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CEL-031

Celek Pharmaceuticals, LLC

Drug Names(s): CP461, OSI-461

Description: CP461 is related to Aptosyn, which is in turn derived from sulindac. Cell Pathways has named Aptosyn and related compounds selective apoptotic antineoplastic drugs (SAANDs), although the nomenclature has limited scientific and clinical relevance. This class of drugs putatively promotes apoptosis by inhibiting a cyclic GMP specific phosphodiesterase. Such inhibition is thought to be independent of other apoptosis mediators such as p53 and Bcl-2. Increased cyclic GMP activity leads to increased Protein Kinase G activity, which in turn is thought to promote caspase activation and apoptosis.

In preclinical investigations, SAANDs in combination with various chemotherapy drugs yielded additive or synergistic antineoplastic effects. OSI-461 and Aptosyn(R) are cGMP phosphodiesterase (cGMP-PDEs) inhibitors which are designed to lead to sustained activation of the intracellular signaling protein, Protein Kinase G (PKG), and subsequent stimulation of apoptosis through the c-Jun kinase pathway. Broad spectrum inhibition of cGMP-PDEs have been shown to lead to elevation in cGMP levels and the sustained activation of PKG. This in turn directly phosphorylates MEKK1 leading to activation of the N-terminal c-Jun kinase (JNK-1) pathway, a known pro-apoptotic signaling pathway, leading to inhibition of tumor growth.

Deal Structure: In February 2003, OSI Pharmaceuticals announced plans to acquire Cell Pathways.

On March 1, 2010, Astellas Pharma announced they will commence a tender offer to acquire all outstanding shares of common stock of OSI Pharmaceuticals for $52.00 per share in cash, or an aggregate of approximately $3.5 billion on a fully diluted basis.

On May 16, 2010, Astellas Pharma and OSI Pharmaceuticals announced that they have entered into a definitive merger agreement under which Astellas will acquire OSI. Under the terms of the merger agreement, Astellas will increase its offer price to $57.50 per share, which represents a premium of 55% to the closing price for OSI's shares of $37.02 on February 26, 2010, the last trading day before the announcement by Astellas of its tender offer. The boards of directors of both companies have unanimously approved the combination. The all-cash transaction is valued at $4.0 billion on a fully diluted basis. The acquisition was completed on June 9,...See full deal structure in Biomedtracker

Partners: Astellas Pharma, Inc.


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