Magenta Therapeutics Demonstrates First-ever Successful Gene Therapy Transplant Without Chemotherapy in Primates Using a Single Dose of Antibody-drug Conjugate - Seite 2

Results from the CD117-ADC Patient Preparation Program

Title: A Single Dose of CD117 Antibody Drug Conjugate Enables Autologous Gene-Modified Hematopoietic Stem Cell Transplant (Gene Therapy) in Nonhuman Primates (Abstract #610)
Presenter: John Tisdale, M.D., Director, Molecular and Clinical Hematology Section, National Institutes of Health, Bethesda, Md.

Magenta’s most advanced patient preparation program, CD117-ADC, targets CD117, a protein expressed on hematopoietic stem cells. CD117-ADC is designed to remove the genetically mutated cells in the bone marrow that cause certain genetic diseases, such as sickle cell disease, enabling curative stem cell transplant or gene therapy.

Results presented by Dr. Tisdale showed:

• A single dose of a tool CD117-ADC fully depleted human hematopoietic stem cells in humanized mouse models.
• A single dose of CD117-ADC selectively depleted hematopoietic stem cells in non-human primates, while sparing immune cells, which are important for recovery following transplant.
• CD117-ADC was engineered to have a fast half-life to clear the body quickly and enabled transplant of the gene-modified cells within days of dosing in non-human primates.
• A single dose of CD117-ADC in non-human primates enabled successful transplant and engraftment of hematopoietic stem cells modified with a lentiviral vector encoding the β-globin gene, the gene that causes sickle cell disease and β-thalassemia.
• Vector copy number was stable beyond three months, the longest time point in the study, suggesting that the gene-modified cells persisted in the body. This was comparable to historical data with multiple doses of busulfan conditioning.
• CD117-ADC was well tolerated in non-human primates with no evidence of the often severe side effects seen with busulfan conditioning, including veno-occlusive disease, weight loss, diarrhea, mucositis, vomiting, pulmonary fibrosis or seizures.
• No ADC-related blood chemistry changes outside normal range were observed.
• These proof-of-concept studies validate the use of CD117-ADC for targeted stem cell depletion prior to transplant and support its use as a new conditioning agent for gene therapy and stem cell transplant without toxic chemotherapy or radiation.

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