Stoke Therapeutics Inc. (stok): Disease-modifying, blockbuster potential in Dravet syndrome; Initiate at Buy, $44 PT

Research evidence excerpt

Stoke Therapeutics Inc. (stok): Disease-modifying, blockbuster potential in Dravet syndrome; Initiate at Buy, $44 PT

Goldman Sachs Stoke Therapeutics Inc. (STOK)

broad payer access in Dravet at rare disease (e.g., Spinraza-like) pricing, given precedent

with other disease modifying therapies. Thus, we model zorevunersen as a potentially

first-to-market disease-modifying therapy, with GSe unadjusted peak sales of ~$1.5B

(75% probability of success), driven by its ability to address both seizure frequency and

non-seizure comorbidities (cognition/behavior).

n Zorevunersen should hit on the Ph3 primary endpoint, which would enable

approval as a treatment for Dravet syndrome in ages 2+. Zorevunersen has shown

deep and sustained reduction on seizures at relevant doses to the Ph3 - in the

Ph1/2a ADMIRAL and MONARCH trials, patients receiving 70mg loading doses (n=9)

saw a median reduction in convulsive seizures of ~85% at 3 months and ~74% at 6

months, with ~58%-91% reduction across 1-month intervals for the first 20 months

of the OLE.

n We view a safety surprise as unlikely, given zorevunersen has been largely

tolerable, including in patients treated >4 years to date. Most common adverse

events on drug have been CSF protein elevations, post-lumbar puncture syndrome,

and procedural vomiting, with only one patient experiencing a treatment-emergent

serious adverse event (Suspected Unexpected Serious Adverse Reaction or SUSAR).

Further, CSF protein elevations, while common, did not have serious/severe related

clinical manifestations and only one patient discontinued due to elevated CSF

protein. Three patient deaths were unrelated over the Ph1/2a and OLE.

n Zorevunersen neurobehavioral data to date gives confidence that statistical

significance in Ph3 is achievable.