Companies Join to Advance OTL-105, Potential Gene Therapy for HAE

Orchard Therapeutics and the Pharming Group are teaming up to research, develop, manufacture, and — possibly — commercialize a gene therapy for hereditary angioedema (HAE), called OTL-105.

“This promising work toward treatment with the potential for durable long-term clinical benefit is encouraging and signifies an ongoing commitment to the HAE community. I look forward to these efforts to identify and carefully advance a potential cure for HAE,” Marc Riedl, MD, a professor of medicine and clinical director of the U.S. Hereditary Angioedema Association Center at the University of California, San Diego, said in a press release.

Most cases of HAE are caused by mutations in the SERPING1 gene, which encodes a protein called C1-inhibitor (C1-INH). This protein normally helps to regulate the activity of other molecules that promote swelling. But this protein is either missing or malfunctions in people with HAE, leading to uncontrolled swelling.

As a gene therapy, the overarching aim of OTL-105 is to deliver a non-mutated version of the SERPING1 gene to patients’ cells, thereby restoring their ability to produce a functional version of the C1-INH protein.

OTL-105 is specifically an ex vivo autologous hematopoietic stem cell gene therapy. In practice, this means that treatment with OTL-105 would first involve harvesting a patient’s hematopoietic stem cells (HSCs), or blood cell precursors, found in the bone marrow.

Next, in a laboratory, patient HSCs are treated with the gene therapy itself, which uses a viral vector to deliver a non-mutated version of the SERPING1 gene. The modified cells are then transplanted back into the patient’s bone marrow, where they can give rise to blood cells that can produce a working C1-INH, restoring its levels in the body.

According to Orchard Therapeutics, preclinical studies to date show the investigational therapy leads to high levels of SERPING1 gene activity in several cell types, and to C1-INH protein production.

Under the partnership’s terms, Pharming will be responsible for clinical development, regulatory filings, and commercialization of the investigational gene therapy, as well as supporting associated costs. Pharming will also fund the therapy’s manufacturing during its preclinical and clinical development. Orchard, in turn, will lead the completion of preclinical research and oversee the therapy’s manufacturing process.

As part of the arrangement, Orchard has received cash payments and investments from Pharming, with the possibility of further payments once certain milestones are met. Pharming has been granted worldwide rights to OTL-105.

“We have partnered with Orchard Therapeutics, a leader in the development of autologous HSC gene therapy, to develop a potentially curative treatment for HAE. This a significant first step in developing a potentially transformative one-time treatment for HAE,” said Sijmen de Vries, MD, CEO of Pharming.