Ligand Earns $2.0 Million Milestone Payment as GlaxoSmithKline Commences Phase III Studies of Eltrombopag in Adults with Previously-Treated Idiopathic Thrombocytopenic Purpura.

SAN DIEGO -- Potential for Future Double-Digit Royalties If Successful

Ligand Pharmaceuticals Incorporated (Pink Sheets:LGND) announced today that the company has earned a $2.0 million milestone payment from GlaxoSmithKline (NYSE:GSK) with that company's commencement of Phase III trials of eltrombopag (SB497115) in adult patients with previously-treated idiopathic thrombocytopenic purpura (ITP). Eltrombopag is an oral platelet growth factor that stimulates the proliferation and differentiation of megakaryocytes, bone marrow cells that mature into blood platelets. ITP is a disorder characterized by low platelet counts leaving patients at risk of episodes of spontaneous bruising, mucosal bleeding, and in severe cases intracranial hemorrhage. If the drug is ultimately approved and marketed, Ligand could receive double-digit royalties on product sales.

GlaxoSmithKline also announced today the details of the Phase III trial. The multi-center Phase III study has a double-blind, randomized, placebo-controlled, parallel group design. Subjects will be randomized to receive eltrombopag or placebo once daily for six weeks.

The study population is comprised of adults with ITP, diagnosed at least six months prior to screening, who have platelet counts less than 30,000/micro-L and who have not responded to previous treatment or have relapsed within three months of previous treatment. Those who achieve a platelet count of at least 50,000/micro-L after 42 days of dosing will be considered treatment responders. Safety and quality of life outcomes also will be assessed. Trial sites are in 33 countries, including Italy, Denmark, Poland, France, Germany, United Kingdom, Spain, Switzerland, Russia, Netherlands, Hong Kong, Pakistan, Mexico, Australia, United States, and Canada.

"We are pleased with the smooth transition of eltrombopag to Phase III studies, which should further support the robust data already collected in Phase II trials," said Andres Negro-Vilar, M.D., Ph.D., Ligand's Executive Vice President of Research and Development and Chief Scientific Officer. "An orally active once-a-day thrombopoietin mimic with strong efficacy and a favorable side effect profile may provide an important treatment option for a large, currently underserved group of patients with platelet disorders."

Top line results of the Phase II trial in ITP -- which had a similar design as the Phase III trial, but tested various dosing levels -- were reported in December 2005, in conjunction with the 47th Annual Meeting of the American Society of Hematology in Atlanta. The study of 97 patients found that eltrombopag, at doses of 75 mg and 50 mg, was successful in elevating platelet counts, compared with placebo (p less than 0.001) in increasing platelet count from a baseline of less than 30,000/micro-L to at least 50,000/micro-L after 42 days of dosing. The 30 mg dose showed limited change from baseline. Further, there were no safety or tolerability events that would preclude advancement to Phase III studies.

About Eltrombopag

Eltrombopag is an investigational small-molecule thrombopoietin receptor agonist that is thought to stimulate the proliferation and differentiation of megakaryocytes, the bone marrow cells that give rise to blood platelets, and thus is considered a platelet growth factor. Because it is a small molecule, the drug is administered as an orally-administered tablet and has less potential than large protein molecules for causing an immune system reaction. Eltrombopag was discovered as a result of a research collaboration between GlaxoSmithKline and Ligand Pharmaceuticals. It is being developed by GlaxoSmithKline.

About Thrombocytopenia 

A reduction in platelet count is the defining characteristic of any type of thrombocytopenia and diagnosis can be confirmed following a routine blood test. Idiopathic thrombocytopenic purpura is an autoimmune disorder that is marked by platelet destruction and/or inadequate platelet production. The onset of symptoms is sometimes unpredictable and patients suffering from thrombocytopenia may be asymptomatic. Thrombocytopenia also can occur as a consequence of chemotherapy treatment, interferon treatment, or chronic liver disease. The prevalence of the disease is not well-established, as there are very few published epidemiologic studies of this disease in the United States. Two epidemiologic studies of incident ITP in Europe found that incidence ranged from 16 to 23 per 1 million persons per year. Based on studies of a managed care population conducted internally at GSK, the prevalence of chronic ITP was estimated as around 77,000 cases over a one-year period in the United States. Thrombocytopenia can impede a variety of medial treatments. It can prevent cancer patients from receiving their full dose of chemotherapy, prevent patients with hepatitis C infection from receiving interferon therapy or lead to dose reductions or discontinuation, and it can prevent or complicate procedures (surgical, dental, etc.) in patients with chronic liver disease and ITP.

About the GSK-Ligand Growth Factor Collaboration

The GSK-Ligand collaboration began in 1995 to capitalize on Ligand's signal transduction expertise and technology to discover small molecule drugs to control hematopoiesis and treat patients with cancer, anemia or platelet deficiencies. The research phase of the collaboration ended in 2001. GSK is responsible for the development and registration of products resulting from the collaboration, and Ligand may earn milestone payments of up to $8 million as a product moves through development. GSK has exclusive worldwide marketing rights to products resulting from the research, and will pay Ligand royalties on a sliding scale up to low double digits on sales of products that make it to market.

About Ligand

Ligand discovers, develops and markets new drugs that address critical unmet medical needs of patients in the areas of cancer, pain, skin diseases, men's and women's hormone-related diseases, osteoporosis, metabolic disorders, and cardiovascular and inflammatory diseases. Ligand's proprietary drug discovery and development programs are based on its leadership position in gene transcription technology, primarily related to Intracellular Receptors (IRs). For more information, go to www.ligand.com.

Caution Regarding Forward-Looking Statements

This news release contains certain forward-looking statements that involve risks and uncertainties and reflect Ligand's judgment as of the date of this release. These statements include those related to clinical trials and trial details, product approval and marketing, further clinical development, future milestone and royalty payments, benefits and usefulness of SB497115, efficacy and side effects, importance as a treatment option and potential patient group. Actual events or results may differ from our expectations. For example, there can be no assurance that SB497115 or other potential drugs will progress through Phase III or later clinical development or receive required regulatory approvals within the estimated time lines or at all, that future milestones or royalties will be earned, or that any such drugs will be beneficial, safe or successfully marketed. Additional information concerning these and other risk factors affecting Ligand can be found in prior press releases as well as in public periodic filings with the Securities and Exchange Commission, available via www.ligand.com. Ligand disclaims any intent or obligation to update these forward-looking statements beyond the date of this release. This caution is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995.