Per the terms of the agreement, Magenta retains all commercial rights to MGTA-117, and AVROBIO likewise retains all commercial rights to its gene therapies. AVROBIO will assume responsibility for clinical trial costs for assessing the combination approach. Specific financial details were not disclosed.

 

“This agreement with Magenta springs from our strategic focus on maintaining technology leadership in gene therapy,” Geoff MacKay, AVROBIO’s president and CEO, said in a news release. “AVROBIO has always led by investing early in technological innovations that further the field of lentiviral gene therapy, such as plato, our proprietary platform designed to optimize the safety, potency and durability of our investigational lentiviral gene therapies. We’re continually assessing new technologies that could be complementary to our plato platform to sustain our cutting-edge advantage and continue to evolve plato’s capabilities.”

 

At present, AVROBIO’S personalized conditioning regimen consists of precision dosing of busulfan, which is broadly considered the gold standard for ex-vivo lentiviral gene therapy. Busulfan is administered to a patient, and therapeutic drug monitoring (TDM) is used to measure how quickly a patient metabolizes the drug to determine the proper dose. Early clinical data of combining AVROBIO’s conditioning regimen with TDM suggest that busulfan is capable of clearing space in a patient’s bone marrow to allow new stem cells to engraft and produce daughter cells that contain the therapeutic gene delivered via gene therapy.

 

“We believe targeted ADCs represent the next generation of medicines to prepare patients for gene therapy or transplant in a targeted, precise way. AVROBIO’s investigational gene therapies complement our platform as well as our focus and commitment to patients. This partnership will allow Magenta to validate our conditioning platform in lentiviral gene therapy applications,” said Jason Gardner, president and CEO of Magenta Therapeutics. “We’ve selected ADCs as the preferred modality for our conditioning programs, as we believe they offer the most promising option for more patients. We have optimized our ADCs for gene therapy and transplant settings, and look forward to collaborating with AVROBIO to evaluate MGTA-117 in specific gene therapy settings. Magenta will continue to develop MGTA-117 in other diseases, including blood cancers and genetic diseases.”

 

MGTA-117 is a CD117-targeted antibody designed for transplants and conjugated to amanitin, a toxin in-licensed from Heidelberg Pharma. This compound is engineered to only deplete hematopoietic stem and progenitor cells, and has demonstrated high selectivity, efficacy, good safety and broad tolerability in non-human primate models. Based on the data, Magenta is hoping to complete IND-enabling studies this year to advance MGTA-117 as an option for aiding in long-term bone engraftment and rapid recovery.

 

“We are planning for the first clinical trial of MGTA-117 to be conducted in patients with acute leukemia who are eligible for transplant. The goal of the study is to show for the first time in the clinic that a single dose of an ADC can be used prior to reduced intensity conditioning to safely enable a stem cell transplant,” Dr. John Davis, chief medical officer and head of research and development at Magenta, reported in a company conference call. “The implications of this study are significant, both for the transplant and gene therapy fields, as well as for the conditioning portfolio as a whole. The first Phase 1 study will measure safety and tolerability, and also stem cell depletion after MGTA-117 is administered as a single agent. We will also look to the ability of MGTA-117 to reduce the numbers of leukemic cells before transplant and identify a dose or doses to move forward into future Phase 2 studies.”

 

“Based on the data that we see in the Phase 1 study, as well as discussions with regulatory agencies, we plan to take MGTA-117 forward in multiple Phase 2 studies, including gene therapy studies in patients with genetic diseases—for example, through our collaboration with AVROBIO—as well as additional studies in patients with blood cancers,” he continued. “Targeted ADC-based conditioning for transplant and gene therapy would represent a meaningful step forward in the transplant field.”

 

“This collaboration is built on a mission we share with AVROBIO: to bring transformative, one-time therapies to all patients who can benefit,” Gardner noted in the conference call.