On April, 14 2016. PharmaMar (MSE:PHM) reported four poster presentations at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) annual meeting, taking place in New Orleans, April 16-20th 2016 (Press release, PharmaMar, APR 14, 2016, View Source [SID:1234510832]). The presentations are based on the latest data obtained on the company’s compounds of marine origin, lurbinectedin, plitidepsin and PM184. Under the heading "Delivering Cures Through Cancer Science", oncologists and investigators from around the world will interchange knowhow and reinforce the links between research and the advancements in patient care.

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PharmaMar will present results from three molecules that are presently under clinical investigation in different types of solid and hematological tumors. Each one of these compounds has a very different mechanism of action. Apart from its direct activity on tumor cells, lurbinectedin (PM1183) also attacks the microenvironment, rendering tumor growth unfeasible. Plitidepsin (Aplidin), targets the eEF1A2 protein, and finally PM184 disrupts the tumor’s blood vessels, causing a reduction in the supply of both nutrients and oxygen to the tumor cells.

"At PharmaMar we have a commitment to the identification of new and novel mechanisms of action from marine compounds that can provide a step forward in the treatment of patients with cancer," explains Carmen Cuevas, Ph.D., R&D Director from the Oncology Business Unit at PharmaMar. "The results that we will present at scientific congresses such as the AACR (Free AACR Whitepaper) show that we are on right path and that we can count on a robust pipeline that will provide new methods for attacking tumor cells." 2
Presentation details are as follows:

PM1183 (lurbinectedin)
PM1183 is compound under clinical investigation, inhibitor of the RNA polymerase II enzyme. It is essential for the transcription process, inhibiting tumor growth, and resulting in tumor death. The antitumor efficacy of PM1183 is being investigated in various types of solid tumors.

Lurbinectedin reduces tumor-associated macrophages and the production of inflammatory cytokines, chemokines and angiogenic factors in preclinical models (abstract No 1284). Paola Allavena et al. Poster presentation, section 18, Monday April 18th, 8:00 am – 12:00 am.

This proves that part of lurbinectedin’s antitumor activity is due to its antiproliferative activity in monocytes and tumor associated macrophages, cells that are essential in the inflammatory microenvironment. Lurbinectedin inhibits transcription, therefore, the production of cytokines and angiogenic factors by these cells. Tumor growth is unfeasible, even when the tumor cells are resistant to the compound.

Lurbinectedin specifically targets transcription in cancer cells, triggering DNA breaks and degradation of phosphorylated Pol II (Abstract No 3039). Gema Santamaría-Nuñez et al. Poster presentation, section 17, Tuesday April 19th , 8:00 am-12:00 am.
Lurbinectedin (PM1183) binds to the DNA in the CG rich regions surrounding the promoter of genes, inhibiting transcription activity. The mechanism involves the ubiquitination and degradation by proteasome of the RNA polymerase II (pol II). The degradation of pol II is directly related to the appearance of DNA damage and the induction of cell death through apoptosis.

Plitidepsin (Aplidin)
Plitidepsin is an antitumor drug of marine origin, at the investigational phase for hematological tumors, including a phase Ib study in relapsed and refractory Multiple Myeloma, in triple combination with bortezomib and dexamethasone, along with a phase II study in Relapsed and Refractory Angioimmunoblastic T-cell Lymphoma. Recently, positive results have been seen in pivotal study in combination with dexamethasone in patients with Multiple Myeloma. 3

Plitidepsin targets the GTP-bound form of eEF1A2 in cancer cells (Abstract No 3015). Alejandro Losada et al. Poster presentation, section 17, Tuesday April 19th, 8:00am-12:00am.

This confirms that the protein eEF1A2 is Aplidin’s pharmacological target. This protein has numerous functions within the tumor cell, some of which have a marked oncogenic character. This assay delves into the peculiarities of the direct interaction of Aplidin with purified GTP bound eEF1A2.

PM184
PM184 is an inhibitor of tubulin polymerization. It is at the clinical development stage for solid tumors, including a Phase II trial in hormone-receptor positive, HER2-negative, locally advanced and/or metastatic breast cancer.

Anti-angiogenic properties of PM184 (Abstract No 3066). Carlos M. Galmarini et al. Poster presentation, section 25, Tuesday April 19th, 8:00am-12:00am.

The tumor cells rapidly growth, needing the supply of a large quantity of nutrients. One of the paths for the treatment of cancer at the moment is to disrupt the blood cells within the tumor, or to stop the development of new cells, cutting the supply of nutrients and oxygen to the tumor cells. Adding to its capacity to specifically eliminate tumor cells, PM184 has shown itself to have a strong intratumor vascular disrupting activity, inhibiting in this extraordinarily effective way, human transplanted tumors in mice.

On April 14, 2016 Cancer Research UK reported that it has shortlisted nine teams for the final stages of its £20m Grand Challenge award* – the world’s most ambitious cancer grant helping scientists attack some of the hardest unanswered questions in cancer research (Press release, Cancer Research UK, APR 14, 2016, View Source [SID:1234510830]).

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World-class multi-disciplinary researchers representing 15 countries and 50 organisations have collaborated to make the shortlist**. The shortlisted teams are led by:

Professor Roy Bicknell from the University of Birmingham, UK, with collaborators from the USA, UK, Netherlands, Sweden and Switzerland will research developing vaccines to prevent non-viral cancers.
Professor Alan Rickinson from the University of Birmingham, UK with collaborators from the USA, Netherlands, UK, Australia, Germany, Switzerland, Japan and China will research how to eradicate EBV-induced cancers from the world.
Professor Sir Mike Stratton from the Wellcome Trust Sanger Institute, UK with collaborators from France, the USA and UK will research how unusual patterns of mutation are induced by different cancer-causing events.
Dr Jelle Wesseling from the Netherlands Cancer Institute, The Netherlands with collaborators from the USA, UK and Netherlands will research how to distinguish between lethal need treating and non-lethal cancers that don’t.
Dr Surinder Sahota from the University of Southampton, UK with collaborators from the USA, UK, Spain and Germany will research how to distinguish between lethal need treating and non-lethal cancers that don’t.
Professor Freddie Hamdy from the University of Oxford, UK with collaborators from Finland, the USA and UK will research how to distinguish between lethal need treating and non-lethal cancers that don’t.
Dr Josephine Bunch from the National Physical Laboratory, UK with collaborators from the UK will find a way of mapping tumour at the molecular and cellular level.
Professor Greg Hannon from the University of Cambridge, UK with collaborators from Switzerland, Ireland, Canada, the USA and UK will find a way of mapping tumour at the molecular and cellular level.
Professor Ehud Shapiro from the Weizmann Institute, Israel with collaborators from Israel, the UK and USA will find a way of mapping tumour at the molecular and cellular level.
Sir Harpal Kumar, Cancer Research UK’s chief executive, said: "One of the driving forces behind our Grand Challenge is the ambition to unite researchers from all sciences around the world so that they can come up with game-changing ideas to solve cancer’s most challenging questions. We’re delighted that our shortlist includes so many talented, multi-disciplinary teams.

"We’ll award at least one of these teams the first ever Grand Challenge later this year and hope that this global approach will go on to help the 14.1 million people diagnosed with cancer around the world annually."

Jim Elliott, member of the Grand Challenge patient panel, said: "When reviewing the applications for the Grand Challenge initiative I was struck by scientists’ enthusiasm to work with people they hadn’t worked with before to tackle the challenges in new ways. Some of the teams were really pioneering – spanning the globe and the sciences. I’m honoured to have been part of this innovative way to research cancer and for the opportunity to make sure that the research coming out of Grand Challenge puts patients at the heart of things."

On April 14,2016 Baxalta Incorporated (NYSE:BXLT) reported that the special meeting of stockholders to adopt the merger agreement with Shire plc (LSE:SHP, NASDAQ:SHPG) will be held on May 27, 2016, at 7:00 a.m. Central Time, for shareholders of record as of the close of business on April 11, 2016 (Press release, Baxalta, APR 14, 2016, View Source [SID:1234510829]). The special meeting will be held at Baxalta’s corporate headquarters, located at 1200 Lakeside Drive, Bannockburn, Illinois 60015.

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For more information, please refer to the merger proxy on Form S-4 that Shire has filed with the Securities and Exchange Commission (SEC).

KAHR-102 is a fusion protein that links portions of two immune and cancer-related membrane proteins; CTLA-4 and FasL (Company Pipeline, KAHR Medical, APR 14, 2016, View Source [SID:1234510828]).

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The functions of KAHR-102 in immune settings are anticipated from its component parts; The CTLA-4 component of KAHR-102 binds to B7 costimulators on antigen-presenting-cells (APC), such as dendritic cells, and thereby prevents them from engaging and triggering their cognate stimulatory CD28 receptor on T cells. The FasL component of the KAHR-102 fusion protein, binds to its cognate Fas receptor, which is upregulated on activated T cells, and thereby triggers apoptosis in these cells. The net effect of combining these blocking and triggering functions is to convert a T cell activating signal into an inhibitory one, leading to immune suppression.

KAHR-102 has also shown significant activity in cancer – both in-vitro and in cancer animal models. The CTLA-4 side of the drug targets to B7 receptors on lymphatic cancer cells, while the FasL side of the drug induces specific apoptosis of these cancer cells.

KAHR-102 forms a homo-hexamer which allows an optimal hexameric FasL structure to be specifically targeted to B7-expressing cells, such as in lymphoma cells.

On April 14, 2016 NanoString Technologies, Inc. (NASDAQ:NSTG), a provider of life science tools for translational research and molecular diagnostic products,reported reported the introduction of nCounter Vantage, a portfolio of assays that power 3D Biology experiments in cancer research, including immuno-oncology (Press release, NanoString Technologies, APR 14, 2016, View Source [SID:1234510827]). The nCounter Vantage portfolio provides a deeper view of cancer and immune biology by enabling multiplexed, digital analysis of DNA, RNA and protein simultaneously in a single experiment. Designed for flexibility, nCounter Vantage products can be mixed and matched, creating many new ways for cancer researchers to apply 3D Biology technology.

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"The nCounter Vantage portfolio will enable researchers to extract much more information from each patient sample to better understand a particular tumor at the genomic and proteomic level as well as its interaction with the immune system," said Dr. Jerome Galon, Research Director of INSERM. "This may lead to the identification of insightful new biomarkers and signatures that could become diagnostics with important clinical utility."

NanoString plans to unveil multiple new nCounter Vantage products at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, to be held in New Orleans, from April 16 through April 20, 2016. These include:

For RNA, two new panels for the detection of fusion genes in lung cancer and leukemia samples
For proteins, two new panels covering solid tumor biology and immune-cell signaling
For DNA, the first of three new panels for the detection of single nucleotide variations
The company will also showcase a new version of its nSolver data analysis software, which will support 3D Biology experiments with new data merging capabilities for combining and comparing multiple panels, analyte types, and custom CodeSets in a single view.

"Because of the complexity of the immune response and tumor biology, it is likely that the next generation of biomarkers in immuno-oncology will need to integrate measurements of DNA, RNA, and protein," said Dr. Alessandra Cesano, Chief Medical Officer of NanoString Technologies. "Using Vantage assays, together with an nCounter instrument, researchers can achieve these multi-analyte measurements simultaneously on a single sample. We believe that this novel capability will pave the way for development of an exciting and more informative new category of clinical diagnostics."

New nCounter Vantage Products Featured at AACR (Free AACR Whitepaper)
The nCounter Vantage Lung Gene Fusion Panel and nCounter Vantage Leukemia Gene Fusion Panel products have been developed for Research Use Only applications, enable highly multiplexed analysis of key disease-driving gene fusions in RNA transcripts, and are commercially available now. The Lung Gene Fusion Panel includes 63 probes targeting fusions involving the ALK, ROS, RET, and NTRK1 genes. The Leukemia Gene Fusion Panel includes 42 probes targeting gene fusions and other key biomarkers expressed in ALL, AML, and CML.

Two new protein panels are initially being made available under product evaluation programs, and are expected to be commercially launched by the end of this year for use separately or in combination with other Vantage RNA and DNA panels. The first new protein panel will analyze 30 key intracellular proteins involved in immuno-oncology, and will form the nCounter Vantage RNA:Protein Immune Cell Signaling Panel when used in combination with the 770 RNA measurements included in the PanCancer Immune Profiling Panel. The second new protein panel is focused on key cancer pathways, and will form the nCounter Vantage RNA:Protein Solid Tumor Pathways Panel when used in combination with the 770 RNA measurements included in the PanCancer Pathways Panel.

In addition, the first of three new nCounter Vantage DNA panels for the detection of single nucleotide variations will be featured at the AACR (Free AACR Whitepaper) meeting. The nCounter Vantage DNA Solid Tumor Panel is designed for highly multiplexed profiling of key cancer driver mutations as well as insertions and deletions (INDELs) from as little as 5 ng of DNA. Several customers are currently involved in a product evaluation program, which will be expanded prior to commercial launch of the panel expected later this year.

At the 2016 AACR (Free AACR Whitepaper) Annual Meeting in New Orleans, Louisiana, NanoString will showcase nCounter Vantage capabilities at booth #2412.