Product Pipeline
Cancer

Corixa is engaged in antigen discovery and product development for many of the world's most widespread forms of cancer, including lymphoma; melanoma; breast, prostate, lung, colon and ovarian carcinoma; and leukemia. According to the American Cancer Society (ACS), new cases for these six diseases in 2000 numbered more than 3.2 million worldwide. Most cancer patients undergo chemotherapy, radiation therapy and surgery, yet the vast majority will likely relapse with malignant disease within 10 years following such therapies. Corixa believes that its vaccines may help many of these patients.

Corixa has identified many gene sequences that may be either uniquely expressed or markedly over-expressed in solid tumors. Patent applications have been filed on several of these tumor gene sequences. The company continues to analyze the immunological characteristics of these and other gene sequences, with the goal of selecting several antigens for use in vaccines for breast, ovarian, colon and prostate cancer.

Building on its progress in cancer antigen discovery, Corixa has initiated other discovery programs focused on additional tumor types, including lung cancer and leukemia. According to the ACS, in the United States alone, 164,100 new lung cancer cases were diagnosed in 2000. An estimated 156,900 patients died in 2000 from this disease. The ACS estimates 30,800 new cases and 21,700 deaths that were caused by leukemia in the U.S. in 2000. Because of the magnitude and severity of these diseases and the lack of effective therapies, Corixa has targeted antigen discovery and vaccine development efforts for lung cancer and leukemia using approaches similar to those we use in other cancers. Our lung cancer antigen discovery program is the subject of a May 1999 collaboration agreement with Zambon Group and a June 1999 collaboration agreement with the pharmaceutical division of Japan Tobacco. In addition to internal discovery efforts for leukemia, the company has in-licensed a novel and patented gene from the Massachusetts Institute of Technology for potential development in a leukemia vaccine. The gene, known as WT-1, is expressed in a significant percentage of most leukemias and may, therefore, be useful as a vaccine antigen.

Recently, several so-called tumor suppressor genes have been discovered. The expression of such genes in tumor cells leads to elimination of the malignant phenotype and a return of the tumor cell to a state resembling normal, under the control of cellular processes that keep the cell from entering a state of rapid division or malignancy. Corixa obtained rights to a particular tumor suppressor gene, called MDA-7, following the company’s acquisition of GenQuest in 1998. Expression of MDA-7 in tumor cells stops tumor cell growth both in both test tube and animal experiments. In 1999, Corixa licensed the MDA-7 gene to Introgen Therapeutics for use in gene therapy applications for the treatment of cancer. Introgen Therapeutics commenced a Phase I clinical trial of MDA-7 in November 2000.


Infectious Disease

Chlamydia trachomitis, or C. trachomitis, causes the most common sexually transmitted disease in the United States While the disease can be transmitted during sexual contact with an infected partner, it often is not diagnosed and treated until well after complications develop. Studies show that as many as 85% of women and 40% of men with chlamydial infections have no symptoms whatsoever. The Centers for Disease Control (CDC) estimates that over 4 million new cases arise each year in the U.S. The highest rates of chlamydial infections are among 15 to 19 year olds, regardless of demographics or geographic location. Complications from the disease include Pelvic Inflammatory Disease, a serious cause of infertility among women of childbearing age. Further, a woman may pass the infection to her newborn during delivery, causing subsequent neonatal eye infection or pneumonia. The World Health Organization estimates that worldwide, approximately 89 million C. trachomitis infections occurred in 1997 alone. Corixa is currently engaged in the identification of C. trachomitis antigens for use in a preventative vaccine for this pathogen. This program is one of the three infectious disease programs covered under a collaboration and license agreement with GlaxoSmithKline.

Chlamydia pneumoniae, or C. pneumoniae, is a major cause of pneumonia, bronchitis and sinusitis. C. pneumoniae is a human pathogen transmitted by the respiratory route. Retrospective studies made using serum bank investigations indicate that C. pneumoniae infection is as prevalent today as it was in 1963. According to the CDC, more than half of U.S. adults, and people from countries worldwide, have antibodies specific to C. pneumoniae. This indicates widespread prior infection. The incidence of pneumonia in the U.S. is about 1 in 80 persons each year, and virtually everyone is infected at some point in life, with reinfection common. Importantly, the CDC reports that one effect of C. pneumonaie infection is atherosclerosis. Seroepidemiological studies have associated C. pneumoniae infection with the related conditions of coronary artery disease, myocardial infarction and cerebrovascular disease. The association of C. pneumoniae with atherosclerosis has been corroborated by the presence of the organism in atherosclerotic lesions throughout the arterial tree, and the near absence of the organism in healthy arterial tissue. Corixa is currently engaged in the discovery of C. pneumoniae antigens for use in a preventative or therapeutic vaccine for this pathogen. This program is one of the three infectious disease programs covered under a collaboration and license agreement with GlaxoSmithKline.

Mycobacterium tuberculosis, or Mtb, infection is among the world's leading causes of death. According to the National Institute of Allergy and Infectious Diseases (NIAID), an estimated 2.0 billion people are infected with Mtb, including approximately 15 million people in the United States. Any of these people may develop active tuberculosis during some stage of their lives. NIAID estimates that each year, approximately 8 million people worldwide contract active tuberculosis and 3 million people die annually from the disease. NIAID predicts that between 2000 and 2020 nearly 1 billion people will be newly infected with tuberculosis, 200 million people will get sick and 35 million will die. In addition, the World Health Organization estimates that more than 50 million people worldwide may be infected with drug- resistant strains of Mtb.

Corixa's goal is to develop specific vaccines for both conventional and drug-resistant strains of Mtb. We have identified vaccine antigens that specifically trigger appropriate helper T cell responses in vitro and that protect animals, including monkeys, from fatal tb infections. These Mtb antigens and the genes encoding them are the subject of several of our patent applications covering composition of matter and vaccine and diagnostic methods of use. We have recently selected a vaccine candidate for Phase I clinical trials targeted for initiation in 2002.

Corixa is also engaged in antigen discovery and vaccine development for infections stemming from Herpes Virus (Type 1 and Type 2) and Candida. Systemic and vaginal Candida infections are a recurring and serious problem for many people on a worldwide basis. We are collaborating with LigoCyte Pharmaceuticals to develop both a novel therapeutic antibody for use in hospital-based systemic infections, and a vaccine that might reduce the incidence of vaginal candidiasis in women who recurrently suffer from this infection. Corixa’s antigen discovery technology may be useful in identifying antigens for use in vaccines that may either prevent or treat the widespread diseases caused by Herpes Virus and Candida, which afflict over 100 million people worldwide. Efforts in Herpes Virus and Candida are currently in preclinical research.


Other Indications

Ischemia-reperfusion injury is damage that can occur in tissue during the oxygen deprivation of interrupted blood flow, or ischemia, and when blood flow is restored after, for example, a heart attack or a planned event such as cardiovascular surgery, angioplasty or organ transplantation. Paradoxically, restoring blood flow to ischemic tissue may induce a complex series of events leading to both reversible and irreversible tissue damage. It is believed that a significant factor in reperfusion injury is the generation of free radical molecules, that attack and damage tissue. This injury can cause several complications, including tissue death, depression of heart function, irregular heart beat and in some cases, death.

Corixa’s synthetic chemistry program has generated a novel cardioprotectant, RC-552™, which has shown in preclinical studies to be fast acting and potent. Potential clinical applications for RC-552 cardioprotectant may include coronary artery bypass graft surgery, aortic valve replacement, angioplasty, non-cardiac surgery in high-risk patients, unstable angina, acute myocardial infarction thrombolytic therapy and organ transplantation. In January 2001, Corixa entered into an agreement with CoPharma to develop and commercialize its cardioprotectant, RC-552. Under the terms of the agreement, CoPharma will develop and commercialize RC-552 for the treatment and prevention of cardiac disorders, neuronal damage and ischemia-reperfusion injuries.

Acne begins with the creation of an anaerobic environment in sebum-clogged skin pores. This environment fosters the growth of Propionibacterium (P. acnes). The release of viable P. acnes from ruptured micromedones fosters exposure to components of the organism that lead to inflammation.

Corixa has been working on a research and development program aimed at development of novel therapeutic and prophylactic treatments for acne. One of the primary goals for the program is the commercialization of an acne vaccine that could be used to either treat or prevent afflicted patients. Corixa commissioned the sequencing of the entire P.acnes genome, a task that is now complete. P. acnes is the major pathogen involved in the development of acne. We have used the resultant proprietary database together with proven Corixa techniques for antigen discovery to characterize over 30 P. acnes proteins that are capable of engendering immune responses. We will continue with this antigen discovery effort to define the constellation of antigens most useful in a vaccine setting. Such antigens, likely formulated with a proprietary Corixa adjuvant, would then be tested in human clinical trials.


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