Halozyme's Phase 2 Insulin-PH20 Study Demonstrates Faster Insulin Absorption and Superior Glucose Control in Type 1 Diabetic Patients

SAN DIEGO--(BUSINESS WIRE)--Jun. 6, 2009-- Halozyme Therapeutics, Inc. (Nasdaq: HALO) today announced Phase 2 results that demonstrated faster insulin absorption and increased peak insulin concentrations in type 1 diabetic patients after co-administration of its recombinant hyaluronidase enzyme (PH20) with Humalog^® (insulin lispro), a mealtime insulin analog. Study results also showed a significant reduction in postprandial blood glucose levels following administration of a standardized test meal, with improvements in both peak glycemic response and total hyperglycemic exposure compared to Humalog alone. Mean glucose levels after the meal challenge remained within current treatment targets throughout the eight hour post meal observation period. The company presented these results at the American Diabetes Association (ADA) 69th Scientific Sessions today in New Orleans.

In addition, Halozyme announced that its first treatment study with three times per day mealtime dosing of Insulin-PH20 in type 1 diabetic patients began in May, ahead of the company's previous guidance for a fourth quarter 2009 start date.

"The faster and shorter blood insulin concentration profile observed for Humalog plus PH20 in this study conducted in type 1 diabetic patients confirms our previous findings seen in healthy volunteers. The shift in the pharmacokinetics of Humalog with PH20 confers a more physiologic insulin profile and results in lower hyperglycemia after a meal," stated Jonathan Lim, M.D., Halozyme's president & CEO. "A more rapidly acting insulin may lead to such patient benefits as fewer incidences of hypoglycemia, insulin dose reduction, greater patient convenience, and less weight gain." The goal of Halozyme's Insulin-PH20 program is to develop a rapid and short-acting insulin product that would more closely mimic the mealtime insulin release that occurs in non-diabetics that could lead to improved treatment for diabetes patients.

ADA Presentation Focused on Humalog, Humulin^® R Data to Come

This Phase 2 study investigated the pharmacokinetics (PK) and glucodynamics (GD) of Humalog and Humulin R with and without Halozyme's PH20 enzyme in 21 type 1 diabetic patients. The results presented today at ADA are for the Humalog portion of the study. Additional results from this study for Humulin R alone and in combination with PH20 have been accepted for presentation at the European Association for the Study of Diabetes (EASD) meeting in the fall.

After fasting and refraining from insulin treatment for 12 hours, patients were titrated to a stabilized 100 mg/dL glucose target with intravenous (IV) glucose and/or insulin. The same optimized dose of insulin lispro (mean 5.7 IU) with and without PH20 enzyme was injected subcutaneously (SC) immediately before a standard meal of 12 oz. Ensure and plasma insulin and glucose concentrations were monitored for 8 hours. The primary endpoint was a PK measure of area under the curve (AUC_0-60) for insulin during the first 60 minutes after the SC injection. Secondary endpoints included other PK measures, glucose excursion outside of the selected target range and hypoglycemia.

Key Findings Described in the Poster Presentation Today

This clinical trial met the primary endpoint and demonstrated faster systemic insulin absorption, greater peak exposure, greater early and reduced late postprandial exposure, and a significant reduction in postprandial hyperglycemia without significant change in hypoglycemia risk. All injections were well tolerated.

• The addition of PH20 significantly reduced postprandial glucose by 40% during the first four hours after administration as measured by 147 mg/dL for the lispro-PH20 combination compared to 174 for lispro alone (p = 0.002). This resulted in less hyperglycemia for the combination treatment without additional hypoglycemia.
• PH20 combined with Humalog increased the AUC_0-60 as a percent of total insulin exposure from 40% to 59 % (p < 0.0001) and to 149% of Humalog alone for the combination treatment. The addition of PH20 significantly increased early insulin absorption during the first 60 minutes after injection.
• The time to maximum (t_max) insulin concentration with co-administration of PH20 was reduced for Humalog by 19 minutes (p < 0.0001) from 49 to 30 minutes. This indicates faster insulin absorption with PH20.
• Co-administration of PH20 increased maximum insulin concentration (C_max) for Humalog by 38% (p = 0.0007) from 45 to 62 pM/IU.

Review of Insulin-PH20 Clinical Trials

A number of clinical trials investigating Halozyme's Insulin-PH20 are currently underway and more trials are planned.

• Type 1 treatment study - This Phase 2 clinical trial, which began in May 2009, will compare regular insulin (non-analog insulin) + PH20 to lispro alone. After a one month observation period that includes dose optimization, patients will be randomized to regular insulin + PH20 or lispro and treated for three months. At the end of three months, patients will crossover to the other study treatment for another three months. The study will evaluate safety and efficacy. Roughly 20 patients will be enrolled and results should be available in 3Q2010. Patients will self administer their insulin on an out-patient basis. ClinicalTrials.gov Identifier: NCT00883558.
• Dose ranging PK study - This Phase 1 clinical trial began in 4Q08 and will determine the optimal insulin/PH20 ratios. Humalog and Humulin R will be tested with and without PH20 across a range of doses of insulin and concentrations of both PH20 and insulin in this euglycemic glucose clamp study and various PK parameters will be measured in approximately 40 healthy subjects. Results of the study will be used to optimize dosing in future trials. ClinicalTrials.gov Identifier: NCT00803972.
• Intra-subject variability - This Phase 1 trial started in 1Q09 and will test regular insulin + PH20, lispro + PH20 and lispro alone. It is a euglycemic glucose clamp study in 18 healthy subjects and will measure PK and GD parameters over eight hours on two separate administrations with the same test dose of each study drug. Information regarding the consistency of insulin absorption and action will be collected and results are expected by the end of the year. ClinicalTrials.gov Identifier: NCT00862849.

About Halozyme Therapeutics, Inc.

Halozyme is a biopharmaceutical company developing and commercializing products targeting the extracellular matrix for the endocrinology, oncology, dermatology and drug delivery markets. The company's portfolio of products and product candidates is based on intellectual property covering the family of human enzymes known as hyaluronidases and additional enzymes that affect the extracellular matrix. Halozyme's Enhanze™ Technology is a novel drug delivery platform designed to increase the absorption and dispersion of biologics. The company has key partnerships with Roche to apply Enhanze Technology to Roche's biological therapeutics for up to 13 targets and with Baxter BioScience to apply Enhanze Technology to Baxter's biological therapeutic compound, GAMMAGARD LIQUID™. The product candidates in Halozyme's research pipeline target multiple areas of significant unmet medical need. For more information visit https://www.halozyme.com.

Safe Harbor Statement

In addition to historical information, the statements set forth above include forward-looking statements (including, without limitation, (i) statements concerning the efficacy and benefits of insulin plus PH20 combinations, (ii) clinical trial results and the conclusions drawn from such trials, and (iii) the initiation and completion of clinical trials) that involve risk and uncertainties that could cause actual results to differ materially from those in the forward-looking statements. The forward-looking statements are also identified through use of the words "believe," "enable," "may," "will," "could," "intends," "estimate," "anticipate," "plan," "predict," "probable," "potential," "possible," "should," "continue," and other words of similar meaning. Actual results could differ materially from the expectations contained in forward-looking statements as a result of several factors, including regulatory approval requirements and competitive conditions. These and other factors that may result in differences are discussed in greater detail in the company's reports on Forms 10-K, 10-Q, and other filings with the Securities and Exchange Commission.

Source: Halozyme Therapeutics, Inc.

HalozymeRobert H. UhlSenior Director, Investor [email protected]