Shift Pharmaceuticals Receives US FDA Orphan Drug Designation for their Lead Compound for SMA

09 March 2020

Shift Pharmaceuticals has received FDA Orphan Drug Designation in the US for their lead compound, E1v1.11, for SMA. Orphan Drug Designation gives incentives to companies to develop drugs intended to treat rare conditions, such as SMA, and should help to expedite the development of E1v1.11 as a potential therapeutic option for SMA.

E1v1.11 aims to treat SMA by targeting the “back-up” gene, SMN2, that is present in SMA patients. E1v1.11, is an antisense oligonucleotide (ASO) optimised with a phosphorodiamidate morpholino oligomer (PMO). This PMO-ASO blocks a regulatory element in SMN2 called Element 1 (E1) thereby allowing SMN2 to produce functional SMN proteins by enhancing the inclusion of exon 7.

Targeting E1 has shown great efficacy, dose-response and target engagement in extending the lifespan of severe SMA mice after a single injection in the central nervous system.  This work was published by Dr. Christian Lorson and his colleagues at the University of Missouri in the journal Molecular Therapy, in 2016. It demonstrates that treatment with E1v1.11 yields a 5-fold increase in mean survival in severe SMA mice with some mice approaching a normal lifespan. The combination of targeting E1 targeting and the use of PMO oligos together yield dramatic extensions in survival in an SMA mouse model with a single administration of PMO.  This work effectively showcases the robust activity of this compound in an important model of disease.

It is hoped that this strategy can provide clinically meaningful benefit to patients.

Further Information

Antisense Oligonucleotides
Molecular Therapy article
About Shift Pharmaceuticals
FDA Orphan Drug Designation