Denali Therapeutics has a PDUFA on Jan 5, 2026 for its lead drug Tividenofusp alfa, based on strong Phase 1/2 data.
Results showed ~90% reduction of CSF heparan sulfate and signals of cognitive and systemic benefit a major step forward for MPS II (Hunter syndrome). The current SoC (Idursulfase) only treats somatic symptoms and cannot cross the BBB. Given the high unmet need, the FDA granted multiple designations: Breakthrough, Fast Track, Orphan, Rare Pediatric Disease. Analysts estimate peak sales potential of around $1B annually if Tividenofusp replaces Idursulfase as the new standard of care.
Compass Trial
A pivotal Phase 2/3 COMPASS trial is ongoing, directly comparing Tividenofusp to Idursulfase, with the goal of proving it can become the new SoC.
Commercialization
Denali retains 100% commercial rights and is already in prelaunch mode, engaging with KOLs, payers, and patient groups. They are building their own sales and medical affairs team, and the company is led by ex-Genentech executives with a proven track record in drug development.
My Move
Normally I avoid BBB-focused plays due to complexity and DNLI’s relatively high market cap.
But with strong cash, multiple FDA designations, and an ongoing pivotal trial, I took a small position. Even in the case of a CRL, downside risk may be cushioned by cash and the potential of positive Phase 3 readout.