Author: [email protected]

GAM: a web-service for integrated transcriptional and metabolic network analysis.

Novel techniques for high-throughput steady-state metabolomic profiling yield information about changes of nearly thousands of metabolites. Such metabolomic profiles, when analyzed together with transcriptional profiles, can reveal novel insights about underlying biological processes. While a number of conceptual approaches have been developed for data integration, easily accessible tools for integrated analysis of mammalian steady-state metabolomic and transcriptional data are lacking. Here we present GAM (‘genes and metabolites’): a web-service for integrated network analysis of transcriptional and steady-state metabolomic data focused on identification of the most changing metabolic subnetworks between two conditions of interest. In the web-service, we have pre-assembled metabolic networks for humans, mice, Arabidopsis and yeast and adapted exact solvers for an optimal subgraph search to work in the context of these metabolic networks. The output is the most regulated metabolic subnetwork of size controlled by false discovery rate parameters. The subnetworks are then visualized online and also can be downloaded in Cytoscape format for subsequent processing. The web-service is available at:View Source
© The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

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CRT and University of Copenhagen announce agreement with ADC Therapeutics to develop antibody treatments for cancer

On April 22, 2016 CRT and The University of Copenhagen reported to have signed a deal with Switzerland-based ADC Therapeutics SA (ADCT) to license antibodies against a cancer-specific cell surface protein (Press release, Cancer Research Technology, 22 22, 2016, View Source [SID1234523187]). The antibodies will be used by ADCT to develop a novel Antibody Drug Conjugate (ADC) that could potentially treat a range of cancers.

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The antibodies – jointly developed by Cancer Research UK and the University of Copenhagen scientists – target a protein overexpressed on the surface of some cancer cells, which is not expressed on healthy cells.

ADCT intends to incorporate the antibodies into a novel ADC therapeutic using its proprietary linker and pyrrolobenzodiazepine (PBD) cytotoxic warhead technology*. The antibodies are expected to selectively target the PBD cytotoxic to cancer cells, sparing normal tissue.

Thomas Bjørnholm, Pro-Vice-chancellor for Research and Innovation, the University of Copenhagen, said: "We are very pleased and proud that research from the University’s Faculty of Health and Medical Sciences has been licensed to ADCT for the development of new cancer therapeutics. Our mission as a public university is precisely to make sure that our leading-edge research is disseminated and is taken to the market together with commercial partners for the benefit of society at large."

Dr Keith Blundy, Cancer Research Technology’s chief executive, said: "This important license deal brings together CRT’s access to world class research and ADCT’s cutting edge technology to develop exciting new therapeutics for cancer.

"We hope this agreement will pave the way for promising new ways to treat a range of cancers in a targeted way without damaging healthy tissue."

Kancera acquires the Fractalkine project

On April 22, 2016 Kancera reported that due to positive efficacy data in disease models of cancer and pain, Kancera’s Board of Directors has decided to exercise the exclusive option to acquire the Fractalkine project (Press release, Kancera, APR 22, 2016, View Source [SID:1234511315]).

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Kancera has previously announced that the company owns an option to acquire exclusive rights to the Fractalkine project (excluding the therapeutic area respiratiory diseases) during an evaluation period of 24 months (from September 2015). The project has now generated positive results in multiple disease models of cancer and pain. The results show desired treatment effects that are important for Kancera´s further product development and commercialization of the project. The results will be published at a later date, in collaboration with the academic partners involved. In light of the positive results Kancera Board have decided to acquire the Fractalkine project. The acquisition will be carried out in connection with the completion of the ongoing transfer of results and know-how from Acturum and AstraZeneca to Kancera. Payment for the project to Acturum Life Science AB will be made into three steps by a total of 6,000,000 shares, of which the first payment is due at the submission of the application for authorization of a clinical trial after an approval by Kancera´s shareholders. In parallel, the company intends to validate a broader use of the drug candidate (KAN0440567) in order to demonstrate its full commercial potential.

About the Fractalkine project

Fractalkine is an immune regulatory factor that sends signals via the CX3CR1 receptor, also called G-protein coupled receptor 13 (GPCR13). In the healthy individual, Fractalkine and its receptor regulate migration of immune cells from the blood capillary wall into areas where the immune system is needed. Animal studies show that Fractalkine and its receptor are not essential for survival and that important immune functions remain intact indicating that inhibition of the Fractalkine signaling by a drug probably will be tolerated without significant adverse effects. Fractalkine and its receptor have been linked to the growth and proliferation of pancreatic, breast and prostate cancer. Also, cancer cells that have the Fractalkine receptor on their surface migrate towards nerve ends that have Fractalkine on their surface. Thus, cancer cells are led to surround and apply pressure on nerves and thereby cancer pain may arise. Another proposed mechanism for how Fractalkine and its receptor affect the development of tumors is that they contribute to the transformation of the body’s macrophages from being a threat against the cancer (the M1 form) to supporting the cancer (the M2 form). This mechanism is also suggested as a predictive factor for responsiveness to the new immuno-oncology drugs that act through PD-1 and PD-L1 such as nivolumab, pembrolizumab and pidilizumab. During 2014 and 2015 studies have been published demonstrating that the absence of Fractalkine in tumor cells is a significant marker for how successful the immuno-oncology treatment is expected to be (see e.g. the publication in Nature on November 27, 2014, Vol. 515, pp 563). In the light of these observations, there are good reasons to further study if inhibition of the Fractalkine signaling with KAN0440567 (AZD8797) has the potential to increase the proportion of patients responding to the new immuno-oncology drugs that act through PD-1 and PD-L1.

Immune Therapeutics Signs Binding Letter of Intent to Acquire Chinese CAR-T Technology and Clinical Data

On Apr 21, 2016 Immune Therapeutics Inc. (OTCQB: IMUN) reported that they have signed a binding Letter of Intent to acquire Chinese Chimeric Super Antigen Receptor T cell (CAR-T) cocktail therapy, Immuno-Oncology patents (pending), manufacturing technology, and clinical data of the aforementioned therapies from Super-T Cell Cancer Company ("STCC") a newly formed corporation (Press release, Immune Therapeutics, APR 21, 2016, View Source [SID:1234514893]).

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"This CAR-T cell technology licensing further accelerates IMUN’s growth in the Immuno-Oncology field as we evaluate paths to commercialization both in China and other Emerging Markets," commented Christopher Pearce, Chief Operating Officer.
CAR-T cell therapy involves engineering cancer patients’ own immune cells to recognize and attack cancer tumors. CAR-T therapy has great potential to improve patient-specific cancer therapy in a profound way. N umerous studies have implicated regulatory T cells as key mediators in the creation of an immunosuppressed microenvironment that enables tumors to escape attack by the host immune system. The Super CAR-T Cocktail therapy has shown promise in early human clinical trials for the treatment of blood cancer, renal, cervical and hepatic cancer.

"We are very impressed by the quality of the work done by Professor Shan and his team, and are excited by the safe and efficacious profile of this novel CAR-T cocktail therapy for cancerous diseases. This is the beginning of a long-term strategic partnership between IMUN and STCC. Together, we will expeditiously continue our quest in developing more affordable, safer, and more effective cancer immunotherapy programs," said Noreen Griffin, Chief Executive Officer of Immune Therapeutics, Inc.
The need in China for new affordable therapies is critical. It is predicted that there will be about 4,292,000 newly diagnosed invasive cancer cases in 2016, corresponding to almost 12,000 new cancer diagnoses on average each day. IMUN believes that once approved it could capture 5% of the market in the first year.

TapImmune Announces Phase 2 Ovarian Cancer Trial Study with AstraZeneca/MedImmune and Sloan Kettering Cancer Institute

On April 21, 2016 TapImmune,Inc. (TPIV), a clinical-stage immunology-oncology company specializing in the development of innovative peptide and gene-based immunotherapeutics and vaccines for the treatment of cancer & metastatic disease, reported plans to initiate a Phase 2 trial of its cancer vaccine, TPIV 200, a multi-epitope anti-folate receptor vaccine (FRalfa), in combination with Astra Zeneca (NYSE: AZN) durvalumab (MEDI4736), an anti-PD-L1 antibody, in patients with platinum-resistant ovarian cancer (Press release, TapImmune, APR 21, 2016, View Source [SID:1234512243]). The study will commence in the second quarter of 2016 at Memorial Sloan Kettering Cancer Center in New York and will be led by Jason Konner, M.D. as Principal Investigator.

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The two Companies will share clinical costs, while TapImmune will supply TPIV 200 and MedImmune will supply Durvalumab (MED14736) for the trials. TapImmune recently obtained Orphan Drug Designation for TPIV 200 in ovarian cancer from the U.S. Food and Drug Administration.

This single arm Phase 2 trial will include 40 women with high-grade ovarian, tubal, or primary peritoneal carcinomas, who have progressed within 6 months of their most recent platinum chemotherapy. The primary objective of the study is to determine the effectiveness of the combination by measuring Overall Response Rate [ORR = Complete Response (CR) + Partial Response (PR)] by RECIST and Progression Free Survival (PFS) rate at 6 months. Secondary endpoints will be safety and immune and correlation of FRalfa-specific immune responses with clinical efficacy.

"This collaboration is a significant event for TapImmune," stated Dr. Glynn Wilson, Chairman and CEO of TapImmune. "We are delighted to bring a leading T-cell vaccine platform into this combination study and to work with AstraZeneca/Medimmune and Sloan Kettering in a patient population that is in dire need of an effective treatment."

"This study is part of a larger Phase 2 strategy for TPIV 200 that is designed to greatly increase our understanding of the vaccine while providing clinical evidence of efficacy," Dr. Wilson added.

TPIV 200 is a multi-epitope peptide vaccine that targets Folate Receptor Alpha, which is overexpressed in multiple cancers including over 90% of ovarian cancer cells. In Phase I clinical studies conducted at the Mayo Clinic in patients with breast and ovarian cancer, this vaccine was shown to be safe and well tolerated and to give robust cellular immune responses in 20 out of 21 evaluable patients.

About Durvalumab (MEDI4736)

Durvalumab is an investigational human monoclonal antibody directed against PD-L1 developed at MedImmune LLC. Signals from PD-L1 help tumors avoid detection by the immune system. Durvalumab blocks these signals, countering the tumor’s immune-evading tactics. Durvalumab is being developed, alongside other immunotherapies, to empower the patient’s immune system and attack the cancer. Durvalumab is being investigated in an extensive clinical trial program, as monotherapy or in combination with tremelimumab, in NSCLC, head and neck, gastric, pancreatic, bladder and blood cancers.