RARE Daily

Magenta and Avrobio Form Collaboration for Conditioning Patients for Gene Therapy

May 6, 2020

Rare Daily Staff

Magenta Therapeutics and Avrobio have entered into a research and clinical collaboration to evaluate the potential utility of MGTA-117, Magenta’s novel targeted antibody-drug conjugate for conditioning patients before they receive one of Avrobio’s experimental lentiviral gene therapies.

The collaboration will combine Magenta’s antibody-drug conjugate (ADC)-based conditioning with Avrobio’s expertise in lentiviral gene therapies to develop therapies that will 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,” said Jason Gardner, president and CEO, Magenta Therapeutics. “This partnership will allow Magenta to validate our conditioning platform in lentiviral gene therapy applications.”

Magenta believes ADCs will be the preferred modality for lentiviral gene therapy conditioning programs, and will continue to develop MGTA-117 in diseases outside the collaboration with Avrobio, including blood cancers and genetic diseases.

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 busulfan conditioning regimen, 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 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 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.

Still, the company is continually assessing new technologies that could be complementary to its platform improve its capabilities, said Geoff MacKay, president and CEO, Avrobio. “This agreement with Magenta springs from our strategic focus on maintaining technology leadership in gene therapy,” he said. Avrobio’s clinical stage rare disease programs include gene therapies targeting Fabry disease, Gaucher disease, Pompe disease, and cystinosis.


Photo: Geoff MacKay, president and CEO, Avrobio

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