building a premier oncology...

Building a Premier Oncology Biotech

September 2017

Forward-Looking Statements

All of the statements in this presentation that are not statements of historicalfacts constitute forward-looking statements within the meaning of the PrivateSecurities Litigation Reform Act of 1995. Examples of such statements includepossible activity, benefits and attributes of PEGPH20, future productdevelopment and regulatory events and goals, anticipated clinical trialresults and strategies, product collaborations, our business intentions andfinancial estimates and results, including projected revenue amounts. Thesestatements are based upon management’s current plans and expectationsand are subject to a number of risks and uncertainties which could causeactual results to differ materially from such statements. A discussion of the risksand uncertainties that can affect these statements is set forth in theCompany’s annual and quarterly reports filed from time to time with theSecurities and Exchange Commission under the heading “Risk Factors.” TheCompany disclaims any intention or obligation to revise or update anyforward-looking statements, whether as a result of new information, futureevents, or otherwise.

1

Oncology PipelineENHANZE® Technology

7 Global Licensing & Collaboration Agreements

3 launched products generating growing revenues from mid single-digit royalties

3 programs in active clinical development

$1.3B in potential milestones for active targets1

PEGPH202: phase 3 asset with HA-High population of ~75,0003 in solid tumors studied

Phase 2 Study 202 data in pancreas cancer supportive of phase 3 design

Emerging applications for PEGPH20 in immuno-oncology

1 Assumes all developmental and commercial milestones achieved and paid to Halozyme for Herceptin SC, Mabthera SC, HYQVIA, Daratumumab SC and targets in development or planned for development.2 PEGPH20 is an investigational drug; safety and efficacy profiles have not been established, nor is it available for commercial distribution.3 Estimated addressable patients in U.S., EU5 based on annual Incidence of 1L Metastatic Pancreatic Cancer, Advanced Non-Small Cell Lung Cancer, 2L Metastatic Gastric Cancer, 2L Stage IV Breast Cancer (HER2-), SEER 18 2006-2012, Globocan 2012, Medscape; and Halozyme estimates for HA-HIGH %.

2

Halozyme Has a Unique Two-Pillar Strategy for Growth

ENHANZE® Technology

Product ENHANZESubcutaneous Alternative

2030Patent Extension1

2014EU patent expiration for

Herceptin IV2

~8 minutes / visit3,4 1.5-6 hours / visitfor MabThera IV3,4

1 European patent: EP2459167B1, U.S. patent: 9345661 2 Generics and Biosimilars Initiative, Aug. 12, 2016 (http://www.gabionline.net/Biosimilars/General/Biosimilars-of-trastuzumab)3 Shpilberg O, et al. British J Cancer. 2013; 109(6):1556–15614 De Cock E, et al. Plos One. 2016; 11(6):e0157957

4

ENHANZE® Value Demonstrated in Three Commercial Products

STRU

CTU

REM

ILEST

ON

ES

FOC

US

5

TARG

ETS

Up to $2B Revenue Potential for Global Collaboration and License Agreement with Bristol-Myers Squibb

Robust ENHANZE® Royalty Growth

$9M

$31M

$51M

2013 2014 2015 2016 2017

GrowingRoyaltyRevenueAverageMid-SingleDigitRoyaltyRateAcrossPartnerships

Ex-U.S. Launch

U.S. Launch

6

1H2017RoyaltyRevenueof$29M,continuedgrowth

expected

6/17

1 ENHANZE royalty revenue will depend upon indications evaluated by partners and market penetration.2 Reflects 2016 sales of all Shire Immunoglobulin Therapies less Halozyme internal estimate for U.S. pediatric sales. Information provided during Shire investor update (Feb. 16, 2017).3 Reflects 2016 sales for Mabthera/Rituxan and Herceptin excluding the U.S. and Japan. Information provided during Roche investor update (Feb. 17, 2017).4 Reflects 2016 U.S. sales for Mabthera/Rituxan. Information provided during Roche investor update (Feb. 17, 2017).5 Information provided during Halozyme investor update (Aug. 8, 2017). 6 Excludes estimates for Mabthera/Rituxan sales in Rheumatoid Arthritis indication in applicable geographies, incorporated from EvaluatePharma, Sept. 2016.

ENHANZE® Approved Product Potential Opportunity

7

$10B+ Opportunity Today

2016 Proprietary Product Sales1

Currently Approved GeographiesCountries Launched5

~80

~60

4B3

1.5B2

7.5B3,4,6

Herceptin

RituxanU.S. Oncology

MabThera

HyQvia

ENHANZE royalty revenue will depend upon indications approved, number of countries in which launches occur and market penetration, among other factors

1 ENHANZE royalty revenue will depend upon indications evaluated by partners and market penetration.2 Mean analyst estimates for global revenue, Bloomberg; Analyst model estimates.

ENHANZE® Portfolio Potential Future Opportunity

8

Future OpportunityProprietary Product Sales1

Currently in Clinical Development

Perjeta

Perjeta

Darzalex

Darzalex

7B2

3.5B2

Additionaltargetsindevelopmentandmultipletargetsprojectedtoenterdevelopment

4B2

5B2

Darzalex2020

2025

Perjeta2020

2025

ENHANZE royalty revenue will depend upon indications approved, number of countries in which launches occur and market penetration, among other factors

June2017:U.S.approvalofRituxanHYCELA™

September2017:LandmarkI-OdealwithBristol-MyersSquibb

September2017:Rochesignsamendedtermsfornewtarget

August2017:LillyinitiatesPhase1trial

Upcoming:JansseninitiationofDaratumumabSCPhase3Trial

Game Changers for ENHANZE®

99

$20MOne-time Upfront

1Assumes all developmental and commercial milestones per target achieved and paid to Halozyme.

Milestones/ Target1

Targets

$37-47M

8

$10M

$37M

1

$8M

$85M

6

$15M

$113M

5

$23M

$130M

9

$25M

$160M

5

20152007 2012 20142006 2017

Recurring Average Mid-single Digit Royalties on Net Sales

$105M

$160M

11

$30M

$160M

1

10

Increasing Value of Agreements Driven by Regulatory and Commercial Success

Lead Oncology Asset: PEGPH20

Our Path to PEGPH20 Value Creation is Clear

12

Strongrationaleforpancreascancerfocus

ConvictionandsupportforPEGPH20inpancreascancer

Definedpathtoseekapproval

Near-termmilestones

1

2

4

3

13

UnmetNeed

• 52%ofpatientshavemetastaticdiseaseatdiagnosis1

• 85%Median1-yearmortalityformetastaticpatients2

• 98%Median5-yearmortalityformetastaticpatients2

PotentialOpportunity

• 65,000 metastaticpancreascancerpatientsdiagnosedannually(U.S.,EU5)3

• 25,000havenegativeprognosticfactor:highlevelsofHyaluronan(HA)4

Pancreas Cancer Focus Based on High Unmet Need and Potential Opportunity

1 SEER 18 2007-2013.2 Statistics adapted from the American Cancer Society's publication, Cancer Facts & Figures 2016.3 SEER 18 2006-2012, Globocan 2012, Medscape.4 Halozyme estimates for HA-High %.

HA (Red) surrounding a single breast cancer cell overexpressing HAS3 (Bright Green)9

1 Whatcott, et al. AACR (2013)2 Rosengren et al, Cancer Res 2016;76(14 Suppl):Abstract # 4886.3 Zhang et al, Oncoimmunology 2016; 5(6)4 Brekken et al. Anticancer Res. 20:3503 (2000)5 Provenzano and Hingorani, Br J Cancer 108:1 (2013)6 Thompson et al. Mol Cancer Ther. 9:3052 (2010)7 Stylianopoulos et al. PNAS. 110:18632 (2013)8Singha et al. . Mol Cancer Ther. 14:523 (2015)9 Rilla et al. JHC. 56:901 (2008)

HA Surrounding a Cancer CellHA is a Structural Carbohydrate that:• Stabilizes the Tumor

Microenvironment (TME)• Is associated with decreased

survival1 and immunosuppression in the TME2,3

• Compromises Access to the Tumor – Increases tumor interstitial

pressure4,5

– Compresses vasculature6,7

– Can decrease therapeutic and immune cell access8

14

Hyaluronan (HA) Can Be a Barrier to Therapeutic and Immune Cell Access to Tumor Cells

RetrospectiveEvaluationofPancreaticCancerSurvivalin~50Patients1

HA-LowMedianSurvival:24.3months

H.R.2.6p=0.037

HA-HighMedianSurvival:9.3months

1 Whatcott et al: Clin Cancer Res 2015, 21:3561-3568. HA staining by HABP. Scoring algorithm assessed percent staining and intensity.2 Annual Incidence, SEER 18 2006-2012, Globocan 2012, Medscape; Estimated HA-High %, Halozyme estimates.3 Not all HA-High patients may be eligible for PEGPH20.

15

Tumor HA Overexpression Associated with Shorter Survival in Pancreas Cancer

InUSandEU-5,estimated25,000HA-Highmetastaticpancreascancersannually(~35-40%)2,3

PEGPH20 Targets Hyaluronan (HA) in the Tumor Microenvironment

PEGPH20

In HA-High Tumor Animal Models, Removal of HA by PEGPH20 Demonstrated to:

Decreaseintratumoral

pressure

Decompressvasculature

Increaseperfusion

Increase access for

therapeutics

Increase access for

immune cells

16

PEGPH20 Directly Addresses Barriers to Effective Therapy in Animal Models

PEGPH20 Increases Tumor Concentration of Cancer Therapy in

Animal Models

PEGPH20 Creates a Less Immunosuppressive Tumor

Microenvironment

In HA-rich animal tumor models, PEGPH20 demonstrated to:

ü Reduce levels of Hyaluronan associated with an immunosuppressive phenotype in some solid tumors2,3

ü Decrease immunosuppressive markers and cell types2

ü Increase CD8+ T cells in tumors4

ü Increase tumor growth inhibition when combined with immune checkpoint inhibitor antibodies2

and chemotherapy5

Increased tumor paclitaxel accumulation*

BxPC3/HAS3 PDA Xenograft Tumors1

89%↑[paclitaxel]tum

**

N A lo n e N + P P -2 4 h r- N0

2

4

6

8

ng

/mg

tis

sue,

pa

clit

axe

l±

StD

ev 43%↑

[paclitaxel]tum

**

1 Osgood et al., AACR PDA Mtg., 2014 and unpublished data2 Rosengren et al, Cancer Res 2016;76(14 Suppl):Abstract # 48863 Zhang et al, Oncoimmunology 2016; 5(6)4 Clift et al. (2017). AACR Annual Meeting, Poster #6415 Thompson et al. Mol Cancer Ther 2010; 9:3052 (2010)

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• Phase 2 open label, randomized, multicenter study

• Designed to evaluate PFS and association with HA levels – Develop Companion Diagnostic algorithm and cut-point – Support Phase 3 trial design

CR, complete response; DCR, disease control rate; DoR, duration of response; HA, hyaluronan; KPS, Karnofsky performance status; ORR, objective response rate; OS, overall survival; PDA, pancreatic ductal adenocarcinoma; PFS, progression-free survival; PR, partial response; SD, stable disease.

18

HALO-202 Explored Association Between HA Levels and Outcomes in Pancreas Cancer

STAGE1• Randomized1:1toPAG:AG• PEGPH20discontinued atclinicalhold (38%ofHA-Highpatients)

• TrainingSetforHAdiagnosticassayscoringalgorithmandthreshold1

PresentedatASCO20162

19

AUG2014

APR2014

DEC2016

FEB2016

MAR2013

CLINICALHOLDIncreasedthromboemboliceventsobservedinPAGarm

HOLDLIFTEDProtocolamendedtoincludeTEscreeningandthromboprophylaxiswithenoxaparin

DATACUTPrimaryendpointachievedwithstatisticalsignificance

ENROLLMENT ENROLLMENT FOLLOW-UP

n=146 n=133

STAGE2• Randomized2:1toPAG:AG• ValidationSettoprospectivelyevaluatescoringalgorithmandthreshold (extracellularmatrixHAstaining≥50%oftheentiretumorsurfaceatanyintensity)

PresentedatASCO20173

1 (Ventana HA RxDx) Co-developed by Halozyme Therapeutics, Inc. and Ventana Medical Systems. 2 Bullock AJ, et al. J Clin Oncol 34, 2016 (suppl; abstract 4104).3 Hingorani, et al., J Clin Oncol 35, 2017 (suppl; abstract 4008).

HALO-202 Evolved to Have Two Stages Allowing Acceleration of Companion Diagnostic Validation

AG8.5months

AG5.2months

PAG9.2months

PAG11.5months

HR:0.51(0.26,1.00);Pvalue:0.048

HR0.96(0.57,1.61)

ProgressionFreeSurvival OverallSurvival

77%improvementinmedianPFS(secondaryendpoint)

ITTPopulation, DataasofDecember2016

20

Encouraging Efficacy Demonstrated in HALO-202 Stage 1 + Stage 2 in Target HA-High Population

AG7.8months

AG4.5months

PAG8.6months

PAG11.7months

HR:0.63(0.21,1.93) HR:0.52(0.22,1.23)

ProgressionFreeSurvival OverallSurvival

TreatedPopulation, DataasofDecember2016

91%improvementinmedianPFS(secondaryendpoint)50%improvementinmedianOS(exploratoryendpoint)

Remainingontreatment:PAG(n=2);AG(n=1)

Remainingontreatmentand/orfollowup:PAG(n=6);AG(n=1)

21

Encouraging Efficacy Demonstrated in HALO-202 Stage 2 in Target HA-High Population

EnoxaparinProphylaxisDose

TERate

PAG AG

Stage1(Dec2016) N/A

43%(32/74)

25%(15/61)

Stage2*(Dec2016)

Startedwith40mg/day

28%(5/18)

29%(2/7)

Startedon1mg/kg/day

10%(7/68)

6%(2/32)

*TEratesforallstage2patientsare14%(12/86) inPAGarmand10%(4/39)inAGarm

22

Achieved Primary Endpoint of Reduction in Incidence of Thromboembolic (TE) Events in Stage 2


PreferredTerm

PAG(n=160)Patients,n(%)

AG(n=100)Patients, n(%)

AnyGrade Grade≥3 AnyGrade Grade≥3

AnyAE 157(98.1) 138(86.3) 93(93.0) 75(75.0)Fatigue 115(71.9) 33(20.6) 66(66.0) 16(16.0)Peripheraledema 101 (63.1) 8(5.0) 26(26.0) 4(4.0)Musclespasms 89(55.6) 20(12.5) 3(3.0) 1(1.0)Nausea 79 (49.4) 8(5.0) 47(47.0) 4(4.0)Diarrhea 64(40.0) 11(6.9) 39(39.0) 5(5.0)Anemia 62(38.8) 27(16.9) 38(38.0) 20(20.0)Alopecia 60(37.5) 1(0.6) 39(39.0) 0(0.0)Decreasedappetite 59(36.9) 7(4.4) 25(25.0) 2(2.0)Neutropenia 54(33.8) 47(29.4) 19(19.0) 18(18.0)Neuropathyperipheral 47(29.4) 10(6.3) 31(31.0) 8(8.0)Vomiting 46(28.8) 5(3.1) 27(27.0) 2(2.0)Dysgeusia 45(28.1) 0 19(19.0) 0Myalgia 41(25.6) 8(5.0) 7(7.0) 0(0.0)Thrombocytopenia 41(25.6) 26(16.3) 17(17.0) 9(9.0)

23

HALO-202 (Stage 1 + Stage 2) Treatment-Related Adverse Events (AEs) in ≥ 25% of Patients


HALO- 202 Findings Support the Ongoing HALO-301 Phase 3 Study

• HALO-202 met primary PFS endpoint and key secondary PFS endpoint in HA-High patients– Data supports HA-High as potential predictive and prognostic

biomarker

• High conviction in the Phase 3 Study based on Study 202 findings– PEGPH20: first targeted therapy with a validated diagnostic cut-off in

pancreas cancer

– HA–High associated with poorer prognosis and may be predictive of longer median PFS and OS with PEGPH20

– Similar patient population as being evaluated in ongoing Phase 3

– Strong signal in both PFS and OS supporting Phase 3 statistical assumptions

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• Randomized (2:1 PAG:AG), double-blind, placebo-controlled, global

• Interim analysis when target number of PFS events reached

• PFS powered with a hazard ratio of 0.59 (to detect a 41% risk reduction for progression)

• First patient dosed in March 2016, study approved in 22 countries with over 200 centers ready to screen or already screening patients

PEGPH20 + ABRAXANE® + gemcitabine (PAG)

ABRAXANE® + gemcitabine (AG) + placebo

1LMetastatic

PDA

High-HA patients

N=420

PrimaryEndpoints:Progression-FreeSurvival(PFS)OverallSurvival(OS)

25

HALO-301|Pancreatic: Global Phase 3 Trial Enrolling in 22 Countries

1 2 3

26

Robust Pan-Tumor Testing With Potential for Initial Response Rate Data By Year-End

Financial Update

August 2017 September 20171 Notes

Net Revenue $115M to $130M $245M to $260M

• Reflects upfront payments from recently signed BMS, Roche agreements

• Continued royalty growth in 2017

OperatingExpenses $240M to $250M $240M to $250M • No change in expense

trajectory

Operating Cash (Burn) / Flow ($75M to $85M) $50M to $60M


• Excludes impact of financing, repayment of debt principal

Year-end Cash $245M to $260M $380M to $395M


• Royalty-backed loan repayment began in 2017

28

2017 Financial Guidance Update

1 Pending HSR review for the agreement with Bristol-Myers Squibb.

Goal Target Date

Study 202: Data Presented at ASCO, ESMO-GI

RITUXAN HYCELA™ approved in U.S. June 2017

New ENHANZE® target Phase 1 study start

Initiation of Genentech/Halozyme Clinical Collaboration trials –Atezolizumab + PEGPH20

Sign New ENHANZE Agreements: Bristol Myers-Squibb, Roche

Initial data to demonstrate PEGPH20 pan-tumor potential Q4 2017

Daratumumab SC Phase 3 start Q4 2017

Support ENHANZE Partners’ Progress 2H 2017

Value Enhancing Milestones: 2H 2017

✓

✓

✓

✓

✓

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Building a Premier Oncology Biotech

September 2017

building a premier oncology...

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