Fragment-based drug discovery, a new paradigm that emerged in the field of drug discovery in the mid-1990s, has been embraced by a number of pharmaceutical and biotechnology companies, thanks to the concept's continued success in identifying quality clinical candidates.
Before we take a look at one of the pioneers of fragment-based drug discovery - Astex Pharmaceuticals Inc. (ASTX), here's what fragment-based drug designing means in a nutshell...
Fragment-based drug discovery approach involves the use of relatively small and simple molecules to bind with a target protein in the making of lead compounds. The binding interactions of the small fragments to the target proteins are understood by X-ray crystallography or other physical techniques like NMR (Nuclear Magnetic Resonance). Speed and decreased attrition rates in drug development are some of the advantages of fragment-based drug discovery over conventional approach.
The fragment-based drug discovery approach of Astex is known as Pyramid and it has been successfully applied to generate lead compounds for the potential treatment of cancer, viral infections, inflammation and Alzheimer's disease.
For readers who are new to Astex Pharma, here's brief overview of its business and the upcoming events to keep an eye on...
Founded in 1991, the company was formerly known as SuperGen Inc. and changed its name to Astex Pharmaceuticals Inc. in September 2011. The company has one marketed drug Dacogen, an anti-cancer therapeutic and eight drugs in development, four of which are currently in or entering Phase II clinical trials, and four of which are currently partnered or optioned to pharmaceutical companies.
In August 2004, Astex Pharma licensed Dacogen to MGI Pharma Inc. , which in turn, sub-licensed the drug to Janssen-Cilag, a Johnson & Johnson company in July 2006. MGI Pharma was acquired by Eisai Corp of North America in January 2008.
Dacogen is currently approved for the treatment of myelodysplastic syndromes, and is available in more than 30 countries worldwide including key markets such as the United States, Brazil, China, India, Russia and Turkey.
Astex receives a royalty on worldwide net sales of Dacogen starting at 20% and escalating to a maximum of 30%. Royalty revenue generated in the nine-month period of 2011 was $45.1 million and in full-year 2011, the royalty revenue forecast is up to $61.5 million.
A supplemental New Drug Application seeking approval for Dacogen in the elderly Acute Myeloid Leukemia indication is under review by the FDA. The U.S. regulatory agency's decision on the additional indication of the drug is expected on March 6, 2012.
Before the FDA makes its final decision on the additional indication for Dacogen, an Oncologic Drugs Advisory Committee is scheduled to make its recommendations regarding the expanded approval for the drug for the treatment of elderly acute myelogenous leukemia on February 9, 2012.
The FDA usually follows the recommendations of its advisory panels, but is not required to do so.
The proposal for Dacogen's approval for the treatment of elderly Acute Myeloid Leukemia is under review in the European Union also , and the European Medicines Agency is expected to determine the outcome within the second quarter of 2012.
The clinical pipeline of Astex includes proprietary research programs and those developed through partnerships with major pharmaceutical firms, fueled by the company's drug discovery engine, Pyramid.
The proprietary research programs of Astex include:
* AT13387, a second generation inhibitor of heat shock protein 90. A phase II trial of AT13387 in combination with Novartis' Gleevec (Imatinib) in unresectable or metastatic gastrointestinal tumors is ongoing. The study is designed to enroll 36 patients and final data on primary outcome measure is expected to be collected in May of this year. AT13387 is also under phase I testing as a single agent in adults with refractory solid tumors and these phase I trials are close to completion.
* AT7519, a cyclin-dependent kinase inhibitor, which has been investigated in two phase I clinical trials in patients with advanced solid tumors. A phase II study of AT7519 in combination with Millennium Pharmaceuticals' Velcade (bortezomib) in patients with multiple myeloma is currently underway. This phase II study is designed to enroll 54 patients and final data on primary outcome measure is expected to be collected in August 2012. In addition, two phase II trials of AT7519 to treat patients with chronic lymphocytic leukemia and mantle cell lymphoma are starting, sponsored by the NCIC Clinical Trials Group in Canada. Novartis has an option to develop and commercialize AT7519.
* AT9283, which is under phase II testing in patients with relapsed or refractory multiple myeloma. The study is designed to enroll 30 patients and final data on primary outcome measure is expected to be collected by June 2013. The compound has been investigated as monotherapy in patients with advanced solid tumors in two phase I trials and the drug candidate is also being evaluated in pediatric patients with solid tumors.
* SGI-110, an inhibitor of DNA methyltransferase. A dose expansion stage of phase I/II clinical trial in myelodysplastic syndromes and acute myeloid leukemia patients is expected to begin in the first half of this year. The company is planning to commence phase II studies with SGI-110 in the second half of 2012.
* Amuvatinib, which is in a clinical proof of concept phase II study in small cell lung cancer. Preliminary results from this study are expected in the fourth quarter of 2012.
The research programs under drug discovery collaborations include,
LEE011, a phase I candidate, derived from collaboration with Novartis; AZD3839, also under phase I testing, derived from collaboration with AstraZeneca; AZD5363, under a phase 1 study in patients with advanced solid tumors, derived from collaboration with AstraZeneca and Fibroblast Growth Factor Receptor inhibitor compound, under pre-clinical development, derived from collaboration with Janssen Pharmaceuticals Inc., a unit of Johnson & Johnson.
Astex Pharma also has a collaboration agreement with GlaxoSmithKline plc to discover, develop and commercialize novel compounds directed against multiple therapeutic targets of interest to the British drug company.
Astex was formerly known as SuperGen Inc. and was trading on the Nasdaq under ticker SUPG. SuperGen became a public company in March 1996 offering its shares at $6 each. In July 2011, SuperGen acquired Astex Therapeutics Ltd, a privately held, UK-based biotechnology company developing targeted therapies, in a deal valued at $55 million. Following the acquisition, the company took on the name of Astex Pharmaceuticals Inc. and began trading on the Nasdaq under the new ticker ASTX beginning September 12, 2011.
Following the successful completion of the acquisition, Astex is optimistic of its position in what it believes is a new era in the company's history.
A quick look at Astex Pharma's balance sheet...
In the third quarter ended September 30, 2011, the company reported a net loss of $1.1 million, or $0.01 per share, on revenue of $16.9 million. Astex Pharma ended 2011 third quarter in a financially strong position, with roughly $128 million in cash, cash equivalents and current and non-current marketable securities.
ASTX has gained more than 18% in the past 1 month. The stock closed Monday's trading at $2.01, up 3.61%.
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