EZSCAN presented to the Ministry of Health Malaysia on the growing problem of diabetes. The presentation highlighted Impeto Medical's Ezscan technology, which provides a non-invasive, quick and easy way to detect diabetes and insulin resistance without the need for fasting or blood draws. This addresses key limitations of existing screening methods and makes diabetes prevention more practical and effective.

1. EZSCAN Presentation to
MINISTRY OF HEALTH MALAYSIA
23th October 2012

2. IMPETO MEDICAL
COMPANY PRESENTATION
2

3. IMPETO MEDICAL HISTORY IN BRIEF
HEADQUARTERS ARE BASED IN PARIS, FRANCE
2010
US FDA approved
2008
10 publications
SFDA approved
2006 Large studies launched
CE marked
In vitro studies
2012
15 patents
Chinese Guidelines
2011
Clinical use proven
US Subsidiary
700+ installations
2009 all over the world
2007 3 patents China Subsidiary
2005 Validation First Ezscan sales 19 publications
Incorporation Clinical + 6 ongoing
First patent studies
Prototypes
3

4. QUALITY MANUFACTURING IN FRANCE
ISO 13485 CERTIFIED FACTORY
4

5. MEDICAL DEVICES ALREADY APPROVED FOR SALES
Europe China Thailand Indonesia
USA Canada Mexico Australia
5

6. • TECHNOLOGY PROVEN BY CLINICAL STUDIES
A STRONG INVOLVEMENT BY KEY OPINION LEADERS
PARTICIPANTS ADA 2012 Investigator meeting
M.A. Abdul-Ghani, J. Chan, B. Freedman,
R. Pop-Busui, P. Schwarz, S. Tesfaye, A Vinik
6

7. WORLD WIDE CLINICAL STUDIES PROGRAM
GERMANY
- Dresden: PI: Pr. Schwarz*
-Dresden: PI: Dr. Viniecki
-Dresden: PI: Pr. Ziemssen
-Dresden: PI: Pr. Schwarz
-Berlin: PI: Pr. Pfeiffer SWEDEN
Completed
- Stockholm: PI: Pr. Rydén
NETHERLANDS
- Amsterdam: PI: Pr. Dekker
FINLANDE
- Tornio: Aino Activ
* Published
UNITED KINGDOM
ePredice
- Sheffield : PI: Pr. Tesfaye
-Ipswich : PI: Pr. Rayman
-Leicester: PI:Pr. Davies
CHINA
-Shanghai: PI Pr. Wang*
FRANCE - Beijing: Pr. Hu (ACE)
- Begin: PI: Pr. Bauduceau*
- Cochin: PI: Pr. Fajac*
- Haut-Lévêque: PI: Pr Gin*
-Val de Grâce: PI: Pr. Ricard
-Toulouse: PI: Dr. Le Traon HONG KONG
USA
- Hong Kong: PI: Pr. Chan*
- Norfolk: PI: Pr. Vinick
-Winston Salem: PI: Pr. Freedman
-Ann Arbor: PI: Pop-Busui - Hong-Kong: PI: Pr. Chan
-Salt Lake city: PI: Smith
-Baltimore: PI: Russell
-San Diego: PI: Schean
COLOMBIA
- Barranquilla: PI: Pr. Tuomilehto
INDIA
- Chennai 1: PI: Pr. Ramachandran*
-Chennai 2: PI: Pr. Ramachandran*
-Pune: PI: Pr. Yajnik
-New Dehli: PI:Anoop Mihra AUSTRALIA
-Hyderabad: PI: Pr. Ramakrishna -Perth: PI: Pr. Davis(Fremantle)
-Melbourne: PI: Pr. Shaw (Ausdiab)
7

8. USA CLINICAL STUDIES PROGRAM
8

9. DIABETES PROBLEM STATEMENT
9

10. DIABETES: A SILENT PANDEMIC
In 2003: 194 million DM!
In 2003: 194 million DM!
In 2025: 333 million DM!
In 2025: 333 million DM!
+
50 % of DM are not aware of it
10% of DM = 50% of the costs !
10

11. MALAYSIA’S GROWING CONCERN
11

12. MALAYSIA’S GROWING CONCERN
12

13. Diabetes is associated with serious complications
Stroke Complications Affecting Cardiovascular
Complications Affecting Cardiovascular
2- to 4-fold increase in System, Vision, and Kidney Function
System, Vision, and Kidney Function
cardiovascular mortality and
stroke5 A. Coronary Artery Disease
A. Coronary Artery Disease
1.1. Major risk of myocardial infarction
Major risk of myocardial infarction
inin Type 2 diabetics
Type 2 diabetics
Diabetic 2.2. Most common cause of death for
Most common cause of death for
Retinopathy diabetics (40 – – 60%)
diabetics (40 60%)
Leading cause 3.3. Diabetics more likely to develop
Diabetics more likely to develop
of blindness Congestive Heart Failure
Congestive Heart Failure
A. Hypertension
A. Hypertension
in adults1,2
1.1. Affects 20 – 60 % of all diabetics
Affects 20 – 60 % of all diabetics
8/10 individuals with 2.2. Increases risk for retinopathy,
Increases risk for retinopathy,
diabetes die from CV nephropathy
nephropathy
events6 3.3. Stroke: Type 2 diabetics are 2 – 6
Stroke: Type 2 diabetics are 2 – 6
times more likely toto have stroke
times more likely have stroke
A. Peripheral Vascular Disease
A. Peripheral Vascular Disease
1.1. Increased risk for Types 1 and 2
Increased risk for Types 1 and 2
diabetics
diabetics
2.2. Development of arterial occlusion
Development of arterial occlusion
Diabetic and thrombosis resulting inin gangrene
and thrombosis resulting gangrene
3.3. Gangrene from diabetes most
Gangrene from diabetes most
Neuropathy
common cause of non-traumatic
common cause of non-traumatic
Diabetic lower limb amputation
lower limb amputation
Nephropathy A. Diabetic Neuropathy
A. Diabetic Neuropathy
Leading cause of
end-stage renal disease3,4
13

14. GUILTY EVOLUTION ?
Homo Australopithecus H. erectus H. sapiens H. McDonald’s
Million years 50 years
14

15. SCIENTIFIC BACKGROUND
15

16. PERIPHERAL NERVOUS SYSTEM
16

17. LONG SUDOMOTOR NERVES ARE VERY SENSITIVE
17

18. SMALL NERVES ARE DAMAGED IN DIABETES
Control Diabetes
Metabolic Syndrome
or prediabetes
Pittenger, Burcus, McNulty, Basta, Vinikl. Diabetes Care 27:1974-79, 2004;
Pittenger,Mehrabyan, Simmons, Rice, Dublin, Barlow,Vinik,
Metab. Syndrome 3:113-121, 2005 18

19. Prevalence of retinopathy vs FPG and 2hPG levels
Diabetes Care 2009
19

20. DIAGNOSE TYPE 2 DIABETES EARLY COMPLICATIONS
Threshold of diabetes diagnosis (glucose, 2hPG,
HbA1C) has been defined by a significant increase
of prevalence of retinopathy.
But retinopathy is irreversible!
Small fiber neuropathy is more sensitive and
reversible, even more when detected early
20

21. SMALL FIBER NEUROPATHY (SFN)
• DETECTION RECOMMENDED BY NEW ADA/EASD GUIDELINES
(exercise, personalized treatments)
• SUDOMOTOR TESTS RECOGNISED AND REIMBURSED (USA)
• INSULIN BENEFIT SHOWED ON SFN IN NORMAL PRACTICE
21

22. EVALUATION OF INSULINO RESISTANCE
Type 2 Diabetes Diabetes Diagnosis
? ? ? Insulin resistance
Proinsulin secretion
Insulin
Blood glucose
Normal Impaired
glucose tolerance IFG glucose tolerance Diabetes
Modified from: DeFronzo RA et al., Diabetes Care 1998
22

23. WHO IS INSULIN RESISTANT?
• 90% of patients with type 2 diabetes
• 60% of patients with CVD
• 55% of patients with hypertension
• 85% of patients with low HDL and high LDL
• 30% of the US population between 40–74 years
(probably 40% of Aisian population)
• 50% of patients with CHD without family history
of diabetes
23

24. PREVENTION: The Sooner The Better!
Diabete Diagnostic
HIGH RISK TO BECOME DIABETIC
Glucose
Intervention is
more efficient and Insulin
less costly
Intervention
Is too late
Normal Impaired
glucose Diabetes
glucose tolerance tolerance
24

25. CHALLENGE TO PREDICT DIABETES
 Quality of the test
 Costs
 Availability
 Handling of the people diagnosed with
increased diabetes risk
25

26. CURRENT METHODS TO DETECT PREDIABETES
• QUESTIONNAIRES: simple, easy to perform, non invasive
• URINARY GLUCOSE: simple non invasive, well accepted by the patient
• CAPILLARY RANDOM BLOOD GLUCOSE: quick, does not require fasting
• FASTING PLASMA GLUCOSE: results easily understandable by the patient
• POST PRANDIAL GLUCOSE: does not require fasting
• HBA1C: does not require fasting , view of last 3 months
• 2H-OGTT: more information on a dynamic process (insulin resistance)
• 1H-OGTT: more precise and more informative than 2H-
OGTT
• A COMBINATION OF ABOVE: increased sensitivity
26

27. EX : From questionnaires…
Diabetes risk based on added risk factors
 BMI ≥ 25 kg/m2 plus at least another risk factor:
0
- Little physical activity
1
- First degree relative to Type2 Diabetes
>
- Ethnic group at risk
K
- Hypertension (140 / 90 mmHg or under antihypertensive treatment)
IS
- HDL Cholesterol 35 mg/dl (0.90 mmol/l)
R
and / or Triglyceride 250 mg/dl (2.82 mmol/)
D
- PCOS
I N
- IGT or IFG Test
F
- Other symptom related to Insulinresistance (overweight, …)
- Cardiovascular event
 Without any above criteria: older than 45
ADA Standards of Medical Care in Diabetes - 2009.
DIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009
27

28. ...to a combination of several blood tests...
# of subjects
Total # of Odds Ratio (95%
Condition developed Risk (%) P
subjects diabetes CI)
HbA1c<5.65%,
224 0 0% 1
1h PG< 155 mg/dl
HbA1c<5.65%
181 7 3.87% 8.92 (1.09-73.18) 0.025
1h PG>155 mg/dl
HbA1c>5.65%
86 3 3.49% 7.78 (0.99-75.8) 0.07
1h PG < 155 mg/dl
HbA1c >5.65%
133 24 18.1% 40.24 (5.38-300.9) <0.0001
1h PG> 155 mg/dl
Schwarz et al, J Clin Endocrinol Metab. 2011 Aug;96(8):2596-600. Epub 2011 Jun 6.
HbA1c + 1hPG for predicting Diabetes
28

29. THEY ARE ALL DIFFICULT TO APPLY IN LARGE SCREENING
• QUESTIONNAIRES: to be adapted, non objectives, low change with lifestyle
improvement
• URINARY GLUCOSE: low sensitivity, not quantitative
• CAPILLARY RANDOM BLOOD GLUCOSE: low sensitivity, inaccuracy of the method
• FASTING PLASMA GLUCOSE: invasive, fasting required, low sensitivity
• POST PRANDIAL GLUCOSE: invasive, long , low sensitivity
• HBA1C: low sensitivity for low values, accuracy of the method used
• 2H-OGTT: sensitivity improved but long, invasive, fasting required
• 1H-OGTT: best sensitivity, Fasting required, long
• A COMBINATION OF ABOVE: to improve sensitivity further, but more
complex
29

30. WHY NONE IS ABLE TO DECREASE THE PREVALENCE RATE?
• QUESTIONNAIRES
• URINARY GLUCOSE
• CAPILLARY RANDOM BLOOD GLUCOSE
• FASTING PLASMA GLUCOSE
• POST PRANDIAL GLUCOSE
• HBA1C
• 2H-OGTT
• 1H-OGTT
• COMBINATION OF ABOVE 30

31. Low values of HbA1c are not significant…
CGM IN A HEALTHY PERSON
Female, 26 years old, HbA1c 5.2%, typical snack-eater
5.9
5.4

Slides with permission from Prof. Hanefeld
31

32. …because Postprandial Glucose PEAKS are not seen!
Increase in fluctuation leads to
increase in oxidative stress
61 years old male patient with IGT, HbA1c 5.0%
Diabetes Starts with Postprandial Glucose Peaks!
Slides with permission from Prof. Hanefeld
32

33. WHY DIABETES PREVENTION IS NOT WELL DEVELOPED
Diabetes risk is not well screened today
Invasive procedures
Fasting is required
Sensitivity of existing tests are too low
Cost of diagnosis is too high because too complex
Diagnosis is done too late
Existing tools are too time consuming for Physicians and Patients
Most significant blood tests require preparation and are time consuming
Blood tests confirmation are often needed due to the lack of robustness of the tests
which is even further time consuming.
Many patients are not coming back after a first test.
AS A RESULT, Diabetes Prevention is not well developed
Procedures are known, scientificaly published (Lifestyle)… but not used in daily practice
No easy sensitive and robust tests exist to follow up patient progresses
 The lack of sensitivity of weight measurement demotivates many people.
33

34. EZSCAN UNIQUE PROPOSITION
Non-invasive
No risk of blood contamination
No patient preparation or fasting required
More sensitive than usual screening methods
Easy to use - Quick and safe procedure
Low operating costs
Immediate objective & quantitative results
Results easily understandable
=>Better motivation of the patient
=>Higher efficacy of prevention
34

35. EZSCAN COMPETITIVE LANDSCAPE
How is eZscan better than • FPG: very low
alternatives? sensitivity, blood draw,
fasting
FSOGTT • OGTT (WHO gold
Efficacy (Test Performance, Accuracy)
OGTT
standard): fasting, too
EZSCAN
long, blood draw
HbA1c • HbA1c: too late,
+/-20% precision,
FPG
result of high glucose
• Questionnaires /
Survey: low sensitivity,
depends on lifestyle
RBG –Finger prick Questionnaires habits which change
quickly and depend on
culture
Effectiveness (Convenience, Low Cost, Ease of Use)
35

36. HOW TO MEASURE SUDOMOTOR FUNCTION?
Classic Sudomotor tests (QSART): developed 20 years ago in the
US (Mayo clinic) and reimbursed by Medicare,
but long, cumbersome, sensitive to environment, expensive.
Modern Sudomotor tests (EZSCAN): a fast, new and more
practical way of doing these well known Sudomotor tests.
IMPETO MEDICAL DID NOT INVENT A NEW CONCEPT:
IMPETO MEDICAL DESIGNED A NEW TECHNOLOGY
TO MAKE SUDOMOTOR FUNCTION MEASUREMENT
PRACTICAL !
36

37. EZSCAN TECHNOLOGY
37

38. A simple method to measure sudomotor function
Degeneration of small C-fiber
innervating sweat glands as observed
in diabetes.
(reproduced from Lauria et al.)
Measurement of Electrochemical Sweat
Conductances, directly dependent from the
glands capability to transfer chlorides and
reflecting small-C fiber status.
Application of a low voltage to
electrodes on hands and feet to
extract chlorides from the sweat.
Electrochemical reaction between
the chlorides of the sweat and the
stainless-steel electrodes.

39. SIMPLE, QUICK & NON-INVASIVE INVESTIGATION
39

40. EZSCAN, new tool for massive screening campaign
40

41. EZSCAN SCORES
Results are easy to explain…
and to understand!
41

42. EZSCAN MOTIVATES THE PATIENT BETTER
42

43. EZSCAN can easily estimate insulin dynamic behavior
GLUCOSE & INSULIN PROFILES DURING FSOGTT
Glucose Insulin
Green=normal; yellow=IR; orange/red=DM
43

44. EZSCAN: ONLY ONE INDICATOR FOR PREVENTION
Diabetes Diagnosis
EZSCAN Evaluation
Type 2 Diabetes Risk fasting glucose
Insulin resistance
HbA1c
FFA
Insulin
2hr gluc
1hr glucose Blood glucose
Risk score use
Normal Impaired
Glucose tolerance IFG Glucose tolerance Diabetes
44

45. PROVEN TECHNOLOGY
PUBLISHED CLINICAL TESTS
45

46. ROBUSTNESS OF THE METHOD
Proven reproducibility, regardless of patient condition
(Schwarz et al. British Journal of Diabetes & Vascular diseases. 011;11(4):204-9)
– Good reproducibility: 5-10% change between two successive measures
– No impact of effort: less than 10% change before and after exercise
– No impact of glycemia: less than 10% change between normal and
hyperglycemia
3%
46

47. CLINICAL STUDIES – Published Papers
good sensitivity, specificity and
reproducibility of EZSCAN for
assessing sudomotor dysfunction
47

48. CLINICAL STUDIES – Published Papers
EZSCAN:
•More sensitive to detect
diabetes and prediabetes
•Better predictive
parameter
EZSCAN… a very useful tool
in diabetes risk diagnostics
48

49. CLINICAL STUDIES – Published Papers
EZSCAN demonstrated good sensitivity
to detect IGT and DM
Measuring ion fluxes… a powerful method
for early detection of IGT and DM
49

50. CHENNAI 1 STUDY : EZSCAN vs FPG
A FPG B EZSCAN
MS DM
n 57 24
FPG>126 mg/dl 1 7
Sensitivity % 2% 29%
FPG>110 mg/dl 2 11
Sensitivity % 4% 46%
EZSCAN 52 22
Sensitivity % 91% 92%
With FPG, we miss 1 DM patient out of 2!
FPG of
no value FPG of limited value
Ramachandran A et al Diabetes Res Clin Pract 2010 88 302
50

51. CLINICAL STUDIES – Published Papers
EZSCAN …very useful to identify subjects at risk
for developing glucose intolerance
51

52. CLINICAL STUDIES – Published Papers
EZSCAN might be useful
in screening diabetes…
52

53. CLINICAL STUDIES – Published Papers
EZSCAN test is a good and simple
screening technique for early
predicting metabolic syndrome…
53

54. EZSCAN screening for insulin resistance
Pr P Schwarz, Dresden, Germany
Objectives To assess the ability of EZSCAN to be used as a screening tool in a German
population of subjects at risk of metabolic diseases
Methods • 114 German subjects at risk of prediabetes or diabetes
• Oral glucose tolerance test (OGTT) with measurement of glucose, insulin, pro-
insulin, C-peptide, free fatty acid
• Insulin sensitivity (Minimal model), Insulin resistance with HOMA-IR and
Matsuda index. Inflammation markers.
• Measurement of electrochemical sweat conductance (ESC) with EZSCAN and
classification of subjects in no risk (green), moderate risk (yellow), high risk
(red)
Main • 29 subjects with Impaired fasting glucose or impaired glucose tolerance
results according to Who classification,
18 moderate risk / 10 high risk according to EZSCAN
• 7 subjects with diabetes according to Who classification
2 had moderate risk / 5 had high risk according to EZSCAN
• No adverse events reported during and after the study
• Results in accordance with a previous study performed in India
54
54

55. EZSCAN is a good prediction for HbA1c progression
P Schwarz
Dresden University
Germany
55
Predictive value of hand and foot ESC for HbA1C 5.7%
16 months in advance vs usual methods
55

56. EZSCAN for early detection of neuropathies in prediabetes
Objectives To evaluate the effect of early treatment intervention on
occurrence of complications in subjects with hyperglycemia
Methods • 15 European centers for diabetes screening
• 3000 subjects with hyperglycemia without clinical evidence of
micro or macrovascular complications
• 4 groups with lifestyle intervention, Metformin, Vildagliptin or
Liraglutide
• 36 months follow-up with new occurrence of:
• Retinopathy (by fondus of eye)
• Impairment of renal function (by creatinin level)
• CAN (by EZSCAN)
• Autonomic neuropathy (by SUDOSCAN)
Pr J Tuomilehto, E-PREDICE, EU commission funded project
56

57. OFFICIAL ENDORSEMENT IN CHINA
BREAKING NEWS: EZSCAN IN THE NEW ‘2012 MEDICAL CONSENSUS’ GUIDE!
57

58. EZSCAN IN THE PRESS IN CHINA
58

59. QUICK EPIDEMIOLOGICAL DATA COLLECTION
(Samples at Medical Congress Events)
Male caucasian
Diabetes Physicians Mean age
Mean age Mean age 46y+/-10
Male/female
45y+/-10 46y+/-10 American/Asian/
Female caucasian African
Diabetes nurses green yellow orange+red Sum Diabetes
FEND 79 14 3 96
Physicians
EASD 84 23 16 123
and IDF
IDF 87 39 53 179
Sum 254 77 72 403
organizations
members 59

60. EZSCAN FOR EASY SCREENING OF LARGE POPULATIONS
In pharmacies (Germany, France, 15,000 patients in the Netherlands
Australia, Canada, Chile…)
Occupational health
60

61. EZSCAN CHOSEN FOR LARGE EPIDEMIOLOGICAL STUDIES
The Australian Diabetes, Obesity and
Lifestyle (AusDiab) study is the largest
Australian longitudinal population
based study (11,247 individuals)
examining the natural history of
diabetes, pre-diabetes, heart disease
and kidney disease.
Dutch diabetes prevention campaign
(15,000+ people screened within less 1 year) 61

62. EZSCAN SELECTED IN EUROPEAN PROGRAM ‘IMAGE’
62

63. PROGRAM ‘IMAGE’ : HOW TO IDENTIFY PEOPLE AT RISK
GE
IMAGE ‘TOOLKIT’
63

64. DEVELOPING A PREVENTION STRATEGY
 be structured – easy to understand
 find people where they are – setting approach
 focus on the individual – empowerment
 involve regular contact with individuals with
prediabetes
 recruit educated lifestyle managers
 continuously evaluate the success of prevention
strategies
 use screening tools that are applicable in a
population setting
 include quality management – prevention
management
64

65. SUMMARY
QUICK ECONOMICAL STUDY
65

66. SUMMARY: WHY EZSCAN?
Diabetes risk is not well screened today
Existing tools are too time consuming for Physicians and Patients
As a result, Diabetes Prevention is not well developed
Rationale in using eZscan for screening large populations :
•Non invasive, no need for fasting and objective
eZscan measures actual damages for each individual
•More sensitive, convenient and quicker than blood test
eZscan allows detecting PREDIABETES on time, when it is reversible, saving future costs
•Complementary no-fasting tool to current gold standards
without preparation, eZscan can scan much larger (100%?) populations,
only applying the burden and costs of standard blood tests
among those 10-15 % people detected at high risk
66

67. DIABETES IN MALAYSIA
Top Ten! Malaysia has one of the highest prevalence in the world!
67

68. Population with diabetes in 2010 and 2030
According to the study of IDF Atlas in 2010, there is 1.8 millions of diabetics in
Malaysia, with a prevalence of 10.9%.
The prevision for 2030 is 3.2 millions of diabetics with a prevalence of 13.4%.
68

69. Evaluation of population to screen
• In Malaysia, the population at risks (people over 40) that will
have to be screen in priority represents 6 778 537 people.
Identified patients will be invited to make an EZSCAN test at the
nearest institution equipped with EZSCAN (pharmacy, hospitals,
clinics etc.).
69

70. COST OF DIABETES IN MALAYSIA
802 million of USD/year
70

71. Benefit of an EZSCAN campaign in Malysia
71

72. MINISTRY OF HEALTH MALAYSIA
Proposed Implementation of
EZSCAN & Tanita MC980
in Government Hospitals,
Clinics and Klinik 1Malaysia
BY
LAZCORP HOLDINGS SDN BHD