Extracellular Tau as a Druggable Antibody Target
Placeholder: why extracellular tau is targeted by monoclonal antibodies.
- N-terminal tau: Target epitope (Placeholder epitope note)
- 6: Tau isoforms (Placeholder isoform note)
- ELISA/SPR: Assay format (Placeholder assay note)
- 12: Candidate mAbs (Placeholder screening note)
Selecting the extracellular tau epitope
Placeholder: epitope mapping and antibody selection criteria.
Placeholder: key insight on extracellular tau targeting.
Blocking Cell-to-Cell Propagation of Pathological Tau
Placeholder: how antibody binding halts trans-synaptic tau spread.
- Trans-synaptic: Spread route (Placeholder route note)
- Sub-nM Kd: Binding affinity (Placeholder affinity note)
- ~70%: Uptake blocked (Placeholder uptake note)
- Tau-PS19 mice: Model system (Placeholder model note)
Neutralizing extracellular tau seeds
Placeholder: mechanism preventing seeding-competent tau uptake.
Placeholder: key insight on blocking propagation.
Dose-Escalation Cohorts in the Clinical Trial
Placeholder: low/medium/high dose cohort design rationale.
- 3: Cohorts (Placeholder cohort note)
- ~180: Participants (Placeholder enrollment note)
- Every 4 wk: Dosing interval (Placeholder schedule note)
- IV infusion: Route (Placeholder route note)
Cohort design and safety monitoring
Placeholder: dose-escalation and safety monitoring approach.
Placeholder: key insight on dosing cohorts.
Tau PET Imaging as a Response Biomarker
Placeholder: tau PET SUVR tracked longitudinally during treatment.
- 18F-flortaucipir: Tracer (Placeholder tracer note)
- 6 months: Scan interval (Placeholder interval note)
- 8 ROIs: Regions tracked (Placeholder ROI note)
- >15%: SUVR reduction goal (Placeholder target note)
Interpreting tau PET signal change
Placeholder: reading SUVR trends as treatment response.
Placeholder: key insight on PET monitoring.
Cognitive Endpoint Assessment and Trial Outcome
Placeholder: cognitive scales used to assess clinical benefit.
- CDR-SB: Primary scale (Placeholder scale note)
- ADAS-Cog: Secondary scale (Placeholder scale note)
- 18 months: Follow-up (Placeholder follow-up note)
- ~30% slowing: Effect size goal (Placeholder efficacy note)
Comparing treatment vs placebo trajectories
Placeholder: cognitive decline trajectory comparison.
Placeholder: key insight on cognitive endpoints.