[December 09, 2017]

Magenta Therapeutics' Lead Targeted Antibody Drug Conjugate Shows Promising Preclinical Results for Non-Genotoxic Conditioning for Bone Marrow Transplant

Magenta Therapeutics, a biotechnology company developing therapeutics to improve and extend the use of curative bone marrow transplant for more patients, today announced the presentation of preclinical data from its CD117 antibody-drug conjugate (ADC (News - Alert)) conditioning program. These data were presented at the 59^th annual meeting of the American Society of Hematology (ASH) in Atlanta, Ga.

Magenta is developing a portfolio of ADC-based conditioning agents that specifically deplete target cells using an approach that may be less toxic than the current chemotherapy-based conditioning regimens for bone marrow transplant. One of Magenta's programs, CD117-ADC, is a conditioning agent that selectively binds to host hematopoietic stem and progenitor cells (HSPCs). CD117 (also known as C-KIT) is highly expressed on HSPCs and an ideal target for conditioning across broad sets of diseases, including hematological malignancies and hemoglobinopathies, with potential applicability in both bone marrow transplant and stem cell gene therapy. CD117 is also frequently overexpressed on tumor cells in patients with acute myelogenous leukemia (AML). The CD117-ADC-based transplant conditioning approach has the potential to limit systemic toxicity for transplant patients and additionally reduce tumor burden in transplant patients with AML.

"For patients undergoing bone marrow transplant, the toxicity and mortality associated with current conditioning protocols remain significant challenges and prevent more patients from benefiting from this life-saving and potentially curative procedure. Current conditioning regimens use highly toxic and non-specific chemotherapy dugs or irradiation that can result in infections, organ failure, infertility and even death," said Michael Cooke, Ph.D., chief scientific officer, Magenta Therapeutics. "Given the significant unmet need for new conditioning options for bone marrow transplant, we are pleased to see that CD117-ADC was capable of selective depletion of human hematopoietic stem cells in the bone marrow of humanized mice and showed anti-leukemia effects in vivo. This conditioning regimen has the potential to increase the number of patients eligible for transplant for both malignant and non-malignant diseases by reducing the toxicity of the procedure."

Non-Genotoxic Conditioning for Hematopoietic Stem Cell Transplant Using a Human Antibody Drug Conjugate Targeting C-KIT (Abstract #1894)

Overview and results, presented by Adam Hartigan, Ph.D., Magenta Therapeutics, include:

• Magenta Therapeutics developed CD117-ADC, a fully human ADC targeting CD117 (also known as C-KIT) capable of depleting both proliferating and quiescent cells.
• Humanized NSG mice treated with a single dose of CD117-ADC had greater than 90% depletion of human hematopoietic stem and progenitor cells in the bone marrow after a single administration of the ADC.
• Magenta scientists demonstrated the specificity of CD117-ADC for hematopoietic stem and progenitor cells in humanized animal studies.
• CD117-ADC demonstrated greater than 90% killing of the human leukemia cell line Kasumi-1, and was equally effective at killing primary human CD34+ bone marrow cells during in vitro culture.
• Preliminary data suggest that a single dose of CD117-ADC is also effective at reducing tumor burden and conferring survival benefits in mice challenged with C-KIT-expressing AML cells.

About Bone Marrow Transplant

Healthy bone marrow stem cells and the blood cells they create are crucial for survival, but certain diseases can affect the bone marrow, interfering with its ability to function properly. A bone marrow transplant is a process to replace unhealthy bone marrow with healthy bone marrow stem cells. Bone marrow transplant can save the lives of patients with blood cancers and genetic diseases and is a potential cure for patients with severe refractory autoimmune diseases. However, the high risks, toxic side effects and complexity of the procedure currently prevent many patients from being able to benefit.

About Magenta Therapeutics

Magenta Therapeutics is a biotechnology company developing therapeutics to revolutionize bone marrow transplant for patients with autoimmune diseases, blood cancers and genetic diseases. By creating a platform focused on critical areas of transplant medicine, Magenta Therapeutics is pioneering an integrated approach to extend the curative power of bone marrow transplant to more patients. Founded by internationally recognized leaders in bone marrow transplant medicine, Magenta Therapeutics was launched in 2016 by Third Rock Ventures and Atlas Venture and is headquartered in Cambridge, Mass. For more information, please visit www.magentatx.com.

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