November 12, 2003

News Release: Lexicon Discovers Gene to Control High Blood Pressure With Direct Link To Human Hypertension

Lexicon Genetics' (Nasdaq: LEXG) study identifying a novel gene target for the control of high blood pressure and detailing the creation of the largest gene trap library in the world has been published in the online Early Edition issue of the Proceedings of the National Academy of Science. The paper, 'Wnk1 kinase deficiency lowers blood pressure in mice: A gene-trap screen to identify potential targets for therapeutic intervention,'is accessible online at www.lexicon-genetics.com and will be published in an upcoming print edition of the journal. The study illustrates the power of Lexicon's OmniBank(R) gene knockout library to identify new targets for potential treatment of human disease. Hypertension is a major public health issue. One in four adults in the United States suffers from high blood pressure and hypertension is the leading diagnosis for patients age 50 and over. Despite over $19 billion in worldwide sales of antihypertensives, a considerable number of patients remain resistant to treatment. Novel treatment strategies are required to address this unmet medical need. Lexicon holds the patent on the human WNK1 gene sequence and has filed patent applications claiming its medical use as a target to develop new therapeutics for high blood pressure.

Lexicon used its gene-trapping technology in a high-throughput, automated process to create the OmniBank library. OmniBank contains 271,860 sequence- tagged mouse ES cell clones, representing gene knockouts for approximately 60% of genes. The study provides data from more than 700 lines of mice produced and evaluated for medically favorable profiles such as low blood pressure. The results demonstrate the highly effective nature of gene-trap insertions to knock out genes. The publication constitutes the first disclosure in the scientific literature of a gene trap technology applied on such a genome-wide scale and coincides with Lexicon's mapping of gene sequences from the OmniBank library onto the human genome (www.lexicon-genetics.com/omnibank/pnas2003 ) and the deposit of these sequences into GenBank at the National Center for Biotechnology Information.

'To date, we have analyzed more than 1,250 potential targets using mouse knockouts, over half of which were derived from our OmniBank library,'said Brian P. Zambrowicz, Ph.D., Lexicon's executive vice president of research. 'The OmniBank library has accelerated the rate of discovery of the functions of human genes.'

Lexicon scientists use knockouts to model the action of potential therapeutics to identify those drug targets responsible for controlling blood pressure as well as other medically important parameters. Mice with reduced levels of the WNK1 gene product demonstrated a medically desirable profile of low blood pressure, consistent with the observation that over-expression of this gene has been directly linked to a form of hypertension in humans, pseudohypoaldosteronism type II. This data provides proof-of-concept for targeting WNK1 with inhibitor drugs to treat hypertension.

'This article represents a culmination of years of work by our scientists to create what is by far the largest mouse embryonic stem cell library in the world,'said Arthur T. Sands, M.D., Ph.D., Lexicon's president and chief executive officer. 'OmniBank allows us to increase the speed at which potential new breakthrough therapies can be brought into development, and we have already harvested more than 20 drug discovery programs from the human genome, including those for hypertension.'

Lexicon uses its OmniBank gene-trap resource, as well as gene-targeting by homologous recombination, to produce knockout mice that are studied to select those with favorable medical profiles to discover new targets for pharmaceutical development. With knowledge of the physiological function and medical utility of these targets, the company develops therapeutic agents with potential to provide breakthrough treatments of human disease. Lexicon's gene targeting and gene trapping technologies are covered by a total of 12 issued patents.

About Lexicon Genetics

Lexicon Genetics is a biopharmaceutical company focused on the discovery of breakthrough treatments for human disease. Lexicon is using gene knockout technology to systematically discover in living mammals, or in vivo, the physiological functions and pharmaceutical utility of genes. The Company's gene function discoveries fuel therapeutic discovery programs in diabetes, obesity, cardiovascular disease, neurological disease, cancer, immune and ophthalmologic disorders. Lexicon has established drug discovery alliances and functional genomics collaborations with leading pharmaceutical and biotechnology companies, research institutes and academic institutions throughout the world to commercialize its technology and turn its discoveries into drugs. Additional information about the Company is available through Lexicon's corporate website, www.lexicon-genetics.com .

Safe Harbor Statement

This press release contains 'forward-looking statements,'including statements about Lexicon's growth and future operating results, discovery and development of products, strategic alliances, and intellectual property, as well as other matters that are not historical facts or information. These forward-looking statements are based on management's current assumptions and expectations and involve risks, uncertainties and other important factors, specifically including those relating to Lexicon's ability to develop drug candidates from its discoveries, achieve its operational objectives, obtain patent protection for its discoveries and establish strategic alliances, that may cause Lexicon's actual results to be materially different from any future results expressed or implied by such forward-looking statements. Information identifying such important factors is contained under 'Factors Affecting Forward-Looking Statements'and 'Business - Risk Factors'in Lexicon's annual report on Form 10-K for the year ended December 31, 2002, as filed with the Securities and Exchange Commission. Lexicon undertakes no obligation to update or revise any such forward-looking statements, whether as a result of new information, future events or otherwise.

SOURCE Lexicon Genetics Incorporated

Chas Schultz, Director, Investor Relations and Financial Analysis of Lexicon Genetics Incorporated, +1-281-863-3421, or This email address is being protected from spambots. You need JavaScript enabled to view it.

WEBSITE This email address is being protected from spambots. You need JavaScript enabled to view it.