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 therapies 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 3 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.

Stem Cell Collection

Revamping Stem Cell Collection 

The majority of stem cell transplants performed today use mobilized peripheral blood as the source of stem cells to rebuild a healthy immune system. The current standard of care for mobilization, a drug called granulocyte-colony stimulating factor (G-CSF), presents a number of challenges for patients, physicians, and the healthcare system:

  • Cannot be used in patients with autoimmune disease or sickle cell disease because of the risk of potentially fatal complications
  • Requires 5 days of dosing before cells can be collected
  • Does not always mobilize reliably or predictably, creating challenges for patients, donors, and apheresis centers
  • Is associated with significant bone pain, often requiring treatment with narcotics, and other side effects

Magenta is developing MGTA-145 as the new first-line standard of care for stem cell mobilization in a broad range of diseases, including autoimmune diseases and genetic diseases. MGTA-145 works in combination with plerixafor to mimic the physiological mechanism of stem cell mobilization. The MGTA-145-based combination is designed to reliably mobilize robust numbers of high-quality stem cells with single-day dosing and collection. Importantly, the MGTA-145-based combination also avoids the need for G-CSF.

We are currently studying MGTA-145 in combination with plerixafor, another mobilization therapy, in a Phase 1 trial in healthy volunteers.

Cell Dose

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 are developing MGTA-456 in a Phase 2 study in patients with inherited metabolic disorders, a set of fatal and rapidly progressive childhood diseases. We have seen early and durable resolution of disease in patients treated to date, suggesting that MGTA-456 has halted the progression of disease. This early resolution and durability of effect have not been seen consistently with other investigational therapies, including gene therapies.

The FDA has recently granted us orphan drug designation for MGTA-456 for the enhancement of cell engraftment in patients receiving stem cell transplant, as well as regenerative medicine advanced therapy (RMAT) designation based on the encouraging clinical data we have presented thus far. We plan to enroll a total of 12 patients in this study, and based on the data, advance into a Phase 3 study in 2020.

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.

Safe Immune Regeneration

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.