REGiMMUNE Corporation (RGI) OKYO, JAPAN--(Marketwired - Mar 9, 2017); is pleased to announce the publication of its Phase 2a clinical trial results for RGI-2001, a novel liposomal formulation of a synthetic derivative of alpha-galactosylceramide, a naturally occurring ligand that binds to CD1d and activates invariant natural killer T cells (iNKT). The company is developing RGI-2001 to ameliorate Graft versus Host Disease (GvHD) after allogeneic hematopoietic cell transplantation. The paper: "Increased Foxp3+Helios+ Regulatory T Cells and Decreased Acute Graft-versus-Host Disease after Allogeneic Bone Marrow Transplantation in Patients Receiving Sirolimus and RGI-2001, an Activator of Invariant Natural Killer T Cells" is now available from the online publication "Biology of Blood and Marrow Transplantation" http://www.bbmt.org/article/S1083-8791(17)30194-5/pdf. This is the first clinical demonstration of a novel therapeutic that potentially expands Foxp3+regulatory T cells (Treg) mediated by the activation of iNKT cells in patients. RGI-2001, which utilizes REGiMMUNE's reVax technology, promotes transplantation tolerance by inducing Tregs. Tregs have been shown to have significant potential for treating GvHD; in studies by independent researchers, Tregs have proven to produce longer patient survival because they could suppress rejection without reducing an anti-tumor graft versus leukemia effect."The studies show that the administration of RGI-2001 was safe and resulted in increased numbers of Tregs vs. conventional CD4+ T cells after allogeneic transplantation in some patients, especially in those treated with the mammalian target of rapamycin inhibitor sirolimus as part of their GvHD prophylaxis regimen," commented Dr. Jack Bui, MD, PhD, Associate Professor, Director of Clinical Flow Cytometry and the Stem Cell Processing Laboratory, Department of Pathology, University of California San Diego. The Phase 2a clinical trial of single-dose RGI-2001 on day 0 in the treatment of 29 patients undergoing allogeneic HCT demonstrated that some patients treated with RGI-2001 had markedly increased the number of Tregs (CD4+CD25+CD127loFoxp3+) within 1 to 3 weeks after HCT. The patients who responded with an increased number of Tregs also had decreased GvHD onset compared with nonresponders. Some of the patients in this subset received sirolimus in addition to the standard of care using calcineurin inhibitors plus methotrexate for immunosuppression after HCT, suggesting potential synergy between sirolimus and RGI-2001 in Treg expansion in vivo. A randomized study is being designed to further evaluate the impact of serial dosing of RGI-2001 on Treg biology and GvHD prevention.
About reVax REGiMMUNE's reVax technology "re-educates" the immune system by inducing immune regulatory cells. reVax technology specifically suppresses the immune system target while maintaining normal immune reaction. In contrast, current technologies such as immunosuppressants broadly down-regulate the immune system, which can cause negative effects including risk of serious infection and toxicity. In addition, reVax works not only as a treatment, but can work as a vaccine in a prophylactic mode, without the need for adjuvants. Traditional vaccine therapies enhance immunoprotective ability against an antigen by immunizing it with a specific adjuvant, which itself can cause negative effects.
Immune system In the past few decades, breakthroughs in biotechnology, genomics and basic science have led to a better understanding of the human immune system and researchers have discovered new ways to treat diseases that affect the immune system. The immune system is a network of organs, glands, and tissues that protects the body from foreign substances. These substances include bacteria, viruses, and other infection-causing parasites and pathogens. Usually, the immune system is extremely effective in performing its work of defending the body, but sometimes an error occurs in this highly complex system, and it can lead health problems. The result can be a simple allergic reaction, as serious as a fatal condition such as cancer or the error can manifest as an autoimmune disorder, such as RA or SLE, in which the body rejects its own constituents as foreign invaders. The functioning of the immune system also calls into play a wide array of substances, most notably antibodies and the two significant varieties of lymphocyte: B cells and T cells. Antibodies, the most well known of the three, are proteins in the human immune system that help fight foreign invaders. B cells (B lymphocytes) are a type of white blood cell that gives rise to antibodies, whereas T cells (T lymphocytes), are a type of white blood cell that plays an important role in the immune response. T cells are a key component in the cell-mediated response, the specific immune response that utilizes T cells to neutralize cells that have been infected with viruses and certain bacteria. There are three types of T cells: cytotoxic, helper, and suppressor T cells. Cytotoxic T cells destroy virus-infected cells in the cell-mediated immune response, whereas helper T cells play a part in activating both the antibody and the cell-mediated immune responses. Suppressor T cells deactivate T cells and B cells when needed, and thus prevent the immune response from becoming too intense.
Immune tolerance The human immune system is designed to attack foreign invasion of disease-causing organisms while it protects normal function by way of unresponsiveness. Tolerance is the key mechanism of the specific unresponsiveness and is maintained by a subset of regulatory T cells called Treg. Tolerance is a direct way to treat immune disorders that are caused by excessive immune reaction against antigens. REGiMMUNE is currently developing products that induce Treg, which leads to antigen specific immune tolerance.
reVax induces Treg REGiMMUNE's proprietary technology platform reVax targets immune tolerance against specific disease-causing antigens through induction of regulatory T cells (Treg). reVax technology uniquely enables target-specific immune suppression, by tolerance induction. Unlike existing immune suppressants which broadly and excessively suppress immunity and cause subsequent issues such as infection and tumor progression, reVax suppresses only unfavorable immune reaction. reVax technology uniquely enables target-specific immune suppression, by tolerance induction.
α-GalCer α-GalCer is a glycolipid. It is a CD1d ligand originally isolated from the marine sponge and developed as an anti-tumor agent. It was evaluated in healthy volunteers and oncology patients and shown to have a good safety profile. Because α-GalCer was found to expand and activate natural killer (NKT) cells and subsequently, Treg, it was later developed as an immune-modulator. A liposomal formulation of α-GalCer injected with an antigen induces regulatory T cells efficiently and leads to an antigen specific immune tolerance. Preclinical models have demonstrated efficacy in many autoimmune disorders including GvHD, TIDM, RA, MS, and SLE. Results from both clinical and preclinical studies have been published in more than 1,000 papers in peer review journals.
reVax fomulation reVax technology uniquely enables target-specific immune suppression, by tolerance induction. Unlike existing immune suppressants which broadly and excessively suppress immunity and cause subsequent issues such as infection and tumor progression, reVax suppresses only unfavorable immune reaction. reVax technology uniquely enables target-specific immune suppression, by tolerance induction. Unlike existing immune suppressants which broadly and excessively suppress immunity and cause subsequent issues such as infection and tumor progression, reVax suppresses only unfavorable immune reaction.
RGI-3100 RGI-3100 is a different formulation of alpha-GalCer that REGiMMUNE is developing as a potential treatment for type 1 diabetes mellitus (TIDM), which results from autoimmune destruction of insulin-producing beta cells of the pancreas. Also known as insulin dependent or juvenile diabetes, the only current treatment for TDIM is injection of insulin, which must be administered lifelong. Several new approaches to treatment are in research by others, including islet transplantation. RGI-3100 is in preclinical development as an alternative approach to T1DM treatment with insulin. It is expected to protect beta cells by restoring normal immunity in people with T1DM by inducing Treg.
RGI-2001 RGI-2001 is a liposomal formulation of alpha-GalCer (a CD1d ligand), which induces regulatory T cells (Treg), a key player in immune tolerance. Treg has been shown to have significant potential for treating Graft-versus-Host Disease (GvHD). In studies by independent researchers, Treg has proven to provide longer patient survival because it reduces rejection without reducing a graft-versus-leukemia/tumor (GvL) effect. Unlike immunosuppressents that destroy entire T cell subsets, RGI-2001 induces Treg while maintaining normal immune cell functions and has the potential to reduce GvHD and improve survival for patients. The company has received orphan drug designation from the US FDA for developing this compound for the prevention of GvHD associated with hematopoietic stem cell transplantation.
Clinical trial A Phase I/II study of RGI-2001 for GvHD associated with hematopoietic stem cell transplantation was initiated in early 2012, following positive preclinical efficacy studies. The safety and efficacy clinical trial is enrolling approximately 50 bone marrow or peripheral blood stem cell transplantation leukemia patients following chemotherapy. The U.S.-based study is being conducted in seven leading cancer centers including the Fred Hutchinson Cancer Research Center, Stanford University Medical Center, the Ohio State University Medical Center, University of California, San Diego and at both Harvard University's Massachusetts General Hospital and Dana Farber Cancer Institute. For information regarding participation in the Phase I/II study of RGI-2001 for GvHD, please visit ClinicalTrials.gov or contact us.
About REGiMMUNE REGiMMUNE Corporation is a biotechnology company focused on the discovery, development and commercialization of immune regulatory therapeutics to treat life-threatening and debilitating conditions, including allergies, autoimmune diseases and transplantation. The company's proprietary platform technology, reVax, induces immune tolerance in an antigen-specific manner through pharmacological induction of regulatory T cells (Treg). Using its reVax technology, REGiMMUNE is developing RGI-2001, which may be the first drug in the class of Treg-inducing agents. The company is also applying its reVax technology to develop a range of pipeline products, including its RGI-1000 series for allergy and its RGI-3100 series for type 1 diabetes. Additionally, REGiMMUNE is developing products for preventing inhibitor formation in enzyme replacement therapies; for inflammatory bowel disease; and for celiac disease with undisclosed partners. The company is seeking pharmaceutical partnership opportunities for its products worldwide, exclusive of Japan. REGiMMUNE is headquartered in Tokyo, Japan and has a US operation in Berkeley, California. For more information, visit www.regimmune.com.
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