and increased resistance to anticancer therapies. in increased hypoxia, decreased immune cell access, All these effects can result and decreased perfusion. intratumoral pressure, blood vessel compression, centrations ofHAinthe TME canleadto increased for asalubricant con tissuesandjoints.acts High withwater tomatrix substancethat form agel-like within the TME of some solid tumors, creates a the connective, epithelial, andneuraltissues glycosaminoglycan, widely throughout distributed uronidase (rHuPH20),catalyticallydegrades HA. This Halozyme’s recombinant humanhyal proprietary Pegvorhyaluronidase alfa,apegylated version of Pegvorhyaluronidase alfa encouraging potential to treat .” ment ofpegvorhyaluronidase alfa,whichhasshown and overcome thisresistance ledto thedevelop immune cells. The ofourscientiststo work understand ofanticancer agents and impedes theaccessibility that oneofthebarriers cold tumorhot.HAisoften ament, effectively thetumororturning priming inthetumormicroenvironagents targeting barriers stated, frontier see a new “We in cancer therapy with solid tumorswithhighHAlevels. of cancertherapiesandusedagainstdifficult-to-treat significant asitmay becombinedwithawiderange breast cancers. The potential for thisnovel therapy is , cancer, gastric andmetastatic lungcancer(NSCLC),tal carcinoma, non-small-cell solid tumors, includingmetastaticpancreatic duc ment for thetreatment ofseveral difficult-to-treat and innate immunecells( and accessfor coadministered anticancertherapies effect by degrading HA,resulting inincreased activity biologic designed toin-class maximize therapeutic chemoresistance. Pegvorhyaluronidase alfaisafirst- reduced drugdelivery, andincreasedperfusion, increase intratumoralpressure, resulting indecreased HAlevels inthe tissues. High TME ofsolidtumorscan of andrepair matrix ture capacity oftheextracellular glucuronic acid, to andamajorcontributor thestruc subunitsof disaccharide hyaluronan (HA),aglycosaminoglycan ofrepeating recombinant humanhyaluronidase thatdegrades pegylatedpegvorhyaluronidase alfa,aproprietary The ofHalozyme’s cornerstone (TME). technology is therapies thattarget thetumormicroenvironment focuses ondeveloping andcommercializing cancer Clinical-stage biotechnology company Halozyme developing pegvorhyaluronidase alfa (PEGPH20) to treat pancreatic and othersolid tumors. accessibility for chemotherapies, agents, andinnate immuno-oncology immune cells. Halozyme is Halozyme is pioneering therapies that remodel the tumor microenvironment to increase pegvorhyaluronidase barriers with Breaking alfa www.halozyme.com Halozyme ADVERTISER RETAINS FORCONTENTADVERTISER SOLERESPONSIBILITY in several tumor types, ated with decreased survival ADVERTISEMENT FEATUREADVERTISEMENT High levels of HA in tumors haveHigh alsobeen associ As Helen Torley, Halozyme’s president andCEO, Pegvorhyaluronidase alfaiscurrently indevelop N Fig. 1 -acetylglucosamine and -acetylglucosamine ). ------clinical studies. All of these programs partners. areexternal in phase grams, three ofwhich are incollaborationwith more than200sites inover 22countries patients with untreated stage launched a phase Halozyme ratio =0.51;95% CI,0.26–1.00; plus gemcitabineonly(hazardwith nab-paclitaxel ment, versus aPFSof5.2 monthsfor patientstreated withPAG(PFS) of9.2 monthswasobserved treat among whomamedianprogression-free survival in patients with HA-high tumors (stage observed nounced benefitofpegvorhyaluronidase alfawas carcinoma,ductal demonstrated that the most pro inpatientswithuntreatedtrial metastaticpancreatic HALO 109-202study, arandomized phase 2clinical the treatment ofpancreatic cancer. from Results the plusgemcitabine(PAG)alfa andnab-paclitaxel for alfa-based program combinespegvorhyaluronidase Halozyme’s mostadvancedpegvorhyaluronidase- Clinical development therapies. antibodies, innate immune cells, and cell-mediated more accessibleto chemotherapies, monoclonal result inatumorthatis blood vessel re-expansion injection. Therapeutically, reduced HAlevels and to the of theenzyme TME following intravenous unmodified rHuPH20,allowing for efficientdelivery increased circulating half-life compared withthatof cells. Pegylation affords pegvorhyaluronidase alfa an and inhibitingthegrowth andmetastasisoftumor of absorption coadministered anticancer therapies, toration ofbloodflow, facilitatingthedispersionand interstitial fluidpressure,normalizing leadingto res cancer,gastric andmetastaticbreast cancers. including pancreatic adenocarcinoma, ductal NSCLC, Fig. 1|Enlisting hyaluronidase to boostdrugaccessibility to tumors ©

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biopharmadealmakers.nature.com |March 2018 | contact Email: [email protected] Tel: +1-848-794-8889 USA California, Diego, San Halozyme Communication and Investor Relations Corporate President, Vice Mazzola, S. Jim Halo Pancreatic 301 3 . Mol. Cancer Ther. J. Clin. Oncol. . http://halo301.com (2017). Macrophage Vasculature Cancer cell T cell T HA https://doi.org/10.1200/

9 , 3052–3056(2010). B9 B9 -

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