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Tolerx, Inc.
Industry Biotechnology
Headquarters Cambridge, Massachusetts

Tolerx, Inc. was a biopharmaceutical company headquartered in Cambridge, Massachusetts. The company was focused on discovering and developing new therapies designed to treat patients by reprogramming the immune system, allowing for long-term remission of immune-related diseases after a short course of therapy. Targeted diseases include type 1 diabetes, rheumatoid arthritis, Inflammatory bowel disease (IBD), cancer, chronic and viral diseases. In 2008, Tolerx was named one of Fierce Biotech’s Fierce 15. [1] In October 2011, Tolerx was shut down due to an unsuccessful Phase III trial in patients recently diagnosed with Type 1 diabetes. [2]


Development programs

Tolerx’s lead product candidate, otelixizumab, also known as TRX4, is a novel monoclonal antibody being developed for the treatment of autoimmune type 1 diabetes and other autoimmune diseases. The efficacy and safety of otelixizumab in the treatment of type 1 diabetes is currently being studied in a pivotal Phase 3 study called DEFEND (Durable-response therapy Evaluation For Early or New-onset type 1 Diabetes). [3] [4] Tolerx entered into a collaboration with Glaxo SmithKline in October 2007 relating to the development and commercialization of otelixizumab. [5] Otelixizumab has been granted Orphan Drug Status by the U.S. Food and Drug Administration. [6]

Additionally, in collaboration with Genentech, Tolerx is developing a modified version of TRX1, a humanized monoclonal antibody that binds to the CD4 receptor found on both T effector and T regulatory cells. The safety and activity of TRX1 was evaluated by Tolerx in a single-dose, placebo-controlled, double-blind Phase 1 clinical trial. The data from the Phase 1 clinical trial showed TRX1 was well tolerated, did not deplete T cells, and had no observed first-dose side effect. [7] The modified version of TRX1, designated MTRX1011A, is being developed for the treatment of autoimmune diseases, which may include rheumatoid arthritis, cutaneous lupus erythematosus (CLE), multiple sclerosis (MS), and systemic lupus erythematosus (SLE). [8]

The Tolerx pipeline also includes two pre-clinical candidates: TRX518, an antibody directed to GITR (glucocorticoid-induced tumor necrosis factor receptor), a surface receptor molecule that has been shown to be involved in inhibiting the suppressive activity of T regulatory cells and extending the survival of T effector cells, [9] and TRX385, a monoclonal antibody that recognizes ILT3, an inhibitory receptor expressed by dendritic cells and monocytes. These pre-clinical candidates may be developed for the treatment of cancer and viral diseases.[ citation needed ]


Herman Waldmann, PhD, FRCPath, MRCP, FRS, FMedSci, [10] Co-Founder, Chairman, Scientific Advisory Board, Professor of Pathology, Head of the Sir William Dunn School of Pathology and Clinical Director of the Therapeutic Antibody Centre (TAC), University of Oxford

“A pioneer in the field of monoclonal antibody production” [11]

Douglas J. Ringler, VMD, [12] [13] Co-Founder, President & CEO

Louis Vaickus, MD [12] [14] Chief Medical Officer

Thomas A. Shea, MBA [15] Chief Financial Officer

Related Research Articles

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Immunosuppressive drugs, also known as immunosuppressive agents, immunosuppressants and antirejection medications, are drugs that inhibit or prevent activity of the immune system.

Rituximab Pharmaceutical drug

Rituximab, sold under the brand name Rituxan among others, is a monoclonal antibody medication used to treat certain autoimmune diseases and types of cancer. It is used for non-Hodgkin lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, granulomatosis with polyangiitis, idiopathic thrombocytopenic purpura, pemphigus vulgaris, myasthenia gravis and Epstein–Barr virus-positive mucocutaneous ulcers. It is given by slow injection into a vein. Biosimilars of Rituxan include Blitzima, Riabni, Ritemvia, Rituenza, Rixathon, Ruxience, and Truxima.

<span class="mw-page-title-main">CD20</span> Mammalian protein found in Homo sapiens

B-lymphocyte antigen CD20 or CD20 is expressed on the surface of all B-cells beginning at the pro-B phase and progressively increasing in concentration until maturity.

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Biological response modifiers (BRMs) are substances that modify immune responses. They can be both endogenous and exogenous, and they can either enhance an immune response or suppress it. Some of these substances arouse the body's response to an infection, and others can keep the response from becoming excessive. Thus they serve as immunomodulators in immunotherapy, which can be helpful in treating cancer and in treating autoimmune diseases, such as some kinds of arthritis and dermatitis. Most BRMs are biopharmaceuticals (biologics), including monoclonal antibodies, interleukin 2, interferons, and various types of colony-stimulating factors. "Immunotherapy makes use of BRMs to enhance the activity of the immune system to increase the body's natural defense mechanisms against cancer", whereas BRMs for rheumatoid arthritis aim to reduce inflammation.


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Otelixizumab, also known as TRX4, is a monoclonal antibody, which is being developed for the treatment of type 1 diabetes and other autoimmune diseases. The antibody is being developed by Tolerx, Inc. in collaboration with GlaxoSmithKline and is being manufactured by Abbott Laboratories.

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Rinat Neuroscience Corporation was a privately held biotechnology company that discovered and developed antibody-based drugs including:

Tolerogenic therapy aims to induce immune tolerance where there is pathological or undesirable activation of the normal immune response. This can occur, for example, when an allogeneic transplantation patient develops an immune reaction to donor antigens, or when the body responds inappropriately to self antigens implicated in autoimmune diseases. It must provide absence of specific antibodies for exactly that antigenes.


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Otilimab is a fully human antibody which has been developed by the biotechnology company MorphoSys. It can also be referred to as HuCAL antibody, HuCAL standing for Human Combinatorial Antibody Library and being a technology used to generate monoclonal antibodies. Otilimab is directed against the granulocyte-macrophage colony stimulating factor (GM-CSF), a monomeric glycoprotein functioning as a cytokine promoting both proliferation and activation of macrophages and neutrophils.


  1. Fierce Biotech’s 2008 Fierce 15
  2. "Exclusive: Tolerx cuts staff, auctioning assets after PhIII failure".
  3. From, a Service from the U.S. National Institutes of Health
  5. Windhover Information “GSK buys rights to Tolerx's diabetes antibody otelixizumab”
  6. Mass High Tech, May 16, 2008, “N.E. drug makers find individual paths into growing diabetes arena”
  7. Vaickus, L.; Stefanich, E; Anand, BS; Fielder, PJ; Vaickus, L (Jan 2006). "Pharmacokinetics/pharmacodynamics of nondepleting anti-CD4 monoclonal antibody (TRX1) in healthy human volunteers". Pharm. Res. 23 (1): 95–103. doi:10.1007/s11095-005-8814-3. PMID   16308668. S2CID   2209907.
  8. Windhover Information “Genentech licenses Tolerx's TRX1 for autoimmune disease”
  9. Jun Shimizu, Ph.D (2002). "Stimulation of CD25+CD4+ regulatory T cells through GITR breaks immunological self-tolerance" (Web). Tokyo Metropolitan Institute of Gerontology. Retrieved 2009-04-15.
  10. Business Week Personal Profile
  11. University of Cambridge “Success Stories”
  12. 1 2 OneMedPlace Profile
  13. Business Week Personal Profile
  14. Business Week Personal Profile
  15. Business Week Personal Profile