CONFIDENTIAL1

PillCamPillCam™™ COLON COLON

Trial ResultsTrial Results

2

AgendaAgenda

First Feasibility Studies – Overview

Study Results of MA-48 Feasibilit

3

Type # of sites PI Subjects Comparative

ArmPresenta

tion Publication

Completed

11 Feasibility 3 Eliakim, Israel 91 Colonoscopy ACG 06 Endoscopy, 10/06

22 Feasibility 1 Deviere, Belgium 41 Colonoscopy UEGW 06 Endoscopy, 10/06

33 Feasibility 1 Lewis, US 51 Colonoscopy, VC ACG 06 Work In

Progress

Work in progress

44 Pivotal 8 Deviere, Belgium 225 / 340 Colonoscopy DDW 07?

55 Pivotal 7 Rex-Eisen, US 25 / 340 Colonoscopy

To commence within few months

66 CRC screening 12 Galmiche, France 600 Colonoscopy

77 Feasibility 1 Sung, China 40 Colonoscopy

88 Feasibility 3 Riemann, Germany 50 Colonoscopy

99 Feasibility 5 PI tbd, Italy 60 Colonoscopy

10 /1110 /11 2 feasibilities 6-8 Munoz/Herrerias, Spain

60 Colonoscopy

Clinical TrialsClinical Trials

4

Conclusions from Feasibility TrialsConclusions from Feasibility Trials

“Colon Capsule Endoscopy showed promising accuracy compared with colonoscopy. This new noninvasive technique deserves further evaluation as a potential CRC screening tool.”

OctoberOctober20062006II

5

Conclusions from Feasibility TrialsConclusions from Feasibility Trials

OctoberOctober20062006

“PillCam Colon capsule endoscopy appears to be a promising new modality for colonic evaluation. Further improvements in the procedure will probably increase capsule examination completion and polyp detection rates. Additional studies are needed to evaluate the accuracy of PillCam Colon endoscopy in other populations with different prevalence levels.”

IIII

6

Capsule Colonoscopy – A Pilot Three Arm, Blinded Trial of Capsule Colonoscopy, Virtual Colonoscopy and ColonoscopyBlair Lewis1, Douglas Rex2, David Lieberman3

Private practice, New York, New York1; Indiana University School of Medicine, Indianapolis, Indiana2; Oregon Health and Science University, Portland, Oregon3

Introduction: Colon capsule endoscopy (CCE) is a new endoscopic capsule for visualization of the colon. The capsule is 31x11mm. It has two imagers and obtains 4 frames per second. It is not a FDA approved device. A blinded trial was being performed to assess the feasibility and efficacy of this technology in screening patients at risk for colon polyps and cancer.

Materials and Methods: At risk volunteers were recruited. Study entry required age over 50 and not having colonoscopy within 5 years or having a family history of colon cancer or the presence of symptoms suspicious for cancer. Volunteers were paid and signed IRB approved consent forms. Patients initially underwent CCE and within 3 weeks took a second preparation and underwent virtual (VC) and standard colonoscopy (SC) on the same day. The colonoscopist was blinded to the findings of the previous tests. At SC, results of the two previous tests were serially unblinded. Results were reviewed. Significant findings were defined as any polyp ≥6mm in size or 3 or more polyps of any size.

Conclusions: Colon capsule endoscopy appears to be a promising new technology for screening the colon for polyps in patients at risk for colorectal cancer.

This feasibility study demonstrates that capsule colonoscopy appears to be a safe and promising new technology for visualizing the colon

This capsule colonoscopy may complement traditional colonoscopy for:

•Contraindicated colonoscopy

•Incomplete colonoscopy

•Patients unwilling to undergo standard colonoscopy

Capsule colonoscopy appears to be more sensitive than virtual colonoscopy in detecting small colon polyps

Inclusion Criteria: Patients between the ages of 50-75

•Indicated for CRC screening, who did not have colonoscopy in last 5 years, OR with current or recent history of IDA

Patients between the ages of 40-75•With family history of colonic polyps or CRC•With FOBT positive

Patients sign an IRB informed consent form

Exclusion Criteria: Dysphagia Known or suspected bowel obstruction High risk for capsule retention and abdominal surgery of the GI tract

within the last six months Contra-indication for any procedure prescribed in the study,

e.g., ingestion of oral sodium phosphate or polyethylene glycol solutions, Tegaserod or Bisacodyl suppository

Congestive heart failure or renal insufficiency or liver disease Cardiac pacemakers or other implanted electro medical-device Pregnancy MRI examination within 7 days after capsule ingestion Current life threatening conditions

Study Overview:• Capsule procedure:

• Day -1: Clear liquids and evening laxative as below• Day 0: Laxatives and prokinetic agents, Capsule ingestion

• Capsule video review by Investigators DR, DL*• Within 3 weeks following Capsule procedure:

• Early morning: Virtual colonoscopy by investigator JM*• Midday: Colonoscopy by investigator BL* then sequential

un-blinding * all investigators blinded to each other

Capsule Colonoscopy Preparation:Day -1 Clear Liquid diet

1800 – 2100 2 Liter PEG

Exam day 700 – 800 1 Liter PEG

815 6mg Tegaserod

830 Capsule ingestion

1040 Boost I (30ml NaP) *

1300 6mg Tegaserod

1400 Boost II (15ml NaP)

1600 Suppository 10mg Bisacodyl - if needed

1700 Regular meal

* Pending verification that the capsule had exited the the stomach using a real-time viewer .

Assessment of Bowel Cleansing:

• Poor - Large amount of fecal residue• Fair - Enough feces or dark fluid present to preclude

a completely reliable examination• Good - Small amount of feces or dark fluid, but not

enough to interfere with examination• Excellent - No more then small bits of adherent feces

Poor Fair Good Excellent

Study Results - Enrollment:• 64 patients screened - 12 failed• 52 enrolled - 1 discontinued• 51 completed trial

-Average age 54 (40-74)-28 Males, 23 Females-31 for screening-16 for family history-3 for blood in stool-1 for personal history of polyps

60%

33%

5%2%

53%

38%

7%3%

59%

35%

4%

57%

33%

11%0%

47%

27%

20%

7%

0%

20%

40%

60%

80%

100%

Ceacum Right Colon Transverse Left Colon Sigmoid-Rectum

Excellent Good Fair Poor

Results - Bowel cleanliness:

Transit Time From Ingestion to Excretion

6%

67%

84% 88% 90%100%

0

5

10

15

20

25

30

35

2:00 4:00 6:00 8:00 10:00 Later

Time [Hours]

Freq

uenc

y

0%

20%

40%

60%

80%

100%

Transit time from ingestion to Transit time from ingestion to excretionexcretion

2%

90%

6%

2%

Results - Capsule Transit:

Capsule Location at 10 hrs

Results - Polyp Detection: Polyps of any size/path were found in 29/51 patients (57%)Polyps of any size/path were found in 29/51 patients (57%)

•60 polyps by un-blinded colonoscopy60 polyps by un-blinded colonoscopy•55 polyps by colonoscopy55 polyps by colonoscopy•94 polyps by capsule colonoscopy94 polyps by capsule colonoscopy•26 polyps by virtual colonoscopy26 polyps by virtual colonoscopy

Adenomatous polyps were found in 15/51 patients (29%)Adenomatous polyps were found in 15/51 patients (29%)•17 total polyps in 15 patients - 3 TVA, 14 TA, 2-15mm, 8 polyps > 6mm17 total polyps in 15 patients - 3 TVA, 14 TA, 2-15mm, 8 polyps > 6mm•16/17 detected by standard colonoscopy (1 missed and found on unblinding)16/17 detected by standard colonoscopy (1 missed and found on unblinding)•12/17 detected by capsule12/17 detected by capsule•5/17 detected by virtual colonoscopy5/17 detected by virtual colonoscopy

Results - Sensitivity and Specificity:Colonoscopy Capsule Virtual Colonoscopy

For any polyp

Sensitivity 93% (95% CI, 85-93%) 83% (95% CI, 72-92%) 38% (95% CI, 27-44%)

Specificity 100% (95% CI, 90-100%) 45% (95% CI, 31-57%) 86% (95% CI, 72-95%)

PPV 100% (95% CI, 92-100%) 67% (95% CI, 58-74%) 79% (95% CI, 56-92%)

NPV 92% (95% CI, 82-92%) 67% (95% CI, 46-83%) 51% (95% CI, 43-56%)

For significant findings *

Sensitivity 89% (95% CI, 77-89%) 56% (95% CI, 38-71%) 33% (95% CI, 20-38%

Specificity 100% (95% CI, 93-100%) 76% (95% CI, 66-84%) 97% (95% CI, 90-99%)

PPV 100% (95% CI, 86-100%) 56% (95% CI, 38-71%) 86% (95% CI, 52-97%)

NPV 94% (95% CI, 88-94%) 76% (95% CI, 66-84%) 73% (95% CI, 67-75%)

* Significant findings: Polyps ≥ 6 mm OR three or more polyps of any size

The Capsule:• 11 x 31mm• Wider angle of view• 2 Frames/second from each side• 10 gig recording device

Ø1

1 m

m

31 mm

Virtual Colonoscopy:• "Top CAT” GE 64-detector VCT was used to scan the patients' cleansed colons. • Data was compiled and reviewed in 2D and 3D on a Vitrea workstation.

Colonoscopy:• Performed under conscious sedation (Demerol/Versed)• Complete in all patients• Limited withdrawal time to less than 10 minutes to limit study effect

Polyp seen at colonoscopy Polyp seen on capsule

III Conclusions from Feasibility Trials – ACG 2006 PosterIII Conclusions from Feasibility Trials – ACG 2006 Poster

7

Capsule Colonoscopy – A Pilot Three Arm, Blinded Trial of Capsule Colonoscopy, Virtual Colonoscopy and ColonoscopyBlair Lewis1, Douglas Rex2, David Lieberman3

Private practice, New York, New York1; Indiana University School of Medicine, Indianapolis, Indiana2; Oregon Health and Science University, Portland, Oregon3

Introduction: Colon capsule endoscopy (CCE) is a new endoscopic capsule for visualization of the colon. The capsule is 31x11mm. It has two imagers and obtains 4 frames per second. It is not a FDA approved device. A blinded trial was being performed to assess the feasibility and efficacy of this technology in screening patients at risk for colon polyps and cancer.

Materials and Methods: At risk volunteers were recruited. Study entry required age over 50 and not having colonoscopy within 5 years or having a family history of colon cancer or the presence of symptoms suspicious for cancer. Volunteers were paid and signed IRB approved consent forms. Patients initially underwent CCE and within 3 weeks took a second preparation and underwent virtual (VC) and standard colonoscopy (SC) on the same day. The colonoscopist was blinded to the findings of the previous tests. At SC, results of the two previous tests were serially unblinded. Results were reviewed. Significant findings were defined as any polyp ≥6mm in size or 3 or more polyps of any size.

Inclusion Criteria: Patients between the ages of 50-75

•Indicated for CRC screening, who did not have colonoscopy in last 5 years, OR with current or recent history of IDA

Patients between the ages of 40-75•With family history of colonic polyps or CRC•With FOBT positive

Patients sign an IRB informed consent form

Exclusion Criteria: Dysphagia Known or suspected bowel obstruction High risk for capsule retention and abdominal surgery of the GI tract

within the last six months Contra-indication for any procedure prescribed in the study,

e.g., ingestion of oral sodium phosphate or polyethylene glycol solutions, Tegaserod or Bisacodyl suppository

Congestive heart failure or renal insufficiency or liver disease Cardiac pacemakers or other implanted electro medical-device Pregnancy MRI examination within 7 days after capsule ingestion Current life threatening conditions

Study Overview:• Capsule procedure:

• Day -1: Clear liquids and evening laxative as below• Day 0: Laxatives and prokinetic agents, Capsule ingestion

• Capsule video review by Investigators DR, DL*• Within 3 weeks following Capsule procedure:

• Early morning: Virtual colonoscopy by investigator JM*• Midday: Colonoscopy by investigator BL* then sequential

un-blinding * all investigators blinded to each other

Capsule Colonoscopy Preparation:Day -1 Clear Liquid diet

1800 – 2100 2 Liter PEG

Exam day 700 – 800 1 Liter PEG

815 6mg Tegaserod

830 Capsule ingestion

1040 Boost I (30ml NaP) *

1300 6mg Tegaserod

1400 Boost II (15ml NaP)

1600 Suppository 10mg Bisacodyl - if needed

1700 Regular meal

* Pending verification that the capsule had exited the the stomach using a real-time viewer .

Assessment of Bowel Cleansing:

• Poor - Large amount of fecal residue• Fair - Enough feces or dark fluid present to preclude

a completely reliable examination• Good - Small amount of feces or dark fluid, but not

enough to interfere with examination• Excellent - No more then small bits of adherent feces

Poor Fair Good Excellent

Study Results - Enrollment:• 64 patients screened - 12 failed• 52 enrolled - 1 discontinued• 51 completed trial

-Average age 54 (40-74)-28 Males, 23 Females-31 for screening-16 for family history-3 for blood in stool-1 for personal history of polyps

60%

33%

5%2%

53%

38%

7%3%

59%

35%

4%

57%

33%

11%0%

47%

27%

20%

7%

0%

20%

40%

60%

80%

100%

Ceacum Right Colon Transverse Left Colon Sigmoid-Rectum

Excellent Good Fair Poor

Results - Bowel cleanliness:

Transit Time From Ingestion to Excretion

6%

67%

84% 88% 90%100%

0

5

10

15

20

25

30

35

2:00 4:00 6:00 8:00 10:00 Later

Time [Hours]

Freq

uenc

y

0%

20%

40%

60%

80%

100%

Transit time from ingestion to Transit time from ingestion to excretionexcretion

2%

90%

6%

2%

Results - Capsule Transit:

Capsule Location at 10 hrs

Results - Polyp Detection: Polyps of any size/path were found in 29/51 patients (57%)Polyps of any size/path were found in 29/51 patients (57%)

•60 polyps by un-blinded colonoscopy60 polyps by un-blinded colonoscopy•55 polyps by colonoscopy55 polyps by colonoscopy•94 polyps by capsule colonoscopy94 polyps by capsule colonoscopy•26 polyps by virtual colonoscopy26 polyps by virtual colonoscopy

Adenomatous polyps were found in 15/51 patients (29%)Adenomatous polyps were found in 15/51 patients (29%)•17 total polyps in 15 patients - 3 TVA, 14 TA, 2-15mm, 8 polyps > 6mm17 total polyps in 15 patients - 3 TVA, 14 TA, 2-15mm, 8 polyps > 6mm•16/17 detected by standard colonoscopy (1 missed and found on unblinding)16/17 detected by standard colonoscopy (1 missed and found on unblinding)•12/17 detected by capsule12/17 detected by capsule•5/17 detected by virtual colonoscopy5/17 detected by virtual colonoscopy

Results - Sensitivity and Specificity:Colonoscopy Capsule Virtual Colonoscopy

For any polyp

Sensitivity 93% (95% CI, 85-93%) 83% (95% CI, 72-92%) 38% (95% CI, 27-44%)

Specificity 100% (95% CI, 90-100%) 45% (95% CI, 31-57%) 86% (95% CI, 72-95%)

PPV 100% (95% CI, 92-100%) 67% (95% CI, 58-74%) 79% (95% CI, 56-92%)

NPV 92% (95% CI, 82-92%) 67% (95% CI, 46-83%) 51% (95% CI, 43-56%)

For significant findings *

Sensitivity 89% (95% CI, 77-89%) 56% (95% CI, 38-71%) 33% (95% CI, 20-38%

Specificity 100% (95% CI, 93-100%) 76% (95% CI, 66-84%) 97% (95% CI, 90-99%)

PPV 100% (95% CI, 86-100%) 56% (95% CI, 38-71%) 86% (95% CI, 52-97%)

NPV 94% (95% CI, 88-94%) 76% (95% CI, 66-84%) 73% (95% CI, 67-75%)

* Significant findings: Polyps ≥ 6 mm OR three or more polyps of any size

The Capsule:• 11 x 31mm• Wider angle of view• 2 Frames/second from each side• 10 gig recording device

Ø1

1 m

m

31 mm

Virtual Colonoscopy:• "Top CAT” GE 64-detector VCT was used to scan the patients' cleansed colons. • Data was compiled and reviewed in 2D and 3D on a Vitrea workstation.

Colonoscopy:• Performed under conscious sedation (Demerol/Versed)• Complete in all patients• Limited withdrawal time to less than 10 minutes to limit study effect

Polyp seen at colonoscopy Polyp seen on capsule

Conclusions: Colon capsule endoscopy appears to be a promising new technology for screening the colon for polyps in patients at risk for colorectal cancer.

This feasibility study demonstrates that capsule colonoscopy appears to be a safe and promising new technology for visualizing the colon

This capsule colonoscopy may complement traditional colonoscopy for:

•Contraindicated colonoscopy

•Incomplete colonoscopy

•Patients unwilling to undergo standard colonoscopy

Capsule colonoscopy appears to be more sensitive than virtual colonoscopy in detecting small colon polyps

Conclusions: This feasibility study demonstrates that capsule colonoscopy appears to be a safe and

promising new technology for visualizing the colon and for screening the colon for polyps in patients at risk for colorectal cancer

This capsule colonoscopy may complement traditional colonoscopy for:

• Contraindicated colonoscopy

• Incomplete colonoscopy

• Patients unwilling to undergo standard colonoscopy

Capsule colonoscopy appears to be more sensitive than virtual colonoscopy in detecting small colon polyps

8

PCCE: European studiesPCCE: European studies

MA-48 Jacques DevièreMA-48 Jacques DevièreErasme University HospitalErasme University Hospital

First European Feasibility StudyFirst European Feasibility Study

** Endoscopy, Vol. 38, October 2006Endoscopy, Vol. 38, October 2006

9

Feasibility Study ObjectivesFeasibility Study Objectives

Prospective pilot evaluation of the

performance and accuracy parameters of

PillCam COLON Capsule compared with

traditional colonoscopy

Evaluation the efficacy of colon

preparation for colon Capsule endoscopy

10

Inclusion CriteriaInclusion Criteria

Patients between the ages of 18-75 years

Patients suspected of having colonic disease referred for traditional colonoscopy

OR

Patients referred for colonoscopy for CRC screening

11

Exclusion CriteriaExclusion Criteria

All usual contra indication for Small Bowel CE

Patients with high risk for capsule retention:• Crohn's disease, SB tumors, radiation enteritis, NSAID,

surgical anastomosis

Patients with contraindications to ingest oral sodium phosphate or polyethylene glycol solution

Patients with known allergy to Domperidone or Bisacodyl suppository

12

Process OverviewProcess Overview

1. Patient signed informed consent

2. Day -1: Clear liquids and evening laxative

3. Examination daya. Laxative and prokinetic agentsb. Ingestion of PillCam COLONc. Traditional colonoscopy performed by investigator #1* following capsule

excretion or at 19:00d. Patient discharged

4. Capsule video reviewed by Investigator #2*

* Both investigators blinded to each other results.

13

Day -1Clear liquids diet (no breakfast)

1800 – 2100 2 liters PEG

Exam day

700 – 800 1 liter PEG

745-800 20mg Domeperidone and Capsule ingestion

1000 Booster I (45ml NaP) *

1400

* Pending verification that PillCam COLON had moved out of the stomach with RAPID Access RT (real-time viewer)

Traditional colonoscopy prep (clear liquid diet and 4 liters Colopeg®)

55% of patients

Preparation and ProcedurePreparation and Procedure

14

Additional intakes for up to 45% of patients

Day -1Clear liquids diet (no breakfast)

1800 – 2100 2 liters PEG

Exam day

700 – 800 1 liter PEG

745-800 20mg Domeperidone and Capsule ingestion

1000 Booster I (45ml NaP) *

1400

* Pending verification that PillCam COLON had moved out of the stomach with RAPID Access RT (real-time viewer)

Traditional colonoscopy prep (clear liquid diet and 4 liters Colopeg®)

55% of patients

1400 Booster II (30ml NaP)

1500 Optional low-fiber snack

1630 10mg Bisacodyl suppository

1900 Traditional colonoscopy

Preparation and ProcedurePreparation and Procedure

15

Poor Large amount of fecal residue

FairEnough feces or dark fluid present to preclude a completely reliable examination

GoodSmall amount of feces or dark fluid, but not enough to interfere with examination

Excellent No more then small bits of adherent feces

Poor Good ExcellentFair

Preparation and Procedure:Preparation and Procedure:Assessment of Colon CleanlinessAssessment of Colon Cleanliness

16

41 Patients enrolled (26 women, mean age 56 years, range 26-75)

• Three patients out of the first five were excluded from the analysis due to technical capsule failure

• One patient could not swallow the Capsule because of excessive anxiety• In one patient Capsule data compilation failed

Results reported for 36 patients

No adverse events (AE) were reported

Results: Demographics and AEResults: Demographics and AE

17

Patient referred CRC screening 41 %

Patients suspected of having colonic disease 59%

Results: Reasons for ReferralResults: Reasons for Referral

18

Results: PreparationResults: Preparation

Overall preparation for PillCam COLON Capsule• Excellent: 33% of cases

• Good: 58%

• Fair: 6%

• Poor: 3%

All patients tolerated the preparation without any significant complaints

19

ResultsResults Location of Location of Capsule at 10 hours post ingestionCapsule at 10 hours post ingestion

3%

3%

84%

3%

7%

20

ResultsResultsTumor and Polyps DetectionTumor and Polyps Detection

21

Case ICase IS

am

ple

S

am

ple

Cases

Cases

Colonoscopy: Carcinoma at sigmoid, patient referred to surgical intervention

PillCam: Large neoplastic mass at sigmoid

PillCam imageColonoscopy image

22

Case IICase IIS

am

ple

Cases

Sam

ple

Cases

Colonoscopy: Tumor at rectum, patient referred to surgical intervention

PillCam: Large rectal neoplastic mass

PillCam images

23

Case IIICase III

PillCam imageColonoscopy image

Colonoscopy:• 8 mm polyp at sigmoid• 5 mm polyp at transversePillCam:• 6-9 mm polyp at sigmoid

Sam

ple

Cases

Sam

ple

Cases

24

PillCam images

Case VICase VI

Colonoscopy: Normal

PillCam: Two polyps (<6 mm) at descending colon

Sam

ple

Cases

Sam

ple

Cases

25

Polyp Findings of Capsule COLON Endoscopy Polyp Findings of Capsule COLON Endoscopy (CCE) and Traditional Colonoscopy(CCE) and Traditional Colonoscopy

*

CCE identified 19 of 25 patients (76%) with positive findings CCE identified 10 of 13 patients (77%) with significant lesions* 2 tumors were detected by both methods

26

Findings of Capsule COLON Endoscopy (CCE) vs. Findings of Capsule COLON Endoscopy (CCE) vs. Traditional ColonoscopyTraditional Colonoscopy

Polyps > 6 mm

Polyps > 6 mm or ≥ 3 polyps

Any kind of polyps

Sens Spec PPV NPV

% 76% 64% 83% 54%

95% CI, % 59-93 35-92 67-98 27-81

% 77% 71% 59% 84%

95% CI, % 54-100 41-88 35-82 68-100

% 60% 73% 46% 83%

95% CI, % 30-90 56-90 19-73 67-98