Mark Versavel, MD, PhD, MBA Sepracor Inc.

1. An Overview of the Development of Eslicarbazepine Acetate (ESL) as Adjunctive Therapy for Partial SeizuresA Novel Experimental Sodium Channel Blocker Mark Versavel, MD, PhD, MBA Sepracor Inc.

2. Blockade of voltage-gated sodium channels (VGSC). Interacts with site 2 of the inactivated state of the channel, with affinity similar to that of carbamazepine. Mechanism of Action of Eslicarbazepine Acetate I II III IV S6 Outside 1 2 3 4 5 6 1 2 3 4 5 1 2 3 4 5 6 1 2 3 4 5 6 6 Inside I N C Pore Eslicarbazepine acetate

3. Eslicarbazepine Acetate: A Simple Metabolic Profile • Eslicarbazepine acetate is hydrolyzed to eslicarbazepine • Eslicarbazepine is the predominant metabolite in both plasma and urine • Glucuronidation is the main metabolic pathway • Eslicarbazepine and its glucuronide correspond to 92% of the total drug material excreted in urine ESL H C 3 O O Hydrolase N O N H 2 Eslicarbazepine H O N O N H 2 UGT 2/3 Eslicarbazepine-GLU H O GLU URINE N O N H 2 1/3

4. Pharmacokinetics of Eslicarbazepine Acetate • Binding to plasma proteins is <40% • t½is 13-20 h in epileptic adult patients • Prolonged t½ in renal impaired subjects that requires dose reduction • Steady state of plasma concentrations is attained after 4 to 5 days of once daily dosing • Linear and dose-proportional PK • PK not affected by gender, age, or food • No significant interactions with other AEDs • May increase concentrations of phenytoin • May reduce the effect of oral contraceptives

5. QD Versus BID: Phase II, 12Week, Double-blind, Adjunctive Fixed Dose Escalation Study (400-1200 mg daily doses) Responder Rate (ITT) Eslicarbazepine acetate QD (n = 50) 60 Eslicarbazepine acetate BID (n = 46) P =0.008 Placebo (n = 47) 50 P = 0.12 40 % of Responders 30 20 10 0 ESL QD Placebo ESL BID

6. Integrated Analysis of 3 Phase III, 26 Week, Adjunctive Fixed Dose Studies: Primary Efficacy Analysis ANCOVA analysis for seizure frequency per 4 weeks over the 12-week maintenance period (ITT)

7. Integrated Analysis of 3 Phase III Studies: Safety Results • Most common AEs: dizziness, somnolence, headache, nausea, vomiting, diplopia, and abnormal coordination • Low incidence of hyponatremia • Small decrease of T4, no decreased thyroid function • Not associated with changes in total cholesterol, low density lipoprotein (LDL) levels, and glucose • No systematic effect on body weight • No clinically meaningful effect on ECG parameters

8. Eslicarbazepine Acetate As Adjunctive Therapy: Summary • Novel blocker of voltage-gated sodium channels • Pharmacokinetics and Pharmacodynamics • Eslicarbazepine acetate is hydrolyzed to eslicarbazepine, which is excreted renally • Prolonged t½ in renal impaired subjects that requires dose reduction • Efficacy • 800 mg and 1200 mg once-daily reduced partial-onset seizures • Maintained reduction in seizure frequency during a 1-year treatment period • Safety and Tolerability • Most common AEs: dizziness, somnolence, headache, nausea, vomiting, diplopia, and abnormal coordination

9. Status of Eslicarbazepine Acetate Studies • Phase III completed ex-US (adjunctive therapy) • Plans for additional epilepsy trials • Monotherapy • Pediatric • Other ongoing trials • Neuropathic pain: Phase II The safety and efficacy of eslicarbazepine acetate for the adjunctive treatment of epilepsy or any other use have not yet been evaluated by the FDA.