Ligand Announces Successful Phase II Results for Captisol®-Enabled Propylene Glycol-Free Melphalan

Ligand Pharmaceuticals Incorporated (NASDAQ: LGND) today announced data from the Phase II study with its Captisol-enabled^®, propylene glycol-free (PG-free) melphalan.

This Phase II study compared the safety, tolerability and pharmacokinetic profiles of a new PG-free melphalan intravenous formulation and the current clinically used intravenous formulation of melphalan (sold as Alkeran®) for multiple myeloma patients undergoing autologous transplantation. This Captisol-enabled product is expected to allow for longer administration durations and slower infusion rates, potentially enabling clinicians to safely achieve a higher dose intensity of pre-transplant chemotherapy.

Trial Highlights and Primary Features of PG-free Melphalan:

• The Phase II trial successfully met all endpoints, and PK analysis revealed that the new PG-free melphalan met the requirements for establishment of bioequivalence to Alkeran
• Based on these Phase II results, the follow-on pivotal study will utilize a dosing regimen comparable to Alkeran. The pivotal study will be designed to expose patients exclusively to the PG-free formulation and will further elaborate safety and efficacy measures for the product
• Captisol-enabled, PG-free melphalan is presented in a simple single-vial system and will provide dosing flexibility as compared to the current two-vial PG format for Alkeran
• Alkeran currently must be used within one hour after formulation. The new PG-free formulation is potentially more stable offering alternate dosing options to clinicians
• Removal of PG significantly changes the potential side-effect profile of melphalan

"This is a unique product with a very compelling therapeutic profile,” said Matthew W. Foehr, Chief Operating Officer of Ligand Pharmaceuticals. "Removal of propylene glycol creates major benefits that we believe will enhance utilization of melphalan in the multiple myeloma treatment setting. Current Alkeran dosing in stem cell transplants for multiple myeloma administers PG at levels higher than the maximum exposure levels recommended by the World Health Organization. This in turn requires increased management and limits dosing. The benefits of a PG-free formula are well understood in the transplant community,” added Foehr.

"This program has a clear and efficient development plan, with an established Orphan Designation and a single remaining pivotal trial,” continued Foehr. "We are very pleased with the results from the Phase II trial, and given these results are currently examining the broader partnering landscape for this program, while positioning ourselves to begin the pivotal trial in 2012.”

Dr. Omar Aljitawi from the University of Kansas Medical Center and Principal Investigator of the Phase IIa clinical study said, "In addition to the obvious benefits of a PG-free formulation, the other key advantage of this new melphalan formulation is that it provides the needed flexibility to enable physicians to safely alter dose intensity of preparative regimen chemotherapy. All of this could lead to better transplant outcomes.”

Ligand worked in partnership with The University of Kansas Cancer Center on the trial, which was partially funded by grants from the Kansas Bioscience Authority.

Current Development Path for Ligand’s Melphalan Program

Ligand is preparing to initiate a 60-patient pivotal trial in 2012. Given the robust data set compiled to date along with the efficient final study design, Ligand believes it will have a submission-ready NDA at the end of this study. Although Ligand is preparing to conduct the trial with the objective to potentially launch the product itself, the company is also currently evaluating entering a partnership for the program as well.

About Ligand’s Captisol-enabled, PG-Free Melphalan Program

Ligand’s Captisol-enabled melphalan program, which has been granted Orphan Drug status by the FDA as a conditioning treatment for use in autologous transplant for patients with multiple myeloma, is a new IV formulation of melphalan (currently sold as Alkeran^® for Injection) that has the potential to offer multiple advantages for clinicians and patients in the multiple myeloma transplant setting. Ligand’s formulation completely avoids the use of propylene glycol, which has been used as a co-solvent in other formulations and has been reported to cause renal and cardiac side-effects that limit the ability to deliver higher quantities of intended therapeutic compounds. The use of the Captisol^® technology to reformulate melphalan is anticipated to allow for longer administration durations and slower infusion rates, potentially enabling clinicians to safely achieve a higher dose intensity of pre-transplant chemotherapy.

About Captisol^®

Captisol is a patent-protected, chemically modified cyclodextrin with a structure designed to optimize the solubility and stability of drugs. Captisol was invented and initially developed by scientists at the University of Kansas’ Higuchi Biosciences Center for specific use in drug development and formulation. This unique technology has enabled five FDA-approved products, including Pfizer’s Vfend^® IV and Baxter International’s Nexterone^®. There are currently more than 20 Captisol-enabled products in development, including Onyx pharmaceuticals’ Carfilzomib program.

About Ligand Pharmaceuticals

Ligand is a biopharmaceutical company with a business model that is based upon the concept of developing or acquiring royalty revenue generating assets and coupling them to a lean corporate cost structure. Ligand’s goal is to produce a bottom line that supports a sustainably profitable business. By diversifying the portfolio of assets across numerous technology types, therapeutic areas, drug targets, and industry partners, we offer investors an opportunity to invest in the increasingly complicated and unpredictable pharmaceutical industry. In comparison to its peers, we believe Ligand has assembled one of the largest and most diversified asset portfolios in the industry with the potential to generate revenue in the future. These therapies address the unmet medical needs of patients for a broad spectrum of diseases including hepatitis, muscle wasting, Alzheimer's disease, dyslipidemia, diabetes, anemia, COPD, asthma, rheumatoid arthritis and osteoporosis. Ligand’s Captisol platform technology is a patent protected, chemically modified cyclodextrin with a structure designed to optimize the solubility and stability of drugs. Ligand has established multiple alliances with the world's leading pharmaceutical companies including GlaxoSmithKline, Merck, Pfizer, Baxter International, Bristol-Myers Squibb, Celgene, Onyx Pharmaceuticals, Lundbeck Inc. and The Medicines Company. Please visit www.captisol.com for more information on Captisol. For more information on Ligand, please visit www.ligand.com.

Follow Ligand on Twitter @Ligand_LGND.

Caution Regarding Forward-Looking Statements

This news release contains forward-looking statements by Ligand 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 of Captisol-enabled Melphalan’s profile, market size and possibility of commercial success, efficacy, potency, competitiveness, and the strength of Ligand’s product portfolio. Actual events or results may differ from our expectations. For example, there can be no assurance that Captisol-enabled Melphalan and Alkeran or other potential Captisol-enabled drugs will progress through clinical development or receive required regulatory approvals within the expected time lines or at all, that further clinical trials will confirm any safety or other characteristics or profile described in this press release, that there will be a market of any size for Captisol-enabled Melphalan, or that Captisol-enabled Melphalan will be beneficial to patients 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.