A Modified AAV Gene Therapy for Cystic Fibrosis

Talee Bio, Inc., Philadelphia PA

Investigators

Abstract

ABSTRACT Talee Bio is developing a gene therapy for cystic fibrosis (CF), the first curative treatment for this disease. CF is an autosomal recessive disease involving any of a number of mutations to the gene for cystic fibrosis transmembrane conductance regulator (CFTR), a membrane channel that influences the composition of mucous secretions in the gut and respiratory tract. CF is primarily characterized by progressive airway infection and inflammation, and, in the majority of individuals, death from respiratory failure. The standard of care for CF includes therapies that address symptoms of the disease (such as bronchodilators, mucolytics, and antibiotics), and those that attempt to modulate the activity of defective (mutated) CFTR. However, none of these treatments are curative. Talee has developed a novel transgene and a number of innovations in a well- characterized delivery vector that collectively will overcome challenges that have previously limited the clinical viability of gene therapy for CF. In this phase 1 proposal, Talee will demonstrate the feasibility of its approach by demonstrating functional transformation of human CF cells in vitro, and the transduction efficiency and distribution of a marker transgene delivered with its proprietary vector. If successful, this work will pave the way to future development in animal models of CF and for safety and PKPD studies (in Phase 2) that will inform a pre-IND meeting with the FDA. Talee Bio is a collaboration among drug development professionals with more than 60 years of combined experience, and academic founders of the company, from the University of Iowa, who have been investigating CF pathogenesis and treatment, including gene therapy strategies, for more than 25 years.