Avrobio is working to make conditioning, a necessary step for some gene therapies, safer. But it’s not stopping at improving current approaches—the company is teaming up with Magenta Therapeutics to see if an antibody-drug conjugate can do the job.
Under the deal, the duo will test Magenta’s lead conditioning program, MGTA-117, alongside at least one of Avrobio’s gene therapies. Each company will hold onto the rights for their respective programs, but Avrobio will pick up the tab for clinical trials involving MGTA-117.
“We believe targeted ADCs represent the next generation of medicines to prepare patients for gene therapy or transplant in a targeted, precise way… This partnership will allow Magenta to validate our conditioning platform in lentiviral gene therapy applications,” said Magenta CEO Jason Gardner, D.Phil., in a statement.
Avrobio’s lead program is a gene therapy for Fabry disease dubbed AVR-RD-01. It is based on CD34+ stem cells that have been modified using a lentiviral vector to carry and express the gene that codes for the enzyme that is missing in Fabry disease. It is also working on treatments for Gaucher disease, Cystinosis and Pompe disease.
Patients undergoing lentiviral gene therapies must first take the chemotherapy drug busulfan in a process called conditioning, which helps the gene-modified stem cells take root in their bone marrow. Avrobio uses therapeutic drug monitoring to tailor busulfan dosing to each patient, to improve the odds of success for its gene therapies while tamping down on side effects. Some patients may be more susceptible to infection and bleeding after conditioning, and they may suffer side effects like nausea, hair loss and mouth sores.
MGTA-117 is made up of an anti-CD117 antibody linked to amanitin, a cell-killing toxin. It is designed to target only hematopoietic, or blood-forming, stem cells and progenitor cells. Animal studies suggest it could clear space in bone marrow for gene-modified stem cells to take root, Magenta said in the statement. The company plans to wrap IND-enabling studies for the antibody-drug conjugate this year.
The deal comes on the heels of a busulfan-focused one for Avrobio. The company joined forces with Saladex Biomedical on Monday to develop a rapid blood test that monitors how quickly patients metabolize the drug. The hope is to get results in minutes, rather than the hours that current methods take, so dosing can be adjusted quickly.
May 6, 2020