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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)
17
• 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
TreatedPopulation, DataasofDecember2016
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
TreatedPopulation, DataasofDecember2016
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
24
• 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
• Reflects upfront payments from recently signed BMS, Roche agreements
• Excludes impact of financing, repayment of debt principal
Year-end Cash $245M to $260M $380M to $395M
• Reflects upfront payments from recently signed BMS, Roche agreements
• 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
✓
✓
✓
✓
✓
29
Building a Premier Oncology Biotech
September 2017
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