A gene therapy for cystic fibrosis using GP64-pseudotyped lentivirus

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ABSTRACT/PROJECT SUMMARY The product that will result from this proposed Phase I/II (Fast-Track) SBIR project will be a gene therapy for cystic fibrosis (CF) that will, following a single inhalational administration, be curative to all people with CF regardless of the specific causative mutation they have. CF is a life-threatening disease caused by any one of the hundreds of documented autosomal recessive mutations in the CFTR gene. Derangement of CFTR interferes with mucociliary transport and antibacterial activity in the airways and gut and a buildup of mucous and susceptibility to airway infections that is ultimately lethal. Current treatments include symptomatic airway support (e.g., mucolytics) or CFTR modulators, none of which address disease progression and many of which have efficacy for only a subset of CF-causative mutations. To date there is no cure for CF and the average life expectancy of a person with CF is 39 years. Gene therapy has the potential to be a game-changer in the field of CF, by offering a universal cure. However, for gene therapy to be considered to be a clinically relevant option for CF, substantial efficacy is still needed – the main limiting factor is the ability of a vector to effectively and efficiently deliver a large payload like CFTR. Talee Bio's academic founders and collaborators at the University of Iowa and Children's Hospital of Philadelphia have more than 25 years of experience in this field. Recently, we developed a proprietary lentivirus gene therapy technology that could address this need for CF, with the ability to carry a large payload and genetically engineered with an envelope protein which increases binding and entry to the surface of airway epithelial cells. Our preliminary data indicate that a prototype of our product can deliver CFTR effectively to airway epithelial cells in vitro and in vivo, that expression persists for at least two years, and that it shows no evidence of genotoxicity. Here we will validate the efficacy of our clinic-ready product (phase 1), and will conduct the initial biodistribution and safety work that will enable a pre-IND meeting with the FDA. Talee Bio is supported by academic collaborators with more than 100 years of collective experience in CF biology, pathology, and gene therapy, and by a management team with demonstrable experience in drug development. Talee has raised financing from a foundation (Emily's Entourage) and from an investor, Phase 1 Ventures, to accelerate the outcomes of this SBIR into the clinic.