Magenta Therapeutics Presents Data Supporting Immune Reset for Autoimmune Diseases

June 5, 2020 12:30 UTC


-- Single dose of CD45-ADC shown to remove disease-causing cells and halt disease in models of multiple sclerosis, systemic sclerosis and inflammatory arthritis --

-- MGTA-145 Phase 1 clinical data for stem cell mobilization provide a strong rationale for studying in patients with autoimmune diseases --


CAMBRIDGE, Mass.--(BUSINESS WIRE)--Magenta Therapeutics(NASDAQ: MGTA), a clinical-stage biotechnology company developing novel medicines to bring the curative power of stem cell transplant to more patients, today reported the presentation of preclinical data showing successful immune reset with a single dose of its CD45-ADC in models of three autoimmune diseases. Magenta also highlighted data from its Phase 1 study of first-line stem cell mobilization therapy MGTA-145. These results were presented this week at the European League Against Rheumatism (EULAR) annual meeting.

“Millions of patients worldwide live with debilitating autoimmune diseases. Immune reset through stem cell transplant – removing the disease-causing cells and rebuilding a healthy immune system -- is the only potentially curative treatment option,” said John Davis Jr., M.D., M.P.H., M.S., Head of Research & Development and Chief Medical Officer, Magenta. “Magenta is developing targeted medicines such as CD45-ADC and MGTA-145 to revolutionize the immune reset process and enable more selected patients with autoimmune diseases to undergo a one-time, curative procedure that is better tolerated.”

Current standard treatment for patients with multiple sclerosis involves years of chronic dosing of medications that do not halt the progression of the disease and have significant side effects. For patients with systemic sclerosis, a potentially fatal disease, there are no approved therapies. Immune reset through stem cell transplant has demonstrated durable remissions in thousands of patients with autoimmune diseases such as multiple sclerosis and systemic sclerosis, and it is recommended by EULAR in treatment guidelines for systemic sclerosis. A pair of comprehensive reviews published in 2017 in Nature journals summarized the clinical transplant results in multiple sclerosis and broader rheumatic autoimmune diseases. The main conclusions from this combined experience in more than 3,000 patients during the past 20 years were that the therapeutic benefit of stem cell transplant is significant across multiple trials in severe autoimmune diseases: Relapsing remitting multiple sclerosis, or RRMS, (five Phase 2 trials) and systemic sclerosis (two Phase 2 trials and two randomized trials) have the most clinical evidence using stringent disease endpoints.

The process for immune reset through transplant involves two main steps: removing the disease-causing cells and replacing them with healthy cells to rebuild the immune system to a healthy state.


Magenta is the only company developing targeted antibody-drug conjugates designed to precisely remove the disease-causing cells in the body without the need for chemotherapy or radiation. Magenta’s CD45-ADC program targets CD45, a protein expressed on immune cells and stem cells, and is designed to remove the cells that cause autoimmune diseases to enable curative immune reset. Preclinical data highlighted in the oral presentation at EULAR showed that a single dose of CD45-ADC removed disease-causing reactive T cells, enabled successful immune reset to halt disease progression and was well tolerated in three models of autoimmune disease.

Multiple Sclerosis

Results showed that a single dose of CD45-ADC removed disease-causing reactive T cells, enabled successful immune reset and rebuild of the immune system and was well tolerated in a reliable murine model of autoimmune disease, the EAE model. Further, a single dose of CD45-ADC significantly reduced disease incidence and delayed disease onset in this model that has successfully provided preclinical proof of concept for many clinically validated standard-of-care therapies.

Systemic Sclerosis

Data showed that a single dose of CD45-ADC eliminated disease-causing effector cells and ameliorated disease in a humanized murine model of systemic sclerosis with skin involvement. Mice treated with CD45-ADC showed clear resolution of skin lesions and regrowth of hair, while animals treated with an isotype ADC showed no improvement.

Inflammatory Arthritis

Data showed that a single dose of CD45-ADC enabled immune reset and rebuild and halted disease progression in a murine model of inflammatory arthritis. The disease-modifying effects of this well-tolerated one-time approach were equivalent to multiple doses of a neutralizing anti-TNFα antibody, which replicates a clinically validated approach to treatment of rheumatoid arthritis.

Magenta has identified a lead antibody for the CD45-ADC and is progressing through IND-enabling studies in 2020.


Magenta is developing MGTA-145 as the new first-line standard of care for stem cell mobilization in a broad range of diseases, including autoimmune diseases, blood cancers and genetic diseases. MGTA-145, a CXCR2 agonist, works in combination with plerixafor, a CXCR4 antagonist, to harness the physiological mechanism of stem cell mobilization and mobilize robust numbers of stem cells. These stem cells are then given to the patient as part of the transplant process to rebuild a healthy new immune system.

Results from the Phase 1 study of MGTA-145 in healthy donors showed:

  • MGTA-145 in combination with plerixafor reliably mobilized sufficient stem cells (median: 4.3 million CD34+ cells/kg) for transplant in a single day.
    • The clinically accepted threshold for a successful transplant is 2 million cells/kg.
  • MGTA-145 was safe and well-tolerated in 79 subjects as a single agent and in combination with plerixafor.
  • MGTA-145 engages CXCR2 on neutrophils to mobilize CD34+ cells into peripheral blood with limited neutrophil activation, which may minimize risk of adverse events typically seen with current standard of care in patients with autoimmune disease.
  • The median percentage of CD34+CD90+ cells (functional stem cells) was 35%, compared to approximately 10% collected with the standard of care.
  • Stem cells collected from the first two subjects dosed in Part D transplanted into humanized mice engrafted more rapidly and at a 10-fold higher level at a 12-week timepoint than cells mobilized with the standard of care.
  • MGTA-145 in combination with plerixafor enables safe, same-day dosing, mobilization and collection of sufficient functional hematopoietic stem cells for transplant.
  • The number of high-quality cells mobilized by MGTA-145 + plerixafor provides a strong rationale for conducting mobilization studies of autologous transplant in autoimmune diseases.

Based on the results of the Phase 1 study, Magenta intends to initiate multiple Phase 2 trials of MGTA-145. The Phase 2 trials will include both allogeneic and autologous transplant settings and will evaluate mobilization and collection of functional cells and engraftment of the cells after transplant to rebuild the immune system. There is potential for Magenta to generate initial Phase 2 data on MGTA-145 in 2020.

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, including express or implied statements regarding Magenta’s 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 regulatory filings, the development of our product candidates and advancement of our preclinical programs, as well as other statements containing the words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” might,” “plan,” “potential,” “project,” “should,” target,” “will” or “would” and similar expressions that constitute forward-looking statements under the Private Securities Litigation Reform Act of 1995. 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, including review under accelerated approval processes; orphan drug designation eligibility; regulatory approvals to conduct trials or to market products; whether Magenta's cash resources will be sufficient to fund Magenta's foreseeable and unforeseeable operating expenses and capital expenditure requirements; risks, uncertainties and assumptions regarding the impact of the COVID-19 pandemic on Magenta’s business, operations, strategy, goals and anticipated timelines; and other risks concerning Magenta's programs and operations are described in additional detail in its Annual Report on Form 10-K filed on March 3, 2020, as updated by its most recent Quarterly Report on Form 10-Q and its other filings made with the Securities and Exchange Commission from time to time. Although Magenta's forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Magenta. As a result, you are cautioned not to rely on these forward-looking statements. Any forward-looking statement made in this press release speaks only as of the date on which it is made. Magenta undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future developments or otherwise.


Magenta Therapeutics:
Manisha Pai, Vice President, Communications & Investor Relations


Source: Magenta Therapeutics

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