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`Halozyme Therapeutics - ViroPharma and Halozyme Announce Positive Data of Subc... Page 1 of 7
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`N EWS RELEASES DETAILS
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`View all News Release
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`ViroPharma and Halozyme Announce Positive Data
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`of Subcutaneous Cinryze® (C1 esterase inhibitor
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`[human]) with Recombinant Human Hyaluronidase
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`(rHuPHZO)
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`03/06/2012
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`- Data Presented at the 2012 Annual Meeting of the American
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`Academy of Allergy Asthma & Immunology (AAAAI) -
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`ORLANDO, Fla, March 6, 2012 /PRNewswire/--ViroPharma Incorporated
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`(NASDAQ: VPHM) and Halozyme Therapeutics (Nasdaq: HALO) today announced
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`the presentation of positive data from ViroPharma‘s Phase 2 subcutaneous trial of
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`Cinryze® (C1 esterase inhibitor [human]) in combination with Halozyme's
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`EnhanzeTM technology, a proprietary drug delivery platform using Halozyme's
`recombinant human hyaluronidase enzyme (rHuPHZO), in patients with hereditary
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`angioedema (HAE), a rare, debilitating and potentially fatal genetic disease. The
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`presentation occurred as part of the late—breaker session at the 2012 annual
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`meeting of the American Academy of Allergy Asthma & immunology (AAAAI), held
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`March 2 to 6, 201 Z in Orlando, Fla. According to the presenters, these data
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`demonstrate that subcutaneous co—administration of Cinryze with rHuPHZO was
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`easy to administer, well tolerated and resulted in sustained physiologically relevant
`C1 INH functional concentrations. The presenters concluded that this innovative
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`http://WWW.halozyme.com/investors/news—releases/news-re]ease—details/ZO] 2/Vi1‘oPha...
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`1 3 04.201 6
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`CSL EXHIBIT 1092
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`CSL EXHIBIT 1092
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`Haiozyme Therapeutics - ViroPharma and Halozyme Announce Positive Data of Subc... Page 2 of 7
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`combination administered subcutaneously as a single injection will be further
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`evaluated for the prevention of HAE attacks.
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`Cinryze is approved in the United States as intravenous (IV) administration for
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`routine prophylaxis against angioedema attacks in adolescent and adult patients
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`with HAE, and in Europe for routine prevention, pre-procedure prevention and
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`acute treatment of angioedema attacks in adolescent and adult patients with HAE.
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`ln poster #5208 entitled, ‘Safety, Pharmacokinetics (PK), and Pharmacodynamics
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`(PD) of Subcutaneous (SC) Cinryze® (Ci inhibitor(Cl lNH) with Recombinant
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`Human Hyaluronidase (rHuPHZO) in Subjects with Hereditary Angioedema (HAE),'
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`Jennifer Schranz, l\/l.D., ViroPharma's vice president of clinical research, and
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`colleagues discussed key study results.
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`Cinryze with rHuPHZO was well tolerated with no serious adverse events (SAEs),
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`and no adverse events (AEs) led to study drug discontinuation:
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`- No subjects experienced an HAE attack during the study;
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`' Mild to moderate injection site reactions were the most frequently reported
`AEs.
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`Cinryze with rHuPH20 delivered physiologically relevant Cl lNH functional
`concentrations
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`- Cinryze 2000U with rHuPH20 resulted in mean C1 lNH functional
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`concentrations greater than or equal to 0.4U/mL for 92 percent of the 72 hour
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`post dosing period as compared to 73 percent for 1000U lV.
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`Addition of rl—luPHZO to Cinryze 2000U resulted in a statistically significant
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`increase in bioavailability of Cl
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`lNH antigen relative to Cinryze 2000U alone;
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`The addition of rHuPHZO to Cinryze resulted in a dose proportional increase of
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`C1 lNH function for Cmax, Cavg, and AUCtauover the 1000 to ZOOOU dose range;
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`No C’l
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`lNH antibodies were detected during the 30 day post treatment follow up
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`after the last dose of Cinryze.
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`”Cinryze administered intravenously has been shown to be a safe and effective
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`option in the management of HAE,” said Drv Schranz. ”But HAE is not a disease for
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`which there is a 'one size fits all' therapy; there are still unmet medical needs for
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`novel therapeutic options to help patients manage their disease in a manner that
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`best suits their lives. ViroPharma is developing subcutaneous delivery of Cinryze in
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`combination with rHuPH20 to provide patients with broader options to help
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`control their disease. The results of this study support further clinical
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`Halozymc Therapeutics — ViroPharma and Halozyme Announce Positive Data of Subc... Page 3 of 7
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`development of the combination, and move us closer to potentially enabling
`prevention-minded patients living with HAE to self administer the drug
`subcutaneously with a single injection per dose."
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`Halozyme‘s Enhanze'l‘M technology, a proprietary drug delivery platform using
`recombinant human hyaluronidase enzyme (rHuPHZO) facilitates the absorption
`and dispersion of drugs or fluids that are injected under the skin. Recombinant
`HuPHZO transiently generates channels in subcutaneous tissues to increase the
`absorption and spread of injected drugs.
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`About the Study
`This open—label, multiple—dose Phase 2 study was conducted in 12 subjects with
`HAE who previously participated in the ViroPharma trial evaluating the
`pharmacokinetics of subcutaneous injections of Cinryze when given alone relative
`to intravenous infusion. Qualified subjects participated in a single i8—day study
`period, followed by a 30-day post—treatment follow-up. A iOOOU or ZOOOU dose of
`Cinryze in combination with rHuPHZO was administered as a single subcutaneous
`injection, twice weekly, allowing within-subject comparison across the different
`methods of administration. Plasma Ci
`lNH functional activity was assessed by
`chromogenic assay and plasma Ci inhibitor antigenic concentration and C4
`complement levels were assessed by ELlSA.
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`Additional information about this subcutaneous Cinryze clinical trial can be found
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`at clinicaltrialsgov.
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`About Cinryze® (Ci esterase inhibitor [human])
`Cinryze is a highly purified, pasteurized and nanofiltered plasma—derived Ci
`esterase inhibitor product.
`in the U.S., Cinryze is approved by the FDA for routine
`prophylaxis against angioedema attacks in adolescent and adult patients with
`HAE.
`in the EU, the product is approved by the EMA for the treatment and pre—
`procedure prevention of angioedema attacks in adults and adolescents with
`hereditary angioedema (HAE), and routine prevention of angioedema attacks in
`adults and adolescents with severe and recurrent attacks of hereditary
`angioedema (HAE), who are intolerant to or insufficiently protected by oral
`prevention treatments or patients who are inadequately managed with repeated
`acute treatment. Cinryze is for intravenous use only.
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`Severe hypersensitivity reactions to Cinryze may occur. Thrombotic events have
`occurred in patients receiving Cinryze, and in patients receiving off-label high dose
`Ci inhibitor therapy. Monitor patients with known risk factors for thrombotic
`events. With any blood or plasma derived product, there may be a risk of
`transmission of infectious agents, e.g. viruses and, theoretically, the QB agent. The
`risk has been reduced by screening donors for prior exposure to certain virus
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`infections and by manufacturing steps to reduce the risk of viral transmission
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`including pasteurization and nanofiltration.
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`The most common adverse reactions in clinical trials associated with Cinryze were
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`rash, headache, nausea, erythema, phlebitis and local reactions at the injection
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`site. Adverse events of sinusitis and upper respiratory infection also were
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`observed in clinical trials. No drug—related serious adverse events (SAEs) were
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`reported in clinical trials.
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`Please visit http://www.viropharma.com/products/cinryze.aspx for the full U.S.
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`Prescribing Information; the prescribing information for other countries can be
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`found at www.viropharma.com.
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`About EnhanzeTM Technology
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`Enhanze‘l‘M technology is a proprietary drug delivery platform using Halozyme's
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`first approved enzyme, recombinant human hyaluronidase or rHuPHZO. When
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`formulated with other injectable drugs, Enhanze technology can facilitate the
`subcutaneous dispersion and absorption of these drugs. Molecules as large as 200
`nanometers may pass freely through the extracellular matrix, which recovers its
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`normal density within approximately 24 hours, leading to a drug delivery platform
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`which does not permanently alter the architecture of the skin. The principal focus
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`of Halozyme's Enhanze technology platform is the use of rHuPHZO to facilitate
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`subcutaneous administration for large molecule biological therapeutics, some of
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`which currently require intravenous administration.
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`About Hereditary Angioedema (HAE)
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`HAE is a rare, severely debilitating, life—threatening genetic disorder caused by a
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`deficiency of CI inhibitor, a human plasma protein. This condition is the result ofa
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`defect in the gene controlling the synthesis of Cl inhibitor. CI inhibitor maintains
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`the natural regulation of the contact, complement, and fibrinolytic systems, that
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`when left unregulated, can initiate or perpetuate an attack by consuming the
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`already low levels of endogenous Ci inhibitor in HAE patients. Patients with Cl
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`inhibitor deficiency experience recurrent, unpredictable, debilitating, and
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`potentially life threatening attacks of inflammation affecting the larynx, abdomen,
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`face, extremities and urogenital tract. Patients with HAE experience approximately
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`20 to 100 days of incapacitation per year. There are estimated to be at least 6,500
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`people with HAE in the United States and at least 10,000 people in the European
`Union.
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`For more information on HAE, visit the HAEi‘s (International Patient Organization
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`for CT Inhibitor Deficiencies) website at www.haei.org and the US. HAE
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`Association’s website at: www.haea.org.
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`About ViroPharma Incorporated
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`ViroPharma Incorporated is an international biopharmaceutical company
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`http://www.halozyme.com/investors/news—re1eases/news-release—details/2012/Vir0Pha... 13.04.2016
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`Halozyme Therapeutics - ViroPharma and Halozyme Announce Positive Data of Subc... Page 5 of 7
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`committed to developing and commercializing novel solutions for physician
`specialists to address unmet medical needs of patients living with diseases that
`have few if any clinical therapeutic options, including Ci esterase inhibitor
`deficiency, treatment of seizures in children and adolescents, adrenal insufficiency
`(Al), and C. difficile infection (CD1). Our goal is to provide rewarding careers to
`employees, to create new standards of care in the way serious diseases are
`treated, and to build international partnerships with the patients, advocates, and
`health care professionals we serve. ViroPharma‘s commercial products address
`diseases including hereditary angioedema (HAE), seizures in children and
`adolescents, and CDI; for full U.S. prescribing information on our products, please
`download the package inserts at http://www.viropharma.com/Products.aspx; the
`prescribing information for other countries can be found at
`
`www.viropharma.com.
`
`ViroPharma routinely posts information, including press releases, which may be
`important to investors in the investor relations and media sections of our
`company‘s web site, www.viropharma.com. The company encourages investors to
`consult these sections for more information on ViroPharma and our business.
`
`About Halozyme
`Halozyme Therapeutics is a biopharmaceutical company dedicated to developing
`and commercializing innovative products that advance patient care. With a
`diversified portfolio of enzymes that target the extracellular matrix, the Company's
`research focuses primarily on a family of human enzymes, known as
`hyaluronidases, that increase the absorption and dispersion of biologics.
`Halozyme‘s pipeline addresses therapeutic areas, such as diabetes, oncology and
`dermatology that have significant unmet medical need. The Company markets
`HYLENEX® recombinant (hyaluronidase human injection) and has partnerships
`with Roche, Baxter, ViroPharma and intrexon. Halozyme is headquartered in San
`Diego, CA. For more information on how we are innovating, please visit our
`corporate website at www.halozyme.com.
`
`ViroPharma Forward Looking Statements
`Certain statements in this press release contain forward-looking statements that
`involve a number of risks and uncertainties. Forward—looking statements provide
`our current expectations or forecasts of future events, including the therapeutic
`indication and use, safety, efficacy, tolerability and potential of Cinryze and our
`focus, goals, strategy, research and development programs, and ability to develop
`pharmaceutical products, commercialize pharmaceutical products, and execute on
`our plans including clinical development activities with Cinryze related to
`subcutaneous administration in combination with rHuPHZO. The safety,
`pharmacokinetics and pharmacodynamics data described in this press release are
`preliminary and additional review ofthe data may reveal additional findings which
`may not be consistent with this press release. The data described in this press
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`http://Www.halozyme.com/investors/news-re]eases/news—release~details/2012/Vir0Pha. .. 13.04.2016
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`release may not be predictive of the results offuture studies and there can be no
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`assurance that that future studies with Cinryze utilizing subcutaneous
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`administration in combination with rHuPHZO will yield positive results or support
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`further development of Cinryze for subcutaneous administration in combination
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`with rHuPHZO. The FDA or EMA may view the data regarding subcutaneous
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`administration of Cinryze in combination with rHuPHZO as insufficient or
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`inconclusive, request additional data, require additional clinical studies, delay any
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`decision past the time frames anticipated by us, limit any approved indications, or
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`deny the approval of Cinryze for subcutaneous administration in combination with
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`rHuPHZO. These factors, and other factors, including, but not limited to those
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`described in our annual report on Form iO—K for the year ended December 31,
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`2011 filed with the Securities and Exchange Commission, could cause future
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`results to differ materially from the expectations expressed in this press release.
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`The forward—looking statements contained in this press release are made as of the
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`date hereofand may become outdated over time. ViroPharma does not assume
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`any responsibility for updating any forward-looking statements. These forward
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`looking statements should not be relied upon as representing our assessments as
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`of any date subsequent to the date ofthis press release.
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`Halozyme Safe Harbor Statement
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`in addition to historical information, the statements set forth above regarding the
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`subcutaneous Cinryze with rHuPHZO product candidate, its possible advantages
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`and attributes, future development and clinical trials plans, possible indications
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`and other statements regarding Halozyme‘s product candidates and potential
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`attributes of these product candidates, involve risk and uncertainties that could
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`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 "expect," ”believe," "enable,“ "may," "will," "could," “intends,” ”estimate,"
`II
`I!
`II N
`I] H
`
`"anticipate,
`
`plan,
`
`predict,
`
`probable," “potential," "possible," "should,"
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`”continue," and other words of similar meaning. Actual results could differ
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`materially from the expectations contained in forward-looking statements as a
`
`result of several factors, including clinical trial results, delays in development,
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`possible adverse events associated with the use of the product candidate,
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`regulatory delays and competitive conditions. These and other factors that may
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`result in differences are discussed in greater detail in the company's reports on
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`Forms lO-K, iO-Q, and other filings with the Securities and Exchange.
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`SOURCE ViroPharma incorporated
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`http://www.halozyme.com/htvestors/news—reieases/neWS—release—details/ZO12/ViroPha. ..
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`1 3.04.2016
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