Lexicon Pharmaceuticals

Last updated
Lexicon Pharmaceuticals, Inc.
Company type Public
Nasdaq:  LXRX
Russell 2000 Component
Industry Pharmaceutical
Founded1995;29 years ago (1995), in The Woodlands, Texas
Headquarters The Woodlands, Texas, U.S.
Key people
  • Lonnel Coats, president and chief executive officer
  • Brian P. Zambrowicz, EVP & Chief Scientific Officer
  • Jeffrey L. Wade, EVP of Corporate Development & Chief Scientific Officer
  • Alan J. Main, EVP of Pharmaceutical Research
  • Pablo Lapuerta, EVP of Clinical Development & Chief Medical Officer
  • James F. Tessmer, VP of Finance and Accounting
RevenueIncrease2.svg $324.1 Million(2019) [1]
Number of employees
225 (2011)
Website lexpharma.com

Lexicon Pharmaceuticals, Inc. is a biopharmaceutical company developing treatments for human disease. The company was founded in 1995 in The Woodlands, Texas under the name Lexicon Genetics, Incorporated by co-founders Professor Allan Bradley, FRS and Professor Bradley's postdoctoral fellow Arthur T Sands. [2] The company has used its patented mouse gene knockout technology and extensive in vivo screening capabilities to study nearly 5,000 genes in its Genome5000 program and has identified over 100 potential therapeutic targets. Lexicon has advanced multiple drug candidates into human clinical trials and has a broad and diverse pipeline of drug targets behind its clinical programs. Lexicon is pursuing drug targets in five therapeutic areas including oncology, gastroenterology, immunology, metabolism, and ophthalmology.

Contents

The company's clinical drug candidates include sotagliflozin (LX4211) for the treatment of type 2 diabetes; LX1033 for the treatment of irritable bowel syndrome and other gastrointestinal disorders; telotristat ethyl (LX1032) for the treatment of the symptoms associated with carcinoid syndrome; and LX2931 for the treatment of autoimmune diseases, such as rheumatoid arthritis.

Company history

A Lexicon Genetics knockout mouse (left) that is a model of obesity, compared with a normal mouse. Knockoutmouse80-72.jpg
A Lexicon Genetics knockout mouse (left) that is a model of obesity, compared with a normal mouse.

Lexicon Pharmaceuticals was founded in September 1995 as a biotech venture of Baylor College of Medicine. The company went public in April 2000 with one of the largest initial public offerings in biotech history ($220 million). [3] In June, 2001 Lexicon purchased a privately owned small chemical library synthesis company, Coelacanth Corporation in Princeton, New Jersey, [4] which became the site for the company's small molecule and medicinal chemistry efforts. The company's original name was Lexicon Genetics Incorporated, but in 2007, the name changed to Lexicon Pharmaceuticals, Inc. to reflect a renewed focus on drug development.

The company initially focused on using gene knockout technology to define the function of genes. This effort complemented and benefited from the international effort to sequence the human and mouse genomes (see Human Genome Project). Using its proprietary gene trapping and gene targeting technologies, the company created the world’s largest repository of genetically modified mouse embryonic stem cells, known as OmniBank, and established a large-scale mammalian knockout program to discover the physiological and behavioral functions of the most druggable mammalian genes. [5] The information collected from this program is stored in the company’s LexVision database, which contains almost 5,000 gene knockouts studied. Over the years, Lexicon evolved from a genomics company into a drug discovery and development company focused on discovering and developing breakthrough treatments for human disease. The company currently has multiple drug candidates in various stages of clinical trials.

In 2016, the company was ranked #8 on the Deloitte Fast 500 North America list. [6]

Technology

Lexicon uses patented gene trapping and gene targeting technologies to generate and study knockout mice to discover the physiological and behavioral effects that result from the disruption of a single gene knockout. [7] Because there is a close similarity in gene function and physiology between mice and humans, with a large majority of human genes having a counterpart in the mouse genome, [8] knockout mouse technology has become a powerful tool in the discovery of new medicines.

The value of Lexicon’s technology in drug discovery has been described in a retrospective analysis by the scientific journal Nature. The conclusion of this analysis was that, in most cases, there was a direct correlation when comparing the physiological characteristics, or phenotypes, of knockout mice to the therapeutic effect of the 100 best-selling drugs of 2001. [9] The tremendous utility of knockout mouse technology was recognized in 2007 with the Nobel Prize in Physiology or Medicine to Drs. Mario Capecchi, Martin Evans, and Oliver Smithies. [10]

In developing small molecule drugs for its validated targets, Lexicon uses medicinal chemistry known as "click chemistry." Dr. K. Barry Sharpless, who was awarded the 2001 Nobel Prize in Chemistry, [11] pioneered this set of powerful and reliable tools for the rapid synthesis of novel compounds. Lexicon uses solution-phase chemistry to generate diverse libraries of optically pure compounds that are built using highly robust and scalable organic reactions that allow the company to generate compound collections of great diversity and to specially tailor the compound collections to address various therapeutic target families. Lexicon’s medicinal chemists design these libraries by analyzing the chemical structures of drugs that have been proven safe and effective against human disease and using that knowledge in the design of scaffolds and chemical building blocks for the generation of large numbers of new drug-like compounds. [12]

Locations

Lexicon operates from two locations found in Texas and New Jersey. The corporate headquarters are in The Woodlands, Texas just north of Houston. This location serves as Lexicon’s primary research facility to discover and validate the company's drug targets and test drug candidates in preclinical research. The company’s clinical development and regulatory team is also based at the corporate headquarters. [13]

Lexicon's campus in Princeton, New Jersey is the home of Lexicon's small molecule medicinal chemistry and preclinical development efforts. This site serves as Lexicon's primary medicinal chemistry site to create new chemical entities for therapeutic development. [13]

Related Research Articles

<span class="mw-page-title-main">Pharmacology</span> Branch of biology concerning drugs

Pharmacology is the science of drugs and medications, including a substance's origin, composition, pharmacokinetics, pharmacodynamics, therapeutic use, and toxicology. More specifically, it is the study of the interactions that occur between a living organism and chemicals that affect normal or abnormal biochemical function. If substances have medicinal properties, they are considered pharmaceuticals.

Gene knockouts are a widely used genetic engineering technique that involves the targeted removal or inactivation of a specific gene within an organism's genome. This can be done through a variety of methods, including homologous recombination, CRISPR-Cas9, and TALENs.

<span class="mw-page-title-main">Medication</span> Substance used to diagnose, cure, treat, or prevent disease

A medication is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy (pharmacotherapy) is an important part of the medical field and relies on the science of pharmacology for continual advancement and on pharmacy for appropriate management.

<span class="mw-page-title-main">Drug discovery</span> Pharmaceutical procedure

In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which new candidate medications are discovered.

<span class="mw-page-title-main">Medicinal chemistry</span> Scientific branch of chemistry

Medicinal or pharmaceutical chemistry is a scientific discipline at the intersection of chemistry and pharmacy involved with designing and developing pharmaceutical drugs. Medicinal chemistry involves the identification, synthesis and development of new chemical entities suitable for therapeutic use. It also includes the study of existing drugs, their biological properties, and their quantitative structure-activity relationships (QSAR).

<span class="mw-page-title-main">Fatty-acid amide hydrolase 1</span> Mammalian protein found in Homo sapiens

Fatty-acid amide hydrolase 1 (FAAH) is a member of the serine hydrolase family of enzymes. It was first shown to break down anandamide (AEA), an N-acylethanolamine (NAE) in 1993. In humans, it is encoded by the gene FAAH.

<span class="mw-page-title-main">Sigma-1 receptor</span> Chaperone protein

The sigma-1 receptor (σ1R), one of two sigma receptor subtypes, is a chaperone protein at the endoplasmic reticulum (ER) that modulates calcium signaling through the IP3 receptor. In humans, the σ1 receptor is encoded by the SIGMAR1 gene.

Conditional gene knockout is a technique used to eliminate a specific gene in a certain tissue, such as the liver. This technique is useful to study the role of individual genes in living organisms. It differs from traditional gene knockout because it targets specific genes at specific times rather than being deleted from beginning of life. Using the conditional gene knockout technique eliminates many of the side effects from traditional gene knockout. In traditional gene knockout, embryonic death from a gene mutation can occur, and this prevents scientists from studying the gene in adults. Some tissues cannot be studied properly in isolation, so the gene must be inactive in a certain tissue while remaining active in others. With this technology, scientists are able to knockout genes at a specific stage in development and study how the knockout of a gene in one tissue affects the same gene in other tissues.

<span class="mw-page-title-main">Free fatty acid receptor 1</span> Protein-coding gene in the species Homo sapiens

Free fatty acid receptor 1 (FFAR1), also known as G-protein coupled receptor 40 (GPR40), is a rhodopsin-like G-protein coupled receptor that is coded by the FFAR1 gene. This gene is located on the short arm of chromosome 19 at position 13.12. G protein-coupled receptors reside on their parent cells' surface membranes, bind any one of the specific set of ligands that they recognize, and thereby are activated to trigger certain responses in their parent cells. FFAR1 is a member of a small family of structurally and functionally related GPRs termed free fatty acid receptors (FFARs). This family includes at least three other FFARs viz., FFAR2, FFAR3, and FFAR4. FFARs bind and thereby are activated by certain fatty acids.

<span class="mw-page-title-main">Prostacyclin receptor</span> Mammalian protein found in Homo sapiens

The Prostacyclin receptor, also termed the prostaglandin I2 receptor or just IP, is a receptor belonging to the prostaglandin (PG) group of receptors. IP binds to and mediates the biological actions of prostacyclin (also termed Prostaglandin I2, PGI2, or when used as a drug, epoprostenol). IP is encoded in humans by the PTGIR gene. While possessing many functions as defined in animal model studies, the major clinical relevancy of IP is as a powerful vasodilator: stimulators of IP are used to treat severe and even life-threatening diseases involving pathological vasoconstriction.

In molecular cloning and biology, a gene knock-in refers to a genetic engineering method that involves the one-for-one substitution of DNA sequence information in a genetic locus or the insertion of sequence information not found within the locus. Typically, this is done in mice since the technology for this process is more refined and there is a high degree of shared sequence complexity between mice and humans. The difference between knock-in technology and traditional transgenic techniques is that a knock-in involves a gene inserted into a specific locus, and is thus a "targeted" insertion. It is the opposite of gene knockout.

High throughput biology is the use of automation equipment with classical cell biology techniques to address biological questions that are otherwise unattainable using conventional methods. It may incorporate techniques from optics, chemistry, biology or image analysis to permit rapid, highly parallel research into how cells function, interact with each other and how pathogens exploit them in disease.

<span class="mw-page-title-main">Genetically modified mouse</span>

A genetically modified mouse or genetically engineered mouse model (GEMM) is a mouse that has had its genome altered through the use of genetic engineering techniques. Genetically modified mice are commonly used for research or as animal models of human diseases and are also used for research on genes. Together with patient-derived xenografts (PDXs), GEMMs are the most common in vivo models in cancer research. Both approaches are considered complementary and may be used to recapitulate different aspects of disease. GEMMs are also of great interest for drug development, as they facilitate target validation and the study of response, resistance, toxicity and pharmacodynamics.

<span class="mw-page-title-main">Knockout rat</span> Type of genetically engineered rat

A knockout rat is a genetically engineered rat with a single gene turned off through a targeted mutation used for academic and pharmaceutical research. Knockout rats can mimic human diseases and are important tools for studying gene function and for drug discovery and development. The production of knockout rats was not economically or technically feasible until 2008.

<span class="mw-page-title-main">Salinomycin</span> Chemical compound

Salinomycin is an antibacterial and coccidiostat ionophore therapeutic drug.

A knockout mouse, or knock-out mouse, is a genetically modified mouse in which researchers have inactivated, or "knocked out", an existing gene by replacing it or disrupting it with an artificial piece of DNA. They are important animal models for studying the role of genes which have been sequenced but whose functions have not been determined. By causing a specific gene to be inactive in the mouse, and observing any differences from normal behaviour or physiology, researchers can infer its probable function.

<span class="mw-page-title-main">Neurolixis</span>

Neurolixis is a biopharmaceutical company focused on novel drugs for the treatment of human central nervous system diseases.

<span class="mw-page-title-main">Deuterated drug</span>

A deuterated drug is a small molecule medicinal product in which one or more of the hydrogen atoms in the drug molecule have been replaced by its heavier stable isotope deuterium. Because of the kinetic isotope effect, deuterium-containing drugs may have significantly lower rates of metabolism, and hence a longer half-life.

Polypharmacology is the design or use of pharmaceutical agents that act on multiple targets or disease pathways.

<span class="mw-page-title-main">Gene doping</span> Hypothetical non-therapeutic use of gene therapy by athletes

Gene doping is the hypothetical non-therapeutic use of gene therapy by athletes in order to improve their performance in those sporting events which prohibit such applications of genetic modification technology, and for reasons other than the treatment of disease. As of April 2015, there is no evidence that gene doping has been used for athletic performance-enhancement in any sporting events. Gene doping would involve the use of gene transfer to increase or decrease gene expression and protein biosynthesis of a specific human protein; this could be done by directly injecting the gene carrier into the person, or by taking cells from the person, transfecting the cells, and administering the cells back to the person.

References

  1. "Lexicon Pharmaceuticals Revenue 2006-2021 | LXRX".
  2. Pennisi, Elizabeth (1997-04-25). "Merck Gives Researchers Knockout Deal". Science. 276 (5312): 527. doi:10.1126/science.276.5312.527a. ISSN   0036-8075. PMID   9148409. S2CID   28451386.
  3. http://moneycentral.hoovers.com/global/msn/factsheet.xhtml?COID=99953 MSN Fact Sheet – IPO center
  4. "SEC Info - Lexicon Pharmaceuticals, Inc./DE - '8-K' for 6/13/01 - EX-99.1". www.secinfo.com.
  5. Raymond CS, Soriano P (September 2006). "Engineering mutations: deconstructing the mouse gene by gene". Dev. Dyn. 235 (9): 2424–36. doi: 10.1002/dvdy.20845 . PMID   16724325.
  6. "2016 Winners by rank" (PDF). Deloitte. Archived from the original (PDF) on 21 November 2016. Retrieved 23 September 2017.
  7. Lexicon Pharmaceutical’s Technology page Archived 2010-07-05 at the Wayback Machine
  8. Church DM, Goodstadt L, Hillier LW, et al. (May 2009). Roberts RJ (ed.). "Lineage-specific biology revealed by a finished genome assembly of the mouse". PLOS Biol. 7 (5): e1000112. doi: 10.1371/journal.pbio.1000112 . PMC   2680341 . PMID   19468303.
  9. Zambrowicz BP, Sands AT (January 2003). "Knockouts model the 100 best-selling drugs--will they model the next 100?". Nat Rev Drug Discov. 2 (1): 38–51. doi:10.1038/nrd987. PMID   12509758. S2CID   20754991.
  10. 2007 Nobel Prize Laureate – Medicine
  11. 2001 Nobel Prize Laureate – Chemistry
  12. Kolb HC, Sharpless KB (December 2003). "The growing impact of click chemistry on drug discovery". Drug Discov. Today. 8 (24): 1128–37. doi: 10.1016/S1359-6446(03)02933-7 . PMID   14678739.
  13. 1 2 "Lexicon Pharmaceutical's locations". Archived from the original on 2008-09-08. Retrieved 2010-07-29.