Data presented at the 2009 American Transplant Congress
REGiMMUNE Corporation has announced that its lead product candidate RGI-2001, in combination with a low-dose of Sirolimus, demonstrated enhanced efficacy in transplantation tolerance induction in models of skin transplantation and acute Graft-versus-Host disease (GvHD). This data was presented in a poster titled “Donor-Specific Tolerance Induction by a Liposomal Formulation of KRN7000 (RGI-2001) Alone and in Combination with Low-Dose Sirolimus” at the 2009 American Transplant Congress being held in Boston.
“We are extremely pleased to present this data,” stated Haru Morita, President and Chief Executive Officer of REGiMMUNE. “The study not only demonstrated the efficacy of RGI-2001 in solid organ transplants; it showed the potential of RGI-2001 to induce antigen-specific transplantation tolerance, which is considered a holy grail in transplantation.”
KRN7000, a synthetic derivative of alpha-galactosylceramide, is a small molecule that potently activates natural killer T (NKT) cells. RGI-2001 is a proprietary liposomal formulation of KRN7000. RGI-2001 monotherapy has shown to induce antigen-specific immune suppression by inducing regulatory T cells (Tregs). Tregs are believed to play a central role in inducing and maintaining immune tolerance. The study was designed to evaluate the efficacy of RGI-2001 in combination with Sirolimus in transplantation tolerance induction in mouse models.
Pharmacological induction of alloantigen-specific tolerance is expected to provide significant clinical benefits in organ transplantation and bone marrow transplantation. The REGiMMUNE study concluded that the addition of a subtherapeutic dose of Sirolimus enhanced the efficacy of RGI-2001 in both models. The combination treatment significantly prolonged the survival of grafts in the skin transplant model over Sirolimus single treatment. Likewise, GvHD mortality was reduced by the combination treatment. In addition, the combination of RGI-2001 with low-dose Sirolimus significantly enhanced Treg induction.
The results indicate the potential of RGI-2001 to be a key component of a novel tolerance induction regimen, avoiding the use of calcineurin inhibitors that are not only associated with high toxicity but suppress Treg activity. The finding suggests the possibility to develop a pharmacological approach to induce long-term transplant tolerance by promoting the body’s intrinsic tolerogenic pathways using RGI-2001.
RGI-2001 is in late preclinical development and REGiMMUNE plans to file an Investigational New Drug (IND) for the prevention of acute GvHD associated with bone marrow transplantation later this year.