-- Poster presentation of MGTA-145 investigator-initiated Phase 2 clinical trial data confirmed previously reported positive topline clinical data for stem cell mobilization and transplant in multiple myeloma --

-- Phase 2 development of MGTA-145 to include new clinical trial designed to optimize the dosing and administration regimen of MGTA-145 plus plerixafor to streamline future clinical development and enhance the potential commercial profile --

-- Oral and poster presentations relating to preclinical transplant studies, including primate results, with tool CD117 antibody drug conjugates (ADC) further validate CD117-specific ADC-based conditioning for autologous stem cell gene therapy and allogeneic transplant --

Magenta Therapeutics (Nasdaq: MGTA), a clinical-stage biotechnology company developing novel medicines designed to bring the curative power of stem cell transplants to more patients, today highlighted three presentations made at the 2021 American Society of Hematology (ASH) Annual Meeting.

Stem Cell Mobilization: ASH Presentation and Clinical Development Plans

The data from an investigator-initiated Phase 2 clinical trial in multiple myeloma, presented on December 13, 2021, at the ASH Annual Meeting and previously reported in a Magenta press release on November 4, 2021, confirmed that MGTA-145 plus plerixafor (i) achieved the primary endpoint for collection of hematopoietic stem cells (HSCs), (ii) was well-tolerated and (iii) mobilized HSCs which were able to successfully engraft with positive 100-day outcomes. The data continue to support MGTA-145 plus plerixafor as a potentially compelling combination with complementary mechanisms of action.

Building upon the encouraging cell collection data from the Phase 2 investigator-initiated trial, Magenta plans to pursue a company-sponsored Phase 2 clinical trial in healthy subjects to further increase cell collection yield through adjustments of the dosing and administration regimen. This is a capital-efficient approach designed to enable expedited enrollment, flexibility in execution and reduced patient variability which will inform planned clinical trial evaluations in multiple myeloma patients and allogeneic stem cell transplant. Magenta will close its current allogeneic clinical trial while continuing to advance its MGTA-145 clinical trial in sickle cell disease in partnership with bluebird bio due to the predicted pharmacology of MGTA-145 and plerixafor in the sickle cell patient setting for HSC gene therapy.

“We believe the current profile of MGTA-145 plus plerixafor, with enhanced cell collection yield, could provide significant clinical benefit to patients and favorably position the product commercially,” said Jeff Humphrey, M.D., Chief Medical Officer, Magenta Therapeutics. “We believe there are dosing and administration adjustments that could further improve cell collection and also expect that this proposed clinical trial will answer key clinical questions which could, ultimately, be major differentiators for the program moving forward.”

Targeted Conditioning: ASH Presentations and Phase 1/2 Clinical Trial

Two presentations relating to Magenta’s MGTA-117 targeted conditioning program were made on December 11-12, 2021, at the ASH Annual Meeting. The first was an oral presentation of non-human primate data supporting the use of a CD117-targeted ADC to condition for HSC gene therapy. The second was a poster presentation of preclinical mouse data that supports the use of a CD117-targeted ADC in combination with lymphodepletion to condition prior to allogeneic HSC transplant. The results from these two presentations were previously disclosed in a press release by Magenta on November 4, 2021.

Gene Therapy. In support of using a CD117-targeted conditioning ADC in gene therapy, Dr. Naoya Uchida, staff scientist at the National Heart, Lung, and Blood Institute, part of the National Institutes of Health (NIH), presented preclinical data generated using a tool CD117-targeted ADC in a clinically relevant and fully immune-competent primate gene therapy model for sickle cell disease. The data was generated as part of an NIH-funded (Grant No. HL006008), joint-research collaboration between Magenta and the NIH. The tool CD117-ADC uses the same antibody and engineering as MGTA-117, and although it utilizes a different payload, the results validate CD117 as a target for ADC-based conditioning because of (i) the value of the ADC’s selectivity to the CD117-expressing hematopoietic stem cells and (ii) the effective cell depletion following delivery of an on-target, cell-killing payload. In primates, a single dose of CD117-ADC led to >99% depletion of stem cells, a reduction previously only achieved by four daily doses of busulfan chemotherapy. The data also showed successful engraftment of gene-modified cells with robust and durable fetal hemoglobin levels.

Magenta’s MGTA-117 clinical candidate uses an amanitin payload which has been shown preclinically to be a potent agent for stem cell depletion. Potent stem cell depletion is critical to making room in the bone marrow for engraftment of the modified cells used in gene therapy (and non-modified stem cells used in transplantation). Importantly, depleting CD117-expressing hematopoietic stem cells in a gene therapy setting may allow for the elimination of busulfan, other chemotherapies and irradiation and their known off-target and damaging adverse effects.

“The results suggest that a single dose of a CD117-targeted ADC can enable comparable levels of gene-therapy cell engraftment to multi-dose busulfan while avoiding many of busulfan’s common toxicities,” said Dr. John Tisdale, Chief of Cellular and Molecular Therapeutics, NHLBI, NIH. “If successfully translated to the clinic, a single dose of a CD117-targeted ADC may improve the risk/benefit profile for patients with hemoglobinopathies who are considering HSC gene-therapy.”

Allogeneic HSC Transplant. In support of using a CD117-targeted conditioning ADC in allogeneic HSC transplant, Magenta presented a poster demonstrating successful use of a tool CD117-ADC in combination with lymphodepleting antibodies that enabled allogeneic transplant in immune-competent murine models. These studies support the therapeutic potential of CD117-targeted ADCs, without the use of toxic chemotherapy, for conditioning in allogeneic HSC transplantation.

Phase 1/2 Clinical Trial. Magenta is on track to open a Phase 1/2 clinical trial this month to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of MGTA-117, a CD117-targeted ADC. Preclinical efficacy and GLP toxicology studies with MGTA-117: (i) enabled selection of the starting dose in this dose-escalating Phase 1/2 clinical trial, (ii) demonstrated that MGTA-117 efficiently depleted stem cells, (iii) showed that MGTA-117 was efficiently cleared from the body in the preclinical models which is especially important for autologous gene therapy or allogeneic stem cell transplants, and (iv) showed that MGTA-117 was well-tolerated. MGTA-117, as a targeted conditioning therapy, is designed to substantially improve against the known safety and tolerability concerns of current non-specific conditioning agents which include busulfan, other chemotherapies, and irradiation. Magenta expects to provide the details of the MGTA-117 clinical trial design at its company presentation at the 2022 JP Morgan Healthcare Conference on January 13, 2022.

About Magenta Therapeutics

Magenta Therapeutics is a clinical-stage biotechnology company developing medicines designed to bring the curative power of stem cell transplants to more patients with blood cancers, genetic diseases and autoimmune diseases. Magenta is combining leadership in stem cell biology and biotherapeutics development with clinical and regulatory expertise and broad networks in the stem cell transplant community to revolutionize immune reset for more patients.

Magenta is based in Cambridge, Massachusetts. For more information, please visit www.magentatx.com.

Follow Magenta on Twitter: @magentatx.

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