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 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.

Wyeth Collaboration

In 1994, we entered into a research and development collaboration with Wyeth-Ayerst Laboratories (now Wyeth) 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. Bazedoxifene, a selective estrogen receptor modulator (SERM), is the product of this collaboration.

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, Wyeth submitted an NDA for bazedoxifene to the FDA for the prevention of postmenopausal osteoporosis. Wyeth also submitted a second NDA for bazedoxifene in the United States in July 2007 for the treatment of osteoporosis and a Marketing Authorization Application, or MAA, to the European Medicines Agency, or EMEA, in September 2007 for the prevention and treatment of osteoporosis. In the U.S. Wyeth has indicated that it will file a complete response in 2009 and expects the FDA 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.

Wyeth is also developing APRELA^TM (bazedoxifene in combination with PREMARIN) as a progesterone-free treatment for menopausal symptoms. Two Phase III studies with bazedoxifene/conjugated estrogens (APRELA^TM), showed reduced number and severity of hot flashes in symptomatic postmenopausal women by up to 80 percent, when compared with placebo. Wyeth expects to file an initial NDA no earlier than the first half of 2010.

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 submitted an NDA for the treatment of osteoporosis in postmenopausal women in 4Q07. The FDA Panel had a positive vote (9-3) on September 8, 2008 that benefits could outweigh its risks, including blood clots and vaginal bleeding for the osteoporosis treatment indication for FABLYN^®.

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. FABLYN^® was submitted for approval in Europe in January 2008. In December 2008 an EU Drug Panel granted a positive opinion for the approval of lasofoxifene in the EU for the treatment of osteoporosis in postmenopausal women at increased risk of fracture. Pfizer has also submitted NDA’s for osteoporosis prevention and vaginal atrophy, and the FDA issued non-approvable letters for both NDA’s.

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.

Schering-Plough Collaboration

The collaboration with Schering-Plough began in October 1998. Schering-Plough completed a Phase II study 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 CXCR2 program, the agreement 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^®.