GlaxoSmithKline Collaboration

In 1995, we entered into a research and development collaboration with SmithKline Beecham (now GlaxoSmithKline) to use our proprietary expertise to discover and characterize small-molecule, orally bioavailable drugs to control hematopoiesis (the formation and development of blood cells) for the treatment of a variety of blood cell deficiencies.

In December 2008, the FDA granted accelerated approval of GSK’s PROMACTA^® for the treatment of thrombocytopenia in patients with chronic immune (idiopathic) thrombocytopenic purpura (ITP) who have had an insufficient response to corticosteroids, immunoglobulins or splenectomy. PROMACTA^® is the first oral TPO receptor agonist therapy for the treatment of adult patients with chronic ITP.

In addition to the accelerated approval granted for GSK’s PROMACTA^® for the treatment of thrombocytopenia in patients with chronic ITP, GSK also reported positive Phase II data in patients with thrombocytopenia associated with hepatitis C and initiated two Phase III trials in patients with hepatitis C in the fourth quarter of 2007 and a Phase III trial in patients with chronic liver disease (CLD) in early 2008.

A Phase II study in patients with oncology-related thrombocytopenia is ongoing and a Phase I study is ongoing in patients with sarcoma receiving the adriamycin and ifosfamide regimen. In December 2008, GSK submitted a marketing authorization application in EU and international for Revolade (Eltrombopag) for the treatment of thrombocytopenia in patients with chronic immune (idiopathic) thrombocytopenic purpura, or ITP.

In June 2009, GSK presented new Phase III results for PROMACTA^® for chronic idiopathic thrombocytopenic purpura (ITP) at the European Hematology Conference in Germany. Data from two long-term studies (RAISE – 197 patients and EXTEND – 144 patients) demonstrated that patients treated with PROMACTA^® experienced significant elevations in platelet counts, as well as a reduction in bleeding and bruising, compared with placebo. In addition, patients experienced a statistically significant improvement in quality of life.  Patients treated with PROMACTA^® reported an increased vitality, reduced fatigue, and an increased ability to participate in the activities of daily living.

In December 2008, Ligand entered into an exclusive, worldwide license agreement with SmithKline Beecham Corporation, doing business as GSK. Pursuant to the terms of the license agreement, we granted GSK the exclusive right to develop, manufacture and commercialize our LGD-4665 product candidate, as well as all other TPO-related molecules discovered by us.

Pfizer Collaboration

We collaborated with Pfizer to develop therapies for osteoporosis. The collaboration produced FABLYN^®, formerly Oporia (lasofoxifene) that Pfizer has advanced through late- stage clinical development. FABYLN^® is a SERM that is being developed for the treatment and prevention of post-menopausal osteoporosis and vaginal atrophy. Pfizer received approval in March 2009 from the European Commission (EC) for FABLYN^® (lasofoxifene) tablets for the treatment of osteoporosis in post-menopausal women at increased risk of fracture. Pfizer announced that it is exploring strategic options for FABLYN^®, including out-licensing or sale.

The original collaboration for bazedoxifene, a selective estrogen receptor modulator (SERM) was with Wyeth Pharmaceuticals (now Pfizer). The collaboration began in 1994 to discover and develop drugs that interact with estrogen and progesterone receptors for use in hormone therapy, anti-cancer therapy, gynecological diseases and central nervous system disorders associated with menopause and fertility control.

VIVIANT^TM (bazedoxifene) is a synthetic drug that was specifically designed to reduce the risk of osteoporotic fractures while at the same time protecting breast and uterine tissue. In June 2006, an NDA for bazedoxifene was submitted to the FDA for the prevention of postmenopausal osteoporosis. A second NDA was also submitted for bazedoxifene in the United States in July 2007 for the treatment of osteoporosis. A complete response was filed in 2009 and the FDA is expected to convene an advisory committee to review the pending NDAs for both the treatment and prevention of postmenopausal osteoporosis with VIVIANT^TM.

In February 2009, CONBRIZA (EU trade name) received positive Committee for Medicinal Products for Human Use (CHMP) opinion in Europe for the treatment of postmenopausal osteoporosis in women at increased risk of fracture.

APRELA^TM (bazedoxifene in combination with PREMARIN^®) is a progesterone-free treatment for menopausal symptoms. In July 2009 Phase III data showing that APRELA^TM significantly reduced the frequency and severity of hot flushes and improved measures of vaginal atrophy when compared to placebo was published in the journal, Fertility and Sterility. An initial NDA is expected to be filed no earlier than the first half of 2010.

Bristol-Myers Squibb Collaboration

The collaboration began in November 1992. Bristol-Myers Squibb is currently conducting Phase II studies for orally active p38 mitogen-activated protein (MAP) kinase inhibitor for treatment of moderate to severe psoriasis, rheumatoid arthritis and atherosclerosis. Phase II studies are expected to be complete in 2009. Positive Phase I results in healthy subjects and in patients with stable RA were reported at 2008 ACR meeting.

Merck Collaboration

The original collaboration was with Schering-Plough (now Merck). The collaboration began in October 1998. A Phase II study is completed in patients with moderate-to-severe COPD in 4Q08. Two separate Phase II studies in asthma were completed in the first quarter as updated on clinicaltrials.gov. In addition to the CXCR2 program, the collaboration has resulted in an enzyme inhibitor that entered Phase II clinical trials in November 2008 for oncology, a candidate for inflammatory diseases that entered Phase I clinical trials in March 2007, a candidate for respiratory diseases that entered Phase I clinical trials in September 2007 and a BACE inhibitor for Alzheimer's disease for which a development milestone was achieved in February 2009.

Celgene Collaboration

The collaboration with Celegene began in January 2003 to evaluate treatment of inflammatory diseases for a drug that entered a Phase I clinical trial in 1Q08. The research phase of the collaboration is complete and Celgene is solely responsible for the funding and management of development and commercialization of this inflammatory disease candidate.

Cephalon Collaboration

The collaboration with Cephalon began in May 2006 to identify active molecules and bring them forward to clinical proof of concept with the goal of yielding novel candidates for drug development in various therapeutic areas. Cephalon will be primarily responsible for the development and commercialization of clinical candidates.

King Pharmaceuticals Collaboration

In February 2007, we completed the sale of our AVINZA^® product line to King Pharmaceuticals, Inc (“King”).  Ligand and King Pharmaceuticals currently have a royalty agreement for AVINZA^®.