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Pendragon Medical Ltd.Pendragon Medical Ltd.

Technology, Study Results and Device Presentation of the truly non-invasive continuous Glucose Monitor PENDRA

Dr. Thomas W. Schrepfer

Pendragon Medical Ltd.Pendragon Medical Ltd.ContentContent

1)1) Glucose MonitoringGlucose Monitoring

2)2) TechnologyTechnology

3)3) DeviceDevice

4)4) The HypoThe Hypo--WarningWarning

5)5) Clinical TrialsClinical Trials

Pendragon Medical Ltd.Pendragon Medical Ltd.Glucose Glucose MonitoringMonitoring

Glucose Monitoring Glucose Monitoring –– A Major ChallengeA Major Challenge

Spot Measurements vs. Continuous MonitoringSpot Measurements vs. Continuous Monitoring

Hyperglycaemia regionHyperglycaemia region

Hypoglycaemia regionHypoglycaemia region

Hyperglycaemia regionHyperglycaemia regionHyperglycaemia regionHyperglycaemia region

Hypoglycaemia regionHypoglycaemia regionHypoglycaemia regionHypoglycaemia region0

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29 .10 .2001 12 :00 30 .10 .2001 00 :00 30 .10 .2001 12 :00 31 .10 .2001 00 :00

Date / TimeDate / Time

glucoseglucose[mg /dl][mg /dl]

FingerprickFingerprickreadingreading

ContinuousContinuousreadingreading

Pendragon Medical Ltd.Pendragon Medical Ltd.MarketMarket

PresentPresent SolutionsSolutions forfor Glucose Glucose TestingTesting

Traditional Traditional fingerfinger prickprick measurementsmeasurements oror alternatealternatesitesite testingtesting (AST)(AST)

••invasiveinvasive••nonnon--continuouscontinuous••painfulpainful

ContinuousContinuous monitoringmonitoring forfor clinicalclinical useuse••invasiveinvasive••usingusing interstitialinterstitial fluidfluid (ISF)(ISF)••changechange of of measurementmeasurement sitesite everyevery fewfew daysdays••no no realtimerealtime readingsreadings

ContinuousContinuous monitoringmonitoring forfor homehome useuse••minimallyminimally invasiveinvasive••usingusing ISF ISF ••no no realtimerealtime readingsreadings••limitedlimited numbernumber of of readingsreadings••skinskin irritationsirritations

Pendragon Medical Ltd.Pendragon Medical Ltd.TechnologyTechnology

Glucose Monitoring

• Fluid extraction from skin• Interstitial fluid harvesting

FIR SpectroscopyOptical rotation of

polarizied lightUltrasonic +NIR Spectroscopy

Energy

Measure Interaction Calculateglucose concentration

Fluid extractionRadiation

(non-invasive)

Impedance Spectroscopy is different


Impedance Spectroscopy

1010--11 f (Hz)101033101022101000

101055 101066 101077 101088 101099 10101010101044101011 10101111

Tissue LymphocyteErythrocyte

Proteins Water

BoundWater

DNA Lipids

β -Dispersion

Measuring permittivity and conductivity of interfacial polarisation processes in the β -Dispersion

Reference: A. Caduff et al, Biosensors & Bioelectronics 2003; J. Phys. D: Appl. Phys.36 (2003) 369–374.


Impact of glucose on electrolytes

+-

--

-

+

+

+ -- +

+

--

++

-

-

--

Am J Med 1999 Apr;106(4):399-403

133134135136137138139140141142

0 2 4 6 8time [h]

[mm

ol/l]

0

5

10

15

20

25

Na+ (mmol/L) Glu (mmol/L)

[mm

ol/l]

( ) ( )000

0

ωεωσ

ωεσ

εωε

σεεωε

jjj

** =

′−′=

+′′−′=

Change of apparent dipole moment due to accumulation of ions on membrane

(interfacial polarisation).


Glucose vs Na in patients with Diabetes

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Glu

cose

[mg/

dl]

133

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Sodi

um [m

mol

/l]

BG Sodiumn=15


Cell reaction on D/L-glucoseOne-cell dielectric spectra

D-Glucose concentration dependance

L-Glucose concentration dependance

Reference: Hayashi Y, Livshits L, Caduff A, Feldman Y. Dielectric spectroscopy study of specific glucose influence on human erythrocyte membranes. J Phys D: Appl Phys 36:369-374, 2003


Sensor coupled to skin

Resonantcircuit

coupled to skin

LSensor

100

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30 35 40 45 50 55 60

|Z|

IZImin

fminResonant circuit to measurechanges in Z

L

C R Z


PENDRAPENDRA®® -- SensorSensor

ArmArm

Sensor plateSensor plate


Calibration

time scale (real time and minute of trial)

Measuredparameters Zy

Fx

T1/2

BG

Baseline

terms additionalbaseline +++++= FTTZglu 423121 αααα

at least 5 calibration points needed to define all coefficients α1 to α4


NI-CGMD readings vs BGM

Day 1Day 1--33

Day 4Day 4--66

Day 7Day 7--99

Tsens

Tdev

Fmin

Fmin

BGM

Pendra

Pendragon Medical Ltd.Pendragon Medical Ltd.DeviceDevice

PENDRAPENDRA®®

CE certified as medical device class type II bCE certified as medical device class type II b


PENDRAPENDRA®®

TheThe devicedevice isis designeddesigned

•• as an as an adjunctiveadjunctive devicedevice to to supplementsupplement bloodblood glucoseglucose measuringmeasuring

•• to to helphelp to to detectdetect trendstrends and and patternspatterns in in glucoseglucose levelslevels

TheThe devicedevice will will helphelp physiciansphysicians to to simplifysimplify thethe controlcontrol of of patientspatients‘‘therapytherapy......

...and ...and thethe patientspatients will will benefitbenefitfromfrom easiereasier selfself--controlcontrol, , whichwhichresultsresults in an in an improvementimprovement of of theirtheirqualityquality of lifeof life


Glucose StatusGlucose Status

Trend Trend IndicatorIndicator

MeasurementMeasurement IndicatorIndicator

CommunicationCommunicationStatusStatus

MemoryMemoryStatusStatus

Glucose Glucose UnitsUnits

BatteryBatteryStatusStatusTimeTime

AccousticAccousticAlarm Alarm

Glucose Glucose ValuesValues

Time Time Mode Mode

Pendragon Medical Ltd.Pendragon Medical Ltd.TheTheHypoHypo--WarningWarning

Approximation of Future Glucose Approximation of Future Glucose ExcursionExcursionPENDRAPENDRA®® isis PessimisticPessimistic

Glu

cose

G

luco

se level

level

TimeTime

Information Information aboutabout glucoseglucoseslopeslope and and itsits excursionexcursion

LimitingLimiting maximal maximal glucoseglucoseexcursionexcursion to to physiologicalphysiologicalrangerange allowsallows a a worstworst casecasescenarioscenario predictionprediction

Hypo Hypo alarmalarm isis triggeredtriggered ififglucoseglucose levellevel will will bebe underunder a a certaincertain limitlimit afterafter a a defineddefinedtimetime

Pendragon Medical Ltd.Pendragon Medical Ltd.AlarmsAlarms

Alarms Alarms areare TriggeredTriggered in in FollowingFollowingSituationsSituations

I) Parameter extractionI) Parameter extractionRiskRisk of of gettinggetting intointo a a hypoglycaemichypoglycaemic statestate in in nearnearfuturefuture ((withinwithin nextnext 20 min)20 min)

Glucose Glucose valuevalue isis at at oror lowerlower as as thethe givengiven thresholdthreshold forforhypoglycaemia II) First glucose calculationII) First glucose calculationhypoglycaemia

TheThe patientpatient isis moremore thanthan a a certaincertain periodperiod ((e.ge.g. 30 min.) in a . 30 min.) in a hyperglycaemichyperglycaemic conditioncondition

III) Corrections and alarmsIII) Corrections and alarmsRapid inRapid in-- oror decreasedecrease of of bloodbloodglucoseglucose


Pendragons’Pendragons’ SSolution for olution for CContinuous ontinuous NNonon--invasive invasive MMonitoring of onitoring of GGlucoselucose (1)(1)

Truly nonTruly non--invasiveinvasive continuouscontinuous realtimerealtime measurementmeasurementss

MeasurementMeasurement frequencyfrequency of 1 per of 1 per minuteminute –– dayday and and nightnight

AdjustableAdjustable alert alert forfor upcomingupcoming hypoglycaemichypoglycaemic conditionsconditionsand and forfor hyperglycaemichyperglycaemic situationssituations

TTrend indicatrend indicatoror for changes of glucosefor changes of glucose

Physician software Physician software forfor patiepatientnt datadata managementmanagement

Patient Patient softwaresoftware to to visualizevisualize glucoseglucose excursionsexcursions

Storage capacity of 1 monthStorage capacity of 1 month


Pendragons’Pendragons’ SSolution for olution for CContinuous ontinuous NNonon--invasive invasive MMonitoring of onitoring of GGlucoselucose (2)

NNo blood sample or interstitial fluido blood sample or interstitial fluid neededneeded

No No needneed of of expensiveexpensive disposablesdisposables

OffersOffers physiciansphysicians and and patientspatients thethe possibilitypossibility ofof tighter tighter control control of of glucoseglucose

Helps to simplify the therapy management (acute and long Helps to simplify the therapy management (acute and long term)term)

ReductionReduction of of diabetesdiabetes complicationscomplications byby continuouscontinuous monitoringmonitoringand and managementmanagement of of hypohypo-- and and hyperglycaemichyperglycaemic conditionsconditions

Pendragon Medical Ltd.Pendragon Medical Ltd.ClinicalClinicalTrialsTrials

Clinical TrialsClinical Trials

Some impressionsSome impressions

Pendragon Medical Ltd.Pendragon Medical Ltd.Results

1. Clinical Experimental Hyper/Hypo Study

Glucose-clamp study

15 patients with diabetes type 1 • Age 27 ± 5.7• Body mass index 23.1 ± 2.3kg/ m2

• HbA1C 6.9 ± 0.8 %

BG kept constant at three different target levels (45, 100, 200 mg/dl) for at least 30 min at each level.

Venous BG was measured by a standard laboratory system

Haematology parameters were measured by BGA.

The raw glucose sensor signals recorded (frequency, impedance) were corrected for temperature and calibrated with reference values from each BG level.


Glucose profile

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Glu

cose

[mg/

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45 mg/dl 45 mg/dl


Glucose vs Sodium in Patients with Diabetes

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200

250

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Glu

cose

[mg/

dl]

133

135

137

139

141

143

145

Sodi

um [m

mol

/l]

BG Sodiumn=15


Clarke Error Grid Analysis

Corresponding Clarke Error Grid analysis:81% in zone A15% in zone B4% in zone D

Correlation coefficient: 0.932

SEP 19.5 mg/dl.

Ref.: A. Caduff, R. Dewarrat, S. Buschor, T. Schrepfer, T. Heise, L. Heinemann, IDF Conference 2003


2. Results2. Results of a of a clinicalclinical experimental experimental trialtrial

Comparison BGM vs. PENDRAComparison BGM vs. PENDRA®®

15 Patients with diabetes15 Patients with diabetes

ClampClamp--Study by means of a Study by means of a BiostatorBiostator®®

GlucoseGlucose--profile:profile:

9090 9090

250250

2h2h 1h1h 2h2h

ResultsResults::

A 81%, B 18%, D 1%, A 81%, B 18%, D 1%, correlation coefficient: 0.958correlation coefficient: 0.958

PE

ND

RA

PE

ND

RA

®®

ComparativeComparative BG (mg/dl)BG (mg/dl)

Clark Error GridClark Error Grid


3. Results3. Results of an of an OutpatientOutpatient TrialTriala) Retrospective Analysis of Dataa) Retrospective Analysis of Data


15 15 PatientsPatients withwith diabetesdiabetes

2 2 daysdays of of inhouseinhouse trainingtraining

7 7 daysdays of of homehome useuse, 24h/d, 24h/d

7 7 –– 10 BG 10 BG readingsreadings per per dayday

ComparativeComparative BG (mg/dl)BG (mg/dl)

PE

ND

RA

PE

ND

RA

®®Clark Error Clark Error GridGrid

ResultsResults::

A 83%, B 15%, D 2%, A 83%, B 15%, D 2%, correlation coefficient: 0.923correlation coefficient: 0.923


b) Real Time Values


15 15 PatientsPatients withwith diabetesdiabetes

2 2 daysdays of of inhouseinhouse trainingtraining

7 7 daysdays of of homehome useuse, 24h/d, 24h/d

7 7 –– 10 BG 10 BG readingsreadings per per dayday

ResultsResults::A 56%, B 37%, C,D,E 7%, A 56%, B 37%, C,D,E 7%, correlation coefficient: correlation coefficient: 0.6400.640


c) Real-Time Tracking of Blood Glucose Profiles with PENDRA

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online reference

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online reference


PENDRAPENDRA®® helpshelps patientspatients in in criticalcritical situationssituations

DuringDuring nightnight

LivingLiving alonealone

DuringDuring workwork (stress (stress relatedrelated hypo‘shypo‘s))

DuringDuring carcar drivingdriving

PENDRAPENDRA®® ImprovesImproves QualityQuality of Lifeof Life

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