History of Targacept, Inc.-RJR's Pharmaceutical Technology.

Anne Landman's Collection

History of Targacept, Inc.-RJR's Pharmaceutical Technology.

Date: 29 Sep 1998
Length: 3 pages
527800079-527800081
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Abstract

Recognizing the connection between some forms of mental illness and nicotine addiction, in 1997 R.J. Reynolds created a wholly-owned biotech research subsidiary to develop nicotine-like compounds to be used in the treatment of mental disorders like Alzheimer's disease, Tourette's syndrome, schizophrenia and other illnesses. RJR created the name of the company, "Targacept," by combining the words "targeted" and "receptors." Targacept's web site is at http://www.targacept.com/wt/page/index . The site's description of Targacept says, "Targacept, Inc. is a biopharmaceutical company engaged in the design, discovery and development of drugs to treat multiple nervous system diseases and disorders by selectively targeting a class of receptors known as neuronal nicotinic acetylcholine receptors, or NNRs." Targacept is located in Winston-Salem, North Carolina, the home of R.J. Reynolds. In this document desribing the origins of Targacept, RJR cites the "many epidemiological studies" that reported a lower risk for smokers for such disorders as Alzheimer's disease, Parkinson's disease and ulcerative colitis. RJR also mentions studies that show that the nicotine patch carries some benefits for people suffering from these diseases. Encouraged by these findings, RJR created Targacept in an effort to profit from marketing nicotine compounds in an entirely different, and safer way. The way that RJR acted regarding epidemiological findings in favor of nicotine contrasts starkly with how they, and the entire tobacco industry, reacted to far greater epidemiological findings that revealed the detrimental health effects of smoking.

The document also shows RJR's pursuit of safer forms of nicotine and nicotine-like compounds while continuing to make and sell cigarettes.

Fields

Notes

See document at http://legacy.library.ucsf.edu/tid/zhz97c00

Quotes

Nicotine's beneficial effects on learning, memory, and other physiological and behavioral endpoints are well documented in scientific literature. However, it is only in the last decade or so that possible therapeutic application of nicotine and nicotine-like compounds became apparent. For example, many epidemiological studies reported a lower risk among smokers for such disorder as Alzheimer's disease, Parkinson's disease, and ulcerative colitis. Following up on these leads, many researchers and clinicians have begun to explore the use of nicotine...in treating such disorders, with exciting results. It has been reported that the nicotine patch improves attention and learning in Alzheimer's patients. In addition, the patch has been shown to reverse the symptoms of ulcerative colitis in at least 50% of cases. Even more striking are studies at the University of Florida and in the UK showing dramatic reduction of symptoms in Tourette's syndrome...

...With this in mind...RJR scientists...have pursued the discovery and development of novel nicotine-like compounds that maintain nicotine's beneficial effects and reduce or eliminate side effects....RJR tested a compound, RJR-2403, in animals and humans with very encouraging results. RJR-2403 shows very good improvement of short and long-term memory in animals that are long lasting, with greatly reduced effects on the cardiovascular and gastrointestinal systems. Furthermore, RJR-2403 has been tested in human volunteers and has been shown to be safe and well tolerated...

In order to progress this area of pharmaceutical discovery as quickly as possible, and to leverage technology which has been developed, RJR has invested (and is seeking additional investment) in nicotinic drug discovery. To expedite the process RJR has developed an extensive portfolio of novel nicotine-like compounds for numerous therapeutic applications in order to position the technology for clinical development by interested pharmaceutical companies. Progress is being made rapidly and many of these compounds are now poised for further development. In order to facilitate this development, RJR has formed a wholly-owned subsidiary, Targacept, Inc., to consolidate the technology and manage the process going forward.

Company

R.J. Reynolds

Author

Presumed corporate author, R.J. Reynolds

Recipient

Presumed corporate recipient, R.J. Reynolds

Region

United States

Type

REPORT

Named Organization

University of Florida

Subject

nicotine

nicotine analogues (Technology)

nicotine patch

nicotine receptor

nicotine technology

Document Images

Page 1: zhz97c00

Progress is being made rapidly and many of these compounds are now poised for 5uther development. In order to facilitate this development, RJR has formed a wholly-owned subsidiary, Targacept, Inc. to consolidate the technology and mange the process going forward. RJR0000000054011380 70016 6401

Page 2: zhz97c00

HISTORY OF TARGACEPT, INC. - RJR's PHARMACEUTICAL TECHNOLOGY RJR has a rich history of diversification. This is based on a solid track record of sound scientific inquiry and broad publication in the scientific literature. One example is investment in Biosource, Inc., a biotechnology company focussed on, among other activities, discovery of new ways to utilize the tobacco plant to produce commercially viable products. Another is AVOCA, an agricultural unit producing various natural products for commercial use. RJR's interest in nicotine is long-standing as part of its effort to understand a key component of its products. The company's contributions in this area of research have resulted in hundreds of scientific papers and abstracts over the years. This knowledge base, in conjunction with numerous investigations in the scientific literature into the biological effects of nicotine, has added significantly to our understanding of this widely consumed natural product. In the 1980's it became apparent that nicotine interacts with many different sites in the body, known as 'receptors', which mediate nicotine's diverse physiological and pharmacological effects. Furthermore, the reason for this diversity of effects is based on the diversity of receptors. We now know that there are at least 16 genes encoding for the various receptor types and that these receptors are expressed throughout the body. Many of the receptor types are present in the brain and this accounts for the well-known cognition-enhancing effects of nicotine. Others are present in the cardiovascular system and mediate nicotine's effects on heart rate and blood pressure, and some are present in the gastrointestinal tract, mediating effects on motility and emesis. Because nicotine itself interacts with all of these receptors it became apparent that to study these systems it was necessary to develop new compounds selective for individual receptor types. In fact, the development of such probes was a major goal of scientists involved in this area of research. RJR scientists have been successful in doing this. As a result, there is now an opportunity to exploit this research and the compounds coming out of the research in a therapeutic setting. Nicotine's beneficial effects on learning, memory, and other physiological and behavioral endpoints are well documented in the scientific literature. However, it was only in the last decade or so that possible therapeutic application of nicotine and nicotine-like compounds became apparent. For example, many epidemiological studies reported a lower risk among smokers for such disorders as Alzhiemer's disease, Parkinson's disease, and ulcerative colitis. Following up RJR0000000054011380 70016 6399

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on these leads, many researchers and clinicians have begun to explore the use of nicotine (e.g., in the form of gum or patch) in treating such disorders, with exciting results. It has been reported that the nicotine patch improves attention and learning in Alzheimer's patients. In addition, the patch has been shown to reverse the symptoms of ulcerative colitis in at least 50% of cases. Even more striking are studies at the University of Florida and in the UK showing dramatic reduction of symptoms in Tourette's syndrome. Finally, researchers at Duke University have recently shown that the patchsignificantly improvessymptoms in adults with attention deficit disorder. Despite these very important findings, it is generally agreed that nicotine itself would not be suitable for therapeutic development. This is based primarily on the fact that nicotine produces a number of side effects such as increased heart rate and blood pressure, and gastrointestinal distress, which render it less useful in a therapeutic context. With this in mind, a number of pharmaceutical companies such as Abbott and SIBIA, as well as RJR scientists, have pursued the discovery and development of novel nicotine-like compounds that maintain nicotine's beneficial effects and reduce or eliminate side effects. For example, Abbott has tested ABT-41 8, a nicotine-like compound, in Alzheimer's disease with positive results. However, side effects were not reduced to acceptable levels. RJR has tested a compound, RJR-2403, in animals and humans with very encouraging results. RJR-2403 shows very good improvement of short and long-term memory in animals that are long lasting, with greatly reduced effects on the cardiovascular and gastrointestinal systems. Furthermore, RJR- 2403 has been tested in human volunteers and has been shown to be safe and well tolerated. SIBIA, another company working in this area, now has two compounds in clinical trials for Alzheimer's disease (SIB-1553) and Parkinson's disease (SIB-1508). Although the clinical development of these novel nicotine-like compounds is progressing rapidly, no one to date has completed studies to prove that these kinds of compounds are effective in treating these diseases. However, based on numerous animal studies, a positive outcome is expected and should be near at hand. In order to progress this area of pharmaceutical discovery as quickly as possible, and to leverage technology which has been developed, RJR has invested (and is seeking additional investment) in nicotinic drug discovery. To expedite the process RJR has developed an extensive patent portfolio of novel nicotine-like compounds for numerous therapeutic applications in order to position the technology for clinical development by interested pharmaceutical companies. RJR0000000054011380 70016 6400

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