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Halozyme Therapeutics

ANALYST AND INVESTOR MEETING
THURSDAY, OCTOBER 15, 2009 New York

Safe Harbor
The Private Securities Litigation Reform Act of 1995 provides a "safe harbor" for forward-looking statements. All safe harbor forward looking statements made in this presentation that are not statements of historical fact constitute forward-looking statements. The matters referred to in forward-looking forward looking statements could be affected by the risks and uncertainties of the Company's business. Such risks inherent to the Company s Company’s business will be described in the Company’s Company s filings, when they occur, with the Securities and Exchange Commission, as well as in its press releases. The Company s Company's actual results may differ materially from those expressed in or indicated by such forward-looking statement.

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AGENDA
Jonathan E. Lim, M.D. President & Chief Executive Officer Introduction d Strategic R i I t d ti and St t i Review Robert J. Little Vice President, Chief Commercial Officer President Leveraging the Technology Across Multiple Partners Gregory I Frost Ph D I. Frost, Ph.D. Vice President, Chief Scientific Officer Discovery and Early Development Pipeline Update Douglas B. Muchmore, M.D. Vice President, Endocrinology Clinical Development Ultrafast Insulin-PH20 Program – Where We Are Going

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Introduction & Strategic Review
Jonathan E. Lim, M.D. President & Chief Executive Officer

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Halozyme is Well Positioned to Generate Current and Future Shareholder Value
• Strong technology foundation and pipeline of commercial, partnered, and clinical stage assets with near-term value drivers – Partnerships with Roche and Baxter worth up to $724 million plus million, royalties; near term launches underway (Hylenex) and anticipated (Enhanze GAMMAGARD, Roche) – Proprietary p g p y programs in clinical development that could g p generate high g value partnerships (e.g., Phase 2 Ultrafast Insulin-PH20 Program) – Investment in high value but low-cost development activities that advance programs to next value inflection point g • Innovative biotech company with strong biologics capabilities that can help drive long-term growth – Scientific focus and expertise in the extracellular matrix (the “Matrix”) Matrix ) – Expertise in maximizing value from multifunctional Matrix platforms (rHuPH20, HTI-501, rHuMMP1ts) – C lt Culture of excellence: E f ll Exceptional t ti l team with extensive bi l i ith t i biologics experience and ability to produce complex recombinant proteins
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Strong patent protection and lifecycle lif l extension Validation through existing partnerships Diversified, robust pipeline/ portfolio

B Biologics Toolbox fo Partners T or s

Novel M Matrix Thera rapeutics

De-risked biological g programs

Halozyme’s Technology Foundation

Increased footprint in high g growth biologics market

Expedited regulatory pathway

Differentiated biologics with best-in-class potential

Differentiated Products
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Existing Alliances Drive Significant Value
Enhanze Technology with Roche (up to 13 biologic targets) • Alliance worth up to $ p $612M ($ ($20M up-front; $111M milestones for first 3 p ;$ exclusive targets; $470M up-front & milestones for 10 additional targets; $11M equity), plus royalties; $48M received to date Enhanze Technology with Baxter BioScience (GAMMAGARD)

• Alliance worth up to $47M ($10M up-front; $37M milestones), plus
royalties; $10M received to date HYLENEX with Baxter Medication Delivery • Alliance worth up to $65M ($10M up-front; $25M milestones; $10M prepaid royalties; $20M equity) plus royalties; $40M received to date equity),

Nearly $100 million of alliance related cash received to date
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Our Vision

To be the best “Matrix Company” in the world by growing our expertise in the science of the extracellular matrix to develop and commercialize meaningful new biotechnology products for patients
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Halozyme’s Robust Pipeline of Multifunctional Platforms Targeting the Matrix
Matrix Targets PH20 Depot Matrix Biologics PEGPH20 PH20 Intravesical PH20 SC

Hyaluronan

rHuCAT-L Collagen g rHuMMP1ts

Other

Other Matrix modifying y g agents

Discovery

Preclinical

Phase 1

Phase 2

Phase 3 Commercial

Development Stage
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Our First Multifunctional Enzyme Platform Targets over $10 Billion in Product Opportunities
Analog-PH20
Phase 2

Hylenex for drugs
Phase 4

Roche g Biologic#1
Phase 1

rHuPH20 Enzyme
Hylenex for fl id f fluids
Launched

Roche Biologics #2 & #3
Phase 1

InsulinPH20
Phase 2

Enhanze IgG
Phase 3

Fluids and small molecules

Peptides

Large molecules

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Culture of Excellence: “The Halo Edge” • Att ti world class bi h Attracting ld l biopharma t l t to key positions talent t k iti
– H. Michael Shepard, Ph.D., VP of Discovery Research (Receptor BioLogix, Canji, Genentech) – Jonathan Leff, M.D., VP and Chief Medical Officer (Roche, Amgen, Merck)

• ~140 employees from nearly 70 companies with competencies across the
drug development value chain, with exception of sales – Highly committed, passionate workforce that has the capabilities and experience to execute Halozyme’s plan and build a great company

• Successful track record with talent initiatives
– Offer acceptance rate was 87% last year; 60% of new employees came from internal referrals – Voluntary turnover remains less than 5% (vs. 10.5% industry average; Radford)
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With Fewer than 150 Employees, Halozyme Has Solid Biologics R&D Expertise Per Capita

Biologics Experience (Enzymes, MoAbs, Gene Rx)

Expression Systems (Mammalian, Bacterial, Viral)

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Halozyme’s Growth Strategy Can Generate Value Over Multiple Time Horizons
Value creation Develop pipeline of proprietary programs • • • • • • Analog-PH20 Insulin PH20 Insulin-PH20 PEGPH20 PH20 Depot HTI-501 rHuMMP1ts Generate value for patients and shareholders • Grow partnership and own product revenue • Other Matrix drugs • Other promising innovations

Build B ild revenue generating engine • Roche Enhanze p g programs • Enhanze GammaGard • Hylenex

Time Capabilities • PH20 drug delivery • Protein engineering • PH20 drug development • Other Matrix drug development • Commercialization in core TA’s alone or with partners • Delivery or development of other promising breakthroughs 14

HALO Pursuing Multi-Billion Dollar Franchise Opportunities Targeting the Matrix

Drug delivery revenue generating engine • Enhanze Technology with Roche (up to 13 biologic targets) • Enhanze Technology with Baxter BioScience (GAMMAGARD) • HYLENEX with Baxter Medication delivery

Proprietary pipeline targeting the Matrix • Ultrafast Insulin-PH20 (diabetes) • PEGPH20 (NME, solid tumors) • Chemophase (bladder cancer) • HTI-501 (NME, dermatology)

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Commercial Opportunities – Leveraging the Technology Across Multiple Partners
Robert J. Little Vice President, Chief Commercial Officer

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Leveraging the rHuPH20 Technology Through Drug Delivery Deals
rHuPH20 technology can be used with a broad range of injectable pharmaceutical products to improve delivery and optimize value • Technology can be applied to multiple pharmaceuticals, especially biologics, to transform them from intravenous (IV) to subcutaneous (SC) administration • Deals provide attractive non-dilutive cash through upfront, milestone, and royalty payments • Cash generated from deals helps to fund Halozyme’s proprietary pipeline

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Enhanze Technology: For Partners with Injectable Biologics and Drugs
Value proposition Increased efficacy • Deliver more drug to intended targets • Allow drugs to work faster • Increased volume of drug at each injection • Change route of administration (IV to SC) j • Reduce adverse injection site reactions • Decrease pain and tissue distortion upon injection • Provide competitive differentiation and reduce COGS • Enable cost-effective self-administration of physician delivered drugs • Extend lifecycle of products coming off patent
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Convenience and compliance

Economic benefits

Enhanze Technology Platform De-Risked Through Progress of Roche and Baxter Collaborations
• Preclinical Safety – high dose chronic and reproductive tox completed in several animal species • Product Development – numerous stable formulations of biologics with PH20 • Regulatory Affairs – U.S. and EU regulatory pathways more clarified • Clinical Development – Enhanze GAMMAGARD in pivotal Phase 3, other clinical studies underway • Manufacturing – two API manufacturing sites established, 2nd generation cell li and scale-up completed ti ll line d l l t d • Commercial – reimbursement and pricing research with partners completed

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Three Partnered Programs Based on Halozyme s Halozyme’s Drug Delivery Technology

1. 1 Enhanze Technology with Roche (up to 13 biologic targets) 2. Enhanze Technology with Baxter BioScience ( (GAMMAGARD) ) 3. HYLENEX with Baxter Medication Delivery
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Roche Enhanze Technology Alliance Moving Forward

• Three targets in Phase 1 clinical trials including third trials,
target which began in September 2009

• Exercised exclusive global rights to a fourth biologic
target in December 2008 and fifth target in June 2009

• Initiation of additional Roche clinical trial plus milestone
possible in 2009

• Clinical progress also expected in 2010

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Recent Public Disclosures Reflect Strong Momentum of Roche-Halo Progress Roche Halo
• 4th exclusive biologic target elected • 1st Phase 1 (n=70, mid-09 completion) • Annual maintenance fees (Dec08)

$612M partnership signed, 3 exclusive biologic targets elected (Dec06)

5th exclusive 3rd Phase biologic 1 begins target elected (Sep09) (Jun09)

YE06

YE07

YE08

YE09

CMC, including manufacturing scale-up, nonclinical, toxicology, and other development activities for product candidates formulated with PH20 (not disclosed) ( )

2nd Phase 1 (n=48, mid-09 completion) p ) (Jan09)

Additional Roche clinical trial plus milestone possible p (2H09)

Baxter BioScience - Enhanze GAMMAGARD Addressable IgG Market Forecast at $8-$9 Billion $8 $9

Market Size Reflects The Broad Clinical Applications Of IgG
Source: Baxter

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Baxter BioScience - Enhanze GAMMAGARD Development Plan Moving Forward Rapidly
• Current market dominated by IV administration • SC IgG available - limited by low bioavailability (62%) and need for weekly
dosing at multiple injection sites

• Phase 1/2a trial showed SC bioavailability equal to 92% of IV administration
with dosing of up to 61 2 grams (612 ml) IgG together with PH20 at up to 300 61.2 mL per hour

• Pivotal Phase 3 for GAMMAGARD with PH20 began December 2008; fully
enrolled with ~ 80 patients in July 2009 ahead of plan 2009,

• Final clinical study reports planned in 1H11 • Pre-launch activities initiated with physician, p p y patient and p y research payer
underway

• SC GAMMAGARD offers convenient, once monthly, self-administration in a
g j gold standard in large g g growing market g single SC injection site; could become g

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HYLENEX – Franchise Potential Could be Worth up to $500M
• $200M U.S. market opportunity in
pediatric hydration alone Addressable U.S. ED Visits (M)
4.0

• 2.4M ED (emergency
department) visits potentially addressable by HYLENEX
1.6 2.4

• Potential for $500M franchise
– Adult hydration – Ex-U.S. markets Ex U.S. – Delivery of small molecule drugs (e.g., pain, infection)

• Paradigm shift in ED medical
practice means slow, gradual uptake and acceptance ED pediatric visits for dehydration only Successful ORT Total IV procedures (incl. ORT failures)

Source: Baxter ORT: Oral rehydration therapy

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HYLENEX – Clinically Meaningful Rehydration Demonstrated in INFUSE Peds 1 Study

Allen, C.H., et al, Recombinant Human Hyaluronidase-Enabled Subcutaneous Pediatric Rehydration, Pediatrics, 2009;124;e859-e868.

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HYLENEX – Favorably Perceived By 9 out of 10 Healthcare Providers and Patients

Allen, C.H., et al, Recombinant Human Hyaluronidase-Enabled Subcutaneous Pediatric Rehydration, Pediatrics, 2009;124;e859-e868.

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HYLENEX – Encouraging Interim Results at ACEP from INFUSE PEDS 2 Study

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HYLENEX – Fully Resourced Launch in Pediatric Hydration Underway • Product launched for pediatric hydration at ACEP in Boston
on Oct 5th

• Two sales forces - dedicated HYLENEX specialty team and
existing Baxter IV team supported by formulary specialists in place l

• 90% acceptance rate onto target formularies, even prior to
published data

• Full team of clinical and scientific medical science liaisons
established

• L Large advocacy program with multiple speaker programs d ith lti l k
have been underway for several months

• Leading national and regional KOLs on board g g
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HYLENEX – An Emerging Strong Value Proposition • • • • • • • •
Enables rehydration with less stress for p y parents and children Makes infusion simple and efficient Facilitates clinically meaningful hydration Potentially benefits over 2 million pediatric patients each year in the U.S. alone Perceived f P i d favorably b 9/10 h lth bl by healthcare providers compared t IV id d to Additional post-marketing clinical data being developed Building a new standard of care for rehydration paradigm shift rehydration, HYLENEX safe and well tolerated in clinical experience

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Strong Alliances Generate Non-dilutive Cash and Leverage Technology

• Three alliances with Roche and Baxter have
provided $98 million of cash so far

• Ability to leverage the technology platform multiple
times through additional alliances

• rHuPH20 drug delivery platform being evaluated by
nearly every large biopharma company

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Discovery and Early Development Pipeline U d t Pi li Update
Gregory I. Frost, Ph.D. Vice President , Chief Scientific Officer

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ECM: Breaking it Down
5 classes of macromolecules
1. Collagens 2. Elastic fibers

3. Hyaluronan 4. Proteoglycans 5. Adhesive glycoproteins
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rHuPH20 SC Preclinical through Commercial
rHuMMP1ts Conditional Collagenase

Discovery Research

rHuPH20Intravesical Phase 2

Matrix Biologics
rHuCAT-L Conditional Proteinase P t i Preclinical PH20 Depot Preclinical
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PEGPH20 Phase 1

How Halozyme is Targeting the Matrix Environment

Delivery

ECM

Disease

Current Matrix Targets COLLAGENS

Candidate Enzymes

Mechanism of Action Focal Proteolysis

Potential Applications Cellulite Dupuytren’s Contracture Fibrosis Fib i Keloids/Scarring SC administration: Fluids, Peptides and Biologics Chemotherapy Delivery Postsurgical Edema, Benign Prostatic Hypertrophy (BPH) Chemonucleolysis Solid Tumors 35

rHuCAT-L rHuMMP1ts

rHuPH20

Transient Focal Hydrolysis

HYALURONAN

PH20 Depot

Prolonged Focal Hydrolysis Prolonged Systemic Hydrolysis

PEGPH20

Matrix Target: Collagen

Type I Collagen - Abundant in skin, tendon, ligament, bone, ligament bone cornea – 88-99% of total collagen 88 99%

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Fibrous Septae: A Potential Target for Enzymatic Contouring?

Potential A P t ti l Approaches h 1) Surgical subscision 2) Enzymatic subscision

Challenge: Ch ll Temporal spatial control of enzyme activity

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Enzymatic Subscision: Focal Digestion of Fibrous Septae with Collagenolytic Enzymes
Dimple

TARGET

Fibrous fibrous septae Septae create dimples
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rHuCathepsin-L (rHuCAT-L) is a Recombinant Human Lysosomal Cysteine Endopeptidase
• Cathepsin-L: an enzyme naturally regulated by an acidic cellular environment • Active at acidic pH but rapidly inactivated at physiological p in p y g pH the extracellular space • Very efficient ‘collagenase’ at pH 5.0 ( pH 5 0 (~pH of lidocaine) T Type I Co ollagen

pH 5.0

Enzyme ‘On’

Enzyme ‘Off’

Dimple

Concept: Temporal Spatial Control of Collagenolytic Activity
1- rHuCAT-L enzyme injected in an active state formulated in artificial lysosomal buffer 2- Enzyme cleaves fibrous septae 3- Body s 3 Body’s natural pH in the Matrix inactivates rHuCAT-L as it diffuses away from injection site 4- Dimple relieved as septae lysed

Adipocytes

Fibrous Septae fibrous septae create dimples

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rHuCAT-L Treatment Leads to pH Conditional Release of Collagen Fragments In Vivo
Rodent perfusion model CATL C pH 5
pH 7.4 pH 5.0 pH 5 0 pH 7.4 + CATL pH 5.0 + CATL

Porcine model Buffer B ff pH 5 Collagenase C ll pH 7.5 gros ss

4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 05 0.0

Hydroxyp proline (ug/mL)

0 min

8 min

16 min

septae lysis

septae control

septae lysis

Trichrome e
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rHuCAT-L Progressing Towards the Clinic

• • • • • • •

rHuCAT-L cell bank Fermentation process development Downstream process development IND enabling CMC activities cGMP production of clinical batches GLP toxicology Final pharmacology and secondary indication evaluation • IND filing

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Second Collagenase Program: rHuMMP1ts (Temperature Specific MMP1 Analog)
MMP1 (Matrix Metalloproteinase 1) • Prototypical interstitial human collagenase yp g • Selectively degrades interstitial collagens (I/III) • Little activity towards blood vessel collagen (IV) • Can temporal spatial enzyme activity be engineered to increase safety at pharmacologically relevant doses?

Collagen Type I/III

Bacterial Collagenase Control  (positive control) (Dermis H&E)

rHuMMP1

In situ collagen release

In situ collagen release 43 by MMP1

ollagen Type I/III Co
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By High Throughput Single AA Mutagenesis, Temperature Specific MMP1 Analogs Identified
2985 cDN NA’s Cons structed

• 199 amino acid (AA) protein • All potential single amino acid substitutions screened • 8 strong hits identified

Product Concept: Inject enzyme at room temperature. Digestion of target until body temperature warms enzyme to inactivate i ti t tsAnalog >40 X 20/37 tsAnalog >40 X 20/37

Wildtype

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Value of New Matrix Platforms

• A positive extension of Halozyme’s expertise in Matrix p y p enzymes, proteins, and delivery • A novel biologic compound generating engine outside the realm of monoclonal antibodies, creating a new class of potential breakthrough therapies • Generation of new high value therapeutic biologics beyond HA and hyaluronidase

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Matrix Target: Hyaluronan in the Tumor Microenvironment
• Tumor extends beyond the cancer cells • Many tumors contain reactive stromal matrix that facilitates tumor progression • Treating the tumor as an organ opens up new opportunities for therapeutic intervention (beyond angiogenesis) ( y g g )

VESSELS STROMA

TUMOR CELLS

PEGPH20

Example: Stromal Matrix Occupies Most of the Pancreatic Cancer Microenvironment
Duct TxN0M0 Duct T3N0M0 Duct T3N0M0 Normal

40x

200x
Blue (Tumor Cells) BROWN (HA rich Stroma)

HA(+++) HA( )

HA(+)
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* Representative images of HA/ Hematoxylin on pancreatic tumor tissue

PEGPH20: Background
Section from Metastatic Breast Cancer
• The Matrix comprises the majority of tumor volume in many tumors

Tumor Matrix

Tumor Matrix

• The functions of the Matrix – Support structure for the cancer pp – Storage for growth factors and cytokines – Altered composition during growth and tissue remodeling • Halozyme’s PEGPH20 degrades Matrix by removing the hyaluronan component of the Matrix • Enhances malignant cell vulnerability to – Chemotherapy – Biotherapeutics – Immune system

Nest of Malignant Cells

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Hyaluronan Overproduction is Common in Malignancy

87% HA High

46% HA High 46% HA High

All HA overexpressing  tumors tested in  tumors tested in xenograft models respond to PEGPH20 and enhance  activity of chemotherapeutic

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PEGPH20 – HA Degradation May Represent A Novel Mechanism for Cancer Treatment

Halo

TUMOR CELL

• HA rich halos found HA-rich on many types of aggressive tumors (breast, prostate (breast prostate, pancreatic) • PEGPH20 collapses p HA dependent pericellular halos on tumor cells • Modulates resistance to chemotherapy

+ Enzyme=Halo degraded

PEGPH20

HA

TUMOR CELL

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Removal of Hyaluronan from the Tumor Matrix Alters Tissue Structure
PC3 Xenografts (H&E) PC3 Xenografts (H&E) X ft

PEGPH20 i.v 8hrs

TUMOR WITH HA

TUMOR WITHOUT HA

PC3 Xenografts (Alcian Blue Stain)

PC3 Xenografts (Alcian Blue Stain)

PEGPH20 i.v 8hrs

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Removal of Hyaluronan from the Tumor Matrix Rapidly Reduces Tumor Interstitial Fluid Pressure (IFP)
1.2 1.1

Norm malized Tu umor IFP

1.0 0.9 0.8 0.7 07 0.6 0.5 0.4 0.3 0.2 0.1 0.0 -20 0 20 40 60 80 100 120

+ API Buffer

D Dosed

>80% reduction in tumor IFP within 1st hour

+ PEGPH20

Time after injection (min)
* IM PC3 tumor pressure in tumor bearing mice measured 20 minutes prior and for 2 hours following IV injection of 10,000 units of PEGPH20 (n=3), or Carrier Buffer (n=3)

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Combinations of PEGPH20 with Docetaxel or Liposomal Doxorubicin Demonstrates Significantly Improved AntiTumor Activity
3000

3000

T Tumor Volume (mm3)

2500

Vehicle PEGPH20
Tumor Volume (m 3 ) mm

2500

Vehicle
2000

2000

15 mg/kg

PEG-PH20 PEG PH20
1500

1500 (0/6) 1000 (4/7)

Taxotere
10 mg/kg

Doxil
1000

500

PEGPH20 + Tax

500
D+P P P D+P P P D+P

Doxil + PEG-PH20

0 -2 0

234

6 7 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36

0 0 3 567 9 10 12 1415 18 21 24 27 30 33 36

Time (days)
T+P P T+P P

Time (Days)

Stromal Matrix
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Tumor IFP
15 mg/kg PEGPH20

Drug Accumulation

Tu umor IFP (mmHg g)

Pre dose Pre-dose

Post dose Post-dose

50 40 30 20 10 0 0 120

PEGPH20 enzyme removes matrix substrate in tumor

Time (minutes)

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PEGPH20 + Gemcitabine Shows Activity
D18-Data (1 Round of Rx)

BXPC-3 Tumor Line • HALO++ w/Aggrecan Tumor Tissue • HA Stroma+ / Tumor Cells+

(%TGI=21% at D18)

(%TGI=62% at D18)

Superior Effect of PEGPH20+Gemcitabine vs. Gemcitabine

D28-Data (2 Rounds of Rx)

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PEGPH20 + Erlotinib Shows Activity
BXPC-3 Tumor Line • HALO++ w/Aggrecan Tumor Tissue • HA Stroma+ / Tumor Cells+
D18-Data (1 Round of Rx)

(%TGI=27% at D18)

(%TGI=63% at D18)

Superior Effect of PEGPH20 + Erlotinib vs. E l ti ib Erlotinib

D28-Data (2 Rounds of Rx)

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PEGPH20 Program - Phase 1 Clinical Trial • Multicenter, open-label, dose evaluation trial of IV administered
PEGPH20 in advanced cancer patients began 1Q09

• Safety and tolerability, PK, and PD data from oncology patients
anticipated 2H10

• Determine maximum tolerated dose & dose-limiting toxicities • Observe patients for evidence of antitumor activity • Study will guide PEGPH20 dose selection for future clinical trials – Phase 1b/2 combination studies – Phase 2 single agent studies

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PEGPH20 Program Summary

• Hyaluronan is a major component of the tumor matrix (e.g., 87% of pancreatic cancer) • PEGPH20 disrupts tumor matrix to enhance cancer cell p sensitivity to chemotherapeutics • Clinical Phase 1 trial currently underway • Complete Phase 1b planned to test combinations with chemotherapy

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Stromal Matrix Target: Hyaluronan in Benign Prostatic Hypertrophy (BPH) yp p y( )

• Affects 50% of men by age 50 75% by age 80 50, • 40-50% of patients, BPH clinically significant • Health care costs > $4.8 billion annually (2004) – Non-surgical intervention  $2.5 billion per year – Surgical intervention  $2.3 billion per y g p year • Most BPH involves smooth muscle proliferation and
overproduction of HA, leading to increased prostate size

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HA Distribution in BPH

Basal Cells

Epithelial Cells

Fibroblasts

Smooth Muscle Cells

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BPH Pathogenesis

Prostate Transitional Zone Growth Due to Epithelial & Stromal Proliferation
37x  Stromal Proliferation Rate

BPH

9x  Epithelial Proliferation Rate

HA Overproduction

Proliferative Stromal Disease

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Removal of Prostate Stromal HA Represents a Novel Mechanism of Action for BPH
Apoptosis of stromal cells following HA removal in rat BPH model
Nontreated Apoptotic cells/section Mean ± SD P-Value PEGPH20 12d TE 7d TE 18d TE 12d TE 14d TE 16d PEGPH20 5d PEGPH20 7d PEGPH20 9d TE 18d PEGPH20 11d 7.8 ± 2.71

0

0.8 ± 1.79

4.6 ± 2.51

1.75 ± 1.71

25.6 ± 20.16 36.8 ± 21.99

13.4 ± 5.73

-

-

0.006

0.001

0.001

0.010

Prostatic weights of BPH rats treated with PEGPH20 and/or Finasteride
Group Control PEGPH20 (2wk) Finasteride (2wk) PEGPH20+Finasteride (2wk) Prostatic Weight (g) Mean ± SD 1.33 ± 0.23 1.08 ± 0.21 1.00 ± 0.19 TE 3wk P Value 0.038 0.007 % Inhibition PEGPH20 Alone 18.8 25.2

0.79 ± 0.17

< 0.0001

41

PEGPH20 + Finasteride

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Next Steps

• Examine dosing schemes, compounds ( g , p (PEGPH20, , PH20 depot) and routes of delivery to optimize therapeutic effect with minimal dosing frequency alone and in combination with standard of care • Evaluate Hyaluronan targeting compounds in canine models of BPH • Relevant safety testing • Clinical evaluation

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Halozyme’s Unique Scientific Core: The Extracellular Matrix

our science begins…

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Ultrafast Insulin-PH20 Program – Where We are Going
Douglas B M h D l B. Muchmore, M D M.D. Vice President, Endocrinology Clinical Development

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Halozyme’s Ultrafast Insulin-PH20 Program
• Goal - To develop best-in-class rapid-acting insulin products that surpass current standards of care • Proprietary insulin formulations of novel PH20 permeation enhancing excipient with – Fast acting analog insulin (Humalog, Novolog, Apidra)  “Analog-PH20” – Short acting regular human insulin (Humulin R)  “Insulin-PH20” • Currently in Phase 2, targeting commercialization by 2014, depending on most attractive product candidate (Analog-PH20 vs. Regular Insulin-PH20)

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Goal of Insulin Therapy – Replicate Normal Physiologic Insulin Response

• Role of fast acting insulin is to replicate normal insulin release response to meal • Current meal time insulin alternatives are still too slow to accomplish this goal p g

Source: Am Fam Physician. 2004 Aug 1;70(3):489-500

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Failure to Match Physiologic Insulin Leads to Unmet Needs and Risk of Adverse Outcomes
Suboptimal glycemic control • Inability to control post meal blood sugar impedes diabetes management – >50% of A1C elevation is due to postprandial hyperglycemic excursions for patients with A1C < 8.4%1 p • <30% of all insulin patients meet ADA A1C goal of <7%2 Hypoglycemia still a problem with current products • 72% of T1DM and 54% of T2DM patients on insulin reported hypoglycemia in the past 3 months2 – In mild form, significant quality of life impact – In severe form can be fatal form, Weight gain • Intensive insulin therapy and hypoglycemia associated with weight gain
1 2

Monnier et al. Diabetes Care (2003) 26:881-85 IMS Data, 2008 GFK Roper Patient Survey, N = 2,000 (projectable)

67

Rise of Multiple Daily Injections in Type 2 DM
Rapid Acting Analog Insulin Market ~$3B and Growing p g g g

100 83 80 80

Intensive

Conventional

72

69

66%

60 40 28 20 17 20

31

34%

0 2000

2002

2004

2006

2008

Definitions: Conventional = 1 – 2 injections/d; Intensive = 3 or more
Source: Roper Starch, 2008

68

Growing Percentage of Type 2 Patients Treated with Insulin Analogs
Rapid Analog Use in Type 2 Diabetes: % of Insulin Users
35 30 25 20 15 10 5 0 2004
Source: Roper Starch Data (U.S. only)

29.5% 25.4 25 4 17.9 19.3 23.1

2005

2006

2007

2008
69

Halo’s Ultrafast Insulin-PH20 Products Better Mimic Physiologic Insulin Response - Phase 1 Data
PK of Insulin Lispro and Regular Insulin with and without PH20
M Mean (± SEM) Im mmunoreactive Insulin (pmo e ol/L)
1500 250

Mea (± SEM) Imm an munoreactive Insulin (U/mL L)

1250

Lispro+rHuPH20

200

1000 150

Regular Insulin+PH20
750 100 500

Lispro
50

250

Regular Insulin

0 0 60 120 180 240 300 360

0

Time (min)

• PH20 Co-formulation With Humalog Reduced Median Tmax By 54% (p=0.0006) • Co-formulation With Humulin Reduced Median Tmax By 64% (p=0.0002)
Vaughn et al. Diabetes Technology and Ther. (2009) 11:345-352

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Phase 2 Meal Study in Type 1 Diabetes
4-way crossover standardized test meal study in type 1 diabetes • Objective: compare PK and glucose profiles in response to regular insulin +/- PH20 and insulin lispro +/- PH20 / / • Primary endpoint: PK AUC0-60 • Secondary endpoints: Multiple PK parameters, glycemic excursion Study design • Stabilize FBS* with glucose/insulin infusion • Up to 3 dose finding visits to optimize post meal (12 oz. Ensure = 60 post-meal oz gm CHO) glycemic response to Lispro + PH20 • Using “optimized” dose, repeat test meal with Lispro alone • Repeat using regular Insulin-PH20 and regular insulin alone Interim data at ADA, New Orleans, June 2009; final data presented at EASD, Vienna Oct 2009 EASD Vienna,
* FBS: Fasting blood sugar

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Phase 2 Lispro-PH20 Data Confirm in T1DM the PK Effects Observed in Phase 1 Study
Do Norm ose malized Immun noreactiv Insuli ve in (pmo ol*kg/L*U  SEM) U )
5000 4000 3000 2000 1000 0 0 60 120 180 240 300 360 420 480
“Fast In”: Exposure in first hour increased 50% (p=.0002)* (p .0002)

Lispro (N=22) Lispro + PH20 (N=37)
“Fast Out”: Exposure after two hours reduced approximately 45% (p=.027) pp y (p )

Time (minutes)

Faster, greater insulin absorption with greater and earlier peak exposure achieved: Cmax increased by 41%, p=.0007; Tmax from 49  30 mins, p<.0001

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PH20 Changes Lispro PK Profile and Leads to Significant Reduction in Post Meal Hyperglycemia Post-Meal
220

Blood Glucos  SE se EM (mg/dL)

200 180 160 140 120 100 80 0 60 120 180 240

Lispro Lispro + PH20
ACE Goal

Time from injection (minutes)
Glycemic response was measured using 60gm CHO liquid test meal; Mean insulin dose = 5.7 U/subject. 73

Phase 2 Regular Insulin-PH20 Data Confirm in T1DM the PK Effects Observed in Phase 1 Study
Dos Normalized se Immun noreactiv Insulin ve n (pmol*kg/L*U  SEM)
5000 4000 3000 2000 1000 0 0 60 120 180 240 300 360 420 480

Regular I R l Insulin (N 19) li (N=19) Regular Insulin+PH20 (N=34)

Time (minutes)

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PH20 Changes Regular Insulin PK Profile and Leads to Significant Reduction in Post Meal Post-Meal Hyperglycemia
220

Blood Glucos  SEM d se M (mg/dL L)

200 180 160 140 120 100 80 0 60 120

Regular Insulin Regular Insulin+PH20

ACE Goal

180

240

Time from injection (minutes)

Glycemic response was measured using 60gm CHO liquid test meal; Mean insulin dose = 6.2 U/subject. 75

PK and Glycemic Responses to Test Meal for Regular Insulin PH20 versus Lispro Alone Insulin-PH20

220

Dose Norm malized Im mmunoreactiv Insulin ve (pmol*kg/ /L*U)

Bl lood Glucos  SEM se (mg/dL L)

5000 4000 3000 2000 1000 0 0 60 120 180 240 300 360 420 480

200 180 160 140 120 100 80 0 60

Regular Insulin+PH20 (N=34) Lispro (N=22)

Regular Insulin+PH20 Lispro

ACE Goal

120

180

240

Time (minutes)

Time from injection (minutes)

Glycemic response was measured using 60gm CHO liquid test meal Mean insulin dose = 5.7 U/subject for Lispro and 6 2 U for Insulin-PH20 57 6.2 Insulin PH20

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PK and Glycemic Excursion Improvements of Lispro PH20 Lispro-PH20 vs. Lispro Alone are Similar to Lispro Alone Improvements vs. Regular Insulin Alone
5000

Dose Norma alized Immunoreactive Insulin e (pmol*kg/L*U  SEM)

220
4000 3000 2000 1000 0 0 60 120 180 240 300 360 420 480

Blo ood Glucose  SEM (m g/dL)

Lispro+PH20 (N=37) Lispro (N=22) (N 22) Regular Insulin (N=19)

200 180 160 140 120 100 80 0 60 120

Lispro Lispro+PH20 Regular Insulin

ACE Goal

180

240

Time (minutes)

Time from injection (minutes)

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Phase 2 Type 1 Diabetes Meal Study Conclusions • Lispro-PH20 and Insulin-PH20 are well tolerated • PK results for these preparations confirm in Type 1 patients
previous findings from Phase 1

• Lispro-PH20 and Insulin-PH20 accelerate insulin absorption
compared t the respective i d to th ti insulin products alone, yielding more li d t l i ldi physiologic mealtime insulin PK profiles

• Greater and earlier peak Lispro-PH20 and Insulin-PH20 exposure
and reduced late exposure compared to respective insulin products alone

• These changes in PK profiles lead to significant reductions in
postprandial hyperglycemia and are meaningful relative to achieving treatment targets

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Upcoming Ultrafast Insulin-PH20 Data Presentations During 4Q09
• PH20 dose response study to determine optimal PH20 concentration – Data to be presented at International Diabetes Federation (Montreal, (Montreal October 18-22) and Diabetes Technology Society (San Francisco, November 5-7) • I t Intra-subject PK/GD variability study completed t clarify d bj t i bilit t d l t d to l if dose reproducibility – Data to be presented at Diabetes Technology Society

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Efficient Development Strategy to Maximize Program Value
• Additional clinical studies to further characterize Ultrafast Insulin-PH20 value
proposition prior to starting pivotal studies – Ph Phase 1 euglycemic glucose clamp study comparing 3 marketed f t l i l l t d i k t d fast acting analog insulins +/- PH20 (first subject dosing performed) – Phase 2 standard meal study in T2DM patients (enrollment completed)

• Ph Phase 3 Enabling studies: E bli t di
– Phase 2 3x/day treatment study in T1DM patients comparing regular Insulin-PH20 to lispro in a 3 month x 3 month crossover design (initiated 2Q09) – Phase 2 3x/day treatment study comparing Analog-PH20 to analog alone (2010)

• Pivotal Phase 3 trials in T1DM and T2DM patients comparing PH20 product
candidate to analog insulin following Phase 2 trials and program review with regulatory authorities

• Halo prepared to partner or proceed to Phase 3 with most attractive product
candidate (Analog-PH20 and/or regular Insulin-PH20)
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Ultrafast Insulin-PH20 Goal – Potential Benefits vs. Standard of Care Analogs
Better glycemic control

• Faster higher insulin concentrations and peak exposure (i e fast in) Faster, (i.e.,
results in early glucose lowering effects and reduced post-meal hyperglycemia, which may lead to better A1C control

• Fast in, fast out profile is ideal for insulin p p applications , p pump pp
Less hypoglycemia

• Reduced late post-meal exposure (i.e., fast out) may result in fewer
hypoglycemic events

• Lowering insulin dose requirements with PH20 to match glycemic control
of analogs may further reduce hypoglycemia Less weight gain

• Fewer hypoglycemic events and lower insulin doses could result in less
self medicating snacking self-medicating snacking, especially in Type 2 patients

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Key Takeaways and Closing Comments
Jonathan E. Lim, M.D. President & Chief Executive Officer

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Balanced Growth Strategy – Multiple Programs Moving Forward p g g
Business Development • Roche has entered the clinic with three biologic compounds • Baxter BioScience in Phase 3 pivotal with GAMMAGARD • Baxter Medication Delivery launching HYLENEX for pediatric hydration • Seeking additional business development deals to leverage the technology and generate non-dilutive cash Proprietary Pipeline • Ultrafast Insulin-PH20 Insulin PH20 – Two scientific presentations for Halo insulins in 4Q09 – Three additional trials underway with results likely mid-2010 – Phase 2 Analog-PH20 3x/day g y treatment study expected to begin 3Q10 • PEGPH20 Phase 1 continues • HTI-501 and other dermatology candidates in preclinical phase • Pi li h significant partnership Pipeline has i ifi t t hi value
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Licensing Strategy for Insulin Program
• Goal is to develop best-in-class ultrafast prandial insulin with unique value relative to current standard of care • Having conversations with multiple players in the diabetes marketplace • Ph Phase 2 treatment studies provide significant d t of i t t t t t di id i ifi t data f interest t t to potential partners – Regular Insulin-PH20 3x/day treatment study data available in mid-2010 – Analog-PH20 3x/day treatment study data available in mid-2011 • Additional high value, low cost clinical pharmacology studies that produce favorable results enhance the value of the program

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Milestones for 2009
• • • • • • • • • • • •
$5.5 million payment from Baxter for HYLENEX, 1Q09 Phase 1 underway for second Roche exclusive target, 1Q09 Initiated I iti t d PEGPH20 Ph Phase 1 1Q09 1, Initiated Insulin-PH20 Phase 2 3x/day treatment study, 2Q09 Presented Analog-PH20 Phase 2 interim data at ADA 2Q09 ADA, $4.25 million payment from Roche for fifth exclusive target, 2Q09 Completion of p p patient enrollment for Phase 3 GAMMAGARD-PH20 by y Baxter, 3Q09 Phase 1 underway for third Roche exclusive target, 3Q09 Presented Insulin-PH20 Phase 2 data at EASD, 4Q09 HYLENEX launched in pediatric hydration by Baxter, 4Q09 Present A l PH20 and Insulin-PH20 variability d t 4Q09 P t Analog-PH20 d I li PH20 i bilit data, Initiation of additional Roche clinical trial plus milestone possible
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Potential Milestones for 2010 • P Presentation of PEGPH20 preclinical d t 2Q10 t ti f li i l data, • Presentation of Analog-PH20 and Insulin-PH20 Phase 1 and 2
studies at ADA 2Q10 ADA,

• Initiation of Analog-PH20 Phase 2 3x/day treatment study, 3Q10 • Completion of PEGPH20 Phase 1 clinical trial 2H10 trial, • Initiation of PEGPH20 Phase 1b chemotherapy combination clinical
trial, 2H10

• Completion of Phase 3 GAMMAGARD clinical trial by Baxter in PID,
4Q10

• Initiation of additional Roche clinical trial(s) plus milestone(s) possible • Additional licensing deal(s) possible • Additional guidance for proprietary programs to be provided in 2010
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What is Halozyme?

An innovative biotech company with strong biologics capabilities and multi-functional Matrix platforms multi functional • Commercial, partnered and clinical stage assets (Roche, BAX, Insulin, PEGPH20) • Enabling biologics delivery platform (rHuPH20) for lifecycle management with strong proof of concept • Oth M t i platforms th t can generate f t Other Matrix l tf that t future value (HTI 501 l (HTI-501, tsMMP) • Ability to produce complex recombinant proteins y p p p • Attracting top level biopharma talent

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HALO’s Unique Investment Thesis • Existing and potential drug delivery partnerships (Enhanze
Technology, HYLENEX) may provide non-dilutive cash to fund proprietary pipeline opportunities and drive near-term value

• Multifunctional enzymes targeting the Matrix (PH20, PEGPH20,
HTI-501), with broad potential and patient benefits across variety of therapeutic uses, drives long-term value

• Strong financial position to execute plan and drive towards key
value inflection points: $89M cash at end of 2Q09, includes $40M equity offering in June

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