Seattle, United States

Benaroya Research Institute

www.benaroyaresearch.org
Seattle, United States

Benaroya Research Institute is a Seattle, Washington non-profit organization which conducts autoimmune disease medical research. It is housed at Virginia Mason Medical Center. Wikipedia.


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BRISBANE, Calif.--(BUSINESS WIRE)--Aimmune Therapeutics, Inc. (Nasdaq:AIMT), today announced the enrollment of its first patient in the Phase 3 RAMSES (ARC007) clinical trial of AR101 for treatment of peanut allergy. AR101 is Aimmune’s investigational biologic oral immunotherapy for desensitization of patients with peanut allergy. The Real-World AR101 Market-Supporting Experience Study in Peanut-Allergic Children Age 4-17 Years, or RAMSES (ARC007), trial is designed to gain experience with AR101 in a real-world setting, without the use of a double-blind, placebo-controlled food challenge (DBPCFC) to confirm peanut allergy. It will assess the safety and tolerability of AR101 versus placebo. The trial follows the same up-dosing and maintenance protocol as Aimmune’s ongoing Phase 3 PALISADE trial, taking place in the United States, Canada, and eight countries in Europe. “The peanut-allergic patients in my practice have been highly motivated to participate in Aimmune’s clinical trials. They’re looking for access to a potential treatment, since peanut allergy patients are at risk for life-threatening anaphylaxis and have to take extra caution with eating. My patients have been happy to have the opportunity to participate in these clinical trials and help with the effort which may lead to an approved product to treat their problem,” said Stanley M. Fineman, M.D., Atlanta Asthma & Allergy. “Not requiring the diagnostic food challenge requirement is more consistent with the way we practice, where the diagnosis of peanut allergy is typically made based on a strong clinical history and corroborating positive skin prick tests and/or elevated blood levels of peanut antibodies.” RAMSES (ARC007) is a randomized, double-blind, placebo-controlled trial enrolling approximately 440 peanut-allergic patients ages 4–17 at multiple sites in the United States and Canada. Patient selection is based on stringent entry criteria, including a well-documented medical history of IgE-mediated reactions to peanut (including anaphylaxis), skin reactivity, and analyses of peanut-specific allergic antibodies. The trial will monitor treatment-emergent adverse events during a six-month up-dosing period, and then, after unblinding, follow patients for at least six months on the maintenance dose of 300 mg of AR101 per day. Aimmune anticipates that the absence of an entry food challenge may improve the tolerability profile of AR101 in early stages of dosing by removing exposure to high levels of peanut allergen that may otherwise prime the immune system prior to treatment. “We’re conducting our RAMSES trial not only to support regulatory filings and real-world market understanding, but also to test whether removing the entry food challenge can lead to improved tolerability of AR101 during early up-dosing. Recent data from our collaborator Dr. Erik Wambre and his colleagues at the Benaroya Research Institute on PALISADE patient samples support the idea that the food challenge may activate the immune system and thus increase the risk of additional allergic reactions in the early up-dosing period that follows,” said Aimmune CMO, Daniel Adelman, M.D. “Also, while some studies1,2 have shown that food allergy patients and caregivers report improvements in quality of life following food challenges, regardless of outcome, the process can be emotionally tough. We’ve been hearing a lot of enthusiasm from our PALISADE sites about starting RAMSES, and many of them have waitlisted patients who are eager to participate in the trial.” For more information about the RAMSES (ARC007) trial, please see: Aimmune Therapeutics, Inc., is a clinical-stage biopharmaceutical company developing treatments for life-threatening food allergies. The company’s Characterized Oral Desensitization ImmunoTherapy (CODIT™) approach is intended to achieve meaningful levels of protection by desensitizing patients with defined, precise amounts of key allergens. Aimmune’s first investigational biologic product using CODIT™, AR101 for the treatment of peanut allergy, has received the FDA’s Breakthrough Therapy Designation for the desensitization of peanut-allergic patients 4-17 years of age and is currently being evaluated in Phase 3 clinical trials. For more information, please see www.aimmune.com. 1. Franxman TJ, Howe L, Teich E, Greenhawt MJ. Oral food challenge and food allergy quality of life in caregivers of children with food allergy. Journal of Allergy and Clinical Immunology: In Practice 2015; 3:50. 2. van der Velde, J.L., Flokstra-de Blok, B.M., de Groot, H., Oude-Elberink, J.N., Kerkhof, M., Duiverman, E.J. et al, Food allergy-related quality of life after double-blind, placebo-controlled food challenges in adults, adolescents, and children. Journal of Allergy and Clinical Immunology 2012; 130:1136–1143.e2. Statements contained in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Such statements include, but are not limited to, statements regarding: Aimmune’s expectations for its RAMSES clinical trial of AR101, including the expectation that the absence of a food challenge in the trial may improve the tolerability of AR101; Aimmune’s expectations regarding the potential benefits of AR101; and Aimmune’s expectations regarding potential applications of the CODIT™ approach to treating life-threatening food allergies. Risks and uncertainties that contribute to the uncertain nature of the forward-looking statements include: the expectation that Aimmune will need additional funds to finance its operations; the company’s ability to initiate and/or complete clinical trials; the unpredictability of the regulatory process; the possibility that Aimmune’s clinical trials will not be successful; Aimmune’s dependence on the success of AR101; the company’s reliance on third parties for the manufacture of the company’s product candidates; possible regulatory developments in the United States and foreign countries; and the company’s ability to attract and retain senior management personnel. These and other risks and uncertainties are described more fully in Aimmune's most recent filings with the Securities and Exchange Commission, including its Quarterly Report on Form 10-Q for the quarter ended March 31, 2017. All forward-looking statements contained in this press release speak only as of the date on which they were made. Aimmune undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made. This press release concerns a product that is under clinical investigation and that has not yet been approved for marketing by the U.S. Food and Drug Administration (FDA) or the European Medicines Agency (EMA). It is currently limited to investigational use, and no representation is made as to its safety or effectiveness for the purposes for which it is being investigated.


Ziegler S.F.,Benaroya Research Institute
Current Opinion in Immunology | Year: 2010

The importance of the epithelium in initiating and controlling immune responses is becoming more appreciated. For example, allergen contact first occurs at mucosal sites exposed to the external environment, such as the skin, airways and gastrointestinal tract. This exposure leads to the production of a variety of cytokines and chemokines that are involved in driving allergic inflammatory responses. One such product is thymic stromal lymphopoietin (TSLP). Recent studies, in both humans and mouse models, have implicated TSLP in the development and progression of atopy and atopic diseases. This review will discuss this work and place TSLP in the inflammatory cascade that leads to allergic disease. © 2010 Elsevier Ltd.


Ziegler S.F.,Benaroya Research Institute
Journal of Allergy and Clinical Immunology | Year: 2012

The importance of the epithelium in initiating and controlling immune responses is becoming more appreciated. For example, allergen contact first occurs at mucosal sites exposed to the external environment, such as the skin, airways, and gastrointestinal tract. This exposure leads to the production of a variety of cytokines and chemokines that are involved in driving allergic inflammatory responses. One such product is thymic stromal lymphopoietin (TSLP). Recent studies in both human subjects and murine models have implicated TSLP in the development and progression of allergic diseases. This review will highlight recent advances in the understanding of the role of TSLP in these inflammatory diseases. Importantly, these insights into TSLP's multifaceted role could potentially allow for novel therapeutic manipulations of these disorders. © 2012 American Academy of Allergy, Asthma & Immunology.


Ziegler A.-G.,TU Munich | Nepom G.T.,Benaroya Research Institute
Immunity | Year: 2010

A combination of genetic and immunological features is useful for prediction of autoimmune diabetes. Patterns of immune response correspond to the progression from a preclinical phase of disease to end-stage islet damage, with biomarkers indicating transition from susceptibility to active autoimmunity, and to a final loss of immune regulation. Here, we review the markers that provide evidence for immunological checkpoint failure and that also provide tools for assessment of individualized disease risk. When viewed in the context of genetic variation that influences immune response thresholds, progression from susceptibility to overt disease displays predictable modalities of clinical presentation resulting from a sequential series of failed homeostatic checkpoints for selection and activation of immunity. © 2010 Elsevier Inc.


Grant
Agency: Department of Health and Human Services | Branch: | Program: STTR | Phase: Phase I | Award Amount: 686.02K | Year: 2011

DESCRIPTION (provided by applicant): The goal of this proposal is for Matrexa to develop a protein product that will prevent intimal hyperplasia in human saphenous vein grafts (SVG) with the objective of reducing the exceedingly high failure rate of thesesurgical procedures. The strategy involves acute pre-treatment of saphenous veins at the time of surgery with proprietary agents, developed by Matrexa. The target for intervention is the large vascular matrix proteoglycan, versican, which is central to smooth muscle growth and hyperplasia, accumulation of atherogenic lipids, and macrophage ingress into developing lesions. We have successfully targeted versican and prevented these events in animal models of atherosclerosis through over expression of the small variant versican V3 (V3) and through over expression of versican antisense sequences. We have also discovered an additional and unexpected benefit of these approaches in that V3 promotes the synthesis and formation of elastic fibers and markedly improves the mechanical properties and stability of treated vessels. Once formed, the elastic fibers will maintain the structural integrity, anti-hyperplastic and anti-inflammatory nature of the vascular wall. We have further discovered, through deletion studies,that exon 3 of V3 contains this elastogenic activity. We recognize, however, that gene delivery and overexpression of V3 is therapeutically problematic for safety and other reasons and we therefore propose to develop and use rV3 protein and small peptidesas therapeutic agents. In preliminary studies we have been successful in producing rV3 which possesses elastogenic activity. The Aims of the project are 1) to prepare rV3 protein in enough quantity and purity to test its bioactivity in biochemical and invitro cell-based assays and 2) to demonstrate the efficacy of rV3 to prevent intimal hyperplasia and promote elastogenesis in ex vivo cultures of human saphenous vein. PUBLIC HEALTH RELEVANCE:This project is designed to develop therapeutic compounds to treat cardiovascular disease, the number 1 killer of human beings in the western world. We have discovered a specific protein that blocks the development of atherosclerosis (fatty deposits in the artery walls that cause hardening of the arteries) in animal models of this disease and now want to use strategies to produce this protein and test its effectiveness as a therapeutic agent to treat artery bypass failure which is among the most common surgeries in the US, with over 500,000 performed per year. Success with this undertaking will have an enormous impact on health care in this country and worldwide.


Patent
Benaroya Research Institute | Date: 2012-06-14

A composition for treating an airway inflammatory disease having high molecular weight, crosslinked hyaluronan and at least one aeroallergen is provided. A method of inducing immune tolerance to one or more aeroallergens in a mammalian subject suffering from or at risk of developing an airway inflammatory disease, and a method of treating a human subject suffering from or at risk of developing an airway inflammatory disease or condition of the lungs are also provided.


Patent
Benaroya Research Institute | Date: 2014-01-30

A method for identifying an autoimmune or demyelinating disease in a subject is described. The method includes (a) FIRST COHORT obtaining a sample comprising CD4^() T cells from a subject; (b) determining a level of IL-6 responsiveness of CD4^(+) T cells from the sample; (c) comparing the level of IL-6 responsiveness determined in step (b) with a level of IL-6 responsiveness of CD4^(+) T cells in a sample from a healthy subject; and (d) identifying the subject as having an autoimmune or demyelinating disease based upon an elevated level of IL-6 responsiveness in the subject. Biomarkers include, for example, IL-6R and/or pSTAT3. Methods for identifying and characterizing multiple sclerosis and relapsing-remitting multiple sclerosis are also described.


Patent
Benaroya Research Institute | Date: 2013-08-23

Provided herein are methods of detecting and/or monitoring the presence or severity of an immune disorder in a subject, including detecting a frequency of a Th2a subset of CD4+ T cells in a biological sample of the subject. In some embodiments, the detecting includes: (a) detecting a frequency of CD4+ T cells in a biological sample of said subject; (b) detecting a frequency of a Th2a subset of the CD4+ T cells in the biological sample; and (c) comparing the frequency of the Th2a subset with the frequency of the CD4+ T cells.


Patent
Benaroya Research Institute and Stanford University | Date: 2014-08-12

Compositions for treating autoimmune, allergic, or atopic disease comprising a compound that inhibits hyaluronan synthesis and a pharmaceutically acceptable carrier are described. In some embodiments, the compound that inhibits hyaluronan synthesis is 4-methylumbelliferone or a metabolite of 4-methylumbelliferone. Methods for treating autoimmune diabetes, multiple sclerosis and/or autoimmune demyelination, including administering to the subject a composition having a compound in an amount effective to inhibit hyaluronan synthesis in a mammalian subject, are also described.


Patent
Benaroya Research Institute | Date: 2016-01-07

Provided herein are methods of detecting and/or monitoring the presence or severity of an immune disorder in a subject, including detecting a frequency of a Th2a subset of CD4+ T cells in a biological sample of the subject. In some embodiments, the detecting includes: (a) detecting a frequency of CD4+ T cells in a biological sample of said subject; (b) detecting a frequency of a Th2a subset of the CD4+ T cells in the biological sample; and (c) comparing the frequency of the Th2a subset with the frequency of the CD4+ T cells.

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