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Interim results presented by UNC’s Joseph Muenzer, MD, PhD, provide preliminary evidence that in vivo genome editing occurred in a clinical trial testing a treatment for Mucopolysaccharidosis Type II (MPS II), also known as Hunter syndrome.

Preliminary molecular and enzymatic evidence of editing of the human genome in vivo (inside the body) was presented today by UNC School of Medicine’s Joseph Muenzer, MD, PhD, at the WORLDSymposium 2019 being held in Orlando, Florida.

This finding was part of the interim results from the Phase 1/2 CHAMPIONS Study evaluating SB-913, a zinc finger nuclease (ZFN) in vivo genome editing product candidate for patients with Mucopolysaccharidosis Type II (MPS II).

MPS II, also known as Hunter syndrome, is a rare genetic disorder caused by a deficiency of iduronate-2-sulfatase (IDS), a lysosomal enzyme which is required to break down or recycle the toxic buildup of glycosaminoglycans (GAGs). Without IDS enzyme activity, GAGs accumulate in cells throughout the body, leading to widespread tissue and organ damage. The current standard-of-care treatment for MPS II is enzyme replacement therapy (ERT), given as weekly intravenous infusions. SB-913 is an investigational product candidate being evaluated to treat MPS II using ZFNs, which are designed to insert a normal copy of the IDS gene into a precise location in the DNA of liver cells. The goal of SB-913 treatment is to enable a patient’s liver to produce a continuous supply of functional IDS enzyme for life.

“The interim results from the CHAMPIONS Study provide preliminary evidence that in vivo genome editing occurred and that genome-edited liver cells are able to generate active IDS enzyme in patients with MPS II,” said Muenzer, a professor of pediatrics and genetics, member of the UNC Children’s Research Institute, and a lead study investigator. “More data are needed to understand whether the small increases in IDS enzyme activity observed can translate into improved outcomes in MPS II patients treated with this first generation of SB-913. I look forward to reviewing additional data later this year from the five patients who have received the high-dose of SB-913.”

The SB-913 treatment was developed by biotechnology company Sangamo Therapeutics, which is sponsoring the CHAMPIONS trial that began in May of 2017.

In the CHAMPIONS study, liver biopsies have been analyzed for three eligible patients – one from the low-dose cohort and two from the mid-dose cohort. In liver tissue samples from both mid-dose cohort patients, a molecular signal of successful genome editing was identified using an assay to detect gene integration.

Muenzer previously presented preliminary safety and efficacy data from the CHAMPIONS study in September 2018. In March 2018, a patient was treated at UNC’s Clinical and Translational Research Center (CTRC) with SB-913. That marked a significant milestone for both Muenzer and the CTRC. It was the first time that Muenzer, a pediatric biochemical geneticist who specializes in disorders such as Hunter syndrome, had the opportunity to administer a gene therapy treatment to a patient with this condition.