1. Martha J. Morrell MD NeuroPace, Inc.
The NeuroPace® RNS System: Clinical Development of Responsive Cortical Stimulation as a Treatment for Medically Refractory Epilepsy
Martha J. Morrell MD
NeuroPace, Inc.

2. NeuroPace Overview
Founded in 1999 to design, develop, manufacture and market implantable responsive neurostimulation devices for treating epilepsy by direct brain stimulation

3. The RNS™ System Approach
Detect abnormal brain electrical activity with electrodes implanted near the area of seizure onset
Stimulate at the time of detection and before a seizure develops
Program detection and stimulation for individual patient
Transmit device and electrocorticogram data to interactive web-based repository
View data on-line at any time to assess clinical response

4. The RNS™ System
Cranially implanted battery powered responsive neurostimulator
Connected to 2 leads (depth and/or subdural) with 4 electrode contacts each

5. The RNS™ System
Neurostimulator detects and stimulates abnormal brain electrical activity with implanted electrodes
Programmer sets detection and stimulation parameters
Programmer and Patient
Data Transmitter send ECoG data to web-based repository for review

6. Patient Data Management System
Caution: Investigational Device. Limited by US Law to Investigational Use Only.Caution: investigational device. Limited by US law to investigational use only.

7. Overview: RNS System Clinical Trials in Epilepsy
Feasibility Trial: completed
Pivotal Trial: on-going
Long-term Treatment Trial: 5 year follow-up all subjects

8. RNS™ System Feasibility Investigation
Designed to assess safety of the RNS™ System and to show preliminary evidence for efficacy as an adjunctive therapy in reducing the frequency of seizures in individuals 18 years of age or older with partial onset seizures that are refractory to two or more antiepileptic medications
Multi-center investigation 3

9. RNS™ System Feasibility Investigation: Inclusion Criteria
18 to 65 years of age with disabling simple, complex partial and/or generalized tonic clonic seizures
Failed treatment with 2 or more antiepileptic drugs
4 or more simple, complex or secondarily generalized TC seizures/month
One or two localized epileptogenic zones 3

10. RNS™ System Feasibility Investigation: Trial Design
Implant
RNS System 1 2 3 4 24
months
Therapy ON -n
Therapy OFF
Baseline: > 3 months
Post-Implant:
28 days
Evaluation: 3-28 day periods
Follow-up: 24 months post-implant
After 2 year Feasibility trial, subjects transition to
Long-term Treatment Trial for additional 5 year follow-up

11. Responder Rate During Efficacy Evaluation Period (2-4 Months Post-Implant, N= 50*)
Responder Rate: patients with > 50% reduction in seizure frequency over most recent 84 days vs. baseline
All disabling seizures*
24% (12/50)
Complex partial seizures
27% (12/44)
Generalized TC seizures
65% (11/17)
Disabling seizures= SPM, CPS and GTC
*5 subjects excluded due to inconsistencies in the data, 1 had no disabling seizures at baseline, 14 subjects randomized to sham stimulation

12. Responder Rate Over Most Recent 84 Days of Data (N = 59
Responder Rate Over Most Recent 84 Days of Data (N = 59*): All Disabling Seizures
Analysis by seizure onset location
Total
47%
Hippocampal
74%
Neocortical
34%
* 5 subjects excluded due to inconsistencies in the data, 1 had no disabling seizures at baseline
Data are current as of 11/2008; not completely verified.

13. Feasibility: Response over Time
FS - Data updated as of 6/24/2008 – Note: the OFF patients were shifted by 111 days so the 3MO data represents 3MO after they were turned ON.
Data are current as of 02/19/2009; not completely verified.

14. RNS™ System Feasibility Investigation: Summary Experience
Safety milestone reached
No unanticipated device related or surgery related serious adverse events
Preliminary evidence for efficacy
Reduction in SP motor, CPS, GTC seizures
Subjects with hippocampal onset had especially good response

15. RNS™ System Pivotal Trial
Randomized, double-blinded, multi-center, sham stimulation controlled
240 patients enrolled at 29 sites
Objective
Demonstrate that the RNS System is safe and effective in reducing the frequency of disabling seizures in adults with medically intractable partial onset seizures

16. RNS™ System Clinical Experience
All epilepsy trials combined
310 subjects enrolled
246 subjects implanted
> 426 patient years of post-implant experience
> 367 patient years of stimulation experience
FS – updated implant years and stim years as of 6/24/2008
Data current as of March 3, 2009; not completely verified.

17. RNS™ System Clinical Trials in Epilepsy
Technology successful
Safety profile appears favorable
No unanticipated device related serious adverse events
Feasibility trial shows evidence for durable efficacy
Future plans
Pivotal trial complete in August 2009
Analysis of clinical response as a function of
Detection and stimulation programming
Epileptogenic region
Epilepsy etiology