1. Pipeline Session: NBI-98854 Human Pharmacokinetics of NBI-98854: A Selective Inhibitor of VMAT2 with an Attractive PK and Safety Profile for Hyperkinetic Movement Disorders

2. VMAT2 Target for Hyperkinetic Movement Disorders Transaxial PET images depicting the preferential distribution of α -[C 11 ]-htbz at basal ganglia in a normal human subject. Koeppe et al., 1999 Kenney and Jankovic, 2006 The only approved medication targeting VMAT2 (Xenazine/Nitoman) has pharmacologic and pharmacokinetic profiles that result in a safety profile which limits clinical utility Tardive dyskinesia Schizophrenia Huntington’s chorea Tardive dystonia Tourette syndrome Dystonia

3. CYP2D6 PM CYP2D6 EMs NBI-98854: The Best in Class VMAT2 Inhibitor Current Option Not Appropriate for All Patients VMAT2-KiD2-Ki (+)-  -DHTBZ 1-4 nM >10  M (-)-  -DHTBZ 200 nM192 nM (+)-β-DHTBZ14 nM >10  M (-)-β-DHTBZ710 nM57 nM 1.Kilbourn, et al., Eur. J. Pharmacol, 1995 2.Mehvar, R. et al Drug Metabolism and Disposition 1986 3.Neurocrine Data Tetrabenazine (TBZ) (±)-  -DHTBZ (Mix of 4 stereoisomers) Human PK Current Treatment Regimen Suboptimal Selectivity Unwanted stereoisomers confer poor selectivity Suboptimal Pharmacokinetics Low bioavailability, high variability Polymorphic CYP2D6-dependent metabolism Requires dose titration bid or tid dosing regimen Side Effects Limit Usefulness Depression, parkinsonism, akathisia

4. Neurocrine’s Solution: Slow Systemic Release NBI-98782 ((+)  - DHTBZ ) (The active metabolite) NBI-98854 VMAT2-KiD2-Ki NBI-98782 (+)  -DHTBZ 1-4 nM >10  M NBI-98854187 nM >10  M Potential advantages over approved therapies Reduced PK variability » qd dosing Improved side effect profile » Parent compound has low VMAT2 activity » The active metabolite is potent, has attenuated C max and is highly selective Very slow Inert

5. Single Ascending Dose Study NBI-98854-0801 5

6. Clinical Safety Summary NBI-98854-0801 NBI-98854 generally safe and well tolerated No Serious Adverse Event (SAE) No clear Treatment Emergent Adverse Event (TEAE) trends or signal » No clinically significant ECG changes or QTcF prolongation » No clinically significant hemodynamic changes » Laboratory values unremarkable » No evidence of sedation, lethargy and somnolence Cog State testing : performance was stable across the study period when compared to placebo and baseline. 6

7. NBI-98854: Human PK at 75 mg C ONFIDENTIAL 7 NBI-98854NBI-98782

8. Human Exposure of the Active Metabolite NBI-98782 Compared with (±)  -Dihydrotetrabenazine C ONFIDENTIAL 8 Each circular dot represents an individual subject, and the horizontal lines represent the means for NBI-98782 after an oral dose of NBI-98854 (75 mg). The square dots bracket the range of concentrations of (±)α-DHTBZ that have been reported in the population of subjects taking 50 mg daily dose of tetrabenazine (FDA approval information for Xenazine ®.

9. NBI-98854 for hyperkinetic movement disorders: Product profile CxT comparison (±)α-DHTBZ vs. NBI-98782 Steady state simulation (75 mg NBI-98854 qd) Single, highly selective small molecule VMAT2 inhibitor Favorable safety and tolerability profile » Reduced Cmax » Selective: no off-target effects/pharmacology » Reduced PK variability » Predictable metabolism » Reduces need for dose titration QD dosing Novel small molecule Scalable manufacturing route Clinically proven MOA Single, highly selective small molecule VMAT2 inhibitor Favorable safety and tolerability profile » Reduced Cmax » Selective: no off-target effects/pharmacology » Reduced PK variability » Predictable metabolism » Reduces need for dose titration QD dosing Novel small molecule Scalable manufacturing route Clinically proven MOA