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Matrix Therapies for Life
Company Overview
September 2008 – UBS Global Life Sciences Conference
Safe Harbor
The Private Securities Litigation Reform Act of 1995
provides a "safe harbor" for forward-looking
statements. All statements made in this
presentation that are not statements of historical
fact constitute forward-looking statements. The
matters referred to in forward-looking statements
could be affected by the risks and uncertainties of
the Company's business. Such risks inherent to the
Company’s business will be described in the
Company’s filings, when they occur, with the
Securities and Exchange Commission, as well as in
its press releases. The Company's actual results
may differ materially from those expressed in or
indicated by such forward-looking statements.
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HALO Investment Highlights
• Recombinant human hyaluronidase (rHuPH20) core technology
validated by partnerships potentially worth up to $724 million in
milestones, plus royalties
– FDA approved product, HYLENEX, has large addressable market
– Enhanze Technology partnerships with Roche and Baxter
• Proprietary product candidates target extracellular matrix (“Matrix”),
focused on oncology, metabolism, and dermatology, including:
– Potential best-in-class prandial insulins for treatment of diabetes
– Two NMEs - target multiple solid tumors and dermatologic conditions
• Attractive valuation with $82 million in cash 2Q08
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Halozyme Targets the Matrix
Matrix Therapies For Life
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Successful Talent Initiatives Underway
Notable recent new hires
• Doug Muchmore, MD – VP, Endocrinology Clinical Development
(Eli Lilly)
• Patrick 0’Connor, PhD – VP, Research (Pfizer, Ardea Biosciences)
• Michael J. LaBarre, PhD – VP, Product Development (Biogen Idec,
Vical)
• James E. Cartoni – VP, Legal (DLA Piper)
Total employees – 121
• 87 – R&D, clinical, regulatory, manufacturing
• 12 – Commercial, project and alliance management
• 22 – HR, finance, IT, legal, corporate
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rHuPH20 Core Technology: Mechanism of Action
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Multiple Strategic Paths for Driving
the Value of rHuPH20
HYLENEX
Low dose FDA-approved rHuPH20 for
delivery of small molecules and fluids
Baxter targeting $500M market
opportunity
Enhanze Technology
Ongoing alliances with Roche and
Baxter BioScience
High dose rHuPH20 for delivery of
large molecules (e.g., monoclonal
antibodies)
Actively seeking additional high
value partnership opportunities
Proprietary rHuPH20 Combinations
Leverages HALO’s unique knowledge
of matrix biology and proven drug
development capabilities to pursue
efficient routes to approval
Generating high value programs for
continued development and/or
partnering
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HALO is Pursuing 4 Multi-Billion Dollar Franchise
Opportunities Targeting the Matrix
Drug Delivery
1. HYLENEX with Baxter Medication
Delivery
2. Enhanze Technology with Roche
(up to 13 biologic targets)
3. Enhanze Technology with Baxter
BioScience (Gammagard® IVIG)
Endocrinology
1. Insulins (diabetes)
2. Bisphosphonates (osteoporosis)
Oncology
3. Mitomycin (bladder cancer)
4. PEGPH20 (NME; solid tumors)
Dermatology
5. HTI-501 (NME)
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HYLENEX Product Highlights
• FDA approved “For use as an adjuvant to increase the absorption and
dispersion of other injected drugs; for hypodermoclysis….”
• HYLENEX global sales and marketing partnership with Baxter
– Alliance worth up to $65M ($10M up-front; $25M milestones;
$10M pre-paid royalties; $20M equity), plus royalties
• Post-marketing clinical trials ongoing
– Pediatric hydration trial enrollment completed May 2008
– Interim data – American Academy of Pediatrics, October 2008
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Enhanze™ Technology:
For Partners with Injectable Biologics and Drugs
Value proposition
Efficacy
• Deliver more drug to intended targets
• Allow drug to work faster
• Increase volume of drug at each injection
Convenience
and compliance
• Change route of administration (e.g., IV to SC)
• Reduce adverse injection site reactions
• Decrease pain and tissue distortion upon injection
Economic
benefits
• Extend lifecycle of products coming off patent
• Provide competitive differentiation and reduce COGS
• Enable inpatient drugs to be injected at home
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Enhanzed Remicade® Demonstrated IV Like
Bioavailability and PK in a Preclinical Model
Serum Antibody Levels (I-125Counts/ml) in rats
2.0E+06
1.8E+06
IgG 10mg/kg local
IgG 10mg/kg local + rHuPH20
1.6E+06
IgG 10mg/kg IV
1.4E+06
1.2E+06
Bioavailability
= 100%
1.0E+06
8.0E+05
Bioavailability
= 94 +/- 7%
6.0E+05
4.0E+05
Bioavailability
= 59 +/- 7%
2.0E+05
0.0E+00
0
10
20
30
Bookbinder, et al. J Controlled Release. 2006;114:230-1
40
50
60
70
Time (Hours)
80
90
100
110
120
130
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Enhanzed Gammagard Can Be Delivered
Monthly by Subcutaneous Route
• Gammagard Liquid (intravenous immunoglobulin) - plasma derived
antibody indicated for primary immunodeficiency, currently given IV
• Difficult to administer SC due to low bioavailability (63%), results in
need for weekly dosing
• SC administration of up to 61.2 grams (612 ml) IgG with rHuPH20 at
ranges of up to 300 mL per hour resulted in bioavailability equal to 92%
of the IV form in Phase I/IIa trial
• Potential for convenient patient self-administration at monthly intervals
SC route of administration with rHuPH20 expected to deliver
significant benefits to patients, prescribers, and payers
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Enhanze Technology Alliances Could Drive
Significant Value
Roche
• Roche alliance worth up to $612M ($20M up-front; $111M milestones
for first 3 exclusive targets; $470M up-front & milestones for 10
additional targets; $11M equity), plus royalties
• Improving manufacturing efficiency, bringing on second API supply
source to support partnered and in-house programs
Baxter
• Baxter BioScience alliance worth up to $47M ($10M up-front; $37M
milestones), plus royalties
• Pivotal Phase III - Gammagard + Enhanze expected 1Q09
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Proprietary Product Candidates Target the Matrix
1. Insulins: rHuPH20 combination for prandial diabetes therapy
2. Bisphosphonates: rHuPH20 combination for osteoporosis
3. Chemophase: rHuPH20 combination with Mitomycin for bladder cancer
4. PEGPH20: Pegylated rHuPH20 targets HA expressing tumors
5. HTI-501: Novel Matrix degrading enzyme for dermatology
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Insulin Program Highlights
• Completed Phase I, prospective, randomized trial assessing safety,
tolerability, PK, and PD of two insulin products injected SC +/- rHuPH20
– Presented at American Diabetes Association in June 2008
– rHuPH20 +/- fast-acting insulin analog (Humalog®)
– rHuPH20 +/- regular insulin (Humulin®)
– Conducted in 26 subjects
• Positive results confirm potential to develop best-in-class therapeutic
within growing, diabetes market
– ~$2.5B prandial US insulin market with 13% CAGR
• Anticipate initiation of Phase II clinical trial 4Q2008
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Significantly Greater Insulin Exposure Immediately
Post Dose and Reduced Insulin Exposure Later
1500
250
Humalog + rHuPH20
1250
200
1000
150
Humulin + rHuPH20
750
100
500
Humalog
50
250
Humulin
0
Mean (± SEM) Immunoreactive Insulin (U/mL)
Mean (± SEM) Immunoreactive Insulin (pmol/L)
PK of Humalog and Humulin with and without rHuPH20
0
0
60
120
180
240
300
360
Time (min)
• rHuPH20 Co-Formulation With Humalog Reduced Median Tmax By 54% (p=0.0006)
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• Co-Formulation With Humulin Reduced Median Tmax By 64% (p=0.0002)
Significantly Faster and Greater Insulin
Exposure, Starting at First Sampling Point
70
Humalog +
rHuPH20
360
60
300
50
240
40
Humulin +
rHuPH20
180
30
Humalog
120
20
60
10
Humulin
0
Mean (± SEM) Immunoreactive Insulin (mU/mL)
Mean (± SEM) Immunoreactive Insulin (pmol/L)
PK of Humalog and Humulin with and without rHuPH20 in first 15 minutes
420
0
0
3
6
9
12
15
Time (min)
Increase In Insulin Concentration From Baseline At 3 Minutes was 3-fold for
Humalog + rHuPH20 (p=0.03) and 24-fold for Humulin + rHuPH20 (p<0.0001)
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Significantly Greater Metabolic Effect Early and
Reduced Metabolic Effect Later
PD of Humalog and Humulin with and without rHuPH20
10
Humulin +
rHuPH20
Mean (± SEM) GIR (mg/kg*min)
9
Humalog +
rHuPH20
8
7
6
Humalog
5
4
Humulin
3
2
1
0
0
60
120
180
240
300
360
Time (min)
• rHuPH20 Co-Formulation With Humalog Reduced Median tGIR* By 46% (p=0.0059)
• Co-Formulation With Humulin Reduced Median tGIR By 63% (p=0.0105)
*Time to maximum glucose infusion rate
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Halozyme’s Proprietary Insulin Formulations Could
Result in Significant Clinical Benefits
Attributes of HALO Insulin Products
Potential Clinical Benefits
Faster and greater insulin
concentrations and greater glucose
lowering activity early (1st 1-2 hrs)
Closer to natural prandial insulin
release, leading to better postprandial glycemic control with
simplified mealtime dosing
Lower insulin concentrations and less
glucose lowering activity later (after 3-4 hrs)
Fewer hypoglycemic events
Significantly lower variability of key
PK and PD variables
Better predictability with each dose
Significantly greater insulin exposure
at early time points for same dose
Lower dose and therefore reduced
insulin dose dependent weight gain
By Improving Post-prandial Diabetes Care, HALO’s Insulin Program
Could Also Reduce the Long-Term Consequences of Diabetes 19
HALO Insulins - Multiple Options for
Value Creation
• Potential for significant advantages over current standard of care and
other compounds in development
• Compelling development path
– Co-formulation with two already approved products
– Potential for efficient regulatory pathways - 505(b)(2) in US
• Halozyme is well positioned to maximize value from insulin programs
– IP protection on rHuPH20 combinations through 2024
– Poised to begin multiple Phase II studies
– Opportunity to develop and/or partner assets
• Target initiation of Phase II clinical trial by end of 2008. Study will
evaluate prandial glycemic control in T1 diabetic patients
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Bisphosphonate Program – Differentiated
Product targeting a >$4B Market
• >$4 billion annual market - long-term oral compliance is poor due to
insufficient efficacy, GI toxicity, and cumbersome dosing regimens; >75%
of patients discontinue therapy within 3 years
• IV BPs - inconvenient, expensive, key prescribers have limited
capabilities to administer them
• IV-administered Reclast® and Boniva® - attractive targets for conversion
to SC with rHuPH20
• Bisphosphonates + rHuPH20 may facilitate IV to SC conversion and help
ensure compliance via convenient annual/semi-annual dosing and
avoidance of GI toxicity
• Target - enter clinic for at least one combination in 4Q08
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Chemophase Program – Targeting Unmet
Medical Need in Superficial Bladder Cancer
• Tumor recurrence rates for superficial bladder cancer are 40-85%;
50% of recurrences occur within the first year
• Chemophase may increase absorption of Mitomycin C into the bladder
wall to decrease recurrence rates
• Ongoing Chemophase Phase I/IIa trial successful in determining MTD
and demonstrating safety and tolerability of induction and maintenance
dosing; positive interim data announced June 2008
• Preparing to consult with regulatory authorities, FDA and Scientific
Advice for EU, to determine optimal regulatory pathway to approval
• Anticipate start of pivotal clinical trials in 2009
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PEGPH20 May Address a Key Limitation of
Chemotherapy Efficacy
Halo
+ Enzyme=Halo degraded
• HA-rich halos found
on many types of
aggressive tumors
(breast, prostate,
pancreatic)
TUMOR
CELL
PEGPH20
TUMOR
CELL
HA
• PEGPH20 collapses HA
dependent pericellular
halos on tumor cells
• Modulates resistance to
chemotherapy
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IV PEGPH20 Degrades Tumor HA and Rapidly
Reduces Tumor Interstitial Fluid Pressure (IFP)
1.00
+ API Buffer
0.75
>80% reduction
in tumor IFP
within 1st hour
0.50
Dosed
Normalized Tumor IFP
1.25
0.25
+ PEGPH20
0.00
-0.25
-20
0
20
40
60
80
100
120
Time after injection (min)
* IM PC-3 tumor pressure 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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IV PEGPH20 Markedly Increases the Antitumor
Activity of Taxotere in HA-Positive Tumor Model
PC3 hormone refractory prostate carcinoma (HRPC) Model
Percent Remaining
Survival in PC3 Prostate Carcinoma
110
100
90
80
70
60
50
40
30
20
10
0
CONTROL
Taxotere (10mg/kg)
PEGrHuPH20
Taxotere (10mg/kg)
PEGrHuPH20
ILS improvement of 225%
for T+PEGPH20 vs. 59% for
T alone
0
10
20
30
40
50
60
70
Days
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PEGPH20 Program: Highlights and Next Steps
• Proof of principle efficacy data presented at AACR July 2008:
Survival increased significantly in mouse tumor model for PEGPH20
plus docetaxel compared to docetaxel alone
• Further evaluation of PEGPH20 in relevant tumor models alone and
in combination with optimal chemotherapy regimens
• Additional studies on-going to support PEGPH20 regulatory filing
• Anticipate start of first Phase I clinical trial 1H09
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HTI-501: Matrix Degrading Enzyme Targets
Cellulite and Other Dermatology Applications
• Enzyme digests the fibrous septae (cords) which cause the characteristic
dimpling associated with cellulite
• HTI-501 degrades collagen at pH 5-6 but is rapidly inactivated by the
body’s natural physiologic pH
• Duration and location of enzyme activity is tightly controlled, which may
confer significant advantages compared to bacterial collagenases
• Established proof of principle efficacy against fibrous septae in obese
rodent and porcine models
• Next steps: Further characterization in relevant pharmacology models
where tight control and repeat use are required
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HTI-501 Matrix Degrading Enzyme Program
Cellulite is Caused by Fibrous Septae
Dimple
TARGET
Fat
Cells
Fibrous
fibrous septae
Septae
create dimples
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Principles of HTI-501
Dimple
1. Enzyme injected in active state
2. Enzyme digests fibrous septae
3. Body inactivates enzyme
Fat
Cells
Fibrous
Septaefibrous septae
create dimples
4. Dimple relieved
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Milestones
•
Presentation of Bisphosphonates pre-clinical data, 2Q08
•
Presentation of PEGPH20 pre-clinical IFP data, 2Q08
•
Presentation of HTI-501 pre-clinical data, 2Q08
•
Presentation of Insulin Phase I data, ADA, 2Q08
•
Release of Chemophase Phase I/IIa data, 2Q08
•
Presentation of PEGPH20 pre-clinical proof of principle data, 3Q08
•
Initiate Insulin Phase II clinical trial, 4Q08
•
Initiate clinical trial for Bisphosphonates program, 4Q08
•
Initiate GammaGard + Enhanze Pivotal Phase III clinical trial, 1Q09
•
Initiate PEGPH20 Phase I clinical trial, 1H09
•
Initiate Chemophase Pivotal Phase III, 2009
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HALO’s Unique Investment Thesis
4 Multi-Billion Dollar Franchise Opportunities Targeting the Matrix
• Drug delivery franchise may provide revenue and non-dilutive cash to
fund proprietary franchises in endocrinology, oncology, dermatology
• Matrix enzymes (rHuPH20, PEGPH20, HTI-501) with broad potential
across variety of therapeutic uses
– rHuPH20 based products with potentially best-in-class profiles, faster time
to market, and lower development risk
– NMEs targeting major indications
• Attractive valuation with $82 million in cash at 2Q08
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