New pre-clinical data for SP-101, an investigational novel recombinant adeno-associated virus (AAV) gene therapy selected for its tropism to human airway epithelia for the treatment of people living with cystic fibrosis (CF), suggest co-administration of SP-101 with doxorubicin functionally corrects human CF airway epithelia by restoring chloride conductance to similar levels as non-CF or small molecule modulator controls. These findings, along with data demonstrating robust cystic fibrosis transmembrane conductance regulator transgene (hCFTRΔR) expression in vivo, were shared in two presentations at the recent 2022 North American Cystic Fibrosis Conference (NACFC) in Philadelphia.
Key findings include:
- In in vitro models of human CF airway epithelia with Class I, II and III mutations, co-administration of SP-101 and doxorubicin restored CFTR-mediated chloride conductance to similar levels as non-CF controls in a dose-dependent manner. SP-101 administration alone (without doxorubicin) was not sufficient to correct CF airway epithelia. These data support the co-development of inhaled SP-101 followed by inhaled doxorubicin for the treatment of CF.
- In wildtype ferrets, inhaled administration of SP-101 followed by inhaled doxorubicin resulted in expression of the human CFTR∆R transgene in all regions of the respiratory tract. hCFTRΔR mRNA expression levels persisted up to three months and were comparable to those of endogenous ferret CFTR.
- In CF ferrets, comparable hCFTRΔR mRNA expression was also evident in the airways, indicating successful transduction despite pre-existing mucus accumulation.
In commenting on the data, Roland Kolbeck, Ph.D., Chief Scientific Officer of Spirovant stated, “The robust hCFTR∆R transgene expression data in vivo, in combination with data demonstrating functional correction of human CF airway epithelia, presented at NACFC this year provide strong support for the administration of inhaled SP-101 followed by inhaled doxorubicin to correct CFTR function and restore respiratory function, which may serve individuals with cystic fibrosis who do not benefit from treatment with available small molecule modulators.”
Full details of these presentations can be accessed through the Publications section on the Spirovant website.
Spirovant is pursuing the development of gene therapies, as we believe in the potential to improve the lives of people with cystic fibrosis and other respiratory diseases