Agilis Steadily Advances Angelman Gene Therapy Development

Agilis Biotherapeutics said its Angelman syndrome gene therapy development is on track, with initial animal studies making way for tests needed before the therapy can be tried in humans.

The Cambridge, Massachusetts, company announced that it plans to choose a lead candidate before consulting the U.S. Food and Drug Administration (FDA) and the European Medicines Agency. A clinical trial is scheduled to begin in 2019.

The company’s gene therapy for Angelman will use a harmless so-called adeno-associated virus (AAV) to carry the UBE3A gene into the brain. Unlike most other genes, in which one copy from the mother and one from the father both contribute to the gene’s function, only the maternal copy of UBE3A is active in the brain. Angelman results if that copy is damaged or mutated, or if a baby accidentally inherits two copies from the father.

Agilis has now analyzed a range of various virus-gene combinations, including a particularly potent one that delivers a gene for a secreted form of the UBE3A protein. Its researchers have also performed proof-of-concept studies with both the normal and secreted forms of the protein in a gold-standard Angelman syndrome animal model.

Moreover, Agilis has tested how the route of administration and dosing of these various combinations affect the drug’s distribution within the brain and how it targets brain structures involved in Angelman development.

Agilis sees several advantages with delivering a gene therapy directly into the brain instead of the bloodstream. It will require lower doses and potentially avoids immune reactions to the virus. It also holds the potential of directly targeting affected cells.

Once the company has selected a therapy candidate, it will perform studies needed to win FDA approval to test the compound in humans. Such studies include toxicology assessments and detailed examinations of how the treatment behaves in the body.

The company’s progress in Angelman gene therapy and other efforts in rare diseases affecting the central nervous system funded by a Series B financing round that raised $23 million earlier this year, officials said.