Tanox

Last updated
Tanox
Company type Subsidiary
Industry Biopharmaceutical
Founded Houston, Texas (1986)
Fateacquired by Genentech (2007)
HeadquartersHouston, Texas, US
Key people
 Nancy Chang (Chairman & Co-Founder)
Tse Wen Chang (Founder)
Products Humanized antibody drugs
Parent Genentech
Website www.tanox.com

Tanox was a biopharmaceutical company based in Houston, Texas. The company was founded by two biomedical research scientists, Nancy T. Chang and Tse Wen Chang in March 1986 with $250,000, which was a large part of their family savings at that time. Both Changs grew up and received college education in chemistry in National Tsing Hua University in Taiwan and obtained Ph.D. degrees from Harvard University. For postdoctoral training, Tse Wen shifted to immunology and did research with Herman N. Eisen at the Center for Cancer Research, M.I.T. The two Changs successively became research managers and worked with a range of monoclonal antibody projects in Centocor, Inc. based in Malvern, Pennsylvania, from 1981 to 1985. [1] The Changs were recruited by Baylor College of Medicine toward the end of 1985 and offered faculty positions in the Division of Molecular Virology. Soon after their arrival, they were encouraged by a high-ranking Baylor official and local business leaders to start a biotech venture in Houston. This was in a period of time when the economy of Houston was in slump as the result of the collapse of the oil industry. [1]

Contents

The Changs rented a corner of about 2000 square feet in a large empty warehouse building on Stella Link Road, located four miles away from the Texas Medical Center, and built laboratories. In 1987, Tanox obtained a $4 million cash infusion from the legendary biotech venture capitalist and investor, Moshe Alafi, [1] who was a founding investor of Cetus, Amgen, Biogen, and a few other successful biotech companies. [2] Nancy was the Chairman, President, and CEO of Tanox in its 21-year history, while Tse Wen was responsible for creating most of the company's proprietary technology and patents. Tanox's major technology was based on a series of inventions and a family of dominant patents, most notably those relating to the "anti-IgE therapy", [3] the "migis concept", [4] and the "anti-CεmX approach", [5] that pertained to the use of humanized antibodies for targeting immunoglobulin E (IgE) and IgE-expressing B lymphocytes for the treatment of allergic diseases.

Tanox was able to recruit many talented scientists, bioengineers, and other professionals, many of whom from the Texas Medical Center. Tanox held an initial public offering and was listed in the NASDAQ in 2000. [6] It eventually occupied the entire warehouse building and established additional R & D facilities in the adjacent land for carrying out various therapeutic antibody programs. [7] Many researchers grew to be top-level research managers in pharmaceutical and large biotech companies.

Tanox became the first major acquisition of Genentech in an all-cash buyout deal (US$919 million) [8] in August 2007 (Genentech itself became wholly owned by Roche in March 2009). The acquisition of Tanox has boosted Roche/Genentech's product pipeline substantially. [7] [8] [9] [10] In addition to the enhancement of the anti-IgE franchise by the increased rights on Xolair (omalizumab) and by the potential utility of TNX-901 (Talizumab), the other pipeline products that have gained considerable prominence include TNX-355 (Ibalizumab), a unique anti-CD4 antibody for treating AIDS, TNX-650 (Lebrikizumab), an anti-interleukin-13 antibody for treating asthma, and TNX-224, an Fab fragment of a humanized antibody against Factor D of the human immune complement system to be tested for treating geographic atrophy associated with dry age-related macular degeneration. [10] Based on Tanox's invention of the “anti-CεmX (also referred to anti-M1’) approach”, Genentech is developing Quilizumab, an antibody specifically targeting mIgE on B cells, for asthma and allergic diseases. [10]

The anti-IgE program

Tanox started the "anti-IgE therapy" program and developed a prototype antibody candidate in 1987, and subsequently converted the mouse antibody candidate into a chimeric form and obtained crucial set of data on the antibody in 1988–89. The Tanox' anti-IgE antibodies were designed to target free IgE in blood and IgE-expressing B lymphocytes for the purpose of intercepting the IgE-mediated pathway, without binding to IgE already bound by the high affinity IgE receptors on mast cells and basophils or bound by the low-affinity IgE receptors on many cell types. An ordinary anti-IgE antibody, if were injected into a patient, would cause a massive activation of mast cells and basophils and hence anaphylactic shocks. [1] [3] By 1989, Tanox had collected data showing that their proposed therapeutic lead anti-IgE antibody could not induce the activation of basophils isolated from the blood of any of many extremely allergic individuals, even under the most permissive conditions. [11] [12]

In order to secure funding to develop the anti-IgE program, the Changs were busily engaged throughout 1989 in trying to find a corporate partner among about 25 pharmaceutical and biotech companies, who were willing to meet with them, to co-develop the anti-IgE therapeutic program. [1] In 1990, Tanox signed a corporate partnership with Ciba-Geigy (Ciba-Geigy merged with Sandoz to form Novartis in 1996) to jointly develop the anti-IgE program. [13] The companies named the antibody candidate CGP51901 (CGP short for "Ciba-Geigy Product"), which humanized form was later created and named TNX-901 or talizumab. With the funding from Ciba-Geigy, Tanox established a 500-liter cGMP bioreactor plant in a space adjacent to the research laboratories in the warehouse building and produced CGP51901 for phase I and II clinical trials.

The joint team from Tanox and Ciba-Geigy received "investigational new drug" (IND) application approval, which is required for the first testing of a new substance in human subjects, for an anti-IgE antibody for the first time, from the U.S. Food and Drug Administration (FDA) in 1991. This was an important milestone in the development history of the anti-IgE program; Tanox scientists had anticipated major difficulty to receive IND approval for an anti-IgE antibody from the FDA, even though they had experimental data to show that CGP51901 would act differently from an ordinary anti-IgE antibody. Subsequently, Tanox/Ciba Geigy carried out a dose-escalating, double-blinded, placebo-controlled single-dose phase I clinical trial on 33 pollen-sensitive subjects with elevated serum IgE levels in Southampton, England. [14] After resolving a few unexpected clinical findings, mainly the accumulating IgE and anti-IgE immune complexes, from the phase I trial, Ciba-Geigy and Tanox ran a successful phase II trial in 153 patients with severe seasonal allergic rhinitis toward mountain cedar pollens in three medical centers in Texas in 1994–1995. [15] The positive clinical trial results, which showed increasing efficacy of CGP51901 over three different dosages (15, 30, or 60 mg in six bi-weekly doses) in improving nasal and ocular symptom scores, impressed the researchers and clinical investigators working on a similar anti-IgE program in Genentech.

In 1996, after a 3-year long lawsuit between Tanox and Genentech [16] was settled out-of-court, Genentech made its first payment of $16 million to Tanox, [17] and Tanox, Novartis, and Genentech formed a tripartite partnership to develop the anti-IgE program. [18] A humanized anti-IgE antibody from Genentech, omalizumab, with identical key binding characteristics as CGP51901, was chosen by a joint program steering committee for further development, because it had a better developed manufacturing process. [18]

Omalizumab, with the trade name Xolair, was approved by the U.S. Food and Drug Administration in 2003 for use in patients 12 years and older with moderate-to-severe allergic asthma. It was subsequently approved in the European Union and many other countries for patients 12 years and older with severe, persistent allergic asthma.

Antibody therapeutics

Among the humanized antibody drugs Tanox developed by itself or with corporate partners:

Other major technologies

Other than the therapeutic antibodies, which target the IgE allergic pathway, immune factors, and CD4, Tanox also possessed several other major patented technologies. Among those, two sets of patents represent landmark inventions in their respectively related fields. Largely because these patents were awarded too far ahead the maturation of the peripheral technologies, they did not bring material financial impact on Tanox. Nonetheless, the creation of these technologies helped germinate the two important fields and enhanced Tanox as a pioneer in the antibody field.

Related Research Articles

<span class="mw-page-title-main">Allergy</span> Immune system response to a substance that most people tolerate well

Allergies, also known as allergic diseases, are various conditions caused by hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic dermatitis, allergic asthma, and anaphylaxis. Symptoms may include red eyes, an itchy rash, sneezing, coughing, a runny nose, shortness of breath, or swelling. Note that food intolerances and food poisoning are separate conditions.

<span class="mw-page-title-main">Hypersensitivity</span> Medical condition

Hypersensitivity is an abnormal physiological condition in which there is an undesirable and adverse immune response to antigen. It is an abnormality in the immune system that causes immune diseases including allergies and autoimmunity. It is caused by many types of particles and substances from the external environment or from within the body that are recognized by the immune cells as antigens. The immune reactions are usually referred to as an over-reaction of the immune system and they are often damaging and uncomfortable.

<span class="mw-page-title-main">Immunoglobulin E</span> Immunoglobulin E (IgE) Antibody

Immunoglobulin E (IgE) is a type of antibody that has been found only in mammals. IgE is synthesised by plasma cells. Monomers of IgE consist of two heavy chains and two light chains, with the ε chain containing four Ig-like constant domains (Cε1–Cε4). IgE is thought to be an important part of the immune response against infection by certain parasitic worms, including Schistosoma mansoni, Trichinella spiralis, and Fasciola hepatica. IgE is also utilized during immune defense against certain protozoan parasites such as Plasmodium falciparum. IgE may have evolved as a defense to protect against venoms.

<span class="mw-page-title-main">Food allergy</span> Hypersensitivity reaction to a food

A food allergy is an abnormal immune response to food. The symptoms of the allergic reaction may range from mild to severe. They may include itchiness, swelling of the tongue, vomiting, diarrhea, hives, trouble breathing, or low blood pressure. This typically occurs within minutes to several hours of exposure. When the symptoms are severe, it is known as anaphylaxis. A food intolerance and food poisoning are separate conditions, not due to an immune response.

<span class="mw-page-title-main">Omalizumab</span> Monoclonal antibody medication

Omalizumab, sold under the brand name Xolair among others, is an injectable medication to treat severe persistent allergic forms of asthma, nasal polyps, urticaria (hives), and immunoglobulin E-mediated food allergy.

<span class="mw-page-title-main">Allergen immunotherapy</span> Medical treatment for environmental allergies

Allergen immunotherapy, also known as desensitization or hypo-sensitization, is a medical treatment for environmental allergies, such as insect bites, and asthma. Immunotherapy involves exposing people to larger and larger amounts of allergens in an attempt to change the immune system's response.

Theralizumab is an immunomodulatory drug developed by Thomas Hünig of the University of Würzburg. It was withdrawn from development after inducing severe inflammatory reactions as well as chronic organ failure in the first-in-human study by Parexel in London in March 2006. The developing company, TeGenero Immuno Therapeutics, went bankrupt later that year. The commercial rights were then acquired by a Russian startup, TheraMAB. The drug was renamed TAB08. Phase I and II clinical trials have been completed for arthritis and clinical trials have been initiated for cancer.

<span class="mw-page-title-main">Monoclonal antibody therapy</span> Form of immunotherapy

Monoclonal antibodies (mAbs) have varied therapeutic uses. It is possible to create a mAb that binds specifically to almost any extracellular target, such as cell surface proteins and cytokines. They can be used to render their target ineffective, to induce a specific cell signal, to cause the immune system to attack specific cells, or to bring a drug to a specific cell type.

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

Pertuzumab, sold under the brand name Perjeta, is a monoclonal antibody used in combination with trastuzumab and docetaxel for the treatment of metastatic HER2-positive breast cancer; it also used in the same combination as a neoadjuvant in early HER2-positive breast cancer.

Erlizumab, also known as rhuMAb, is a recombinant humanized monoclonal antibody that was an experimental immunosuppressive drug. Erlizumab was developed by Genentech under a partnership with Roche to treat heart attack, stroke, and traumatic shock.

Ocrelizumab, sold under the brand name Ocrevus, is a medication used for the treatment of multiple sclerosis (MS). It is a humanized anti-CD20 monoclonal antibody. It targets CD20 marker on B lymphocytes and is an immunosuppressive drug. Ocrelizumab binds to an epitope that overlaps with the epitope to which rituximab binds.

Reslizumab, sold under the brand names Cinqair and Cinqaero, is a humanized monoclonal antibody against human interleukin-5 (IL-5). Reslizumab binds specifically to IL-5, a key cytokine responsible for the differentiation, maturation, recruitment and activation of human eosinophils. By binding to human IL-5, it blocks its biological function; consequently survival and activity of eosinophils are reduced. The benefits with reslizumab are its ability to reduce the exacerbation rate and improve lung function and asthma-related quality of life in patients with severe eosinophilic asthma and with at least one previous asthma exacerbation in the preceding year. The most common side effects are increased blood creatine phosphokinase, myalgia and anaphylactic reactions.

Talizumab (TNX-901) is a humanized monoclonal antibody that was under development by Tanox in Houston, Texas as a new-concept therapeutic for allergic diseases. The unique anti-IgE antibody was designed to target immunoglobulin E (IgE) and IgE-expressing B lymphocytes specifically, without binding to IgE already bound by the high affinity IgE receptors on mast cells and basophils. Talizumab was tested in clinical trials at National Jewish Medical and Research Center and other medical centers and allergy clinics across the U. S. and shown to be able to prevent allergic reactions to accidental exposure to peanuts, which is contained in many kinds of foods.

Ibalizumab, sold under the brand name Trogarzo, is a non-immunosuppressive humanised monoclonal antibody that binds CD4, the primary receptor for HIV, and inhibits HIV from entering cells. It is a post-attachment inhibitor, blocking HIV from binding to the CCR5 and CXCR4 co-receptors after HIV binds to the CD4 receptor on the surface of a CD4 cell. Post-attachment inhibitors are a subclass of HIV drugs called entry inhibitors.

Lebrikizumab, sold under the brand name Ebglyss is a humanized monoclonal antibody used for the treatment of atopic dermatitis.

Quilizumab (INN) is a humanized monoclonal antibody designed for the treatment of asthma. It binds to IGHE.

Ligelizumab is a humanized IgG1 monoclonal antibody designed for the treatment of severe asthma and chronic spontaneous urticaria. It is an anti-IgE that binds to IGHE an acts as an immunomodulator.

<span class="mw-page-title-main">Nancy T. Chang</span> Biochemist

Nancy Tang Chang, née Tang Nanshan, is a biochemist who cofounded Tanox in 1986 to address medical needs in the areas of allergy, asthma, inflammation and diseases affecting the human immune system. Tanox took an innovative approach in developing an asthma drug that focused on the allergy-related basis of asthma, Xolair. In June 2003, the U.S. Food and Drug Administration (FDA) approved Xolair, the first biotech product cleared for treating those with asthma related to allergies. Tanox was also active in the development of TNX-355, an antibody for the treatment of HIV/AIDS. In 2007, Tanox was sold to Genentech for $919 million. Dr. Chang grew Tanox from an idea to a substantial publicly traded company, doing innovative science. Following her success with Tanox, she has become an angel investor in health-care entrepreneurships and performs philanthropic work in community health-education projects.

Tse Wen Chang is an immunology researcher, whose career spans across academia and industry. His early research involving the Immunoglobulin E (IgE) pathway and antibody-based therapeutics lead to the development of omalizumab, a medication that has been approved for the treatment of severe allergic asthma and severe chronic spontaneous urticaria. Chang is a cofounder of Tanox, a biopharmaceutical company specialized in anti-IgE therapies for the treatment of allergic diseases. After Tanox's tripartite partnership with Genentech and Novartis was forged in 1996, Chang returned to his alma mater, the National Tsing Hua University in Taiwan and served as the Dean (1996–1999) of the College of Life Sciences. Chang was appointed by the Taiwanese government as President of the Development Center for Biotechnology (DCB) in 2000, and served as a Science and Technology Advisor of the Executive Yuan from 2002 to 2006. From 2006 to 2016, he was tenured as Distinguished Research Fellow at the Genomics Research Center, Academia Sinica. He founded Immunwork, Inc. in 2014.

Lirentelimab is a humanized nonfucosylated monoclonal antibody that targets sialic acid-binding Ig-like lectin 8 (SIGLEC8). In a randomized clinical trial, lirentelimab was found to improve eosinophil counts and symptoms in individuals with eosinophilic gastritis and duodenitis. Adverse reactions include infusion reactions, which are mild to moderate and typically occur following the first infusion.

References

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