Profusa IMPLANTABLE BIOSENSOR FOR LONG-TERM

CONTINOUS MONITORING OF BODY CHEMISTRY

November 2016

Frederic GAUME

VISION/ OPPORTUNITY

TECHNOLOGY AND CURRENT APPLICATIONS

FUTURE DEVELOPMENTS

2

TO UNLEASH EVERYONE’S

REAL TIME BIOCHEMISTRY TO

BE A PART OF THE WORLD’S

DIGITAL TOOLBOX

GRAND VISION BUT DIFFICULT TO ACCOMPLISH –

OUR DESIGN PRINCIPLES, STARTING WITH PATIENTS

4

1 2 3 Clinical Grade & On-Demand

Data

Consumer

User Experience

Broad

Access

Decisions in real time, informed by actionable biochemistry,

utilized by most of us, will improve care for everyone

Triggering timely, actionable medical decisions

Passive data collection, no user action required

Low COGS Combined with mass adoption

Clinical grade wearable

PROFUSA ACHIEVEMENTS TO DATE &

CURRENT PIPELINE

• Founded 2009

• South Fan Francisco, CA and College Station, TX

• 27 Employees

• Series A&B funding

• >$20 million grants

support

• CE clearance of first product Sept 2016

• Strong network of collaborators

5

Programs Indications Uses Status Market

Size

Lumee

Tissue O2

Peripheral

Arterial

Disease

Intra & Post

operative patient

monitoring

CE Sept

2016

2-3B USD

Glucose Pre-diabetic/

Type 2

diabetes

Consumer Health

Insight from Glucose

level evolution

First in man

H1 2017

$$B USD

Type 1

diabetes

Continuous Glucose

Monitoring of

patients

First in man

H1 2017

$$B USD

Multi

Analytes

COPD At home

management of

COPD patients

Concept

Proven

$B USD

Blood Gas

Patient monitoring in

trauma/ ER centers

Concept

Proven

$B USD

PROFUSA SITES AND COLLABORATORS

6

Dr. Tejal Desai

• Nanosphere stability

Dr. Bruce Klitzman

• Physiology

• Long-term rat studies

Dr. Mike McShane

• Optical instrumentation

• Algorithm development

• Synthetic chemistry

• Hydrogel development

• Optics instrumentation

• Clinical testing

• Quality and manufacturing

• All business functions

SF

Well utilized dye

synthesis hoods

6 lab bays

TX • Pre-clinical testing

• Oxidase sensor

development

Chem lab space within animal facility

VISION/ OPPORTUNITY

TECHNOLOGY AND CURRENT APPLICATIONS

7

WHY OTHERS HAVE FAILED – THE AVASCULAR

FOREIGN BODY RESPONSE (FBR)

8

Biological response that has

been the “death sentence” of

in-body sensors

Sensor

Needle

Collagen

Blood Vessel

/ Capillaries

Immune

Cells

Se

ns

or

sig

na

l

Days to weeks

ERROR

BLOOD

LEVEL

Typical poor sensor

performance

FREQUENT

SENSOR ”DROP-OUT”

MEET THE PROFUSA SENSOR – SOLVES AN UNSOLVABLE

BARRIER FOR MORE THAN 5 DECADES

9

• Micro hydrogel sensor – 250 microns

diameter; 3 mm length

• Embedded fluorescence sensing

chemistry

• Hypodermic needle placement in

the subcutaneous space

• Non-invasive optical signal

collection

• Clinical-grade data

• Demonstrated >24 month longevity

in humans

• Multi-analyte capable

HOW PROFUSA SENSORS WORK…

OXYGEN EXAMPLE

10

Excitation light is shined on the skin surface and reaches the

proprietary sensor element

1 3 The fluorescent signal from the sensor travels to the surface of the skin, captured by the reader. The

data acquisition process takes seconds.

2 Sensor is embedded with fluorescent dye that is sensitive to oxygen. The fluorescent signal

correlates to tissue oxygen

OUR SENSOR MEASURES OXYGEN CONCENTRATION

IN THE TISSUE

11

Lumee

O2 TISSUE MONITORING - PROFUSA’S

FIRST BIOSENSOR

12

15

months

3

months

2 years and

going…

13

Fiber optic probes (Oxylyte) are large and

disrupt the tissue. In contrast, our tissue-

integrating hydrogel sensors do not cause

mechanical stress and minimally displace

tissue)

Fluorescent overlay of sensor signal

MEASURING OXYGEN SENSORS IN RATS USING

AN IVIS IMAGER

EXAMPLE EXPERIMENTAL SETUP ON PIGS

14

32 Readers attached to anesthetized and awake pigs

Anesthetized Awake (in sling)

CONFIDEN

TIAL

15

SMALL, ADAPTABLE READER FORM-FACTOR

16

injector

Reader

Console

TISSUE OXYGEN PROGRAM – 1ST PRODUCT: CE MARK IN SEPTEMBER 2016

PAD/ CLI A GLOBAL EPIDEMIC WITH A LARGE IMPACT

ON HEALTHCARE

CONFIDENTIAL 17

PAD

15-19M

Cancer 12-15M

PAD

15-30%

Breast Cancer 11%

US Annual

Cost of PAD

160 – 290 B USD Key Risk Factors:

• Age

• Diabetes

• Smoker

150,000 amputations / year from PAD/CLI

US Prevalence

US 5Y Mortality

CLI AS 1ST INDICATION FUNCTIONAL LIMB PRESERVATION 1) REVASCULARIZATION TO INCREASE FOOT PERFUSION

2) WOUND CARE

3) SURVEILLANCE

18

6 Months

• Foot ulcers & infections =

most common cause for

hospital admission of

diabetics

• US foot ulcer cost: $10-20k

/ episode1

• 6-12 month to wound

healing

• Complete ulcer healing:

~60-80%2

1.Rogers L et al. The Right to Bear Legs - An Amendment to

Healthcare: How Preventing Amputations Can Save

Billions for the US Health-care SystemJournal of the

American Podiatric Medical Association 2008;98:166-186

2.Hoffman et al: Complete ulcer healing as Primary Endpoint in Studies on Critical Limb Ischemia? A Critical

Reappraisal EJVES, 33, 311-16 (2007)

UNMET NEED – PERFUSION IS KEY AND ITS

QUANTIFICATION DIFFICULT TASC-II RECOMMENDS TCPO2 MEASUREMENTS FOR ALL CLI PATIENTS

19

? ?

~20-30k USD

> 100k USD

Very diverse clinical outcome and costs

When is

good,

good enough?

Success, wound healed, no amputation

Partial success, 2nd revascularization

required, minor amputations

Wound does not heal, major

amputation required

BTK surgery

~60-80k USD

20

INTRA-OP, LUMEE DATA COLLECTED FROM A 90 Y.O.,

CLASS 4 CLI PATIENT

A

B

C

Balloon inflate

Balloon deflate

0.8

1

1.2

1.4

2

3

0.6

0.8

1

20 30 40 50

Time elapsed (min)

0.6

0.8

1

20 40 60 80

0.8

1

1.2

1.4

Recover

y Rm.

Stent

Time elapsed (min)

A A B B C C

21

ABI 1.0 NA NA 1.07 NA

Sensilase

(mmHg)

NA 45 67 47 43

2 3

4

0.5

0.7

0.9

1.1

1.3

Post-op D7 D14 D21 D28

POST-OP, LUMEE DATA COLLECTED FROM THE SAME PATIENT

Summary of First-in-Man Study Results

• 48 sensors were injected into a total of 14 people for a cumulative exposure time of 336 subject-days

• Primary endpoint was successfully met; the

positive sensor detection rate was 97.2% (n=212)

• There were no reported adverse events (AE) related to the research materials. A total of 26

AEs reported; 18 of which were mild bruising related to the sensor injection.

J Vasc Surg 2015; 61:1501-10

VARIETY OF PRE-CLINICAL APPLICATIONS

Sensor 2 (Avg Rad) Sensor 3 (Avg Rad)

6/24/2013

14:30 15:00 15:30

0

0.5

1

Re

lativ

e O

2

Tumor Metabolism

22

Gut Microbiome O2

Stroke/TBI Research Flaps/Reconstruction

`

Re

lative

O

2

Hypoxia in Pigs

Pasted Series Pasted Series

11/26/2013

10:30 11:00 11:30

0

0.5

1

0

0.2

0.4

0.6

0.8

Re

lative

se

nso

r si

gn

al

Porcine Diabetes

Glu

co

se (

mg

/dL)

VISION/ OPPORTUNITY

TECHNOLOGY AND CURRENT APPLICATIONS

FUTURE DEVELOPMENTS AND APPLICATIONS

TINY SENSORS, GREAT BIG WORLD !

23

DIGITAL HEALTH TRANSFORMATION

Digital Health, by creating actionable patient data to aid in the

treatment and/or prevention of diseases outside of the traditional care

setting, will reduce inefficiencies and unlock significant value for all

stakeholders

400B USD

is spent treating

chronic care

patients in the

hospital setting

About 40% of the $3T the US spends

on healthcare

each year could

have been

avoided

Fees for Services

Supply Centric Model Value Based Healthcare /

Population Health Management

Demand Driven / Patient Centric

LIMITATIONS OF CURRENT TECHNOLOGIES DESPITE A CLEAR VISION AND SIGNIFICANT INVESTMENT FROM ALL

STAKEHOLDERS - FEW ADVANCES

CONFIDENTIAL 25

Accessibility

Data Value

Clinical

Grade

Nice to

have

Physicians

Hospitals

Consumers Patients

Seamless Experience

Ease of Use

Data of clinical value

Glucose, EEG, Labs, MRI…

Sweet spot

that enables

digital health!!

X

X

Hospital Devices

Steps, Pulse,

Sleep, location …

Wearables

PROFUSA SENSOR PLATFORM DESIGN PRINCIPLES & TECHNOLOGY ENABLEMENT TO OWN THE

“SWEET SPOT”

CONFIDENTIAL 26

Accessibility

Data Value

Clinical Grade

Nice to have

Physicians Hospitals

Consumers Patients

Seamless Experience

Ease of Use

Data of

clinical

value

Current Offerings

Sweet spot that

enables digital

health!!

X

X

Clinical grade data

• Focus on clinical validated analytes

• CLI management use case

• CGM impact on diabetic health

Seamless experience

• >2 years longevity in humans

• Ease of sensor implantation

• Non-invasive data acquisition

Broad Access

• Low COGS

• Leverage currently available infrastructure – cellular network, cloud, bluetooth

• >150x more data for similar costs today in first 2 applications

Enablement Proof

PROFUSA’S DATA CAN HELP TRANSFORM HEALTHCARE

27

First three

apps

Nbr Patients

Cost B USD

PAD WW

USA

200M1

20M1

200-

250B1

Diabetes WW

USA

Type I&II

415M1

30M1

Total

675B1

300B1

COPD WW

USA

200-330M2

24M3

>100B

50B

Profusa WW

USA

~1 B

70M

1,000B

>400B

Source: http://www.medpagetoday.com/cardiology/peripheralarterydisease/40803 http://www.reuters.com/article/sc-the-sage-group-idUSnBw096339a+100+BSW20150909 1 International Diabetes Foundation 2015 Atlas 2 GSK http://www.gsk.com/media/930531/copd-infographic.pdf 3 http://www.lung.org/assets/documents/research/copd-trend-report.pdf

How am I doing ? Real time information to optimize self-management

Am I paying based on Value? Increased Cost effectiveness

Can I prevent complications of chronic disease? Allocate & manage resources optimally across diseases

How can I demonstrate the value of my products? Develop Integrated patient care approaches as services

Can I identify high risk patients? Better know & manage population

Is he compliant? Improved

communication

Patient

Provider

Payer

Physicians

Industry

Care

Giver

Gvt

Insurer

How is my patient progressing? Improve & personalize care

Can I keep this patient home? Focus resources on care of higher need patients

9 new single

sensors beyond O2 and glucose

1) lactate

2) potassium

3) sodium

4) chloride

5) calcium

6) pH

7) bicarbonate/CO2

8) urea

9) creatinine

Develop algorithms and

instrumentation to read

multiple signals accurately through skin

Sensing chemistries

Multi-plexed panels

NEW $7.5M DARPA GRANT FOR MULTI-ANALYTE SENSING

Metabolism Training optimization

Fatigue detection Trauma and sepsis

Blood Gases COPD Surgical trauma ICU monitoring Training optimization

Dehydration Renal Disease

Hydratation monitoring

CHF Training optimization

TECHNOLOGY DEVELOPMENT PATHWAYS:

CONFIDENTIAL 29

Mobile

rechargeable

patches

Phone Readers

for Intermittent

Sensing

Thin-film,

Disposable

Blue-tooth from

Patch

Clothing-integrated readers

Helmet-based readers

Clinic-based

cabled reader

(O2 only)

TODAY TOMORROW

FUTURE

GREAT BIG WORLD - THE DATA ECOSYSTEM

30

Sensor

luminescence

signal

Skin reader

patch Data processing Wireless IN

Patient

Smartphone Wireless IN Cellular or wireless

OUT

Cloud DB • Data

aggregation

• Algorithms • Event detection • Message push

Patient

Smartphone

UI

Physician/

Caregiver/

EMR/?

Pad/

Smartphone

Patient: • Biovotion • geolocation; • other physiologic

data (HR, HRV)

External: • App searches

• Climate alerts • iBeacons • Other

Patient

Action

Real-time

Biochemistry

Data

Aggregation Patient

Engagement

Patient

Behavior

Modification

MONITORING HUMAN HEALTH IN A

WAY NEVER POSSIBLE BEFORE

• Tissue-integrating

biosensors

• Multiplexed

parameters

• Digital/mobile health

PROFUSA’S MISSION IS TO MAKE OUR BODY’S CHEMISTRY EASILY ACCESSIBLE TO IMPROVE HEALTH AND WELLNESS.

WE ARE DEDICATED TO BECOMING THE LEADER IN REAL-TIME

BIOSENSORS THAT PROVIDE UNPRECEDENTED INSIGHTS INTO OUR

OVERALL HEALTH STATUS AND PERFORMANCE.

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