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Research

Inflammation is a critical response to potential danger signals and damage in organs in our body.

Inflammation is a critical response to potential danger signals and damage in organs in our body. But with autoimmune diseases such as rheumatoid arthritis, lupus, ulcerative colitis, Crohn’s disease and many others, our own immune system turns against our organs. These painful and debilitating conditions take an immense toll on people’s quality of life and many of these diseases are poorly managed by existing treatments that provide only symptomatic relief.

Iain Kilty: What We’re Working on

For decades, doctors relied on steroids to suppress immune response. Though an important option, steroids come with many potentially harmful side effects. Fortunately, science has continued to advance, and today we have the opportunity to transform the management of inflammatory diseases with new classes of therapies that target other key proteins and pathways in the body.

As science evolves beyond broad immunosuppression and into more selective agents, patients living with autoimmune and inflammatory disease have new hope.

As science evolves beyond broad immunosuppression and into more selective agents, patients living with autoimmune and inflammatory disease have new hope. Pfizer scientists operate with a sense of urgency, focused on three areas with the greatest unmet need:

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Rheumatology Investigating therapies for rheumatoid arthritis and lupus
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Gastroenterology Looking at the next wave of medicines in ulcerative colitis, Crohn’s disease and nonalcoholic steatohepatitis (NASH)
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Medical Dermatology Focusing on the next generation of medicines for atopic dermatitis, psoriasis, vitiligo and alopecia areata

Innovation in I&I will remain focused on enabling patients to thrive in remission and to attain cures. It is believed that in the longer term, this will be achieved by evolving the treatment paradigm in inflammation beyond broad immunosuppression. In the clinic, more selective inhibition of pro-inflammatory adaptive pathways is being targeted to deliver transformational induction and maintenance of remission with lower safety risks. Emerging approaches are aimed at promoting restoration of the immune system and tissue health to deliver cures.

Emerging approaches are aimed at promoting restoration of the immune system and tissue health to deliver cures.

Precision medicine is embedded in all of our investigational programs in Inflammation and Immunology, where we seek to better understand the underlying disease biology and identify the group of patients who will respond best to certain treatments. Pfizer sees particular promise in combination therapies to reduce remission rates.

Lovisa Afzelius: What We’re Working On

Technologies/Approach

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JAK pathwayOur janus kinase (JAK) inhibitor programs are at the heart of our R&D efforts in a number of autoimmune diseases in addition to rheumatoid arthritis. We’re advancing our leading science on the JAK pathway to develop tailored therapies for lupus, psoriasis, ulcerative colitis and alopecia areata – all areas in which we have ongoing clinical trials.
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Immune ToleranceActivation of the immune system by self-antigens is the basis of every autoimmune disease. Immunological tolerance is the term describing a host of normal physiological processes to prevent this activation from happening. Current treatments for autoimmune diseases result in broad immunosuppression, occasionally resulting in infection or insufficient tumor surveillance. We believe the future of treatment for autoimmune disease is specific restoration of self-tolerance rather than immunosuppression, and have established a group in R&D dedicated to this effort.
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Big data Every day we generate massive amounts of data in our clinical trials and laboratory experiments that enable us to describe diseases in greater and greater detail. The data includes both how patients and clinicians describe symptoms and response to treatment as well as data that describes the effects a drug has on the body’s molecular and cellular mechanisms. Together this forms a unique knowledge database. With the help of advanced analytics we are able to interrogate this “Big Data” to drive our understanding what targets and pathways may best help resolve disease and what treatment would be best for each patient.

Collaborations

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23andMeSince 2014, Pfizer and 23andMe have engaged in an expanding collaboration to help foster research in several different autoimmune and inflammatory diseases including lupus, ulcerative colitis and Crohn’s disease. Our work explores the underlying genetic factors associated with these diseases in the hope of developing new or improved treatments. In addition to enrolling over 15,000 individuals within two separate research initiatives focused on inflammatory bowel disease and lupus, respectively, our most recent partnership gives Pfizer access to 23andMe’s unique research platform and analysis of the company’s genotyped population of over 800,000 individuals who have consented to participate in research. This wealth of patient data offers yet another opportunity to better understand potential links between genetic traits and disease.
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BioRapPfizer recently entered into a collaboration, option and license agreement with BioRap Technologies, Ltd., the technology transfer company of the Rappaport Institute of Biomedical Research at the Technion – Israel Institute of Technology. The collaboration is based on work of Dr. Nathan Karim at the Rappaport Institute who has developed a monoclonal antibody that appears to drive the development activity of regulatory T cells – a cell type that plays a role in controlling autoimmunity. This antibody may offer a new potential treatment for certain autoimmune diseases, including inflammatory bowel disease (IBD) and multiple sclerosis (MS).

Work with Us

If you’re interested in collaborating with our Inflammation and Immunology teams, visit our Immunoscience Partnering and Inflammation and Immunology pages to learn more about the work we’re pursuing..

Meet Some of Pfizer’s Inflammation and Immunology Researchers

Selected Publications from the Inflammation and Immunology Research Unit

Discovery of a novel JAK3-selective inhibitor: Functional differentiation of JAK3-selective inhibition over pan-JAK or JAK1-selective inhibition ACS Chemical Biology Telliez JB, Dowty ME, Wang L, Jussif J, Lin T, Li L, Moy E, Balbo P, Li W, Zhao Y, Crouse K, Dickinson C, Symanowicz P, Hegen M, Banker ME, Vincent F, Unwalla R, Liang S, Gilbert AM, Brown MF, Hayward M, Montgomery J, Yang X, Bauman J, Trujillo JI, Casimiro-Garcia A, Vajdos FF, Leung L, Geoghegan KF, Quazi A, Xuan D, Jones LH, Hett E, Wright K, Clark JD, Thorarensen A. October 28 2016
Efficacy and Pharmacology of the NLRP3 Inflammasome Inhibitor CP-456,773 (CRID3) in Murine Models of Dermal and Pulmonary Inflammation The Journal of Immunology Primiano MJ, Lefker BA, Bowman MR, Bree AG, Hubeau C, Bonin PD, Mangan M, Dower K, Monks BG, Cushing L, Wang S, Guzova J, Jiao A, Lin LL, Latz E, Hepworth D, Hall JP. September 15 2016
Inhibiting complex IL-17A and IL-17RA interactions with a linear peptide Nature, Scientific Reports Liu S, Desharnais J, Sahasrabudhe PPV, Jin P, Li W, Oates B, Shanker S, Banker ME, Chrunyk B, Song X, Feng X, Griffor M, Jimenez J, Chen G, Tumelty D, Bhat A, Bradshaw C, Woodnutt G, Lappe R, Thorarensen A, Qiu X, Withka J, Wood L. May 17 2016
Oral and inhaled p38 MAPK inhibitors: effects on inhaled LPS challenge in healthy subjects European Journal of Clinical Pharmacology Singh D, Siew L, Christensen J, Plumb J, Clarke GW, Greenaway S, Perros-Huguet C, Clarke N, Kilty I, Tan L. August 13 2015
Network pharmacology of JAK inhibitors Proceedings of the National Academy of Sciences Moodley D, Yoshida H, Mostafavi S, Asinovski N, Ortiz-Lopez A, Symanowicz P, Telliez JB, Hegen M, Clark JD, Mathis D, Benoist C. June 24 2016
Parsing the Interferon Transcriptional Network and Its Disease Associations Cell Mostafavi S, Yoshida H, Moodley D, LeBoité H, Rothamel K, Raj T, Ye CJ, Chevrier N, Zhang SY, Feng T, Lee M, Casanova JL, Clark JD, Hegen M, Telliez JB, Hacohen N, De Jager PL, Regev A, Mathis D, Benoist C, Immunological Genome Project Consortium. January 28 2016
Soluble Fn14 Is Detected and Elevated in Mouse and Human Kidney Disease PLoS One Sharif MN, Campanholle G, Nagiec EE, Wang J, Syed J, O'Neil SP, Zhan Y, Brenneman K, Homer B, Neubert H, Karim R, Pullen N, Evans SM, Fleming M, Chockalingam P, Lin LL. May 12 2016