Genzyme Corporation - library.corporate-ir.netlibrary.corporate-ir.net/library/89/892/89274/items/292385/Section... · These presentations contain forward-looking statements regarding

Genzyme Corporation

Investor & Analyst Day

May 7, 2008 Analyst Day

2

Agenda

Welcome and safe harbor P. FlaniganOpening comments H. TermeerResearch & Development R. GregoryManufacturing M. BamforthLSDs D. MeekerQ&A for first session presentersRenal J. ButlerOncology M. Enyedy

Biosurgery A. Merrifield

Q&A for second session presenters Break

Transplant J. Lobacki

Alemtuzumab - MS T. MurdockMipomersen J. GeraghtyFinance M. WyzgaQ&A for third session presentersConcluding comments H. Termeer

1:00 1:05

1:15 1:301:30 1:401:40 2:152:15 2:30

1:05 1:15

2:30 2:552:55 3:103:10 3:253:25 3:403:40 3:503:50 4:054:05 4:204:20 4:304:30 4:404:40 4:554:55 5:05

p.m.

3

Forward-Looking Statement

These presentations contain forward-looking statements regarding Genzymes financial outlook and business plans and strategies, including without limitation its: anticipated EPS and revenue CAGR through 2011; 2008 and 2011 EPS guidance; forecasted tax rate through 2011; plans to seek regulatory approvals of existing products for use in new indications and new geographies, including Clolar for MDS and adult AML,

Renvela for CKD, alemtuzumab for MS, Campath and Sepra, the timetables therefore and the impact of such approvals on the company; plans and estimated timetables for new and next-generation product filings, approvals and launches, including for Synvisc-ONE, Mozobil,

mipomersen, Genz-112638 and GC1008, and the assessment of the market potential of such products; expectations for Myozyme regulatory filings and actions; projected Renal revenues through 2012; projected Oncology revenues for 2008 and Oncology and Biosurgery revenue CAGR through 2011; expectations for Thymoglobulin manufacturing and supply; Phase 2 and 3 clinical trials planned for 2008; and drivers of future growth.

These statements are subject to risks and uncertainties that could cause actual results to differ materially from those forecasted. These risks and uncertainties include, among others, Genzymes ability to: successfully complete preclinical and clinical development of its products, including Mozobil, alemtuzumab-MS, and Genz-112638; expand the use of current and next-generation products in existing and new indications and geographies, including Renvela, Synvisc-ONE and

Clolar; obtain and maintain regulatory approvals for products and manufacturing facilities, including Myozyme produced at the 2000L scale in the US and

at the 4000L scale in Europe and the timing of receipt of such approvals; manufacture its products, including Thymoglobulin and its LSD therapies in a timely and cost effective manner and in sufficient quantities to meet

demand; continue to successfully acquire and collaborate on new programs, including finalizing the license of mipomersen from Isis; and the risks and uncertainties described in Genzyme's SEC reports filed under the Securities Exchange Act of 1934, including the factors

discussed under the caption "Risk Factors" in Genzyme's 2007 Annual Report on Form 10-K. Genzyme cautions investors not to place substantial reliance on the forward-looking statements contained in these presentations. These statements speak only as of todays date (except financial guidance, which was last updated April 21st) and Genzyme undertakes no obligation to update or revise the statements.

Opening Comments

Henri Termeer, Chairman, CEO, President


5

Our Focus

Committed topatients.

Committed to delivering

strong, sustainable growth.

6

A Clear Financial Commitment

5-year Non-GAAP EPS CAGR(2006 to 2011E) 20%

2008E Non-GAAP EPS $3.90

2011E Non-GAAP EPS $7.00

7

World Class Global Capabilities

Improving the healthcare of >1,000,000 patients per year

Research &Development3 major centersof excellence

Manufacturing

12 facilities

Selling &Marketing

~90 countries

8

Most Prescribed Products by Indication

8

PRODUCT INDICATION RANKING

Cerezyme Gaucher disease Number 1

Fabrazyme Fabry disease Number 1

Aldurazyme MPS-1 disease Number 1

Myozyme Pompe disease Number 1

Renagel Hyperphosphatemia Number 1

Synvisc Osteoarthritis pain of the knee Number 1

Seprafilm Adhesion barrier Number 1

Carticel Repair of symptomatic, cartilage defects Number 1of the femoral condyle

Epicel Skin graft for deep dermal/full Number 1thickness burns

Thymoglobulin Solid organ transplant rejection Number 1

Thyrogen Therapeutic: adjunct to radioactive iodine Number 1to ablate thyroid remnantsDiagnostic: adjunct to detect recurringthyroid cancer

Clolar Relapsed/refractory pediatric ALL Number 1

Twelveno. 1

products

9

24 Phase 2 Trials Underway or Planned for the Next 12 Months

SeprasprayOBGYN Surgery

CholestagelElevated Cholesterol

rhASM*Niemann-Pick

ClolarPediatric ALL

GC-1008*Melanoma

ThymoglobulinMyelodysplastic

Syndrome

SeprasprayAbdominal Surgery

TSHGoiter

GENZ-112638Gaucher Disease

Clolar*High Risk Pediatric

ALL

GC-1008*Combination Trial in

Cancer

Mozobil*Bone Marrow

Transplantation

AAV-NTNParkinsons Disease

GC-1008*Liver Fibrosis

AlemtuzumabMultiple Sclerosis

Clolar1st-Line Adult AML

GENZ-644470*Hyperphosphatemia

Mozobil2nd-line BMT

HIF1-alpha Peripheral Artery

Disease

GC-1008*Idiopathic Pulmonary

Fibrosis

Campath2nd-Line CLL

Clolar (oral)Myelodysplastic

Syndrome

Hectorol*Psoriasis

Mozobil*Chemosensitization

CLL

*Trials planned to begin over the next 12 months

10

8 Phase 3 Programs Underway or Planned for the Next 12 Months

1. MACI vs. Microfracture2. GENZ-112638 Program for Gaucher Disease*

Treatment nave Maintenance

3. Alemtuzumab Program for Multiple Sclerosis Treatment naive Treatment experienced

4. Campath + Fludarabine for 2nd-line Chronic Lymphocytic Leukemia5. Clolar for Relapsed/Refractory Adult Acute Myelogenous Leukemia6. Clolar for Myelodysplastic Syndrome*7. Mipomersen for hypercholesterolemia

Homozygous familial hypercholesterolemia High-risk hypercholesterolemia*

8. Fabrazyme Early Intervention (FIELD trial)*

*Programs planned to begin over the next 12 months

11

13 Approvals Expected Through 2012

Myozyme manufacturing (2000L in the US)

Synvisc-One for osteoarthritic pain

Synvisc in Japan for osteoarthritic pain

Alemtuzumab for multiple sclerosis

Mipomersen for HoFH

GENZ-112638

Campath in combination with Fludarabine for 2nd-line CLL

Mozobil for BMT

Clolar for adult AML

Myozyme manufacturing (4000L in Europe)

Renvela in the US for CKD

Renvela in Europe for Dialysis and pre-dialysis

SepraSpray in Europe

2008 2009 2010-2012

22 New

6 New

5 New8

13Total cumulative approvals

12

Sustainable Revenue Growth

In millions

$0

$1,000

$2,000

$3,000

$4,000

$5,000

$6,000

$7,000

02 03 04 05 06 07 08E 09E 10E 11E

Transplant

Biosurgery

Renal

Other1

LSDs

Genetics / Dx

Includes currently marketed products and follow on products (Synvisc/Synvisc-One, Renagel/Renvela) plus Mozobil. 1Includes Oncology and Thyrogen

Early R&D: A Driver of Sustainable Growth

Richard J. Gregory, Ph.D., Sr. Vice President


14

Agenda

Genzyme R&D today Structure, approach, core competencies and focus areas

Early R&D pipeline 3 brief examples

Summary

15

Genzyme R&D Clear Focus

Genetics/Diagnostics

Science OperationsBMRA Biomedical &

Regulatory Affairs

Genzyme R&D(~2,000 FTE)

Primary responsibility forearly R&D of therapeutics

16

Genzyme Science: An Engine of Productivity

845 employees

1/3 with advanced degree (Ph.D., M.D., D.V.M.)

Network of active external collaborations around the world Expanding our reach Building relationships

Named a top employer by Science magazine for the last five years

Genzyme awarded the National Medal of Technology

17

First Class Research Facilities

FraminghamCenter of Excellence for rProteins, Cell Therapy

& Gene Therapy

ExpansionComplete 2008

WalthamCenter of Excellence for

Small Molecule, Polymer and Biomaterials R&D

ExpansionCompleted 2006

Cambridge UKCenter of Excellence for

Humanized mAbs

Opened 2004

18

Beijing Expansion Planned for 2010

19

The Broadest Array of Technology Platforms in the Industry

47%rProtein & Ab

13%Gene Therapy

3%Cell Therapy

28%Small Molecule

5%Therapeutic

Polymer4%

Biomaterial

R&D Investment by Platform

20

Early R&D Drives New Product DevelopmentTherapeutic Portfolios

25%Renal/MineralMetabolism

25%Oncology

13%IMD/Transplant

10%Orthopaedics &

Biosurgery

6%Cardiovascular 21%

Genetic Disease& Neurology

21

Robust Early R&D Pipeline

Pre-clinical or early clinical development programs

Phase 2 trials underway or planned to begin over the next 12 months

Percent of Genzymes current products and clinical development programs entering pipeline at research phase

48

24

50%

22

Agenda

Genzyme R&D today Structure, approach, core competencies and focus areas

Early R&D pipeline 3 brief examples

Summary

23

MarketedProductsDiscovery

PreclinicalResearch

PreclinicalDevelopment Pivotals

ClinicalResearch

Internally Originated Discovery Programs

Preclinical Candidates

Drugs inClinic

Marketed Drugs

Clinical Candidates

Drugs inClinic

Marketed Drugs

Genzyme R&D Our Mission

DISCOVERINSIDE:

DISCOVER OUTSIDE OPPORTUNITIES:

DISCOVERMORE:

24

DISCOVER INSIDE TGF- Antagonism to Inhibit Post-MI Pathologic Remodeling

Infiltration of inflammatory cells

TGF- upregulationsuppresses inflammation

TGF- activation of r-SMAD contributes to ECM deposition and scarring

Adapted from Frangogiannis et. al. Cardiovasc Res (2007)

I/R

Inflammation(day 0-3)

Remodeling(day 3-5 )

Infarctarea

Optimaltiming

25

Reduced Infarct Size & Improved Regional Function with Anti-TGF-

0

1

2

3

4

5

6

7

8

% LV Fibrosis/total LV (g)

1D11-D3 n=111D11-D5 n=1513C4 n=10Vehicle n=11

Reduced Infarct Size Improved Wall Motion

Normal

Vehicle 13C4 1D11-3d 1D11-5d0

0.2

0.4

0.6

0.8

1.0

1.2

AWM/PWM

26

DISCOVER OUTSIDE Leveraging Internal Capabilities

Genzyme Gene Therapy

17 clinical studies completed or in progress

Current R&D programs Genetic diseases Peripheral vascular disease Macular degeneration Neuroscience

World-class manufacturing Pilot facility in Framingham 60,000 sq ft facility in San Diego

Strong intellectual property position Adenoviral, AAV, non-viral vectors

A magnet for external opportunities

27

L-Tyrosine L-Dopa DopamineTH AADC

Hypothesis (Bankiewicz/UCSF): Loss of response to L-Dopa in Late disease is driven by lack of enzyme

(AADC) that converts L-DOPA to dopamine

DISCOVER OUTSIDE AADC Gene Therapy for Parkinsons Disease

28

post postpre

AAV-Lac-Z

pre

AAV-AADC

K. Bankiewicz et al Molecular Therapy Vol 14, 564-570 (2006)

DISCOVER OUTSIDE AADC Gene Therapy for Parkinsons Disease

Excellent proof of concept data in primates >6 years expression from single treatment Significant functional improvement and responsiveness to L-Dopa

AAV-AADC project integrated from Avigen Currently in a Phase 1 trial (M. Aminoff / UCSF) Phase 2 studies with AAV-NTN in earlier stage Parkinsons are being

conducted in partnership with Ceregene; data expected in H1:09

29

DISCOVER MORE Campath & CXCR4 Antagonists

Leukemic cells home to the bone marrow and are retained there by mechanisms similar to those used by stem cells including CXCR4/SDF-1 interactions

Malignant cells within the bone marrow niche are resistant to therapy

Pro-survival signals from marrow stromal cells

Drugs which disrupt the CXCR4/SDF-1 interaction should mobilize malignant cells and potentially increase their susceptibility to therapy

30

Start treatment Stop treatment

B104 Disseminated Lymphoma Tumor Model

Kaplan Meier Survival

DISCOVER MORE Synergy Between Campath and CXCR4 Inhibition

Bill Siders, Yanping Hu, Matt Gale

0 10 20 30 40 50 60 70 800

25

50

75

100

Days post tumor cell injection

Percentsurvival

Campath vs. Campath/AMD p=0.0331

MS(days)

Untreated 24Campath 30AMD3465 29Campath/AMD(5mg/kg) 54Campath/AMD(1mg/kg) 54

31

S U M M A R Y:

R&D, A Driver of Sustainable Growth

Broad technology base

Strong R&D activities in focused areas

Outstanding track record of product development and approvals

Merging genetics, diagnostics and therapeutic development to deliver on the promise of personalized medicine

Delivering transformative therapies to patients with serious disease

Operations: Supporting Sustainable Growth

Mark Bamforth, Sr. Vice President


33

Agenda

Strategic role of operations

Building capacity for the future

Leveraging operations

34

Buildcapacity &capabilities

Developnewproducts

Supplyapprovedproducts

Leverage Through Operational Excellence

Improving the healthcare of ~1M patients

35

Powerful, Broad Technology Base

Biologics Protein Therapies Monoclonal Antibodies Polyclonal Antibodies Gene Therapy

Synthetic Chemistry Polymer Therapeutics Small Molecule Therapeutics

Biomaterials, Devices & Cell Therapy Human Cell Therapy Biomaterial-based Devices Bulk Biomaterials

Diagnostics Products and Services Intermediates, Reagents & Rapid Tests Reproductive and Oncology Diagnostics

Genzymes high level of technical expertise provides great flexibility

36

Biomaterials, Devices,Cell TherapySynthetic MoleculesBiologics

Manufacturing a Broad Range of Products

Cerezyme Fabrazyme Myozyme Aldurazyme Thyrogen Campath Thymoglobulin

Renagel Renvela Cholestagel Clolar Hectorol

Synvisc Synvisc-ONE Seprafilm Bulk HA Carticel MACI Epicel

37

Biologics Manufacturing

Allston Landing, Boston, MABulk Biologics, Fill & Finish

Framingham, MABulk Biologics

Lyon, FranceBulk Polyclonal Antibodies

Geel, BelgiumBulk Biologics

Waterford, IrelandSolid Oral Dosage, Fill & Finish

San Diego, CAGene Therapy

38

Synthetic Molecule Manufacturing

Liestal, SwitzerlandChemical Synthesis

Haverhill, UKChemical Synthesis, Final Product Distribution


39

Biomaterials & Device Manufacturing

Framingham, MABiomaterials & Devices

Ridgefield, NJBiomaterials & Devices, Fill & Finish

40

Cell Therapy Manufacturing

Sidney St, Cambridge, MACell Therapy

Perth, AustraliaCell Therapy

Copenhagen, DenmarkCell Therapy Beijing, China

Cell Therapy, R&D Center(2010E)

41

Balancing Risk with Manufacturing

Sidney St, Cambridge, MACell Therapy

Perth, AustraliaCell Therapy

Copenhagen, DenmarkCell Therapy

Beijing, ChinaCell Therapy, R&D Center

(2010E)


Ridgefield, NJBiomaterials & Devices, Fill & Finish

Framingham, MABiomaterials & Devices

Liestal, SwitzerlandChemical Synthesis

Haverhill, UKChemical Synthesis, Final Product Distribution

Allston Landing, Boston, MABulk Biologics, Fill & Finish

Framingham, MABulk Biologics

Lyon, FranceBulk Polyclonal Antibodies

Geel, BelgiumBulk Biologics

San Diego, CAGene Therapy

42

Agenda




43

Demonstrated Ability to Grow

Commercial Products Supplied

9 1012

14 15

18 19

44

Investing Today for Future Supply

$0

$50

$100

$150

$200

$250

$300

$350

$400

2002 2003 2004 2005 2006 2007 2008E

Manufacturing Capital Investments ($M)

45

Investing in ERT Supply

Note: Aldurazyme and Elaprase are supplied by partner companies

9,000L13,000L

21,000L25,000L

29,000L

Pre-2004 2004 2009E 2011E 2012E

ProductsCerezymeFabrazyme Myozyme

Capacity Development(perfusion cell culture)

Current Supply~5,000 patients~2,000 patients~1,000 patients

from ~13,000L of perfusion capacity

46

3 45

7

10

Pre-2008 2008 2009E 2011E 2012E

Capacity Development(purification product lots per week)

Investing in Thymoglobulin Supply

ProductsThymoglobulin

Current Supply~45,000 patients

Planned Capacity110,000 patients

47

Products

75

350

650760

950

Pre-2001 2001 2003 2008E 2009E

Capacity Development(metric tons of polymer capacity per annum)

Investing in Phosphate Binder Supply

RenagelRenvela

Current Supply~350,000 patients

combined

Planned Capacity>1,000,000 patients

combined

48

Agenda




49

Leveraging Investments in Operations

Genzyme Product Gross Margin (%)

2002A 2003A 2004A 2005A 2006A 2007A 2008E 2011E

Leverage from past investments and

increased utilization

Start-up of new facilities and product mix changes

Forecast increased leverage by 1-2%

50

S U M M A R Y:

Clear Manufacturing Strategy

Ensuring the supply of safe, high quality products to patients globally

Investing in capacity to meet future growth in demand

Continuously improving operational efficiency to improve margins

Lysosomal Storage DiseaseContinued Strong Growth

David P. Meeker MD, President


52

Strong Revenue Growth

Aldurazyme @ 100%

Four innovative therapies

Myozyme

Aldurazyme

Fabrazyme

Cerezyme

Other

$M

2000 2001 2002 2003 2004 2005 2006 2007

$539 $578$646

$833

$1,094

$1,321$1,523

$1,891

CAGR = 20%

53

Agenda

Myozyme a successful global launch

Fabrazyme untapped potential

Cerezyme a remarkable story

54

Myozyme: Our Most Successful Launch

900 Plus Patients on Therapy

*Reflects the first full fiscal year after launch

$M

$100M

$200M

$300M

0 1 year* 2 year 3 year

Aldurazyme

Fabrazyme

CerezymeMyozyme

55

Myozyme Treatment Effect

Week 12 Week 78

31 Year Old First Symptoms at Age 23

56

Myozyme: Building A Global Franchise

Revenues (Approvals & NPB) Additional Presence (direct & distributors)Approvals

Approved in 42 countries

57

US Myozyme Regulatory Update

Material from 160L and 2000L processes is different

BLA to be filed on 2000L using LOTS results

Action expected by YE:08E with product available Q1:09E

MTAP program (~140 patients) closed to new patients

4000L scale up ongoing with European filing planned for Q4:08E

58

Growth: The Late Onset Population

* Infants defined as

59

Undiagnosed Pools of Patients

Kishnani, Bali DUMC; personal communication

Limb Girdle Dystrophy Elevated CK Levels

Clinical diagnosis

17 subtypes

Signs mimic Pompe

Samples tested at Duke from patients

with weakness:

Age>3 (n=303)

52 (17%) Pompe+

104 subjects, high CK, no signs of muscle disease

7 (6.7%) with confirmed Pompe Disease

BiochemicalDiagnosis

60

Late Onset Treatment Study (LOTS)

90 patients

2:1 randomization

18-month follow up

Co-primary endpoints: 6 minute walk test (6MWT) and forced vital capacity (FVC)

61

Baseline Patient Demographics

Total

Age at 1st symptoms mean yrs (SD) 28 (12%)

Age at Diagnosis mean yrs (SD) 35 (13%)

Ventilator Use (%) 31 (34%)

Time since 1st Ventilator Use - mean yrs (SD) 4.1 (4%)

Walking Device Use (%) 39 (43%)

62

Significant Improvement in 6 Minute Walk Test

-5

0

5

10

15

20

25

30

35

0 10 20 30 40 50 60 70 80 90

ANCOVA p-value = 0.0347WMW p-value = 0.0283

Myozyme

Placebo

Weeks from Baseline

Change in Mean Distance

Walked(Meters)

63

Significant Improvement in FVC

-5

-4

-3

-2

-1

0

1

2

3

4

5

0 10 20 30 40 50 60 70 80 90

ANCOVA p-value = 0.0055WMW p-value = 0.0026

Change in Mean %

Predicted

Weeks from Baseline

Myozyme

Placebo

64

LOTS Safety Data Are Consistentwith Previous Studies

AE 39 (100.0%)

IAR 22 (56.4%)

SAE 37 (94.9%)

Death 6 (15.4%)

Seroconversion 35 (92.0%)

Studies 1602, 2403, 1702 (160L) 39 patients

60 (100.0%)

17 (28.3%)

13 (21.7%)

1 (3.3%)

59 (100.0%)

30 (100.0%)

7 (23.3%)

6 (20.0%)

0 (0%)

Myozyme Placebo

LOTS (2000L) 90 patients

65

The Role for Newborn Screening

Early Intervention Optimal Outcomes

66

Genzymes Role in NBS for LSDs

Supporting technology invention, development and dissemination

Partnership with CDC Foundation to provide reagents to NBS laboratories without charge

Available for Pompe disease, Fabry disease, Gaucher disease, andNiemann-Pick A/B since Jan. 2008

Continuing work on MPS I, MPS II, MPS VI, and MLD

67

Legislative Update

IL SB1566 signed November 5, 2007 Provide all newborns with expanded screening tests for the presence of

certain LSDs known as Krabbe, Pompe, Gaucher, Fabry, and Niemann-Pick Goal - within 3 years after the effective date

SACHDGCNC (Secretarys advisory committee on heritable disorders and genetic diseases in newborns and children)

Pompe disease has been nominated for inclusion in the newborn screening uniform panel

Advisory board moved Pompe disease to the evidence review committee

68

Improvednewbornscreening

Future of NBS for LSDs

NBS panels will continue to grow / change

Under evaluation in many countries

20+ newborn screening labs are establishing LSD NBS methods

Early diagnosis and intervention may make a significant difference in patient outcomes

69

Global NBS Initiatives for Pompe

Pilot program at National Taiwan University Hospital newborn screening lab identified 6 newborns out of 206,088 screened

6/6 had normal muscle tone and strength 5/6 had cardiomyopathy All on Myozyme

70

The Advantage of Early Diagnosis

At Diagnosis Normal muscle tone and strength At 20 m Cardiomegaly improved, good head control, walks

Diagnostic EKG

Diagnostic x-ray After 3 m of Myozyme Before first dose @ 29 d After 6 m of Myozyme

Before first dose @ 29 d After 6 m of Myozyme

Muscle biopsies

HE

stai

nPA

S st

ain

Chest x-raysBEFORE AFTER BEFORE AFTER

71

Agenda




72

Strong Growth Since Launch

2003 2004 2005 2006 2007

$81

$210

$305$359

$424CAGR = 51%

$M

73

Fabry NBS (What Is the Incidence?)

Pilot study in Torino, Italy (Amer J Hum Gen 79:2006) 12 Fabry disease patients in 37,104 screened

Pilot study at National Taiwan University Hospital 9 Fabry disease patients in 137,592 screened

1 Patient 5 affected family members

74

The Family Reunion

75

>40 Members Affected

76

Putting It All Together

Damage fibrosis

Natural history

Goals of therapy

Management paradigm

77

Clinical Condition

Fabry Disease Progression

Cellular GL-3 storage

TissueInvolvement

OrganFailure

ClinicalDisease

Sub-clinicalDisease

Pure Fabry

Complicated Fabry

Fibrosis.?

Burden of Disease

Time

78

Baseline Biopsy(Age 48)

Baseline Biopsy(Age 18)

Phase 3 Fabrazyme trial

Renal Fibrosis Occurs Earlyand Increases with Age

Tubular atrophy and interstitial scarring

Globally sclerosed glomerulusNo glomerulosclerosis

No interstitial scarringNo tubular atrophy

79

Renal Fibrosis Starts Early

20 21-25 26-30 31-35 >35

36%50%

80%

83%92%

n=11 n=8 n=6 n=6 n=13

Thurburg B, Oral Presentation, WORLD, 2008

Average age of ERT initiation: 35 years

Percent of patients affected with FSGS +/or GS

80

Cardiac Fibrosis

European Heart Journal doi:10.1093/eurheartj/ehi143

81Note: 25 composite events based on 82 patients.

Importance of Early Intervention:Phase 4 Fabrazyme Data

Placebo13 Events (42%)

0 5 10 15 20 25 30 35 40

Event Rate (%)

Time in Study (Months)

0%

10%

20%

30%

40%

50%

60%

Fabrazyme12 Events (24%)

82

What Is the Role of Biomarkers?

To select the right dosefor the patient

83

Optimal Biomarker: Correlates with Changes in Disease Activity

Plasma GL 3 Reduction is necessary but not sufficient Rapidly normalizes with 1 mg/kg of Fabrazyme Reduction is dose dependent

Urinary GL 3 Variable measure: Assay-Collection No clinical correlation with renal function = shed

cells in the urine Reasonable marker of enzyme activity

within the same patient

We do not have a good biomarker for clinical activity

84

What Have We Learned about Dose?

0.2mg/kg Including head to head trial in the Netherlands

0.3mg/kg Phase 1 / 2 Maintenance trial 1mg/kg followed by 0.3 mg/kg

1mg/kg

Antibodies?

Key: Measure antibodies in a standardized assay

85

Effect of Fabrazyme Dose on Plasma GL-3 Clearance

Plasma GL-3 concentrations were reduced in a dose-dependent manner in three dose regimens evaluated

Phase 1/2 Fabrazyme trial

86

Plasma GL-3: Peak IgG titers (n=20)

0.0

2.0

4.0

6.0

8.0

10.0

12.0

14.0

16.0

0 6 12 18 24 30 36 42 48 54 60 66 72 78 84 90 96

Pla

sma

GL-

3

Weeks

Plasma GL-3

Neg

Medium

High

Negative Titer < 6400 Titer 6400N = 3 N = 11 N = 7

0.3 mg1 mg

87

Replagal & Antibody Formation

FDA Briefing Document

88

Fabrazyme 0.2mg/kg & Replagal 0.2mg/kgUrinary GL 3 in IgG-positive and IgG-negative patients

Treatment, months

Urinary CTH,mmol/s4hr

0

1000

2000

3000

4000

0 6

ULN

IgG negative IgG positive

89

Evolving Disease Management Paradigm

Monitor Organ specific examinations Monitor antibody status and available biomarkers

Early fibrosis Treat early

Established disease Full dose

Early with no organ damage Possibility for dose individualization?

90

Intervening Early with a Lower Dose

FIELD STUDY (0.5 mg/kg) Objective: treat at first indication of active disease We know what to monitor

Critical organs Antibody status Biomarkers

Convenience and economic benefit

FIELD Study

5 Year Trial

Fabrazyme 0.5 mg/kg q2w

Fabrazyme 1.0 mg/kg q4w

91

Agenda




92

A Remarkable Therapy

93

Solid Consistent Growth

$M

2003 2004 2005 2006 2007

$739$839

$932$1,007

$1,133CAGR = 11%

94

Robust Registry Continues

448672 897

1,149 1,3601,694 1,848

2,0432,397

2,6612,906

3,3373,815

4,2724,572

4,882 5,004

1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 Mar-08

Patient #5,000 enrolled in China 19 peer-reviewed publications submitted or published from registry data

Patients Enrolled in ICGG Gaucher Registry

95

Where Is the Unmet Need?

Convenience

Central Nervous System

96

Dosing Convenience (Q2/Q4 Study)

A multicenter, randomized, dose frequency study 102 patients

Candidate population: Patients who have achieved therapeutic goals and are clinically stable Cerezyme therapy for 2 years at 20 to 60 U/kg/Q2

Management paradigm: Individualize dose and dosing frequency Decision based on regular comprehensive monitoring

97

Success Achieving Therapeutic Goals

0

20

40

60

80

100

12 months 24 months

Cerezyme every 2 weeks Cerezyme every 4 weeks

Oral Presentation, WORLD, 2008

88%

98

The Future: Genz-112638

Phase 2 open-label, international trial 26 adults with Gaucher disease Type I Dose: 50 or 100 mg by mouth twice daily Study status: on-going; completely enrolled

Evaluate safety, efficacy and pharmacokinetics

Duration: 1 year Followed by Extension study

99

Phase 2 Overview

25 patients treated 26 weeks: 21 patients 52 weeks: 13 patients

Baseline characteristics Ages 18-55 years 7 males, 10 females All Caucasian; 4 Jewish-Ashkenazi

Mean (Range)Hemoglobin 11 g/dL (8.1-14.6)

Platelets 69,740/mm3 (45,500 -114,000)

Spleen 19.9 MN (8.2-59.7 MN)

100

Reduction in Plasma GL-1

Mean Plasma GL-1ug/mL

3.6 ug/mL 2.8 ug/mL NormalRange

Baselinen=25

Week 26n=21

Study Visit

Week 52n=12

101

Reduction in Spleen Volume

Mean % Change from BL in MN Spleen Volume

- 27%

- 40%

Baselinen=25

Week 26n=21

Week 52n=11

Study Visit

102

Increase in Hemoglobin Level

Mean Change fromBaseline (g/dL)

0.9 g/dL

1.3 g/dL

Baselinen=25

Week 26n=17

Week 52n=13

Study Visit

103

Increase in Platelet Count

18%

34%

Baselinen=21

Week 26n=17

Week 52n=13

Study Visit

Mean %Change

104

Reduction in Chitotriosidase

-30%

-50%

Mean %Change

Baselinen=26

Week 26n=20

Week 52n=12

Study Visit

105

Preliminary Safety Data

Acceptable safety profile as of April 9, 2008 (n=26)

7 related adverse events reported in 6 patients All mild and transient Diarrhea (2), abdominal cramps (2), headache, palpitations and

asymptomatic NSVT

6 patients have been withdrawn Pregnancy (3) NSVT (2) Osteonecrosis progression by MRI

106

Next Steps

Complete Phase 2 study

QT study ongoing

Phase 3 program to begin H1:09E Treatment-nave study Maintenance study in Cerezyme

treated patients

AdvancingProgram

107

S U MM A R Y:

Meeting the Unmet Medical Need Globally

Cerezyme registered

Cerezyme available(named basis; Genzyme sponsored charitable programs)

108

S U MM A R Y:

Growth Set to Continue

Myozyme: Early in launch

Fabrazyme: Later but significant untapped potential

Cerezyme: The gold standard

GENZ-112638: A meaningful choice

109

Question and Answer

Moderator:

Geoff McDonough, M.D., Sr. Vice President and General Manager, LSDs

Panel:

Rich Gregory, Ph.D., Sr. Vice President, Head of Research

Mark Bamforth, Sr. Vice President, Operations

David Meeker, M.D., President, LSDs

Joan Keutzer, Ph.D., Vice President, Scientific Affairs

Genzyme CorporationInvestor & Analyst DayAgendaForward-Looking StatementOpening CommentsHenri Termeer, Chairman, CEO, PresidentOur FocusA Clear Financial CommitmentWorld Class Global CapabilitiesMost Prescribed Products by Indication24 Phase 2 Trials Underway or Planned for the Next 12 Months8 Phase 3 Programs Underway or Planned for the Next 12 Months13 Approvals Expected Through 2012Sustainable Revenue GrowthEarly R&D: A Driver of Sustainable GrowthRichard J. Gregory, Ph.D., Sr. Vice PresidentAgendaGenzyme R&D Clear FocusGenzyme Science: An Engine of ProductivityFirst Class Research FacilitiesBeijing Expansion Planned for 2010The Broadest Array of Technology Platforms in the IndustryEarly R&D Drives New Product DevelopmentRobust Early R&D Pipeline AgendaGenzyme R&D Our MissionDISCOVER INSIDE TGF-b Antagonism to Inhibit Post-MI Pathologic RemodelingReduced Infarct Size & Improved Regional Function with Anti-TGF-bDISCOVER OUTSIDE Leveraging Internal CapabilitiesDISCOVER OUTSIDE AADC Gene Therapy for Parkinsons DiseaseDISCOVER OUTSIDE AADC Gene Therapy for Parkinsons DiseaseDISCOVER MORE Campath & CXCR4 AntagonistsDISCOVER MORE Synergy Between Campath and CXCR4 InhibitionS U M M A R Y:R&D, A Driver of Sustainable GrowthOperations: Supporting Sustainable GrowthMark Bamforth, Sr. Vice PresidentAgendaLeverage Through Operational ExcellencePowerful, Broad Technology Base Manufacturing a Broad Range of ProductsBiologics ManufacturingSynthetic Molecule ManufacturingBiomaterials & Device ManufacturingCell Therapy ManufacturingBalancing Risk with ManufacturingAgendaDemonstrated Ability to GrowInvesting Today for Future SupplyInvesting in ERT SupplyInvesting in Thymoglobulin SupplyInvesting in Phosphate Binder SupplyAgendaLeveraging Investments in OperationsS U M M A R Y:Clear Manufacturing StrategyLysosomal Storage DiseaseContinued Strong Growth David P. Meeker MD, PresidentStrong Revenue GrowthAgendaMyozyme: Our Most Successful LaunchMyozyme Treatment EffectMyozyme: Building A Global FranchiseUS Myozyme Regulatory Update Growth: The Late Onset PopulationUndiagnosed Pools of PatientsLate Onset Treatment Study (LOTS)Baseline Patient DemographicsSignificant Improvement in 6 Minute Walk TestSignificant Improvement in FVCLOTS Safety Data Are Consistentwith Previous StudiesThe Role for Newborn ScreeningGenzymes Role in NBS for LSDsLegislative UpdateFuture of NBS for LSDsGlobal NBS Initiatives for PompeThe Advantage of Early DiagnosisAgendaStrong Growth Since LaunchFabry NBS (What Is the Incidence?)The Family Reunion>40 Members AffectedPutting It All TogetherFabry Disease ProgressionRenal Fibrosis Occurs Earlyand Increases with AgeRenal Fibrosis Starts EarlyCardiac FibrosisImportance of Early Intervention:Phase 4 Fabrazyme DataWhat Is the Role of Biomarkers?Optimal Biomarker: Correlates with Changes in Disease ActivityWhat Have We Learned about Dose? Effect of Fabrazyme Dose on Plasma GL-3 ClearancePlasma GL-3: Peak IgG titers (n=20)Replagal & Antibody FormationFabrazyme 0.2mg/kg & Replagal 0.2mg/kgUrinary GL 3 in IgG-positive and IgG-negative patientsEvolving Disease Management ParadigmIntervening Early with a Lower Dose AgendaA Remarkable TherapySolid Consistent Growth Robust Registry Continues Where Is the Unmet Need?Dosing Convenience (Q2/Q4 Study)Success Achieving Therapeutic GoalsThe Future: Genz-112638Phase 2 OverviewReduction in Plasma GL-1Reduction in Spleen VolumeIncrease in Hemoglobin Level Increase in Platelet Count Reduction in ChitotriosidasePreliminary Safety DataNext Steps S U M M A R Y:Meeting the Unmet Medical Need Globally S U M M A R Y:Growth Set to ContinueQuestion and Answer

Documents

Genzyme Corporation - library.corporate-ir.netlibrary.corporate-ir.net/library/89/892/89274/items/292385/Section... · These presentations contain forward-looking statements regarding