Oventus: Innovators in Sleep Apnoea Treatment

Combination Therapy

6 August 2018

Why Do We Need Combination Therapy?

2

CPAP adherence is poor

• Adherence is poor

• 50-60% abandon CPAP within first 12 months1,2

• Adherence (hours of use) rates range from 30-60%3

• Non adherent users

• Start skipping nights during week one of treatment

• Remain non adherent4

• 16 years after this pattern of poor adherence was first described in the literature it remains largely unchanged4

1Propescu et al 2001; 2Galetke et al 2011; 3Weaver and Sawyer 2010 ; 4Weaver & Sawyer 2009

Trending Away From FFM

• FFM masks require higher pressure

than nasal masks to maintain patency.

Valentin A et al. Sleep J 2011

• Pressure in FFM causes more upper

airway obstruction than a nasal mask

by either displacing the mandible

posteriorly or increasing upper airway

collapsibility by virtue of mouth-

opening. Tero, Sleep J 2011

• First choice for Mouth breathers

• Increased Reimbursement ($20-40) DME

• Proactively Rx @ VA due to long wait times for PAP intervention (bad press)

FFM – Now Reconsidered Why Prescribed?

Results of Poor Mask Fit

of patients quit CPAP therapy within the first year

• Poor mask fit leads patients, on average, to try 3–5

generic masks in the first month.

• Patients who switched their mask are at a seven-fold

higher risk for abandoning therapy after switch than

those who did not.

• Mask acceptance is correlated with fewer mask leaks

(p=0.002) and higher pressure therapy (p=0.042)

50%

1. Borel JC, Tamisier R, Dias-Domingos S, et al. Type of mask may impact on continuous positive airway pressure adherence in apneic patients. PLoS One 2013;8:e64382. Budhiraja R, Parthasarathy S,Drake CL, et al. Early CPAP use identifies subsequent adherence to CPAP therapy. Sleep 2007;30:320–4

2. J Clin Sleep Med 2016;12(9):1227–1232 and Deshpande et al.J Clin Sleep Med 2016;12(9):1263–1268- Rohit Budhiraja, MD1,2; Jessie P. Bakker, BS, MS, PhD13. Valentin A et al. Sleep J 20114. Tero, Sleep J 20115. Bachour et al. Sleep J 2016

Clinical Pathway Triage O2 Vent Airway™

O2Vent Airway™

Oral Appliances Not Efficacious For All Patients

• Mandibular advancement splints (MAS) are not as efficacious as continuous positive airway pressure (CPAP)

• Effectiveness of both treatments on general health outcomes, cognitive function, and quality of life appears to be equivalent

• The main barrier for the implementation of MAS treatment in clinical practice is the interindividual variability in response to MAS treatment.

• Several prediction tools have been proposed to enhance patient selection for MAS treatment

• Phenotyping obstructive sleep apnea patients may reveal patient characteristics that enable the prediction of response to MAS treatment

Bamagoos AA1, Sutherland K2, Cistulli PA3. Sleep Med Clin. 2016 Sep;11(3):343-52. doi: 10.1016/j.jsmc.2016.04.002. Epub 2016 Jun 17. Mandibular Advancement Splints.

6

Patients

experienced

significant

improvement in

snoring using

O2Vent

7

Our Sleep Treatment Platform is personalising sleep medicine

* Traditional Jaw Advancement mouth guard

Traditional

lower jaw

advancement

(competitor

products)

Oventus

O2Vent™

Oventus

O2Vent™ +

EPAP

Oventus

O2Vent™ +

Connect

Mandibular

advancement

splints

41%1

of patients

treated

successfully

54%1 of

patients treated

successfully

78%2 of

patients

treated

successfully

100%3 of

patients

treated

successfully

1. Karen McCloy, Damian Lavery, Julia Moldavtsev, Airway open-airway closed: The effect of mandibular advancement therapy for obstructive sleep apnoea with and without a novel in-built airway. Abstract Submitted Sleep DownUnder

Brisbane 2018

2. Victor Lai, Benjamin Tong, Carolin Tran, Andrea Ricciardiello, Michelle Donegan, Nicholas Murray, Jayne Carberry and Danny Eckert Combination therapy with mandibular advancement and expiratory positive airway pressure valves

reduces OSA severity. Abstract Submitted Sleep DownUnder Brisbane 2018

3. Amatoury J, Tong B, Nguyen C, Szollosi I, Eckert DJ THE ROLE OF A NOVEL ORAL APPLIANCE THERAPY DEVICE ON PHARYNGEAL PRESSURE SWINGS AND CPAP REQUIREMENTS DURING SLEEP IN OBSTRUCTIVE

SLEEP APNEA: A PILOT STUDY. Abstract Supplement AADSM Boston 2017 * AHI < 10 and 50% reduction

More patients achieving success* with minimal intervention

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60

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120

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Cumulative Treatment Success Using Oventus Treatment Platform

MAS MAS + AIRWAY

MAS + AIRWAY + EPAP MAS + PAP

What Is Oventus Airway Technology Doing and

How Can Clinicians Use it?

• Ability to treat nasal obstructers as well as non-nasal obstructers

– Lavery D, Hart C et al. Safety and Efficacy of a Novel Oral Appliance in the Treatment of Obstructive Sleep Apnea. Journal of Dental

Sleep Medicine Vol.4 No.3 July 2017

– Benjamin Tong, Jason Amatoury, Jayne Carberry and Danny Eckert. The effects of posture and mandibular advancement on nasal

resistance and obstructive sleep apnea treatment outcome with a novel oral appliance therapy device. Neuroscience Research

Australia (NeuRA) and the University of New South Wales, Sydney, Australia. Poster and Abstract World Sleep Prague 2017.

• Where Mandibular advancement alone may not be able to

– Zeng B, Ng AT, Qian J, Petocz P, Darendeliler MA, Cistulli PA. Influence of nasal resistance on oral appliance treatment outcome in

obstructive sleep apnea. Sleep 2008 Apr;31(4):543-7

– Ng AT1, Qian J, Cistulli PA. Oropharyngeal collapse predicts treatment response with oral appliance therapy in obstructive sleep

apnea. Sleep 2006 May;29(5):666-7

– Prescinotto R1, Haddad FL2, Fukuchi I3, Gregório LC2, Cunali PA4, Tufik S2, Bittencourt LR5. Impact of upper airway abnormalities

on the success and adherence to mandibular advancement device treatment in patients with Obstructive Sleep Apnea Syndrome.

Braz J Otorhinolaryngol. 2015 Nov-Dec;81(6):663-70. doi: 10.1016/j.bjorl.2015.08.005. Epub 2015 Sep 7.

A Personalised Approach to Medicine

What Is Oventus Airway Technology Doing and

How Can Clinicians Use it?

• Reduces pharyngeal pressure swings (collapsibility) and reduces residual events

compared to MAS alone

– Walsh J, Pantin C, Lim A, Maddison K, Baker V, Szollosi I, McArdle N, Hillman D, Eastwood P. The Effect of a Novel Oral Appliance

Therapy on Obstructive Sleep Apnoea: Preliminary Results. Abstract Sleep DownUnder Auckland 2017

– Amatoury J, Tong B, Nguyen C, Szollosi I, Eckert DJ THE ROLE OF A NOVEL ORAL APPLIANCE THERAPY DEVICE ON

PHARYNGEAL PRESSURE SWINGS AND CPAP REQUIREMENTS DURING SLEEP IN OBSTRUCTIVE SLEEP APNEA: A PILOT

STUDY. Abstract Supplement AADSM Boston 2017

A Personalised Approach to Medicine

What Is Oventus Airway Technology Doing and

How Can Clinicians Use it?

• MAS + Airway Increases response rate in MAS non-responders.

– Karen McCloy, Damian Lavery, Julia Moldavtsev, Airway open-airway closed: The effect of mandibular advancement therapy for

obstructive sleep apnoea with and without a novel in-built airway. Abstract Submitted Sleep DownUnder Brisbane 2018

• MAS + Airway + EPAP Increases response rate in MAS + Airway non-responders

– Victor Lai, Benjamin Tong, Carolin Tran, Andrea Ricciardiello, Michelle Donegan, Nicholas Murray, Jayne Carberry and Danny Eckert

Combination therapy with mandibular advancement and expiratory positive airway pressure valves reduces OSA severity. Abstract

Submitted Sleep DownUnder Brisbane 2018

A Personalised Approach to Medicine

What Is Oventus Airway Technology Doing and

How Can Clinicians Use it?

• Reduces CPAP pressure requirements, eliminates the need for a full face mask and

allows mouth breathing while delivering nCPAP

– Amatoury J, Tong B, Nguyen C, Szollosi I, Eckert DJ THE ROLE OF A NOVEL ORAL APPLIANCE THERAPY DEVICE ON

PHARYNGEAL PRESSURE SWINGS AND CPAP REQUIREMENTS DURING SLEEP IN OBSTRUCTIVE SLEEP APNEA: A PILOT

STUDY. Abstract Supplement AADSM Boston 2017

– Benjamin Tong, Carolin Tran, Andrea Ricciardiello, Michelle Donegan, Nicholas Murray, Alan Chiang, Irene Szollosi, Jason Amatoury

and Danny Eckert. Combination therapy with CPAP plus MAS reduces CPAP therapeutic requirements in incomplete MAS

responders. Abstract Submitted Sleep DownUnder Brisbane 2018

• Treating nasal obstruction patients where traditional CPAP may not be able to

– Sugiura T, Noda A, Nakata S, Yasuda Y, Soga T, Miyata S, Nakai S, Koike Y. Influence of nasal resistance on initial acceptance of

continuous positive airway pressure in treatment for obstructive sleep apnea syndrome. Respiration. 2007;74(1):56-60. Epub 2005

Nov 18.

A Personalised Approach to Medicine

How Oventus Airway Technology is truly differentiatedDelivers consistent airflow. Addresses common sites of obstruction.

Combining mandibular advancement with its proprietary oral airway, Oventus Airway Technology uniquely addresses both sites of primary upper airway blockage and

secondary airway collapse. 12

• Oventus Airway Technology addresses multiple levels of obstruction.

• Mandibular positioning primarily manages tongue based obstruction, i.e. 20% of primary obstructions1

• Allowing airflow through Oventus ‘Airway Technology has a similar effect to pumping via CPAP2

• Oventus improves efficacy of oral appliance therapy by 30-50% 2,3

Source: 1. Genta PR, et al. CHEST DOI: 10.1016/j.chest.2017.06.017; 2. Amatoury J, et al. Abstract Supplement ADSM Boston 2017 3. Walsh J, et al. Abstract Sleep Downunder Auckland 2017

No EffectSomeEffect

Definite Effect

Level of Obstruction or Resistance

Incidence of primary

collapse (%)

Mandibular Advancement

Device (MAD)

Mandibular Positioning

Airway Therapy (Oventus Airway

Technology)

What is nasal EPAP?

Braga, C. W., et al. (2011).

Functional Residual Capacity

Upper Airway Area

• Mechanical one-way valve (ProventTM) applied over each nostril

• Provides high resistance to expiration -> high airway pressures during expiration -> reduces upper airway collapsibility

• Hyperinflation of lungs -> increased ‘tracheal traction’ -> reduces upper airway collapsibility

Friedman, M., et al. (2016).

Care of Prof Danny Eckert NeuRA

Could Nasal EPAP Complement MAS?

Apnoea-hyponoea index (AHI): number of apnoeic (≥90% airflow cessation) or hypopnoeic (>30% airflow cessation with arousal/>3% oxygen desaturation) events/hour of sleep

Oxygen Desaturation Index (ODI): number of >3% oxygen desaturations/hour of sleep

1. Nasal EPAP therapy reduces AHI, ODI, arousals per hour and daytime sleepiness

2. MAS primarily widens retro-palatal region and nasal EPAP may widen the hypo-pharyngeal region

3. ~50% of patients on MAS therapy have incompletely resolved OSA

Colrain, I. M., et al. (2008).Could combination therapy of MAS with nasal and oral EPAP reduce OSA severity in these patients?

AHI with nasal EPAP

Care of Prof Danny Eckert NeuRA

ORAL ePAP “Oventus ExVentTM”

• Mouth breathing results from increased resistance in the nose and/or soft palate collapse

• Increased resistance leads to negative pressure swings that cause arousals and a switch to mouth breathing

• Mouth breathing leads to a highly unstable airway

• Oventus Airway Technology + controlled exhalation reduces negative pressure swings and AHI while simultaneously increasing internal pressure in the airway and/or maintaining stability during exhalation with or without nCPAP

• The valve at the front of the airway or “ExVentTM” achieves this

Controlling Mouth BreathingIMPROVING UPPER AIRWAY PHYSIOLOGY

Oventus Airway Technology + PEEP delivering low

resistance inhalation and controlled exhalation

Neg pressure swings reduced due to air being delivered through device airway and oropharyngeal airway, supported by PEEP

Low resistance

inhalation and

PEEP targeted

to the

oropharynx via

O2 ExVent and

Oventus Airway

Increased nasal

resistance

Soft Palate

Collapses and a

switch to device

breathing

occurs

Could Nasal EPAP Complement MAS?

Apnoea-hyponoea index (AHI): number of apnoeic (≥90% airflow cessation) or hypopnoeic (>30% airflow cessation with arousal/>3% oxygen desaturation) events/hour of sleep

Oxygen Desaturation Index (ODI): number of >3% oxygen desaturations/hour of sleep

1. Nasal EPAP therapy reduces AHI, ODI, arousals per hour and daytime sleepiness

2. MAS primarily widens retro-palatal region and nasal EPAP may widen the hypo-pharyngeal region

3. ~50% of patients on MAS therapy have incompletely resolved OSA

Colrain, I. M., et al. (2008).Could combination therapy of MAS with nasal and oral EPAP reduce OSA severity in these patients?

AHI with nasal EPAP

Care of Prof Danny Eckert NeuRA

• 69 % of previous O2VentTM treatment failures improved their treatment outcome

• 44% of O2VentTM treatment failures achieved >50% AHI RDN

• 33% of previous O2VentTM treatment failures achieved AHI ≤ 10

• Appears to work well in patients with increased nasal resistance

• The increased nasal resistance may be working as a natural PEEP valve

Sydney NeuRA Study – Effect of Oral EPAP on MAD + Oventus

Airway Technology Treatment Failures (n=13)

• Oro-nasal EPAP “ONEPAP”

• Titratable true PEEP valve delivering constant pressure on exhalation

• 54% of previous O2VentTM treatment failures achieve AHI ≤ 10 & >50% RDN

• 31% of previous treatment failures AHI ≤ 5

In Development - Launch 2019

Sydney NeuRA Study – Effect of Oro-nasal EPAP on MAD + Oventus Airway Technology Treatment Failures (n=13)

• “Flapper” has a linear flow-pressure curve

• The harder the patient exhales the higher the pressure ramps to

• This can cause discomfort and/or feelings of claustrophobia

• A true PEEP valve the maximum pressure can be set by adjusting the titration mechanism

• The curve flattens out at a certain pressure level even as flow increases.

A True Titratable PEEP Valve vs “Flapper”

In Development - Launch 2019

• Positional obstructive sleep apnoea [POSA], commonly defined as supine to non-supine apnoea hypopnea index (AHI) ratio of ≥ 2).

• Twenty patients with sdOSA

• Sleep positional trainer (SPT) reduced the time spent in supine sleeping position compared to baseline and MAD therapy

• Both MAD and SPT were individually effective in reducing the overall apnea/hypopnea index (AHI) significantly when compared to baseline from 20.8 (15.1; 33.6)/h at baseline to 11.0 (6.7; 13.8)/h and to 11.1 (3.5; 17.7)/h with MAD or SPT, respectively

• The combination of SPT + MAD further reduced the overall AHI to 5.7 (3.6; 7.4), which was significantly lower than with MAD alone (p < 0.001) and SPT alone (p < 0.008), respectively

Dieltjens M1, Vroegop AV, Verbruggen AE, Wouters K, Willemen M, De Backer WA, Verbraecken JA, Van de Heyning PH, Braem MJ, de Vries N, Vanderveken OM. A promising concept of combination therapy for positional obstructive sleep apnea. Sleep Breath. 2015 May;19(2):637-44. doi: 10.1007/s11325-014-1068-8. Epub 2014 Oct 22.

MAD + Positional Therapy

FOR SUPINE DEPENDENT OSA

NeuRA Nasal Resistance Study (n=7)

• Results: Awake nasal resistance tended to increase from seated, to supine, to lateral body positions (2.5±0.7, 3.6±1.2, 4.3±1.6 cmH2O/ml/s, respectively)

• Mandibular advancement did not systematically alter nasal resistance in either the seated (3.1±0.9 cmH2O/ml/s) or supine positions (4.7±2.1 cmH2O/ml/s).

• Oral appliance therapy reduced the median supine non-REM AHI from 34.4 [5.1, 55.0] to 7.0 [3.1, 22.7] events/h sleep, p=0.03).

• CPAP pressure required to eliminate all obstructive events on the combination therapy was reduced from 9.4 ± 2.3 to 7.3 ± 1.4 cm H₂O (p = 0.001)

• The residual apnea hypopnea index on the MAD decreased from 11.2 ± 3.9 to 3.4 ± 1.5 on the combination therapy (p < 0.001).

• The number of oxygen desaturations was also less with the combination therapy than with MAD (p < 0.001)

• Both the MAD and the combination therapy were effective in reducing daytime sleepiness from 12.7 ± 2.1 at baseline to 9.7 ± 3.1 (p = 0.04) and 7.5 ± 4.1 (p = 0.007), respectively.

El-Solh AA1, Moitheennazima B, Akinnusi ME, Churder PM, Lafornara AM. Combined oral appliance and positive airway pressure therapy for obstructive sleep apnea: a pilot study. Sleep Breath. 2011 May;15(2):203-8. doi: 10.1007/s11325-010-0437-1. Epub 2010 Nov 10

MAD + PAP

• 14 male patients were included.

• The residual AHI and ODI on combination therapy (CT) was lower than that on MAD or PAP

• The residual % TST-SpO2<90% was lower than that on MAD and similar to that on PAP.

• The therapeutic pressure on CT was on average 9.2 cm H2O lower than that on PAP 19cm H2O

• For the 11 patients who completed CT, only CT reduced ESS compared to pretreatment value

• No treatment had significant impact on % slow wave sleep or overnight change of blood pressure

• For patients who completed CT, the average usage was 5.9±1.7 hr/night at 12th week and 6.4±1.5 hr/night at a median follow-up of 36.5-months.

Liu HW1,2, Chen YJ3, Lai YC4, Huang CY3, Huang YL5, Lin MT2,6, Han SY7, Chen CL8, Yu CJ5, Lee PL5,9. Combining MAD and CPAP as an effective strategy for treating patients with severe sleep apnea intolerant to high-pressure PAP and unresponsive to MAD. PLoS One. 2017 Oct 26;12(10):e0187032. doi: 10.1371/journal.pone.0187032. eCollection 2017.

MAD + PAP

• 92 OSA patients aged 25 to 85 years (mean 55 years)

• Mean polysomnogram-determined diagnostic AHI value was 37.6 (standard deviation (sd): 25.9)

• Half (n=46) met the diagnostic threshold for severe OSA (AHI ≥30), a quarter (n=23) had moderate OSA (AHI 15–29.9), and the remainder (n=23) had mild OSA (AHI 5–14.9)

• 65 patients (70.7%) tolerated PAP/MAS therapy, having used it for 14.0 months on average (sd: 11.1)

• Tolerance was higher in patients with severe OSA (76.1%) than mild OSA (69.8%), this difference was not statistically significant (P = 0.421)

• Patients with severe OSA were more likely to have had the follow-up polysomnogram than those with mild OSA (P = 0.023)

• In these patients, AHI values decreased from an untreated mean of 48.0 (sd: 28.3) events/hour to a treated mean of 3.1 events/hour (sd: 3.8) (P < 0.001), indicating that, on average, PAP/MAS eliminated OSA.

http://www.sleepreviewmag.com/2015/03/dental-clinicians-observations-combination-therapy-pap-intolerant-patients/

MAD + PAP

• Reduced pressure

requirements by 66%

• Simultaneous nCPAP delivery

and physiologic mouth

breathing

• Mask and strap free ultra low

pressure PAP delivery

Pilot Study O2VentTM T +/- PAP Connection

In Development - Launch 2019

Amatoury J, Tong B, Nguyen C, Szollosi I, Eckert DJ THE ROLE OF A NOVEL ORAL APPLIANCE THERAPY DEVICE ON PHARYNGEAL PRESSURE SWINGS AND CPAP REQUIREMENTS DURING SLEEP IN OBSTRUCTIVE SLEEP APNEA: A PILOT STUDY. Abstract Supplement AADSM Boston 2017

O2VentTM W AND OPTIMATM + EXVENTTM +/- Nasal epap or cpap

O2VentTM Connect PAP Connection

Oventus Airway Technology – Coming Soon….

• Nasal PAP delivers pressure and flow

• Controlled exhalation with easy inhalation allows

mouth breathing while putting a floor under

pharyngeal pressure

P-CritPharyngeal Airway

Trachea

PAP P +Q

Controlled Exhalation

All of These Results Can Be Achieved From SeptemberO2VENTTM W AND OPTIMATM + EXVENTTM +/- NASAL EPAP OR CPAP

How Can we use the Oventus Treatment Platform to Enhance Patient Outcomes?

The Oventus Treatment Platform Cumulative Success*

• MAS 41% Treatment success1

• Oventus O2VentTM 54% Treatment success1

• Oventus O2VentTM + EPAP 78% Treatment Success2

• Oventus O2VentTM + Connect 100% Treatment Success3

1. Karen McCloy, Damian Lavery, Julia Moldavtsev, Airway open-airway closed: The effect of mandibular advancement therapy for obstructive sleep apnoea with and without a novel in-built airway. Abstract Submitted Sleep DownUnder Brisbane 2018

2. Victor Lai, Benjamin Tong, Carolin Tran, Andrea Ricciardiello, Michelle Donegan, Nicholas Murray, Jayne Carberry and Danny Eckert Combination therapy with mandibular advancement and expiratory positive airway pressure valves reduces OSA severity. Abstract Submitted Sleep DownUnder Brisbane 2018

3. Amatoury J, Tong B, Nguyen C, Szollosi I, Eckert DJ THE ROLE OF A NOVEL ORAL APPLIANCE THERAPY DEVICE ON PHARYNGEAL PRESSURE SWINGS AND CPAP REQUIREMENTS DURING SLEEP IN OBSTRUCTIVE SLEEP APNEA: A PILOT STUDY. Abstract Supplement AADSM Boston 2017

*AHI ≤ 10 and >50% reduction

A Personalised Approach to Medicine

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Cumulative Treatment Success Using Oventus Treatment Platform

MAS MAS + AIRWAY MAS + AIRWAY + EPAP MAS + PAP

WHERE TO NEXT?

Pharma and Behavioral Therapy

Ludovico et al Sleep Breath 2017

Targeted non-CPAP Interventions for OSA

Eckert et al, Am J Resp Crit Care Med (2013) & Carberry et al, Chest (2018)

100% anatomical compromise

(but of variable magnitude)

36% poor muscle

responsiveness

36% unstable respiratory

control (high loop gain)

37% low arousal threshold

MAD + Pharma

Combination therapy: Supplemental O2 and a hypnotic

(eszopiclone) reduces OSA Severity

Edwards et al, Sleep (2016)

Oventus OptimaTM

ExVentTM and ONEPAPTM

Comprehensive Dental Sleep Treatment Platform

Designed specifically for Sleep Groups• The Dental Sleep Program is comprehensive and will assist Sleep Groups to maximise patient outcomes

by providing the systems, support, training and resources required to run a professional Dental Sleep Medicine clinic utilising Oventus’ proprietary airway technology and digital workflow

QUESTIONS?

THANK YOU