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Archive - Jan 2019


January 15th

HUGE DISCOVERY REPORTED IN CELL: Activated PMN Exosomes Are Pathogenic Entities That Cause Destruction in COPD Lung; COPD Is Fourth-Leading Cause of Death in World

University of Alabama at Birmingham (UAB) researchers have found a novel, previously unreported pathogenic entity that is a fundamental link between chronic inflammation and tissue destruction in the lungs of patients with chronic obstructive pulmonary disease (COPD). COPD is the fourth-leading cause of death in the world. This pathogenic entity -- exosomes from activated polymorphonuclear leukocytes (PMNs) -- caused COPD damage when the small, subcellular particles, collected from purified PMNs, were instilled into the lungs of healthy mice. Remarkably, the UAB researchers also collected exosomes from the lung fluids of human patients with COPD and the lung fluids of neonatal ICU babies with the lung disease bronchopulmonary dysplasia; when those human-derived exosomes were instilled into the lungs of healthy mice, they also caused COPD lung damage. Damage was primarily from PMN-derived exosomes from the human lungs. "This report seems to provide the first evidence of the capability of a defined non-infectious subcellular entity to recapitulate disease phenotype when transferred from human to mouse," said J. Edwin Blalock, PhD, Professor of Pulmonary, allergy and Critical Care Medicine in the UAB Department of Medicine. "I think this could be a very profound discovery. A lot of what we have found here will apply in other tissues, depending on the disease." Other diseases marked by immune cell inflammation and tissue destruction include heart attacks, metastatic cancer and chronic kidney disease. The activated PMN exosomes may also contribute to lung damage in othelung diseases that have excessive PMN-driven inflammation, such as cystic fibrosis. The study is reported in the prestigious journal Cell.

PMWC 2019 Will Include Two Sessions on Real-World Evidence (RWE); World’s Premier Conference on Precision Medicine Will Take Place in California’s Silicon Valley Jan 20-23; Registration Still Open

The Precision Medicine World Conference 2019 (PMWC 2019) will be held January 20-23 at the Santa Clara Convention Center in California’s Silicon Valley and will include two sessions focused specifically on real-world data (RWD) and real-world evidence RWE). These sessions will bring together top experts, including representatives from Qiagen and N-of-One (400 Speaker Program). Please see additional details on these PMWC sessions on RWD and RWE at the end of this note. Registration for this outstanding PMWC conference is still open and can be accomplished at this link ( In a January 15, 2019 PMWC release, Tal Behar, Co-Founder & President, PMWC Silicon Valley, noted that the FDA has created a framework for evaluating the use of RWE to support additional indications for approved drugs, as well as to satisfy drug post-marketing study requirements. This framework lays out the Agency’s approach to developing guidelines for using RWD in drug regulation. Qiagen announced last week that it has entered into an agreement to acquire N-of-One (both Qiagen & N-of-One will be presenting at PMWC 2019), a molecular decision support company and pioneer in clinical interpretation services for complex genomic data. N-of-One has built a proprietary somatic cancer database of more than 125,000 patient samples. Its technology helps pathologists create reports for clinicians that include genetic variant interpretation, DNA change, effect, and causative condition. RWE collected from a variety of sources offers new insights and opportunities to make better clinical decisions, understand clinical outcomes, and to enable better-informed regulatory decisions.

January 14th

Exosomes from Nischarin-Expressing Cells Reduce Breast Cancer Cell Motility & Tumor Growth; Researchers Conclude That "Nischarin-Expressing Exosomes in Combination with Drugs Will Likely Have Very Good Therapeutic Effect on Breast Cancer Patients"

Dr. Suresh K Alahari discovered the novel protein, Nischarin, which is involved in a number of biological processes, including the regulation of breast cancer cell migration and movement. Although his lab has shown that Nischarin functions as a tumor suppressor, research continues to uncover new information that may lead to better treatments. In the current study, the research team investigated Nischarin's function in exosome release. Exosomes are nano-sized vesicles (fluid-filled sacs) containing proteins, and genetic and other material involved in both physiological and pathological processes. Tumor-derived exosomes contain various signaling messengers for intercellular communication involved in tumor progression and metastasis of cancer. Tumor exosomes influence the interactions of various types of cells within the tumor microenvironment, regulating tumor development, progression, and metastasis. Primary tumors release exosomes that can enhance seeding and growth of metastatic cancer cells. Among the researchers' findings: Nischarin regulates cell attachment and alters the properties of exosomes. Exosomes from Nischarin-positive cells reduce breast cancer cell motility and adhesion, as well as tumor volume. Nischarin-positive cells release fewer exosomes, and cell survival is decreased. Co-culturing breast cancer cells with Nischarin-positive exosomes decreases tumor growth and lung metastasis. "This novel role for the tumor suppressor Nischarin not only increases our understanding of the exosome biology, but can be translated to identifying new targets for modulating cancer metastasis," notes Dr. Alahari.

January 14th

Major Business Announcements at JP Morgan Healthcare Conference (Jan 7-10) Herald Clinical Advances That Will Be Described at PMWC 2019 in Silicon Valley (Jan 20-23), World’s Premier Conference on Precision Medicine

According to a recent release, Tal Behar (pics at end), Co-Founder & President of PMWC Silicon Valley, believes that the recently concluded JP Morgan Healthcare Conference in San Francisco ( (January 7-10), which was jam-packed with major business announcements, sets the stage perfectly for PMWC’s 16th Precision Medicine World Conference, which will take place Sunday through Wednesday January 20-23 at the Santa Clara Convention Center in Silicon Valley. The annual JPMorgan Healthcare Conference is the largest and most informative healthcare investment symposium in the industry, bringing together industry leaders, emerging fast-growth companies, innovative technology creators, and members of the investment community. See below for links to media highlights and wrap-ups of the just-concluded JP Morgan Healthcare Conference. The program for the upcoming PMWC Conference in Silicon Valley can be reviewed here ( and registration at the pre-event rate can be accomplished here ( The theme of PMWC 2019 is “How Do We Accelerate Precision Medicine and Deliver on Its Promises?" Ms. Behar said that the themes of the news highlights from the JPMorgan Healthcare conference align well with the upcoming PMWC agenda, and that this premier precision medicine conference will go beyond the buzz and dig deep to understand how to leverage data, genomics, and artificial intelligence (AI) to transform clinical care. PMWC 2019 Silicon Valley will focus on the relevance and developments of genomics medicine and new applications in clinical diagnostics, and contains several tracks that are dedicated to AI, immunotherapy, genomics medicine, and more.

January 10th

Elemental Mechanism Driving “Transcriptional Pausing”--Which Controls Gene Expression in All Living Organisms--Revealed by Work at UW-Madison; Study Also Reveals New Understanding of RNA Polymerase

A study published online on January 8, 2019 in eLife, and led by University of Wisconsin–Madison Professor of Biochemistry and Bacteriology Robert Landick, PhD, and his research team, reveals, for the first time, the elemental mechanism behind transcriptional pausing, a phenomenon that underlies the control of gene expression in all living organisms. The work also provides new understanding of the enzyme RNA polymerase, an important drug target for treating conditions such as Clostridium difficile infections and tuberculosis. The findings could ultimately improve our understanding of how certain drugs work against the enzyme and aid in actively targeting it. Gene expression is the process by which DNA is translated into all the proteins and other molecules living organisms need. Although it is a process that all introductory biology students learn about very early, scientists are still a long ways from fully understanding it. The process occurs in two steps. Transcription is the first, where RNA polymerase reads the information on a strand of DNA, which is then copied into a new molecule of messenger RNA (mRNA). In the second stage, the mRNA moves on to be processed (“translated”) into proteins by ribosomes. To help control gene expression levels, “transcriptional pausing” by RNA polymerase can occur between the two stages, providing a kind of “roadblock” where transcription may be terminated or modulated by the cell if need be. “A sequence that causes pausing of RNA polymerases in all organisms, from bacteria to mammals, halts the enzyme in a paused state from which longer-lived pauses can arise,” explains Dr. Landick. “As the fundamental mechanism of this elemental pause is not well defined, we decided to explore this using a variety of biochemical and biophysical approaches.”

Mn+2 Activates NLRP3 Inflammasome Signaling, Propagates Exosomal Release of Inflammasome Adaptor Protein ASC in Microglial Cells; Welders Exposed to Manganese-Containing Fumes Had Plasma Exosomes with More ASC Than Controls; Association with Parkinson’s

Researchers from Iowa State University (ISU) and Penn State Health Milton S. Hershey Medical Center have reported work showing that manganese activates NLRP3 inflammasome signaling and propagates exosomal release of inflammasome adaptor protein ASC [apoptosis-associated speck-like protein containing CARD)]in microglial cells. Their article was published online on January 8, 2019, in Science Signaling. At the outset, the scientists, led by senior author Anumantha G. Kanthasamy, PhD, ISU Chair of Biomedical Sciences & Eminent Scholar in Veterinary Medicine, state that chronic occupational exposure to manganese is associated with the development of Parkinson’s disease. They note that others had earlier found that exposure of primed microglial cells or mice to manganese increased NLRP3 inflammasome expression and activation. Manganese caused mitochondrial dysfunction in treated microglial cells and stimulated their release of exosomes containing the inflammasome adaptor protein ASC. The effects of manganese on inflammasome activation were sensitive to reduced endocytosis and transferable by exposure of cells to purified exosomes from ASC-sufficient cells. Similarly, serum exosomes from welders contained more ASC protein and were more inflammatory than those from normal donors, suggesting that occupational manganese exposure may increase systemic inflammasome activation due to exosome-mediated transfer of ASC. The authors note that chronic, sustained inflammation underlies many pathological conditions, including neurodegenerative diseases, and that divalent manganese (Mn2+) exposure can stimulate neurotoxicity by increasing inflammation. In the current study, the researchers examined whether Mn2+ activates the multiprotein NLRP3* inflammasome complex to promote neuroinflammation.

January 8th

Scientists ID Transcription Factor (Tcf7) Required for Success of Immune Checkpoint Blockades in Cancer Therapy; Finding May Advance Understanding of How These Therapies Elicit Their Response

There have been many success stories for immune checkpoint blockade therapies, both in preclinical models and in patients with cancer. But many questions remain about exactly how such immunotherapies elicit their response and what determines when and where checkpoint blockade therapy succeeds or fails at reinvigorating the immune system to eradicate cancer. A new study led by investigators from Brigham and Women's Hospital in Boston, in collaboration with colleagues at the Broad Institute, also in Boston, examines the effects of immune checkpoint blockade therapies on different populations of T-cells, a key class of immune cells in tumors. The team's surprising results point to a population of T-cells that has been overlooked in the past and have led to the identification of a molecular factor that may be predictive of response to treatment. The investigators' findings were published online on January 8, 2019 in Immunity. The article is titled “Checkpoint Blockade Immunotherapy Induces Dynamic Changes in PD-1−CD8+ Tumor-Infiltrating T Cells.” "Our study takes advantage of the observation that there is great diversity in the T-cells within tumors. When we looked at the effect of therapies on different cell populations, we were surprised and puzzled to find that even T-cells that don't express checkpoint inhibitors showed significant changes at the genetic level," said co-corresponding author Ana Anderson (photo), PhD, Associate Scientist at the Brigham, and Associate Professor of Neurology at Harvard Medical School. "These are cells that have largely been ignored before. Our study broadens the focus of what checkpoint blockade therapy may be doing and how it mediates its effects." Dr.

January 6th

Bristol-Myers Squibb to Acquire Celgene for $74 Billion to Create a Premier Innovative Biopharma Company; Combined Company Will Have More Than $1 Billion in Annual Sales

On January 3, 2018, Bristol-Myers Squibb Company (NYSE:BMY) and Celgene Corporation (NASDAQ:CELG) announced that they have entered into a definitive merger agreement under which Bristol-Myers Squibb will acquire Celgene in a cash and stock transaction with an equity value of approximately $74 billion. Under terms of the agreement, Celgene shareholders will receive 1.0 Bristol-Myers Squibb share and $50.00 in cash for each share of Celgene. Celgene shareholders will also receive one tradeable Contingent Value Right (CVR) for each share of Celgene, which will entitle the holder to receive a payment for the achievement of future regulatory milestones. The Boards of Directors of both companies have approved the combination. The transaction will create a leading focused specialty biopharma company well-positioned to address the needs of patients with cancer, inflammatory and immunologic disease, and cardiovascular disease through high-value innovative medicines and leading scientific capabilities. With complementary areas of focus, the combined company will operate with global reach and scale, maintaining the speed and agility that is core to each company’s strategic approach. Based on the closing price of Bristol-Myers Squibb stock of $52.43 on January 2, 2019, the cash and stock consideration to be received by Celgene shareholders at closing is valued at $102.43 per Celgene share and one CVR (as described below). When completed, Bristol-Myers Squibb shareholders are expected to own approximately 69 percent of the company, and Celgene shareholders are expected to own approximately 31 percent.

PMWC 2019 Silicon Valley Has Grown to World's Largest Precision Medicine Conference – Jan 20-23 in Santa Clara Convention Center

PMWC (Precision Medicine World Conference), the preeminent precision medicine global gathering that attracts recognized leaders, top international researchers and medical professionals, and innovators across the healthcare and biotechnology sectors, announced, on January 3, 2019, that PMWC 2019 Silicon Valley has grown to be the largest precision medicine conference, which, for the first time, will be held at the Santa Clara Convention Center in California January 20-23. Thousands of healthcare leaders, representing a variety of companies, technologies, research teams, and medical centers, with leadership roles in precision medicine are expected to attend. Over 400 speakers will be featured in more than 60 sessions. The conference will touch upon relevant topics such as how big data sciences and artificial intelligence (AI) applications advance precision medicine; how new emerging technologies drive genomics and medical practices; how patient data has become so valuable and how it impacts regulatory policy; how continuous advancements in immunotherapy are changing the way cancer is treated; and how thriving genome initiatives such as Genomic England are improving health care. The conference will recognize individuals who play a significant role in transforming today’s health care by advancing precision medicine into the clinic. This year's distinguished group of awardees includes Dr. Feng Zhang, Professor of Neuroscience at the Broad Institute (Harvard/MIT), who made vital contributions to the development of optogenetics and CRISPR technologies, and Dr. Carl June, Professor of Immunotherapy at the University of Pennsylvania, who was a crucial contributor to the development of the revolutionary CAR-T immunotherapy for cancer.

January 3rd

Bill & Melinda Gates Foundation Funds Evox Therapeutics to Support Development of Cell-Targeted, Exosome-Based Approaches to More Effectively Deliver Nucleic Acid-Based Anti-Infective Drug

On December 10, 2018, Evox Therapeutics Ltd ('Evox' or the 'Company'), a leading exosome therapeutics company, announced that it has secured an undisclosed amount of funding from the Bill & Melinda Gates Foundationn. The funds will be used to support the Company's development of cell-targeted exosome-based approaches to more effectively deliver a nucleic acid-based anti-infective drug. Evox is engineering exosomes, the body's natural vesicular delivery system, to enable a wide variety of drugs to reach previously inaccessible tissues and compartments, such as crossing the blood-brain barrier to deliver drugs to the central nervous system, intracellular delivery of biologics, and extra-hepatic delivery of RNA therapeutics. Dr Antonin de Fougerolles, CEO of Evox, commented: "We are pleased to be working with the Bill & Melinda Gates Foundation to maximize the effectiveness of their therapeutic drug through cell- and tissue-targeted exosome-mediated delivery. The foundation has a reputation for working with partners that can drive meaningful change - this funding is a testament to the quality of our platform and its potential application in areas of high medical need." Evox Therapeutics is a privately held, Oxford-based biotechnology company focused on harnessing and engineering the natural delivery capabilities of extracellular vesicles, known as exosomes, to develop an entirely new class of therapeutics. Backed by leading life sciences venture capital groups and supported by a comprehensive intellectual property portfolio, Evox's mission is to positively impact human health by creating novel exosome-based therapeutics for the treatment of various severe diseases with limited options for patients and their families.