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MolecularMD Corp. Obtains License to Commercialize Predictive Diagnostic Based on Actionable Biomarker, DDR2, for Uses in Lung Cancer and Targeted Kinase Therapy

MolecularMD Corp. recently announced that it has entered into a license agreement granting the company exclusive patent rights to cancer diagnosis technology. Specifically, MolecularMD has obtained rights to commercialize patent-pending intellectual property pertaining to DDR2 mutations for diagnostic, prognostic and predictive uses for humans in the area of lung cancer. Such patent rights are jointly-owned by The Broad Institute and Dana-Farber Cancer Institute. The inventors named on the patent are Drs. Matthew Meyerson, Peter Hammerman, and Alexis Ramos.

About DDR2 Mutations in Lung Cancer

Research into understanding the genetic basis of cancer has led to identification of novel biomarkers that have been successfully exploited with targeted therapies. In non-small cell lung cancer (NSCLC), several such targets have been discovered for adenocarcinoma including EGFR, ALK, and MET. Unfortunately, these therapeutic targets are not relevant for squamous cell carcinoma (SCC), which is the second most frequent histological subtype in NSCLC. Recent discoveries identified mutations in the discoidin domain receptor 2 (DDR2) of SCC patient tumors that are oncogenic and also responsive to existing drugs targeting kinase inhibition. DDR2 is a membrane receptor tyrosine kinase involved in cell adhesion, proliferation and migration. In xenograft models, DDR2-mutant tumors regressed under treatment with the tyrosine kinase inhibitor, dasatinib. Remarkably, an SCC patient with no detectable EGFR mutation had a long-term response to the combination of erlotinib plus dasatinib. This patient was found to harbor a DDR2 mutation further suggesting that DDR2 mutations may be clinically relevant. Given the availability of a variety of therapies targeting tyrosine kinases, these findings provide a rationale for designing clinical trials for patients with SCC using existing FDA-approved drugs such as dasatinib, imatinib, nilotinib and ponatinib as well as novel, selective tyrosine kinase inhibitors for DDR2.

MolecularMD is developing DDR2 diagnostic assays, including next-generation sequencing tests, for clinical trials exploring efficacy of targeted therapies and DDR2 clinical utility. MolecularMD provides comprehensive clinical trial support through its CLIA-certified and CAP-accredited Clinical Reference Laboratory. In addition, MolecularMD provides IVD development and manufacturing capability to support companion diagnostic device commercialization. MolecularMD will also support commercialization of DDR2 technology through sublicensing to clinical reference laboratories and diagnostic assay developers and manufacturers.

According to Dr. Greg Cox, MolecularMD’s Director of Licensing, “DDR2 is potentially the first actionable biomarker available for SCC patients, whose treatment options are currently limited to chemotherapy. It’s exciting that these patients may benefit from existing FDA-approved targeted therapies, and we are eager to support clinical trials examining these novel treatment possibilities and enable widespread access to DDR2 diagnostics.”

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

Nektar Presents Target-Specific Biomarkers Being Assessed in Ongoing Phase 3 BEACON Study of Etirinotecan Pegol for the Treatment of Metastatic Breast Cancer at the 2013 American Society of Clinical Oncology Annual Meeting

Nektar Therapeutics (NASDAQ:NKTR) recently announced that it presented a series of target-specific biomarkers that are being evaluated in the development of etirinotecan pegol for the treatment of breast cancer. Etirinotecan pegol is a unique, next generation, targeted topoisomerase I inhibitor currently in Phase 3 clinical development as a potential treatment for patients with locally recurrent or metastatic breast cancer. The BEACON (BrEAst Cancer Outcomes with NKTR-102) Phase 3 Study is a randomized, open-label, international study that is evaluating single agent etirinotecan pegol in patients who have previously received an anthracycline, a taxane and capecitabine (ATC) versus a comparator arm consisting of an active single agent treatment of physician’s choice (TPC).

“One of our objectives in treating metastatic breast cancer is to prospectively identify patients that will respond to specific treatments so they can achieve the optimal individualized care,” said Hope Rugo, M.D., Director of Breast Oncology and Clinical Trials Education at the UCSF Helen Diller Comprehensive Cancer Center and Member of the BEACON Study investigator steering committee. “The goal of evaluating these important biomarkers in patients enrolled into the BEACON study is to help us understand which breast cancer patients might have the best clinical outcomes from treatment with etirinotecan pegol.”

A series of assays for target-specific pharmacodynamic biomarkers for etirinotecan pegol, including the molecular target topoisomerase I, have been established and are being measured in the Phase 3 BEACON study. The biomarkers were identified from Circulating Tumor Cell (CTC) samples which were collected prior to patient treatment. Additional CTC patient samples are being collected at regular intervals during treatment and at the end of treatment. Preliminary results from the initial pre-dose samples found CTCs in over 90% of patient samples, with a median of 200 CTCs per 7.5 mL blood draw. Patient participation in the CTC sub-set of the BEACON study is projected to be over 75%. Measurements of each biomarker expression over time will be analyzed in order to identify potential predictive biomarkers for clinical response to etirinotecan pegol.

“We are pleased to have identified several baseline pharmacodynamic biomarkers, which are target-specific such as topoisomerase 1, and which can be reliably measured over the patient’s treatment period,” said Robert Medve, M.D., Chief Medical Officer of Nektar Therapeutics. “The measurement of these biomarkers in the BEACON study will help us understand and shape the future treatment of patients with etirinotecan pegol. Enrollment in the BEACON study is well ahead of schedule and we expect to complete the target enrollment of 840 patients in the third quarter of 2013.”

Circulating Tumor Cells are cancer cells shed from either the primary tumor or its metastases that circulate in the peripheral blood. CTCs are emerging tumor biomarkers, collected through a minimally invasive blood draw, providing a “liquid” biopsy sample and allowing for post-treatment monitoring of the patient. CTCs provide well-defined targets for the understanding of tumor biology and tumor cell dissemination, which offers a unique approach to identify novel therapeutic targets and understand resistance to established therapies.

Source: Nektar Therapeutics

Entelos and ISB Announce Collaborative Gene Expression Breakthrough

Entelos Holding Corp. (“Entelos” or “the Company”), a premier provider of physiologicalsystemmodeling and services, and Seattle-based Institute for System Biology (ISB), the nonprofit pioneers of the systems approach to study the molecular causes of diseases, today announced the successful integration of gene expression data into quantitative physiological simulations. This proprietary capability improves understanding of the gene expression and disease outcomes to radically improve the predictive discernment of the complex nature of disease, yielding insights into novel therapeutic targets, biomarkers, and patient selection that should support a new era of precision medicine.

Entelos and ISB worked together to define a scientifically sound and scalable methodology to provide breakthrough capabilities for both the modeling and systems pharmacology communities. It addresses business-critical problems in both pharmaceutical research and healthcare. “This workflow is transformative for understanding the role of molecular interactions and their impact on pharmaceutical R&D and healthcare decision making,” stated Entelos Founder and CTO, Tom Paterson. “By utilizing our computer models, we are able to use all identified correlations across gene network studies to decipher genetic influence on the disruptions identified as disease. As an example, the new capabilities were able to help us clearly define from a pool of 51 potential biomarkers, and which biomarkers identified non-responders and responders for anti-IL1 therapies for rheumatoid arthritis.”

“The mapping and application of clinical gene expression data sets a new standard and role for quantitative physiological modeling within the drug discovery and development process,” stated Entelos President and CEO, Shawn O’Connor. “It’s only due to the unique depth and breadth of the Entelos quantitative physiological models that these sorts of mappings and analyses can be carried out across the entire pathophysiology of a disease. This is the beginning of truly understanding and leveraging the human genome for therapeutic success”

“As the interconnected features of the disease space become increasingly more visible, we are continuing to look for new ways to decipher the elaborate data that hides therapeutic success“ said Dr. Lee Hood, co-founder and president of Institute for Systems Biology and recipient of the National Medal of Science. “This approach represents a breakthrough capability for deriving insights from those data sets.”

This demonstrated convergence of top-down functional systems biology and bottom-up molecular systems biology provides an approach for using clinical gene expression data to investigate a wide diversity of diseases, to decipher disease complexity, and to understand variability and reduce uncertainty in populations and sub populations. Entelos and ISB are now seeking commercial partners to advance additional existing disease models (Atherosclerosis, Type 2 Diabetes, Hypertension, Rheumatoid Arthritis, etc.) and generate new in silico applications.

Source: Entelos