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Cell Biology

FDA Approves Elixirgen Therapeutics IND Application for Therapy for Telomere Biology Disorders with Bone Marrow Failure – Herald-Mail Media

BALTIMORE, June 4, 2020 /PRNewswire/ -- Elixirgen Therapeutics, Inc., a Baltimore-based biotechnology company focused on the discovery, development, and commercialization of therapies for genetic diseases and vaccines, received confirmation from the U.S. Food and Drug Administration (FDA) that its Investigational New Drug (IND) application for its lead candidate, EXG34217, was approved on May 23, 2020. EXG34217 is an autologous cell therapy for telomere biology disorders with bone marrow failure.

The FDA's approval allows Elixirgen Therapeutics to proceed with its planned Phase I/II, open label, single center clinical trial to assess the safety and tolerability of EXG34217 at Cincinnati Children's Hospital Medical Center (ClinicalTrials.gov Identifier: NCT04211714). This program's treatment paradigm uses Elixirgen Therapeutics' proprietary ZSCAN4 technology to extend the telomeres of the hematopoietic stem cells of the patients.

About Elixirgen Therapeutics, Inc.Elixirgen Therapeutics, Inc. is a Baltimore-based biotechnology company co-founded by Akihiro Ko and Minoru Ko, MD, PhD, which is focused on curing humanity's ailments through innovations in stem cell biology.The company's experienced team of researchers has a wide variety of specialties, enabling it to use both basic and translational research approaches to developing therapies for genetic diseases and vaccines. For more information visit https://ElixirgenTherapeutics.com

Forward-Looking StatementsThis press release may contain "forward-looking" statements, including statements regarding the effectiveness of EXG34217 to treat telomere biology disorders with bone marrow failure and statements relating to the planned clinical trials of EXG34217. Actual results may differ materially from those set forth in this press release due to the risks and uncertainties inherent in drug research and development. In light of these and other uncertainties, the forward-looking statements included in this press release should not be regarded as a representation by Elixirgen Therapeutics that its plans and objectives regarding EXG34217 will be achieved. Any forward-looking statements in this press release speak only as of the date of this press release, and Elixirgen Therapeutics undertakes no obligation to update or revise the statementsin the future, even if new information becomes available.

Contact:Media RelationsElixirgen Therapeutics, Inc.(443) 869-5420Media@ElixirgenTherapeutics.com

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FDA Approves Elixirgen Therapeutics IND Application for Therapy for Telomere Biology Disorders with Bone Marrow Failure - Herald-Mail Media

Cell Biology

Relief Therapeutics and NeuroRx Expand Clinical Trial Evaluating RLF-100 in Critically Ill COVID-19 Patients with Respiratory Failure to Houston…

HOUSTON, June 11, 2020 (GLOBE NEWSWIRE) -- RELIEF THERAPEUTICS Holding AG (SIX:RLF) Relief and its U.S. partner, NeuroRx, Inc. today announced that Houston Methodist Hospital is participating in their Phase 2 clinical trial evaluating RLF-100 as a research intervention for critically ill patients with COVID-19 and respiratory failure. RLF-100 is a patented formulation of Aviptadil, (synthetic human vasoactive intestinal polypeptide or VIP), which targets alveolar type 2 cells in the lungs that are a major target of the SARS-CoV-2 virus. VIP is known from numerous animal models of lung injury and lung disease to inhibit inflammatory cytokines and to protect pulmonary epithelial cells that line the air sacs (alveolae) of the lungs.

The multicenter clinical trial will enroll patients with COVID-19 and respiratory failure in the hopes that RLF-100 can decrease mortality in this condition and help to improve the ability of the patients lungs to transfer oxygen to the body. Based on recent FDA guidance, the trial has been expanded to include patients treated with high flow nasal oxygen and noninvasive forms of ventilation, instead of only enrolling patients on mechanical ventilators.

The Principal Investigator at Houston Methodist Hospital is J. George Youssef, M.D., assistant professor of Critical Care Medicine & Pulmonology. Dr. Youssef was a co-investigator in the earlier study evaluating RLF-100 as a treatment for Acute Respiratory Distress (ARDS), a primary cause of COVID-19 related deaths, under the late Professor Sami Said, who discovered VIP in 1970 and treated the first patients.

We are encouraged by findings from the previous clinical trial of RLF-100 as a treatment for ARDS in patients with sepsis which showed seven out of eight patients on mechanical ventilation experienced substantial improvement and six ultimately left the hospital alive, Dr. Youssef said. If the early ARDS results can be replicated in critically ill COVID-19 patients with respiratory failure, this approach could present a significant advancement in the treatment of these patients.

Jonathan Javitt, M.D., MPH, CEO of NeuroRx, added, We at NeuroRx are enormously excited to have Dr. Youssef join our study, in light of his long involvement in the VIP story. While we can read about Dr. Saids breakthrough, Dr. Youssef witnessed it firsthand and participated in the early clinical care of patients. Its rare to have science come full circle in service of patients.

The trial is being led by NeuroRx, Inc., the US development partner of Relief Therapeutics, whose clinical operations are based in Radnor, PA. Patients are being treated under an FDA Investigational New Drug clearance, as part of the FDAs Corona Treatment Acceleration Program (CTAP). Details of the study are posted on clinicaltrials.gov NCT04311697.

About VIP in Lung Injury

Vasoactive Intestinal Polypeptide (VIP) was first discovered by the late Dr. Sami Said in 1970. Although first identified in the intestinal tract, VIP is now known to be produced throughout the body and to be primarily concentrated in the lungs. VIP has been shown in more than 100 peer-reviewed studies to have potent anti-inflammatory/anti-cytokine activity in animal models of respiratory distress, acute lung injury and inflammation. Most importantly, 70% of the VIP in the body is bound to a rare cell in the lung, the Alveolar Type II cell, that is critical to transmission of oxygen to the body. VIP has a 20-year history of safe use in humans in multiple human trials for sarcoidosis, pulmonary fibrosis, asthma/allergy and pulmonary hypertension.

COVID-19-related deaths are primarily caused by Respiratory Failure. Before an acute deterioration in lung function, there is evidence of early viral infection of the alveolar type 2 cells. These cells are known to have angiotensin converting enzyme 2 (ACE2) receptors at high levels, which serve as the route of entry for the SARS-CoV-2 into the cells. Coronaviruses are shown to replicate in alveolar type 2 cells, but not in the more numerous type 1 cells.1,2Since type 2 alveolar cells have high concentrations of VIP receptors on their cell surfaces, the research hypothesis is VIP administration could specifically protect these cells from injury.

Injury to the type 2 alveolar cells is an increasingly plausible mechanism of COVID-19 disease progression.3 These specialized cells replenish the more common type 1 cells that line the lungs. More importantly, type 2 cells manufacture surfactant that coats the lung and are essential for oxygen exchange. Other than RLF-100, no currently proposed treatments for COVID-19 specifically target these vulnerable type 2 cells.

About RLF-100

RLF-100 (Aviptadil) is a patented formulation of Vasoactive Intestinal Polypeptide (VIP)that was developed based on Dr. Saids original work and was originally approved for human trials by the FDA in 2001 and the European Medicines Agency in 2005. VIP is known to be highly concentrated in the lungs and to inhibit a variety of inflammatory cytokines. Reliefs predecessor company, Mondo Biotech, was awarded Orphan Drug Designation in 2001 by the U.S. FDA for Aviptadil in the treatment of Acute Respiratory Distress Syndrome and in 2005 for treatment of Pulmonary Arterial Hypertension. Mondo was awarded Orphan Drug Designation by the European Medicines Agency in 2006 for the treatment of acute lung injury and in 2007 for the treatment of sarcoidosis. Both the U.S. FDA and the EMEA have granted Investigational New Drug licenses for human trials of Aviptadil.

About RELIEF THERAPEUTICS Holding AG

The Relief group of companies focus primarily on clinical-stage projects based on molecules of natural origin (peptides and proteins) with a history of clinical testing and use in human patients or a strong scientific rationale. Currently, Relief is concentrating its efforts on developing new treatments for respiratory disease indications.

Relief Therapeutics holds orphan drug designations from the U.S. Food and Drug Administration and the European Union for the use of VIP to treat ARDS, pulmonary hypertension, and sarcoidosis. Relief Therapeutics also holds a U.S. patent4 for RLF-100 and proprietary manufacturing processes for its synthesis.

RELIEF THERAPEUTICS Holding AG is listed on the SIX Swiss Exchange under the symbol RLF.

About NeuroRx, Inc.

NeuroRx draws upon more than 100 years of collective drug development experience and is led by former senior executives of Johnson & Johnson, Eli Lilly, Pfizer, and AstraZeneca, PPD. In addition to its work on RLF-100, NeuroRx has been awarded Breakthrough Therapy Designation and a Special Protocol Agreement to develop NRX-101 for the treatment of suicidal bipolar depression and is currently in Phase 3 trials. Its Board of Directors and Advisors includes Hon. Sherry Glied, former Assistant Secretary, U.S. Dept. of Health and Human Services; Mr. Chaim Hurvitz, former President of the Teva International Group, Lt. Gen. HR McMaster, the 23rd National Security Advisor, Wayne Pines, former Associate Commissioner of the U.S. Food and Drug Administration, Judge Abraham Sofaer, and Daniel Troy, former Chief Counsel, U.S. Food and Drug Administration.

Disclaimer: This communication expressly or implicitly contains certain forward-looking statements concerning RELIEF THERAPEUTICS Holding AG, NeuroRx, Inc. and their businesses. Such statements involve certain known and unknown risks, uncertainties and other factors, which could cause the actual results, financial condition, performance or achievements of RELIEF THERAPEUTICS Holding AG and/or NeuroRx, Inc. to be materially different from any future results, performance or achievements expressed or implied by such forward-looking statements. RELIEF THERAPEUTICS Holding AG is providing this communication as of this date and does not undertake to update any forward-looking statements contained herein as a result of new information, future events or otherwise.

CORPORATE CONTACTS

Jonathan C. Javitt, M.D., MPHChief Executive OfficerNeuroRx, Inc.ceo@neurorxpharma.com

Yves Sagot, Ph.D.Relief Therapeutics Holding, SAyves.sagot@relieftherapeutics.com

MEDIA CONTACT

Gloria GasaaturaLifeSci Communicationsggasaatura@lifescicomms.com646-970-4688

1 US 8,178,489 Formulation for Aviptadil

2 Jonathan C. J. Perspective: The Potential Role of Vasoactive Intestinal Peptide in treating COVID-19 Authorea, DOI:10.22541/au.158940764.42332418

3 Mason R. J. (2020). Pathogenesis of COVID-19 from a cell biology perspective.The European respiratory journal,55(4), 2000607. https://doi.org/10.1183/13993003.00607-2020

4US 8,178,489 Formulation for Aviptadil

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Relief Therapeutics and NeuroRx Expand Clinical Trial Evaluating RLF-100 in Critically Ill COVID-19 Patients with Respiratory Failure to Houston...

Cell Biology

New study may help develop therapeutics for tongue cancer – India Education Diary

New Delhi: A team of researchers from IIT Madras, Cancer Institute, Sree Balaji Dental College and Hospital, Chennai, and Indian Institute of Science (IISc) Bengaluru have identified a specific microRNA (miRNAs) called miR-155 that is over-expressed in tongue cancer. MicroRNAs (miRNAs) are small Ribo Nucleic Acid. They are non-coding RNAs involved in the regulation of a variety of biological and pathological processes, including the formation and development of cancer. This finding is important in that molecular strategies can potentially be devised to manipulate miR-155 expression to develop therapeutics for tongue cancer.

The main function of miRNA is to silence the expression of the other genes. If the silence oncogenes then the cancer will be suppressed. On the other hand, if they suppress tumour suppressor gene, the cancer will progress. Accordingly, miRNA can act as oncogenes or tumour suppressor genes depending on what they act upon. There are only two therapeutic approaches that can be possible. If the miRNA has been shown to work as oncogenes, then one wants to inhibit; this is known as miRNA inhibition therapy. If the miRNA acts as tumour suppressor genes, then you want to introduce to the system so that tumour can be suppressed; such therapy is called miRNA replacement therapy, said, Prof. Karunagaran, Head, Department of Biotechnology, IIT Madras, while speaking with India Science Wire. miRNA manipulation is being combined with conventional cancer treatment methods such as chemotherapy, radiotherapy, and immunotherapy, and the study reported by collaborative team can enable such emerging therapeutics for cancer.

Elaborating about this research, Prof. Karunagaran said, miRNA is already known to be an oncogene in tongue cancer and has been found to play important roles in many cancers, in carcinogenesis (start of cancer), malignant transformation and metastasis the development of secondary cancer. The miRNAs associated with cancer are called Oncomirs.

Further, Prof. Karunagaran added, Many of the oncomirs affect cancer by suppressing the performance of tumour-suppressing agents that can prevent growth and spread of cancer cells, although some oncomirs are also involved in preventing tumour growth itself. It is, therefore, important to identify the types of miRNAs that are associated with both suppression and proliferation of cancer cells.

miRNAs affect cancer growth through inhibiting or enhancing the functions of certain proteins. For example, it has been shown that a type of protein called programmed cell death 4 (pdcd4) helps in stopping cancer cells from growing and spreading. Inhibition of this protein has been known to cause spread of oral, lung, breast, liver, brain and colon cancers.

The team has gone beyond showing the connection between miR-155 and pdcd4. They have also shown that knocking out miR-155 causes death of cancer cells, arrests the cell cycle, and regresses tumour size in animal models and reduces cell viability and colony formation in bench top assays.

Adding on, Shabir Zargar, research scholar said, While it has been long suspected that miR-155 downregulates pdcd4, there have, hitherto, been no evidence for such interaction.

The collaborative team headed by Prof. Karunagaran has shown that miR-155 is overexpressed in tongue cancer cells and tongue tumour tissues. This overactivity of miR-155 hinders the action of pdcd4, which, in turn, causes spread and growth of cancer of the tongue.

Our study has shown that the restoration of pdcd4 levels through molecular manipulation of miR-155 can lead to potential therapeutic developments for cancers, especially of tongue cancer, said Prof. Karunagaran.

The research findings have been published in the journal Molecular and Cellular Biology. The research team included Shabir Zargar, Vivek Tomar, Vidyarani Shyamsundar, Ramshankar Vijayalakshmi, Kumaravel Somasundaram, and Prof. Karunagaran.

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New study may help develop therapeutics for tongue cancer - India Education Diary

Cell Biology

The 2019 3Rs prize awarded to two pieces of novel research – News-Medical.Net

Reviewed by Emily Henderson, B.Sc.Jun 10 2020

The 2019 3Rs prize has been jointly awarded to Dr Francesca Nunn and Dr Marta Shahbazi for papers describing research that reduces the number of chickens and mice respectively. The 3Rs prize is awarded by the NC3Rs and sponsored by GSK.

- Nunn F, et al (2019). A novel, high-welfare methodology for evaluating poultry red mite interventions in vivo. Veterinary Parasitology. 267:42-46. doi.org/10.1016/j.vetpar.2019.01.011

- Shahbazi, MN, et al (2017). Pluripotent state transitions coordinate morphogenesis in mouse and human embryos. Nature. 552:239-243. doi.org/10.1038/nature24675

Dr Francesca Nunn, a post-doctoral scientist at the Moredun Research Institute

Francesca and colleagues developed and optimized a device to improve the testing of treatments against poultry red mites, reducing the number of hens used in field trials.

Poultry red mites are a blood feeding ectoparasite. They are a global problem for the egg industry, affecting the welfare of laying hens through irritation and anaemia. Mites are controlled using chemicals, however, repeated use has led to resistance and recent research efforts have focused on developing vaccines and novel biopesticides.

Assessment of vaccine control methods is initially done in vitro using blood assays before field trials are conducted, with 750 to 800 hens exposed to mites for each vaccine candidate, with an adjuvant control group. In vitro assays can be unreliable, for example, due to high levels of non-specific mite mortality. As a consequence, vaccine efficacy measured in vitro is not always translated into mite population reduction in field trials.

Francesca developed an "on-hen" mite feeding device that improves the screening of vaccine candidates to avoid unnecessary field trials. The device consists of a mesh pouch containing approximately 100 mites that have been starved for three weeks. The pouch is fitted to the thigh of the vaccinated hen - the mesh is large enough to allow the mites' mouth parts to access the hen's skin but small enough to contain the mites. Four hens are used per vaccine candidate and after three hours, the mesh is removed and the mites are recovered and maintained in 96-well plates for up to six days to assess mortality.

The device has already been used to provide data that has prevented seven vaccines and vaccine delivery methods from going into field trials. The initial pre-screening using the on-hen device involved 56 hens in total, each exposed to 100 mites for three periods of three hours - the field studies would have used almost 5,500 birds exposed to 10,000 mites for 100 days.

The on-hen device has been used by academic and commercial laboratories in the UK and internationally. By varying the size of the mesh, the device has the potential to be used in research on other parasites.

Dr Marta Shahbazi, a research leader at the MRC Laboratory of Molecular Biology

Marta and colleagues have developed advanced 3D cultures of human and mouse embryonic stem cells to mimic the development of the embryo at implantation and the subsequent morphogenesis and formation of the amniotic cavity, providing an opportunity to replace and reduce the use of live mice in some developmental biology studies.

Implantation of an embryo into the uterus is a critical step with a high rate of pregnancies lost at this stage. Studying implantation and other early embryonic events is technically and ethically challenging. The majority of work is carried out in mice, typically genetically modified animals where associated surgery and breeding of large numbers of animals are required.

Marta's research has shown that it is possible to minimise this use with reproducible and novel 3D cultures of mouse embryonic stem cells that reliably mimic development at the time of, and beyond, implantation, avoiding the need for recipient mice for embryo transfer and the subsequent culling of animals to access early stage embryos.

Marta and colleagues have previously described an in vitro method to culture human embryos beyond the point of implantation, overcoming the technical challenges that have traditionally limited the use of human embryos in research. The winning paper builds on this by reporting comparative functional experiments using mouse and human embryonic stem cell 3D cultures that have identified key factors involved in the remodelling of the embryo at implantation to form the amniotic cavity. This has revealed a previously unknown link between cell potency and tissue shape, with a loss of stem cell "nave pluripotency" (that is the ability to become any cell type in the organism) triggering the formation of the cavity and developmental progression of the embryo. The use of the 3D cultures for these studies replaced the use of 500 mice and importantly by demonstrating that they can be used to answer fundamental biological questions, the research has led to multiple groups worldwide adopting the cultures, further reducing the use of animals.

Professor Kevin Shakesheff, Chair of the NC3Rs Board and 3Rs Prize Panel said: "The vibrancy of research into the 3Rs was evident from the quality and breadth of the papers we considered. The winning papers and authors demonstrate that 3Rs research can the quality of science and unlock new types of experiments with wide applicability. Both papers are making an impact across the world and the prizes are richly deserved."

GSK is incredibly proud of being able to support the important work done by the NC3Rs and it was a real pleasure to participate in the presentation of these awards as the quality of the science was truly outstanding. The ambition to reduce, refine and replace that is at the core of the work that we are happily able to recognise in the winners is more crucial than ever. The need to ensure that every intervention, measurement and outcome helps to move science and the development of medicines forward is especially critical today in the context of Covid19 where great, reproducible, impactful science has to lead the way."

Dr Rab Prinjha, GSK Vice President of Adaptive Immunity and Immuno-epigenetics

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The 2019 3Rs prize awarded to two pieces of novel research - News-Medical.Net

Cell Biology

Princeton Researchers Catalog the Gut Microbiomes Impact on Medications – SciTechDaily

Study investigates potential for the intestinal microbial community to alter drug safety and efficacy.

Researchers at Princeton University have developed a systematic approach for evaluating how the microbial community in our intestines can chemically transform, or metabolize, oral medications in ways that impact their safety and efficacy.

The new methodology provides a more complete picture of how gut bacteria metabolize drugs, and could aid the development of medications that are more effective, have fewer side effects, and are personalized to an individuals microbiome.

The study was published today (June 10, 2020) in the journal Cell.

Researchers at Princeton created a system for evaluating how the bodys gut bacteria alter the safety and efficacy of everyday drugs. The system can be used in pharmaceutical research to improve drug discovery and development. Credit: Janie Kim. Published in Cell

Previous studies have examined how single species of gut bacteria can metabolize oral medications. The new framework enables evaluation of a persons entire intestinal microbial community at once.

Basically, we do not run and hide from the complexity of the microbiome, but instead, we embrace it, said Mohamed S. Donia, assistant professor of molecular biology. This approach allows us to gain a holistic and more realistic view of the microbiomes contribution to drug metabolism.

The team used the approach to evaluate the gut microbiomes effect on hundreds of common medications already on the market. The intestines are the primary region where pills and liquid medications are absorbed into the body.

The researchers identified 57 cases in which gut bacteria can alter existing oral medications. Eighty percent of those had not been previously reported, emphasizing the potential of the method for revealing unknown drug-microbiome interactions.

These alterations range from converting the medicine into an inactive state which can reduce its efficacy to converting the drug into a form that is toxic, potentially causing side effects.

The framework could aid drug discovery by identifying potential drug-microbiome interactions early in development, informing formulation changes. The approach can also help during clinical trials to better analyze the toxicity and efficacy of drugs being tested.

The intestines are home to hundreds of species of bacteria. The makeup of these communities what kinds of bacteria and how many of each species can vary considerably from person to person.

This inter-person variability underscores why studying a single bacterial species makes it impossible to compare the microbiomes metabolism of drugs between individuals, Donia said. We need to study the entire intestinal microbial community.

The researchers found that some peoples microbiomes had little effect on a given drug, while other microbiomes had a significant effect, demonstrating how important the community of bacteria rather than just single species is on drug metabolism.

Everyones microbiome is unique, and we were able to see this in our study, said Bahar Javdan, an M.D.-Ph.D. student in molecular biology and a co-first author on the study. We observed three main categories drugs that were consistently metabolized by all the microbiomes in our study, drugs that were metabolized by some and not by others, and drugs that were not subject to any microbiome-derived metabolism.

The methodological approach could be valuable for personalizing treatment to the microbiome of each patient. For example, the framework could help predict how a certain drug will behave, and suggest changes to the therapeutic strategy if undesired effects are predicted.

This is a case where medicine and ecology collide, said Jaime Lopez, a graduate student in the Lewis-Sigler Institute for Integrative Genomics and a co-first author on the study, who contributed the computational and quantitative analysis of the data. The bacteria in these microbial communities help each other survive, and they influence each others enzymatic profiles. This is something you would never capture if you didnt study it in a community.

The framework involves four steps for systematically evaluating the intestinal microbiomes effect on drugs.

First, the researchers collected 21 fecal samples collected from anonymous donors and cataloged the bacterial species living in each individual. They found that the donors each had a unique microbial community living in their guts, and that the majority of these personalized communities can be grown in a lab culturing system that they developed.

Next, they tested 575 FDA-approved drugs to see if they are chemically modified by one of the 21 cultured microbiomes, and then tested a subset of the drugs with all the cultured microbiomes. Here, they found microbiome-derived metabolites that had never been previously reported, as well as ones that have been reported in humans and associated with side effects but their origins were unknown. They found cases where all the donor microbiomes performed the same reactions on the drug, and others where only a subset did.

Then they examined the mechanisms by which some of the modified drugs are altered by the cultured microbiomes. To understand exactly how the transformations occurred, they traced the source of the chemical transformations to particular bacterial species and to particular genes within those bacteria. They also showed that the microbiome-derived metabolism reactions that are discovered in this manner can be recapitulated in a mouse model, the first step in adapting the approach for human drug development.

###

Reference: Personalized mapping of drug metabolism by the human gut microbiome by Bahar Javdan, Jaime G. Lopez, Pranatchareeya Chankhamjon, Ying-Chiang J.Lee, Raphaella Hull, Qihao Wu, Xiaojuan Wang, Seema Chatterjee and Mohamed S. Donia, 10 June 10, 2020, Cell.DOI: 10.1016/j.cell.2020.05.001

Additional contributors to the study were postdoctoral research associates Pranatchareeya Chankhamjon, Qihao Wu and Xiaojuan Wang; graduate student in molecular biology Ying-Chiang J. Lee, graduate student at Cambridge University Raphaella Hull; and Seema Chatterjee, research lab manager.

Funding for this study was provided by the Princeton Department of Molecular Biology, the National Institutes of Health, the New Jersey Commission on Cancer and the National Science Foundation.

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Princeton Researchers Catalog the Gut Microbiomes Impact on Medications - SciTechDaily

Immunology

European Academy of Allergy and Clinical Immunology: Launch of the EAACI Guidelines for the Use of Biologicals in Patients With Severe Asthma -…

ZRICH, June 8, 2020 /PRNewswire/ -- EAACI has launched its Guidelines for the use of Biologicals in Patients with Severe Asthma at the EAACI Digital Congress 2020.

Prof. Marek Jutel, EAACI President began by highlighting the significant burden of severe asthma on patients, families and healthcare systems. "Management of severe asthma proves to be difficult due to disease heterogeneity, coexisting comorbidities and especially because of complexities in care pathways and differences in national and regional healthcare systems. Better understanding of the mechanisms of the disease has enabled a stratified approach to the management of severe asthma, supporting the use of targeted treatments with biologicals. However, many unmet needs remain: how to select a certain biological as they all target overlapping disease phenotypes? How to enhance response? What are the best strategies to enhance the respondent's rate? What is the optimal duration of treatment and its cost-effectiveness? And what is the appropriate regimen - in the clinic or home-based?"

What is novel in the EAACI guidelines for the management of severe asthma is the inclusion of the GRADE approach in formulating recommendations for each biological and asthma outcome, separate recommendations for exacerbations, for lung function and more.

"It is clear that biologicals in the context of severe asthma is a very rapidly evolving field. After the first EAACI position paper on Biologicals and allergic diseases, these EAACI Guidelines for the use of Biologicals in Patients with Severe Asthma represent a desk reference tool of utmost importance for healthcare providers, patients, regulators and healthcare systems providing specific recommendations for each biological in the context of each independent outcome," says Prof. Oscar Palomares, Complutense University of Madrid, Past Chair of EAACI Biologicals Working Group, current EAACI ExCom member and Biologicals Guidelines Project Co-Chair.

A management algorithm for the use of biologicals in the clinic is further proposed, together with future approaches and research priorities. "EAACI advocates for a triple decision chart based on phenotypic traits, biomarkers and outcomes, added to this is shared decision making to reset individual goals and define response together with the patient. Efficacy is tested after 4-6 months - if there is a response, intervention is to be continued according to the preset target and while continuously monitoring for safety. Real life evidence must be collected through registries, real world trials and health economics indicators as the basis for the next steps. If the response is suboptimal it is important to look at the airway inflammation and to the airway hyperreactvity. If the eosinophilic inflammation persists, several factors can be improved, for example adherence to background controller treatment or other options can be considers such as switching to a biological targeting a different path, or checking for other immune mechanisms. If neutrophilic inflammation is present macrolides can be considered. If there is no inflammation non-T2 asthma approaches like dual bronchodilators and in very selective cases bronchial thermoplasty can be considered," says Prof. Dr. Ioana Agache, University of Brasov Romania, Biologicals Guidelines Project Co-Chair and EAACI Past President.

The rising use of biologicals (monoclonal antibodies) in modern medicine, their remarkable potential and possible challenges were also discussed at the EAACI Digital Congress 2020 by its Special Guest, Sir Gregory Paul Winter, Nobel Prize Winner for Biochemistry in 2018.

"For inflammatory disease monoclonal antibodies are finding their place on the front line. Although inflammatory diseases such as severe asthma can be treated with chemical drugs such as corticosteroids their broad mechanism of action may also bring a range of undesirable side effects including fluid retention, hypertension and bone loss, particularly with extended use. Ideally treatments should have a more specific mode of action and avoid these side effects. That is why monoclonal antibodies which have such specific modes of action in blocking the interaction of key proteins or receptors are so attractive. And the availability of a range of therapeutic monoclonal antibodies against proteins involved in inflammation provides the opportunity to identify in the clinic those targets which are most relevant. Over the last 30 years biologicals have become increasingly important in medicine. The limitations in early use of biologicals were overcome by the recombinant DNA technology leading to a tsunami of therapeutic monoclonal antibodies. These biologicals are of high efficiency and exquisite specificity, they have a long half-life in serum and properties and functions can be tailored to order. Their impact has already been immense and likely to become greater still," says Sir Gregory Winter, University of Cambridge, Nobel Prize Laureate 2018.

Under these promising auspices, EAACI hopes its new Guidelines will be a cornerstone for clinicians, researchers, scientific societies and medical agencies in the years to come.

About EAACI:

The European Academy of Allergy and Clinical Immunology (EAACI) is an association of clinicians, researchers and allied health professionals founded in 1956. EAACI is dedicated to improving the health of people affected by allergic diseases. With more 12 000 members from 124 countries and over 75 National Allergy Societies, EAACI is the primary source of expertise in Europe and worldwide for all aspects of allergy.

Logo - https://mma.prnewswire.com/media/1177661/EAACI_Digital_Congress_2020_Logo.jpg

Contact: EAACI Headquarters Hagenholzstrasse 111, 3rd Floor 8050 Zurich CH- Switzerland Tel: +41799561865 communications@eaaci.org http://www.eaaci.org

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European Academy of Allergy and Clinical Immunology: Launch of the EAACI Guidelines for the Use of Biologicals in Patients With Severe Asthma -...

Immunology

Immune modulation can cure severe and often fatal fungal infection in children – News-Medical.Net

In the June 11 issue of the New England Journal of Medicine, a team of UCLA physicians and scientists describes the first case of immune modulation being used to cure a severe and often fatal fungal infection. The team "retuned" a 4-year-old's immune system so that it could fight off disseminated coccidioidomycosis.

The case, originally reported by UCLA in 2019, could pave the way for a new treatment for the infection, which affects hundreds of Americans each year, primarily in the Southwest, and kills approximately 40% of the people who contract it.

The technique described in the study could also suggest a new paradigm for treating other severe fungal infections, bacterial infections such as tuberculosis, and severe viral infections such as influenza and COVID-19.

"Immune modulation isn't currently part of the strategy with any of these severe infections," said Dr. Manish Butte, the report's senior author, who holds the E. Richard Stiehm Endowed Chair in Pediatric Allergy, Immunology and Rheumatology at the David Geffen School of Medicine at UCLA.

"Our case suggests that rather than hoping to get the upper hand with more and more antibiotics or antifungals, we can have some success by combining these established approaches with the new idea of programming the patient's immune response to better fight the infection."

Each year, more than 100,000 people are infected with Coccidioides fungi, which reside in the soils of California, Arizona and West Texas. Most people who are infected are asymptomatic, and about 20,000 experience the minor respiratory illness commonly known as Valley fever.

The vast majority of people with Valley fever respond well to antifungal medications, but approximately 1% of the infections progress to disseminated coccidioidomycosis, in which the infection spreads rapidly throughout the body, leading to bone and tissue damage, and in many cases death.

Historically, severe infections have been seen as bad luck. Doctors haven't looked at how we can harness the immune systems of these patients to fight the infection."

Dr Manish Butte, Study Senior Author, University of California Los Angeles (UCLA) Health Sciences

According to a 2019 study in the International Journal of Environmental Research and Public Health, California spends between $700 million and $900 million a year in direct and indirect costs related to the care of people infected by the cocci fungus, including more than $300 million to care for the approximately 200 people with disseminated coccidioidomycosis.

The boy who was treated by Butte and his team had previously been treated with high doses of multiple antifungal medicines, but by the time he arrived at UCLA, he could barely walk or talk and required a feeding tube to eat.

When UCLA physicians homed in on the patient's immune system, they concluded that his T cells -; the white blood cells that play a key role in the body's immune response -; were failing to properly recognize the invading fungus. The T cells were responding as though the infection was a parasitic infection rather than a fungal one.

That prompted the team to supplement the boy's antifungal medications with an immune stimulator called interferon-gamma. And Dr. Maria Garcia-Lloret, a pediatric allergist and immunologist, suggested adding yet another medication, dupilumab, which was developed as a medication for allergic diseases and had never before been used to treat infections.

Dupilumab is a prescription drug that has not been approved by the FDA as a treatment for disseminated coccidioidomycosis.

The combination of immune modulators restored the proper programming to the patient's T cells -; and the boy's infection went away in a month.

The UCLA research team cites that the immunomodulatory approach has the potential to enhance the ability of patients to clear other types of fungal, bacterial, and viral infections that are not responding to established therapies.

In partnership with the Bakersfield, California-based Valley Fever Institute and the drugs' manufacturers -; Horizon Therapeutics, Regeneron Pharmaceuticals and Sanofi Genzyme -; the UCLA researchers are planning to test the two drugs on other people with disseminated coccidioidomycosis. They also plan to study the approach for treating other types of severe infections.

Source:

Journal reference:

Tsai, M., et al. (2020) Disseminated Coccidioidomycosis Treated with Interferon- and Dupilumab. The New England Journal of Medicine. doi.org/10.1056/NEJMoa2000024.

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Immune modulation can cure severe and often fatal fungal infection in children - News-Medical.Net

Immunology

UW-Madison on quest to cure "COVID toes" in children – WMTV

MADISON, Wis. (WMTV)-- UW-Madison researchers are now trying to figure why some children suffer from a condition called "COVID toes."

In a release, UW Health said on Wednesday that dermatologists at the university and elsewhere have seen an uptick in red to purple bruise-like blisters and bumps on otherwise healthy children.

Some doctors thought that there could be a link to the painful condition and COVID-19, coining the phrase "COVID toes."

The issue could also be connected to a rare skin condition called "chilblains." That condition results in a higher protein that helps kill viral infections, according to the UW.

At UW Health, all of the children with COVID toes have been healthy and lacked both current and previous symptoms of COVID-19. We want to better understand how their immune system may have been able to combat the virus," said Dr Lisa Arkin, assistant professor of dermatology and pediatrics at the UW's School of Medicine and Public Health.

During the study, researchers will collect samples from a number of participants, including blood, saliva, and archived tissue from previous procedures.

Our approach is unique, instead of studying the sickest patients we aim to study those that stayed relatively healthy, once we figure that out we can use this science to treat the sickest most vulnerable patients, said Dr. Beth Drolet, chair of dermatology at the UW's School of Medicine and Public Health. We have leading experts in dermatology, immunology, rheumatology, genetics and virology all working together to get answers as fast as we can.

To learn more about how to participate in this research study, call (608) 287-2640 or (608) 287-2006 or email clinicaltrials@dermatology.wisc.edu.

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UW-Madison on quest to cure "COVID toes" in children - WMTV

Immunology

COVID-19 cases will go up as Alberta reopens many activities: health experts – EverythingGP

By Canadian Press

Jun 10, 2020

EDMONTON Health experts say it makes sense for Alberta to take the next step in reopening itseconomy, but warn there will be an uptick in COVID-19 cases due to the inability to physically distance in some situations.

Premier Jason Kenneyannounced on Tuesday thateverything from casinos, gyms and arenasto spas, movie theatres andpools will be allowed to reopen on Friday.

Dr. Christopher Mody, whos the head of microbiology, immunology and infectious disease at the Cumming School of Medicine at the University of Calgary, says Albertas case numbers support moving forward.

There were 356 active cases on Tuesday, with 46 people in hospital and six of those in intensive care.

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COVID-19 cases will go up as Alberta reopens many activities: health experts - EverythingGP

Immunology

Collaborating in Innovative Medical R&D to combat the pandemic, Alphamab Oncology and Institut Pasteur Shanghai Announce Partnership to Co-develop…

DetailsCategory: AntibodiesPublished on Wednesday, 10 June 2020 11:06Hits: 223

SUZHOU, China I June 9, 2020 I Alphamab Oncology (stock code: 9966 HK) announced that Jiangsu Alphamab Biopharmaceuticals Co., Ltd. ("Jiangsu Alphamab"), a wholly-owned subsidiary of the Company, has entered a partnership agreement with Institut Pasteur of Shanghai, Chinese Academy of Sciences ("Institut Pasteur Shanghai") on the co-development, manufacturing and commercialization of therapeutic antibody for Corona Virus Disease 2019 (COVID-19) worldwide.

According to a report on June8, more than 7.10 million people have been diagnosed with COVID-19 infection worldwide, but there are still no vaccines or medicines available for prevention or treatment. Neutralizing antibody targeting proteins on the surface of virus can effectively inhibit the virus' binding and entry into target cells to block infection, therefore it can be considered to be useful to protect or treat patients with COVID-19 infection. Among various potential solutions, the optimized mixed antibodies solution not only amplify the therapeutic effect due to synergistic effect, but also can solve the virus escaping issue due to COVID-19 virus' mutation, and minimizes the risk of "Antibody-dependent enhancement".

This cooperation will fully leverage not only Institut Pasteur Shanghai 's prowess in research and development, and prior research findings in the area of infectious diseases, but also Alphamab Oncology's strong R&D and its proprietary Mixed Antibodies Platform, to develop COVID-19 neutralizing antibody with good safety and high neutralizing activity, complete clinical trials soon to provide antibody treatment options, effectively improve the prevention capabilities, reduce the mortality rate, and contribute to disease prevention and control for China and the world. Meanwhile, Pasteur's global R&D network could also help expedite the completion of clinical trial.

According to the agreement, Alphamab Oncology and Institut Pasteur Shanghai will form a joint project team. Alphamab Oncology is responsible for providing its proprietary Mixed Antibodies Platform, constructing humanized antibodies and recombinant engineered cell lines, carrying out PK study, clinical trials, manufacturing, and commercialization. Institut Pasteur Shanghai is responsible for the comprehensive analysis of neutralizing activity of COVID-19 antibodies.

Dr. Ting Xu, Founder, Chairman and CEO of Alphamab Oncology commented, "Since the end of 2019, COVID-19 has ravaged the world and has become the major global public health issue. We plan to partner with Institut Pasteur Shanghai by leveraging our proprietary antibody technology platform, extensive experiences in antibody drug R&D and established manufacturing platform to accelerate the development of COVID-19 antibodies to combat COVID-19, prevent subsequent outbreaks and contribute to the further prevention and control of this epidemic."

Dr. Hong Tang, Director General and Legal Representative of Institut Pasteur Shanghai commented, "Since the outbreak of the Coronavirus, the Institut Pasteur Shanghai has been focusing on R&D Projects including virus detection and origin tracing, antibody drug and vaccine, and has achieved quite a few progress. This partnership with Alphamab Oncology on COVID-19 neutralizing antibody drughas demonstrated not only the innovation capability of our research and development team, but also a result of the reform of Chinese Academy of Sciences and the capable platform of Shanghai Science and Innovation Center. Our institute will collaborate with industry players to accelerate drug development and contribute to the prevention and control of pandemic as soon as possible."

About Alphamab Oncology

Alphamab Oncology is a biopharmaceutical company focusing on innovative biologics medicine for oncology. On December 12, 2019, the Company was listed in the mainboard of Hong Kong Stock Exchange with stock code 9966.

Alphamab has fully integrated proprietary biologics platforms in bi-specifics and protein engineering. Its highly differentiated in-house pipeline consists of eight anti-cancer drug candidates, four of which have advanced into Phase I III clinical development phases in China, US and Japan.

The Company also has state-of-the-art manufacturing capability designed and built to meet NMPA and EU/FDA's cGMP standards.

Alphamab Oncology is committed to further develop its robust pipeline in oncology/immunology to benefit patients around the world. Visit http://www.alphamabonc.com for more information.

About Institut Pasteur Shanghai

Institut Pasteur of Shanghai of Chinese Academy of Sciences was established in October 11, 2004.It is the only national research institute dedicated to the basic research and development of relevant technologies for human infectious diseases within the Academy. The Institute focuses on key scientific subject such as the fundamental laws of pathogenic microorganisms' activities, and the pathogenic mechanism of major infectious diseases, to promotes the innovation and development of etiology, immunology and vaccinology to solve key issues such as the discovery of pathogen and biological treatment (antibodies, vaccines, etc. ), with a focus on providing scientific and technological support and solutions for public health and biosecurity of China.It is actively participating the building of Shanghai Science and Innovation Center. The infectious diseases' prevention and treatment platform, a functional platform which it is responsible for, will provide solid scientific support for the prevention and control of infectious diseases in Shanghai and Yangtze River Delta Region in China.

SOURCE: Alphmab

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Collaborating in Innovative Medical R&D to combat the pandemic, Alphamab Oncology and Institut Pasteur Shanghai Announce Partnership to Co-develop...