Hansa Biopharma has granted an exclusive worldwide license to Sarepta Therapeutics to develop and promote imlifidase as a gene therapy pre-treatment for people with muscular dystrophy who would otherwise be unable to receive such therapy.
Sarepta’s gene therapy strategy is to use a harmless adeno-associated virus (AAV) vector — named AAVrh74 — to deliver gene-modifying treatments to the muscle cells of people with Duchenne (DMD) and limb-girdle muscular dystrophy (LGMD).
However, some patients already have immunoglobulin type G antibodies (IgG) that target and neutralize AAVs. That would make them ineligible for gene therapies based on such vectors.
Hansa’s imlifidase is an enzyme that rapidly cleaves IgG antibodies, thereby suppressing the immune response against AAVs.
“One of the current limitations of gene therapy is the inability to treat patients who have pre-existing neutralizing antibodies to the AAV vector,” Doug Ingram, president and CEO at Sarepta, said in a press release. “While our AAVrh74 vector has been associated with a low screen out rate for neutralizing antibodies, even that low rate is inconsistent with our mission.”
In early, pre-clinical models as well as in later clinical models, this technology showed its ability “to clear the IgG antibodies that prevent dosing AAV-based gene therapies,” Ingram said.
“If successful, this could offer the potential of extending our gene therapy treatments to DMD and LGMD patients who would otherwise have been denied access,” he added.
Sarepta also has two so-called exon skipping therapies approved to treat DMD patients: Exondys 51 (eteplirsen) and Vyondys 53 (Golodirsen). The idea behind exon skipping is to hide, or mask, specific exons — the actual protein-coding sequences — in genes.
Duchenne is caused by a mutation in the DMD gene, which carries the instructions for the protein dystrophin, essential for muscle cell integrity. DMD has 79 exons that need to be stitched together after the conversion to RNA to produce dystrophin.
Exon-skipping therapies are made of antisense oligonucleotides. They are intended to mask or exclude a damaged or lost exon, forcing the protein production machinery to “skip” that exon to allow the remaining segments to generate a smaller, but functional version of dystrophin.
LGMD, meanwhile, can occur as a result of mutations in many different genes, which typically code for proteins required for muscle maintenance and repair. Sarepta currently has five gene therapy programs addressing different LGMD subtypes.
Under the terms of the new agreement, Hansa will receive an upfront payment of $10 million. Based on development, regulatory, and sales milestones, the company is eligible for additional fees up to a total of $397.5 million.
“We see significant potential for our enzyme technology in the gene therapy space overall, and we are excited to partner with Sarepta, a leading player in the field, to use the unique features of imlifidase,” said Søren Tulstrup, president and CEO at Hansa.
Hansa will collect revenues from all sales of imlifidase as well as royalties based on gene therapy sales generated from treating IgG antibody-positive patients with imlifidase pre-treatment.
“As we expand our leadership position in genetic medicine and build out our gene therapy engine, one of Sarepta’s central ambitions is to find scientific solutions that bring our potentially life-saving therapies to the greatest number of the rare disease patients we serve,” Ingram said.