Cytokinetics And GlaxoSmithKline Announce Seven Presentations At The 2002 Annual Meeting Of The American Association For Cancer Research
Broad Alliance to Generate First IND in 2002
South San Francisco, CA - April 8, 2002
Cytokinetics, Inc. and GlaxoSmithKline plc announced today that seven abstracts related to their broad strategic collaboration will be presented at the 2002 Annual Meeting of the American Association for Cancer Research (AACR) in San Francisco. The series of oral and poster presentations arising from their collaboration focuses on the potential pharmaceutical utility for novel small molecules specifically directed to kinesin spindle protein (KSP), a mitotic kinesin protein essential for proper DNA division in cells. The companies intend to file an Investigational New Drug (IND) application with the U.S. Food & Drug Administration during 2002.
Cytokinetics and GlaxoSmithKline will jointly unveil at AACR the results of intensive research efforts in the field of mitotic kinesins and novel small molecules targeting these enzymes for potential applications in the treatment of cancer. These presentations address an array of related topics that extend from the characterization of mitotic kinesins as attractive anti-cancer drug discovery targets to a comprehensive disclosure of the advanced scientific work supportive of impending clinical investigations of an advanced inhibitor of KSP.
Specific highlights of the presentations to be made over the course of the scientific meeting include the breadth of antitumor activity that Cytokinetics and GlaxoSmithKline have observed in multiple preclinical studies of cancer. These studies span more than ten different models, including human colon cancers and carcinomas of the breast, ovary, lung and pancreas, measuring the activities of KSP inhibitors relative to standard controls including irinotecan, topotecan, gemcitabine, paclitaxel, vinblastine, and cyclophosphamide. Details of preclinical antitumor activity are complemented by observations demonstrating the absence of treatment-associated neuropathy in animal models. The pharmacological studies are accompanied by additional presentations describing the depth of biological research which supports the continued evaluation of these agents as potential anti-cancer pharmaceuticals. These range from broad transcriptional profiling demonstrating the overexpression of KSP and other mitotic kinesins in human cancers to detailed biochemical studies describing the molecular mechanism by which these inhibitors block KSP enzymatic activity.
These preclinical data lead to the hypotheses that KSP inhibitors may be clinically effective anti-tumor agents, and that such agents may be well tolerated by cancer patients. However, the clinical relevance of the findings needs to be determined. Cytokinetics and GlaxoSmithKline are actively planning clinical studies to test these hypotheses.
“We are pleased to have this exciting opportunity to share with the scientific community a number of presentations covering the scientific breadth of our efforts and key achievements in the field of mitotic kinesins,” stated Dr. James Sabry, Cytokinetics’ President and Chief Executive Officer. “In addition, we look forward to the pending initiation of human clinical trials with GlaxoSmithKline and the continuation of progress in translating our powerful leadership position in this field into potential novel pharmaceuticals for cancer patients and treating physicians.”
“GlaxoSmithKline, through our broad strategic alliance with Cytokinetics, is highly committed to fully exploring the opportunity to identify multiple anti-cancer drugs with novel mechanisms of action, yet directed to a clinically validated target, the mitotic spindle,” said Dr. Allen Oliff, GlaxoSmithKline's Senior Vice President, Center of Excellence for Drug Discovery - Oncology. “We are encouraged by the preclinical data arising from our joint efforts and are planning a comprehensive development effort for mitotic kinesin inhibitors under the collaboration.”
Background
Kinesins are enzymes that translate energy released by hydrolysis of ATP into mechanical force along intracellular filaments in order to carry out important biological functions. Mitotic kinesins are a functional subgroup of kinesins that work in an ordered fashion to facilitate mitosis, the division of DNA during cell division. These cytoskeletal motor proteins act in concert in a mechanical cascade to carry out the events of mitotic spindle formation and function. Academic and biopharmaceutical research activities have demonstrated that these enzyme targets are amenable to small molecule perturbation thereby disrupting mitotic spindle function, interrupting DNA and cell division and inducing apoptosis or cell death. KSP is required at the earliest stages of mitosis, and is the mitotic kinesin for which the biological function is best understood.
Historical experience has demonstrated that important progress is often made in clinical medicine with the introduction of pharmaceuticals that act by novel mechanisms of action. Existing anti-mitotics (taxanes and vinca alkaloids) are all directed at tubulin, the intracellular protein that comprises the mitotic spindle, and are perhaps the most clinically and commercially successful anti-cancer agents. Since their introduction 20 years ago, these agents have dramatically advanced cancer patient care and have served as a cornerstone of modern chemotherapy. However, use of these agents is severely constrained by dose-limiting toxicities related to the broad role tubulin plays in important cellular processes unrelated to mitosis. In contrast, mitotic kinesins represent a family of newly identified enzymes that each appears to perform discrete and non-redundant roles in mitotic spindle formation and function. Unlike tubulin, mitotic kinesins are expressed only in proliferating cells and appear to play no role outside mitosis. Inhibitors of mitotic kinesins may therefore represent next generation anti-mitotics, by targeting the mitotic process specifically. Clinical investigators in oncology are excited about the potential of these newer agents as they are oriented toward a new set of molecular targets within a well-validated pharmaceutical space.
Abstracts being presented
These abstracts will be available upon request or can be downloaded at
http://aacr02.agora.com/planner/default.asp:
1. Abstract Number 325: Inhibitors of the mitotic kinesin KSP: Biochemical mechanism of action (Poster presentation by Dr. Roman Sakowicz, Cytokinetics, Inc., South San Francisco, CA, on Sunday, April 7, 2002, Section 11, 8:00 AM – 12:00 PM).
2. Abstract Number 1335: SB-715992, a potent and selective inhibitor of the mitotic kinesin KSP, demonstrates broad-spectrum activity in advanced murine tumors and human tumor xenografts (Poster presentation by Dr. Jeffrey Jackson, GlaxoSmithKline, King of Prussia, PA, on Sunday, April 7, 2002, Section 14, 1:00 PM – 5:00 PM).
3. Abstract Number 1336: A pharmacodynamic marker of mitosis demonstrates the anti-mitotic activity of SB-715992, an inhibitor of the mitotic kinesin KSP (Poster presentation by Dr. Jeffrey Jackson, GlaxoSmithKline, King of Prussia, PA, on Sunday, April 7, 2002, Section 14, 1:00 PM – 5:00 PM).
4. Abstract Number 1337: Breadth of anti-tumor activity of CK0238273 (SB-715992), a novel inhibitor of the mitotic kinesin KSP (Poster presentation by Mr. Paul Gonzales, Institute for Drug Development, San Antonio, TX, on Sunday, April 7, 2002, Section 14, 1:00 PM – 5:00 PM).
5. Abstract Number 3648: Mitotic kinesin-targeted antitumor agents: Discovery, lead optimization and anti-tumor activity of a series of novel quinazolinones as inhibitors of kinesin spindle protein (KSP) (Poster presentation by Dr. Whitney Smith, Cytokinetics, Inc., South San Francisco, CA, on Tuesday, April 9, 2002, Section 9, 8:00 AM – 12:00 PM).
6. Abstract Number 3300: Inhibitors of the mitotic kinesin KSP: Discovery and proof of principle anti-tumor activity (Oral presentation by Dr. Kenneth W. Wood, Cytokinetics, Inc., South San Francisco, CA, Minisymposium, Inhibition of Cell Cycle Regulation, Experimental/Molecular Therapeutics 29, on Tuesday, April 9, 2002, 10:25 AM – 10:40 AM).
7. Abstract Number 5375: Utilization of gene expression profiles to identify mitotic kinesins (Poster presentation by Dr. Christophe Béraud, Cytokinetics, Inc., South San Francisco, CA, on Wednesday, April 10, 2002, Section 10, 8:00 AM – 12:00 PM).
About Cytokinetics
Founded in 1998 and privately held, Cytokinetics is dedicated to the discovery, development and commercialization of a novel class of therapeutics resulting from its leadership position in the emerging field of cytoskeletal pharmacology. The cytoskeleton is a complex, dynamic framework that impacts all aspects of cell function including cell division, cell motility, intracellular transport, muscle contractility and regulation of cellular organization. Cytokinetics’ R&D efforts incorporate proprietary Cytometrix™ cellular phenotyping technologies and are focused on serving pharmaceutical needs in cancer, cardiovascular and infectious diseases. For more information, please visit the company’s web site at www.cytokinetics.com.
About GlaxoSmithKline
GlaxoSmithKline -- one of the world's leading research-based pharmaceutical and healthcare companies -- is committed to improving the quality of human life by enabling people to do more, feel better and live longer. GlaxoSmithKline is committed to the research, development, manufacturing and marketing of therapeutic and supportive care products for hematology and oncology patients. For company information, visit GlaxoSmithKline at www.gsk.com.
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