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Novartis AG

Drug Names(s): SB-497115-GR, TPO agonist, eltrombopag, Revolade (EU)

Description: Eltrombopag is an orally active, selective, small molecule, non-peptidyl TpoR agonist utilizing Ligand's STAT technology. STATs are a family of proteins that play a key role in the signal transduction pathway for biologically important hormones such as the interferons, interleukins and hematopoietic growth factors. Thebinding of these hormones to their receptors on the surface of cells triggers the activation of specific STATs. These activated STATs enterthe cell nucleus and bind to specific target genes, thereby altering gene expression and affecting physiologic functions such as hematopoiesis and immune response.

TPO is the major cytokine involved in the formation of megakaryocytes and thrombocytes. Megakaryocytes are the precursor bone marrow cells from which platelets are derived. TPO has multilineage effects in hematopoiesis, acting in synergy witherythropoietin (EPO) and granulocyte-colony stimulating factor (G-CSF) to enhance proliferation and survival of committed erythroidprogenitors and primitive hematopoietic stem cells.

Deal Structure: The GSK-Ligand collaboration began in 1995 to capitalize on Ligand's Signal Transducers and Activators of Transcription (STAT) 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 milestonepayments of up to $8 million. GSK has exclusive worldwide marketing rights to products resultingfrom 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.

In February 2005, Ligand earned a $1 million milestone payment from GSK with the company's commencement of phase II trials for eltrombopag. Ligand could receive additional milestonepayments and royalties on net product sales. The royalties would be payable on annual worldwide net sales according to the following...See full deal structure in Biomedtracker

Partners: Ligand Pharmaceuticals, Inc.

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