On January 31, 2018 SignalRx Pharmaceuticals Inc., a clinical-stage company focused on developing new and more effective oncology drugs with designed multiple target-selected inhibition profiles, reported the publication of key research in the journal Proceedings of the National Academy of Sciences (doi: 10.1073/pnas.1613091114 PNAS January 30, 2017) (Press release, SignalRx, JAN 31, 2017, http://www.ireachcontent.com/news-releases/signalrx-pharmaceuticals-announces-breakthrough-results-on-novel-anti-cancer-dual-pi3k-brd4-inhibition-paradigm-in-pnas-publication-612341103.html [SID1234527325]).

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SignalRx Pharmaceuticals Inc., in collaboration with researchers at the University of California, San Diego School of Medicine and Moores Cancer Center, led by Dr. Donald L. Durden, Professor and Associate Director of Pediatric Oncology at the Moores UCSD Cancer Center, and senior scientific advisor at SignalRx along with Dr. Tatiana Kutateladze, Professor at the University Colorado, Department of Pharmacology, report on key preclinical findings using the small molecule SF2523 designed to inhibit the key cancer targets PI3K and BRD4.

Key results include:

Designed dual inhibition: The dual inhibitor SF2523 inhibits the acetyl-lysine binding of the epigenetic reader protein BRD4 as well the kinase activity of PI3K thus simultaneously disrupting two orthogonal cancer driving mechanisms that promote undesirable effects from the oncogene MYC which is responsible for activating the immuno-oncology targets CD47 and PD-L1. X-ray crystal structures of SF2523 bound to BRD4 isoforms were obtained and are consistent with in silico modeling predictions and thus provide insights for further investigations.
Mode of action: SF2523 blocks both PI3K and BRD4 signaling in vitro and in vivo promoting maximal MYC down-regulation.
Anticancer activity in vivo: SF2523 markedly inhibits cancer cell growth and metastasis in mouse models of neuroblastoma and an orthotopic pancreatic metastatic tumor model.
Safe in vivo profile: Most importantly, the dual PI3K/BRD4 inhibitor SF2523 is dramatically much safer in vivo than the administration of two separate inhibitors in combination (PI3K and BRD4). This proof of concept shows that designing 1 drug with the attributes of 2 distinct drugs (2 drugs in 1) can eliminate or significantly reduce unwanted added toxicity of combination drugs providing an exciting opportunity for the exploration of more sophisticated combinations for maximal anticancer efficacy.
SF2523, as discussed in the manuscript, inhibits phosphatidylinositol 3-kinase (PI3K) which, in addition to drive cancer on its own, also inhibits the epigenetic reader bromodomain-containing protein 4 (BRD4). This new anticancer paradigm harnesses the synergistic impact of inhibiting simultaneously PI3K and BRD4 to maximally inhibit MYC activity by enhancing MYC degradation (PI3K inhibition) and blocking MYC production (inhibition of MYC transcription via BRD4 inhibition). MYC inhibition is an important oncology outcome of this new anticancer paradigm because inactivation of MYC down-regulates immuno-oncology targets CD47 and PD-L1. This down-regulation offers a novel immune-oncology approach alone or in combination with checkpoint inhibitors.

SF2523 has arisen from SignalRx’s platform technology for cancer therapeutics that enables the engineering of one small molecule to inhibit two or more molecular targets in the cancer and stromal cell for maximum anticancer efficacy and unprecedented safety in vivo. While most anti-cancer drugs are made with a single cancer target in mind, the lead compound SF2523 was designed to inhibit two or more key orthogonal signaling biomolecules simultaneously within the cancer cell.

The cancer targets for this new technology approach are selected based on forward genetics and the discovery of important cancer synthetic lethalities for therapeutic exploitation. This effective engineering approach is in contrast to the industry paradigm which relies on random screening efforts of large collections of compounds hoping to find interesting dual-target activities. With SignalRx’s technology, it is possible now to molecularly design dual and triple inhibitory chemotypes for maximum in vivo antitumor activity while maintaining a safety advantage over using combinations of drugs to attempt similar attacks on cancer targets.

SignalRx is seeking a partner to accelerate the development of SF2523 and SF2535 into first-in-man clinical trials based on the promising profile of its PI3K/BRD4 inhibitors shown so far. Since these are single molecules with a single PK/PD and toxicity profile, there is a great opportunity to develop them as single therapeutics and streamline their development in combination therapies focused on companion diagnostics built around synthetic lethality discoveries in human cancers such as kinome adaptation mediated by BRD4.

On January 31, 2017 NanoString Technologies, Inc. (NASDAQ:NSTG), a provider of life science tools for translational research and molecular diagnostic products, reported that Humana has issued a positive coverage decision for the Prosigna Breast Cancer Gene Signature Assay (Press release, NanoString Technologies, JAN 31, 2017, View Source [SID1234517618]). Humana and its more than 13 million members join other payors now covering Prosigna, collectively representing more than 175 million covered lives throughout the United States.

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This positive coverage decision is in line with updated ASCO (Free ASCO Whitepaper) guidelines released in February of 2016, wherein Prosigna is considered medically necessary to assess the necessity of adjuvant chemotherapy in ER-positive, HER2-negative, node-negative breast cancer patients, when adjuvant chemotherapy is not precluded due to any other factor.

"Coverage by Humana is another important milestone in making our Prosigna test available to all indicated patients," said Brad Gray, president and chief executive officer of NanoString Technologies. "Our team has done an outstanding job of working with both national and regional payors to ensure that their patients have access to this state-of-the-art test."

The updated healthcare policy for Humana, which now includes the Prosigna Assay, is available on its website:
View Source;searchtype=freetext&policyType=both

About the Prosigna Breast Cancer Prognostic Gene Signature Assay and 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), hormone receptor-positive (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 formalin-fixed paraffin embedded (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 Breast Cancer Assay and, when operated in the "Life Sciences" mode, process translational research experiments and multiplexed assays developed by the laboratory.

In the United States, the Prosigna Assay is 510(k) cleared for use on the nCounter Dx Analysis System, and is available for diagnostic use when ordered by a physician. The Prosigna Assay has been CE-marked and is available for use by healthcare professionals in the European Union and other countries that recognize the CE Mark, as well as Canada, Israel, Australia, New Zealand and Hong Kong. In the U.S., the Prosigna Assay is indicated in female breast cancer patients who have undergone surgery in conjunction with locoregional treatment consistent with standard of care, either as:

(1) a prognostic indicator for distant recurrence-free survival at 10 years in postmenopausal 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 or (2) a prognostic indicator for distant recurrence-free survival at 10 years in postmenopausal women with Hormone Receptor-Positive (HR+), lymph node-positive (1-3 nodes), Stage II breast cancer to be treated with adjuvant endocrine therapy alone, when used in conjunction with other clinicopathological factors. The device is not intended for patients with four or more positive nodes.

For more information, please visit www.prosigna.com.

On January 30, 2017 Lytix Biopharma, a clinical-stage biopharmaceutical company developing novel cancer immune therapies, reported that it has been awarded a NOK 15.9 million grant from The Norwegian Research Council (User-driven Research-based Innovation) to support the investigation of LTX-315’s ability to make ’’cold tumors hot’’ and Phase II trial in Triple Negative Breast cancer (TNBC) (Press release, Lytix Biopharma, JAN 30, 2017, View Source [SID1234517595]).

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Recent developments in immunotherapy have demonstrated a significant clinical impact in the field of cancer treatment. However, it is well known that immune therapy works better when there are immune effector cells present in the tumour microenvironment compared to if they are absent. When the tumour lacks immune effector cells, they are called "cold" and when immune effector cells are present they are named "hot". Preclinical studies have shown that the Lytix compound LTX-315 has the potential to make cold tumours hot and thus increase the overall patient response of combinations with other cancer treatments, for example immune checkpoint inhibitors.

Forty-two patients have so far been treated with LTX-315 alone, in two Phase I trials, and positive signals from these patients form the basis for this project. The primary objective for this project is to document in both preclinical and clinical studies that LTX-315 increase the infiltration of immune effector cells in the tumour and make the "cold" tumour "hot" in combination with immunotherapy. The clinical study will be performed in patients with Triple Negative Breast Cancer, a subtype of breast cancer. These patients have today limited treatment possibilities and the medical need for better treatments is high.

On January 30, 2017) The Addario Lung Cancer Medical Institute ("ALCMI"), the Bonnie J. Addario Lung Cancer Foundation ("ALCF") and Scancell Holdings PLC ("Scancell") reported a collaboration to evaluate the use of Scancell’s second innovative cancer vaccine, SCIB2, from its ImmunoBody platform to treat non-small cell lung cancer ("NSCLC") (Press release, Scancell, JAN 30, 2017, View Source [SID1234517594]).

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Scancell’s ImmunoBody cancer vaccine platform is a novel immunotherapy treatment under development that stimulates the immune system to potentially treat and prevent cancer. The Company
recently successfully completed a Phase 1/2 clinical trial with SCIB1 in patients with melanoma.

The Addario Advanced Collaboration Program brings patients into clinical trials from ALCMI’s extensive research consortium of international researchers and member institutions and ALCF’s patient support programs. ALCMI plans to assist Scancell in the design and development of a Phase 1/2 clinical trial with SCIB2 in patients with NSCLC which is planned to begin in 2018 and complete approximately 18 months later.

"This partnership enables us to access an important clinical program that could also accelerate the development of this groundbreaking immunotherapy technology," said ALCMI President and COO
Steven Young. "Combining our two foundations’ unique resources will increase patient engagement with the goal to bring new treatment options to non-small cell lung cancer patients," added Bonnie J. Addario, a 12-year lung cancer survivor and founder and chair of ALCF and founder of ALCMI.

According to the Centers for Disease Control and Prevention, lung cancer accounts for 27 percent of all cancer deaths, more than breast, prostate and colon cancer combined. More than 228,000 people receive a cancer diagnosis in the United States alone and more than 160,000 will not survive. It remains one of the most difficult cancers to treat.

"Immunotherapy has dramatically improved many patients’ outcomes across various cancer types. One of the next steps is how we can further enhance the immune response to cancer. Early clinical data on ImmunoBody suggests it is extremely well tolerated and may significantly improve outcomes, which would be ideal. I’m excited to work with Scancell and hopeful that we will take another important step in the fight against lung cancer," said Jacob M. Sands, MD, assistant
professor, medical oncology, Lahey Hospital & Medical Center in Burlington, Massachusetts.

SCIB2 has the potential to complement existing treatments and has potential value where current treatments either do not work or are not available. By stimulating immune responses to specific lung
cancer antigens, SCIB2 should assist the body in targeting and fighting NSCLC, leading to longer survival rates.

"We have generated preclinical data that suggests that SCIB2 could be the ideal complement to existing and emerging checkpoint inhibitor therapies to treat NSCLC and so provide an effective new potential treatment option for patients with this devastating disease," said Scancell CEO Richard
Goodfellow.

This announcement contains inside information for the purposes of Article 7 of Regulation (EU) 596/2014 (MAR).

On January 30, 2017 Tempus, a technology company focused on helping doctors personalize cancer care, and the University of Michigan are partnering to help researchers and physicians to identify customized treatment opportunities for pancreatic cancer patients (Press release, Tempus, JAN 30, 2017, View Source [SID1234517597]).

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As part of the new collaboration, Tempus will provide genomic and transcriptomic sequencing and analysis for pancreatic cancer patients being treated at the University of Michigan. Utilizing bioinformatics and its machine learning platform, Tempus will help physicians analyze these data sets to identify patterns and potentially actionable treatments.

Pancreatic cancer is the third leading cause of cancer-related death in the United States and anticipated to become the second by around 2020. The disease kills more people than breast cancer and has a five-year survival rate of just nine percent.

"Though pancreatic cancer patients face some of the toughest odds, they do not yet have access to a host of targeted therapies with proven effectiveness in the same way that other diseases have, in part because there isn’t enough patient, treatment and outcome data to identify patterns that might lead to actionable treatments," said Eric Lefkofsky, Co-founder and CEO of Tempus. "At Tempus, we are proud to be leading an effort to make that data available to researchers and physicians on the frontlines of care."

The University of Michigan Comprehensive Cancer Center is one of 47 Comprehensive Cancer Centers in the U.S. designated by the National Cancer Institute, and has been a leader in pancreatic cancer, from both a clinical and research perspective, for the past several decades.

"The University of Michigan Comprehensive Cancer Center is committed to providing researchers and physicians with the tools and resources they need to battle pancreatic cancer," said Diane Simeone, Director of the Gastrointestinal Oncology Program. "We are pleased to partner with Tempus, a company that shares our commitment to innovation and collaboration in the pursuit of better treatment options for patients battling this disease."

Tempus provides molecular sequencing and clinical analytic solutions for top academic centers, hospital systems, associations, and healthcare providers.