Treatment Goals for OSA Patients

• Reduce Symptoms• Improve Quality of Life• Reduce Accident Risk• Minimize Cardiovascular

and Other Health Risks

Clinical Data Update Summary of published long-term 3-year outcomes data

Inspire Therapy for Obstructive Sleep ApneaFor OSA patients unable to tolerate or get

consistent benefit from CPAP

Consequences of Untreated Obstructive Sleep Apnea (OSA)

*Excerpt from a sleep study of an Inspire therapy candidate

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• Untreated OSA can have devastating effects on heart and brain health, impair quality of life and increase motor vehicle and occupational accident risk

AIRFLOW

Airway Obstruction:47 seconds

Airway Obstruction:86 seconds

• During sleep, OSA patients experience repetitive airway obstructions followed by oxygen desaturations

1. Artz et al., Am J Respir Crit Care Med 2005 2. Young et al., Sleep 2008 3. Peppard et al., N Engl J Med 2000 4. Tregear et al., J Clin Sleep 2009 5. Shahar et al., Am J Respir Crit Care Med 2001 6. Lindberg et al., Am J Respir Crit Care Med 2001 7. Reichmuth et al., Am J Respir Crit Care Med 2005 8. Smith et al., CHEST 2002 9. Gottlieb et al., S Circulation. 2010

OXYGEN SATURATION LEVEL

84% 74%

• Moderate to severe OSA patients can experience hundreds of obstructions and desaturations each night90%

INCREASED RISK DUE TO UNTREATED OSA

Desaturation (45.13s) [13] Desaturation (91.83s) [24]

Odds RatioHazard RatioRelative Risk

OSA Treatment Shown to Reduce Cardiovascular Events

• Untreated severe OSA (AHI of 30+) is associated with an increased risk of both fatal and non-fatal cardiovascular events

• Consistent treatment with Continuous Positive Airway Pressure1 (CPAP) or an AHI

The Hypoglossal Nerve (Cranial Nerve XII)The Basis for Inspire Upper Airway Stimulation Therapy

• Motor nerve

• Controls the muscles and movements of the tongue

• Mild stimulation of the distal hypoglossal nerve restores upper airway muscle tone

• Increase in muscle tone can prevent the tongue and other soft tissues from collapsing and obstructing the airway during sleep

Adapted from IVLine.org

Stimulation Synched with BreathingThe Inspire System Delivers Therapy When Airway is

Most Vulnerable to Collapse

• Fully implanted system that uses well-established technologies and surgical techniques

• Breathing sensor monitors a patient’s breathing cycle

• Rhythmic, mild stimulation is delivered to the hypoglossal nerve through the stimulation cuff

• Mild stimulation is delivered during inspiration, when the OSA patient’s airway is most vulnerable to collapse

1

2

3

1) Stimulation Cuff2) Generator3) Breathing Sensor

Safiruddin, et al. European Respiratory Journal, January 2015

Stimulation Effect on Airway Anatomy

No Stimulation Mild Stimulation

Obstructed Airway

Palate Palate180% increase

in airway dimension130% increase

in airway dimension

Tongue Base Tongue Base

Open Airway

*Endoscopy images of an Inspire therapy recipient

At therapeutic titrated levels, Inspire therapy prevents the airway from collapsing to

facilitate unobstructed breathing

Stimulation Effect During Sleep

• Airflow and breathing stabilized

• Normal SaO2 levels restored

• Uninterrupted sleep continues without arousals

*Sleep study of an Inspire therapy recipient

Inspire therapy turned on

Airflow

Breathing

SaO2

Severe OSA Events OSA Events Resolved

Inspire Therapy Clinical Evidence Development

12 peer-reviewed publications as of November 2015

ONGOING STUDIES

STAR PHASE III TRIAL WITH RANDOMIZED

CONTROLLED WITHDRAWAL STUDY

Safety/Efficacy

FDA Approval

Long-Term Follow-Up

Cost Effectiveness

8 Peer-Reviewed Publications

European Post-Approval Study

US Post-Approval Study

Multiple Single Center Experience Projects

European Randomized Controlled Study

First in Man

Patient Selection

Implant Technique

Safety/Efficacy

4 Peer-Reviewed Publications

INSPIRE 1, 2, 3 FEASIBILITY STUDIES

Peer-Reviewed STAR Trial Outcomes Publications:

One Year: Upper Airway Stimulation for Obstructive Sleep Apnea. Strollo et al. The New England Journal of Medicine. January 2014

Randomized Study:

Randomized Controlled Withdrawal Study of Upper Airway Stimulation on OSA. Woodson et al. Otolaryngology Head and Neck Surgery. September 2014

18 Months: Upper Airway Stimulation for Obstructive Sleep Apnea—Durability of the Treatment Effect at 18 months. Strollo et al. SLEEP. June 2015

Two Year: Upper Airway Stimulation for Obstructive Sleep Apnea: Self-Reported Outcomes at 24 months. Soose et al. Journal of Clinical Sleep Medicine. July 2015

Three Year: Three Year Outcomes of Cranial Nerve Stimulation for Obstructive Sleep Apnea: The STAR Trial. Woodson et al. Otolaryngology Head and Neck Surgery. November 2015

Inspire Therapy Long-Term Objective Outcomes

Patients using Inspire therapy experienced significant decreases in both AHI and ODI from baseline to 12 months. These significant improvements were maintained over the 36-month follow-up period.

Reduced  OSA  Severity:  AHI

29.3  

9.0   9.7  6.2  

0.0  

5.0  

10.0  

15.0  

20.0  

25.0  

30.0  

35.0  

Baseline  N=126  

12  Month  N=124  

18  Month  N=121  

36  Month  N=98  

Apnea  Hy

popnea  Index  

Results  in  median  All  p  values  <  0.01  vs.  baseline  

Reduced  OSA  Severity:  ODI

25.4  

7.4   8.6  

4.8  

0.0  

5.0  

10.0  

15.0  

20.0  

25.0  

30.0  

Baseline  N=126  

12  Month  N=124  

18  Month  N=121  

36  Month  N=98  

Oxygen  De

saturaKo

n  Index  

Results  in  median  All  p  values  <  0.01  vs.  baseline  

All p values < 0.01 vs. baseline. Results in median.

All p values < 0.01 vs. baseline. Results in median.

OXYGEN DESATURATION INDEX (ODI)

APNEA HYPOPNEA INDEX (AHI)

Improved  Day8me  Func8oning:  FOSQ

14.6  

18.2   18.4  18.8  

10  11  12  13  14  15  16  17  18  19  20  

Baseline  N=126  

12  Month  N=123  

18  Month  N=123  

36  Month  N=110  

 FuncKo

nal  O

utcomes  o

f Sleep QuesKonnaire

 

Normalized daytime functioning  

Results  in  median  All  p  values  <  0.01  vs.  baseline  

Reduced  Day8me  Sleepiness:  ESS  Scale

11.0  

6.0   6.0   6.0  

4  

5  

6  

7  

8  

9  

10  

11  

12  

Baseline  N=126  

12  Month  N=123  

18  Month  N=123  

36  Month  N=110  

Epworth  Sleepiness  S

cale  

Normalized  dayKme  sleepiness  

Results  in  median  All  p  values  <  0.01  vs.  baseline  

Inspire Therapy Long-Term Patient Reported Outcomes

Patients using Inspire therapy reported significant improvements and normalization of both daytime sleepiness and daytime functioning. These significant improvements were reported at 12 months and were sustained at 36-month follow up.

All p values < 0.01 vs. baseline. Results in median.

All p values < 0.01 vs. baseline. Results in median.

EPWORTH SLEEPINESS SCALE (ESS)

FUNCTIONAL OUTCOMES OF SLEEP QUESTIONNAIRE* (FOSQ)

* Importantly, all 5 FOSQ subscale variables showed clinically significant improvements. FOSQ subscale variables include (1) activity, (2) productivity, (3) social, (4) intimacy and (5) vigilance.

Inspire Therapy Adherence

86%  81%   81%  

93%  86%   87%  

0%  

10%  

20%  

30%  

40%  

50%  

60%  

70%  

80%  

90%  

100%  

12  Month  N  =  124  

24  Month  N  =  117  

36  Month  N  =  108  

Use  every  night  (%)   Use  at  least  5  nights  a  week  (%)  

Patient Self-Reported

From  STAR  database  

Inspire Therapy Patient and Partner Experience

Sleep apnea affects not only patients but their bed partners as well. Snoring, a common sleep apnea symptom, was significantly impacted in patients using Inspire therapy from baseline. Additionally, fewer partners left the room due to their partner’s snoring.

PARTER REPORTED SNORING OUTCOMES

THERAPY ADHERENCE

Bed partner leaves roomNo or soft snoring

Therapy adherence remained high throughout the three-year follow-up period.

50%

40%

30%

20%

10%

0%

30%

BaselineN=108

5%

12 MonthN=103

4%

18 MonthN=103

3%

36 MonthN=97

100%

80%

60%

40%

20%

0%

17%

BaselineN=108

86%

12 MonthN=103

87%

18 MonthN=103

80%

36 MonthN=97

Inspire Therapy Patient Selection Considerations

Patients use the handheld sleep remote to turn the therapy on before bed and off upon waking.

Inspire therapy is FDA-approved and available at over 50 leading medical centers in the United States. It is intended for people who:

• Have been diagnosed with moderate to severe OSA (AHI 20-65)• Cannot tolerate or get consistent benefit from CPAP• Are not significantly overweight

People who meet these basic criteria can be referred to a specialist who can evaluate sleep parameters, assess the airway anatomy and determine if Inspire therapy is right for them.

In addition, Inspire therapy is approved and available in over 8 European countries.

Visit www.inspiresleep.com to review risks, benefits and expectations associated with Inspire therapy. Risks associated with the surgical implant procedure are low but may include infection and temporary tongue weakness. Most patients acclimate well to the presence of the Inspire system and to the therapeutic stimulation. Some patients may require post-implant adjustments to the system’s settings in order to improve effectiveness and ease acclimatization.

Additional Resources:www.InspireSleep.com844 OSA HELP (844-672-4357)

© Inspire Medical Systems, Inc. 2015. All Rights Reserved. 800-132-001 Rev A Nov 2015

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