Magenta’s mission is to revolutionize stem cell transplant as the treatment for immune and blood diseases.
Stem cell transplant is a curative approach for a variety of severe blood cancers but is seldom used outside of cancer due to toxicities associated with the transplant procedure. Recent clinical data show that stem cell transplant can cure patients suffering from sickle cell disease, inherited metabolic disorders and severe autoimmune diseases. By developing safer and more effective therapeutics for conditioning, next generation products for stem cell mobilization and novel therapeutics for stem cell expansion, Magenta’s products will enable more patients to access the curative power of HSCT.
Timeline of stem cell transplant
Bone marrow stem cell transplantation has a long history and today more than 1 million patients have undergone this life saving procedure. The first transplant was performed in the late 1950s by E. Donnall Thomas where a leukemia patient was transplanted with bone marrow from her identical twin. This was followed by transplants using non-genetically identical “allogenic” bone marrow for patients with genetic diseases (1968) and leukemia (1970). Several decades of work were required to transform bone marrow transplant from a risky experimental therapy to a mainstay of treatment for blood cancers. For his pioneering work in stem cell transplant Dr Thomas was awarded the Nobel Prize in Medicine in 1990. The use of stem cell transplant continues to grow with data showing that it can cure patients suffering from sickle cell disease and severe autoimmunity. In addition, stem cells grown in the laboratory have been used to treat leukemia patients and the first stem cell based “gene therapy” product was approved to treat children born with severe immune deficiency.
Despite this progress stem cell transplant remains a high-risk procedure due to the toxicity of the agents used to condition the patient for transplant, complications of the transplant procedure, a lack of available stem cells for many patients and the difficulty of growing stem cells in the laboratory. Magenta is developing products to address each of these challenges for patients.
The Patient Journey
Stem cell transplant involves several steps. The patient, primary caregivers (e.g., oncologist, hematologist, rheumatologist, neurologist), a team of transplant doctors, and other specialty staff work together during each phase of the process.
1. Upon referral, the transplant team completes the evaluation of the patient’s medical condition and determines their eligibility for a stem cell transplant.
2. The patient’s (autologous) or donor’s (allogeneic) stem cells are harvested through apheresis after they have been mobilized from the bone marrow by giving medication that makes the bone marrow release a large number of stem cells into the bloodstream. Alternatively, the stem cells are removed from the pelvis bone with anesthesia.
3. A few days before the transplant, the patient will receive “conditioning” treatment (in a single day or in divided doses over a several days) which is a very high dose of chemotherapy with or without radiation. The conditioning treatment will destroy many cells in the patient’s body to create space in the bone marrow for the new transplanted stem cells, and will suppress the immune system to lower the chance of stem cell rejection. Conditioning is very toxic and associated with many acute and long term side effects.
4. After the transplant, the new stem cells engraft and begin to produce new red blood cells, white blood cells and platelets. The high doses of chemotherapy and radiation destroy the bone marrow, leaving the patient susceptible to infections during this period. If the stem cells are from an allogeneic donor, there is a risk of graft versus host disease (GVHD), in which transplanted cells (graft) recognize the patient’s body (host) as foreign and attack it. Engraftment usually occurs within two to four weeks after the transplant, but it takes much longer for full immune system to recover.
5. After a full immune recovery, and if there are no complications, the patient can go back to a normal life
Magenta has built an exceptional team of industry-leading scientists with extensive experience in hematopoietic stem cell biology, antibody therapeutics and drug development. With expertise in all aspects of stem cell biology including state-of-the-art methods for cell culture, in vivo testing and genetic manipulation Magenta is uniquely positioned to identify and develop novel therapeutics to transform stem cell transplant. Our three focus areas are novel targeted therapeutics for patient conditioning, rapid and efficient agents for stem cell harvesting, and new methods to promote stem cell growth during culture in the laboratory.
Preparing the patient for transplant
Prior to receiving a transplant, patients are conditioned to eliminate existing stem cells, diseased cells and to prevent rejection of the incoming stem cells. Currently this involves the use of highly toxic agents originally developed to treat cancer and procedures such as irradiation that kill cells non-specifically. Magenta scientists have shown that antibodies recognizing stem cells linked to drugs can be used to safely and selectively remove stem cells. The improved safety of these targeted conditioning agents will allow stem cell transplant to be used in patients that cannot tolerate current conditioning protocols and in patients where stem cell transplant is thought to be too dangerous.
Stem cell harvesting
Stem cells normally are found in the bone marrow but following treatment with growth factors can be “mobilized” from the bone marrow to the blood where they can be harvested for use. This mobilization process results in stem cells that engraft the patient more quickly reducing the time spent in the hospital. Current stem cell harvesting procedures take 5 or more days and some patients do not achieve enough stem cells for a transplant. The alternative is to have bone marrow withdrawn from the pelvis under general anesthesia. Magenta scientists have discovered new molecules that result in the robust mobilization of large numbers of stem cells, thereby providing a readily available source of stem cells for more patients.
Stem cell expansion
Stem cell based therapies are being developed to treat a variety of diseases. Many of these therapies require culture of stem cells in the laboratory to introduce therapeutic genes or correct genetic mutations, however current methods for growing stem cells in the laboratory are not effective. Magenta scientists have discovered methods that allow expansion of stem cells and maintain the ability to be transplanted. These methods will improve the outcomes of stem cell based therapies and provide increased access to transplant for patients that do not have a matched adult donor.
Magenta is honored to have assembled a distinguished group of scientific founders, including Drs. Hoggatt, Czechowicz and Palchaudhuri, each of whom are emerging as leaders in their field.