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Cell Reports Publication Elucidates Role of FACT as Accelerator of Tumor Transformation and Potential Marker and Target of Aggressive Cancers

Cleveland BioLabs, Inc. (Nasdaq:CBLI), Incuron, LLC, a joint venture between CBLI and Bioprocess Capital Ventures, and Roswell Park Cancer Institute (RPCI) today announced the publication of studies describing the Facilitates Chromatin Transcription (FACT) complex as an accelerator of tumor transformation and a potential marker and target for aggressive cancers in Cell Reports, a peer-reviewed journal. FACT is the molecular target for Curaxins, a new class of anti-cancer compounds being developed by Incuron. The reported studies were led by scientists at RPCI.

The FACT complex is involved in chromatin remodeling during transcription, replication, and DNA repair. These studies confirm an association between FACT and cancer by showing that FACT is expressed at higher levels in tumor cell lines than in normal cells in vitro and that elimination of FACT expression leads to reduced growth and decreased survival of tumor cells. The published work concludes that FACT’s role in cancer likely involves selective chromatin remodeling of genes that stimulate proliferation, inhibit cell death and differentiation, and regulate cellular stress responses, making it an enabler of oncogene-induced transformation.

In addition, the studies establish a statistically significant association between the frequency and level of FACT expression and tumor aggressiveness. The studies demonstrated that FACT is predominantly expressed in aggressive undifferentiated cancers that result in poor overall patient survival because of the development of metastatic disease, irrespective of tumor size at the time of diagnosis. This increases the potential value of FACT as a prognostic marker, as FACT positivity of a primary tumor could be used at a very early stage to determine the risk of future metastatic disease.

“This recent publication builds upon our previous work showing that FACT is the molecular target of Curaxins,” noted Katerina Gurova, M.D., Ph.D., a researcher in the Department of Cell Stress Biology at RPCI and lead author. “The data presented in the Cell Reports publication indicate that FACT is a promising marker and target for subtypes of cancer characterized by high grade and aggressiveness, and poor prognosis. This, together with the absence of FACT expression in most normal tissues, suggests that pharmacological inhibition of FACT using Curaxins could be an effective strategy to treat types of cancer for which there are currently few treatment options.”

Jean Viallet, M.D., Chief Development Officer at Cleveland BioLabs, stated, “We are evaluating the enormous body of data collected by our collaborators on FACT expression and its role in cancer progression in an effort to focus our next trials with our lead Curaxin drug candidate, CBL0137. Our plan is to enrich the upcoming study of the intravenous administration of CBL0137 in patients with metastatic or unresectable advanced solid tumors and lymphomas by including patients whose tumor types are dependent on transcriptional oncogenes.”

In March 2013, a Notice of Allowance was received from the U.S. Food and Drug Administration for an Investigational New Drug Application for intravenous administration of CBL0137. A Phase 1 single-agent dose-escalation study of oral administration of CBL0137 in patients with advanced solid tumors that are resistant or refractory to standard-of-care treatment is ongoing in the Russian Federation.

Study: Facilitates Chromatin Transcription Complex Is an “Accelerator” of Tumor Transformation and Potential Marker and Target of Aggressive Cancers

Source: Cleveland BioLabs

MicroConstants Expands Biomarker Testing and Analysis Services for Preclinical and Clinical Diagnostic Research

MicroConstants, a Contract Research Organization (CRO) specializing in regulated bioanalysis and DMPK, recently announced the appointment of Doinita Serban, Ph.D. as director of biomarker research to oversee the expansion of biomarker testing and analysis services for preclinical and clinical diagnostic research. Doinita’s extensive experience with biomarker assay development, validation, and profiling of disease panels, coupled with the implementation of the Luminex platform, will enable MicroConstants to broaden their biomarker analysis capabilities to include additional assay formats, such as multiplex immunoassays, gene expression and profiling assays.

SAP and Technical University Munich Decode Human Proteome and Make Data Available for Biomedical Research

SAP AG (NYSE: SAP) and Technical University Munich (TUM) recently announced ProteomicsDB, a new offering based on the SAP HANA® platform that stores protein and peptide identifications from mass spectrometry-based experiments. The proteomic data assembled in the new offering resulted in the identification of proteins mapping to over 18,000 human genes. This represents 90 percent coverage of the human proteome. Data stored and analyzed within ProteomicsDB can be used in basic and biomedical research for discovering therapeutic targets and developing new drugs as well as enhanced diagnosis methods.

As personalized medicine is on the rise, the healthcare field is discovering the opportunities of big data analysis. The result of a joint project between the TUM Chair of Proteomics and Bioanalytics, SAP and the SAP Innovation Center, ProteomicsDB is a major step forward in human proteomics. It currently contains more than 11,000 datasets from human cancer cell lines, tissues and body fluids and enables real-time analysis of this highly dimensional data and creates instant value by allowing to test analytical hypothesis.

ProteomicsDB is based on the SAP HANA for rapid data mining and visualization. It has been built to enable public sharing of mass spectrometry-based proteomic datasets as well as to allow users to access and review data prior to publication. The database is backed with 50 TB of storage, 2 TB RAM and 160 processing units. A direct interface to the programming languages L, C++ and R allows more flexible calculations than are possible with standard SQL. The Web interface is built on a JavaScript framework for HTML5 and optimized for Google Chrome but also available under Internet Explorer and Mozilla Firefox. An easy-to-use and fast Web interface allows users to browse and upload data to the repository as well as browsing the human proteome, including protein level information such as protein function and expression.

ProteomicsDB will be available free of charge. The database will be a valuable asset for researchers in the field of life sciences as well as for the pharmaceutical and biotechnology industry. Insights from analyzing the inherent datasets can be used in biomedical research and for example in developing new drugs that operate in a more targeted way without adversely influencing other cellular processes, helping to reduce side effects.

“The vast amounts of molecular data generated in biomedical research increasingly challenge the ability of scientists to see ‘the forest for the trees,” said Prof. Dr. Bernhard Kuster of TUM. “ProteomicsDB is a significant step ahead in our research aiming at a better understanding of human disease and more informed future treatments. The software helps us and others to store, integrate and analyze experimental data in real time, allowing us to study more complex biological systems at greater depth than previously possible.”

Source: SAP

Kinexus Launches DrugKiNET KnowledgeBase with 105,000 Experimentally Tested Protein Kinase Drug Interactions

Kinexus Bioinformatics Corporation, a world-leader in the study of molecular intelligence systems, announced the launch of its DrugKiNET KnowledgeBase (www.drugkinet.ca) for the identification and development of drug candidates that potently and selectively inhibit human protein kinases. This open-access website features quantitative data on the effects of over 800 chemical compounds on more than 400 protein kinases following careful annotation of hundreds of experiments documented in the scientific literature. This data was then used to train two different proprietary algorithms to predict the inhibitory effects of 550 of these compounds on 500 human protein kinases. This information can guide biomedical researchers in the discovery of new therapeutic targets for existing drugs, and aid in the design of promising new drugs.

At least 538 different protein kinases regulate each other and another approximately 21,500 diverse protein targets to coordinate all of the operations in living cells through complex molecular communications and control networks. Kinases are well recognized by the pharmaceutical and biotech industry as highly productive targets for drug development with applications for cancer, diabetes, Alzheimer’s disease and many other diseases. In fact, over 400 human disease have been linked to genetic mutations in the genes that encode protein kinases or the direct actions of environmental toxins that target protein kinases. Over the last decade, more than two dozen kinase inhibitors have already been approved for clinical use, primarily for cancer treatment. By targeting inappropriately active kinases, these small molecule drugs essentially re-program cancer cells for their demise.

Over the last year, Kinexus and their collaborators in the Mathematics of Information Technology and Complex Systems (MITACS) groups at the University of British Columbia and Simon Fraser University have worked to identify the specific parts of different protein kinases that are critical for recognition by each of 550 different compounds that have been experimentally shown to inhibit one or more kinases. These parts, termed Inhibitor Determining Residues (IDR’s), may be involved in recognizing and binding drugs, and their identification within DrugKiNET can facilitate further optimization of even more potent and specific protein kinase inhibitory drugs. Previously, Kinexus and its partners identified Substrate Determining Residues (SDR’s) in protein kinases that were important for recognition of their protein targets and deposited this information in their open-access PhosphoNET Knowledgebase (www.phosphonet.ca).

“We believe that DrugKiNET is an extremely unique and powerful resource for the biomedical research community,” commented Dr. Steven Pelech, President and Chief Scientific Officer of Kinexus and a professor in the Department of Medicine at the University of British Columbia. “Over a third of all pharmaceutical drug development is presently focused on protein kinase inhibitory drugs, but we expect this to increase even more, since the vast majority of protein kinases have yet to be pursued as drug targets, and definition of the precise roles of different kinases in non-cancer-related diseases is still in its infancy.”

Dr. Pelech added, “We are excited by the prospect that our algorithms can define new protein kinase targets for existing drugs, and that they can identify in the genes that encode protein kinases the specific mutations that may alter their sensitivities to these drugs. As Kinexus has the capability of testing the effects of drug candidates on over 350 different purified protein kinases in-house, we also have the ability to experimentally validate many of our drug predictions for our clients.”

Kinexus is a private, biotechnology company engaged in the research and development of innovative methods to map, track and manipulate cellular communication networks. The application of this knowledge positions Kinexus and its clients in drug development, rational drug design, disease diagnosis and personalized therapies to improve human health. Kinexus currently has agreements with over 1700 research laboratories in companies, universities, government institutions and hospitals in over 35 different countries. To learn more about the diverse proteomics and bioinformatics services offered by Kinexus, please visit www.kinexus.ca or call toll-free at 1-866-KINEXUS.

Source: Kinexus Bioinformatics Corporation

Vermillion’s OVA1 Receives New Statement by Society of Gynecologic Oncology

Vermillion, Inc.’s (NASDAQ: VRML), a multivariate diagnostics company focused on gynecologic cancers and women’s health, OVA1® has received a new statement on clinical validation and medical use issued by the Society of Gynecologic Oncology (SGO).

Citing peer-reviewed publications from two pivotal clinical studies of OVA1® versus standard of care, the statement also referred to OVA1 use within the context of the American Congress of Obstetricians and Gynecologists’ (ACOG) 2011 Committee Opinion, “The Role of the Obstetrician-Gynecologist in the Early Detection of Epithelial Ovarian Cancer.” This guideline, updated from a previous version issued in 2002, covers the management of adnexal masses, including serum markers for ovarian cancer detection.

SGO stated: “…The test may be useful in identifying women who should be referred to a gynecologic oncologist. Recent data have suggested that the OVA1 test along with physician clinical assessment may improve detection rates of malignancies among women with pelvic masses planning surgery.” The complete statement on OVA1 clinical validation and medical use is available on SGO’s website here.
This second SGO statement on OVA1 since its FDA clearance in 2009 represents another significant step toward acceptance of OVA1 as the standard of care for pre-surgically evaluating the risk of ovarian cancer in women with adnexal masses.

The new statement does two things:

  • Refers to publications of OVA1’s two pivotal clinical studies, comprised of the original FDA validation study published in June 2011 and the OVA500 “intended use” study published in 2013. Together, this offers an extensive, peer-reviewed proof source for physicians and payers to assess OVA1’s clinical performance and comparative medical benefits versus today’s standard of care.
  • Places OVA1 use in the context of current ACOG practice guidelines, where CA125 has been used off-label for many years to predict malignancy before surgery, although with inferior performance.

Two key developments in 2013 underlined the timeliness of this updated statement by SGO. The first was the publication of the company’s second pivotal clinical study, OVA500, in the February edition of Gynecologic Oncology. OVA500 was led by Dr. Robert E. Bristow, director of Gynecologic Oncology Services at UC Irvine Healthcare in Orange, California. The second development was a study in the June edition of the journal Obstetrics and Gynecology, which made the front page of the New York Times under the headline, “Widespread Flaws Found in Ovarian Cancer Treatment.” This study, also led by Dr. Bristow, reported that most women with ovarian cancer “are treated by doctors and hospitals that see few cases of the disease and lack expertise in the complex surgery and chemotherapy that can prolong life.” Dr. Bristow said, “If we could just make sure that women get to the people who are trained to take care of them, the impact would be much greater than that of any new chemotherapy drug or biological agent.”

After reviewing the SGO statement, Dr. Hector Chapa, MD, FACOG and medical director of the Women’s Specialty Center in Dallas observed: “This new statement by SGO affirms the important role which OVA1 should play in the workup of patients with an adnexal mass, and particularly before surgery is undertaken by a surgeon uncertified in the gynecologic oncology specialty. This is important because a large number of malignancies are discovered after a surgery where the mass was thought to be benign after negative CA125 or physical examination. Now, we await an updated guideline from ACOG, replacing CA125 with the greatly improved sensitivity and negative predictive value of OVA1. After all, ACOG first mentioned excitement about OVA1 in the Gynecology Practice bulletin of March 2011, prior to publication of the two clinical studies cited by SGO. I believe the new SGO statement is a very positive advance for patients, physicians and health insurance companies alike.”

Vermillion President and CEO Thomas McLain commented: “We highly value the support SGO has provided in two statements about the benefits of OVA1 testing. For patients with ovarian cancer, Vermillion understands that timely access to a trained gynecologic oncology specialist is critical. Optimal treatment, survival and post-surgical outcomes all depend upon improvements in the detection of ovarian malignancies of all types, and as early as possible. OVA1 directly addresses the difficult challenge of identifying the more than 22,000 ovarian malignancies that are associated with 300,000 gynecologic surgeries performed every year. We look forward to supporting ACOG’s review of this new clinical data and the SGO statement. We are committed to working to improve the standard of care for all gynecologic surgery patients at risk of ovarian cancer.”

Source: PR Newswire