Out-licensed

Key to our strategy is collaboration through partnering or out-licensure. By out-licensing to collaborators with extensive expertise in related areas, ZymoGenetics maximizes the likelihood of commercial success, long-term asset and shareholder value.

Out-licensed Product Candidates

Atacicept (formerly TACI-Ig)

TACI is a member of the tumor necrosis factor receptor family of proteins. Atacicept is a soluble form of the TACI receptor that binds to two ligands, BLyS and APRIL, that are implicated in B-cell survival, maturation and antibody production. In August 2008, ZymoGenetics converted to a worldwide royalty license, granting Merck Serono exclusive worldwide rights for atacicept. Merck Serono is investigating atacicept in a Phase 2/3 clinical trial in patients with systemic lupus erythematosus, a Phase 2 clinical trial in patients with rheumatoid arthritis, and a Phase 2 clinical trial in patients with multiple sclerosis.

Augment™ Bone Graft (formerly GEM-OS1TM)/Augment™ Injectable Bone Graft (formerly GEM-OS2TM)

Augment Bone Graft/Augment Injectable Bone Graft is a combination of platelet-derived growth factor (PDGF-BB) and a synthetic bone matrix. PDGF-BB is a growth factor that stimulates the growth of a variety of cell types, including bone forming cells. PDGF-BB was out-licensed to BioMimetic Therapeutics, Inc., who is developing Augment Bone Graft for the treatment of fractures in open surgical settings and Augment Injectable Bone Graft for the treatment of fractures in closed surgical settings and for prophylactic bone augmentation. BioMimetic completed a pivotal trial in Canada and is conducting pivotal trials in the United States and Europe to evaluate Augment Injectable Bone Graft for use in foot and ankle fusion procedures. Other clinical studies are also being conducted to evaluate Augment Injectable Bone Graft for fracture repair.

rFactor XIII

rFactor XIII is a recombinant version of a protein that is involved in blood clotting. rFactor XIII was out-licensed to Novo Nordisk in October 2004. Novo Nordisk is conducting a Phase 3 clinical trial investigating rFactor XIII in patients with congenital Factor XIII deficiency and is planning to begin a Phase 2 study in patients undergoing cardiac surgery in 2009.

Fibroblast growth factor-18 (FGF-18)

FGF-18 is a novel member of the fibroblast growth factor family of proteins. Preclinical data generated by ZymoGenetics suggest that FGF-18 may be useful for healing cartilage damaged by injury or disease. FGF-18 was out-licensed to Merck Serono in October 2004. Merck Serono is conducting a Phase 1 clinical trial investigating FGF-18 as a treatment for patients with osteoarthritis.

Interleukin-17 receptor C (IL-17RC)

IL-17RC is a soluble receptor that binds to both IL-17A and IL-17F, two closely related cytokines highly expressed in a variety of inflammatory and autoimmune diseases. In August 2008, Merck Serono acquired an exclusive license to develop and commercialize IL-17RC worldwide.

Interleukin-20 (IL-20)

IL-20 is a member of the IL-10 cytokine family. Preclinical data generated by ZymoGenetics suggest that IL-20 may play an important role in the regulation of skin inflammation and the pathology of psoriasis. Novo Nordisk licensed the rights to IL-20 outside North America in September 2001 and North America in March 2004. Novo Nordisk is conducting a Phase 1 clinical trial investigating an antibody to IL-20 as a treatment for patients with psoriasis.

Interleukin-22 receptor subunit alpha (IL-22RA)

IL-22RA is a cytokine receptor that signals both IL-20 and IL-22 activities and which is a potential target for the treatment of psoriasis. ZymoGenetics out-licensed IL-22RA to Merck Serono in October 2004.

Interleukin-21 monoclonal antibody (IL-21 mAb)

Cell biology experiments and preclinical models of inflammatory diseases suggest that IL-21 is a key mediator of inflammation, and over-expression patterns of IL-21 and its receptor in inflamed tissues of human diseases further support the role of IL-21 in the disease process. IL-21 mAb is a potential therapeutic treatment for autoimmune and chronic inflammatory disorders. ZymoGenetics out-licensed IL-21 mAb to Novo Nordisk in December 2009.

Out-licensed Commercial Products

ZymoGenetics participated in the discovery or development of six recombinant protein products marketed by other companies. ZymoGenetics has earned royalties on sales of all these products except for NovoSeven and NovoRapid, for which the company received a one-time payment to satisfy future royalty obligations prior to separation from Novo Nordisk in 2000. Additionally, due to recent patent expirations, ZymoGenetics no longer receives royalties on GlucaGen or Novolin sales.

Novolin® (insulin) and insulin analogs

Novolin and insulin analogs are marketed by Novo Nordisk worldwide for the treatment of diabetes. In collaboration with Novo Nordisk, ZymoGenetics developed a process for the production of recombinant human insulin in yeast that is used by Novo Nordisk.

NovoSeven® (recombinant Factor VIIa)

NovoSeven is a protein involved in the generation of blood clots, marketed worldwide by Novo Nordisk for the treatment of hemophilia patients. ZymoGenetics cloned the human Factor VII gene and developed the process for the production of activated recombinant human Factor VII, or recombinant Factor VIIa, which led to the establishment of the manufacturing process that Novo Nordisk currently uses to produce this protein.

Regranex® (platelet-derived growth factor)

Regranex is a growth factor approved for the treatment of non-healing diabetic ulcers. In December 2008, One Equity Partners LLC announced the acquisition of Regranex from Ethicon Inc. Regranex will be marketed and distributed by Systagenix Wound Management, a new company created by One Equity Partners LLC. ZymoGenetics cloned the gene that codes for platelet-derived growth factor and demonstrated the importance of this protein in stimulating wound healing.

GEM 21S® (platelet-derived growth factor)

GEM 21S is a combination of a platelet-derived growth factor with a synthetic bone matrix, developed by BioMimetic Therapeutics, Inc. and marketed by Osteohealth Company, a division of Luitpold Pharmaceuticals, Inc. for the treatment of bone loss and gum tissue recession associated with advanced periodontal disease. ZymoGenetics cloned the gene that codes for platelet-derived growth factor, the active agent in GEM 21S.

GlucaGen® (glucagon)

GlucaGen is a protein marketed by Novo Nordisk, Bedford Laboratories and Eisai Co., Ltd. for use as an aid for gastrointestinal motility inhibition and for the treatment of severe hypoglycemia in diabetic patients treated with insulin. In collaboration with Novo Nordisk, ZymoGenetics developed a production process that is currently used by Novo Nordisk in the manufacture of GlucaGen.

Cleactor™ (tPA analog)

Cleactor is a modified form of the protein tissue plasminogen activator (tPA), marketed in Japan by Eisai Co. for the treatment of heart attacks. In collaboration with Eisai Co., ZymoGenetics developed a modified tPA, which has enhanced properties that allow it to be given as a single injection.