The National Institutes of Health (NIH) has picked long-time UC Berkeley neuroscientist John Ngai to head its BRAIN Initiative, a multibillion-dollar federal research push to develop new tools that will help scientists understand how the brain works and lead to new treatments for brain dysfunction.

The BRAIN Initiative aims to revolutionize our understanding of the brain and brain disorders, said NIH director Francis Collins today (Wednesday, Jan. 29) in announcing the appointment. We welcome Dr. Ngais leadership in steering this groundbreaking 21st century project.

As director of what formally is the NIH Brain Research through Advancing Innovative Neurotechnologies Initiative, Ngai will help steer about $500 million in research dollars this year to the most promising projects around the country. From 2014, when the first awards were given, through 2019, the initiative distributed $1.3 billion, and it is expected to disperse $5.2 billion by 2025.

In the first five years of the BRAIN Initiative, we have seen some remarkable advances in technologies for monitoring, as well as for perturbing activity in the brain, some of which have led to new innovations in treating patients with devices such as deep brain stimulators in the areas of epilepsy and Parkinsons disease, Ngai said. By continuing to develop new tools for understanding how the brain works, we hope to provide the basis for future clinical treatments.

Dr. Ngais appointment comes at a propitious time as the BRAIN Initiative enters a new and important phase, said Walter Koroshetz, director of NIHs National Institute of Neurological Disorders and Stroke (NINDS). Dr. Ngai will provide the initiative the clear vision the project needs to navigate through this critical period.

Ngai, the Coates Family Professor of Neuroscience at UC Berkeley, was a guest of the White House in 2013 when the initiative was first announced and together with nine Berkeley colleagues received one of the first NIH BRAIN Initiative grants to help classify cells in the brain. Over the past five years, the initiative has funded hundreds of research projects nationwide that have led to several breakthroughs, including the creation of systems for studying the circuits involved in generating behavior in animal models, the development of a computer program that can mimic natural speech from peoples brain signals and the construction of a brain cell parts list.

Most of the money comes from the annual budgets of 10 NIH institutes led by the NINDS and the National Institute of Mental Health (NIMH). Congress has appropriated additional funds each year since the passage of the 21st Century Cures Act in 2013.

Ngai will begin his new position in mid-March, overseeing the long-term strategy and day-to-day operations of the initiative with oversight by the directors of the 10 institutes participating in the BRAIN Initiative. He will retire from UC Berkeley as an emeritus professor and move his lab to new quarters in Bethesda, Maryland, home of the NIH.

Ngai first joined the UC Berkeley Department of Molecular and Cell Biology in 1993, after earning his Ph.D. in biology in 1987 from the California Institute of Technology and working as a postdoctoral fellow at Columbia University College of Physicians and Surgeons from 1988 until 1992. It was at Columbia, in the lab of future Nobel Laureate Richard Axel, that he initiated his studies of the bodys olfactory system: our sense of smell. At the time, it was one of the last of the five senses to be thoroughly studied, Ngai said, and he applied his training in molecular biology to unearthing the genes involved in receiving and processing information.

Neuroscientist John Ngai was appointed director of the NIH BRAIN Initiative. (UC Berkeley photo by Brittany Hosea-Small)

As new tools came along, he probed deeper and has in recent years employed the latest technology, single cell sequencing, to discover all the genes expressed in specific neurons. His latest interest is how the olfactory system repairs itself. As director of the Helen Wills Neuroscience Institute from 2011 to 2013, Ngai helped bring engineers and physical scientists into the institute to join biologists.

This was the vision that (former UC Berkeley professors) Corey Goodman and Carla Shatz had when they founded the institute in 1999, with the encouragement of then-Executive Vice Chancellor and Provost Carol Christ, now UC Berkeleys chancellor, Ngai said. To drive and accelerate the future of neuroscience requires the development of new tools and the incorporation of ideas from fields outside of biology. The BRAIN Initiative has enabled us to realize that vision in a grand way.

John has helped put UC Berkeley in the vanguard of the technology-centered approach that is the focus of the BRAIN Initiative, said Paul Alivisatos, UC Berkeleys vice chancellor and provost and one of the scientists who helped catalyze early discussions that laid the foundation for the initiative. This foresight to incorporate our unparalleled strengths in the physical and engineering sciences with our preeminence in neurobiology prepared Berkeley to leverage these new technologies five years ago to accelerate discovery and treatments in the neurosciences. That approach will continue to drive our research in the future.

Ngai also is director of the Functional Genomics Laboratory in the California Institute for Quantitative Biosciences, or QB3, a multi-campus initiative that fosters the development of biology as a quantitative, predictive science, with applications in health, energy and the environment. On the national level, Ngai has provided extensive service on NIH study sections, councils and steering groups, including as co-chair of the NIH BRAIN Initiative Cell Census Consortium Steering Group.

Ngai was born in New York City to Chinese immigrants who came to this country in 1947 to complete their medical training. He grew up with his two older sisters just outside of New York City in Teaneck, New Jersey. Science and medicine were the usual topics of conversation over dinner, as his parents were both faculty members at Columbia University College of Physicians and Surgeons, where his father a neuroscientist himself was professor and chair of anesthesiology and his mother a professor of pharmacology. He attended Pomona College in Claremont, California, and graduated with a bachelors degree in chemistry and zoology in 1980. His many honors include awards from the Sloan Foundation, Pew Charitable Trusts and McKnight Endowment Fund for Neuroscience.

Ngai said he will miss UC Berkeley, but is thrilled by the chance to head up one of the nations top biomedical priorities.

For the past 27 years, it has been such an amazing privilege for me to draw inspiration from the brilliant students, colleagues and staff at the worlds greatest public university, he said. I will take the lessons I learned here at Berkeley to my new role in enabling BRAIN Initiative investigators to unlock the secrets of the brain and lay new foundations for treating human brain disorders. The skys the limit.

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Cell Biology

The Future of Antivenom May Involve Mini Lab-Grown Snake Glands – Smithsonian.com

January 30, 2020 medical

For the first time, scientists have grown miniature, venom-producing glands in the lab using coral snake embryos, according to a news study published in the journal Cell. Why might researchers want to create artificial venom glands, you ask?

The project was initially aimed to establish proof-of-concept more than anything else. Three graduate students at the Hubrecht Institute in the Netherlands had wondered: If lab-grown organs could be made that acted like mouse and human tissues, would it work for other animals, like reptiles?

Luckily, they were working in molecular geneticist Hans Clevers lab. Clevers is a prominent expert in stem cell research who pioneered research on the lab-grown organ imitationscalled organoidsa decade ago. Since then, researchers have created miniature human kidneys, livers, and brains in petri dishes.

On Fridays, members of the Clevers Lab are allowed to work on unstructured projects. To put their question to the test, Clevers students Yorick Post, Jens Puschhof, and Joep Beumer, would need a source of reptilian stem cells. As it happened, one of the researchers knew a guy: a snake breeder who could supply them with fertilized eggs, as STAT News Andrew Joseph reports.

They started with the egg of a Cape coral snake, removing the embryos venom glands and placing them in a dish. Then, they followed nearly the same protocol as they did with human cells, giving the cells ample supply of growth-inducing chemicals and storing them at a comfortable temperatureabout 89 degrees Fahrenheit, about ten degrees lower than the temperature used for human cells.

Soon, the plates held one-millimeter-long white blobs producing dangerous venom. With the organoids alive and well, the researchers told Clevers what theyd done, Leslie Nemo at Discover reports. If theyd told him beforehand, he would have told them it probably wouldnt work, Clevers tells the Atlantics Ed Yong. The chemicals they used were designed for human stem cells, and very little was known about stem cells in snakes. Still, the researchers were able to grow organoids from nine species of snakes.

Its a breakthrough, University of Costa Rica snake venom toxicologist Jos Mara Gutirrez, who was not involved in the study, tells Erin Malsbury at Science magazine. This work opens the possibilities for studying the cellular biology of venom-secreting cells at a very fine level, which has not been possible in the past, Malsbury says.

By looking closely at the organoids, Clevers team gained new insight into how multiple kinds of cells work together to produce the specific mixture of toxins and proteins that results in fully-developed venom.

Venomous snake bites kill between 81,000 and 138,000 people every year, according to the World Health Organization, and cause three times as many amputations and disabilities. The antidote to a snakebite is an antivenom, but each of thousands of venomous snakes have a different biteeach requiring a unique treatment. Even snakes of the same species can produce a slightly different venoms if they live in different regions.

Right now, antivenoms are produced using much the same process as was invented in the 19th century: a live snake is milked for its venom, that venom is injected into a horse. Horses have been used for antivenom production for years because of their docile nature and big veins, as Douglas Main wrote for Popular Mechanics in 2016. They are first injected with adjuvant, which stimulates their immune system to produce enough antibodies to neutralize the venom. Then, researchers take a sample of their blood and separate the antivenom from other component of blood, like plasma, in a centrifuge.

Clevers now hopes to create a bank of dozensand eventually thousandsof organoids from dangerous snakes and other reptiles that could aid in the effort to manufacture effective antivenoms.

"We could just sample one tissue once, and we have a source of [that snakes] venom for eternity," Clevers tells Discover.

Clevers is working with the Dutch biologist Freek Vonk, who he calls the Dutch Steve Irwin, to get samples of the snake species he hopes to include in the venom gland biobank. (Vonk works at Naturalis Biodiversity Center in Leiden and also has some excellent Dutch science tunes available on Spotify.)

With venom from organoids more easily available, the hope is to skip the horse in the antitoxin-production process. Researchers could instead use the organoid-produced venom to test an array of molecules for neutralizing abilities.

It will be interesting to see how the cost of producing venom using this system compares to the cost of purchasing venom milked from live snakes, since cost of antivenom is a key impediment to its wider use in countries where snakebite is a huge issue, like India and Nigeria, as Bangor University molecular zoologist Anita Malhotra tells the Atlantic.

Antivenoms made from lab-grown venom glands are likely years away, but the organoids could also be a big step for studying toxin production in more detail than previously possible. With the cells isolated from the rest of the snake, researchers might be able to look at how they can produce toxic chemicals without damaging themselves, for example.

Clevers tells Discover, We do the most interesting work when we dont have a proposal and just try things.

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Cell Biology

Dr. Edith Widder vouches for ocean conservation through exploration – The Wichitan

January 30, 2020 medical

Colin StevensonMarine Biologist Edith Widder recounts her experiences from a Summer 2019 expedition where she recorded the first footage of a giant squid in US waters. Jan. 28.

Colin StevensonWidder closes with a quote from Jacques Cousteau before opening to questions from the audience. Jan. 28.

Colin StevensonAn audience member asks Widder about her experiences as a woman in a scientific field. In response, Widder recounts her mother as a role model and how she wasnt put into an engineering program due to her gender. Jan. 28.

Colin StevensonAfter an audience member asks about her view on environmentalism, Widder expands her earlier point that many environmentalists use a theme of fear, while she believes they should use hope to invoke better reactions. Jan. 28.

Colin StevensonEdith Widder explains the importance of bioluminescence research, referencing its use in cell biology studies as support. Jan. 28.

Colin StevensonAfter being asked about her 6-to-8-hour experiences in submersibles, Widder answers how cold and dark it seems, with potential bioluminescence always around her. Jan. 28.

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Cell Biology

GIOSTAR Announces Medical Breakthrough in Biotechnology and Lifesciences To Manufacture Abundant, Safe Red Blood Cells From Stem Cells – Benzinga

January 30, 2020 medical

GIOSTAR/HEAMGEN has developed and secured patented technology to manufacture lifesaving mature red blood cells from stem cells. The red blood cells are made utilizing a bioreactor that permits the production of mature red blood cells, under strictly controlled conditions, for transfusion therapy and replaces the need for a human blood donor. GIOSTAR/HEAMGEN mature red blood cells are safe and not compromised by inadequate pathogen detection and inactivation of diseases such as hepatitis C, HIV, hepatitis B and syphilis. The red blood cells are O-Negative (Universal Donor) to eliminate incompatibility and allosensitization reactions.

ATLANTA (PRWEB) January 29, 2020

"There are three main problems for blood transfusions," stated Dr. Anand Srivastava, Founder and Chairman of GIOSTAR. "First we have to match the blood type. Second, there's not enough blood available every single time. And third, when we transfer blood from one person to another person, there is always a chance of the transfer of disease."

Watch a feature interview with Dr. Anand Srivastava on The DM Zone with host Dianemarie Collins.

The World Health Organization (WHO) published the first detailed analysis on the global supply and demand for blood in October 2019 and found that 119 out of 195 countries do NOT have enough blood in their blood banks to meet hospital needs. In those nations, which include every country in central, eastern, and western sub-Saharan Africa, Oceania (not including Australasia), and south Asia are missing roughly 102,359,632 units of blood, according to World Health Organization (WHO) goals. While total blood supply around the world was estimated to be around 272 million units, in 2017, demand reached 303 million units. That means the world was lacking 30 million units of blood, and in the 119 countries with insufficient supply, that shortfall reached 100 million units.

The global market opportunity for GIOSTAR/HEAMGEN technology presents not only a profitable and scalable business opportunity but also a significant social and environmental impact. The global market is estimated to be at least $ 85 Billion/year.

GIOSTAR/HEAMGEN has identified early entry global markets to include Military, Trauma, Asia (replace Hepatitis C contaminated blood products), Africa (AIDS contaminated blood), Newborns, Thalassemia patients, Allosensitized sickle cell disease patients. South Sudan was found to have the lowest supply of blood, at 46 units per 100,000 people. In fact, the country's need for blood was deemed 75 times greater than its supply. In India, which had the largest absolute shortage, there was a shortfall of nearly 41 million units, with demand outstripping supply by over 400 percent. Strategic investments are needed in many low-income and middle-income countries to expand national transfusion services and blood management systems. Oncology is a major user of blood transfusion but if countries don't have the capacity to manage the bulk of oncology, it will limit complex surgery options.

GIOSTAR/HEAMGEN has acquired the exclusive license to the patent for the technique for stem cell proliferation from University of California San Diego (UCSD). The founding team of GIOSTAR/HEAMGEN is comprised of the scientists and clinicians who were involved in creating the Intellectual Property at UCSD and has already achieved PROOF OF CONCEPT - the optimized lab scale proliferation of mature red blood cells - at UCSD as part of their research.

GIOSTAR/HEAMGEN is currently looking for strategic partnerships (Contact Doug@DMProductionsLLC.com) to accelerate the development of donor-independent red blood cells manufacturing capabilities and advance the proof of concept work already done (patented) around the manufacture of safe, universal donor, human red blood cells. GIOSTAR/HEAMGEN will also develop a full automated proprietary bioreactor using robotic technology to produce abundant quantities of red blood cells with a goal for cost-effective commercialization of fresh, human, universal donor Red Blood Cells (RBCs).

ABOUT GIOSTAR

Dr. Anand Srivastava is a Chairman and Cofounder of California based Global Institute of Stem Cell Therapy and Research (GIOSTAR) headquartered in San Diego, California, (U.S.A.). The company was formed with the vision to provide stem cell based therapy to aid those suffering from degenerative or genetic diseases around the world such as Parkinson's, Alzheimer's, Autism, Diabetes, Heart Disease, Stroke, Spinal Cord Injuries, Paralysis, Blood Related Diseases, Cancer and Burns. GIOSTAR is a leader in developing most advance stem cell based technology, supported by leading scientists with the pioneering publications in the area of stem cell biology. Company's primary focus is to discover and develop a cure for human diseases with the state of the art unique stem cell based therapies and products. The Regenerative Medicine provides promise for treatments of diseases previously regarded as incurable.

GIOSTAR is world's leading Stem cell research company involved with stem cell research work for over a decade. It is headed by Dr Anand Srivastava, who is a pioneer and a world-renowned authority in the field of Stem Cell Biology, Cancer and Gene therapy. Several governments and organizations including USA, India, China, Turkey, Kuwait, Thailand, Philippines, Bahamas, Saudi Arabia and many others seek his advice and guidance on drafting their strategic and national policy formulations and program directions in the area of stem cell research, development and its regulations. Under his creative leadership, a group of esteemed scientists and clinicians have developed and established Stem Cell Therapy for various types of autoimmune diseases and blood disorders, which are being offered to patients in USA and soon it will be offered on a regular clinical basis to the people around the globe.

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Cell Biology

Validating the In-Silico Model for Toxicity Studies – News-Medical.net

January 30, 2020 medical

Any experimental model or simulation must adhere to a series of validity requirements that confirm its applicability and reliability. This article will discuss the process by which in silico methods are verified before their use in preliminary toxicity studies.

Image Credit: Gorodenkoff/Shutterstock.com

In silico toxicology (IST), which is also denoted as computational toxicology, refers to the integration of modern computer technology with molecular biology to create a thorough risk assessment of new chemicals before the initiation of any cell or animal experiments. While IST methods are primarily used in the pharmaceutical industry during early drug development processes, they are also being investigated for their potential usefulness in assessing the toxicity of environmental chemicals. Some of the most widely applied IST methods include quantitative structure-activity relationships (QSAR) tests, pharmacophores, homology models, machine learning, data mining, network analysis tools and much more.

While the exercise of validating an experimental model can be performed by any individual or organization, the European Regulation on Registration, Evaluation, Authorization, and Restriction of Chemicals (REACH) requires that the manufacturer and/or importer of any chemical is responsible for its subsequent analysis and safety evaluation.

Legislative bodies REACH in the EU and the Organization for Economic Co-operation and Development (OECD) of the United States recognize both the lack of data that is currently available on both the toxicological and physicochemical properties of many chemicals, as well as the limited laboratory capacity that exists to measure these effects in real-time. To support the accurate use of new alternative methods of toxicity testing like IST, both REACH and the OECD have created general rules for the use of such methods.

Between 2002 and 2004, several international meetings were held to establish general rules that could be applied to the validation of QSAR and SAR techniques, both of which are widely used in academic, industrial and governmental institutions around the world. The conclusion of these meetings determined that for a QSAR method to be applied for regulatory purposes, it must adhere to five distinct criteria. Of these criteria include a defined endpoint, an unambiguous algorithm, a defined domain of applicability, appropriate measures of robustness, predictivity, and goodness-of-fit and, if possible, a mechanistic interpretation.

Once it has been established that a given IST method, such as a QSAR model, adheres to the OECD validation principles, it is required that all of the information gathered during its validation is documented in report formats such as the QSAR Model Reporting Format (QMRF). In addition to providing its scientific validity, researchers must also include what specific toxicological effect or mechanism is being predicted by the given IST model, as well as its version number, type of methodology, training set size and content.

Since many IST models often exhibit a limited applicability domain, which refers to the ability of these models to only make predictions that apply for a specific set of chemicals, this domain must be explicitly discussed before its use for any new chemical. To further increase the reliability of any IST prediction, it is recommended that researchers combine additional independent or complementary IST models in their review.

Raunio, H. (2011). In Silico Toxicology Non-Testing Methods. Frontiers of Pharmacology 2; 33. DOI: 10.3389/fphar.2011.00033.

Myatt, G. J., Ahlberg, E., Akahori, Y., Allen, D., Amberg, A., et al. (2018). In silico toxicology protocols. Regulatory Toxicology and Pharmacology 96; 1-17. DOI: 10.1016/j.yrtph.2018.04.014.

Tichy, M., & Rucki, M. (2009). Validation of QSAR models for legislative purposes. Interdisciplinary Toxicology 2(3); 184-186. DOI: 10.2478/v10102-009-0014-2.

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Immunology

THSTI to hold basic course on Immunology – BSI bureau

January 30, 2020 medical

Faridabad-based Translational Health Science and Technology Institute will be conducting the third edition of its basic course in Immunology from March 16 to 18.

Dr. Shiv Pillai, Professor, Harvard Medical School, Boston along with Dr. Dipankar Nandi from the Department of Biochemistry, Indian Institute of Science, Bengaluru will be covering the various topics of this domain.

The target audience for this course are Masters and PhD students, research associates and post-doctoral fellows, early career investigators. However, the course is open to other investigators also who would like to update on the knowledge of Immunology.

The last years course was attended by more than 250 participants comprising faculty members, research fellows and PhD students from institutes across the country. Researchers at Banaras Hindu University, AIIMS Delhi, PGIMER Chandigarh, SRM Sonipat, Tezpur University and others could attend by joining a live streaming session.

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THSTI to hold basic course on Immunology - BSI bureau

Immunology

Immunologist Wendy Havran Dies – The Scientist

January 30, 2020 medical

Immunologist Wendy Havran, who had been researching the role of gamma-delta T cells in wound healing at the Scripps Research Institute since 1991, died from complications following a heart attack on January 20, according to a Scripps statement. She was 64.

The entire Scripps Research community is stunned and saddened by this tragic loss, Scripps colleague Jamie Williamson says in the statement. Wendy not only made significant contributions to the field of immunology and wound healing, but she inspired countless Scripps Research graduate students and postdocs through her enthusiastic mentorship spanning nearly three decades.

Havran was born on September 1, 1955, in Houston, Texas. Her father was an engineer while her mother was an elementary teacher.

She began her undergraduate degree at Duke University in 1973 with the initial desire to practice medicine. She began to stray from that path during her sophomore year when she started research under hematologist Gerald Logue. While working as a lab technician after graduation in 1977, she met thenDuke professor John Cambier, who introduced her to immunology. She instantly knew how she wanted to spend her career. It just clicked, and there was no going back, she told The Scientist in a 2019 profile. I wanted to understand how the immune system worked.

She pursued her doctorate at the University of Chicago, working in a T cell immunology lab. She became well-versed in creating monoclonal antibodies, as the lab was the first to be able to isolate and clone T cells capable of surviving and multiplying in culture.

Defending her thesis after four years in the program, Havran moved on to the lab of James Allison at the University of California, Berkeley, to work on gamma-delta T cells, a subgroup of unconventional T cells with gamma and delta T cell receptor chains, which were still relatively novel at the time. One notable accomplishment during this period was a paper published in 1990, showing for the first time that while gamma-delta T cells are scarce in areas such as the spleen and lymph nodes, they abound in epithelial tissue that makes up skin and intestines.

Dermatologists were convinced that there were no T cells in the skin, so this finding was very unexpected, Havran told The Scientist. These cells were unique because T cells typically each express a unique T-cell receptor that recognizes a unique antigen, but these cells all expressed the same T-cell receptor, so they were basically clones.

When it was time for Havran to establish her own lab, she continued her gamma-delta T cell research at Scripps. Early on, she found evidence that these cells contribute to wound healing. Later studies would find that they also help with tissue repair in the intestines. The last paper she published appeared in Nature Immunology and explained how gamma-delta T cells and immunoglobulins work in concert to suppress tumors by healing damaged epithelial tissue.

In addition to being dedicated to the work in her lab, Havran was passionate about mentoring up-and-coming scientists, and she was awarded the Scripps Research Outstanding Mentor Award in 2018. During her acceptance speech, she claimed that mentoring is one of the best parts of her job.

Havran is survived by her father, two sisters, three nieces, and two nephews.

Lisa Winter is the social media editor forThe Scientist. Email her at lwinter@the-scientist.com or follow her on Twitter @Lisa831.

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Immunology

Prescient Intelligence & Insight Announces Recent Appointments to the Senior Team – BioSpace

January 30, 2020 medical

LONDON, Jan. 29, 2020 /PRNewswire/ --Prescient, a biopharma product and portfolio strategy partner, announces the recent appointment of three new senior members to its Intelligence & Insight business: Jeanne Penn, Ben Kebble and Dr. Mladen Tomich. They join the existing Intelligence & Insight team, shaping the competitive strategy of Prescient's clients through enhanced decision support.

Jeanne Penn joins Prescient after spending more than 25 years providing strategic insight and planning support to the biopharmaceutical industry. Since completing her MSc, Jeanne has held leadership roles at various companies, including EMD Serono and Genzyme. She brings a depth of biopharma experience in brand and strategic planning, indication prioritization, competitive intelligence, workshop design and facilitation and integration of multiple external perspectives to inform decision making. At Prescient, Jeanne will leverage her expertise in rare diseases, multiple sclerosis, immunology, inflammatory diseases and fertility to grow and develop client relationships and lead client engagements.

Ben Kebble joins Prescient after spending more than 15 years at Genzyme, MedImmune/AstraZeneca, Cancer Research UK and several biotech companies, where his responsibilities have included leading a global competitive intelligence function, running drug discovery projects, alliance management and business development. Ben has completed a BSc in animal biology, an MBA and postgraduate courses in project management. At Prescient, Ben will leverage his expertise in oncology and his broader experience in respiratory disease, immunological and infectious diseases and emerging therapeutic technologies to lead multiple client engagements in both the R&D and commercial settings.

Dr. Mladen Tomich joins Prescient after spending more than 10 years in drug discovery, real-world data analysis and pharmaceutical market intelligence. Since completing his PhD in microbiology, Mladen has held research and commercial roles at various companies, including Merck & Co. and MedImmune/AstraZeneca, where he led projects focused on the discovery of novel anti-infectives for the treatment and prevention of serious bacterial infections. He brings a depth of functional and therapeutic experience and will lead client engagements in immunology, infectious diseases, vaccines and rare diseases.

"Our clients need a specialist partner who has the disease area, functional and market expertise required to develop business-relevant, actionable and impactful insight from data and intelligence," said Dr. Rakesh Verma, Prescient's EMEA and APAC President. "Jeanne, Ben and Mladen bring the deep subject matter expertise and industry knowledge that is critical to our clients' businesses."

Biographies and contact information for the Prescient Intelligence & Insight team can be found on http://www.PrescientHG.com.

About Prescient

At Prescient, science is at the core of everything we do. We are a biopharma product and portfolio strategy partner that specializes in turning the science of molecules into optimal patient outcomes and client value. Across therapeutic areas, we help develop winning strategies. When companies partner with us, a molecule in their hands has greater potential for success than the same science in the hands of their competitors.

Prescient Intelligence & Insight, a Prescient Healthcare Group business, offers best-in-class biopharmaceutical intelligence by providing impactful insight and decision support to product and portfolio teams from early clinical development through to loss of exclusivity.

Prescient has been a portfolio company of Baird Capital since 2017. For more information, please visit: http://www.PrescientHG.com.

Contact:Christina Maffei+1 908 342 3556232815@email4pr.com

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Immunology

Study reveals why more than a week of keto may not be beneficial – News-Press Now

January 30, 2020 medical

If the start of the new year led you to go on the ketogenic diet in an effort to lose weight, a new study suggests you may have been on it a little too long.

Researchers at Yale University have conducted a mice study to review the effects of the keto diet. They discovered that beyond a week, the benefits begin to cease.

The study was recently published in Nature Metabolism and results indicate that over a limited time period, consuming a high-fat, low-carb diet can possibly offer health benefits to humans, Yale News reported. They include lowering the risk of diabetes and inflammation. The diets positive effects are related to immune cells called gamma delta T-cells, immune cells that protect the tissue and lower the risk of diabetes and inflammation. However, the same cells are also tied to negative effects of keto.

Vishwa Deep Dixit, Ph.D., lead author of the study who is a a professor of comparative medicine and immunology at the Yale School of Medicine, said keto tricks the body into burning fat. The body acts as if its in starvation mode when the low consumption of carbohydrates causes glucose levels to drop. Despite the body not actually being in starvation mode, it begins burning fat instead of carbohydrates. That leads to the release of ketone bodies, which are an alternative source of fuel. As ketone bodies burn in the body, gamma delta T-cells expand throughout.

Dixit said this process improves metabolism and reduces diabetes risk and inflammation. He said mice showed decreased blood sugar levels and inflammation after a week on keto.

However, when the body acts as if its in starvation mode, researchers found fat gets stored in the body at the same time that fat breakdown occurs. As mice continue the high-fat diet, Dixit said they start to store more fat than they can burn and obesity and diabetes begins to develop.

They lose the protective gamma delta T-cells in the fat, Dixit said.

Our findings highlight the interplay between metabolism and the immune system, and how it coordinates maintenance of healthy tissue function, said comparative medicine postdoctoral fellow Emily Goldberg, who discovered that the keto diet expands gamma-delta T cells in mice.

Despite the findings of the mice trial, however, Dixit said long-term human clinical trials are needed.

Before such a diet can be prescribed, a large clinical trial in controlled conditions is necessary to understand the mechanism behind metabolic and immunological benefits or any potential harm to individuals who are overweight and pre-diabetic, Dixit said.

The results come after Dr. Donald Hensrud of the Mayo Clinic voiced opposition to the diet. Hensrund, author of The Mayo Clinic Diet Book, said the keto is not the magic formula people believe it is.

People want to believe, he said. They want an easy way out. They want the magic panacea.

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Immunology

Lilly and Incyte Announce Positive Top-Line Results from the North American (BREEZE-AD5) Phase 3 Study of Oral Selective JAK Inhibitor Baricitinib in…

January 30, 2020 medical

INDIANAPOLIS, Jan. 30, 2020 /PRNewswire/ -- Eli Lilly and Company (NYSE: LLY) and Incyte (NASDAQ: INCY) announced today that baricitinib met the primary endpoint in BREEZE-AD5, an investigational Phase 3, randomized, placebo-controlled study evaluating the safety and efficacy of baricitinib for the treatment of adult patients with moderate to severe atopic dermatitis (AD). The primary endpoint was defined by the proportion of patients achieving at least a 75% or greater change from baseline in their Eczema Area and Severity Index (EASI) at Week 16.

"Today's results, together with the previously reported positive top-line results from our Phase 3 trials, reinforce our commitment to pursue the first oral JAK inhibitor treatment in the U.S. for individuals living with the chronic and often relapsing skin condition that is AD," said Lotus Mallbris, M.D., Ph.D., vice president of immunology development at Lilly.

BREEZE-AD5 is a multicenter, double-blind, randomized, placebo-controlled study designed for and conducted in North America, evaluating the efficacy and safety of the 1-mg and 2-mg doses of baricitinib monotherapy for the treatment of adult patients with moderate to severe AD. In this study, the 2-mg dose of baricitinib met the primary endpoint as defined by the proportion of participants achieving EASI75 at Week 16, and key secondary endpoints including another measure of skin inflammation defined by clear or almost clear skin and at least 2 points improvement on the validated Investigator's Global Assessment for AD (vIGA 0 or 1 at Week 16), and reduced itch severity.

Placebo (n=147)

Baricitinib 1-mg (n=147)

Baricitinib 2-mg (n=146)

EASI75 at Week 16, n (%)

12 (8.2)

19 (12.9)

43 (29.5)***

vIGAa of 0 or 1 at Week 16, n (%)

8 (5.4)

19 (12.9)*

35 (24.0)***

4-point improvement in Itch NRS atWeek 16, n (%)

7 (5.7)

21 (15.9)*

33 (25.2)***

P n.s. * P 0.05, and *** P0.001 for baricitinib compared to placebo by analysis unadjusted for multiplicity. Non-responder imputation upon rescue with Topical corticosteroid (TCS).

avIGA = validated Investigator's Global Assessment.

The safety profile in BREEZE-AD5 was consistent with the known safety findings of baricitinib in AD. The most common treatment-emergent adverse events (TEAEs) included upper respiratory tract infections, nasopharyngitis, and diarrhea. No venous thromboembolic events (VTEs) or deaths were reported in the trial.

"The results show the potential that baricitinib could offer as an additional treatment option to patients where there are otherwise limited choices," said Eric Simpson, MD, MCR, Professor of Dermatology and Director of Clinical Research at Oregon Health & Science University in Portland, and global Principal Investigator for the BREEZE-AD5 clinical development program.

Lilly recently submitted baricitinib for regulatory review in Europe as a treatment for patients with moderate to severe AD and plans to submit for approval in the U.S. and Japan in 2020. The full results from the BREEZE-AD5 study will be disclosed at future scientific venues and in peer-reviewed journals.

Baricitinib is approved for the treatment of adults with moderately to severely active rheumatoid arthritis (RA) in more than 60 countries, including the U.S., member states of the EU and Japan, and is marketed as OLUMIANT.

Indication and Usage for OLUMIANT (baricitinib) tablets (in the United States) for RA patientsOLUMIANT (baricitinib) 2-mg is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more tumor necrosis factor (TNF) antagonist therapies. Limitation of Use: Use of OLUMIANT in combination with other JAK inhibitors, biologic disease-modifying antirheumatic drugs (DMARDs), or with potent immunosuppressants such as azathioprine and cyclosporine is not recommended.

IMPORTANT SAFETY INFORMATION FOR OLUMIANT (baricitinib) TABLETS

WARNING: SERIOUS INFECTIONS, MALIGNANCY, AND THROMBOSIS

SERIOUS INFECTIONS: Patients treated with Olumiant are at risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. If a serious infection develops, interrupt Olumiant until the infection is controlled. Reported infections include:

Carefully consider the risks and benefits of Olumiant prior to initiating therapy in patients with chronic or recurrent infection.

Closely monitor patients for the development of signs and symptoms of infection during and after treatment with Olumiant including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy.

MALIGNANCIES: Lymphoma and other malignancies have been observed in patients treated with Olumiant.

THROMBOSIS: Thrombosis, including deep venous thrombosis (DVT) and pulmonary embolism (PE), has been observed at an increased incidence in patients treated with Olumiant compared to placebo. In addition, there were cases of arterial thrombosis. Many of these adverse events were serious and some resulted in death. Patients with symptoms of thrombosis should be promptly evaluated.

WARNINGS AND PRECAUTIONS

SERIOUS INFECTIONS: The most common serious infections reported with Olumiant included pneumonia, herpes zoster and urinary tract infection. Among opportunistic infections, tuberculosis, multidermatomal herpes zoster, esophageal candidiasis, pneumocystosis, acute histoplasmosis, cryptococcosis, cytomegalovirus and BK virus were reported with Olumiant. Some patients have presented with disseminated rather than local disease and were often taking concomitant immunosuppressants such as methotrexate or corticosteroids. Avoid Olumiant in patients with an active, serious infection, including localized infections. Consider the risks and benefits of treatment prior to initiating Olumiant in patients:

Closely monitor patients for infections during and after Olumiant treatment. Interrupt Olumiant if a patient develops a serious infection, an opportunistic infection, or sepsis. Do not resume Olumiant until the infection is controlled.

Tuberculosis Before initiating Olumiant evaluate and test patients for latent or active infection and treat patients with latent TB with standard antimycobacterial therapy. Olumiant should not be given to patients with active TB. Consider anti-TB therapy prior to initiating Olumiant in patients with a history of latent or active TB in whom an adequate course of treatment cannot be confirmed, and for patients with a negative test for latent TB but who have risk factors for TB infection. Monitor patients for TB during Olumiant treatment.

Viral Reactivation Viral reactivation, including cases of herpes virus reactivation (e.g., herpes zoster), were reported in clinical studies with Olumiant. If a patient develops herpes zoster, interrupt Olumiant treatment until the episode resolves.

The impact of Olumiant on chronic viral hepatitis reactivation is unknown. Screen for viral hepatitis in accordance with clinical guidelines before initiating Olumiant.

MALIGNANCY AND LYMPHOPROLIFERATIVE DISORDERS: Malignancies were observed in Olumiant clinical studies. Consider the risks and benefits of Olumiant prior to initiating therapy in patients with a known malignancy other than a successfully treated non-melanoma skin cancer (NMSC) or when considering continuing Olumiant in patients who develop a malignancy. NMSCs were reported in patients treated with Olumiant. Periodic skin examination is recommended for patients who are at increased risk for skin cancer.

THROMBOSIS: Thrombosis, including DVT and PE, has been observed at an increased incidence in Olumiant-treated patients compared to placebo. In addition, arterial thrombosis events in the extremities have been reported in clinical studies with Olumiant. Many of these adverse events were serious and some resulted in death. There was no clear relationship between platelet count elevations and thrombotic events. Use Olumiant with caution in patients who may be at increased risk of thrombosis. If clinical features of DVT/PE or arterial thrombosis occur, evaluate patients promptly and treat appropriately.

GASTROINTESTINAL PERFORATIONS: Gastrointestinal perforations have been reported in Olumiant clinical studies, although the role of JAK inhibition in these events is not known. Use Olumiant with caution in patients who may be at increased risk for gastrointestinal perforation (e.g., patients with a history of diverticulitis). Promptly evaluate patients who present with new onset abdominal symptoms for early identification of gastrointestinal perforation.

LABORATORY ABNORMALITIES:Neutropenia Olumiant treatment was associated with an increased incidence of neutropenia (absolute neutrophil count [ANC] <1000 cells/mm3) compared to placebo. Avoid initiation or interrupt Olumiant treatment in patients with an ANC <1000 cells/mm3. Evaluate at baseline and thereafter according to routine patient management.

Lymphopenia Absolute lymphocyte count (ALC) <500 cells/mm3 were reported in Olumiant clinical trials. Lymphocyte counts less than the lower limit of normal were associated with infection in patients treated with Olumiant, but not placebo. Avoid initiation or interrupt Olumiant treatment in patients with an ALC <500 cells/mm3. Evaluate at baseline and thereafter according to routine patient management.

Anemia Decreases in hemoglobin levels to <8 g/dL were reported in Olumiant clinical trials. Avoid initiation or interrupt Olumiant treatment in patients with hemoglobin <8 g/dL. Evaluate at baseline and thereafter according to routine patient management.

Liver Enzyme Elevations Olumiant treatment was associated with increased incidence of liver enzyme elevation compared to placebo. Increases to 5x and 10x upper limit of normal were observed for both ALT and AST in patients in Olumiant clinical trials.

Evaluate at baseline and thereafter according to routine patient management. Promptly investigate the cause of liver enzyme elevation to identify potential cases of drug-induced liver injury. If increases in ALT or AST are observed and drug-induced liver injury is suspected, interrupt Olumiant until this diagnosis is excluded.

Lipid Elevations Treatment with Olumiant was associated with increases in lipid parameters, including total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol. Assess lipid parameters approximately 12 weeks following Olumiant initiation. Manage patients according to clinical guidelines for the management of hyperlipidemia.

VACCINATIONS: Avoid use of live vaccines with Olumiant. Update immunizations in agreement with current immunization guidelines prior to initiating Olumiant therapy.

ADVERSE REACTIONSAdverse reactions (1%) include: upper respiratory tract infections (16.3%, 14.7%, 11.7%), nausea (2.7%, 2.8%, 1.6%), herpes simplex (0.8%, 1.8%, 0.7%) and herpes zoster (1.0%, 1.4%, 0.4%) for Olumiant 2 mg, baricitinib 4 mg, and placebo, respectively.

USE IN SPECIFIC POPULATIONSPREGNANCY AND LACTATION: No information is available to support the use of Olumiant in pregnancy or lactation. Advise women not to breastfeed during treatment with Olumiant.HEPATIC AND RENAL IMPAIRMENT: Olumiant is not recommended in patients with severe hepatic impairment or in patients with severe renal impairment.

Please click to access full Prescribing Information, including Boxed Warning about Serious infections, Malignancies, and Thrombosis, and Medication Guide.

BA HCP ISI 11OCT2019

About BREEZE-AD5BREEZE-AD5, a multicenter, double-blind, randomized, placebo-controlled, Phase 3 study in adult patients with moderate to severe atopic dermatitis (AD). BREEZE-AD5, designed for and conducted in North America, evaluated the efficacy and safety of the 1-mg and 2-mg doses of baricitinib monotherapy for the treatment of adult patients with moderate to severe AD. The primary endpoint was defined by the proportion of participants achieving Eczema Area and Severity Index 75 (EASI75) at Week 16. BREEZE-AD5 completes the read out from the BREEZE development program, following the recent topline results from BREEZE-AD4. BREEZE-AD1, -AD2 and -AD7 results were disclosed in 2019.

About OLUMIANTOLUMIANT is a once-daily, oral JAK inhibitor approved in the U.S. for the treatment of adults with moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more TNF inhibitor therapies, and approved outside of the U.S. for patients with moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more DMARDs.1 There are four known JAK enzymes: JAK1, JAK2, JAK3 and TYK2. JAK-dependent cytokines have been implicated in the pathogenesis of a number of inflammatory and autoimmune diseases.2 OLUMIANT has greater inhibitory potency at JAK1, JAK2 and TYK2 relative to JAK3; however, the relevance of inhibition of specific JAK enzymes to therapeutic effectiveness is not currently known.1 OLUMIANT is approved in more than 60 countries.

About Atopic DermatitisAtopic dermatitis (AD), or atopic eczema, is a chronic, relapsing skin disease characterized by intense itching, dry skin and inflammation that can be present on any part of the body.3 AD is a heterogeneous disease both clinically and biologically, but may be characterized by chronic baseline symptoms of itch, redness and skin damage that are often punctuated with episodic, sometimes unpredictable, flares or exacerbations.4,5 AD affects approximately 1-3% of adults worldwide.6

Moderate to severe AD is characterized by intense itching, resulting in visibly damaged skin.7 Like other chronic inflammatory diseases, AD is immune-mediated and involves a complex interplay of immune cells and inflammatory cytokines.8

About Lilly in DermatologyBy following the science through unchartered territory, we continue Lilly's legacy of delivering innovative medicines that address unmet needs and have significant impacts on people's lives around the world. Skin-related diseases are more than skin deep. We understand the devastating impact this can have on people's lives. At Lilly, we are relentlessly pursuing a robust dermatology pipeline to provide innovative, patient-centered solutions so patients with skin-related diseases can aspire to live life without limitations.

About Eli Lilly and Company Lilly is a global healthcare leader that unites caring with discovery to create medicines that make life better for people around the world. We were founded more than a century ago by a man committed to creating high-quality medicines that meet real needs, and today we remain true to that mission in all our work. Across the globe, Lilly employees work to discover and bring life-changing medicines to those who need them, improve the understanding and management of disease, and give back to communities through philanthropy and volunteerism. To learn more about Lilly, please visit us at http://www.lilly.com and newsroom.lilly.com/social-channels. P-LLY

About Incyte Incyte is a Wilmington, Delaware-based, global biopharmaceutical company focused on finding solutions for serious unmet medical needs through the discovery, development and commercialization of proprietary therapeutics. For additional information on Incyte, please visit Incyte.com and follow @Incyte.

This press release also contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995) about OLUMIANT (baricitinib) as a treatment for patients with rheumatoid arthritis and as a potential treatment for patients with moderate- to severe atopic dermatitis, and reflects Lilly's and Incyte's current beliefs. However, as with any pharmaceutical product, there are substantial risks and uncertainties in the process of development and commercialization. Among other things, there can be no guarantee that OLUMIANT will receive additional regulatory approvals or be commercially successful. For further discussion of these and other risks and uncertainties, see Lilly's and Incyte's most recent respective Form 10-K and Form 10-Q filings with the United States Securities and Exchange Commission. Except as required by law, Lilly and Incyte undertake no duty to update forward-looking statements to reflect events after the date of this release.

1 Olumiant Prescribing Information, 2019.2 Walker JG and Smith MD. J Rheumatol. 2005;32;1650-1653.3 Zuberbier T, Orlow SJ, Paller AS, et al. Patient perspectives on the management of atopic dermatitis. The Journal of Allergy and Clinical Immunology. 2006;118: 226-32.4 Thijs JL, Strickland I, Bruijnzeel-Koomen C, et. al. Moving toward endotypes in atopic dermatitis: identification of patient clusters based on serum biomarker analysis. The Journal of Allergy and Clinical Immunology. 2017.5 Langan SM, Thomas KS, Williams HC. What is meant by "flare" in atopic dermatitis? A systematic review and proposal. Arch Dermatol. 2006;142:1190-1196.6 Nutten S. Atopic dermatitis: global epidemiology and risk factors. Annals of Nutrition and Metabolism. 2015;66(suppl 1): 8-16.7 Yosipovitch G, Papoiu AD. What causes itch in atopic dermatitis? Current Allergy and Asthma Reports. 2008;8:306-311.8 Weidinger, S, Novak, N. Atopic dermatitis. The Lancet Volume 387. 2016;10023:1109-1122.

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Lilly and Incyte Announce Positive Top-Line Results from the North American (BREEZE-AD5) Phase 3 Study of Oral Selective JAK Inhibitor Baricitinib in...