Mustang flying high as 'bubble boy' gene therapy aces small study

Red blood cells
MB-107 is based on blood-forming stem cells taken from a patient’s own bone marrow. (Pixabay)

They’re using the “c” word. Mustang Bio’s stock leapt more than 400% in after-hours trading Wednesday on the news that a gene therapy it licensed from St. Jude Children’s Research Hospital cured eight infants with X-linked severe combined immunodeficiency (X-SCID)—also known as “bubble boy” syndrome. 

The treatment, known as MB-107, uses a lentiviral vector to deliver a working copy of the gene IL2RG to babies with X-SCID. The disease is caused by mutations in the IL2RG gene, which codes for a protein the immune system needs to work properly. Infants with X-SCID have white blood cells called lymphocytes that don’t develop and function normally, leaving them unable to fight off infections. 

MB-107 is based on hematopoietic—blood-forming—stem cells taken from a patient’s own bone marrow. An engineered lentivirus is used to deliver a normal copy of IL2RG into those cells, which are then reinfused back into the patient after they have been given a low dose of the cancer drug busulfan. Busulfan’s role is to help the gene-modified stem cells take root in the patient’s bone marrow and start making new blood cells. 

The phase 1/2 study, published in the New England Journal of Medicine, showed that MB-107 restored immune function in seven out of eight infants within three to four months. Specifically, the researchers saw that the treatment raised the number of natural killer cells, B cells and T cells—all types of lymphocytes—in these infants to normal levels. The eighth child lagged behind on the T cell count at first, but developed them after getting a second dose of gene-modified stem cells. The children were followed a median of 16.4 months. 

The findings build on data presented at the American Society of Gene & Cell Therapy annual meeting one year ago. At the time, six of the eight patients “achieved reconstituted immune systems” within three to four months after treatment. Mustang licensed the treatment three months later. 

RELATED: Mustang Bio picks up St. Jude’s ‘bubble boy’ gene therapy

“The results have been very good thus far. We’ve been able to restore a full immune system pretty quickly,” said the study leader, Ewelina Mamcarz, M.D., in a statement. “All of these patients were able to come off of isolation and they’ve returned home with immune systems that were fully functional. We had patients come to us with very severe infections and they cleared them through the emergence of this newly developed immune system.” 

“We are excited to continue working with St. Jude to evaluate MB-107 in this clinical trial, and we look forward to transferring the IND to Mustang by the end of this year, after which patients’ cells from all three participating clinical trial sites will be processed in our Worcester, Mass., facility,” said Mustang Chief Medical Officer Martina Sersch, M.D., Ph.D., in the statement.

As of Thursday’s close, Mustang’s stock settled down at $5.64, 112% of its price before the news dropped the day before. 

The company could file for FDA approval by the end of 2021, Mustang CEO Manny Litchman told Bloomberg. 

The current standard of care for babies with X-SCID is a bone marrow transplant from a genetically matched sibling. But as one might imagine, not all patients have a sibling at all, let alone one who is a suitable donor. Some patients end up getting bone marrow from a parent or another donor, but this type of treatment only partially restores immunity, said the National Institutes of Health (NIH), one of the study sites, in a statement. The other sites were St. Jude and UCSF Benioff Children’s Hospital.

“These patients require lifelong treatment and may continue to experience complex medical problems, including chronic infections,” the agency said.

If MB-107 ultimately proves to be a cure, it would offer infants who tend to succumb to infections in the first year or two in life “the hope of developing a wholly functional immune system and the chance to live a full, healthy life,” to use the words of Anthony Fauci, M.D., director of NIH's National Institute of Allergy and Infectious Diseases.