Category Archives: Immunology

Immunology

Improving CAR-T therapy for cancer by regulating 2 proteins – FierceBiotech

Chimeric antigen receptor T-cell (CAR-T) therapies that are made from a patients own T cells haveproven effective in blood cancers, and they are showingpromise for treating solid tumors, too. But scientists are still looking for ways to fine-tune this form of immunotherapy.

Now, scientists at the University of North Carolina (UNC) at Chapel Hill havefound new methods for either dialing up CAR-T cells cancer-killing effects when needed or dampening their activity to avoid severe side effects. The technique involvestwo proteins that are responsible for stimulating the cells. The team published the results in Cancer Cell.

In immunology, its always about balance; you don't want to have too much T-cell activation, and you don't want T-cell activation to be too low, the studys co-first author Peishun Shou, Ph.D., said in a statement. We wanted to keep the T-cell activation and tumor killing at a suitable or sustainable level.

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Shou worked in a team led by UNC Lineberger Comprehensive Cancer Centers Gianpietro Dotti, M.D. In 2018, Dottis team developed CARs that can target a protein called CSPG4, and they showed the treatment worked in mice with glioblastoma.

For the current study, the researchers zeroed in on two different types of CARs, whichare differentiated by the signals that activate them. CAR-T cells tumor-regression ability is first triggered by a signal called CD3-zeta, which is commonly used as the main CAR component to recognize markers on tumors. But the cellsalso require co-stimulatory moleculeseither CD28 or 4-1BB proteinin addition to CD3-zeta to further boosttheir activation.

The UNC team found that they could improvethe activityof T cellsthat areco-stimulated by 4-1BBby increasing the expression of a tyrosine kinase called LCK.

What we found is that the LCK molecule can bind to the CAR, enhancing the CAR-T cell activation and signaling transduction, which therefore will help CAR-T cells get a better tumor-killing effect, Shou said.

RELATED:Redesigned CAR-T eliminates dangerous cytokine release syndrome in lymphoma trial

Use of CAR-T therapy has been linked to a dangerous side effect called cytokine release syndrome, so scientists have also been working on methods to rein in CAR-T activitywhen necessary.

Shou and colleagues found such a safety switch in CAR-T cells that are co-stimulated by CD28. They showed that an enzyme called SHP1 attenuates T-cell activity. They discovered that adding a drug named AP21967which is an analog to Pfizers immunosuppressive drug Sirolimus (rapamycin)can pull SHP1 to the CAR to reduce cytokine release. Whats more, the transient recruitment of SHP1 didnt kill the CAR-T cells or impair their antitumor effects, the researchers demonstrated in a mouse model.

Many other efforts have been made to reduce CAR-Ts toxic side effects. For example, a research team led by the University of Southern California Norris Comprehensive Cancer Center developed a CAR variant called CD19-BBz(86) that didnt trigger any serious side effect in 25 lymphoma patients.

As for4-1BB, it's a target that has already attracted some interest among drug developers. Pfizer is developing utomilumab (PF-05082566), a 4-1BB agonist, to leverage the receptors T-cell stimulation effect. The drug is being paired with Pfizer and Merck KGaAs anti-PD-L1 immunotherapy Bavencio in a phase 2 study in solid tumors.

The UNC scientists want to use their findings on CD28 and 4-1BB to improve CAR-T treatments against blood cancers and to potentially make them viable for solid tumors.

Researchers in the CAR-T immunotherapy field now want to solve the solid tumor problem, Shou said. Solid tumors have an immunosuppressive microenvironment, so you need stronger CAR-T activation.

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Improving CAR-T therapy for cancer by regulating 2 proteins - FierceBiotech

Immunology

Coronavirus outbreak in US may depend on this: ‘We just don’t know yet’ says infectious disease doc – Home – WSFX

A top infectious disease doctor warned that the likelihood of preventing a U.S. outbreak of the coronavirus dependson whether the virusis transmitted by peoplewho are not exhibiting symptoms.And that information, he warned, is something that world health experts do not know yet.

You could be carrying it and not know so you wouldnt have the symptoms. Doesnt that make it extremely dangerous? Wall Street Journal columnist Mary Anastasia OGradyasked a panel of doctors on Fox NationsDeep Dive.

The Chinese Ministry of Health has said that they believe this is possible, that people can be spreading it before they show symptoms, said Dr. Stephen Morse, who is a professor of epidemiologyat the Columbia University Medical Center.

But thats why were doing a lot of screening at the airports based largely on geography, he continued. But once it spreads further, its going to be hard to be that targeted.

I agree that we have heard that from the Chinese, but we havent seen the evidence thats behind that, saidDr. Mark Mulligan, whois a senior professor in the NYU Langone Department of Medicine anddirector of both NYU Langone Vaccine Center and theDivision of Infectious Diseases and Immunology.

We do know you can have asymptomatic infection, he went on. There are reports of people that were shown to be infected but we dont know that those people can transmit.

The World Health Organization on Thursday declared the newcoronavirus outbreaka global emergency, as38 new deaths and 1,737 new infected cases have been reported in the last 24 hours.

In general, the transmission occurs when an ill person is coughing a lot. When youre sicker, you have more virus around. It may be that older people get more illness and transmit more. Younger people, less illness, maybe transmit less. But we dont know everything yet., Dr. Mulliganwarned.

Roughly 99 percent of all cases of the virus have appeared in China but it has spread to at least 18 countries.

The American officials are all saying, Dont panic, dont panic. But you can be carrying the disease without showing the symptoms, you have all this air travel going on, its already gotten out of China. How reasonable is it to think that were not going to have a serious outbreak here? asked OGrady.

I dont think we should panic, saidDr. Janette Nesheiwat,the medical director at CityMD,an urgent care practice in New York City. But we should remain on alert and be vigilant because it can take up to two weeks for symptoms to appear.

We know that the usual sort of shoe leather, public healthsteps of isolationof cases, contact tracing, quarantining of them works, notedMulligan. So I think if those things also work for this novel coronavirus, that we do have the opportunity to contain it.

However, Mulligan cautioned if it is shown that individuals can carry and transmit the virus without exhibiting symptoms that would be a troubling discovery.

We think that we have a real opportunity [to contain coronavirus], assuming there arent any curves like this thing about asymptomatic individuals transmitting. If that were true, that would change things, he concluded.

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Fox News Vandana Rambaran contributed to this report.

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Coronavirus outbreak in US may depend on this: 'We just don't know yet' says infectious disease doc - Home - WSFX

Immunology

This week: Coronavirus, vaping and drugs of abuse – WRVO Public Media

China is dealing with the outbreak of a respiratory illness caused by a new coronavirus. Thousands of people have been infected; some have died. And more cases are being diagnosed in people all over the world, including a relatively small number in the United States.

Providing perspective on this outbreak is Stephen Thomas, MD, a professor of medicine and microbiology and immunology at Upstate and its chief of infectious disease.

Also on "HealthLink on Air" this week, toxicologist Christine Stork from the Upstate New York Poison Center talks about vaping dangers and the most common drugs of abuse. Tune in this Sunday, February 2 at 6 a.m. and 9 p.m. for "HealthLink on Air."

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This week: Coronavirus, vaping and drugs of abuse - WRVO Public Media

Immunology

THSTI to hold basic course on Immunology – BSI bureau

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

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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Immunologist Wendy Havran Dies - The Scientist

Immunology

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

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

Immunology

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

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

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…

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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Company Codes: NASDAQ-NMS:INCY, NYSE:LLY

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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...

Immunology

Innate Immune Activation Behind Asthma Attacks from Common Cold – University of Michigan Health System News

While rhinoviruses, the culprit behind the so-called common cold, are generally harmless, for kids with asthma, colds often trigger asthma attacks. In fact, colds are the number one cause of asthma exacerbation in children and adults. Michigan Medicine researchers Marc Hershenson, M.D., division director of pediatric pulmonology at C.S. Mott Childrens hospital and Mingyuan Han, Ph.D. a postdoctoral fellow and their team are investigating why this is.

In a new paper in the journal Mucosal Immunology, they describe how the inflammasome, part of the immune response that turns on inflammation and other processes to fight pathogens like bacteria and viruses and other harmful substances, is activated by rhinoviruses in a mouse model. This activation sensitizes the airway in both normal mice and allergic mice. This finding points to the inflammasome as a possible target for treatment of cold-induced asthma attacks.

Paper cited:Inflammasome activation is required for human rhinovirus-induced airway inflammation in naive and allergen-sensitized mice, Mucosal Immunology. DOI: 10.1038/s41385-019-0172-2

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Innate Immune Activation Behind Asthma Attacks from Common Cold - University of Michigan Health System News

Immunology

Global Flow Cytometry Market Size is Projected to Reach USD 6.4 Billion by 2025 from USD 4.0 Billion in 2019, Growing at a CAGR of 8.3% -…

DUBLIN--(BUSINESS WIRE)--The "Flow Cytometry Market by Technology (Cell-based, Bead-based), Product (Analyzer, Sorter, Reagents, Consumables, Software), End user (Academia, Research Labs, Hospitals, Clinical Laboratories, Pharma-Biotech Cos), Application - Global Forecasts to 2025" report has been added to ResearchAndMarkets.com's offering.

The key factors driving the growth of this market include technological advancements in flow cytometers, the increasing adoption of flow cytometry in research and clinical trials, growing focus on immunology and immuno-oncology research, increasing incorporation of AI platforms in flow cytometry workflows and advancements in flow cytometry software, high incidence and prevalence of target diseases, and the availability of novel products.

The bead-based technology segment is expected to grow at the fastest rate during the forecast period.

By technology, the flow cytometry market is classified into cell-based and bead-based. In 2019, the cell-based flow cytometry segment accounted for the largest share of the market. However, the bead-based flow cytometry segment is expected to grow at the highest CAGR during the forecast period. The growth of the bead-based flow cytometry segment can be attributed to the procedural advantages offered by this technology over other cell-based technology, such as the capacity to detect multiple analytes (also known as multiplexing), high reproducibility, stability, and speed.

The reagents and consumables segment is expected to grow at the highest CAGR during 2019-2025.

On the basis of product and service, the flow cytometry market is categorized into reagents and consumables, instruments, services, software, and accessories. The reagents and consumables segment is expected to witness the highest growth during the forecast period due to the development and commercialization of high-quality application-specific reagents and assays and continuous requirement of flow cytometry reagents by end-users (due to the increasing number of flow cytometry-based research activities).

The Asia Pacific to witness the highest growth during the forecast period (2019-2025)

North America is expected to hold the largest share of the global flow cytometry market in 2019 followed by Europe. However, the Asia Pacific is expected to grow at the fastest rate during the forecast period. The increasing participation of China, India, Japan, Australia, and South Korea in flow cytometry-based research; expansion of research infrastructure in the region; and public-private finding aimed towards boosting advance research practices are the key factors responsible for the growth of this market in the Asia Pacific.

Key Benefits of Buying the Report

This report focuses on various levels of analysis-industry trends, market shares of top players, and company profiles, which together form basic views and analyze the competitive landscape, emerging segments of the flow cytometry market, and high-growth regions and their drivers, restraints, challenges, and opportunities. The report will help both established firms as well as new entrants/smaller firms to gauge the pulse of the market and garner greater market shares.

Key Topics Covered:

1 Introduction

1.1 Objectives of the Study

1.2 Market Definition

1.3 Study Scope

1.4 Currency Used for the Study

1.5 Stakeholders

2 Research Methodology

2.1 Research Data

2.2 Market Estimation Methodology

2.3 Data Triangulation Methodology

2.4 Research Assumptions

2.5 Research Limitations

3 Executive Summary

4 Premium Insights

4.1 Flow Cytometry: Market Overview

4.2 Flow Cytometry Products & Services Market, 2019 vs. 2025

4.3 Market, By Application, 2019 vs. 2025

4.4 Market, By End User, 2019 vs. 2025

4.5 Geographical Snapshot of the Market

5 Market Overview

5.1 Introduction

5.2 Market Dynamics

5.2.1 Drivers

5.2.2 Restraints

5.2.3 Opportunities

5.2.4 Challenges

5.3 Regulatory Challenges

5.4 US Reimbursement Scenario

6 Flow Cytometry Market, By Technology

6.1 Introduction

6.2 Cell-Based Flow Cytometry

6.3 Bead-Based Flow Cytometry

7 Flow Cytometry Market, By Product & Service

7.1 Introduction

7.2 Reagents & Consumables

7.3 Flow Cytometry Instruments

7.4 Services

7.5 Software

7.6 Accessories

8 Flow Cytometry Market, By Application

8.1 Introduction

8.2 Research Applications

8.3 Clinical Applications

8.4 Industrial Applications

9 Flow Cytometry Market, By End User

9.1 Introduction

9.2 Academic & Research Institutes

9.3 Hospitals & Clinical Testing Laboratories

9.4 Pharmaceutical & Biotechnology Companies

10 Flow Cytometry Market, By Region

10.1 Introduction

10.2 North America

10.3 Europe

10.4 Asia Pacific

10.5 Latin America

10.6 Middle East and Africa

11 Competitive Landscape

11.1 Introduction

11.2 Competitive Leadership Mapping

11.3 Competitive Leadership Mapping: Major Market Players (2018)

11.4 Competitive Leadership Mapping: Emerging Companies/SMEs/Start-Ups (2018)

11.5 Competitive Scenario (2016-2019)

11.6 Global Market Share Analysis, Top Three Market Players (2018)

12 Company Profiles

12.1 Becton, Dickinson and Company

12.2 Beckman Coulter

12.3 Thermo Fisher Scientific

12.4 Merck KGaA

12.5 Luminex Corporation

12.6 Agilent Technologies

12.7 Sony Biotechnology

12.8 Bio-Rad Laboratories

12.9 Miltenyi Biotec

12.10 Enzo Life Sciences, Inc.

12.11 Sysmex Partec

12.12 Biomrieux SA

12.13 Cytonome/St, LLC

12.14 Stratedigm, Inc.

12.15 Apogee Flow Systems

12.16 Cytek Biosciences, Inc.

12.17 Other Companies

12.17.1 Sartorius AG

12.17.2 Union Biometrica, Inc.

12.17.3 Nanocellect Biomedical, Inc.

12.17.4 On-Chip Biotechnologies Co., Ltd.

For more information about this report visit https://www.researchandmarkets.com/r/8ln964

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Global Flow Cytometry Market Size is Projected to Reach USD 6.4 Billion by 2025 from USD 4.0 Billion in 2019, Growing at a CAGR of 8.3% -...