“a solution for obstructive sleep apnea: closed loop neuromodulation : ”

Mark Christopherson Vice President Product Development, Inspire Medical Systems, Inc.

NANS, December 6, 2012

“A Solution for Obstructive Sleep Apnea: Closed Loop Neuromodulation: ”

• The Inspire Therapy is Investigational Use Only in the United States• Mark Christopherson is an employee of Inspire Medical Systems

• A loss of muscle tone during sleep allowing the upper airway to narrow or close… a physiologic issue

Definition of Obstructive Sleep Apnea

AHI = Apnea/Hypopnea Index is number of events per hour

Sufferers stop breathing for periods of up to 20-30 seconds as many as 40-50 times per hour

Breathing cessations eventually cause the brain to send what is essentially a wake-up call to the body

Many co-morbidities have been directly linked with Obstructive Sleep Apnea…

Early Mortality

High Blood Pressure

Congestive Heart Failure

Stroke

Neuro-cognitive Problems

Daytime Sleepiness

Job Impairment

Fatigue-related accidents

Health Consequences of OSA

Prevalence of OSA and Clinical Treatment Guidelines – United States

Surgical Intervention

Oral Appliance

CPAP

Remain Untreated

Fail CPAP30%-60%

Moderate to Severe OSA in

>30 yrs old:

Diagnosed20%

Many patients remain untreated or undertreated

+13 million patients

Moderate to Severe OSA Treatments

Invasiveness Low High

Intr

usiv

enes

s Lo

wH

igh (CPAP) • Gold standard

• ~1 mil units per year• Low compliance 50%

Maxillofacial advancement

• Facial reconstruction

• Good clinical results• <2k procedures / yr

Upper Airway Stimulation addresses and unmet need: Less invasive, durable results, high patient compliance

Inspire therapy

UPPPSurgical removal: tonsils,

uvula, adenoids, soft palate

• Variable results• Painful recovery• 40k procedures /

yr

The Inspire System

• No removing / altering anatomy

• Straightforward, scalable procedure

• Fast post-op recovery

• Non invasive therapy titration

Neurostimulation works WITH patient’s physiology

The Inspire System Closed-loop Synchronized Stimulation

Stimulation Lead - Self sizing cuff - Multiple stimulation vectors

Implanted Pulse Generator (IPG) - Commercial grade technology platform - 6-8 year projected longevity

Respiration Sensor - Secure, stable location - Direct measurement of respiratory effort

Upper Airway Neuro-anatomy &Stimulation Site

Stimulation Site:

Medial branch of the hypoglossal nerve, activates only protrusors (genioglossus, geniohyoid), distal to retractors (styloglossus and hyoglossus)

Styloglossus (SG)

Hypoglossal Nerve (XII)

Hyoglossus (HG)

Superior root of ansa cervicalis Genioglossus (GG)

Geniohyoid (GH)Thyrohyoid

Stimulation Site

Superior Longitudinal

Inferior Longitudinal

Mauer JT 2012

Cuff Electrode Placement on the Hypoglossal Nerve

Sensor Location: Minimally Invasive

Sensor Incision/Dissection: • Within Intercostal muscles2

3

4

5

Typical Stimulation Parameters:2.5 volts, 90 microseconds, 33 Hz

Stimulating Pulses

Sen

sor S

igna

l Expiratory

Inspiratory

Upper Airway StimulationImmediate effect on stabilizing airway

Therapy OFF Therapy ON

EEG

EMGNasal

ThermChestAbdm

SaO2

30 second

Therapy activated

Stimulation turned off

Sleep Study – Apneic events return upon Turning the Inspire system OFF

Airflow obstructionsSnoring

Effort shows patientis trying to breath

Inspire Clinical Trial Experience

Inspire 1

Proof of Principle Trial

• 8 patients

• Completed in 2001

• Demonstrated therapy concept

• Publication: Archives Otolaryngology Head Neck Surgery 2001

Inspire 2&3

Feasibility Trials

• 34 patients

• Completed in 2010

• Demonstrated safety and patient selection

• Publication: Laryngoscope 2012

Inspire STAR

Pivotal Trial(Phase 3)

• 126 patients

• Completed in Q1 2012

• 12-month data follow-up period

• Data will be submitted for FDA commercial approval

Feasibility Trial - AHI ResponsePatients meeting Pivotal Selection Criteria (N=18)

Baseline Last0.0

5.0

10.0

15.0

20.0

25.0

30.0

35.0

40.0

45.0

50.0

AHI

11.6 ±934 ±6.2

AHI = Apnea-Hypopnea Index

Inspire Therapy: 20 years of Clinical Research and Product Development Experience

Feasibility Studies 2&3

Complete

STARPivotal Trial

Implants Complete

2nd GenTechnology

Development

Target for FDA approval

& US commercial

launch

MedtronicFeasibility

Study 1 Complete

20122000

• Inspire is a spin out from Medtronic

• 170+ global implants conducted at 25+ global clinical sites

• Commercially available in Europe (CE Mark received in 2010)

• The Inspire system is for Investigational Use Only in the United States

• Mark Christopherson is an employee of Inspire Medical Systems

2007

Inspire Therapy Aims to Improve Comfort, Convenience and Utilization

Patient uses Controller to: - Start, stop, pause therapy

Inspire therapyCPAP therapy

• Clinically effective• Utilization / compliance 40-

70%