Ligand Advances LGD2226 to Human Development Track for Androgen-Related Disorders; Target Male Hormone Replacement, Male and Female Sexual Dysfunction and Osteoporosis.

Business Editors/Health & Medical Writers

BIOWIRE2K

SAN DIEGO--(BW HealthWire)--March 21, 2000

Ligand Pharmaceuticals Incorporated (Nasdaq:LGND) announced today that it has moved onto human development track a clinical candidate, LGD2226, that it believes represents the first selective androgen receptor modulator ("SARM") for the treatment of major androgen-related diseases and disorders, such as osteoporosis, male hormone replacement, male and female sexual dysfunction, and cachexia (wasting).

SARMs are a novel class of orally active non-steroidal molecules that target modulation of the androgen receptor. SARMs are designed to enhance the beneficial effects of androgen receptor activation while reducing or eliminating the undesired side effects, such as liver toxicity and increased risk of prostate cancer, associated with the use of currently marketed steroidal full androgen agonists.

"The strength of the LGD2226 pre-clinical data suggests the potential value of this novel SARM compound and is, in our opinion, a major breakthrough in the field of androgen therapy," said Andres Negro-Vilar, Senior Vice President of Research and Development, and Chief Scientific Officer. "The use of Ligand's molecular and cellular approaches and our expertise in developing tissue-selective nuclear receptor modulators, combined with a strong proprietary position in human androgen receptor technology, enabled Ligand scientists to achieve this important scientific milestone."

In a series of comprehensive pre-clinical studies carried out in established animal models, LGD2226 dosed once daily in long-term studies was able to fully maintain muscle and bone mass at doses much lower than those of a comparator, fluoxymesterone, an orally active steroidal androgen. In those studies, LGD2226 at doses that were fully effective on bone and muscle had a significantly reduced impact on prostate growth. The ability to minimize or eliminate the concerns of increased prostate cancer risk associated with the use of steroidal androgens clearly represents an additional advantage. LGD2226 was also shown to restore sex behavior in an animal model that evaluates the activity of these agents in restoring or enhancing libido and sexual drive.

Current androgen therapies include testosterone, in injectible or transdermal delivery forms that limit its use and range of therapeutic applications, and oral steroidal androgens, such as fluoxymesterone. The use of oral androgens has been limited by the concerns of potential liver toxicity of 17-alkylated steroidal molecules and by the relatively low efficacy achieved with those molecules compared to testosterone.

LGD2226 is one of a family of molecules that Ligand is developing to address the multiple therapeutic applications of SARMs. As a result of their potential to build bone while preventing bone loss, these novel SARMs represent important new therapeutic opportunities for the treatment of both male and female osteoporosis. These agents also show distinct promise for the treatment of sexual dysfunction, not only in hypogonadal or elderly males but, importantly, in women. The combined activity of restoring sexual drive in postmenopausal women while providing anabolic activity in bone, alone or in combination with estrogen replacement therapy, would address a large unmet market need.

"Ligand's leadership in the field of SARMs, combined with our already established strength in the field of Selective Estrogen Receptor Modulators (SERMs), positions the company at the forefront of innovation and advanced product development in broad therapeutic areas of women's and men's health, such as hormone replacement, osteoporosis, cardiovascular disease, breast and prostate cancer, and sexual disorders," said Chairman, President and CEO David E. Robinson. "LGD2226 is the result of Ligand's substantial investment over the past five years in the androgen field and holds potential to be one of Ligand's future big drugs for which we have retained worldwide rights. While the field of SARMs is so large as to require some partnering activities to capture its full potential, we intend to retain important molecule and field rights for ourselves as well."

Data on the utility and activity of SARMs and results of the pre-clinical studies with LGD2226 are expected to be presented by Ligand scientists at upcoming meetings, including at the National Institutes of Health workshop organized by the National Institute of Aging in Bethesda, MD, April 26-28; at the Federation of National European Menopause Societies in Prague, April 29-May 1; and at the Endocrine Society's 82nd Annual Meeting in Toronto, June 21-24.

Ligand Pharmaceuticals Incorporated

Ligand Pharmaceuticals Incorporated discovers, develops and markets new drugs that address critical unmet medical needs of patients in the areas of cancer, skin diseases, and men's and women's hormone-related diseases, as well as osteoporosis, metabolic disorders and cardiovascular and inflammatory diseases. In addition to the recently approved Targretin(R) capsules, Ligand had two drugs approved during 1999 for marketing in the U.S. -- ONTAK(R) and Panretin(R) gel -- that are being marketed through its specialty cancer and HIV-center sales force in the U.S. Targretin(R) gel is currently under review by the FDA for marketing approval in the U.S., and two additional oncology-related products -- Morphelan(TM) (licensed from Elan) and Panretin(R) capsules -- are in late-stage development. Ligand's proprietary drug discovery and development programs are based on its leadership position in gene transcription technology, primarily related to Intracellular Receptors (IR) and Signal Transducers and Activators of Transcription (STATs).

Except for the historical information contained herein, this news release may contain certain forward looking statements by Ligand and actual results could differ materially from those described as a result of factors including, but not limited to the following. There can be no assurance that LGD2226 or any compound or product in the Ligand pipeline will be successfully developed for osteoporosis, hormone replacement therapy, male or female sexual dysfunction or any other indication; that results achieved in animal models will be supportive of regulatory filings required to initiate human clinical trials; that results from more advanced clinical trials will be consistent with earlier results; that regulatory filings will be made and regulatory approvals will be granted in a timely manner or at all; that LGD2226 or any other Ligand product will be accepted by physicians for prescribing, by patients for use and by insurance companies / agencies for reimbursement; that Ligand will retain any or all of its rights to LGD2226 or license any of its rights to SARMs to a collaborative partner; that Ligand and/or its collaborative partners will successfully develop potential products; or that Ligand will be able to hire and retain qualified personnel. Additional information concerning these and other factors affecting Ligand's business can be found in press releases as well as in Ligand's public periodic filings with the Securities and Exchange Commission, available at our website at http://www.ligand.com. Ligand disclaims any intent or obligation to update these forward-looking statements beyond the date of this release.

Note: Panretin(R)and Targretin(R)are registered trademarks of Ligand Pharmaceuticals Incorporated, and ONTAK(R)is a registered trademark of Seragen, Inc., a wholly owned subsidiary of Ligand.

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