Digital health COULD DIGITAL SOLUTIONS HELP UNLOCK SLEEP, ONE OF BIOLOGY'S BLACK BOXES? - Bryan, Garnier & Co
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Digital health COULD DIGITAL SOLUTIONS HELP UNLOCK SLEEP, ONE OF BIOLOGY’S BLACK BOXES? HEALTHCARE WHITE PAPER JULY 2020
Contents In the past decade, digital solutions have
emerged to help patients manage chronic
diseases such as diabetes, hypertension and
asthma, which affect 147 million adults in the
United States alone.
SLEEP: A PUBLIC HEALTH PRIORITY COSTING BILLIONS 2 Using cognitive, behavioural and psychological methods, these
Poor sleep is one of the world’s most common health problems 2 solutions have gained momentum in recent years, buoyed by
technological advances and compelling medico-economic
Poor sleep costs up to USD700 billion across five OECD countries 2
evidence that has driven payers to extend coverage. This trend
Treatments exist, but come with limitations 4 has led to the emergence of successful companies such as
Hypnotics: purely symptomatic and the de facto first-line treatment 5 Livongo, Omada Health and Big Health.
CBTi: a gold standard, but not yet a first-line treatment 5 Digital adoption has now spread to mental health care,
DIGITAL IS DISRUPTING CARE AND TREATMENT 8 especially in relation to sleep. Poor sleep is one of the most
common health problems, leading to increased healthcare
Digital therapeutics: a 10-year journey finally bearing fruit 8 costs and lost productivity across the world. Evidence of
A business opportunity mostly driven by US employers for now 10 behavioural solutions for sleep problems indicates that annual
savings of up to USD1,000 in healthcare costs per patient are
SLEEP CARE IS DIGITAL HEALTH’S NEXT BIG OPPORTUNITY 12
possible, which should lead to strong adoption by payers who
Recent studies have confirmed the medico-economic case for digital 12 are early adopters of innovative solutions for driving healthcare
sleep solutions costs down.
US employers are now embracing digital solutions for sleep 13
Finally, we believe that digital solutions will improve our
THE FUTURE OF SLEEP HEALTH: 14 understanding of sleep, which remains one of the “black
A BIG-DATA REVOLUTION IN THE MAKING
boxes” of biology. The new generation of accurate and
Outdated technology has limited our understanding of sleep 14 reliable sleep-monitoring wearables will contribute to a better
understanding of sleep by enabling big data analysis, and will
Recent advancements in data acquisition opened the door to a big data 15
revolution in sleep have potential applications in the early diagnosis of cognitive
disorders, treatments and remote monitoring at large scale.
Big data in sleep has unlimited potential 16
Monitoring: from clinical to post-market studies 16
Vincent Meunier Victor Floc’h
Diagnosis: a tool to diagnose degenerative diseases 16 Managing Director Analyst
Investment Banking Equity Research
Treatments: strong potential beyond behavioural therapies 17 Healthcare Biotech & Medtech
CONCLUSION 18
1
Sleep: a public health
priority costing billions
Poor sleep is one of the bolsters the immune system and wellbeing1. Yet, in many countries, Poor sleep is very common across
world’s most common impacts on both brain function people get one to two hours less the United States, affecting four out
health problems and behaviour. of sleep each night than their of 10 adults and leading the Centers
forebears did 50-100 years ago. for Disease Control and Prevention
Sleep is a crucial biological process Getting enough quality sleep at the (CDC) to classify it as a serious
which plays an essential role in right times contributes to mental and public health concern. But it is not
regulating our emotions, behaviour physical health, as well as quality of exclusively a US problem. Poor sleep
and physiology. While not all of its life. Sleep experts agree that most affects people across OECD countries
functions are fully understood, sleep adults need at least seven hours CASE STUDY including the United Kingdom, Japan,
restores energy, promotes healing, of sleep for optimal health and Germany and Canada.
The proportion of people getting
less than the recommended hours
of sleep is rising. This trend is
A disruptive solution for associated with lifestyle factors
FIG. 1: PREVALENCE OF SLEEP PROBLEMS IN THE ADULT POPULATION sleep apnoea relating to the 24/7 society, including FIG. 2: POOR SLEEP IS THE CORNERSTONE OF SEVERAL CHRONIC DISORDERS
psychosocial stress, an unbalanced
POOR SLEEP CHRONIC SLEEP As shown in Fig.1, obstructive diet, physical inactivity and the
COUNTRIES Cognitive Depression/ Heart disease
SYMPTOMS INSOMNIA APNEA sleep apnoea (OSA) is increasingly excessive use of electronic media2. decline anxiety
prevalent, and is associated Poor sleep is Poor sleepers have
Insomnia more than
with a significant social, health Poor sleep costs up to associated with a 27% higher risk
USA 56% 10% 11% and economic impact. The USD700 billion across 23% increased risk
doubles the risk
of developing
of cardiovascular
events
of Alzheimer’s
gold-standard OSA treatment five OECD countries depression and
China 40% 15% 4% is continuous positive airway
anxiety
pressure (CPAP), however Insufficient sleep is associated
Japan 23% 13% 3% compliance rates can be low, with a range of negative health Chronic pain Cancer
resulting in a high unmet medical and social outcomes. It has been Short sleep has Night shift work
Germany 33% 6% 7% need for patients not suitable for linked with seven of the fifteen leading been found to has been found
this treatment. Nyxoah’s solution causes of death in the United States, result in chronic to increase breast
UK 36% 7% 3% uses a device implanted under the including heart disease, cancer, stroke,
pain such as
arthritis
cancer risk by
up to 9%
chin and a disposable patch worn accidents, diabetes, septicaemia
France 34% 13% 7% on the chin every night. The patch and hypertension, contributing
wirelessly stimulates the nerves of to increase healthcare costs3. Obesity
Diabetes Alcoholism
India 30% 19% 4% the tongue to make it contract and
People with Lack of sleep & addiction
prevent obstruction of the airway. insomnia are 1.5x increases levels Insomnia interferes
Italy 30% 7% 4% Thanks to its discreet form factor
and easy implantation, Nyxoah’s
more likely to
develop diabetes
of the hormone
ghrelin, which
with ability to quit
alcohol and
over 10 years causes hunger addictive
Canada 40% 13% 6% Genio has the potential to disrupt
the way we treat sleep apnoea.
1: N
ational Sleep Foundation’s updated sleep duration
recommendations: final report. Sleep Health, 1(4), 233-243 |
behavior
Hirshkowitz, M. et al. (2015)
Source: Company Data; Bryan, Garnier & Co 2: T
he Human Sleep Project | Roenneberg, 2013 Source: Digitally Diagnosing and Treating Sleep: No Longer a Dream | 7 Wire Ventures | February 2020
3: M
ortality in the United States | Kochanek, K.D. et al. 2013
2 | Digital health 3
Sleep problems have been associated and in turn, reduce healthcare costs Treating sleep problems could Digital solutions have the potential to for sleep problems. Even though they are still only symptomatic treatments.
with both higher healthcare utilization and improve quality of life. therefore substantially reduce make CBTi widely available, while are associated with a challenging safety The American College of Physicians
and costs. These can include costs the associated costs and negative driving the costs down. profile, hypnotics were used by 6-10% guidelines state that they should be
related to direct care, such as Alongside sleep’s impact on health health impacts. of US adults in 20104. used alongside the “gold-standard”
outpatient visits and prescription and wellbeing, evidence suggests Hypnotics: purely non-pharmacological approach.
medications; and indirect costs, for that it plays an important part in Treatments exist, but symptomatic and the de In 2019, the US FDA added a Boxed
example increased use of healthcare determining cognitive and workplace come with limitations facto first-line treatment Warning to some of the most CBTi: a gold standard,
for related problems that are performance. Poor sleep leads widespread hypnotics for risk of serious but not yet a first-line
exacerbated by poor sleep. Research to traffic and industrial accidents, The two most widely accepted Drug treatment, with a class of injuries caused by “complex sleep treatment
shows that poor sleep is linked with medical errors and lower productivity. treatments for sleep problems are drugs known as “hypnotics”, is only behaviours” (e.g. sleepwalking).
increased inpatient care, including pharmacotherapy and cognitive indicated as a short-term solution for This followed decades of safety warnings CBTi is a psychological treatment
the number of days hospitalized and Taken as a whole, the social burden of behavioural therapy for insomnia (CBTi), poor sleep and is inappropriate for related to sleep medications, such designed to break patterns of
increased emergency visits. Inpatient poor sleep is substantial, with direct and a psychological treatment. Due to its the long-term management of chronic as the risk of abuse or dependence. maladaptive thinking and behaviour.
care is the healthcare category most indirect costs exceeding 1% of GDP long-term effects and safety, CBTi sleep problems. As a “symptomatic” It helps identify and thoughts and
impacted by poor sleep. in some of the largest industrialized is considered the “gold standard” treatment, it addresses only the New additions to the therapeutic arsenal, behaviours that cause or worsen sleep
countries. In the US, costs are thought treatment for sleep problems. However, symptoms of the problem rather than such as orexin receptor antagonists, problems and replace them with habits
Effective management of poor sleep to exceed USD400 billion per year, its widespread use has been limited the underlying cause. However, with have recently been introduced. that promote sound sleep. Unlike
has potential to help decrease the with employer-based health plans due to a shortage of specialists and access to CBTi limited, hypnotics are However, while they address some of hypnotics, CBTi helps overcome the
severity of related health problems shouldering much of the cost burden. associated high costs. the most commonly used treatment the limitations of current hypnotics, they underlying causes of sleep problems.
FIG. 3: ECONOMIC COSTS OF INSUFFICIENT SLEEP ACROSS FIVE OECD COUNTRIES FIG. 4: THE VICIOUS CYCLE OF POOR SLEEP
AND HOW CBTI FOR SLEEP CAN HELP OVERCOME IT
GDP
UNITED KINGDON
$50 BILLION Negative
emotions
1.86% GERMANY
$60 BILLION
CANADA 1.35% 1.56%
$21.4 BILLION
2.92%
UNITED STATES
2.28% $411 BILLION JAPAN
$138 BILLION The vicious cycle
of poor sleep
Negative Negative
thoughts behaviour
Cognitives techniques Behavioural techniques
Source: Why Sleep Matters—The Economic Costs of Insufficient Sleep | Rand Health | January 2017 Source: CBT for insomnia – the science behind Sleepio | Big Health 4: Kripke DF, Langer RD, Kline LE. Hypnotics’ association with
mortality or cancer: a matched cohort study. BMJ Open | 2012
4 | Digital health 5
FIG. 5: COMPONENTS OF CBTI FOR SLEEP PROBLEMS
COMPONENT DESCRIPTION
This aims to identify, challenge, and replace dysfunctional beliefs and attitudes about sleep and insomnia.
Cognitive therapy Such misconceptions may include unrealistic expectations of sleep, fear of missing out on sleep, and
overestimation of the consequences of poor sleep.
Behavioral instructions aimed at strengthening the association between bed and sleep and preventing
conditioning of the patient to associate bed with other stimulating activities. Such instructions include
Stimulus control
avoiding nonsleep activities in the bedroom; going to bed only when sleepy; and leaving the bedroom
when unable to sleep for 15–20 min, returning to bed only when sleepy.
Behavioral instructions to limit time in bed to match perceived sleep duration in order to increase sleep
Sleep restriction drive and further reduce time awake in bed. Time allowed in bed is initially restricted to the average time
perceived as sleep per night and then adjusted to ensure sleep efficiency remains >85%.
General recommendations relating to environmental factors, physiologic factors, behavior, and habits
that promote sound sleep. Specific instructions include advice on control of the bedroom environment,
Sleep hygiene
including avoiding visual access to a clock; regular sleep scheduling and avoiding long daytime naps;
and limiting alcohol, caffeine, and nicotine intake, especially before bed.
Any relaxation technique that the patient finds effective can be used to limit cognitive arousal and
Relaxation reduce muscular tension to facilitate sleep. Specific techniques that may be used include meditation,
mindfulness, progressive muscle relaxation, guided imagery, and breathing techniques.
Source: Cognitive Behavioural Therapy for Chronic Insomnia | Trauer et al. | August 2015
CBTi trains people to use techniques However, CBTi’s biggest challenge
that address the mental factors is its inherent lack of scalability.
associated with insomnia, such Traditionally delivered face-to-face
as a “racing mind”, and to overcome by a specialist psychological therapist,
the negative emotions that it is dependent on a rare and expensive
accompany the experience of being resource. It seems inconceivable
unable to sleep. It comprises five that any face-to-face therapy could
components, which are outlined replace, for example, the 80 million
in Fig. 5. prescriptions for hypnotics that are
written each year in the US5.
CBTi has achieved gold-standard
status as an insomnia treatment. This is why digital solutions represent
And because of the limited an unprecedented opportunity to
likelihood of side effects, it has been widen access to CBT for sleep to
recommended by American College as many people as possible. They
of Physicians as the first line-treatment have the potential to make this gold 5: Brain-Disabling Treatments in Psychiatry: Drugs, Electro-
shock and the Psychopharmaceutical Complex, Edition 2
for adults with sleep problems. standard a first-line treatment. | Peter R. Breggin, MD | 2007
6 | Digital health 7
Digital is disrupting
care and treatment
Digital therapeutics: As shown in Fig.6, DTx make so, to make it infinitely scalable and
a 10-year journey finally particular use of cognitive, accessible to millions of people. CASE STUDY CASE STUDY
bearing fruit behavioural and psychological
therapies, reflecting their intent to Omada Health’s success paved the
Advances in digital technology have effect behaviour change at scale. way for digital delivery of behavioural
converged with medical science, therapy for conditions beyond
allowing digital health to become In 2002, a study6 showed the potential diabetes. Since then, multiple
a critical part of routine clinical of intensive behavioural intervention digital therapeutics companies have
Omada Health, one of the first companies to Hinge Health extended the reach of digital
care. This has led to the launch to reduce people’s risk of developing emerged in various therapeutic areas,
demonstrate clear ROI from a digital solution solutions to musculoskeletal conditions
of a new category of therapeutics type 2 diabetes by targeting diet and supported by a clearer business
that integrate digital technology: exercise in a face-to-face setting. model that relies on US private
Omada’s programme consists of a year-long With nearly 40,000 cumulative participants since
digital therapeutics (DTx). This led companies including Omada payers. For example, Hinge Health
educational curriculum and personalized health inception, more than 100 employer customers and
Health to attempt to deliver the followed Omada’s path, but focusing
coaching, using devices to track people’s nutrition, up to USD4,000 of savings in healthcare costs at
DTx deliver evidence-based intervention digitally, and in doing on musculoskeletal issues.
activity and weight. A peer-reviewed study has one year per patient from its digital programme,
interventions to prevent, manage reported strong clinical outcomes in more than 200 Hinge Health proved that the Omada business
or treat medical disorders and participants, confirming the effectiveness of digital- model was scalable beyond metabolic conditions.
diseases. They are driven by high- based behavioural therapy. Omada proved that its Hinge’s massive USD90 million raise of the beginning
quality software programs and FIG. 6: CONCEPTUAL POSITION OF DTX IN RELATION
TO EXISTING THERAPEUTIC OPTIONS solution led to a significant reduction in risk for Type 2 of 2020 is further confirmation of strong investor
operate as a standalone therapy diabetes, stroke and heart disease, resulting in a ROI appetite for the digital health space.
or to optimize current medication of over USD1,300 per person per year for the payer.
and treatments.
The emergence of this new class of
therapeutics has been driven by the Surgery
need to care for an ageing global Pharmaco-therapy Radiation
population using fewer resources. Physical therapy
DTx could extend physicians’ reach
by overcoming the constraints of
time, place and personnel to build
a “one-to-many” model of care.
DTx
Cognitive
Behavioral
Psychological therapy
6: Diabetes Prevention Program Research Group | New Source: Digital therapeutics and clinical pharmacology | Chung | March 2019
England Journal of Medicine | 2002
8 | Digital health 9
FIG. 7: EXAMPLES OF DIGITAL THERAPEUTICS UNDER DEVELOPMENT OR ON THE MARKET FIG. 8: MOST AMERICANS ARE INSURED BY THEIR EMPLOYERS
COMPANY NAME PRODUCT NAME DESCRIPTION THERAPEUTIC AREA
US US POPULATION
POPULATION
reSET® An adjunct therapy to standard, outpatient treatment for 323Mn
323Mn
Pear Therapeutics CNS
reSET-OTM Substance Use Disorder (SUD)
91% 9%
Propeller Health Combined software and hardware program to improve
RESPIMAT® Respiratory
& Boehringer Ingelheim asthma and COPD control and optimize healthcare utilization HEALTH INSURANCE NO
INSURANCE
Utilizing adaptive sensory stimulus software for the treatment of ADHD 295Mn 29Mn
Akili Interactive AKL-T01 CNS
delivered through an engaging video game experience
67% 33%
Delivering reminiscence therapy to Alzheimer’s sufferers in
Dthera Sciences DTHR-ALZ CNS
a scalable and personalized manner. PRIVATE COVERAGE PUBLIC COVERAGE
Sleep improvement program featuring Cognitive Behavioral Therapy 217Mn 122Mn
Big Health SpleepioTM CNS
(CBT) techniques.
16% 56% 19% 17% 5%
AI-based digital diagnostics and personalized therapeutics
Cognoa Various CNS Pediatrics
for pediatric behavioral healthcare. DIRECT EMPLOYER – FULLY & SELF-INSURED MEDICAID MEDICARE MILITARY
Delivery of physical exercises, behavioral therapy, and 52Mn 181Mn 62Mn 56Mn 16Mn
KAIA Motion coach Musculo-skeletal
education for chronic back pain patients.
Glooko MIDS Insulin mobile dose calculator for adults with Type 2 diabetes. Metabolism Source: Prescription Digital Therapeutics | Mark Goad | February 2019
Engaging individuals with Type 2 diabetes, hypertension, and obesity,
WellDoc BlueStar ®
Metabolism
and their providers, to improve self-management and outcomes.
Personalized digital program to help people prevent the onset of diabe-
Omada Health, Noom, Etc
tes and other chronic diseases.
Metabolism Employers are doubly concerned
MedRhythms
Neurologic music therapy to address motor, speech, and
CNS
with maintaining employee health, CASE STUDY
cognitive dysfunction caused by neurologic disease or injury. both to improve productivity and
Source: Digital therapeutics and clinical pharmacology | Chung | March 2019 retention and to avoid high healthcare around USD2.5bn. Since then,
costs, especially in the US. They flawless operational execution
have a strong motivation to support contributed to drive the stock
improvements in healthcare that push price to an all-time high, making
More recently, the US FDA gave aligning its solutions with traditional as there is with traditional
the boundaries of innovation. Livongo’s success confirms Livongo currently worth USD6.0bn.
the green light to Akili Therapeutics’ pharmacotherapies that are usually pharmacological interventions.
the appeal of an employer-based
game-based therapy for children with only available on prescription. Livongo has pioneered a new
The outstanding success of digital business model
attention deficit hyperactivity disorder However, the recent ending of Juniper Research expects that in the business model, convincing
health group Livongo, a US-listed Livongo is best known for its multinationals, government bodies
(ADHD). This move is a landmark collaboration between Sandoz medium term, most revenue will come
company with a market cap of diabetes management application, and pharmacy benefit managers
decision in several respects: it is and Pear has been a major blow from direct payments from employers,
USD6bn, suggests that a go-to-market which helps patients manage to pay for its technology, which
the first game to be marketed as for the prescription-based approach. with public health interest confined
strategy focusing on big US employers their blood sugar levels using enables users to manage chronic
a therapy for any type of condition; to a handful of markets7. This makes
can deliver fast, strong growth if a Bluetooth-enabled blood conditions while contributing
and it is the first digital therapeutic A business opportunity sense, given that most Americans are glucose meter and associated to drive down healthcare costs.
the technology is backed by a solid
intended to improve symptoms mostly driven by US insured by their employers, who are app that provides personalized
medico-economic case. This stands out from companies
associated with ADHD. employers for now early adopters of innovative solutions recommendations for diet, exercise,
such as Pear Therapeutics or
for driving healthcare costs down. and related behavioural changes.
Click Therapeutics, which focus
As a prescription-based therapy, and Commercialized digital therapeutics
In July 2019, Livongo delivered one on prescription-based business
in contrast with Omada and Hinge’s are new, so there is no well- models. We believe Livongo’s
of the most high-profile digital health
employer-based business model, Akili established framework for the pricing IPOs ever. Following successive outstanding success compared to
has followed the approach of Pear and reimbursement of new products. price raises, the company raised others makes a strong case for the
7: D
igital Therapeutics & Wellness: Disruption, Innovation
Therapeutics, which specializes in It is unlikely that there will be a singular Opportunities & Forecasts 2019-2024 | Juniper Research | USD355m, claiming a market value employer-based business model.
prescription digital therapeutics, by approach to securing reimbursement, May 2019
10 | Digital health 11
Sleep care is digital health’s
next big opportunity
Recent studies have Big Health, a digital health company More specifically, Big Health showed
confirmed the medico- focused on sleep, has conducted that its digital sleep improvement
economic case for digital a study evaluating the impact of programme based on cognitive and
sleep solutions poor sleep and mental health on behavioural techniques (Sleepio)
medical and pharmacy claims led to an average USD1,068 adjusted
On top of the economic costs of for employee populations across savings in health costs per person
sleep problems, recent research has multiple industries. While it confirmed per year, corresponding to 18%
also looked at the individual cost bad sleep’s impact on productivity adjusted savings in total healthcare
impact. Those studies are all the more (poor sleepers were found 3.5x less costs at the 18-month follow-up.
important as they raise awareness productive at work) and mental health While this result did not reach
of the financial burden for payers and (3.7x more likely to be stressed), statistical significance, it contributes
help them to make informed decisions the most important takeaway to the argument that digital
about the allocation of resources. relates to the total annual healthcare administration of behavioural therapy
claims spending for employees for sleep disorders can help reduce
with sleep problems. On average, healthcare costs, while paving the
these employees cost over 2.4 times way for more innovative solutions
CASE STUDY as much as those without insomnia, in this area.
representing a difference of
USD 7,600 per employee. (Fig. 9).
Big Health: one of the very
first DTx solution dedicated
to poor sleep
FIG. 9: INDIVIDUALS WITH INSOMNIA COST 2.4X MORE
Big Health has developed Sleepio, US employers are With a clearer view of clinical The majority said they would be
a digital sleep improvement now embracing digital outcomes and achievable savings, willing to change their behaviours —
program comprising cognitive and +$7.6k more costly on average solutions for sleep employers are taking a closer look exercise more, for example —
behavioural techniques. Available at digital solutions for sleep. to reduce their insurance premiums.
via web and mobile applications, Historically, sleep has been at the According to the 24th Willis Towers
it has the potential to scale to +$9k +$7.7k +$7.6k +$7.4k +$6.7k top of employees’ considerations but Watson report Best Practices in Overall, we are witnessing an
large populations. Several studies employers have been reluctant to Health Care Employer Survey, 56% alignment between different
have shown that it was able to $13,442
$14,729 cover it as the economics are not clear. of US employers are now planning stakeholders — employers,
$13,368
help people make significant $11,428 $11,688
Castlight’s 2018 The State of Digital to implement a sleep plan by 2021. vendors, employees —contributing
improvements in their sleep, $7,329 Health report highlighted that good McKinsey’s 2018 Consumer Health to the adoption of digital solutions
$6,680
$5,398
confirming that poor sleep should $3,765 $4,036 sleep is one of the top three health Insights Survey found that the to reduce sleep problems.
be the next condition to benefit goals for employees and that 70% of innovative feature of insurance plans We expect multiple players to
Professional Manufacturing Technology Pharmaceutical Energy
from advances in digital solutions. services employees are likely to use a sleep most appreciated by consumers emerge to replicate Livongo’s
Source: The State of Sleep and Mental Health | Big Health
solution if it is offered by their employer. was an incentive to change behaviour. success in metabolic diseases.
12 | Digital health 13
The future of sleep health:
a big-data revolution in the making
Outdated technology has One reason for this lack of sleep monitoring or for measuring Overall, PSG is expensive, costing While options such as actigraphy less burdensome, designed to be
limited our understanding understanding is that most of what sleep outside laboratory conditions. 1,500-$2,000 per night in the US. and heart rate sensing are available worn for multiple nights at home to
of sleep we know comes from laboratory It is also time and resource-intensive, to monitor sleep outside of a laboratory, enable longitudinal data collection,
studies, with people instructed to A PSG sleep study is typically with an expert needing one to two none have demonstrated comparable and require minimal or no expert
Great advances have been made in sleep in controlled conditions with a single overnight assessment hours to score a night of clinical results to PSG, because a single supervision. However, most have
understanding sleep. We now know electrodes fastened to their heads. that usually takes place in a sleep PSG recordings. Yet the cumbersome metric such as heart rate alone is reported mediocre accuracy and
which brain regions are involved in Since the 1960s, polysomnography centre. It records physiological signals nature of the PSG process means not enough to provide sophisticated reliability compared to PSG.
sleep and how the internal circadian (PSG) has been the standard including electroencephalographic it does not reliably capture a patient’s sleep stage classification.
clock works. However, there remain technique for sleep measurement (EEG), electromyographic (EMG), typical sleep. The Dreem Headband is establishing
many unknowns, for example around in clinical and laboratory settings, and electrooculographic (EOG) More recently, a new group of itself as an affordable, comfortable,
the role of genetic and environmental as well as to diagnose sleep disorders. activity, as well as breathing In response, industry and academia devices has emerged for home and user-friendly alternative to
factors in sleeping patterns and the However, its use is limited as it effort, airflow, pulse, and blood have invested heavily in the development sleep monitoring that uses EEG PSG. Illustrated in Fig.11, it features
quantity of sleep needed. remains impractical for long-term oxygen saturation. of smaller, less obstructive and more electrodes to measure brain activity. physiological signal acquisition and
portable devices for the continuous These include headbands and automatic sleep analysis using a deep
monitoring of sleep. devices placed around the ear. learning algorithm along with five dry
FIG. 10: POLYSOMNOGRAPHY (PSG) Unlike traditional PSG, these more EEG electrodes, a 3-D accelerometer
This is motivated by a desire to compact devices are usually cheaper, and a pulse oximeter.
enable data acquisition in larger
participant groups, over more
extended periods and in a more FIG. 11: ILLUSTRATION OF THE DREEM HEADBAND
natural setting, by reducing both
the cost of monitoring and the
burden to participants.
Recent advancements in
data acquisition opened
the door to a big data
revolution in sleep
To understand the role of sleep
in health and disease, sleep
must be monitored in a natural
environment and in a non-obstructive
way to ensure that data is as
representative of typical sleep
as possible. This needs low-cost,
wearable sleep detection systems
that give reliable sleep architectures
in real-life settings.
Sleep test – PSG | Image courtesy of Dreem Dreem Headband | Image courtesy of Dreem
14 | Digital health 15
Through a direct comparison FIG. 12: OVERVIEW OF THE ROLE OF BIG DATA IN SLEEP RESEARCH Treatments: strong apnoea (OSA), a potentially serious
to PSG in 25 subjects over one potential beyond sleep disorder causing breathing
night, the Dreem Headband showed Potential role of big data Definition Examples behavioural therapies to repeatedly stop and start during
reliable recording of high-quality Explaining the Emergence of new digital sleep, recent studies have suggested
Understanding
sleep EEG, heart rate, and breathing mechanisms of sleep biomarkers Sleep-related technologies are not that kinaesthetic stimulation could
data while being considerably more Using new technologies only useful for monitoring but may reduce apnoea duration during sleep.
Remote monitoring for
Monitoring for non-intrusive sleep
comfortable and easier to install clinical trials also be used to aid interventions While technical limitations remain,
monitoring
than PSG. It was able to acquire such as sleep advice for behavioural we believe that advancements in
Alzheimer's disease
EEG during sleep with sufficient Predicting an individual’s change, sleep tracking and optimized hardware and algorithms could allow
Parkinson’s disease
Diagnosis risk of developing
signal quality; reliably measure Obstructive Sleep Apnoea, alarms based on sleep stage. this treatment to become a reality
conditions
breathing and heart rate during Narcolepsy For example, in obstructive sleep in the mid-term.
sleep; and perform automatic Personalizing treatment Moderate Sleep Apnoea,
Treatment and clinical decision- Adherence CPAP therapy
sleep staging classification with
making Depression
performance similar to that of
a consensus of five scorers using Source: Bryan, Garnier & Co
medical-grade PSG data.
These results make the Dreem
Headband an ideal candidate for
high-quality large-scale longitudinal
sleep studies in the home or Monitoring: from clinical Diagnosis: a tool to
laboratory environment. Along with to post-market studies diagnose degenerative
other new technologies, it should diseases
contribute to leveraging the big Advancements in sleep measurement
data potential for sleep. wearables make it possible to deploy Several studies have linked sleep
remote sleep monitoring at scale, with conditions including Alzheimer’s
Big data in sleep has in the large populations that are Disease (AD) and Parkinson’s Disease
unlimited potential required for late-phase clinical trials. (PD). Research has shown that the
Monitoring can be also be used primary pathological features of AD
Recent advances in sensing to provide better and earlier evidence were associated with both objective
technology, big data analytics, of treatment efficacy, facilitating and subjective changes in sleep,
and artificial intelligence will allow drug development. On top of that, suggesting that sleep monitoring
continuous sleep monitoring, we expect low-burden monitoring could help diagnose AD, while
which is going to impact a wide to facilitate sleep data collections treatment for sleep deficiencies
and growing range of key areas. in trials, and to potentially increase could delay the progression of AD.
We expect technologies that trial participation and reduce attrition. Recent work on PD identified REM
digitalize sleep will disrupt the way Finally, it could be particularly sleep behaviour disorder as an early
we understand, monitor, diagnose interesting for big pharmaceutical biomarker for PD, suggesting that
and treat a vast list of medical companies looking to gather data better sleep screening could result
conditions far beyond sleep itself. for post-market surveillance studies. in earlier treatment.
16 | Digital health 17Conclusion
We believe that digitalization of sleep and ubiquitous sleep
monitoring will have important implications for the characterization
of sleep, diagnostics and therapeutics. Large epidemiological studies
exploring the impact of sleep will be possible thanks to large-scale
collection of longitudinal sleep data with “lab-level” wearables.
We expect digital solutions for sleep to thrive, supported by
additional medico-economic evidence that drives adoption from
private and then public payers. Beyond sleep, those solutions
should expand their footprint into brain health. In the medium-term,
sleep-based diagnosis of medical conditions should become
a reality and facilitate better and earlier diagnosis and decision-
making for patients.
Finally, Big Health’s recent USD39m Series B funding round
highlighted the strong appetite from investors for digital solutions
dedicated to poor sleep. We believe that several other companies
will emerge in the near future with innovative digital solutions for
sleep, driven in particular by employers, who are more willing than
ever to tackle this costly public health priority.
18 | Digital health 19White paper authors Corporate transactions
Vincent Meunier Victor Floc’h
Managing Director Analyst Bryan, Garnier & Co leverage in-depth sector expertise to create fruitful and long-lasting relationships between investors
Investment Banking Equity Research and sector leading growth companies.
Healthcare Biotech & Medtech
vmeunier@bryangarnier.com vfloch@bryangarnier.com
Acquired by Acquired by Private Placement Initial Public Offering Series B Fundraising
Healthcare and Technology senior management team
Undisclosed Undisclosed €39 000 000 $150 000 000 €32 000 000
INVESTMENT BANKING Sole Advisor to the Seller Sole Advisor to the Buyer Sole Financial Advisor Joint Bookrunner Sole Financial Advisor
Olivier Garnier Greg Revenu Hervé Ronin
Managing Partner Managing Partner Partner About Bryan, Garnier & Co
ogarnier@bryangarnier.com grevenu@bryangarnier.com Healthcare
hronin@bryangarnier.com
Pierre Kiecolt-Wahl Vincent Meunier Sandrine Cailleteau Bryan, Garnier & Co is a European, full-service growth-focused independent investment banking partnership founded in 1996.
Partner Managing Director Managing Director The firm provides equity research, sales and trading, private and public capital raising as well as M&A services to growth companies
Head of ECM Healthcare & Technology Healthcare and their investors. It focuses on key growth sectors of the economy including Technology, Healthcare, Consumer and Smart
pkiecoltwahl@bryangarnier.com vmeunier@bryangarnier.com scailleteau@bryangarnier.com Industries & Services. Bryan, Garnier & Co is a fully registered broker dealer authorized and regulated by the FCA in Europe and
the FINRA in the U.S. Bryan, Garnier & Co is headquartered in London, with additional offices in Paris, Munich, Stockholm, Oslo,
Thibaut De Smedt Olivier Beaudouin Guillaume Nathan Reykjavik as well as New York and Palo Alto. The firm is a member of the London Stock Exchange.
Partner, Application Software Partner Partner, Digital Media
& IT Services Technology & Smart Industries & Business Services
tdesmedt@bryangarnier.com obeaudoin@bryangarnier.com gnathan@bryangarnier.com
Bryan, Garnier & Co Healthcare & Technology Equity Research coverage*
Stanislas de Gmeline Philippe Le Sann Christophe Alleman
Partner, Business Services Managing Director Executive Advisor
& Technology Technology calleman@bryangarnier.com HEALTHCARE TECHNOLOGY
sdegmeline@bryangarnier.com plesann@bryangarnier.com
Falk Müller-Veerse Gregg Blake Stefan Kaltenbacher
Partner, Germany Partner, US Managing Director,
fmuellerveerse@bryangarnier.com Healthcare Germany, Healthcare
gblake@bryangarnier.com skaltenbacher@bryangarnier.com
Phil Walker William Pay Ståle Schmidt
Managing Director, UK Managing Director, Managing Director,
Healthcare China Norway
pwalker@bryangarnier.com wpay@bryangarnier.com sschmidt@bryangarnier.com
EQUITY RESEARCH ANALYST TEAM
Eric Le Berrigaud Jean-Jacques Le Fur Olga Smolentseva, PhD
Managing Partner Pharmaceuticals Biotech
Pharmaceuticals jjlefur@bryangarnier.com osmolentseva@bryangarnier.com
*Selection
eleberrigaud@bryangarnier.com
Dylan van Haaften Gregory Ramirez David Vignon 13 Analysts | 75 stocks covered
Equity Research Analyst Equity Research Analyst Equity Research Analyst
Medtech Software & IT Services Software & Payments With more than 150 professionals based in London, Paris, Munich, Stockholm, Oslo and Reykjavik as well as New York and
dvanhaaften@bryangarnier.com gramirez@bryangarnier.com dvignon@bryangarnier.com Palo Alto, Bryan, Garnier & Co combines the services and expertise of a top-tier investment bank with a long-term client focus.
20 | Digital healthLONDON PARIS MUNICH NEW YORK
Beaufort House 26 Avenue des Champs-Elysées Widenmayerstrasse 29 750 Lexington Avenue
15 St. Botolph Street 75008 Paris 80538 Munich New York, NY 10022
London, EC3A 7BB France Germany USA
UK
T: +44 (0) 20 7332 2500 T: +33 (0) 1 56 68 75 00 T: +49 89 242 262 11 T: +1 (0) 212 337 7000
Authorised and regulated by the Financial Regulated by the Financial Conduct FINRA and SIPC member
Conduct Authority (FCA) Authority (FCA) and the Autorité de Contrôle
prudential et de resolution (ACPR)
STOCKHOLM OSLO REYKJAVIK PALO ALTO
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Floor 0250 Oslo 105 Reykjavik Alto
111 51 Stockholm Norway Iceland California (CA)
Sweden 94 301 USA
T: +46 722 401 080 T: +47 22 01 64 00 T: +354 554 78 00 T: +1 650 283 1834
Regulated by the Norwegian Financial FINRA member
Supervisory Authority (Norwegian FSA)
DISCLAIMER
This document is based on information available to the public and other sources deemed reliable. No representation or warranty, express or implied, is or will
be made in relation to, and no responsibility or reliability is or will be accepted by Bryan Garnier & Company or any of its officers, employees or advisers as to
the accuracy or completeness of this document or any other written or verbal information available to the recipient or its advisers. While all reasonable care
has been taken to ensure that the facts stated are accurate and the opinions given are fair and reasonable, neither we nor any of our affiliated companies nor
any of our, or their directors, representatives or employees, accepts responsibility or liability for any loss or expense arising directly or indirectly from the use
of this document or its or its contents. This document is not and should not be construed as an offer, or a solicitation of any offer, to buy or sell securities.
Bryan, Garnier & Co is authorised and regulated by the Financial Conduct Authority (FCA) in the United Kingdom.
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