Magenta demonstrates gene therapy transplant without chemotherapy in primates
Magenta Therapeutics announced that new results from its CD117-ADC patient preparation program were presented at the 61st Annual Meeting of the American Society of Hematology. These results, which were highlighted in an oral presentation at ASH by John Tisdale, M.D., Director, Molecular and Clinical Hematology Section, National Institutes of Health, showed the first-ever successful transplant of gene-modified cells in non-human primates using a targeted, single-agent antibody-drug conjugate, without the use of chemotherapy or radiation. 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 beta-globin gene, the gene that causes sickle cell disease and beta-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.