Something I keep thinking about regarding $ARWR’s CNS competitors. $IONS and $ALNY are both building subq brain delivery while running deep intrathecal pipelines. Nothing forces them to pick. What they could use is a reason to drop intrathecal and focus on subq. A trial where tau falls beautifully in spinal fluid and the patient barely moves gives management exactly that. The program stays alive, but someone has to explain the gap, and saying “we didn’t reach enough of the brain” is the only answer that doesn’t indict the target. It points at the route instead. CELIA with diranersen already ran that experiment. Tau down 50-65% in CSF, PET down in every region, dose-response primary missed, and higher doses did no better than 60mg. If more drug doesn’t help, either tau lowering has a ceiling or the drug never got where it needed to go. Prediction: within 18 months at least one of them quietly drops an intrathecal CNS candidate with no safety reason given. Over a longer horizon I’d expect many more, because neither company ends up carrying a franchise that size on a route they’re actively replacing. No hold, no announcement. It just stops appearing on the pipeline slide while the shuttle work keeps coming up on calls. Watch the slides, not the press releases.
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