.

On July 20, 2015 CEL-SCI reported that it has added a second clinical site for its Phase I clinical trial evaluating peri-anal wart immunotherapy in HIV/HPV co-infected men and women with its investigational cancer immunotherapy Multikine* (Leukocyte Interleukin, Injection) (Press release, Cel-Sci, JUL 20, 2015, View Source [SID:1234506530]). Dr. Joel Palefsky, world renowned scientist and Key Opinion Leader (KOL) in human papilloma virus (HPV) research and the prevention of anal cancer, has joined the study as a Principal Investigator at the University of California San Francisco (UCSF). UCSF becomes the second clinical site for the study. The first site, the U.S. Naval Medical Center San Diego, continues to enroll patients under a Cooperative Research and Development Agreement (CRADA).

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Dr. Joel Palefsky is the Chair of the HPV Working Group of the AIDS Malignancy Consortium (AMC) and is the head of the AMC HPV Virology Core Lab at UCSF. The AMC is a U.S. National Cancer Institute-supported clinical trials group founded in 1995 to support innovative trials for AIDS-related cancers. The AMC is composed of over 37 clinical trials sites worldwide, five Working Groups, an Administrative Office, a Statistical Office, and an Operations and Data Management Office. Collectively, these components develop and oversee the scientific agenda, manage the groups’ portfolio of clinical trials and other scientific-based studies, and help to develop new protocols. Dr. Palefsky has extensive experience in the biology of HPV infection, HPV infection in HIV-positive men and women, HPV vaccines and in the design and implementation of multiple clinical research trials of HPV-related disease.

Having published over 280 papers, Dr. Palefsky is Principal Investigator of the ANCHOR study, an $89 million NIH-funded study of the efficacy of secondary prevention of anal cancer. He is also the Principal Investigator on several laboratory-based and clinical research studies of HPV-associated neoplasia, particularly in the setting of HIV infection. He also specializes in the molecular biology and development of new treatments for HPV. Dr. Palefsky is the founder and immediate past president of the International Anal Neoplasia Society and is currently president of the International Human Papillomavirus Society. He is actively involved in training students in clinical and translational research. Dr. Palefsky has led the Doris Duke Charitable Foundation (DDCF) program at UCSF since its inception in 2001 and has been the leader of the Clinical Translational Science Awards (CTSA) TL1 program at UCSF since its inception in 2006.

"We are very pleased to welcome Dr. Palefsky as a Principal Investigator for our Phase I study and we believe his interest in Multikine is a very important testament of our immunotherapy’s potential in the treatment of HPV related diseases in HIV infected patients," stated CEL-SCI Chief Executive Officer Geert Kersten. "Dr. Palefsky is widely recognized as one of the world’s top researchers in the field HPV infection in HIV co-infected patients. With his participation through UCSF we anticipate rapid patient enrollment in our Phase I study."

Anal and genital warts are commonly associated with HPV, the most common sexually transmitted disease. The U.S. Center for Disease Control and Prevention (CDC) has named HPV the 4th largest health threat the U.S. will face in 2014. According to the CDC, 360,000 people in the U.S. get genital warts each year. Persistent HPV infection in the anal region is thought to be responsible for up to 80% of anal cancers. HPV is an even more significant health problem in the HIV infected population as individuals are living longer as a result of greatly improved HIV medications, but have difficulty clearing HPV due to their compromised immune system.

About Multikine for HIV/HPV Co-infected Patients

Multikine is being given to HIV/HPV co-infected patients with peri-anal warts based on the results obtained in a Multikine Phase I study conducted at the University of Maryland in which the investigational immunotherapy Multikine was given to HIV/HPV co-infected women with cervical dysplasia. In these patients, visual and histological evidence of clearance of lesions was observed. Elimination of a number of HPV strains was also determined by in situ polymerase chain reaction (PCR) performed on tissue biopsy collected before and after Multikine treatment. The study investigators reported that the study volunteers in this study all appeared to tolerate the Multikine treatment with no reported serious adverse events. The treatment regimen utilized in the Multikine cervical study in HIV/HPV co-infected patient volunteers is identical to the regimen being administered in the current Phase I study of HIV/HPV co-infected patient volunteers with peri-anal warts that is in progress at the U.S. Naval Medical Center San Diego and the University of California San Francisco.

About Multikine

Multikine (Leukocyte Interleukin, Injection) is an investigational immunotherapeutic agent that is being tested in an open-label, randomized, controlled, global pivotal Phase 3 clinical trial as a potential first-line treatment for advanced primary squamous cell carcinoma of the head and neck. Multikine is designed to be a different type of therapy in the fight against cancer: one that appears to have the potential to work with the body’s natural immune system in the fight against tumors.

Multikine is also being tested in a Phase 1 study under a Cooperative Research and Development Agreement ("CRADA") with the U.S. Naval Medical Center, San Diego, as a potential treatment for peri-anal warts in HIV/HPV co-infected men and women. CEL-SCI has also entered into two co-development agreements with Ergomed Clinical Research Limited to further the development of Multikine for cervical dysplasia/neoplasia in women who are co-infected with HIV and HPV and for peri-anal warts in men and women who are co-infected with HIV and HPV.

On July 16, 2015 Cellectis reported the publication of a study in Cancer Research describing the applicability of TALEN-mediated genome editing to a scalable process, which enables the manufacturing of third-party CAR T-cell immunotherapies (Filing, 6-K, Cellectis, JUL 16, 2015, View Source [SID:1234506351]).

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Adoptive immunotherapy using autologous T-cells endowed with chimeric antigen receptors or CARs has emerged as a powerful means of treating cancer. However, a limitation of this approach is that autologous CAR T-cells must be generated on a custom-made basis.

To overcome the limitations of patient-derived CAR T-cell therapies, TALEN mediated gene inactivation can be used to generate non-alloreactive T-cells from third-party donors in a robust, scalable manufacturing process, thus allowing "off-the-shelf" CAR T-cell immunotherapies.

Laurent Poirot Ph.D. and his collaborators use this TALEN-mediated editing approach to develop a process for the large-scale manufacturing of T-cells deficient in expression of both their T-cell receptor (TCR) and CD52, a protein targeted by alemtuzumab, a chemotherapeutic agent. Functionally, T-cells manufactured with this process do not mediate graft-versus-host reactions, and are rendered resistant to destruction by alemtuzumab. These characteristics enable the administration of alemtuzumab concurrently or prior to engineered T-cells, supporting their engraftment.

Furthermore, endowing the TALEN-engineered cells with a CD19 CAR led to efficient destruction of CD19+ tumor targets even in the presence of the chemotherapeutic agent.

CAR T-cell immunotherapies can therefore be used in an "off-the-shelf" manner akin to other biological immunopharmaceuticals.

Laurent Poirot, Ph.D., Head of Early Discovery

Dr. Laurent Poirot studied physics and biology at the Ecole Polytechnique in France, before earning his Ph.D. at the Strasbourg University (France) and the Harvard Medical School in Boston. He then joined the Genomics Institute of the Novartis research foundation in San Diego as a postdoctoral fellow, where he studied the development of high throughput in vivo and in vitro approaches for the study of gene functions in immune cells. He joined Cellectis in 2009 as a Project Leader, and has been working as Head of Early Discovery since 2013.

Multiplex genome edited T-cell manufacturing platform for "off-the-shelf" adoptive T-cell immunotherapies

Laurent Poirot1, Brian Philip2, Cécile Schiffer Mannioui1, Diane Le Clerre1, Isabelle Chion-Sotinel1, Sophie Derniame1, Pierrick Potrel1, Cécile Bas1, Laetitia Lemaire1, Roman Galetto1, Céline Lebuhotel1, Justin Eyquem1,3, Gordon Weng-Kit Cheung2, Aymeric Duclert1, Agnès Gouble1, Sylvain Arnould1, Karl Peggs2, Martin Pule2, Andrew M. Scharenberg4 and Julianne Smith1

1 Cellectis, Paris, France
2 Department of Haematology, UCL Cancer Institute, University College London, London, UK
3 Current address: Memorial Sloan-Kettering Cancer Center, New York, NY
4 Current address: Department of Pediatrics, University of Washington, Seattle Children’s Research Institute, Seattle, WA

View Source

On July 16, 2015 NanoString Technologies reported that the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology for breast cancer have been updated to acknowledge that the PAM50 gene signature, commercialized as the Prosigna Breast Cancer Prognostic Gene Signature Assay, has been clinically validated for prediction of prognosis (Press release, NanoString Technologies, JUL 16, 2015, View Source [SID:1234506352]).

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"In line with our expectations, Prosigna is now recognized in the NCCN guidelines as providing clinically validated prediction of a woman’s risk of breast cancer recurrence," said Brad Gray, President and Chief Executive Officer of NanoString Technologies. "Discussion of Prosigna in the NCCN guidelines following our first submission is an important achievement, and we believe it establishes a solid foundation upon which we can continue to build the market for Prosigna."

The NCCN Guidelines are an authoritative source of information to help healthcare professionals make informed decisions about cancer care, and are often used by public and private payors to establish coverage policies. Prosigna’s acknowledgement in the NCCN Guidelines resulted from a review by a multidisciplinary panel of experts from NCCN member institutions, and is based on requests and clinical data submitted in June 2014. The newly updated guidelines (version 3.2015) appear on the NCCN website.

About the Prosigna Breast Cancer Prognostic Gene Signature Assay and nCounter Dx Analysis System

The Prosigna Assay provides a risk category and numerical score for assessment of the risk of distant recurrence of disease at 10 years in postmenopausal women with node-negative (Stage I or II) or node-positive (Stage II), hormone receptor-positive (HR+) breast cancer. Based on the PAM50 gene signature initially discovered by Charles Perou, Ph.D. and colleagues, the Prosigna Assay is an in vitro diagnostic tool that utilizes gene expression data weighted together with clinical variables to generate a risk category and numerical score to assess a patient’s risk of distant recurrence of disease. The Prosigna Assay measures gene expression levels of RNA extracted from formalin-fixed paraffin embedded (FFPE) breast tumor tissue previously diagnosed as invasive breast carcinoma.

The Prosigna Assay requires minimal hands-on time and runs on NanoString’s proprietary nCounter Dx Analysis System, which offers a reproducible and cost-effective way to profile many genes simultaneously with high sensitivity and precision.

The nCounter Dx Analysis System is a highly automated and easy-to-use platform that utilizes a novel digital barcoding chemistry to deliver high precision multiplexed assays. The system is available in the multi-mode FLEX configuration, which is designed to meet the needs of high-complexity clinical laboratories seeking a single platform with the flexibility to run the Prosigna Breast Cancer Assay and, when operated in the "Life Sciences" mode, process translational research experiments and multiplexed assays developed by the laboratory.

In the United States, the Prosigna Assay is available for diagnostic use when ordered by a physician. The Prosigna Assay has been CE-marked and is available for use by healthcare professionals in the European Union and other countries that recognize the CE Mark, as well as Canada, Israel, Australia, New Zealand, Turkey, South Africa and Hong Kong.

In the U.S., the Prosigna Assay is indicated in female breast cancer patients who have undergone surgery in conjunction with locoregional treatment consistent with standard of care, either as:

(1) a prognostic indicator for distant recurrence-free survival at 10 years in postmenopausal women with Hormone Receptor-Positive (HR+), lymph node-negative, Stage I or II breast cancer to be treated with adjuvant endocrine therapy alone, when used in conjunction with other clinicopathological factors or (2) a prognostic indicator for distant recurrence-free survival at 10 years in postmenopausal women with Hormone Receptor-Positive (HR+), lymph node-positive (1-3 nodes), Stage II breast cancer to be treated with adjuvant endocrine therapy alone, when used in conjunction with other clinicopathological factors. The device is not intended for patients with four or more positive nodes.

For more information, please visit www.prosigna.com.

On July 16, 2015 Navidea Biopharmaceuticals reported the results of voting at its 2015 Annual Meeting of Stockholders (the Annual Meeting) held July 16, 2015 (Press release, Navidea Biopharmaceuticals, JUL 16, 2015, View Source;p=RssLanding&cat=news&id=2068607 [SID:1234506354]). Approximately 80 percent of outstanding shares were represented at the meeting.

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At the Annual Meeting, Navidea’s stockholders:

Elected Gordon A. Troup to the Navidea Board of Directors to serve for a term of three years; and
Ratified the appointment of BDO USA, LLP to act as the Company’s independent registered public accounting firm for 2015.
The final results are subject to verification by the independent election inspectors and will be reported in a Form 8-K to be filed by Navidea with the Securities and Exchange Commission in the next few days.

Following the formal business portion of the Annual Meeting, Rick Gonzalez, Navidea President and CEO, made a brief presentation to stockholders in attendance at the Annual Meeting, including overviews on the following:

Lymphoseek (technetium Tc-99m tilmanocept) injection U.S. commercialization and life cycle management activities; and
Manocept CD206 targeting platform update, including a discussion of Macrophage Therapeutics development activities.