RARE Daily

Magenta and Beam Collaborate to Evaluate Conditioning Regimen for Base Editing Therapies

June 15, 2020

Rare Daily Staff

Magenta Therapeutics and Beam Therapeutics entered into a non-exclusive research and clinical collaboration agreement to evaluate the potential utility of MGTA-117, Magenta’s novel targeted antibody-drug conjugate for conditioning of patients with sickle cell disease and beta-thalassemia who are receiving Beam’s base editing therapies.

Sickle cell disease (SCD) is an inherited blood disorder in which red blood cells are abnormally shaped in a crescent, or “sickle” shape, which restricts the flow in blood vessels and limits oxygen delivery to the body’s tissues, leading to severe pain and organ damage.

Beta thalassemia is an inherited blood disorder that reduces the production of hemoglobin, an iron-containing protein in red blood cells that carries oxygen to cells throughout the body. In people with beta thalassemia, low levels of hemoglobin lead to a lack of oxygen in many parts of the body, and anemia, which can cause pale skin, weakness, fatigue, and more serious complications.

Beam is pursuing two differentiated base editing approaches to treat these hemoglobinopathies: its hereditary persistence of fetal hemoglobin (HPFH) program to precisely and robustly elevate fetal hemoglobin, which could be used in treatments for both sickle cell disease and beta-thalassemia, as well as a novel approach to directly correct the sickle causing point mutation.

“Base editing has the potential to offer lifelong treatment for patients with many diseases, including sickle cell disease and beta-thalassemia. Our novel base editors create precise single base changes in genes without cutting the DNA, enabling durable correction of hematopoietic stem cells with minimal effects on cell viability or genomic integrity,” said John Evans, CEO of Beam. “Combining the precision of our base editing technology with the more targeted conditioning regimen enabled by MGTA-117 could further improve therapeutic outcomes for patients suffering from these severe diseases.”

Conditioning is a critical component necessary to prepare a patient’s body to receive the edited cells, which carry the corrected gene and must engraft in the patient’s bone marrow to be effective. Today’s conditioning regimens rely on nonspecific chemotherapy or radiation, which are associated with significant toxicities. Magenta’s antibody drug conjugate MGTA-117 precisely targets only hematopoietic stem and progenitor cells, sparing immune cells. It has shown high selectivity, potent efficacy, wide safety margins and broad tolerability in non-human primate models. MGTA-117 may be capable of clearing space in bone marrow to support long-term engraftment and rapid recovery in patients.

Beam has demonstrated the ability to edit individual DNA bases in hematopoietic stem cells at high efficiency and with little impact on the viability of edited cells relative to unedited cells using its novel base editing technology. Combining MGTA-117 with Beam’s HPFH and Makassar base editors could meaningfully advance the treatment of patients with sickle cell disease or beta-thalassemia.

“We believe patients will benefit from a more precise process to remove hematopoietic stem cells and prepare them to receive genetic medicines,” said Jason Gardner, president and CEO of Magenta. “Magenta has developed targeted ADCs as the preferred modality for our conditioning programs, and we have designed MGTA-117 specifically to optimize it for use with a genetically-modified cell product delivered in a transplant setting.”

Beam will be responsible for clinical trial costs related to development of Beam’s base editors when combined with MGTA-117, while Magenta will continue to be responsible for all other development costs of MGTA-117. Magenta will also continue to develop MGTA-117 in other diseases, including blood cancers and genetic diseases. Each company will retain all commercial rights to their respective technologies.

Magenta plans to complete IND-enabling studies this year and initiate clinical studies in 2021.

Photo: John Evans, CEO of Beam Therapeutics

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