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 seconds as many as 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 CPAP 30%-60% Moderate to Severe OSA in >30 yrs old: Diagnosed 20% Diagnosed 20% Many patients remain untreated or undertreated +13 million patients

Moderate to Severe OSA Treatments InvasivenessLow High Intrusiveness Low High (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 UPPP Surgical 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 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 muscles

Typical Stimulation Parameters: 2.5 volts, 90 microseconds, 33 Hz Stimulating Pulses Sensor Signal Expiratory Inspiratory

Upper Airway Stimulation Immediate effect on stabilizing airway Therapy OFF Therapy ON EEG EMG Nasal Therm Chest Abdm SaO 2 30 second Therapy activated

Stimulation turned off Sleep Study – Apneic events return upon Turning the Inspire system OFF Airflow obstructions Snoring Effort shows patient is 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 Q month data follow- up period Data will be submitted for FDA commercial approval

Feasibility Trial - AHI Response Patients meeting Pivotal Selection Criteria (N=18) 34 ±6.2 AHI = Apnea-Hypopnea Index

Inspire Therapy: 20 years of Clinical Research and Product Development Experience Feasibility Studies 2&3 Complete STAR Pivotal Trial Implants Complete 2 nd Gen Technology Development Target for FDA approval & US commercial launch Medtronic Feasibility Study 1 Complete 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%