Building a Premier Oncology Biotech

Transcription

1 Building a Premier Oncology Biotech May 208

2 Forward-Looking Statements All of the statements in this presentation that are not statements of historical facts constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 995. Examples of such statements include possible activity, benefits and attributes of PEGPH20, future product development and regulatory events and goals, anticipated clinical trial results and strategies, product collaborations, our business intentions and financial estimates and results, including projected revenue amounts. These statements are based upon management s current plans and expectations and are subject to a number of risks and uncertainties which could cause actual results to differ materially from such statements. A discussion of the risks and uncertainties that can affect these statements is set forth in the Company s annual and quarterly reports filed from time to time with the Securities and Exchange Commission under the heading Risk Factors. The Company disclaims any intention or obligation to revise or update any forward-looking statements, whether as a result of new information, future events, or otherwise.

3 Halozyme Two Pillar Strategy Removing Biological Barriers to Treatment ENHANZE Enhancing Delivery of Treatments PEGPH20 Late Stage Investigational New Product ENHANZE image from The 5 Steps to Infuse HYQVIA. 2

4 ENHANZE Pillar

5 207: Transformative Year for ENHANZE Pipeline June 207: RITUXAN HYCELA U.S. FDA Approval Aug 207: Initiate Phase trial Sept 207: Landmark -target I-O deal Sept 207: Expanded collaboration, new target Nov 207: Initiate Phase 3 trials, daratumumab SC Dec 207: Four-target collaboration 4

6 Commercial Products Driving Robust ENHANZE Royalty Growth Growing Royalty Revenue Average Mid-Single Digit Royalty Rate Across Partnerships $64M $5M $3M $9M Ex-U.S. Launch U.S. Launch 6/7 Quarterly reporting lag in 207; expect to see revenue reflected in

7 ENHANZE : ~$ Billion Royalty Revenue Potential in 2027 Based on marketed products and targets projected to be in clinical testing in 208 $B ~$ Billion $500M Approved Products Potential Future Products,2 Assumes additional products, including Darzalex and Opdivo (nivolumab), are globally approved and launched in multiple indications Includes projections for subcutaneous versions of targets not approved or commercially available. Innovator revenues based on Bloomberg analyst projections. Conversion rates based on Halozyme internal projections. 2 6 Royalty revenue projection includes targets selected but not yet disclosed.

8 ENHANZE Progress and Value Acceleration in Products products Darzalex 2 Darzalex Perjeta /Herceptin 3 2 Perjeta /Herceptin Lilly Target 3 6 BMS PD- ALXN 20 Lilly Target Roche Target 2 Undisclosed Targets Approved and Commercialized Phase Phase 3 7

9 ENHANZE Offers Four Paths for Differentiation and Value Creation for Partners Reduced Treatment Burden and Healthcare Costs 2 Potential for Competitive Differentiation 3 New Intellectual Property and Exclusivity 4 Changing US Reimbursement and Care Landscape 8

10 Increasing Value of Agreements Driven by Regulatory and Commercial Success One-time Upfront $20M $0M $8M $5M $23M $25M $05M $30M $40M Milestones/ Target $37-47M $37M $85M $3M $30M $60M $60M $60M $60M Targets Recurring Average Mid-single Digit Royalties on Net Sales Assumes all developmental and commercial milestones per target achieved and paid to Halozyme. 9

11 Phase 3 Oncology Asset: PEGPH20

12 Pancreatic Ductal Adenocarcinoma (PDA): The Need 65,000 people diagnosed with metastatic pancreas cancer each year 55,250 will die within 2 months of diagnosis 2 By 2030, pancreas cancer projected to be the 2 nd leading cause of cancer death 3 High levels of Hyaluronan (HA) associated with poor survival in pancreas cancer 4 SEER , Globocan 202, DRG Epidemiology data. 2 Statistics adapted from the American Cancer Society's publication, Cancer Facts & Figures Rahib et al, Cancer Res Whatcott, et al. AACR (203)

13 Hyaluronan (HA) Can Be a Barrier to Therapeutic and Immune Cell Access to Tumor Cells HA is a Structural Carbohydrate that: Stabilizes the Tumor Microenvironment (TME) Is associated with decreased survival and immunosuppression in the TME 2,3 HA Surrounding a Cancer Cell Compromises Access to the Tumor Increases tumor interstitial pressure 4,5 Compresses vasculature 6,7 Can decrease therapeutic and immune cell access 8 Whatcott, et al. AACR (203) 2 Rosengren et al, Cancer Res 206;76(4 Suppl):Abstract # Zhang et al, Oncoimmunology 206; 5(6) 4 Brekken et al. Anticancer Res. 20:3503 (2000) 5 Provenzano and Hingorani, Br J Cancer 08: (203) 6 Thompson et al. Mol Cancer Ther. 9:3052 (200) 7 Stylianopoulos et al. PNAS. 0:8632 (203) 8 Singha et al.. Mol Cancer Ther. 4:523 (205) 9 Rilla et al. JHC. 56:90 (2008) HA (Red) surrounding a single breast cancer cell overexpressing HAS3 (Bright Green) 9 2

14 Tumor HA Overexpression Associated with Shorter Survival in Pancreas Cancer Retrospective Evaluation of Pancreatic Cancer Survival in ~50 Patients HA-Low Median Survival: 24.3 months HA-High Median Survival: 9.3 months H.R. 2.6 p=0.037 In US and EU-5, estimated 25,000 HA-High metastatic pancreas cancers annually (~35-40%) 2,3 Whatcott et al: Clin Cancer Res 205, 2: HA staining by HABP. Scoring algorithm assessed percent staining and intensity. 2 3 Annual Incidence, SEER , Globocan 202, Medscape; Estimated HA-High %, Halozyme estimates. 3 Not all HA-High patients may be eligible for PEGPH20.

15 PEGPH20 Targets Hyaluronan (HA) in the Tumor Microenvironment In HA-High Tumor Animal Models, Removal of HA by PEGPH20 Demonstrated to: Decrease intratumoral pressure Decompress vasculature Increase perfusion Increase access for therapeutics Increase access for immune cells PEGPH20 4

16 PEGPH20 Targets and Degrades Hyaluronan Before PEGPH20 MPA# After + PEGPH20 Gemcitabine Hard Fibrotic Hypovascular Soft Cellular Hypervascular Provenzano, et al. Cancer Cell. 202,2(3):48. 5

17 PEGPH20 Directly Addresses Barriers to Effective Therapy in Animal Models n g /m g tis s u e, p a c lita x e l S td e v PEGPH20 Increases Tumor Concentration of Cancer Therapy in Animal Models PEGPH20 Creates a Less Immunosuppressive Tumor Microenvironment BxPC3/HAS3 PDA Xenograft Tumors In HA-rich animal tumor models, PEGPH20 demonstrated to: Increased tumor paclitaxel accumulation* 89% [paclitaxel] tum 43% ** [paclitaxel] tum ** Reduce levels of Hyaluronan associated with an immunosuppressive phenotype in some solid tumors 2,3 Decrease immunosuppressive markers and cell types 2 2 Increase CD8 + T cells in tumors 4 0 N A lo n e N + P P -2 4 h r- N Increase tumor growth inhibition when combined with immune checkpoint inhibitor antibodies 2 and chemotherapy 5 Osgood et al., AACR PDA Mtg., 204 and unpublished data 2 Rosengren et al, Cancer Res 206;76(4 Suppl):Abstract # Zhang et al, Oncoimmunology 206; 5(6) 4 Clift et al. (207). AACR Annual Meeting, Poster #64 5 Thompson et al. Mol Cancer Ther 200; 9:3052 (200) 6

18 HALO-202 Explored Association Between HA Levels and Outcomes in Pancreas Cancer Phase 2 open label, randomized, controlled 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. 7

19 HALO-202 Evolved to Have Two Stages Allowing Acceleration of Companion Diagnostic Validation STAGE Randomized : to PAG:AG PEGPH20 discontinued at clinical hold (38% of HA-High patients) Training Set for HA diagnostic assay scoring algorithm and threshold Presented at ASCO STAGE 2 Randomized 2: to PAG:AG Validation Set to prospectively evaluate scoring algorithm and threshold (extracellular matrix HA staining 50% of the entire tumor surface at any intensity) Presented at ASCO MAR 203 ENROLLMENT APR AUG ENROLLMENT FEB FOLLOW-UP n = 46 n = 33 DEC 206 CLINICAL HOLD Increased thromboembolic events observed in PAG arm HOLD LIFTED Protocol amended to include TE screening and thromboprophylaxis with enoxaparin DATA CUT Primary endpoint achieved with statistical significance (Ventana HA RxDx) Co-developed by Halozyme Therapeutics, Inc. and Ventana Medical Systems. 2 Bullock AJ, et al. J Clin Oncol 34, 206 (suppl; abstract 404). 3 Hingorani, et al., J Clin Oncol 35, 207 (suppl; abstract 4008). 8

20 Encouraging Efficacy Demonstrated in HALO-202 Stage + Stage 2 in Target HA-High Population Progression Free Survival Overall Survival AG 5.2 months HR: 0.5 (0.26,.00); P value: PAG 9.2 months AG 8.5 months PAG.5 months HR 0.96 (0.57,.6) 77% improvement in median PFS (secondary endpoint) ITT Population, Data as of December 206 9

21 Encouraging Efficacy Demonstrated in HALO-202 Stage 2 in Target HA-High Population Progression Free Survival Overall Survival HR: 0.63 (0.2,.93) HR: 0.52 (0.22,.23) AG 4.5 months PAG 8.6 months AG 7.8 months PAG.7 months Remaining on treatment: PAG (n=2); AG (n=) Remaining on treatment and/or follow up: PAG (n=6); AG (n=) 9% improvement in median PFS (secondary endpoint) 50% improvement in median OS (exploratory endpoint) Treated Population, Data as of December

22 Achieved Primary Endpoint of Reduction in Incidence of Thromboembolic (TE) Events in Stage 2 Enoxaparin Prophylaxis Dose PAG TE Rate AG Stage (Dec 206) N/A 43% (32/74) 25% (5/6) Stage 2* (Dec 206) Started with 40 mg/day Started on mg/kg/day 28% (5/8) 0% (7/68) 29% (2/7) 6% (2/32) *TE rates for all stage 2 patients are 4% (2/86) in PAG arm and 0% (4/39) in AG arm Treated Population, Data as of December 206 2

23 HALO-202 (Stage + Stage 2) Treatment-Related Adverse Events (AEs) in 25% of Patients PAG (n = 60) Patients, n (%) AG (n = 00) Patients, n (%) Preferred Term Any Grade Grade 3 Any Grade Grade 3 Any AE 57 (98.) 38 (86.3) 93 (93.0) 75 (75.0) Fatigue 5 (7.9) 33 (20.6) 66 (66.0) 6 (6.0) Peripheral edema 0 (63.) 8 ( 5.0) 26 (26.0) 4 ( 4.0) Muscle spasms 89 (55.6) 20 (2.5) 3 ( 3.0) (.0) Nausea 79 (49.4) 8 ( 5.0) 47 (47.0) 4 ( 4.0) Diarrhea 64 (40.0) ( 6.9) 39 (39.0) 5 ( 5.0) Anemia 62 (38.8) 27 (6.9) 38 (38.0) 20 (20.0) Alopecia 60 (37.5) ( 0.6) 39 (39.0) 0 ( 0.0) Decreased appetite 59 (36.9) 7 ( 4.4) 25 (25.0) 2 ( 2.0) Neutropenia 54 (33.8) 47 (29.4) 9 (9.0) 8 (8.0) Neuropathy peripheral 47 (29.4) 0 ( 6.3) 3 (3.0) 8 ( 8.0) Vomiting 46 (28.8) 5 ( 3.) 27 (27.0) 2 ( 2.0) Dysgeusia 45 (28.) 0 9 (9.0) 0 Myalgia 4 (25.6) 8 ( 5.0) 7 ( 7.0) 0 ( 0.0) Thrombocytopenia 4 (25.6) 26 (6.3) 7 (7.0) 9 ( 9.0) Treated Population, Data as of December

24 HALO- 202 Findings Support the Ongoing HALO-30 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 23

25 HALO-30 Pancreatic: Global Phase 3 Trial Enrolling in 22 Countries L Metastatic PDA High-HA patients N= PEGPH20 + ABRAXANE + gemcitabine (PAG) ABRAXANE + gemcitabine (AG) + placebo Primary Endpoints: Progression-Free Survival (PFS) Overall Survival (OS) Randomized (2: PAG:AG), double-blind, placebo-controlled, global Project to achieve target number of PFS events between December 208 and February 209, triggering final data collection, cleaning and interim analysis 24

26 PEGPH20 Pancreas Cancer Program De-risking Event Timeline Phase 2 randomized, controlled HALO-202 study initiated 206 Companion Diagnostic algorithm and cutpoint established Initiated Phase 3 HALO-30 study 207 HALO-202 data supportive of Phase 3 trial design Validated companion diagnostic HALO-30 ongoing at >200 centers in 22 Countries Project target PFS events between December 208 and February 209 with data to follow 25

27 ~$B Potential Sales Opportunity in HA-High Metastatic Pancreatic Ductal Adenocarcinoma (PDA) 65,000 Diagnosed Metastatic PDA Annually US and EU 5 25,000 Estimated number of HA-High patients ~$B Projected potential global sales opportunity for successful therapy in metastatic PDA % of population 2 SEER , Globocan 202, DRG Epidemiology data. 2 Halozyme estimates for HA-High %. 3 DRG Epidemiology data, Halozyme internal estimates. 26

28 Robust Pan-Tumor Testing of PEGPH20 Breast Cancer Gastric Cancer, NSCLC Pancreas Cancer, Gastric Cancer Gall Bladder Cancer, Cholangiocarcinoma No further clinical development planned on the Phase 2 portion of study. 2 Pending acceptance of data to medical forum. 27

29 Financial Update

30 208 Financial Guidance 208 Net Revenue Royalty Growth Product Sales $5M to $25M 25% - 30% API product orders lower as a result of planned partner manufacturing transition Does not include potential new ENHANZE agreements Operating Expenses $230M to $240M Disciplined expense control, flat to 207 Operating Cash Burn Debt Repayment ($75M) to ($85M) ~($95M) Excludes impact of financing, repayment of debt principal Includes royalty-backed and Oxford/SVB loans Year-end Cash $305M to $35M Cash runway into

31 Core Elements of Value Creation in 208 ENHANZE 25%-30% Royalty Revenue Growth Multiple catalysts 5 Phase starts 4 Phase 3 Darzalex trials ~$B royalty potential in 2027 PEGPH20 - Pancreatic Phase 3 PFS Events: Dec. 208 Feb. 209 ~$B potential sales opportunity Financial Cash balance exiting 208 of $305M-$35M PEGPH20 - Pan-Tumor Potential data from two trials Capabilities Readiness for PEGPH20 BLA/MAA submissions in 209 Support ENHANZE partner progress 30

32 Building a Premier Oncology Biotech May 208