Development of OSSM-007, cryopreserved interferon-gamma primed allogeneic MSCs, for treatment of steroid refractory acute graft versus host disease
Grant Award Details
Grant Type:
Grant Number:
CLIN1-14070
Investigator(s):
Disease Focus:
Human Stem Cell Use:
Award Value:
$3,457,858
Status:
Active
Grant Application Details
Application Title:
Development of OSSM-007, cryopreserved interferon-gamma primed allogeneic MSCs, for treatment of steroid refractory acute graft versus host disease
Public Abstract:
Therapeutic Candidate or Device
OSSM007: cryopreserved, interferon-gamma-primed bone marrow mesenchymal stem cells (BM-MSC)
Indication
acute Graft versus host disease (aGVHD) resulting from hematopoietic cell transplantation
Therapeutic Mechanism
Immunomodulation of host-reactive T cells to induce operational tolerance of donor HSC-derived lymphocytes through direct cell-to-cell contact and secreted paracrine factors. Interferon-gamma priming of MSCs enhances therapeutic effects through establishing the cells in a immunosuppressive state prior to treatment. Primed cells are able to quickly activate regulatory T cells as well as direct suppress host-reactive T cell activity.
Unmet Medical Need
Systemic steroid therapy is the standard first-line treatment for aGVHD; however, the disease becomes refractory to systemic steroid therapy in 35–50% of patients. Mortality rates for patients who fail to respond to first-line steroid therapy are 80% due to very limited alternative treatments.
Project Objective
Commence Phase 1 clinical trial
Major Proposed Activities
OSSM007: cryopreserved, interferon-gamma-primed bone marrow mesenchymal stem cells (BM-MSC)
Indication
acute Graft versus host disease (aGVHD) resulting from hematopoietic cell transplantation
Therapeutic Mechanism
Immunomodulation of host-reactive T cells to induce operational tolerance of donor HSC-derived lymphocytes through direct cell-to-cell contact and secreted paracrine factors. Interferon-gamma priming of MSCs enhances therapeutic effects through establishing the cells in a immunosuppressive state prior to treatment. Primed cells are able to quickly activate regulatory T cells as well as direct suppress host-reactive T cell activity.
Unmet Medical Need
Systemic steroid therapy is the standard first-line treatment for aGVHD; however, the disease becomes refractory to systemic steroid therapy in 35–50% of patients. Mortality rates for patients who fail to respond to first-line steroid therapy are 80% due to very limited alternative treatments.
Project Objective
Commence Phase 1 clinical trial
Major Proposed Activities
- Address clinical hold CMC issues, including OSSM-007 manufacturing reproducibility and stability of product
- Develop a matrix of predictive potency assays and demonstrate utility in a mouse aGVHD model
- Refine the clinical dosing regimen by conducting a dose escalation study in a humanized mouse model of aGVHD
Statement of Benefit to California:
Steroid-refractory acute Graft-versus-host-disease (SR-aGVHD) is a severe health concern given the 80% mortality rate associated with the disease. There are no effective treatments currently available, thus, SR-aGVHD patients face a very poor prognosis. Development of OSSM-007 has to the potential to extend the lifespans of this patient population by reducing disease severity and, potentially, reversing the course of the disease.