Gene Therapy

Overview

Spirovant Sciences, a biotechnology company located in Philadelphia, is a leader in the development of gene therapies for cystic fibrosis (CF) and other lung diseases.

Overcoming Barriers of Gene Therapy for Cystic Fibrosis

Gene therapy intends to compensate for genetic defects by introducing a copy of the genes that express functional proteins to address the underlying cause of the disease. Gene therapy is the only mutation-agnostic approach to treating cystic fibrosis. A key feature of the Spirovant programs for cystic fibrosis is the delivery of genetic material to the target cells effectively and efficiently at functionally relevant levels.

Cystic Fibrosis – The Disease

Cystic fibrosis is a life-threatening, autosomal recessive genetic disease with no cure. Cystic fibrosis is caused by mutations of the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR), a channel that conducts chloride and bicarbonate ions across epithelial cell membranes. Derangement of CFTR interferes with mucociliary transport and antibacterial activity in the airways and gut, which leads to a buildup of mucus and susceptibility to airway infections that is ultimately lethal.

Cystic fibrosis is primarily characterized by progressive airway infection and inflammation, and, in most individuals, death from respiratory failure. There are an estimated 75,000 cystic fibrosis patients worldwide.

Current Treatment Options

The standard of care for cystic fibrosis includes therapies that address symptoms of the disease, such as bronchodilators, mucolytics, and antibiotics, and those that attempt to modulate the activity of defective CFTR, such as correctors of CFTR trafficking or potentiators of impaired ion channel activity. None of the current treatments prevent continued disease progression and many have efficacy for only a subset of cystic fibrosis-causative mutations.

Technology Overview

Spirovant has developed a number of innovations in multiple viral vectors that collectively have the potential to overcome challenges that have previously limited the clinical viability of gene therapy for cystic fibrosis. Currently, Spirovant has two proprietary technologies: an adeno-associated (AAV) viral gene therapy platform and a lentiviral gene therapy platform. Both are delivered as aerosolized therapies, and each has been optimized to be highly tropic to human airway epithelia.

AAV Platform

Our AAV platform consists of a highly optimized transgene payload, a novel AAV capsid, and an augmenter, which collectively drive the high expression of the functional CFTR proteins in human airway epithelia.

Lentivirus Platform

Our lentiviral platform is pseudotyped with an envelope protein which has demonstrated superior capability to transduce human airway epithelia from apical surfaces.  Because it integrates into the genome with minimal risk of genotoxicity, our lentiviral platform has the potential to be a single administration, long-lasting genetic treatment for cystic fibrosis.

Pipeline

Spirovant is the only company developing both AAV and lentivirus gene therapy candidates for cystic fibrosis.