On September 9, 2015 RedHill Biopharma Ltd. (Nasdaq:RDHL) (TASE:RDHL) ("RedHill" or the "Company"), an Israeli biopharmaceutical company primarily focused on late clinical-stage, proprietary, orally-administered, small molecule drugs for inflammatory and gastrointestinal (GI) diseases, including cancer, reported that the National Cancer Institute (NCI) has awarded a $2 million Small Business Innovation Research Program (SBIR) grant to support the planned Phase II study with YELIVA (ABC294640) for the treatment of refractory or relapsed multiple myeloma (Press release, RedHill Biopharma, SEP 9, 2015, View Source [SID:1234507433]).

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The grant covers a three year period and was awarded to Apogee Biotechnology Corporation ("Apogee") in conjunction with Duke University. RedHill acquired the rights to YELIVA (ABC294640), a proprietary, first-in-class, orally-administered sphingosine kinase-2 (SK2) selective inhibitor, from Apogee in March 2015.

RedHill plans to initiate the Phase II study of YELIVA (ABC294640) for the treatment of refractory or relapsed multiple myeloma by the end of 2015. The open-label, dose escalation Phase II study will be conducted at Duke University Medical Center and is planned to enroll up to 77 patients with refractory or relapsed multiple myeloma who have previously been treated with proteasome inhibitors and immunomodulatory drugs. Dr. Yubin Kang, MD, Associate Professor in the Division of Hematologic Malignancies and Cellular Therapy in the Department of Medicine at Duke University Medical Center, will be the lead investigator for the study, which received Institutional Review Board (IRB) approval from Duke University (DUHS IRB).

The primary objectives of the first portion of the study (Phase Ib) are to assess safety and determine the maximum tolerated dose (MTD) in this group of patients. Secondary objectives include assessment of antitumor activity and determination of the pharmacokinetic (PK) and pharmacodynamic (PD) properties of YELIVA (ABC294640) in refractory or relapsed multiple myeloma patients.

The primary objectives of the second portion of the study (Phase II) are to assess the overall treatment response rate and overall survival. Secondary objectives include evaluating the treatment response of YELIVA (ABC294640) in patients with refractory or relapsed multiple myeloma after three cycles of treatment and evaluation of pharmacodynamic markers.

YELIVA (ABC294640) is a proprietary, first-in-class, orally-administered sphingosine kinase-2 (SK2) selective inhibitor, with anti-cancer and anti-inflammatory activities, targeting multiple oncology, inflammatory and GI indications. SK2 is an innovative molecular target for anti-cancer therapy because of its critical role in catalyzing the formation of the lipid-signaling molecule sphingosine 1-phosphate (S1P), which is known to regulate cell proliferation and activation of inflammatory pathways. By inhibiting SK2, YELIVA (ABC294640) could potentially be effective in treating multiple oncology, inflammatory, and gastrointestinal indications.

RedHill recently initiated a Phase I/II clinical study in the U.S. evaluating YELIVA (ABC294640) in patients with refractory/relapsed diffuse large B-cell lymphoma (DLBCL), primarily in patients with HIV-related DLBCL, also supported by a grant from the NCI Small Business Technology Transfer (STTR) program. A third Phase II clinical study is planned to evaluate YELIVA (ABC294640) as a radioprotectant to prevent mucositis in cancer patients undergoing therapeutic radiotherapy.

The ongoing and planned Phase II studies follow numerous successful pre-clinical studies conducted with YELIVA (ABC294640) in GI, inflammation, radioprotection and oncology models, as well as a Phase I study in patients with advanced solid tumors, supported by grants from the National Cancer Institute (NCI) and the FDA’s Office of Orphan Products Development (OOPD). RedHill recently announced that the last patient has completed the final scheduled follow-up visit in the Phase I study with YELIVA (ABC294640). Preliminary positive data from the Phase I study was presented by Apogee at the November 2013 Molecular Targets and Cancer Therapeutics meeting. The analysis of the study is currently ongoing and top-line results are expected to be announced early in the fourth quarter of 2015. A full analysis and the final Clinical Study Report (CSR) are expected by the end of the year or early 2016.

The studies with YELIVA (ABC294640) are registered on www.ClinicalTrials.gov, a web-based service by the U.S. National Institute of Health which provides public access to information on publicly and privately supported clinical studies.

About YELIVA (ABC294640):

YELIVA (ABC294640) is a first-in-class, proprietary sphingosine kinase-2 (SK2) selective inhibitor, administered orally, with anti-cancer and anti-inflammatory activities, targeting multiple potential oncology, inflammatory and gastrointestinal indications. By inhibiting the SK2 enzyme, YELIVA (ABC294640) blocks the synthesis of sphingosine 1-phosphate (S1P), a lipid that promotes cancer growth and pathological inflammation. YELIVA (ABC294640) was originally developed by U.S.-based Apogee Biotechnology Corp. and completed multiple successful pre-clinical studies in oncology, inflammation, GI, and radioprotection models, as well as the ABC-101 Phase I clinical study in cancer patients with advanced solid tumors. A Phase I/II clinical study evaluating YELIVA (ABC294640) in patients with refractory/relapsed diffuse large B-cell lymphoma (DLBCL) has been initiated in the U.S. The development of YELIVA (ABC294640) was funded to date primarily by grants and contracts from U.S. federal and state government agencies.

(Filing, 10-Q, Peregrine Pharmaceuticals, SEP 9, 2015, View Source [SID:1234507438])

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On September 9, 2015 Varian Medical Systems (NYSE: VAR) reported that it is collaborating with two leading Cape Town universities to launch Africa’s first ‘Access to Care’ program, designed to train cancer caregivers in delivering advanced conformal radiotherapy treatments (Press release, InfiMed, SEP 9, 2015, View Source [SID:1234507423]).

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The three-month course, which will be delivered in conjunction with Cape Peninsula University of Technology and the University of Cape Town’s department of radiation oncology, aims to train and support radiation therapy departments to implement and maintain 3D conformal radiation therapy treatment programs at their hospitals. In many cases, the delegates’ only experience of radiotherapy will have been older cobalt-based 2D treatments.

"As radiation oncology becomes increasingly precise and cancer centers worldwide can offer ever more advanced treatments for their patients, many parts of the developing world are still significantly under-equipped with too few machines to treat their rapidly growing cancer populations," says Michael Sandhu, who heads Varian Oncology Systems’ new global market development team. "Developing regions are starting to invest in new equipment to address this capacity gap but they are often hindered by a lack of qualified staff to plan treatments and run the equipment. ‘Access to Care’ is one of the ways in which Varian, as the global leader in radiation oncology, is seeking to bridge the skills gap between well-equipped countries and developing nations."

The Access to Care program will be offering two courses a year in South Africa and each program will be attended by four teams of radiation oncologists, medical physicists and radiotherapy therapists from participating hospitals from across the African continent. The course includes three weeks of classroom-based training at Groote Schuur Hospital in Cape Town, which is equipped with a virtual linear accelerator and four workstations, followed by a 10-week remote mentorship program. A separate software lab equipped with 10 workstations is available for students to practice contouring and treatment planning – important steps in the radiotherapy process. The classroom is linked to Varian’s virtual education environment hosted in its European headquarters in Cham, Switzerland.

"The training of cancer specialists and their teams enters a new era with the Access to Care program, which is at the leading edge of training globally and will help towards better and safer care of patients with cancer," said Professor Raymond Abratt, retired head of radiation oncology at Groote Schuur Hospital and the University of Cape Town, and current chairperson of the South African Society of Clinical and Radiation Oncologists (SASCRO), at a program launch event that took place in Cape Town today. "Radiation Oncology is an important component of cancer treatment in Africa and I congratulate all those involved in realizing this exceptional facility and the associated training programs."

Access to Care also offers training programs in Vietnam and has plans to commence a similar project in Algeria. "There is some real momentum behind our ‘Access to Care’ training programs and we are excited about the chance to help provide greater access to advanced cancer treatments in developing nations," says Jose-Manuel Valentim, Varian’s director market development in the EMEIA and APAC regions.

Cancer in Africa
According to a 2013 study published in Lancet Oncology, only 23 out of 52 African countries have radiotherapy available for patients. The World Health Organization reports that by 2030 there will be some 1.6 million new cancer cases in Africa each year, resulting in 1.2 million deaths. The most common cancers in Africa are cancers of the cervix, breast, lung, liver and prostate.

Varian has installed more than 100 radiotherapy treatment systems in Africa over the last 25 years. The company recently announced major projects in Algeria, Egypt and South Africa. Varian has also installed equipment in several sub-Saharan nations including Ghana, Angola, Kenya, and Madagascar.

On September 9, 2015 Aduro Biotech, Inc. (Nasdaq:ADRO) reported that it has entered into a clinical trial agreement with Incyte Corporation (Nasdaq:INCY) to evaluate the safety, tolerability and preliminary efficacy of Aduro’s lead LADD immunotherapy, CRS-207, in combination with Incyte’s oral indoleamine dioxygenase 1 (IDO1) inhibitor, epacadostat (INCB24360), in patients with ovarian cancer (Press release, Aduro BioTech, SEP 9, 2015, View Source;p=RssLanding&cat=news&id=2086398 [SID:1234507459]).

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The combination of both investigational immunotherapeutic agents, which have different but complementary mechanisms directed at enhancing the body’s own immune defenses, may provide unique synergies in fighting cancer. Incyte’s epacadostat has been shown in vitro and in preclinical tumor models to enhance activities of multiple types of immune cells by reducing the immune suppression characteristic of the tumor microenvironment. Aduro’s CRS-207 has been shown to stimulate immune cell activity, with particular targeting mechanisms that seek and attack tumor cells that express mesothelin like those found in ovarian cancer.

"There’s a growing body of evidence and enthusiasm in the field of oncology to combine therapeutic agents with different mechanisms that may result in very powerful approaches to treating tough cancers," said Stephen T. Isaacs, chairman, president and chief executive officer of Aduro. "Incyte is a leader in the field of cancer immunotherapy and we’re pleased to join forces with them to study a novel approach to treating ovarian cancer."

Rich Levy, M.D., chief drug development officer of Incyte added, "This clinical trial collaboration with Aduro is an important opportunity to further investigate the therapeutic value of epacadostat in advanced ovarian cancer. Research partnerships like this one help us deliver on our goal of advancing innovative science to improve patients’ lives."

The Phase 1/2 trial, which is being funded equally between the two companies, is designed to test combinations of CRS-207 with two dose levels of epacadostat in dose escalation and then will expand to a Phase 2 evaluating the combination at the optimal dose level compared to CRS-207 alone based on safety and tumor biomarkers. The study plans to enroll up to 40 patients in Phase 1 and up to 86 patients in Phase 2 with platinum-resistant ovarian, fallopian or peritoneal cancers. The trial is expected to begin enrolling patients in early 2016.

Under the terms of the collaboration, Aduro and Incyte will collaborate on a non-exclusive basis to evaluate the combination. Aduro will be responsible for conducting the study and the results will be used to determine whether further clinical development of this combination is warranted.

About Epacadostat

Indoleamine 2,3-dioxygenase 1 (IDO1) is an immunosuppressive enzyme that has been shown to induce regulatory T cell generation and activation, and allow tumors to escape immune surveillance. Epacadostat is an orally bioavailable small molecule inhibitor of IDO1 that has nanomolar potency in both biochemical and cellular assays and has demonstrated potent activity in enhancing T lymphocyte, dendritic cell and natural killer cell responses in vitro, with a high degree of selectivity. Epacadostat has shown proof-of-concept clinical data in patients with unresectable or metastatic melanoma in combination with the CTLA-4 inhibitor ipilimumab, and is currently in four proof-of-concept clinical trials with PD-1 and PD-L1 immune checkpoint inhibitors in a variety of cancer types.

About CRS-207

CRS-207 is one of a family of product candidates based on Aduro’s live-attenuated, double-deleted (LADD) Listeria monocytogenes immuno-oncology platform that are designed to induce potent innate and adaptive immune responses. CRS-207 has been engineered to express the tumor-associated antigen mesothelin, which is over-expressed in many cancers including mesothelioma and pancreatic, non-small cell lung, ovarian and gastric cancers.

On September 9, 2015 NanoString Technologies, Inc., (NASDAQ:NSTG) a provider of life science tools for translational research and molecular diagnostic products, reported that the PAM50 gene signature, commercialized as the Prosigna Breast Cancer Gene Signature Assay, has been added to the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Clinical Practice Guidelines (Press release, NanoString Technologies, SEP 9, 2015, View Source [SID:1234507424]). The updated guidelines recognize Prosigna’s value to provide additional prognostic and predictive information that complements the pathologic assessment predicting the benefit of adjuvant chemotherapy.

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"In cases of clinical uncertainty, the decision to use chemotherapy in early stage breast cancer patients is a challenge. Chemotherapy can have devastating short-term and long-term consequences for many patients and therefore should be used only when we have very good reasons, either related to high risk of relapse or aggressive tumor biology," said Dr. Miguel Martin, Professor of Medicine and Chair of the Spanish Group for Breast Cancer Research-GEICAM. "Prosigna is a new and robust tool to help clinicians assess tumor biology and risk of recurrence, which may help determine the appropriateness of systemic chemotherapy."

Prosigna was acknowledged as having achieved level 1B evidence for its prognostic value and is recommended for use to predict the benefit of chemotherapy. The conclusion of the guideline panel places Prosigna at parity with other established gene expression assays. The updated ESMO (Free ESMO Whitepaper) Guidelines are consistent with the recently updated St. Gallen International Breast Cancer Guidelines, which both suggest a patient’s risk of recurrence should be assessed by tumor biology and burden of disease. Additionally, the ESMO (Free ESMO Whitepaper) Guidelines indicate that the decision to use systemic adjuvant chemotherapy should be based on the intrinsic subtype, which can be efficiently determined using the CE-marked version of the Prosigna Assay. The guidelines further recommend specific systemic treatment strategies for each identified molecular subtype.

The ESMO (Free ESMO Whitepaper) Clinical Practice Guidelines are developed by an international panel of experts in accordance with ESMO (Free ESMO Whitepaper) operating procedure for assessing levels of clinical evidence. The ESMO (Free ESMO Whitepaper) Clinical Practice Guidelines for Breast Cancer are available at: View Source

"We’re pleased with the decision of the ESMO (Free ESMO Whitepaper) Clinical Practice Guideline committee to recognize the value of Prosigna for informing the use of chemotherapy in breast cancer," said Brad Gray, President and Chief Executive Officer of NanoString Technologies. "This is the third European clinical practice guideline to include Prosigna, and should support our continued success in bringing breast cancer recurrence testing to patients."

About the Prosigna Assay and the nCounter Dx Analysis System

The Prosigna Assay provides a risk category and numerical score for assessment of the risk of distant recurrence of disease at 10 years in postmenopausal women with node-negative (Stage I or II) or node-positive (Stage II or IIIA), HR+ breast cancer. Based on the PAM50 gene signature initially discovered by Charles Perou, Ph.D. and colleagues, the Prosigna Assay is an in vitro diagnostic tool that utilizes gene expression data weighted together with clinical variables to generate a risk category and numerical score to assess a patient’s risk of distant recurrence of disease. The Prosigna Assay measures gene expression levels of RNA extracted from FFPE breast tumor tissue previously diagnosed as invasive breast carcinoma.

The Prosigna Assay requires minimal hands-on time and runs on NanoString’s proprietary nCounter Dx Analysis System, which offers a reproducible and cost-effective way to profile many genes simultaneously with high sensitivity and precision.

The nCounter Dx Analysis System is a highly automated and easy-to-use platform that utilizes a novel digital barcoding chemistry to deliver high-precision multiplexed assays. The system is available in the multi-mode FLEX configuration, which is designed to meet the needs of high-complexity clinical laboratories seeking a single platform with the flexibility to run the Prosigna Assay and, when operated in the "Life Sciences" mode, process translational research experiments and multiplexed assays developed by the laboratory.

The Prosigna Breast Cancer Prognostic Gene Signature Assay Intended Use:

In the European Union, and other countries that recognize the CE mark, as well as Canada and Australia, the Prosigna Assay is indicated in female breast cancer patients who have undergone either mastectomy or breast-conserving surgery in conjunction with locoregional treatment consistent with standard of care, either as:

a. A prognostic indicator for distant recurrence-free survival at 10 years in post-menopausal women with Hormone Receptor-Positive (HR+), lymph node-negative, Stage I or II breast cancer to be treated with adjuvant endocrine therapy alone, when used in conjunction with other clinicopathological factors.

b. A prognostic indicator for distant recurrence-free survival at 10 years in post-menopausal women with Hormone Receptor-Positive (HR+), lymph node-positive (1-3 positive nodes, or 4 or more positive nodes), Stage II or IIIA breast cancer to be treated with adjuvant endocrine therapy alone, when used in conjunction with other clinicopathological factors.