Magenta Therapeutics and AVROBIO Announce Collaboration to Evaluate Targeted Antibody-Drug Conjugate as a Potential Conditioning Regimen for Lentiviral Gene Therapies

On May 6, 2020 Magenta Therapeutics (Nasdaq: MGTA) and AVROBIO, Inc. (Nasdaq: AVRO) reported a research and clinical collaboration agreement to evaluate the potential utility of MGTA-117, Magenta’s novel targeted antibody-drug conjugate (ADC) for conditioning patients before they receive one of AVROBIO’s investigational lentiviral gene therapies (Press release, Magenta Therapeutics, MAY 6, 2020, View Source [SID1234557198]).

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The collaboration will combine Magenta’s leadership in ADC-based conditioning with AVROBIO’s expertise in lentiviral gene therapies and is expected to further the two companies’ shared mission to enable patients to live free from disease. Under the collaboration, Magenta and AVROBIO will jointly evaluate MGTA-117 in conjunction with one or more of AVROBIO’s investigational gene therapies. Magenta will retain all commercial rights to MGTA-117. AVROBIO will retain all commercial rights to its gene therapies and will be responsible for the clinical trial costs related to the evaluation of MGTA-117 with AVROBIO’s gene therapies.

"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, D.Phil., President and Chief Executive Officer, 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."

"This agreement with Magenta springs from our strategic focus on maintaining technology leadership in gene therapy," said Geoff MacKay, AVROBIO’s President and Chief Executive Officer. "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."

MGTA-117, Magenta’s most advanced conditioning program, is a CD117-targeted antibody engineered for the transplant setting and conjugated to amanitin, a toxin in-licensed from Heidelberg Pharma. It is designed to precisely deplete only hematopoietic stem and progenitor cells and has shown high selectivity, potent efficacy, wide safety margins and broad tolerability in non-human primate models, suggesting that it may be capable of clearing space in bone marrow to support long-term engraftment and rapid recovery in humans. Magenta plans to complete IND-enabling studies this year.

AVROBIO currently uses a personalized conditioning regimen with precision dosing of busulfan, an extensively validated conditioning agent generally considered to be the gold standard for ex vivo lentiviral gene therapy, based on decades of general use and administration to hundreds of patients treated with lentiviral gene therapy candidates. The treating clinician uses therapeutic drug monitoring (TDM) to evaluate how quickly the patient metabolizes busulfan and adjusts the dose regimen accordingly with the goal of achieving the optimum result. AVROBIO has reported early clinical data with this precision conditioning regimen with TDM in its own clinical trials, adding to a body of data that suggest busulfan can effectively clear space in the patient’s bone marrow, where stem cells engraft, produce generations of daughter cells carrying the therapeutic gene and make the functional protein the patient needs to maintain cellular health.