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

CAMBRIDGE, Mass.--(BUSINESS WIRE)--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 programs 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 WashingtonDate 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.

About Magenta Therapeutics

Headquartered in Cambridge, Mass., Magenta Therapeutics is a clinical-stage biotechnology company developing novel medicines for patients with autoimmune diseases, blood cancers and genetic diseases. By creating a platform focused on critical areas of unmet need, Magenta Therapeutics is pioneering an integrated approach to allow more patients to receive one-time, curative therapies by making the process more effective, safer and easier.

Forward-Looking Statement

This press release may contain forward-looking statements and information within the meaning of The Private Securities Litigation Reform Act of 1995 and other federal securities laws, including express or implied statements regarding Magentas future expectations, plans and prospects, including, without limitation, statements regarding expectations and plans for presenting pre-clinical and clinical data, the anticipated timing of our clinical trials, and the development of our product candidates. The use of words such as may, will, could, should, expects, intends, plans, anticipates, believes, estimates, predicts, projects, seeks, endeavor, potential, continue or the negative of such words or other similar expressions can be used to identify forward-looking statements. The express or implied forward-looking statements included in this press release are only predictions and are subject to a number of risks, uncertainties and assumptions, including, without limitation: uncertainties inherent in clinical studies and in the availability and timing of data from ongoing clinical studies; whether interim results from a clinical trial will be predictive of the final results of the trial; whether results from preclinical studies or earlier clinical studies will be predictive of the results of future trials; the expected timing of submissions for regulatory approval or review by governmental authorities; regulatory approvals to conduct trials or to market products; risks, uncertainties and assumptions regarding the impact of the COVID-19 pandemic on Magentas business, operations, strategy, goals and anticipated timelines; and other risks concerning Magenta are described in additional detail in its risks set forth under the caption Risk Factors in Magentas most recent Annual Report on Form 10-K filed on March 3, 2020, as updated by Magentas most recent Quarterly Report on Form 10-Q and its other filings with the Securities and Exchange Commission. In light of these risks, uncertainties and assumptions, the forward-looking events and circumstances discussed in this press release may not occur and actual results could differ materially and adversely from those anticipated or implied in the forward-looking statements. You should not rely upon forward-looking statements as predictions of future events. Although Magenta believes that the expectations reflected in the forward-looking statements are reasonable, it cannot guarantee that the future results, levels of activity, performance or events and circumstances reflected in the forward-looking statements will be achieved or occur. Moreover, except as required by law, neither Magenta nor any other person assumes responsibility for the accuracy and completeness of the forward-looking statements included in this press release. Any forward-looking statement included in this press release speaks only as of the date on which it was made. We undertake no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events or otherwise, except as required by law.

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Magenta Therapeutics Presents Data at Annual Meeting of American Society of Gene and Cell Therapy Demonstrating Cells Mobilized with MGTA-145 in a...