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The immune reset
CAMBRIDGE, Mass.—In mid-November, Magenta Therapeutics presented new results at the American College of Rheumatology (ACR) Annual Meeting in Atlanta that showed a successful immune reset with just a single dose of its CD45-ADC in murine models of three different autoimmune diseases: multiple sclerosis, systemic sclerosis and inflammatory arthritis. 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 in order to enable curative immune reset.
Currently, the only treatment available for patients with multiple sclerosis involves years of chronic dosing of medications that do not halt the progression of the disease, and for patients with systemic sclerosis, which is potentially fatal, 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 the European League Against Rheumatism (EULAR) in treatment guidelines for systemic sclerosis.
The process of immune system reset involves removing the disease-causing cells and replacing them with healthy cells to rebuild the immune system to a healthy state. At this time, 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.
Data from the multiple sclerosis model showed that disease-causing reactive T cells were removed by just a single dose of CD45-ADC, enabling a successful immune reset and rebuild of the immune system. This treatment was well tolerated by the mice. Also of note are data showing that a single dose of CD45-ADC significantly reduced disease incidence and delayed disease onset in this model, which has provided preclinical proof of concept for many clinically validated standard-of-care therapies.
In models of systemic sclerosis, data showed the elimination disease-causing effector cells and ameliorated disease from a single dose of CD45-ADC in humanized models with skin involvement. Further results showed resolution of skin lesions and regrowth of hair.
In inflammatory arthritis, a single dose of CD45-ADC enabled immune reset and rebuild and halted disease progression in the mice. This is equivalent to multiple doses of a neutralizing anti-TNFα antibody, which is a clinically validated tactic for treating rheumatoid arthritis.,
“Millions of patients worldwide live with debilitating autoimmune diseases, with no options for curative therapy,” said Dr. John Davis, chief medical officer at Magenta. “Magenta is developing targeted medicines such as CD45-ADC to enable more patients with autoimmune diseases to undergo a one-time, curative immune reset. The data presented at ACR provide important proof of concept for our immune reset platform across a broad range of diseases, including multiple sclerosis and systemic sclerosis. We expect to declare a development candidate and progress this medicine into IND-enabling studies next year as we work to allow more patients to live their lives without autoimmune disease.”
In other news, Magenta has officially exercised its option with Heidelberg Pharma for exclusive worldwide development and marketing rights for antibody-drug conjugates using an amanitin payload and targeting CD45. In conjunction, Magenta will make an undisclosed milestone payment to Heidelberg. The companies signed an exclusive multitarget research agreement in March 2018 that granted Magenta access to Heidelberg Pharma’s proprietary amanitin toxin-linker platform technology. Magenta may leverage Heidelberg’s amanitin technology for up to four exclusive targets to produce novel Antibody Targeted Amanitin Conjugates. In turn, Heidelberg Pharma stands to receive development and sales-related milestone payments totaling $85 million per selected target.
Most recently, Magenta also announced Regenerative Medicine Advance Therapy designation by the FDA for MGTA-456, a one-time cell therapy for the treatment of multiple inherited metabolic disorders. MGTA-456 is a cell therapy designed to halt the progress of inherited metabolic disorders by delivering stem cells that regenerate a new immune system in patients. The company is currently studying MGTA-456 in a Phase 2 clinical trial in patients older than 6 months of age with Hurler syndrome, cerebral adrenoleukodystrophy, metachromatic leukodystrophy or globoid cell leukodystrophy at Cincinnati Children’s Hospital, Duke University, Emory University and the University of Minnesota.