Slide 1: PEGPH20: The Science & The Strategy
PEGPH20: The Science & The Strategy January 7, 2015 Exhibit 99.2 1
Slide 2: Forward-Looking Statements
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 1995. Examples of such statements include future product development and regul
Slide 3: Halozyme: Two Potential Drivers of Future Growth and Value
Halozyme: Two Potential Drivers of Future Growth and Value ENHANZE™ (rHuPH20) 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 PEGylated form of rHuPH20 Investigational new drug in phase 2 development PEGPH20 3
Slide 4: PEGPH20 Goal: Improving Targeting of Co-Administered Cancer Drugs
PEGPH20 – Investigational new drug – Intended to target Hyaluronan (HA), a key component of the tumor microenvironment (TME) – Potential to increase tumor-selective access of co-administered anticancer therapy into tumors that accumulate high levels of hyaluronan (HAhigh) • Small molecule chemothe
Slide 5: Clinical Focus Informed By HAhigh Expression, 5-yr Mortality, and Incidence
Clinical Focus Informed By HAhigh Expression, 5-yr Mortality, and Incidence Initial Focus Areas Highlighted in Blue Jacobetz, et al. Gut. 2013;62:112–120. GLOBOCAN 2012, American Cancer Society; Halozyme Analysis. 5
Slide 6: Targeting Large Markets With Poor Survival Rates
1L Stage IV Pancreatic Cancer 2L Stage IIIB/IV Non Small Cell Lung Cancer Annual Incidence (US and EU 5) ~100,000 ~80,000 Estimated % with HAhigh 40-60% 35-45% 5 Year Survival 5% 16.8% Overall Survival with Current Standard of Care 8.5 months (Abraxane® plus gemcitabine) 7-8 months (docetaxel, Alimt
Slide 7: 2015 Financial Guidance
2015 Financial Guidance 2015E Comments Net Revenues $85M - $95M Royalties, sales of rHuPH20 to partners, Hylenex sales and collaboration revenues Operating Expenses1 $145M - $155M R&D driven by clinical trial enrollment Cash Burn $35M - $45M Does not include new ENHANZE™ deals NOTE: 1) Includes ~$20
Slide 8: Today's Agenda
Today’s Agenda Introduction and Objectives Helen Torley, MB, ChB, MRCP President and Chief Executive Officer Halozyme Therapeutics PEGPH20 Mechanism of Action Christopher Thanos, PhD Director, Biotherapeutics Halozyme Therapeutics Exploring Combinations of PEGPH20 With Cancer Therapies Curt Thompson
Slide 9: Today's Agenda
Today’s Agenda Introduction and Objectives Helen Torley, MB, ChB, MRCP President and Chief Executive Officer Halozyme Therapeutics PEGPH20 Mechanism of Action Christopher Thanos, PhD Director, Biotherapeutics Halozyme Therapeutics Exploring Combinations of PEGPH20 With Cancer Therapies Curt Thompson
Slide 10: PEGPH20: Mechanism of Action
PEGPH20: Mechanism of Action Christopher Thanos, PhD Director, Biotherapeutics Halozyme Therapeutics 10
Slide 11: Hyaluronan (HA): A Physical Barrier to Cancer Therapy Access
Hyaluronan (HA): A Physical Barrier to Cancer Therapy Access HA is a polysaccharide Stabilizes the TME via binding to extracellular and cell surface components Helps create a barrier to entry of cancer therapeutics into tumor – Increased tumor interstitial pressure 1,2 – Vasculature compressio
Slide 12: HAhigh Tumor Microenvironment
HAhigh Tumor Microenvironment Illustration of TME HAhigh results in – Increased tumor interstitial pressure (IP) – Compression of blood vessels – Poor anti-cancer therapy access to tumor Malignant cell (+cancer stem cells) HA Collagen Cancer-associated fibroblasts Endothelial Cell Lymphocyte Pericyt
Slide 13: Measurement of HA Has Evolved Over the Clinical Development Program
TSG6 Link (∆Hep) TSG-6 Link (∆Hep) Human IgG Fc HTI-601 = biotin-TSG-6-∆Hep-Fc Measurement of HA Has Evolved Over the Clinical Development Program Recombinant Protein Cartilage Derived Higher specificity Lower specificity Pathologist assisted computer image analysis Pathologist assessed Lower inter-
Slide 14: HA Accumulation Similar In Primary Tumor and Metastasis
HA Accumulation Similar In Primary Tumor and Metastasis Archived biopsies from breast adenocarcinoma samples stained with HTI 601 HAhigh Primary Breast Cancer HAhigh Paired Brain Metastasis Jadin, et al. Submitted for publication 2014. 14
Slide 15: Accumulation of HA Accelerates Tumor Progression In Animal Model
Accumulation of HA Accelerates Tumor Progression In Animal Model Koyama (Itano), et al. Am. J. Pathol. 2007,170:1086. Has2∆Neo Control 450 0 50 100 150 200 250 300 350 400 Tu m or V ol um e (m m 3 ) Days after Tumor Appearance HER2/Neu/HAS2 Transgenic Mouse Model 1 3 5 7 9 11 13 15 HAhigh HER2/Neu/H
Slide 16: Accumulation of HA Drives Tumor Progression in Pancreatic Cancer Model
Accumulation of HA Drives Tumor Progression in HAhigh Animal Model of Pancreatic Cancer Modified from Kultti, et al. Biomed Res Int. 2014 Mice were inoculated with either HAlow parental BxPC3 cells or HAhigh BxPC3/HAS3 cells and tumor growth monitored. BxPC3 Pancreatic Human Xenografts 0 2 4 6 8 1 0
Slide 17: Tumor HA Accumulation Associated with Shorter Survival
Tumor HA Accumulation Associated with Shorter Survival Pancreatic Cancer Retrospective Study Survival of pancreatic cancer patients categorized according to staining intensity for HA in tumor biopsies. N=43 HAhigh, 32/43 (74%) Median Survival: 299 days HAlow, 11/43 (26%) Median Survival: 738 days P
Slide 18: Non-Clinical Approach: Validated Methods, Confirmation in Independent Labs
Non-Clinical Approach: Validated Methods, Confirmation in Independent Labs Assessment of PEGPH20 (single agent and enhanced combination) antitumor activity in validated models – HAhigh human xenograft models – Patient derived (PDx) HAhigh tumor models – Genetically engineered mouse models of pancr
Slide 19: PEGPH20-Mediated HA Depletion Selectively Impacts HAhigh Tumors
PEGPH20-Mediated HA Depletion Selectively Impacts HAhigh Tumors In Animal Model 0 2 4 6 8 1 0 1 2 2 5 0 5 0 0 7 5 0 1 0 0 0 1 2 5 0 1 5 0 0 1 7 5 0 2 0 0 0 P E G P H 2 0 4 .5 m g /k g V e h ic le T im e (D a y s ) T u m o r V o lu m e ( m m 3 ) ± S E M NSCLC PDx Model Example 0 3 6 9 1 2 1 5 1 8 2 1
Slide 20: PEGPH20-Mediated HA Removal Reduces Tumor Interstitial Pressure
PEGPH20-Mediated HA Removal In Animal Model Reduces Tumor Interstitial Pressure, Decompressing Vessels Normalization of Tumor IP PEGPH20-mediated Vessel Expansion -2 0 0 2 0 4 0 6 0 8 0 1 0 0 1 2 0 0 .0 0 .2 0 .4 0 .6 0 .8 1 .0 1 .2 0 .0 1 5 0 .1 5 1 .5 4 .5 1 5 C o n t r o l T im e a ft e r t r e a
Slide 21: Tumor Reperfusion Post PEGPH20 Results In Increased Drug Accumulation
Tumor Reperfusion Post PEGPH20 Administration Results In Increased Drug Accumulation in Tumor Animal Model Osgood et al., AACR, Pancreatic Cancer Mtg., May 2014 ABRAXANE® Treated BxPC3/HAS3 Pancreatic Xenograft Tumors Mice (n≥4) received nab-paclitaxel (10 mg/kg, IV) ± PEGPH20 (1 mg/kg, IV). Mice sa
Slide 22: PEGPH20 Evaluated With Multiple Cancer Therapeutics Across Broad Range of Sizes
PEGPH20 Evaluated With Multiple Cancer Therapeutics Across Broad Range of Sizes In preclinical studies, PEGPH20 was shown to improve therapeutic efficacy independent of size, charge or PK of the therapeutic. 0 .1 1 1 0 1 0 0 1 0 0 0 1 0 0 0 0 1 0 0 0 0 0 S ize (n m ) monoclonal antibodies (e.g. cetu
Slide 23: PEGPH20 Enhances Penetration Into HAhigh Tumor but Not Normal Tissue
PEGPH20 Enhances Penetration Into HAhigh Tumor but Not Normal Tissue In Animal Model Fluorophore-labelled dextrans (2,000,000 Da) were injected into tumor-bearing KPC mice. Tumor Vehicle Intestine Kidney Liver PEGPH20 KPC Genetically Engineered Mouse Model of PDA Jacobetz, et al, Gut. 2013 23
Slide 24: HAhigh Tumor Microenvironment
HAhigh Tumor Microenvironment Illustration of TME HAhigh results in – Increased tumor interstitial pressure (IP) – Compression of blood vessels – Poor anti-cancer therapy access to tumor Malignant cell (+cancer stem cells) HA Collagen Cancer-associated fibroblasts Endothelial Cell Lymphocyte Pericyt
Slide 25: PEGPH20 Drives Multiple Changes In the Tumor Microenvironment
PEGPH20 Has Been Shown In Animal Models to Drive Multiple Changes In the Tumor Microenvironment Illustration of TME (Post PEGPH20) Expected TME Post PEGPH20 Administration: – Reduced tumor interstitial pressure – Expansion of blood vessels Malignant cell (+cancer stem cells) HA Collagen Cancer-assoc
Slide 26: PEGPH20 Drives Multiple Changes In the Tumor Microenvironment
PEGPH20 Has Been Shown In Animal Models to Drive Multiple Changes In the Tumor Microenvironment Illustration of TME (Post PEGPH20) Expected TME Post PEGPH20 Administration: – Reduced tumor interstitial pressure – Expansion of blood vessels Malignant cell (+cancer stem cells) HA Collagen Cancer-assoc
Slide 27: PEGPH20 Plus Chemotherapy Can Result in Increased Tumor Cell Death
PEGPH20 Plus Chemotherapy Can Result in Increased Tumor Cell Death In Animal Models Illustration of TME (Post PEGPH20 plus Chemotherapy) Expected TME Post PEGPH20 plus Chemotherapy Administration: – Reduced tumor interstitial pressure – Expansion of blood vessels – Increased anti-cancer therapy acce
Slide 28: PEGPH20 Rapidly Reverses High Tumor Pressure Allowing Increased Drug Access
PEGPH20 In Animal Models Rapidly Reverses High Tumor Pressure Allowing Increased Anti-Cancer Drug Access to Tumor Hyaluronan Degradation PEGPH20 In Animal Models Tumor Interstitial Pressure Reduced Tumor Vasculature Expansion Increased Diffusion and Delivery of Therapeutics Into Tumor/Metastases, bu
Slide 29: Today's Agenda
Today’s Agenda Introduction and Objectives Helen Torley, MB, ChB, MRCP President and Chief Executive Officer Halozyme Therapeutics PEGPH20 Mechanism of Action Christopher Thanos, PhD Director, Biotherapeutics Halozyme Therapeutics Exploring Combinations of PEGPH20 With Cancer Therapies Curt Thompson
Slide 30: Nonclinical Exploration of Combinations of PEGPH20 With Cancer Therapies
Nonclinical Exploration of Combinations of PEGPH20 With Cancer Therapies Curt Thompson, PhD Senior Director, Pharmacology Halozyme Therapeutics 30
Slide 31: PEGPH20 Increased Survival With Gemcitabine and Abraxane in Animal Model
In Pancreatic Cancer Animal Model, PEGPH20 Increased Survival When Combined with Gemcitabine and Abraxane® HAhigh AsPC1/HAS3 Pancreatic Xenografts Osgood, et al. AACR, Pancreatic Cancer: Innovations in Research and Treatment, May 2014, in New Orleans. Mice (n≥12) received PEGPH20 (37.5 µg/kg, IV, 2x
Slide 32: PEGPH20 Doubled Survival With Docetaxel in NSCLC Animal Model
In NSCLC Animal Model, PEGPH20 Doubled Survival When Combined with Docetaxel HAhigh LUM697 NSCLC Patient Derived Human Xenografts Mice (n≥12) received PEGPH20 (37.5 µg/kg, IV, 2x/wk) ± D (5 mg/kg, IV, q7d). Percent survival defined as (a) time to tumor volume ≥2000 mm3, (b) time to ≥20% bodyweight l
Slide 33: PEGPH20 With Halaven Resulted In Tumor Regression in TNBC Model
In Triple Negative Breast Cancer Animal Model, PEGPH20 Resulted In Tumor Regression Combined with Halaven® Individual Tumor Growth Plot -100 0 100 200 300 400 500 600 700 800 900 Tu m or V ol % c ha ng e PEGPH20 +Halaven® HAhigh HCC1806/HAS3 Xenografts 6/7 regressions Huang, et al. Halozyme Therapeu
Slide 34: PEGPH20 Enhanced Antibody Access in Ovarian Cancer Model
In Ovarian Cancer Animal Model, PEGPH20 Enhanced Antibody Access Trastuzumab labeled with AF488 48h post treatment Anti-PD-L1 labeled with AF488 48h post treatment Increased Trastuzumab Accumulation Singha, et al. Mol Cancer Ther. Epub Dec 2014. – PEGPH20 + PEGPH20 – PEGPH20 + PEGPH20 HAhigh SK-OV3/
Slide 35: PEGPH20 Enhanced shIDO-ST and Neutrophil Influx
In Pancreatic Cancer Animal Model, PEGPH20 Enhanced shIDO-ST and Neutrophil Influx Luc-expressing Orthotopic PDA Tumors (KPC Derived) PE G P H 20 + sh ID O -S T sh ID O -S T A lo ne Immuno- fluorescence staining (5x) w/Mab against ST or neutrophils, 96h post-treatment Tumor (DAPI stained) Tumor Neut
Slide 36: PEGPH20 Facilitated shIDO-ST-mediated Tumor Regression
In Pancreatic Cancer Animal Model, PEGPH20 Facilitated shIDO-ST-mediated Tumor Regression shIDO-ST (5e6 CFU/mouse, qd3x, d14-16), PEGPH20 (2.25 mg/kg, 1x d13) Luc-expressing Orthotopic PDA Tumors (KPC Derived) Manuel, et al. (City of Hope), AACR, Pancreatic Cancer Mtg, May 2014, in New Orleans 0 1 0
Slide 37: PEGPH20 Enhanced Immune Cell Access into HAhigh Tumor
In Ovarian Cancer Animal Model, PEGPH20 Enhanced Immune Cell Access into HAhigh Tumor Human primary NK cells labeled with PKH26 co-injected with trastuzumab, 48h post Human primary T cells labeled with PKH26, 48h post-treatment Increased Primary T Cell Accumulation Increased Natural Killer (NK) Cell
Slide 38: PEGPH20 Plus Trastuzumab and NK Cells Inhibited Tumor Growth
In Ovarian Cancer Animal Model, PEGPH20 Plus Trastuzumab and NK Cells Inhibited Tumor Growth Increased Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) SKOV3/HAS2 Tumor Xenografts Tu m or v ol um e (m m 3 ) Singha, et al. Mol Cancer Ther. Epub Dec 2014. 38
Slide 39: PEGPH20 Nonclinical Summary
PEGPH20 Nonclinical Summary PEGPH20, an investigational drug, depletes HA content of tumors in animal studies – Reduced tumor interstitial pressure resulting in increased tumor perfusion – Increased tumor access of • Small molecules • Monoclonal antibodies including immune checkpoint inhibitors •
Slide 40: Today's Agenda
Today’s Agenda Introduction and Objectives Helen Torley, MB, ChB, MRCP President and Chief Executive Officer Halozyme Therapeutics PEGPH20 Mechanism of Action Christopher Thanos, PhD Director, Biotherapeutics Halozyme Therapeutics Exploring Combinations of PEGPH20 With Cancer Therapies Curt Thompson
Slide 41: From Theory to Initial Clinical Experience
From Theory to Initial Clinical Experience Sunil R. Hingorani, MD, PhD Associate Member, FHCRC Director, Center for Accelerated Translation in Pancreas Cancer 41
Slide 42: Sobering Realities of Pancreas Cancer
Increasing incidence with unabated mortality Eludes detection until late stages Metastasizes early and widely during disease progression Modest survival improvement in last 3 decades Highest 1, 5, and 10 year mortalities of any cancer Sobering Realities of Pancreas Cancer 42
Slide 43: Pancreas Cancers are Hypoperfused
Pancreas Cancers are Hypoperfused: They Have a Decreased Blood Supply CT Scan MRI Scan Von Hoff, et al. Cancer Cell. 2009,16:708. 43
Slide 44: Pancreas Cancer as a Solid Tumor Organ: Desmoplastic Response
Pancreas Cancer as a “Solid Tumor Organ”: Multi-faceted Desmoplastic Response Cancer epithelium Stroma (everything else) Pancreas Cancer Histology 44
Slide 45: Changing the Game: Altering Intratumoral Physical Dynamics
Changing the Game: Altering Intratumoral Physical Dynamics to Advantage in Pancreas Cancer PI > Pv and diffusion and convection limited PI < Pv and diffusion and convection favorable PI < Pv and permanent remodeling of the tumor microenvironment Provenzano, et al. Cancer Cell. 2012,21(3):418. PEGPH2
Slide 46: Breaching the Pancreas Cancer Sanctuary: Changing Disease Biology
Before • Hard • Fibrotic • Hypovascular MPA#1 + GemcitabineAft r • Soft • Friable • Hypervascular Breaching the Pancreas Cancer Sanctuary: Changing Disease Biology with PEGPH20 Provenzano, et al. Cancer Cell. 2012,21(3):418. KPC Mouse Model 46
Slide 47: Breaching the Pancreas Cancer Sanctuary: Newly Vulnerable Disease
Normal Pancreas Pancreas Cancer Pancreas Cancer Treated with PEGPH20 Drug Lectin Breaching the Pancreas Cancer Sanctuary: Creating a Newly Vulnerable Disease Provenzano, et al. Cancer Cell. 2012,21(3):418. 47
Slide 48: Combination Therapy Significantly Improves Survival in KPC Mice
G = 55.5d, G+P = 91.5d; *p=0.004 Combination Therapy Significantly Improves Survival in KPC Mice Randomized, Blinded, Placebo-controlled Preclinical Trial in KPC Pancreas Cancer Model Provenzano, et al. Cancer Cell. 2012. 48
Slide 49: Decreased Metastatic Burden With PEGPH20 + Gemcitabine in KPC Mice
Decreased Metastatic Burden With PEGPH20 + Gemcitabine Therapy in KPC Mice Provenzano, et al. Cancer Cell. 2012. Treatment (n=10) % Met Disease % Liver Mets % Lung Mets % Lymph Node Mets GEM + Vehicle 93 73 40 73 GEM + PEGPH20 43 43 21 36 Gemcitabine dosed 1x/wk @ 3-wk on / 1-wk off schedule; PEGPH2
Slide 50: Clinical Proof of Concept in Phase 1b Trial in Advanced Pancreatic Cancer
Clinical Proof of Concept Demonstrated in Phase 1b Trial in Advanced Pancreatic Cancer Halozyme Study 201 Study Objectives Primary – Assess safety and tolerability of PEGPH20 in combination therapy – Establish recommended phase 2 dose (RP2D) of PEGPH20 in combination with gemcitabine in patients w
Slide 51: Study 201 PEGPH20 Treatment-Related AEs
Study 201 PEGPH20 Treatment-Related AEs (≥10% in Total Incidence) *One Grade 5 event reported: cerebrovascular accident. Adverse Events N = 28 Grade 3/4 All Grades Incidence, % Any AE 7 (25.0) 24 (85.7) Muscle spasms 2 (7.1) 15 (53.5) Myalgia 0 11 (39.3) Arthralgia 0 8 (28.6) Edema peripheral 1 (3.6
Slide 52: Study 201: Example of HA Target Modulation
Study 201: Example of HA Target Modulation Hingorani, et al. ASCO 2013 (abstract 4010). Post-treatment biopsy (6 wks of therapy) 0 50 100 150 200 250 300 H S co re 0 50 100 150 200 250 300 Pre-treatment biopsy 52
Slide 53: Study 201: Example of Increased Perfusion after PEGPH20
Study 201: Example of Increased Perfusion (Ktrans) after PEGPH20 Hingorani et al., ECCO 2013 (abstr 2598) Hingorani et al., J Clin Oncol 2013 (abstr 4010) Baseline: Mean = 0.14 min–1 Median = 0.10 min–1 24-hr Post 1st Dose: Mean = 0.20 min–1 Median = 0.17 min–1 53
Slide 54: Study 201: Example of Radiographic Response
Study 201: Example of Radiographic Response (PR) at EOC1 Baseline Sum Target L = 83.2 mm TL3 Diameter: 19.3 mm Volume: 1.5 cm3 TL3 Diameter: 10.2 mm Volume: 0.33 cm3 EOC1 Sum Target L = 56.1 mm Hingorani, et al. ASCO 2013 (abstr 4010) 54
Slide 55: Final Results of Study 201: HAhigh as Response Predictor
Final Results of Study 201 Exploratory Analyses Support Potential for HAhigh as Response Predictor Single-arm Phase1b Evaluation PEGPH20+gemcitabine in Stage IV Metastatic Pancreatic Ductal Adenocarcinoma Source: Study 201 Final Report ORR% (n)* Median PFS (days) OS (days) Gem+PEGPH20 29% (7/24) 154
Slide 56: Summary: PEGPH20+Gemcitabine in Models and Patients
Pancreas cancer primary tumors and metastases effectively exclude chemotherapeutics PEGPH20 alters unfavorable hydrodynamics to promote drug penetration PEGPH20 seems well-tolerated in patients Patients with high intratumoral HA levels appear to benefit most from PEGPH20 Summary: PEGH20+Gemc
Slide 57: Today's Agenda
Today’s Agenda Introduction and Objectives Helen Torley, MB, ChB, MRCP President and Chief Executive Officer Halozyme Therapeutics PEGPH20 Mechanism of Action Christopher Thanos, PhD Director, Biotherapeutics Halozyme Therapeutics Exploring Combinations of PEGPH20 With Cancer Therapies Curt Thompson
Slide 58: Clinical Development Plan Update
Clinical Development Plan Update Athena Countouriotis, MD Chief Medical Officer Halozyme Therapeutics 58
Slide 59: Non-Clinical Observations Inform Our Clinical Development Strategy
Robust Non-Clinical Observations Inform Our Clinical Development Strategy HAhigh present in many patients with common solid tumors Evaluate PEGPH20 in multiple tumor types PEGPH20 inhibits tumor growth in HAhigh animal tumor models Select HAhigh patients through development of Companion Diagnostic P
Slide 60: Hypothesized Results for PEGPH20 with Abraxane and Gemcitabine
Hypothesized Results for PEGPH20 in Combination with Abraxane® and Gemcitabine In Pancreatic Cancer Abraxane® + gemcitabine (AG) PEGPH20 + AG (PAG) High HA Low HA Highest PFS (HAhigh) Lowest PFS (Poor prognosis - HAhigh) Moderate PFS (Low HA, likely = AG) Moderate PFS (Better prognosis - Low HA) PEG
Slide 61: Study 202: Ongoing Trial of PEGPH20 with Abraxane and Gemcitabine
Study 202: Ongoing Trial of PEGPH20 with Abraxane® and Gemcitabine PEGPH20 + Abraxane® + gemcitabine Abraxane® + gemcitabine Stage IV Metastatic PDA N=260 KPS 70-100 Biopsy Tissue Primary endpoints: PFS Rate of TE events Secondary endpoints: PFS by HA level ORR OS H A LO -2 02 Total Sites 44 (US onl
Slide 62: Companion Diagnostic Approach Designed to Meet FDA Standards
Referring Institution CURRENT Central Lab FUTURE Companion Diagnostic Current Approach Designed With Goal of Meeting FDA Standards and Expectations for a Companion Diagnostic Diagnostic Biopsy Embed Process Section Stained Slide IHC-based Stain Unstained Section Digital Image Score With Partner U.S.
Slide 63: Study History and Status
Study 202 History and Status Clinical Hold: based on DMC finding of potential imbalance in TE events between treatment arms Protocol Amendment Add ~100 patients 2:1 PAG to AG randomization Exclude high Thromboembolic Event risk patients Add LMWH to both arms Additional primary endpoint: ev
Slide 64: Interim Analysis Study 202
Conducted to evaluate further the level of HA accumulation (ie HAhigh) to assist in the development of our companion diagnostic and our clinical development plan in pancreatic and NSCLC Important caveats – Open database, ongoing study – Data verification ongoing Interim Analysis Study 202 64
Slide 65: Study 202: Response Rate Analysis Populations
Study 202: Response Rate Analysis Populations Populations Evaluated PAG n= AG n= Analysis Randomized to Trial in Stage 1 77 69 Data Through April 9th, 2014 Response Rate Population Safety population: received study drug prior to Clinical Hold 74 61 Overall Response Rate HA response rate population:
Slide 66: Early Data Suggest Higher ORR with PEGPH20 Particularly in HAhigh
Results: Early Data Suggest Higher ORR with PEGPH20 Particularly in HAhigh ORR based on independent, blinded central review Safety data presented on slides 71-73 MPACT Study ORR Results: Von Hoff D. NEJM. 2013,369:1691 – Abraxane® plus gemcitabine, 23% vs gemcitabine, 7% Study 202 Interim Analys
Slide 67: Progression Free Survival Interim Results
Progression Free Survival Study 202 Interim Results: Analysis Population No. with events / total evaluated patients; median PFS in months HR P-value PAG vs AG PAG arm n=61 AG arm n=45 Safety w/HA 34/61; 5.5 30/45; 4.8 0.64 0.086 HA High 12/25; 9.2 15/23; 4.3 0.38 0.031 HA Low 22/36; 4.8 15/22; 5.6 0
Slide 68: Early Data Suggests Increased PFS In HAhigh Patients
Results: Early Data Suggests Increased PFS In HAhigh Patients Treated with PEGPH20 PFS In Patients with HAhigh K -M Est ia m te of P rogress io n Free S ur vi va l (% ) 0 10 20 30 40 50 60 70 80 90 100 Treatment Group PAG AG PAG: 9.2 MonthsAG: 4.3 Months K -M E st im at e of P ro gr es si on F re e
Slide 69: Study 202: Interim ORR and PFS Data Summary
ORR: 71% PFS: 9.2 months ORR: 29% PFS: 4.3 month ORR: 50% PFS: 4.8 months ORR: 50% PFS: 5.6 months Study 202: Interim ORR and PFS Data Summary PAG AG High HA Low HA ORR data through April 9th and reflects PAG or AG treatment PFS data through December 5th and reflects PAG AG treatment in PAG arm 69
Slide 70: Overall Safety Profile
Overall Safety Profile Treatment Related AEs >25% Patients PAG N=74 Patients, n (%) AG N=61 Patients, n (%) Preferred Term Grade 3+ Any Grade Grade 3+ Any Grade Any AE 61 (82.4) 73 (98.6) 45 (73.8) 57 (93.4) Fatigue 13 (17.6) 50 (67.6) 11 (18.0) 39 (63.9) Nausea 5 (6.8) 41 (55.4) 2 (3.3) 27 (44.3) A
Slide 71: Adverse Events Leading to Discontinuation
Adverse Event PAG AG AE leading to discontinuation 13/74 (18%) 13/61 (21%) AEs resulting in discontinuation occurring in >1 patient, either arm Pneumonitis 3 0 Pulmonary embolism 2 0 Acute renal failure 0 2 Adverse Events Leading to Discontinuation 71
Slide 72: Study 202: Stage 1 Thromboembolic Events
Parameters PAG AG Patients, N 74 61 Patients with TEs, n (%) 31 (41.9) 15 (24.6) Patients with PE, n (%) 16 (21.6) 6 (9.8) Patients with DVT, n (%) 16 (21.6) 9 (14.7) Patients with Arterial TE, n (%) 7 (9.4) 0 Grade 1 and 2 events, (% of N) 21 15 Grade ≥3 events (% of N) 23 5 Study 202: Stage 1 Inte
Slide 73: Pancreatic Cancer: Planned Next Steps
Pancreatic Cancer: Planned Next Steps Meeting with FDA (end Q1 target) – Discuss potential registration-seeking trial in HAhigh Stage 4 Pancreatic Ductal Adenocarcinoma patients Gain EMA scientific advice on proposed protocol 73
Slide 74: Non Small Cell Lung Cancer – Significant Unmet Medical Need
Non Small Cell Lung Cancer – Significant Unmet Medical Need Over 160K newly diagnosed 1L and 84K 2L patients annually (US & 5EU) Survival times remain low with no curative therapy – In 1st line non-biomarker population OS is 10-12 months and PFS is 4-6 months – In 2nd line OS is 7-8 months and P
Slide 75: Phase 1b/2 PRIMAL Study in NSCLC Initiated
Phase 1b/2 PRIMAL Study in NSCLC Initiated Dose escalation PEGPH20 + docetaxel 75mg/m2 N=Up to 240 Schedule A PEGPH20 Q21d Schedule B PEGPH20 2/W Q21d PEGPH20 + docetaxel docetaxel N = 170 HAhigh 1:1R Phase 1b Phase 2 PEGPH20 + docetaxel in HAhigh Platinum Failed NSCLC Patients Total Sites Phase 1b
Slide 76: Exploring PEGPH20 with Anti PD1 Antibody in HAhigh Tumors
Dose Escalation Endpoints: DLT, MTD, RP2D, PK of PEGPH20 and safety profile Dose Expansion Phase 1b expansion end points: ORR, DCR, DOR, PFS Plan to initiate study Q3 2015 Exploring Combination of PEGPH20 with an Anti PD1 Antibody in HAhigh Tumors—HALO 107-101 Dose escalation PEGPH20 + PD1 Inhib
Slide 77: Key Projected Program and Data Milestones
Key Projected Program and Data Milestones FDA Discussion Registration-seeking Trial Stage1 202 Efficacy and Safety Data Q1 2016 Pancreatic Cancer NSCLC Additional Cancer Q4 2015Q3 2015Q2 2015Q1 2015 Complete Enrollment 202 Stage2 Results Study 202 Target for First Patient Enrolled New Trial First Pa
Slide 78: Today's Agenda
Today’s Agenda Introduction and Objectives Helen Torley, MB, ChB, MRCP President and Chief Executive Officer Halozyme Therapeutics PEGPH20 Mechanism of Action Christopher Thanos, PhD Director, Biotherapeutics Halozyme Therapeutics Exploring Combinations of PEGPH20 With Cancer Therapies Curt Thompson
Slide 79: Non-Clinical Observations Inform Our Clinical Development Strategy
Robust Non-Clinical Observations Inform Our Clinical Development Strategy HAhigh present in many patients with common solid tumors Evaluate PEGPH20 in multiple tumor types PEGPH20 inhibits tumor growth in HAhigh animal tumor models Select HAhigh patients through development of Companion Diagnostic P
Slide 80: PEGPH20 Goal: Improving Targeting of Co-Administered Cancer Drugs
PEGPH20 Goal: Improving Targeting of Co-Administered Cancer Drugs Encouraging data from Phase1b and 2 pancreatic cancer trials supportive of potential for efficacy benefit in HAhigh tumors – FDA and EMA feedback sought for registration trial initiation 2015 Clinical testing underway in additiona
Slide 81: Question and Answer
Question and Answer