Our novel targeted therapeutics are designed to transform patient preparation, stem cell expansion and stem cell harvesting, and reduce post-transplant complications such as Graft-Versus-Host Disease.
Before a transplant, patients are conditioned to remove existing stem cells in the bone marrow and diseased cells, and to prevent rejection of the incoming stem cells. This process currently uses highly toxic agents originally developed to treat cancer, and procedures such as radiation that kill cells in a non-specific manner. The toxic nature of these treatments prevents many patients from getting a transplant.
Magenta scientists have shown that antibodies that recognize stem cells linked to drugs can be used to safely and selectively remove stem cells and diseased cells.
The improved safety of these targeted conditioning agents may extend the use of curative bone marrow transplant to patients who cannot tolerate current conditioning methods and in patients where bone marrow transplant is currently thought to be too dangerous.
Stem Cell Expansion
Stem cell based therapies are being developed to treat a variety of diseases, including malignant and non-malignant conditions. To be effective, these therapies need to deliver the optimal number of healthy stem cells (cell dose) to patients.
Many patients do not have a matched stem cell donor for transplant. Unexpanded cord blood transplants are used in patients who do not have a matched sibling donor, but finding a well-matched cord and engraftment of the cord blood unit can be a challenge due to the low number of stem and progenitor cells available in many banked umbilical cords.
In other cases — such as gene editing and gene therapy — delivering a high number of cells modified with the curative gene technology could be directly correlated with the effectiveness of these approaches.
Magenta scientists are developing methods that allow expansion of stem cells and maintain the ability of the cells to be transplanted. These methods will allow for an optimal number of healthy stem cells to be delivered to patients and may improve the outcomes of stem cell based therapies.
Our most advanced clinical-stage program, MGTA-456, is being investigated in a variety of transplant settings. By expanding the number of cord blood stem cells, MGTA-456 has the potential to improve overall survival by allowing more patients to have access to better HLA-matched cord blood units.
We are also advancing earlier-stage programs focused on gene-modified stem cell expansion.
Stem Cell Harvesting
In addition to cord blood, stem cells can be harvested in two ways: Directly from the patient, in an autologous transplant, or from a donor, in an allogeneic transplant.
In an allogenic donation, stem cells in the bone marrow are normally withdrawn from the pelvis through a bone marrow harvest, a painful procedure performed with the patient under general anesthesia.
Alternatively, following treatment with growth factors, either donors’ or patients’ stem cells can be “mobilized” to the blood to be harvested for use. Current stem cell mobilizing procedures take five or more days and some patients do not achieve enough stem cells for a transplant.
Magenta scientists have developed new modalities that result in the robust mobilization of large numbers of stem cells to the blood in a single day, thereby providing a readily available source of higher quality stem cells for more patients.
There are a variety of potential complications post-transplant. One of the most common complications is graft-versus-host disease (GvHD), in which donor stem cells attack the recipients’ own body, both acutely and chronically post-transplant.
Magenta is pursuing new therapies that can target GvHD-causing donor T-cells, and reduce the occurrence of acute GvHD without sacrificing the beneficial effects of the donor graft.
Deplete Hematopoietic stem cells (HSCs) and immune cells
Deplete immune cells
Expand cord blood outside the body
Expand stem cells outside the body for gene therapy/editing
Deplete allo-activated immune response