Our Programs

Currently, only a fraction of patients receive a transplant because the risks and challenges outweigh the potential for a cure.

Immune reset through transplant is a 2-step process:

Step 1: Removing the disease-causing cells
Step 2: Replacing them with healthy cells to rebuild the immune system to a healthy state

All stem cell transplants are categorized as either autologous or allogeneic, depending on the source of the healthy cells for the transplant. In an autologous transplant, used for conditions such as autoimmune diseases and multiple myeloma, the patient’s own stem cells are used. This is also the case for stem cell gene therapy for genetic diseases such as sickle cell disease. In an allogeneic transplant, used for conditions such as acute leukemia, patients receive cells from a stem cell donor.

Our comprehensive portfolio of novel therapies is designed to change the treatment landscape in both autologous and allogeneic transplant.

We’re developing medicines to improve all aspects of the transplant journey, including patient preparation, stem cell collection, cell dose and safe immune regeneration.

Patient Preparation

Precisely Removing Disease-Causing Cells

Current methods to condition patients before transplant are dependent on toxic, nonspecific chemotherapy or radiation. These pre-transplant treatments are associated with significant side effects, including infertility, cancer, organ damage and even death. These risks understandably prevent many patients from undergoing a life-saving and potentially curative transplant procedure. We’re here to change that.

Our solution: We have developed three profiles — CD45-ADC, CD117-ADC, and C300 — that will precisely remove the disease-causing cells in the body, without the need for chemotherapy or radiation, and make room for the incoming healthy cells to rebuild a functioning immune system.

Current Development Plans:

Our CD45-ADC program includes targeted antibody-drug conjugates (ADCs) that are designed to reset the immune system for patients with autoimmune diseases. Our ADCs target CD45, a protein expressed on immune cells and blood stem cells.

Our CD117-ADC program includes targeted ADCs designed to enable blood and immune system rebuild in patients with genetic diseases treated via gene therapy or stem cell transplant. Our ADCs target CD117, a protein expressed on blood stem cells.

Both CD45-ADC and CD117-ADC may also work to allow patients with blood cancers to achieve durable remissions through stem cell transplant.

Revamping Stem Cell Mobilization and Collection

Magenta is developing MGTA-145 to be the first-line therapy for same-day mobilization and collection of hemopoietic stem cells (HSCs) to enable successful rebuilding of the blood and immune system for all patients. MGTA-145 has the potential to be used across a broad range of diseases, including blood cancers, autoimmune diseases and genetic diseases, such as sickle cell disease.

MGTA-145, a CXCR2 agonist, works in combination with plerixafor, a CXCR4 antagonist, to harness the physiological mechanism of stem cell mobilization to rapidly and reliably mobilize HSCs for collection and transplant.

MGTA-145 has the potential to become the first medicine approved for the mobilization of stem cells in patients with genetic and autoimmune diseases. MGTA-145 also has the potential to replace the current standard of care for patients and allogeneic donors who currently rely on the use of granulocyte-colony stimulating factor (G-CSF), which takes five or more days to mobilize stem cells, does not mobilize reliably, causes significant bone pain and results in other side effects.

MGTA-145 Latest Results & Next Steps

In the first half of 2020, Magenta completed its Phase 1 trial of MGTA-145 in healthy volunteers, demonstrating MGTA-145 was well tolerated and enables same-day dosing, mobilization and collection of sufficient functional stem cells for transplant.

In May 2020, the U.S. FDA’s Office of Orphan Products and Development granted Orphan Drug Designation to MGTA-145 for the mobilization of HSCs to the peripheral blood for collection and subsequent transplant.

In May 2020, data presented at the American Society of Gene & Cell Therapy’s annual meeting showed MGTA-145 enables same day mobilization of functional HSCs that can be gene modified with CRISPR/Cas9 and mediate durable engraftment in preclinical models.

Stanford University is currently conducting a Phase 2 trial studying MGTA-145, in combination with plerixafor, in the mobilization and engraftment of hematopoietic stem cells for autologous transplantation in multiple myeloma patients.

Magenta intends to initiate multiple Phase 2 trials of MGTA-145 to include both allogeneic and autologous transplant settings across multiple diseases. These trials will evaluate mobilization and collection of functional HSCs and engraftment of the cells after transplant.

Rebuilding Healthy Immune Systems Through Higher Doses of Better-Matched Cells

Stem cell transplant is the only disease-modifying treatment option in many genetic diseases and certain blood cancers. But unfortunately, due to low cell dose and poor matching, transplants fail in up to 40% of patients.

MGTA-456 is a cell therapy designed to provide a high dose of stem cells that are well matched to the patient.

We previously demonstrated clinical proof of concept for MGTA-456 in 36 patients with blood cancers. One hundred percent of these patients were successfully engrafted, and this work is being continued in a Phase 2 investigator-initiated study in patients with acute leukemias at the University of Minnesota.

Reducing Post-Transplant Complications

Graft-versus-host disease (GvHD) is a reaction that commonly develops after an allogeneic transplant, when stem cells are donated to the patient from another person. This reaction is a result of the donor immune cells recognizing the patient’s cells as foreign and attacking them. Acute GvHD typically occurs within weeks of a patient receiving a stem cell transplant and can severely damage the liver, skin and gastrointestinal system. Current treatments for acute GvHD prevention include the use of nonspecific agents to suppress the immune system, which is correlated with an increased risk of infection and poor immune function.

Our G100 program is designed to selectively eliminate only the cells that cause acute GvHD and is to be dosed at the time of transplant. By specifically targeting the cells that arise shortly after transplant, this therapy is intended to allow regeneration of a healthy immune system in the patient.