Ligand Collaborator Drug Shows Encouraging Results in Thrombocytopenia; GlaxoSmithKline Releases Phase II Data; Ligand Drug for Thrombocytopenia Targeted for IND Filing 1H'06.

SAN DIEGO -- Ligand Pharmaceuticals Incorporated (Pink Sheets:LGND) announced today that results reported by GlaxoSmithKline (NYSE:GSK) in phase II studies of eltrombopag, SB-497115 ("115"), a small-molecule drug that mimics the activity of thrombopoietin (TPO), a protein factor that promotes growth and production of blood platelets, were promising.

On November 30, 2005, during a review of its oncology portfolio, GSK presented data from a phase II dose-ranging clinical trial that showed 115 significantly raised platelet counts in adult patients. GSK described the phase II studies well underway in three major indications: idiopathic thrombocytopenia purpura (ITP), hepatitis C (HCV) and chemotherapy-induced thrombocytopenia (CIT). The phase II results in adult patients with chronic ITP that had failed at least one prior therapy and with platelet counts less than 30,000 showed that 66% of patients receiving the 50 mg dose and 87% of patients treated with 115's highest dose (75 mg/day) had counts greater than or equal to 50,000 after six weeks and many of those had reached normal platelet levels within the first two to three weeks of treatment.

In comparison, only 13% of placebo-treated patients showed platelet increases greater than or equal to 50,000 after six weeks. The frequency of side effects was comparable between patients treated with placebo and those treated with eltrombopag. Additional data presented at the meeting showed encouraging results in an interim analysis in a phase II study in HCV patients.

"We are pleased to see that our vision of the early 1990's of the emergence of an exciting, new TPO pharmaceutical market is now rapidly being translated to concrete product assets with great potential to meet unmet patient needs and for shareholder value. The assets eltrombopag and SB-539448 resulted from a collaboration agreement GSK entered into with Ligand in 1995, and which incorporated TPO as a target in 1997 while an internal program initiated following completion of the collaborative program has produced LGD4665, now targeted for IND filing in the first half of 2006," said David E. Robinson, Chairman, President and Chief Executive Officer of Ligand Pharmaceuticals. "We believe the size and potential of the emerging thrombocytopenia market will clearly support multiple once-a-day oral product entries and therefore have made LGD4665 our top new chemical entity product development priority."

In February 2005, Ligand earned a $1 million milestone payment from GSK with the company's commencement of phase II trials for eltrombopag. If the drug continues in development and ultimately is approved and marketed, Ligand could receive additional milestone payments and royalties on net product sales. The royalties would be payable on annual worldwide net sales according to the following tiered royalty schedule:

up to $100 million                  5%
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              between $100-$200 million           7%
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              between $200-$400 million           8%
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              above $400 million                 10%
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While the size of the emerging thrombopoietin market is difficult to estimate, recently published estimates in research analyst reports at Merrill Lynch and Lehman Brothers suggest the potential worldwide market could be between 2.5 and 4.5 billion dollars per year. Ligand earned an additional milestone of $2 million June of 2005 when GSK initiated phase I development of a second oral TPO drug, SB-559448 which, if developed, would result in similar milestones and royalties.

"GSK's efficacy and safety data from both phase II studies is impressive, confirming and extending previously presented phase I data in normal volunteers to two distinct patient populations (ITP and HCV) with chronic thrombocytopenia," said Andres Negro-Vilar, M.D. PhD, Ligand's Executive Vice President of Research and Development and Chief Scientific Officer. "The data further highlights the promising nature of the oral TPO mimic program jointly initiated in 1997 by GSK and Ligand."

Ligand has its own TPO-mimic oral drug candidate, LGD4665, in preclinical development and plans to file an IND in the first half of 2006. This candidate was selected from a group of novel oral mimics synthesized at Ligand. These molecules were profiled to have in vitro efficacy and selectivity equal to or better than TPO in predictive human cell models and to have a better profile of efficacy and potency than other oral mimics currently in clinical development.

"We are very excited about LGD4665's profile of potency and efficacy as important characteristics of a follow-up product in a large, underserved market," said Dr. Negro-Vilar. "The two principal targets for clinical development are currently chemotherapy-induced thrombocytopenia and liver disease-induced thrombocytopenia, which represent the two largest market segments for drugs of this type."

About Thrombocytopenia and Oral TPO Mimics

Thrombocytopenia (decreased platelet count) is a common side effect of many chemotherapies and can lead to uncontrolled bleeding, thus representing a significant problem in the treatment of cancer patients. Similarly, thrombocytopenia is commonly seen in patients undergoing myeloablative therapies or in those with leukemias or metastatic tumors. Ligand estimates, based on available data, that approximately 20 to 25 percent of the more than one million patients who undergo chemotherapy each year experience thrombocytopenia. These estimates do not include patients suffering from idiopathic thrombocytopenia or the large number of patients -- estimated at more than two million -- with hepatitis or other diseases affecting liver function. Currently, thrombocytopenia patients have few therapeutic options other than frequent platelet transfusions. The frequency and chronicity of treatment with platelet restoring factors such as TPO could vary depending on the underlying cause of thrombocytopenia.

The development of an oral TPO mimic by GSK in collaboration with Ligand represents a potential major breakthrough in this field, with the added benefit of an orally active molecule which enhances the potential for chronic use and for easier adjustment to the dosing regimen. In addition, small molecule oral mimics are not expected to lead to formation of TPO antibodies, which has affected the development of earlier peptidic TPO products. There are no currently approved oral TPO agents for the treatment or prevention of thrombocytopenias.

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 forward-looking statements within the meaning of section 21E of the Securities Exchange Act of 1934, as amended, 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 results, a new TPO pharmaceutical market, IND filing, market size and potential, product development, approval, entries and marketing, further development, milestone and royalty payments, benefits and usefulness of SB-497115 and LGD4665, potential potency, efficacy and success of these drugs and maturation of our portfolio. Actual events or results may differ from our expectations. For example, there can be no assurance that SB-497115 or LGD4665 or other potential drugs will progress through further clinical development or receive required regulatory approvals within the expected time lines or at all, that future clinical trials will confirm any results presented here, that any future milestones or royalties will be earned, or that any drugs will be beneficial 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.