Shift Pharmaceuticals is developing a drug to treat all forms of Spinal Muscular Atrophy (SMA) by targeting an important “back-up” gene, SMN2 that is present in all SMA patients. Antisense oligos (ASOs) targeting regulatory elements in SMN2 including Element1 (E1) are particularly effective in shifting SMN2 to produce a functional protein.
Our optimized strategy in targeting the inhibitory element, Element 1, employs Phosphorodiamidate Morpholino antisense oligos (PMOs). A particular MO variant, E1 v1.11, shows 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 published by our Chief Scientific Officer, Christian L. Lorson and his colleagues at the University of Missouri in Molecular Therapy, demonstrates that treatment with E1 v1.11 yields a 5-fold increase in mean survival in severe SMA mice with some mice approaching a normal lifespan (See our embedded Powerpoint presentation). The combination of optimized 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 academic work effectively showcases the robust activity of the lead compound in an important model of disease.
Antisense technology is finally entering into a phase of clinical successes and we believe our strategy can provide clinically meaningful benefit to patients that have previously had little reason for hope.