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.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"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.

On April 14, 2016 Trillium Therapeutics Inc. (Nasdaq:TRIL; TSX: TR) an immuno-oncology company developing innovative therapies for the treatment of cancer, reported it will be providing an update on its SIRPaFc immune checkpoint inhibitor program, targeting the CD47 protein, at the 107th Annual Meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) (Filing, 6-K, Trillium Therapeutics, APR 14, 2016, View Source [SID:1234510766]). The meeting will be held April 16-20, 2016 in New Orleans, LA. Details of the poster presentation, entitled "SIRPαFc, a CD47-Blocking Cancer Immunotherapeutic, Triggers Phagocytosis of Lymphoma Cells by Both Classically (M1) and Alternatively (M2) Activated Macrophages", are listed below:

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Date: Monday April 18, 2016
Time: 1:00 pm – 5:00 pm (CT)
Session Category: Immunology
Session Title: Immune Checkpoints 1
Abstract #: 2345
Presenter: Dr. Natasja Nielsen Viller
Location: Section 26

The company will present data demonstrating that its SIRPaFc fusion protein, which targets the CD47 "do not eat" signal, promotes the phagocytosis of lymphoma cells by diverse types of macrophages. The studies also assess the impact of macrophage polarizing agents on drug activity and delineate the role of different Fc gamma receptors in promoting tumor cell killing by SIRPaFc.

"Macrophages are heterogeneous and certain types, notably M2s, are often implicated in tumor progression," commented Trillium’s Chief Scientific Officer, Dr. Robert Uger. "Our data indicate that TTI-621, our CD47-blocking decoy receptor, enables all macrophage subsets tested, including M2s, to kill tumor cells. These results suggest that TTI-621 is able to convert otherwise pro-tumor macrophages into efficient anti-tumor effector cells. Rather than ablating M2 macrophages in the tumor microenvironment, these data support using TTI-621 to unleash their tumoricidal function."

Resistance to BRAF inhibitors is a major clinical problem. Here, we evaluate BI-847325, an ATP-competitive inhibitor of MEK and Aurora kinases, in treatment-naïve and drug-resistant BRAF-mutant melanoma models. BI-847325 potently inhibited growth and survival of melanoma cell lines that were both BRAF inhibitor naïve and resistant in 2D culture, 3D cell culture conditions, and in colony formation assays. Western blot studies showed BI-847325 to reduce expression of phospho-ERK and phospho-histone 3 in multiple models of vemurafenib resistance. Mechanistically, BI-847325 decreased the expression of MEK and Mcl-1 while increasing the expression of the proapoptotic protein BIM. Strong suppression of MEK expression was observed after 48 hours of treatment, with no recovery following >72 hours of washout. siRNA-mediated knockdown of Mcl-1 enhanced the effects of BI-847325, whereas Mcl-1 overexpression reversed this in both 2D cell culture and 3D spheroid melanoma models. In vivo, once weekly BI-847325 (70 mg/kg) led to durable regression of BRAF-inhibitor naïve xenografts with no regrowth seen (>65 days of treatment). In contrast, treatment with the vemurafenib analog PLX4720 was associated with tumor relapse at >30 days. BI-847325 also suppressed the long-term growth of xenografts with acquired PLX4720 resistance. Analysis of tumor samples revealed BI-847325 to induce apoptosis associated with suppression of phospho-ERK, total MEK, phospho-Histone3, and Mcl-1 expression. Our studies indicate that BI-847325 is effective in overcoming BRAF inhibitor resistance and has long-term inhibitory effects upon BRAF-mutant melanoma in vivo, through a mechanism associated with the decreased expression of both MEK and Mcl-1.
©2015 American Association for Cancer Research (AACR) (Free AACR Whitepaper).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Binimetinib is a potent, selective MEK1/2 inhibitor with demonstrated efficacy against BRAF- and RAS-mutant tumors. Retinal adverse events associated with MEK inhibitors have been reported in some cases. The aim of this study was to assess single-agent binimetinib, with detailed ophthalmologic monitoring, in Japanese patients with advanced solid tumors.
This was an open-label phase I dose-escalation and dose-expansion study (NCT01469130). Adult patients with histologically confirmed, evaluable, advanced solid tumors were enrolled and treated with binimetinib 30 or 45 mg twice daily (BID). The primary objective was to determine the maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) of single-agent binimetinib in Japanese patients.
Twenty-one patients were enrolled; 3 and 8 patients had documented BRAF and KRAS mutations, respectively. Two of 6 patients (33 %) receiving binimetinib 45 mg BID in dose-escalation experienced recurrent grade 2 retinal adverse events (AEs) which were reversible, and this dose was declared the MTD and RP2D. All patients experienced ≥1 AE suspected to be treatment related; the most common (>50 %) were blood creatine phosphokinase increase (76 %), retinal detachment and aspartate aminotransferase increase (62 % each), and diarrhea (52 %). There were no complete or partial responses; 14 patients (67 %) had stable disease, which lasted >180 days in 5 patients. Expression of phospho-ERK decreased in the skin following binimetinib treatment at both dose levels, indicating target inhibition.
Binimetinib demonstrated efficacy and acceptable safety in Japanese patients with solid tumors, supporting the 45 mg BID dose of binimetinib as the RP2D.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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.