Month: April 2016

Differential expression between human dermal papilla cells from balding and non-balding scalps reveals new candidate genes for androgenetic alopecia.

Androgenetic alopecia (AGA) is a common heritable and androgen-dependent hair loss condition in men. Twelve genetic risk loci are known to date but it is unclear which genes at these loci are relevant for AGA. Dermal papilla cells (DPC) located in the hair bulb are the main site of androgen activity in the hair follicle. Widely used monolayer-cultured primary DPC in hair-related studies often lack dermal papilla (DP) characteristics. In contrast, immortalised DPC have high resemblance to intact DP. We derived immortalised human DPC lines from balding (BAB) and non-balding (BAN) scalp. Both BAB and BAN retain high proportions of DP signature gene and versican protein expression. We performed expression analysis of BAB and BAN and annotated AGA risk loci with differentially-expressed genes. We found evidence for AR but not EDA2R as the candidate gene at the AGA risk locus on chromosome X. Further, our data suggest TWIST1 and SSPN to be the functionally relevant AGA genes at the 7p21.1 and 12p12.1 risk loci, respectively. Down-regulated genes in BAB compared to BAN were highly enriched for vasculature-related genes, suggesting that deficiency of DPC from balding scalps in fostering vascularisation around the hair follicle may contribute to the development of AGA.
Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

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!


Curis Announces Presentation of Preclinical Data from CUDC-907, CA-170 and PD-L1/TIM-3 Antagonist and CA-4948 Programs at AACR Annual Meeting

On April 11, 2016 Curis, Inc. (NASDAQ:CRIS), a biotechnology company focused on the development and commercialization of innovative and effective drug candidates for the treatment of human cancers, reported that Curis scientists and its collaborator, Aurigene will present data from multiple programs at the Annual Meeting of American Association of Cancer Research (AACR) (Free AACR Whitepaper) to be held from April 16 – 20, 2016 in New Orleans, LA (Press release, Curis, APR 11, 2016, View Source [SID:1234510647]).

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!

Curis researchers will present data for its proprietary targeted cancer drug candidate, CUDC-907, an oral inhibitor of histone deacetylase (HDAC) and phosphoinositide 3-kinase (PI3K). Curis’ collaborator, Aurigene will present data from the immuno-oncology programs, including CA-170 (previously AUPM-170), a first-in-class oral, small molecule immune checkpoint antagonist targeting programmed death ligand-1 (PD-L1) and V-domain Ig suppressor of T cell activation (VISTA), as well as the PD-L1/ T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) antagonist program. In addition, Aurigene will present data from the interleukin-1 receptor associated kinase 4 (IRAK4) inhibitor program, including the lead compound CA-4948. Curis has exclusive licenses to CA-170 and CA-4948 under a collaboration agreement with Aurigene established in 2015.

Additional information on the presentations can be found below and abstracts can be accessed at www.aacr.org.

Poster Presentations

Date/Time: Wednesday, Apr 20, 2016, 8:00 AM – 12:00 PM
Session Title: Cellular Responses to Anticancer Drugs
Presentation Title: Novel dual HDAC & PI3K inhibitor, CUDC-907, for MYC-driven malignancies
Abstract Number: 4634

Date/Time: Wednesday, Apr 20, 2016, 8:00 AM – 12:00 PM
Session Title: Immune Modulating Agents 2
Presentation Title: Oral immune checkpoint antagonists targeting PD-L1/VISTA or PD-L1/Tim3 for cancer therapy
Abstract Number: 4861

Date/Time: Wednesday, Apr 20, 2016, 8:00 AM – 12:00 PM
Session Title: Novel Chemotherapies
Presentation Title: Efficacy and safety of highly selective novel IRAK4 inhibitors for treatment of ABC-DLBCL
Abstract Number: 4798

Aduro Biotech Chief Scientific Officer to Highlight the Potential of STING Activation in Cancer Immunotherapy in a Major Symposium at the 2016 American Association for Cancer Research Annual Meeting

On April 11, 2016 Aduro Biotech, Inc. (Nasdaq:ADRO), reported that the company’s chief scientific officer, Thomas W. Dubensky, Jr., Ph.D., will be a featured speaker at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2016 Annual Meeting being held April 16-20 in New Orleans, Louisiana (Press release, Aduro BioTech, APR 11, 2016, View Source;p=RssLanding&cat=news&id=2155861 [SID:1234510645]). Dr. Dubensky’s presentation is part of a Major Symposium, "Cancer Immunotherapy: Small Molecule Approaches," taking place on April 20, 2016, during which he will highlight Aduro’s landmark first-in-human immunotherapeutic approach in cancer to target the Stimulator of Interferon Genes (STING) pathway.

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 presentation will focus on ADU-S100, a novel synthetic cyclic dinucleotide (CDN) that is one of a family of proprietary small molecules being developed by Aduro that broadly activates the human STING receptor. STING is expressed in immune cells that are present in the tumor microenvironment (TME) and is a central and potent mediator of the innate immune response, a necessary step in the development of effective tumor-specific immunity. Activation of the STING pathway has been shown to correlate with infiltration of lymphocytes and a "T-cell inflamed TME" in patients with melanoma. Stimulation of STING induces signaling through several innate immune response pathways, resulting in the expression of various interferons, cytokines and T cell recruitment factors that amplify and strengthen immune activity. Dr. Dubensky will discuss preclinical data demonstrating that the direct engagement of STING through the intratumoral injection of ADU-S100 resulted in effective, durable and systemic anti-tumor activity. The data suggest that the resulting tumor regression is due to an acute pro-inflammatory cytokine response and induction of tumor-specific CD8+ T cell immunity. Preclinical data will be presented which also demonstrate the potential synergistic effects of combining ADU-S100 and immune checkpoint inhibitors, including anti-PD1. In addition, Dr. Dubensky will present an overview of the Phase 1 clinical trial to evaluate the safety, tolerability and possible anti-tumor activity of ADU-S100 given by intratumoral injection to patients with advanced cutaneously accessible solid tumors or lymphomas.

"We are excited to share this new research and planned Phase 1 clinical trial, which highlights ADU-S100, Aduro’s lead STING activator candidate, and its translational potential for treating patients with metastatic solid tumors and lymphomas," said Dr. Dubensky. "Our data suggest that the stimulation of a local immune response in the TME can result in a sustained and effective tumor-specific immune response against metastases throughout the body. This observation reinforces the importance of the STING signaling pathway in cancer immunotherapy and the potential of ADU-S100 to be used alone or in combination treatment approaches for advanced cancer patients."

Based on these promising preclinical results, Aduro and Novartis, as part of a collaboration focused on STING pathway activator compounds in the field of oncology, will initiate a Phase 1 dose escalation trial with ADU-S100 in patients with cutaneously accessible metastatic solid tumors or lymphomas who have no other treatment options.

Aduro will also be presenting a poster at AACR (Free AACR Whitepaper) on Monday, April 18, 2016 titled "STING Activation in the Tumor Microenvironment with a Synthetic Human Cyclic Dinucleotide Leads to Potent Anti-Tumor Immunity." This will provide additional details on preclinical research showing the effectiveness of ADU-S100 in activating the STING receptor and inducing an immune response across diverse tumor models.

Details of the presentations:

Oral Presentation "SY39-02: Direct activation of STING in the tumor microenvironment leads to potent and systemic tumor regression and immunity," Wednesday, April 20, 2016 10:55 AM – 11:20 AM, New Orleans Theater C. Morial Convention Center
Poster Presentation "STING Activation in the Tumor Microenvironment with a Synthetic Human Cyclic Dinucleotide Leads to Potent Anti-Tumor Immunity," Monday, April 18, 2016 8:00 AM – 12:00 PM, Section 24

Celgene and Juno Announce Celgene Exercised Option to Develop and Commercialize CD19-directed Product Candidates

On April 11, 2016 Celgene Corporation (NASDAQ: CELG) and Juno Therapeutics, Inc. (NASDAQ: JUNO) reported that Celgene exercised its option to develop and commercialize the Juno CD19 program outside North America and China(Press release, Juno, APR 11, 2016, View Source [SID:1234510661]).

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!

With the exercise of this option, Celgene will pay Juno a fee of $50 million and the companies will now share global development expenses for products in the CD19 program. Celgene has commercial rights outside of North America and China and will pay Juno a royalty at a percentage in the mid-teens on any future net sales of therapeutic products developed through the CD19 program in Celgene’s territories. Juno retains commercialization rights in North America and China.

This Smart News Release features multimedia. View the full release here: View Source

Juno currently has three CD19-directed product candidates in clinical development, including JCAR015, JCAR017, and JCAR014. JCAR015 is in a Phase II trial for adults with relapsed or refractory (r/r) acute lymphoblastic leukemia (ALL). JCAR017 is in two separate Phase I trials, one in pediatric patients with r/r ALL and another in patients with r/r non-Hodgkin lymphoma (NHL).

JCAR014 is in a Phase I trial in three different indications, adult r/r/ ALL, r/r NHL, and r/r chronic lymphocytic leukemia (CLL), as well as a trial in combination with AstraZeneca’s investigational programmed death ligand 1 (PD-L1) immune checkpoint inhibitor, durvalumab.

"Our CD19-directed portfolio of drug candidates has shown encouraging efficacy and manageable toxicity in trials to date across a range of B cell malignancies, and we are pleased that Celgene has decided to opt in to the CD19 program. Celgene’s development and commercial expertise, particularly in hematologic malignancies, make them our ideal partner and will accelerate our global development capabilities for patients with ALL, CLL, and NHL," said Hans Bishop, Juno’s President and Chief Executive Officer. "The long-term collaboration with Celgene is an important component of our plan to develop our engineered T cell platform rapidly and effectively for the benefit of patients around the world, and we are encouraged by the progress we are making together."

"Our decision to move forward with the Juno CD19 program underscores our commitment to the long-term collaboration with Juno and our strong desire to deliver important new treatment options to patients with serious hematologic malignancies," said Robert Hershberg, M.D., Ph.D., Chief Scientific Officer for Celgene. "CD19-based CAR T therapies hold great promise in B cell malignancies including acute lymphoblastic leukemia, non-Hodgkin lymphoma, and chronic lymphocytic leukemia. Further, the lessons learned from CD19 will inform additional targets and approaches as the Celgene-Juno collaboration evolves."

NanoString Technologies and HalioDx Enter Into Collaboration Agreement to Jointly Develop and Commercialize Novel Gene Expression Assays in Immuno-oncology

On April 11, 2016 NanoString Technologies, Inc. (NASDAQ:NSTG), a provider of life science tools for translational research and molecular diagnostic products, and HalioDx SAS, a diagnostic company in immuno-oncology, reported they have entered into an agreement to jointly develop and commercialize advanced gene expression assays for assessing the response to immunotherapies (Press release, NanoString Technologies, APR 11, 2016, View Source [SID:1234510648]).

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!

Under this collaboration agreement, NanoString and HalioDx will jointly develop innovative immune gene expression assays on the NanoString nCounter Analysis System based on discoveries of Dr. Jérôme Galon, Research Director at the Institut National de la Santé et de la Recherche Médicale (Inserm) and his team (Inserm UMRS1138) at Cordeliers Research Center. NanoString and HalioDx will jointly offer products and associated services to academic, pharmaceutical and biotechnology customers worldwide.

The products and services to be developed under the collaboration will enable researchers and drug developers to use assays to assess responses to immunotherapies and select patients who are most likely to benefit from the therapies. This collaboration expands both companies’ leadership in precision immuno-oncology and offers the potential for companion diagnostic collaborations with biopharmaceutical partners in the future.

"HalioDx is very excited to jointly develop with NanoString our innovative predictive and prognostic immune gene expression signatures on the nCounter platform, one of the best multi-analyte testing platforms for translating gene expression signatures to routine diagnostic use. At HalioDx, we want to develop diagnostic solutions that can be easily used in routine clinical practice settings and we selected the nCounter platform because of its robustness, turn-around time, and compatibility with formalin-fixed-paraffin-embedded tissue samples. Our co-developed immune gene expression assays will complement the breakthrough Immunoscore IHC assay, to foster the development of more precise immunotherapies," said Vincent Fert, co-founder and CEO of HalioDx.

"This collaboration with HalioDx adds another powerful tool to the nCounter immuno-oncology toolkit to support our customers’ efforts in developing clinically validated predictive biomarkers for cancer immunotherapies. With the ability to process small tissue samples with minimal hands-on time, NanoString’s nCounter technology provides a powerful solution to researchers and drug developers who are in search of biomarkers for precision oncology, and is ideally suited to answering complex questions in translational research in the field of immuno-oncology," said Brad Gray, President and Chief Executive Officer of NanoString Technologies.