Magenta Therapeutics (NASDAQ:MGTA), a clinical-stage biotechnology company developing novel medicines to bring the curative power of blood and immune reset to more patients, presented preclinical data on its stem cell mobilization therapy clinical candidate, MGTA-145, this week at the annual meeting of the American Society of Gene and Cell Therapy (ASGCT).
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 John Davis Jr., M.D., M.P.H., M.S., Head of Research & Development and Chief Medical Officer, Magenta Therapeutics. “These data provide further confirmation that cells obtained with MGTA-145 can be used in gene therapy and gene editing settings across various genetic diseases. These are encouraging findings for the breadth of applications for MGTA-145, showing safe and robust mobilization of functional cells that can be used for stem cell transplant, as well as for gene therapy applications, expanding the program’s potential for even more patients beyond the 150,000 patients presently eligible in the U.S. and Europe.”
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)
Presenter: Kevin Goncalves, Ph.D., Magenta Therapeutics, Cambridge, Mass.
Date and Time: Tuesday, May 12, 2020 – 3:45-5:30pm
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 Gene Marking in Peripheral Blood Cells (Abstract #810)
Presenter: Chang Li, Ph.D., Division of Medical Genetics, Department of Medicine, University of Washington
Date and Time: Wednesday, May 13, 2020 – 5:30-6:30pm
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.