InFUSEInFUSE™™ Bone Graft / Bone Graft /LT-CAGE LT-CAGE ™ ™ Lumbar Tapered Lumbar Tapered

Fusion DeviceFusion Device

IDE Clinical ResultsIDE Clinical ResultsG960065G960065

Hallett H. Mathews, M.D.Hallett H. Mathews, M.D.Richmond, VirginiaRichmond, Virginia

Primary study objective met Primary study objective met

High fusion ratesHigh fusion rates

Shorter operative times and less Shorter operative times and less blood lossblood loss

Avoided complications and pain Avoided complications and pain associated with bone graft harvestingassociated with bone graft harvesting

Important Findings

InFUSE™Bone Graft versus InFUSE™Bone Graft versus Autograft Harvested Autograft Harvested

from Iliac Crestfrom Iliac Crest

Clinical Trial ResultsClinical Trial Results

Clinical Trial DesignClinical Trial DesignOpen Surgical ApproachOpen Surgical Approach

Prospective, randomized controlled Prospective, randomized controlled designdesign

Investigational Treatment - Investigational Treatment - LT-CAGE LT-CAGE™ ™ Device / InFUSEDevice / InFUSE™ ™ Bone Graft Bone Graft

Control Treatment - Control Treatment - LT-CAGE LT-CAGE ™ ™ Device / autogenous boneDevice / autogenous bone

Study ObjectivesStudy Objectives

Primary Objective Primary Objective

Equivalence in Overall SuccessEquivalence in Overall Success

Secondary ObjectivesSecondary Objectives

Study Entrance CriteriaStudy Entrance Criteria

Single levelSingle level

Symptomatic degenerative disc disease Symptomatic degenerative disc disease

Inclusion/exclusion criteriaInclusion/exclusion criteria

Patient EvaluationPatient Evaluation

PreoperativelyPreoperatively

Surgery/DischargeSurgery/Discharge

Postoperatively:Postoperatively:

6 Weeks, 3 Months, 6 Months6 Weeks, 3 Months, 6 Months

12 Months, 24 Months12 Months, 24 Months

Patient PopulationPatient Population

PatientsPatients

- 143 received InFUSE™ Bone Graft- 143 received InFUSE™ Bone Graft

- 136 received autogenous bone graft- 136 received autogenous bone graft

16 Investigational Centers16 Investigational Centers

Demographic InformationDemographic Information

InFUSE™ Autograft

Age (yrs.) 43 42

Weight (lbs.) 179 181

Height (in.) 68 68

Sex (% male) 55 50Worker’s Compensation (%) 33 35Spinal Litigation (%) 33 35

Surgery DataSurgery Data

InFUSE™ Autograft

Operative Time (hrs.) 1.3 2.0

Blood Loss (ml) 110 153

Hospital Stay (days) 3.1 3.3

Study Results Based Study Results Based on 24-Month Data on 24-Month Data

Overall SuccessOverall Success

FusionFusion

15 point improvement in Oswestry score15 point improvement in Oswestry score

Neurological maintenance or Neurological maintenance or improvementimprovement

No serious adverse event possibly No serious adverse event possibly associated to the deviceassociated to the device

No second surgery failureNo second surgery failure

Overall Success Rates Overall Success Rates

58.860.856.3

59.7

0

10

20

30

40

50

60

70

80

InFUSE

Autograft

Achieved Primary ObjectiveAchieved Primary Objective

Safety OverviewSafety Overview

Adverse eventsAdverse events

Second surgery proceduresSecond surgery procedures

Antibody formationAntibody formation

Adverse EventsAdverse Events

Adverse EventsAdverse Events

InFUSE™ Autograft

Possibly Relatedto Device (%) 11.9 13.2Rated Serious (%) 7.7 8.8

At least 1 event (%) 79.0 80.1

Comparison of Adverse EventsComparison of Adverse Eventsin Investigational and Controlin Investigational and Control

Treatment GroupsTreatment Groups

Differences noted in:Differences noted in:

Graft Site Events - Graft Site Events -

Occurred in 6% of control groupOccurred in 6% of control group

None in investigational groupNone in investigational group

UrogenitalUrogenital

Resolved prior to dischargeResolved prior to discharge

Adverse EventsAdverse Events

Typical for patient populationTypical for patient population

Not unanticipatedNot unanticipated

Second Surgery ProceduresSecond Surgery Procedures

ClassificationsClassifications

RevisionsRevisions

RemovalsRemovals

Supplemental FixationsSupplemental Fixations

ReoperationsReoperations

OtherOther

ClassificationsClassifications

Revisions - FailureRevisions - Failure

Removals - FailureRemovals - Failure

Supplemental Fixations - FailureSupplemental Fixations - Failure

ReoperationsReoperations

OtherOther

Second SurgeriesSecond Surgeries

InFUSE™ Autograft

Revisions 0 (0.0) 0 (0.0)

Removals 2 (1.4) 0 (0.0)

SupplementalFixations

10 (7.0) 14 (10.3)

Reoperations 6 (4.2) 4 (2.9)

Other 31 (21.7) 28 (20.6)

Assessment of Antibody FormationAssessment of Antibody Formation

rhBMP-2

Bovine Type I Collagen

Human Type I Collagen

Comparision ofComparision ofAuthentic Positive ResponsesAuthentic Positive Responses

Similar for both groupsSimilar for both groups

One patient in each group had positive One patient in each group had positive response to rhBMP-2. (<1%)response to rhBMP-2. (<1%)

13% in each group had positive response 13% in each group had positive response to bovine Type I collagen.to bovine Type I collagen.

None of these patients had positive results None of these patients had positive results for human Type I collagen. for human Type I collagen.

Safety SummarySafety Summary

Investigational and Control group rates Investigational and Control group rates are are similarsimilar for: for:

Adverse events and second surgery Adverse events and second surgery procedures procedures

Antibody responsesAntibody responses

InFUSE™ Bone Graft eliminates InFUSE™ Bone Graft eliminates graft harvesting adverse events graft harvesting adverse events and pain and pain

InFUSE™ Bone Graft / InFUSE™ Bone Graft / LT-CAGE™ DeviceLT-CAGE™ Device

Safe for its intended useSafe for its intended use

Effectiveness OverviewEffectiveness Overview

InFUSEInFUSE™™ Bone Graft / LT-CAGE Bone Graft / LT-CAGE™™ Device Device

patients had:patients had: High fusion ratesHigh fusion rates

Pain reliefPain relief

Maintenance or improvement in Maintenance or improvement in neurological statusneurological status

FusionFusion

Primary endpointPrimary endpoint

CT scans and radiographs utilizedCT scans and radiographs utilized

Two teams of independent reviewersTwo teams of independent reviewers

Fusion CriteriaFusion Criteria

RadiographicRadiographic

- Bridging trabecular bone- Bridging trabecular bone

- Segmental stability- Segmental stability

- Lucent line criteria- Lucent line criteria

No “pseudarthrosis” second surgeryNo “pseudarthrosis” second surgery

Fusion Success Rates Fusion Success Rates

96.9 94.592.6 88.7

0102030405060708090

100

12 Months 24 Months

InFUSEAutograft

Oswestry Low Back PainOswestry Low Back PainDisability QuestionnaireDisability Questionnaire

Mean Oswestry ScoresMean Oswestry Scores

0

10

20

30

40

50

60

70

InFUSEAutograft

Oswestry Success Oswestry Success 15 Point Improvement15 Point Improvement

76.973.075.2 73.1

0

10

20

30

40

50

60

70

80

90

100

12 Months 24 Months

InFUSEAutograft

Neurological Status MeasurementsNeurological Status Measurements

Motor FunctionMotor Function

SensorySensory

ReflexesReflexes

Straight Leg RaiseStraight Leg Raise

Neurological Success Rates Neurological Success Rates

82.884.7 83.381.8

0

10

20

30

40

50

60

70

80

90

100

12 Months 24 Months

InFUSEAutograft

Secondary Effectiveness EndpointsSecondary Effectiveness Endpoints

Back painBack pain

Leg painLeg pain

Disc height maintenanceDisc height maintenance

SF-36SF-36

Back Pain Results - 24 Months Back Pain Results - 24 Months

InFUSE™ Autograft

Success Rate 74.6 % 78.7%

Mean PointImprovement 8.4 8.1

Graft Site Pain in Control PatientsGraft Site Pain in Control PatientsMean ScoresMean Scores

0

5

10

15

20

Graft Site Appearance Graft Site Appearance in Control Patients in Control Patients

12 Months 24 Months

Appearance -Fair or Poor 16.1% 16.4%

Use of InFUSE™Bone Graft Use of InFUSE™Bone Graft eliminates:eliminates:

Negatives of Graft-site Negatives of Graft-site Appearance, Pain and MorbidityAppearance, Pain and Morbidity

Laparoscopic Clinical TrialLaparoscopic Clinical Trial

Data augment safety profileData augment safety profile

Supports approval of implantation Supports approval of implantation methodmethod

Identical protocol to open studyIdentical protocol to open study

134 Investigational patients134 Investigational patients

14 Sites14 Sites

Surgery Data - LaparoscopicSurgery Data - Laparoscopic

2 days shorter hospital stay2 days shorter hospital stay

45% treated on outpatient basis45% treated on outpatient basis

Returned to work 20 days soonerReturned to work 20 days sooner

Overall Success Rates - Overall Success Rates - Laparoscopic StudyLaparoscopic Study

68.160.8

56.3

69.2

0

10

20

30

40

50

60

70

80

12 Months 24 Months

InFUSE

Autograft from OpenStudy

Safety Results - Comparable to Safety Results - Comparable to Open Surgical Treatment GroupOpen Surgical Treatment Group

Laparoscopic Versus Control Laparoscopic Versus Control 24 Months 24 Months

Fusion Equivalent

Oswestry Success Equivalent

Neurological Success Equivalent

Back Pain Equivalent

Leg Pain Equivalent

SF-36 Success Equivalent

Disc Height Success Equivalent

Fusion Success Rates - Fusion Success Rates - Laparoscopic StudyLaparoscopic Study

94.1 94.292.6 88.7

0102030405060708090

100

12 Months 24 Months

InFUSE

Autograft from OpenStudy

Case HistoriesCase Histories

Control Treatment GroupControl Treatment Group

37 year old female37 year old female

L5 - S1 LevelL5 - S1 Level

Control Treatment GroupControl Treatment Group

38 year old female38 year old female

L5 - S1 LevelL5 - S1 Level

Open Surgical Approach Open Surgical Approach InFUSE™ Treatment Group InFUSE™ Treatment Group

42 year old male42 year old male

L4 - L5 LevelL4 - L5 Level

Open Surgical Approach Open Surgical Approach InFUSE™ Treatment Group InFUSE™ Treatment Group

36 year old male36 year old male

L5 - S1 LevelL5 - S1 Level

As demonstrated in As demonstrated in animal and human studies:animal and human studies:

CT scans most practical and CT scans most practical and definitive method for detecting definitive method for detecting bone formation and determining bone formation and determining fusion.fusion.

Patient Satisfaction - 24 Months Patient Satisfaction - 24 Months

InFUSE™ Autograft

Satisfied with results ofsurgery

81.2% 80.4%

Helped as much as theythought they would be

74.6% 76.6

Would have the surgeryagain for same condition

82.0% 76.7

ConclusionsConclusionsOpen Surgical ApproachOpen Surgical Approach

Clinical TrialClinical Trial

Achieved Primary Objective - Overall Success Achieved Primary Objective - Overall Success Rate Statistically Equivalent to ControlRate Statistically Equivalent to Control

Benefits - Shorter Operative Times and Less Benefits - Shorter Operative Times and Less Blood Loss than ControlBlood Loss than Control

Important Benefits of Important Benefits of InFUSE™ Bone Graft / LT-CAGE™InFUSE™ Bone Graft / LT-CAGE™

Lumbar Tapered Fusion DeviceLumbar Tapered Fusion Device

Induces bone formationInduces bone formation

Eliminates the need to harvest autogenous Eliminates the need to harvest autogenous bone graft in spinal fusion proceduresbone graft in spinal fusion procedures

Conclusions - Laparoscopic Surgical Conclusions - Laparoscopic Surgical Approach Clinical TrialApproach Clinical Trial

Achieved Primary Objective - Overall Achieved Primary Objective - Overall Success Rate Statistically Equivalent (and Success Rate Statistically Equivalent (and Superior) to ControlSuperior) to Control

Benefits - Shorter Hospital Stays and Faster Benefits - Shorter Hospital Stays and Faster Return to WorkReturn to Work

InFUSE™ Bone Graft / LT-CAGE™InFUSE™ Bone Graft / LT-CAGE™Lumbar Tapered Fusion DeviceLumbar Tapered Fusion Device

SAFE AND EFFECTIVESAFE AND EFFECTIVE