Halozyme at UBS Global Life Sciences Conference (PPT)


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  • Halozyme at UBS Global Life Sciences Conference (PPT)

    1. 1. Company Overview September 2008 – UBS Global Life Sciences Conference Matrix Therapies for Life
    2. 2. 2 Safe Harbor The Private Securities Litigation Reform Act of 1995 provides a "safe harbor" for forward-looking statements. All statements made in this presentation that are not statements of historical fact constitute forward-looking statements. The matters referred to in forward-looking statements could be affected by the risks and uncertainties of the Company's business. Such risks inherent to the Company’s business will be described in the Company’s filings, when they occur, with the Securities and Exchange Commission, as well as in its press releases. The Company's actual results may differ materially from those expressed in or indicated by such forward-looking statements.
    3. 3. 3 HALO Investment Highlights • Recombinant human hyaluronidase (rHuPH20) core technology validated by partnerships potentially worth up to $724 million in milestones, plus royalties – FDA approved product, HYLENEX, has large addressable market – Enhanze Technology partnerships with Roche and Baxter • Proprietary product candidates target extracellular matrix (“Matrix”), focused on oncology, metabolism, and dermatology, including: – Potential best-in-class prandial insulins for treatment of diabetes – Two NMEs - target multiple solid tumors and dermatologic conditions • Attractive valuation with $82 million in cash 2Q08
    4. 4. 4 Halozyme Targets the Matrix Matrix Therapies For Life
    5. 5. 5 Successful Talent Initiatives Underway Notable recent new hires • Doug Muchmore, MD – VP, Endocrinology Clinical Development (Eli Lilly) • Patrick 0’Connor, PhD – VP, Research (Pfizer, Ardea Biosciences) • Michael J. LaBarre, PhD – VP, Product Development (Biogen Idec, Vical) • James E. Cartoni – VP, Legal (DLA Piper) Total employees – 121 • 87 – R&D, clinical, regulatory, manufacturing • 12 – Commercial, project and alliance management • 22 – HR, finance, IT, legal, corporate
    6. 6. 6 rHuPH20 Core Technology: Mechanism of Action
    7. 7. 7 HYLENEX Multiple Strategic Paths for Driving the Value of rHuPH20 Low dose FDA-approved rHuPH20 for delivery of small molecules and fluids High dose rHuPH20 for delivery of large molecules (e.g., monoclonal antibodies) Leverages HALO’s unique knowledge of matrix biology and proven drug development capabilities to pursue efficient routes to approval Proprietary rHuPH20 Combinations Enhanze Technology Baxter targeting $500M market opportunity Ongoing alliances with Roche and Baxter BioScience Actively seeking additional high value partnership opportunities Generating high value programs for continued development and/or partnering
    8. 8. 8 HALO is Pursuing 4 Multi-Billion Dollar Franchise Opportunities Targeting the Matrix Drug Delivery 1. HYLENEX with Baxter Medication Delivery 2. Enhanze Technology with Roche (up to 13 biologic targets) 3. Enhanze Technology with Baxter BioScience (Gammagard® IVIG) Endocrinology 1. Insulins (diabetes) 2. Bisphosphonates (osteoporosis) Oncology 3. Mitomycin (bladder cancer) 4. PEGPH20 (NME; solid tumors) Dermatology 5. HTI-501 (NME)
    9. 9. 9 • FDA approved “For use as an adjuvant to increase the absorption and dispersion of other injected drugs; for hypodermoclysis….” • HYLENEX global sales and marketing partnership with Baxter – Alliance worth up to $65M ($10M up-front; $25M milestones; $10M pre-paid royalties; $20M equity), plus royalties • Post-marketing clinical trials ongoing – Pediatric hydration trial enrollment completed May 2008 – Interim data – American Academy of Pediatrics, October 2008 HYLENEX Product Highlights
    10. 10. 10 • Change route of administration (e.g., IV to SC) • Reduce adverse injection site reactions • Decrease pain and tissue distortion upon injection Convenience and compliance • Extend lifecycle of products coming off patent • Provide competitive differentiation and reduce COGS • Enable inpatient drugs to be injected at home Economic benefits Value proposition • Deliver more drug to intended targets • Allow drug to work faster • Increase volume of drug at each injection Efficacy Enhanze™ Technology: For Partners with Injectable Biologics and Drugs
    11. 11. 11 IgG 10mg/kg local Bioavailability = 59 +/- 7% 0.0E+00 2.0E+05 4.0E+05 6.0E+05 8.0E+05 1.0E+06 1.2E+06 1.4E+06 1.6E+06 1.8E+06 2.0E+06 0 10 20 30 40 50 60 70 80 90 100 110 120 130 Time (Hours) SerumAntibodyLevels(I-125Counts/ml)inrats IgG 10mg/kg IV Bioavailability = 100% IgG 10mg/kg local + rHuPH20 Bioavailability = 94 +/- 7% Enhanzed Remicade® Demonstrated IV Like Bioavailability and PK in a Preclinical Model Bookbinder, et al. J Controlled Release. 2006;114:230-1
    12. 12. 12 • Gammagard Liquid (intravenous immunoglobulin) - plasma derived antibody indicated for primary immunodeficiency, currently given IV • Difficult to administer SC due to low bioavailability (63%), results in need for weekly dosing • SC administration of up to 61.2 grams (612 ml) IgG with rHuPH20 at ranges of up to 300 mL per hour resulted in bioavailability equal to 92% of the IV form in Phase I/IIa trial • Potential for convenient patient self-administration at monthly intervals SC route of administration with rHuPH20 expected to deliver significant benefits to patients, prescribers, and payers Enhanzed Gammagard Can Be Delivered Monthly by Subcutaneous Route
    13. 13. 13 Roche • Roche alliance worth up to $612M ($20M up-front; $111M milestones for first 3 exclusive targets; $470M up-front & milestones for 10 additional targets; $11M equity), plus royalties • Improving manufacturing efficiency, bringing on second API supply source to support partnered and in-house programs Baxter • Baxter BioScience alliance worth up to $47M ($10M up-front; $37M milestones), plus royalties • Pivotal Phase III - Gammagard + Enhanze expected 1Q09 Enhanze Technology Alliances Could Drive Significant Value
    14. 14. 14 Proprietary Product Candidates Target the Matrix 1. Insulins: rHuPH20 combination for prandial diabetes therapy 2. Bisphosphonates: rHuPH20 combination for osteoporosis 3. Chemophase: rHuPH20 combination with Mitomycin for bladder cancer 4. PEGPH20: Pegylated rHuPH20 targets HA expressing tumors 5. HTI-501: Novel Matrix degrading enzyme for dermatology
    15. 15. 15 Insulin Program Highlights • Completed Phase I, prospective, randomized trial assessing safety, tolerability, PK, and PD of two insulin products injected SC +/- rHuPH20 – Presented at American Diabetes Association in June 2008 – rHuPH20 +/- fast-acting insulin analog (Humalog®) – rHuPH20 +/- regular insulin (Humulin®) – Conducted in 26 subjects • Positive results confirm potential to develop best-in-class therapeutic within growing, diabetes market – ~$2.5B prandial US insulin market with 13% CAGR • Anticipate initiation of Phase II clinical trial 4Q2008
    16. 16. 16 Significantly Greater Insulin Exposure Immediately Post Dose and Reduced Insulin Exposure Later 0 60 120 180 240 300 360 0 250 500 750 1000 1250 1500 0 50 100 150 200 250 Humulin Time (min) Mean(±SEM)ImmunoreactiveInsulin(pmol/L) Mean(±SEM)ImmunoreactiveInsulin(µU/mL) • rHuPH20 Co-Formulation With Humalog Reduced Median Tmax By 54% (p=0.0006) • Co-Formulation With Humulin Reduced Median Tmax By 64% (p=0.0002) PK of Humalog and Humulin with and without rHuPH20
    17. 17. 17 Significantly Faster and Greater Insulin Exposure, Starting at First Sampling Point 0 3 6 9 12 15 0 60 120 180 240 300 360 420 0 10 20 30 40 50 60 70 Humalog + rHuPH20 Humulin + rHuPH20 Humalog Humulin Time (min) Mean(±SEM)ImmunoreactiveInsulin(pmol/L) Mean(±SEM)ImmunoreactiveInsulin(mU/mL) PK of Humalog and Humulin with and without rHuPH20 in first 15 minutes Increase In Insulin Concentration From Baseline At 3 Minutes was 3-fold for Humalog + rHuPH20 (p=0.03) and 24-fold for Humulin + rHuPH20 (p<0.0001)
    18. 18. 18 0 60 120 180 240 300 360 0 1 2 3 4 5 6 7 8 9 10 Humulin Time (min) Mean(±SEM)GIR(mg/kg*min) Significantly Greater Metabolic Effect Early and Reduced Metabolic Effect Later PD of Humalog and Humulin with and without rHuPH20 • rHuPH20 Co-Formulation With Humalog Reduced Median tGIR* By 46% (p=0.0059) • Co-Formulation With Humulin Reduced Median tGIR By 63% (p=0.0105) *Time to maximum glucose infusion rate
    19. 19. 19 Halozyme’s Proprietary Insulin Formulations Could Result in Significant Clinical Benefits Attributes of HALO Insulin Products Closer to natural prandial insulin release, leading to better post- prandial glycemic control with simplified mealtime dosing Fewer hypoglycemic events Potential Clinical Benefits Lower dose and therefore reduced insulin dose dependent weight gain Better predictability with each dose Faster and greater insulin concentrations and greater glucose lowering activity early (1st 1-2 hrs) Significantly greater insulin exposure at early time points for same dose Significantly lower variability of key PK and PD variables By Improving Post-prandial Diabetes Care, HALO’s Insulin Program Could Also Reduce the Long-Term Consequences of Diabetes Lower insulin concentrations and less glucose lowering activity later (after 3-4 hrs)
    20. 20. 20 HALO Insulins - Multiple Options for Value Creation • Potential for significant advantages over current standard of care and other compounds in development • Compelling development path – Co-formulation with two already approved products – Potential for efficient regulatory pathways - 505(b)(2) in US • Halozyme is well positioned to maximize value from insulin programs – IP protection on rHuPH20 combinations through 2024 – Poised to begin multiple Phase II studies – Opportunity to develop and/or partner assets • Target initiation of Phase II clinical trial by end of 2008. Study will evaluate prandial glycemic control in T1 diabetic patients
    21. 21. 21 Bisphosphonate Program – Differentiated Product targeting a >$4B Market • >$4 billion annual market - long-term oral compliance is poor due to insufficient efficacy, GI toxicity, and cumbersome dosing regimens; >75% of patients discontinue therapy within 3 years • IV BPs - inconvenient, expensive, key prescribers have limited capabilities to administer them • IV-administered Reclast® and Boniva® - attractive targets for conversion to SC with rHuPH20 • Bisphosphonates + rHuPH20 may facilitate IV to SC conversion and help ensure compliance via convenient annual/semi-annual dosing and avoidance of GI toxicity • Target - enter clinic for at least one combination in 4Q08
    22. 22. 22 Chemophase Program – Targeting Unmet Medical Need in Superficial Bladder Cancer • Tumor recurrence rates for superficial bladder cancer are 40-85%; 50% of recurrences occur within the first year • Chemophase may increase absorption of Mitomycin C into the bladder wall to decrease recurrence rates • Ongoing Chemophase Phase I/IIa trial successful in determining MTD and demonstrating safety and tolerability of induction and maintenance dosing; positive interim data announced June 2008 • Preparing to consult with regulatory authorities, FDA and Scientific Advice for EU, to determine optimal regulatory pathway to approval • Anticipate start of pivotal clinical trials in 2009
    23. 23. 23 PEGPH20 May Address a Key Limitation of Chemotherapy Efficacy • HA-rich halos found on many types of aggressive tumors (breast, prostate, pancreatic) • PEGPH20 collapses HA dependent pericellular halos on tumor cells • Modulates resistance to chemotherapy HA TUMOR CELL + Enzyme=Halo degraded Halo PEGPH20 TUMOR CELL
    24. 24. 24 IV PEGPH20 Degrades Tumor HA and Rapidly Reduces Tumor Interstitial Fluid Pressure (IFP) * IM PC-3 tumor pressure measured 20 minutes prior and for 2 hours following IV injection of 10,000 units of PEGPH20 (n=3), or Carrier Buffer (n=3) -20 0 20 40 60 80 100 120 -0.25 0.00 0.25 0.50 0.75 1.00 1.25 Dosed Time after injection (min) NormalizedTumorIFP + API Buffer + PEGPH20 >80% reduction in tumor IFP within 1st hour
    25. 25. 25 IV PEGPH20 Markedly Increases the Antitumor Activity of Taxotere in HA-Positive Tumor Model ILS improvement of 225% for T+PEGPH20 vs. 59% for T alone PC3 hormone refractory prostate carcinoma (HRPC) Model
    26. 26. 26 PEGPH20 Program: Highlights and Next Steps • Proof of principle efficacy data presented at AACR July 2008: Survival increased significantly in mouse tumor model for PEGPH20 plus docetaxel compared to docetaxel alone • Further evaluation of PEGPH20 in relevant tumor models alone and in combination with optimal chemotherapy regimens • Additional studies on-going to support PEGPH20 regulatory filing • Anticipate start of first Phase I clinical trial 1H09
    27. 27. 27 HTI-501: Matrix Degrading Enzyme Targets Cellulite and Other Dermatology Applications • Enzyme digests the fibrous septae (cords) which cause the characteristic dimpling associated with cellulite • HTI-501 degrades collagen at pH 5-6 but is rapidly inactivated by the body’s natural physiologic pH • Duration and location of enzyme activity is tightly controlled, which may confer significant advantages compared to bacterial collagenases • Established proof of principle efficacy against fibrous septae in obese rodent and porcine models • Next steps: Further characterization in relevant pharmacology models where tight control and repeat use are required
    28. 28. 28 TARGET fibrous septae create dimples Fat Cells Fibrous Septae Dimple HTI-501 Matrix Degrading Enzyme Program Cellulite is Caused by Fibrous Septae
    29. 29. 29 fibrous septae create dimples 1. Enzyme injected in active state 2. Enzyme digests fibrous septae 3. Body inactivates enzyme Fat Cells Fibrous Septae 4. Dimple relieved Dimple Principles of HTI-501
    30. 30. 30 Milestones • Presentation of Bisphosphonates pre-clinical data, 2Q08 • Presentation of PEGPH20 pre-clinical IFP data, 2Q08 • Presentation of HTI-501 pre-clinical data, 2Q08 • Presentation of Insulin Phase I data, ADA, 2Q08 • Release of Chemophase Phase I/IIa data, 2Q08 • Presentation of PEGPH20 pre-clinical proof of principle data, 3Q08 • Initiate Insulin Phase II clinical trial, 4Q08 • Initiate clinical trial for Bisphosphonates program, 4Q08 • Initiate GammaGard + Enhanze Pivotal Phase III clinical trial, 1Q09 • Initiate PEGPH20 Phase I clinical trial, 1H09 • Initiate Chemophase Pivotal Phase III, 2009
    31. 31. 31 HALO’s Unique Investment Thesis 4 Multi-Billion Dollar Franchise Opportunities Targeting the Matrix • Drug delivery franchise may provide revenue and non-dilutive cash to fund proprietary franchises in endocrinology, oncology, dermatology • Matrix enzymes (rHuPH20, PEGPH20, HTI-501) with broad potential across variety of therapeutic uses – rHuPH20 based products with potentially best-in-class profiles, faster time to market, and lower development risk – NMEs targeting major indications • Attractive valuation with $82 million in cash at 2Q08