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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.

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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]).

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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.

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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]).

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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.

ARIAD Announces Initiation of Randomized, First-Line Phase 3 Trial of Brigatinib in Treatment of ALK-Positive Non-Small Cell Lung Cancer

On April 11, 2016 ARIAD Pharmaceuticals, Inc. (NASDAQ:ARIA) reported the initiation of a randomized, first-line Phase 3 clinical trial of brigatinib, its investigational anaplastic lymphoma kinase (ALK) inhibitor, in adult patients with ALK-positive locally advanced or metastatic non-small cell lung cancer (NSCLC) who have not previously been treated with an ALK inhibitor (Press release, Ariad, APR 11, 2016, View Source [SID:1234510646]).

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The ALTA 1L (ALK in Lung Cancer Trial of BrigAtinib in 1st Line) trial is designed to assess the efficacy of brigatinib in comparison to crizotinib based on evaluation of the primary endpoint of progression free survival (PFS).

"We are pleased to be advancing brigatinib into a pivotal Phase 3 trial as a potential new therapy for patients with ALK+ NSCLC who have not yet received an ALK inhibitor," said Tim Clackson, Ph.D., president of research and development and chief scientific officer of ARIAD. "We believe that the encouraging results shown in our preclinical and ongoing Phase 1/2 studies suggest brigatinib has the potential to improve outcomes for ALK+ NSCLC patients as compared to treatment with crizotinib."

Trial Design

The ALTA 1L trial is a randomized, open-label, multicenter, international study that is designed to compare the efficacy and safety of brigatinib to crizotinib in adult patients with ALK+ NSCLC who have not previously received an ALK inhibitor. The trial is expected to be conducted at approximately 150 investigational sites in North America, Europe and the Asia Pacific region. Patients in the trial must be at least 18 years of age, have stage IIIB or stage IV NSCLC with ALK rearrangement, have received no more than one regimen of systemic anticancer therapy in the locally advanced or metastatic setting, and have not received prior therapy with an ALK inhibitor.

Approximately 270 patients are expected to be randomized one-to-one to receive brigatinib (90 mg given orally once daily for seven days followed by escalation to 180 mg once daily) or crizotinib (250 mg given orally twice daily). ARIAD expects to complete patient enrollment in the ALTA 1L trial in 2018.

The primary endpoint of the trial is progression free survival (PFS), per RECIST criteria as assessed by a blinded Independent Review Committee (BIRC). Tumor response assessments will be performed every eight weeks. Key secondary endpoints include objective response rate (ORR), intracranial ORR, intracranial PFS, duration of response, overall survival (OS), safety and tolerability. Health related quality of life data will also be assessed.

"This head-to-head study will directly test brigatinib against crizotinib in the TKI-naïve ALK+ setting – where innovative therapies are needed to improve response rates and to delay progression that can occur through the emergence of secondary resistance mutations in ALK and progression in the central nervous system," said D. Ross Camidge, M.D., Ph.D., director of thoracic oncology at the University of Colorado. "In patients who have experienced crizotinib failure, brigatinib has already exhibited very impressive progression free survival and marked activity in patients with CNS metastases – features that suggest that in the ALK TKI-naive setting, it could potentially change patients’ natural history by better suppressing ALK+ disease from the beginning."

About Brigatinib

Brigatinib is an investigational, targeted cancer medicine discovered internally at ARIAD Pharmaceuticals, Inc. It is in development for the treatment of patients with ALK+ NSCLC. Brigatinib received Breakthrough Therapy designation from the FDA in October 2014 for the treatment of patients with ALK+ NSCLC whose tumors are resistant to crizotinib on the basis of an ongoing Phase 1/2 trial. Brigatinib is currently being evaluated in the global Phase 2 ALTA trial in ALK+ NSCLC patients who have progressed on crizotinib, which is anticipated to form the basis for a new drug application planned for submission later in 2016.

Kyoto University and Sumitomo Dainippon Pharma Launch Second Stage of Joint Research Project for Innovative Oncology Therapeutics (DSK Project)

On April 11, 2016 Kyoto University (Kyoto, Japan; President: Juichi Yamagiwa) and Sumitomo Dainippon Pharma Co., Ltd. (Osaka, Japan; President: Masayo Tada) ("Sumitomo Dainippon Pharma") reported the launch of second stage of the DSK Project, a framework for joint research aimed at discovering innovative anti-cancer drugs, diagnostic tools and therapeutic methods (Press release, Dainippon Sumitomo Pharma, APR 11, 2016, View Source [SID:1234510640]).

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In this new stage of the DSK Project, Kyoto University and Sumitomo Dainippon Pharma will conduct unique drug discovery research focusing on the regulatory mechanisms of interactions with cancer cells, immune cells, and stroma cells in tumor microenvironment by the approaches of molecular/cellular biology and clinical aspects.

Kyoto University is strongly committed to collaborative projects between industry and academia on the institutional level through its Medical Innovation Center (MIC) – The first open innovation laboratory in Japan. The mission of the MIC is to discover innovative medicines and therapeutic methods as well as to develop researchers in related fields. For instance, the University provides intensive, advanced cancer treatments at its Kyoto University Cancer Center and is engaged in state-of-the-art basic research through its Graduate School of Medicine as it seeks to develop new diagnostic tools and groundbreaking therapeutic methods for fighting cancer.

Sumitomo Dainippon Pharma pursues extensive research and development (R&D) approaches including its internal research expertise, in-licensed technologies, and joint research with venture companies and universities in a quest for innovative pharmaceutical products. The Company focuses on the therapeutic areas of psychiatry & neurology and oncology. Within oncology, Sumitomo Dainippon Pharma aims to develop innovative products under the integrated global R&D system between the DSP Cancer Institute of Sumitomo Dainippon Pharma in Japan and Boston Biomedical, Inc. in the United States.

Kyoto University and Sumitomo Dainippon Pharma have agreed to establish a joint cancer R&D laboratory within the MIC for the purpose of launching second stage of the DSK Project. Dr. Shinji Uemoto, Dean of the Kyoto University Graduate School of Medicine and Faculty of Medicine, will serve as a project director, and cancer immunology specialist Dr. Nagahiro Minato, Specially Assigned Professor of the Kyoto University Graduate School of Medicine, will work as a project mentor, core cancer research groups at the Graduate School of Medicine and their counterparts at 2 the research groups at Sumitomo Dainippon Pharma will work closely to develop unique and innovative anti-cancer drugs, diagnostic tools and therapeutic methods from the new perspective of "cancer and host response."

* Initial stage of the DSK Project was announced on March 15, 2011.

Summary

Second stage of DSK Project:

Purpose: Development of unique and innovative anti-cancer drugs, diagnostic tools, and therapeutic strategies through discovering novel regulatory mechanisms of cancers cells interacted with immune and stroma cells in tumor microenvironment.

* Stroma cells are non-cancerous cells that exist in cancer tissues, such as fibroblasts, immune cells, pericytes, endothelial cells and inflammatory cells.

Term:

5 years from April 2016

Organization: The Alliance Management Committee, Research Promotion Committee, and Intellectual Property Committee constitute the leadership structure of the DSK Project, with each committee having an equal number of members from Kyoto University and Sumitomo Dainippon Pharma.

Under the overall management by Dr. Shinji Uemoto, Dean of the Kyoto University Graduate School of Medicine and Faculty of Medicine, and research activity coordination by Dr. Nagahiro Minato, Specially Assigned Professor of the Kyoto University Graduate School of Medicine, Kyoto University’s core research groups (immunology, gastroenterology, genome informatics) and Sumitomo Dainippon Pharma’s satellite research groups will conduct the Project in the Medical Innovation Center, University Hospital, West Campus.