Research and Development Initiatives
Thrombopoietin (TPO) Program
In the last decade, the Ligand TPO program has focused on developing proprietary drug candidates that mimic the activity of thrombopoietin. Thrombopoietin is used in the treatment or prevention of thrombocytopenia, with indications in a variety of conditions, including: Idiopathic Thrombocytopenic Purpura (ITP), cancer, hepatitis C, and other disorders of blood cell formation. Collectively, these indications represent a large market with multiple unmet medical needs.
In 1997, we formed a research and development alliance with SmithKline Beecham (now GlaxoSmithKline), and since then, our partner now has two TPO mimetics in clinical trials: TPO Mimetics: PROMACTATM(eltrombopag) is a small-molecule TPO mimetic that is being developed by GlaxoSmithKline for thrombocytopenia. GlaxoSmithKline submitted an NDA for PROMACTATM in 4Q07 and in March 2008, received FDA review acceptance and was granted priority review for use in treatment in short-term Idiopathic Thrombocytopenic Purpura (ITP). In addition, GlaxoSmithKline initiated two Phase III trials in 4Q07 for hepatitis C and is currently studying the drug in chemotherapy-induced thrombocytopenia (CIT).
For more information about these clinical trials, please see“Collaborative Research and Development Programs – Thrombopoietin (TPO) Mimetics Collaborative Program –GlaxoSmithKline Collaboration.”
Selective Androgen Receptor Modulators (SARM) Program
Ligand has pioneered the development of tissue selective Selective Androgen Receptor Modulators (SARMs), a novel class of non-steroidal, orally active molecules that selectively modulate the activity of the androgen receptor in different tissues.
Given the wide-ranging effects of SARMs, the potential for treating a variety of diseases and disorders in men and women is very large. For example, tissue-selective androgen receptor agonists may provide benefit in the treatment of, osteoporosis, sexual dysfunction, frailty and hypogonadism. In addition, tissue-selective androgen receptor antagonists may prove useful in the treatment of prostate cancer, acne, and androgenetic alopecia.
To address this and other medical needs, Ligand formed a research and development alliance with TAP Pharmaceutical Products in 2001. Though the research stage of this collaboration ended in June, 2006, TAP continues to develop the lead SARM compound and completed Phase I clinical trials in 4Q07. Please see the “Selective Androgen Receptor Modulators (SARM) Collaborative Programs” section below for details.
As part of the terms of our alliance with TAP, we are developing LGD-3303, which was selected from a pool of compounds available for development. Preclinical studies with LGD-3303 indicate potential efficacy in the treatment of osteoporosis, sexual dysfunction, frailty and hypogonadism. Promising in vivo rodent studies suggest a favorable profile with anabolic effects on bone, and an absence of the prostatic hypertrophy side effect typically seen with available androgens.
In February 2008, Ligand announced the addition of LGD-4033 to its SARM program.
Erythropoiein (EPO) Research Program
We are developing small molecule agonists for the EPO receptor. EPO stimulates the differentiation of blood marrow stem cells to form red blood cells. Various recombinant human EPO derivatives are marketed for the treatment of anemia due to renal failure or cancer chemotherapy (e.g., Aranesp, Epogen, Eprex, and Procrit). We believe that a small molecule agonist for the EPO receptor would provide additional benefit in the treatment of anemia and the convenience of oral administration compared to recombinant human protein therapeutics. EPO and TPO act on the same bone marrow hematopoietic stem cell to guide the development of blood cells. We expect that our prior experience in developing small molecule TPO mimetic drugs will lead to increased efficiency in discovering small molecule EPO mimetic drugs.
Selective Glucocorticoid Receptor Modulators (SGRM) Program
Ligand is researching Selective Glucocorticoid Receptor Modulators (SGRMs) for their potentially favorable effects in inflammation, cancer, and other indications. Our efforts are focused on optimizing a library of compounds to identify one or more promising candidates to enter human trials.