Press Release Details
Magenta Therapeutics Presents Data at Annual Meeting of American Society of Gene and Cell Therapy Demonstrating Cells Mobilized with MGTA-145 in a Phase I Trial Are Effective in Gene Therapy Settings
– MGTA-145 was shown to be a rapid, reliable, efficient and G-CSF-free method to obtain high numbers of functional HSCs in a Phase 1 trial; the cells could be gene modified and engraft in animals. MGTA-145 could be used to improve collection and gene therapy outcomes –
– Additional preclinical data show MGTA-145 serves as efficient, same-day mobilization regimen for in vivo HSC gene therapy in animals, which could be applicable in treating sickle cell disease and other genetic disorders –
Magenta is developing MGTA-145 as a first-line standard of care for hematopoietic stem cell (HSC) mobilization in a broad range of diseases, including autoimmune diseases, blood cancers and genetic diseases, such as sickle cell disease. MGTA-145, a CXCR2 agonist, acts in combination with plerixafor, a CXCR4 antagonist, and met all endpoints in a Phase I trial showing reliable same-day mobilization and collection of HSCs for genetic modification and transplant. MGTA-145 has been dosed in more than 100 healthy volunteers.
Magenta intends to initiate multiple Phase 2 trials of MGTA-145 and generate initial Phase 2 data in 2020. These trials, which will include both allogeneic and autologous transplant settings, will evaluate mobilization and collection of functional HSCs and their engraftment in patients after transplant to rebuild the blood and immune systems.
“MGTA-145 has the potential to fundamentally transform the standard of care for stem cell mobilization, collection and engraftment for patients and donors,” said
MGTA-145 Preclinical Data
These data demonstrate that MGTA-145, in combination with plerixafor, enables the same-day mobilization of sufficient functional HSCs that can be gene modified and engrafted.
Title: MGTA-145, in Combination with Plerixafor, Rapidly Mobilizes Large Numbers of HSCs in Humans That Can Be Gene Edited with CRISPR/Cas9 and Mediate Superior Engraftment to Standard-of-Care (Abstract #123)
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In a limit dilution study using CD34+ cells from a Phase 1 healthy volunteer study, same-day, single-dose mobilization with MGTA-145, in combination with plerixafor, led to 10x higher numbers of engrafting human HSCs in NSG mice, as compared to current standard-of-care approaches. Higher engraftment was confirmed by congenic mouse transplant models in primary and secondary recipients, indicating durable engraftment with MGTA-145 plus plerixafor mobilized blood.
To determine whether MGTA-145 plus plerixafor mobilized blood CD34+ cells could be efficiently gene-modified for use in a variety of therapeutic applications, CD34+ cells from two healthy donors were edited with CRISPR/Cas9 targeting beta-2-microglobulin. Ninety percent editing was achieved, and these cells were successfully engrafted in an NSG mouse model.
This same-day mobilization and collection regimen could potentially offer a significant improvement of cell collection protocols and autologous gene therapy outcomes for a variety of genetic diseases.
Title: MGTA-145/Plerixafor-Mediated HSC Mobilization and Intravenous Gene Therapy in Mice Allows for Efficient in vivo HSC Transduction and Stable
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These results show, for the first time, that MGTA-145 plus plerixafor can enable robust, same-day mobilization of large numbers of stem cells in animal models that can be efficiently modified in vivo by gene therapy without transplant, which could be applicable in patients with sickle cell disease or other genetic disorders.
The data show that the one-hour MGTA-145 + plerixafor mobilization regimen was superior compared to the five-day G-CSF + plerixafor approach, yielding less leukocytosis, lower cytokine release after virus delivery, better cost effectiveness and, potentially, improved performance in models of hemoglobinopathies.
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