TRX103 for prevention of GvHD in patients receiving HLA mismatched related or unrelated allogeneic HSCT for the treatment of hematologic malignancies.
Grant Award Details
Grant Type:
Grant Number:
CLIN1-14840
Investigator(s):
Disease Focus:
Human Stem Cell Use:
Award Value:
$4,000,000
Status:
Active
Grant Application Details
Application Title:
TRX103 for prevention of GvHD in patients receiving HLA mismatched related or unrelated allogeneic HSCT for the treatment of hematologic malignancies.
Public Abstract:
Therapeutic Candidate or Device
An allogenic, off the shelf, engineered regulatory T cell product that mimics the function of T regulatory Type 1 (Tr1) cells.
Indication
Prevention of acute and chronic Graft versus Host Disease (GvHD) in patients undergoing mismatched stem cell transplant.
Therapeutic Mechanism
GvHD is driven by the reaction of allogenic donor T cells to host target tissues and antigens. TRX103 will suppress GvHD by secretion of IL-10 and other cytokines in target tissues and organs, as well as through the stimulation of production of de-novo Tr1 cells in patients.
Unmet Medical Need
GvHD affects patients undergoing mismatched hematopoietic stem cell transplant (HSCT) and is a major cause of morbidity and mortality. Only ~50% of HSCT patients are disease and relapse-free (GRFS) after one year. TRX103 will broaden access to transplants, while reducing the burden of GvHD.
Project Objective
IND submission completed.
Major Proposed Activities
An allogenic, off the shelf, engineered regulatory T cell product that mimics the function of T regulatory Type 1 (Tr1) cells.
Indication
Prevention of acute and chronic Graft versus Host Disease (GvHD) in patients undergoing mismatched stem cell transplant.
Therapeutic Mechanism
GvHD is driven by the reaction of allogenic donor T cells to host target tissues and antigens. TRX103 will suppress GvHD by secretion of IL-10 and other cytokines in target tissues and organs, as well as through the stimulation of production of de-novo Tr1 cells in patients.
Unmet Medical Need
GvHD affects patients undergoing mismatched hematopoietic stem cell transplant (HSCT) and is a major cause of morbidity and mortality. Only ~50% of HSCT patients are disease and relapse-free (GRFS) after one year. TRX103 will broaden access to transplants, while reducing the burden of GvHD.
Project Objective
IND submission completed.
Major Proposed Activities
- Preclinical in vitro and in vivo studies to characterize the TRX103 product and determine its safety and efficacy in preclinical models of disease.
- Process development, optimization and technology transfer to partner CDMO for production of the TRX103 product to enable IND submission.
- Process Development, engineering and clinical manufacturing runs of the TRX103 product to enable IND submission.
Statement of Benefit to California:
Mismatched hematopoietic stem cell transplants have worse outcomes than matched transplants, due to higher incidence and severity of GvHD. The proposed research will enable human trials of a novel product, TRX103 in these patients. Should the research achieve its objective, Californians will have access to a therapy that will broaden access to curative stem cell transplants, while reducing the (significant) risks associated with GvHD.