Halozyme Therapeutics, Inc. · NASDAQ:HALO
Halozyme Therapeutics — Investor Presentation (October 2013)
46 slides from Halozyme Therapeutics's investor presentation, Oct 31, 2013
Slide 1: Halozyme Therapeutics: Thinking Outside the Cell
Halozyme Therapeutics, Inc. Thinking Outside the Cell™ October 2013 Gregory Frost Chief Executive Officer Exhibit 99.1
Slide 2: Safe Harbor
2 <#> Safe Harbor 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 1995. These forward-looking statements and all references to financial estimates are ba
Slide 3: Thinking Outside the Cell = Extracellular Matrix (ECM)
3 <#> Thinking Outside the Cell = Extracellular Matrix (ECM) Complex matrix of proteins and carbohydrates that surround the cell Composition unique to every organ and disease state Cell ECM
Slide 4: Company Focus: Harnessing Recombinant Human Enzymes
4 <#> New Routes of Delivery or Improved Efficacy Company Focus Harnessing Recombinant Human Enzymes Modify Specific Components of ECM Proprietary Human Enzymes • Convert biologics from IV administration to SC injection • Reduce number of SC injections • Improve efficacy of existing therapies • Targ
Slide 5: Product and Product Candidates
5 <#> Product and Product Candidates Therapeutic Area Use / Indication Preclinical Phase 1 Phase 2 Phase 3 Filed Approved PROPRIETARY PRODUCT CANDIDATES HYLENEX® recombinant (hyaluronidase human injection) Various Peptide, small molecule, and fluid delivery Analog Insulin-PH20 (pen market) Endocrino
Slide 6: Partnered Programs Near-Term Growth Engine
6 <#> Partnered Programs Near-Term Growth Engine • Alpha 1 antitrypsin (pre-clinical) • IV to SC • First 2 exclusive targets for Primary & Specialty Care (PCSK-9) • Pfizer elected 3rd and 4th exclusive targets since deal signing • IV to SC or improved dosing frequency UP TO 2 ADDITIONAL TARGETS Roya
Slide 7: Roche Royalty Opportunities Are Near-Term
7 <#> Roche Royalty Opportunities Are Near-Term • Fixed dose SC co-formulation reduces dosing time to 5 minutes* • 92% preference by patients§ • Line Extension Approval and EU Launch, 3Q2013 • Filed in multiple countries (ex-US/Japan) Herceptin SC Formulation (Breast Cancer) MabThera SC Formulation
Slide 8: Roche Initial Territories Represent Significant Opportunity
8 <#> Roche Initial Territories Represent Significant Opportunity • EU approval 3Q2013 • EU application filed Dec 2012
Slide 9: Baxter HyQvia May Increase Patient Convenience
9 <#> Baxter HyQvia May Increase Patient Convenience • SC dosing • Dosed monthly • Single administration site Other IgGs HyQ • Dosed monthly • Single administration site IV Dosing • Dosed weekly • Multiple injection sites SC Dosing • All endpoints (primary and secondary) were met • Fewer systemic ad
Slide 10: Partnered Programs Yielding Lucrative Revenue Short- and Long-Term
10 <#> Partnered Programs Yielding Lucrative Revenue Short- and Long-Term 6 Targets ROYALTY RATES: Commensurate with past deals MabThera $7B Herceptin $6B + 6 additional targets ROYALTY RATES: Mid-single digits HyQ $1.2B ROYALTY RATES: Mid-single digits A1AT – TBD ROYALTY RATES: Tiered ~10%
Slide 11: Proprietary Programs Long-Term Value Growth Drivers
11 <#> Novel matrix-remodeling enzyme targeting collagen for aesthetics and scarring HTI-501 (rHuCathepsin-L) Systemically acting enzyme for targeting HA-expressing tumors PEGPH20 (pegylated rHuPH20) FDA approved (150U) for the dispersion and absorption of other injected drugs and fluids Hylenex Rec
Slide 12: First Proprietary Product: HYLENEX recombinant
12 <#> First Proprietary Product: HYLENEX recombinant (hyaluronidase human injection) Indicated to increase dispersion and absorption of other injected drugs and fluids • Establishing base with hospital and surgery center markets – Regional anesthesia – Hydration and extravasation – Captured >50% ma
Slide 13: Hyaluronidase for Insulin Pumps
13 <#> 6:00 10:00 14:00 18:00 22:00 2:00 6:00 Hyaluronidase for Insulin Pumps A Novel Approach to More Physiologic Insulin Absorption P lasma I n s u li n L e v e ls Pumps Pumps + Hyaluronidase Normal insulin secretion Breakfast Lunch Dinner
Slide 14: More Physiologic Glucodynamic Profile with Hylenex
14 <#> 0 60 120 180 240 300 80 100 120 140 160 180 200 220 Time After Meal (min) G lu co se ( m g/ dL SE M ) Hylenex + analog Analog alone AACE post prandial glucose target More Physiologic Glucodynamic Profile with Hylenex Source: Halozyme late-breaking poster presented at ADA 2012, Muchmore, et
Slide 15: CONSISTENT Phase 4 Study
15 <#> CONSISTENT 1 Phase 4 Study Testing Hylenex in a real world environment CSII + Hylenex CSII Control CSII + Hylenex 2 years A1C, PPG HE/Safety A1C, PPG HE/Safety 400 Adult T1DM 3 1 Studying the use of Hylenex in conjunction with rapid analog insulins for adults with Type 1 diabetes on insulin p
Slide 16: Three Steps to Commercial Readiness
16 <#> Additional studies in relevant patient populations Phase 4 Clinical Trials Multiple device options Device Approvals New fill and finish lines Manufacturing Scale Up Hylenex in Insulin Pumps Three Steps to Commercial Readiness
Slide 17: PEGPH20 in Pancreatic Cancer: Promising Shift in Treatment Paradigm
17 <#> PEGPH20 in Pancreatic Cancer Promising Shift in Treatment Paradigm Access and Response Restored CTX + PEGPH20 Tumor Environment Disrupted PEGPH20 Tumor Environment Protects Cancer Cells CTX Depletion of HA matrix from the tumor microenvironment hits key pathways •Rapid normalization of tumor
Slide 18: PDA Phase 1b Data Presented at ASCO & ESMO
18 <#> PDA Phase 1b Data Presented at ASCO & ESMO Future studies for other malignancies planned for 2014 1 2 3 4 5 6 7 8 Weeks Restage/Cycle 2 Cycle 1 Treatment until disease progression PEGPH20 Gem 1 2 3 4 28 Stage IV PDA 1.0 µg/kg 1.6 µg/kg 3.0 µg/kg Single-arm Phase 1b trial evaluating PEGPH20 +
Slide 19: Two PDA Phase 2 Studies Starting 2013
19 <#> Two PDA Phase 2 Studies Starting 2013 Future studies for other malignancies planned for 2014 PEGPH20 + Abraxane + Gem until disease progression Abraxane + Gem until progression 126 Stage IV Metastatic PDA KPS 70-100 Biopsy Tissue 1:1 PEGPH20 + mFOLFIRINOX until disease progression mFOLFIRINOX
Slide 20: HTI-501 (rHuCAT-L) A Novel Conditionally Active Biologic
20 <#> HTI-501 (rHuCAT-L) A Novel Conditionally Active Biologic Multiple conditions involve collagen pathologies • Cellulite, keloid scars, Dupuytren’s contracture HTI-501 (recombinant human cathepsin-L) • Targeted digestion of collagen through unique mechanism • Extracellular pH provides focal cont
Slide 21: Financials Well Positioned for 2013 and Beyond
21 <#> Financials Well Positioned for 2013 and Beyond 2012 2013 2014+ $76M in cash June 30, 2013 $45-50M 2013 estimated net cash burn Partner Royalties start 2013 Cash flow positive expected as early as end of 2014 Well-financed to support proprietary product launches and advance pipeline
Slide 22: Strategies to Ensure Success: Poised for a Pivotal Year in 2013
22 <#> Advance proprietary programs • Advance clinical trials for PEGPH20 • Complete HTI-501 Phase 2 clinical trial Secure revenue streams from existing channels • Support EMA filings and launch of Herceptin SC and MabThera SC • Advance insulin pump commercialization Strategies to Ensure Success Poi
Slide 23: Slide 23
Slide 24: Phase 1b Trial of Gemcitabine Combined with PEGPH20
A Phase 1b Multicenter International Clinical Trial of Gemcitabine Combined with PEGPH20 (PEGylated Recombinant Human Hyaluronidase) in Patients with Stage IV Previously Untreated Pancreatic Cancer
Slide 25: Introduction to Hyaluronan (HA)
25 <#> Introduction to Hyaluronan (HA) • A glycosaminoglycan (GAG) polymer of 2,000-25,000 repeating disaccharide units • HA cross-links tumor extracellular matrix via binding to other proteoglycans • Within a tumor microenvironment (TME) several cell types can generate HA, including stromal and mal
Slide 26: PEGPH20
26 <#> PEGPH20 n CH2 CH2 OCH2 O CH3 N H O CH2 CH2 OO CH2 CH3 N H O n CH2 CH2 OO CH2 CH3 N O H n n CH2 CH2 OCH2 O CH3 N H O CH2 CH2 OO CH2 CH3 N O H n Systemic delivery of PEGylated rHuPH20 (PEGPH20) depletes tumors of HA Depletion of tumor HA remodels tumor microenvironment • Rapid normalization of
Slide 27: HA Synthase Drives Microvilli and Pericellular Matrix
27 <#> Hyaluronidase HA/GFP HA Synthase Control HA/GFP-HA Synthase Rilla et al., J Histochem Cytochem, 2008 HA Synthase Drives Microvilli and Pericellular Matrix
Slide 28: Clinical Trial Objectives
28 <#> Clinical Trial Objectives Primary • Establish the recommended phase 2 dose (RP2D) of PEGPH20 in combination with gemcitabine in patients with Stage IV previously untreated PDAC Secondary • Assess the safety and tolerability of PEGPH20 in combination therapy • Assess tumor response using RECIS
Slide 29: Clinical Trial Design
29 <#> Clinical Trial Design • Phase 1b, open-label, multicenter (US and Russia), dose-escalation clinical trial of PEGPH20 in combination with gemcitabine in treatment naïve stage IV pancreatic patients • 3-6 patients were to be enrolled in the dose escalation cohort and 14 patients were to be enro
Slide 30: Clinical Trial Design: Dosing Schema
30 <#> Clinical Trial Design 1 2 3 4 5 6 7 8 Weeks Dosing Schema Restage/Cycle 2 Cycle 1 Treatment continues until disease progression PEGPH20 Gem 1 2 3 4
Slide 31: Patient Selection
31 <#> Patient Selection Key eligibility criteria: • Newly diagnosed, previously untreated, histologically-confirmed Stage IV PDA with documented disseminated neoplasm to the liver and/or the lung. • One or more metastatic tumors measurable on CT scan per RECIST 1.1 criteria • Acceptable liver and r
Slide 32: PEGPH20 PK and PD Profiles
32 <#> PEGPH20 PK and PD Profiles • Plasma concentrations (Cmax) of PEGPH20 were proportional to dose • PEGPH20 PK indicated a long terminal half-life (1-3 days) with slow clearance (0.5 – 2 mL/hr/kg) • Cycle 1 Week 1 vs. Cycle 1 Week 4 PK profiles indicate no significant changes • Administration of
Slide 33: Demographic and Baseline Characteristics
33 <#> Demographic and Baseline Characteristics Parameter (N = 28) Median age, years (range) 59 (27-82) Male/Female 14/14 Site of metastatic disease Liver Lung Abdomen/peritoneal Lymph nodes 25 (89%) 6 (21%) 10 (36%) 6 (21%) CA 19-9 baseline level Normal Elevated Median Range 6 22 11
Slide 34: PEGPH20 Treatment-Related Adverse Events
34 <#> PEGPH20 Treatment-Related Adverse Events (≥10% in Total Incidence, Worst Grade) Adverse Event (N=28) Grade 1/2 Grade 3/4 All Grades Any AE 18 (64%) 6 (21%) 24 (85%) Fatigue 6 (21%) 1 (4%) 7 (25%) Edema peripheral 5 (18%) 1 (4%) 6 (22%) Muscle spasms 14 (50%) 0 14 (50%) Myalgia 9 (32%) 0 9 (32
Slide 35: Efficacy Assessment
35 <#> Efficacy Assessment • Response was assessed by independent central radiology using RECIST 1.1 criteria • Baseline core biopsy was optional in the dose escalation phase and required in the expansion cohort • Exploratory analyses were conducted to assess the combination treatment effect based o
Slide 36: Ten Patients Experienced PR as Assessed by Central Radiology
36 <#> Ten Patients Experienced PR as Assessed by Central Radiology • PEGPH20/Gemcitabine response rate 42% (21.9%-61.4%) (95% CI) (ITT population at 1.6 and 3.0 µg/kg dose levels) • Twenty patients have at least one baseline and one follow up scan • 6 patients had clinical progression in Cycle 1 –
Slide 37: Summary of Overall Response (RECIST 1.1)
37 <#> Response Category No. of Subjects Comment 28 24 patients treated at 1.6 and 3.0 µg/kg PR (Partial Response) 10 0/4 PR at 1.0 µg/kg 2/4 PR at 1.6 µg/kg 8/ 20 PR at 3.0 µg/kg SD (Stable Disease) 9 SD = reductions in tumor mass ranging from -5 % to -28.8% PD (Progressive Disease) 6 2 rPD and 4 c
Slide 38: PEGPH20 + Gemcitabine Treatment Reduced Serum CA19-9
38 <#> PEGPH20 + Gemcitabine Treatment Reduced Serum CA19-9 -100 -80 -60 -40 -20 0 20 40 60 80 100 120 140 160 180 200 ** * * * * 3.0 g/kg 1.0 g/kg 1.6 g/kg * PR * Ch an ge fr om B as eli ne ( % ) • Elevated CA19-9 is defined as >37 U/mL • 12 of 14 patients experienced CA19-9 response • 6/14 (43%
Slide 39: HA Assessment in Tumor Biopsy
39 <#> HA Assessment in Tumor Biopsy • Baseline core biopsy was optional in the dose escalation phase and required in the expansion cohort • The method of HA scoring was prospectively defined for tumor-cell associated and stromal associated tissue • Staining was semi-quantified by an independent boa
Slide 40: HA Target Modulation Observed in Patient 007-405
40 <#> HA Target Modulation Observed in Patient 007-405 • 64 year old Caucasian male • Initial diagnosis: 8/24/2012; Received the first PEG dose (3 µg/kg): 9/11/2012 • Baseline biopsy: 8/24/2012; Post dose biopsy: 10/24/2012 (6 weeks) • A 42% depletion of HA in tumor biopsy was observed at Week 6 HA
Slide 41: Patient Achieved PR and Partial Metabolic Response by EOC1
41 <#> PET CT Baseline EOC1 EOC3 PET Patient 414 Achieved PR and Partial Metabolic Response by EOC1
Slide 42: Patient 414 Achieved Complete Biochemical Response in CA 19-9
42 <#> • A 30.0% reduction in tumor burden (partial response by RECIST 1.1) was observed by EOC1 • A 52 % reduction in FDG uptake on PET/CT (partial metabolic response by EORTC criteria) was observed at EOC1 • CA19-9 was reduced from 150,000 U/mL at baseline to 35.9 U/mL at Cycle 7 (ULN: 37 U/mL), a
Slide 43: Patients with Tumor Cell Associated HA-high had Longer PFS and OS
43 <#> Tumor biopsies were fixed in 10%NBF and embedded in paraffin. 5µm sections were prepared and stained for HA with a biotinylated HABP (HA binding protein) probe followed by streptavidin-HRP and hematoxylin counter stain. Staining was semi- quantified by an independent board certified pathologi
Slide 44: Phase 1b Conclusions
44 <#> • 28 patients were enrolled and received at least one dose of study drug. 24 patients were treated at either 1.6 or 3.0 µg/kg; RP2D is 3.0 µg/kg • MSEs (muscle spasm, myalgia and arthralgia) were the most common treatment-related adverse events and restricted to grade 1 and 2; chronic therapy
Slide 45: Conclusions and Ongoing Phase 2 Studies
45 <#> • PEGPH20 in combination with gemcitabine is well tolerated in stage IV PDA patients • Confirmation of combination treatment effect (ORR, PFS and OS) based on HA levels will be further evaluated in the on-going randomized phase 2 studies where biopsy is a requirement for patient enrollment •
Slide 46: Acknowledgement
46 <#> Patients and their supporting families Sunil R Hingorani1MD, PhD, William P Harris2MD, Joseph Thaddeus Beck3MD, Boris A Berdov4MD, Stephanie A Wagner5MD, Eduard M Pshevlotsky6MD, Sergei A Tjulandin7MD, Oleg A Gladkov8MD, Randall F Holcombe9MD, Lisa Schechet10, Ping Jiang 10MD, Joy Zhu10MD, Ph
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