Unprecedented Viral Protection

At Chimerix, we’re on a mission to discover and develop much-needed medicines that protect immunocompromised patients from potentially devastating viral infections. For people with weakened immune systems and patients undergoing bone marrow transplants, common viruses can quickly become life-threatening.

More than 81,000 stem cell transplants (also called bone marrow or hematopoietic cell transplants) are performed each year worldwide, 38,100 in the European Union and 22,500 in the United States.1 Frequently, stem cell transplants are performed to treat patients with certain cancers of the blood and bone marrow, or to address genetic diseases. Due to chemotherapy and the immune suppression associated with stem cell transplants, patients are highly susceptible to viral, bacterial and fungal infections. A recent study showed that nearly two thirds of allogeneic stem cell transplant recipients experienced two or more viral infections, and that infection with multiple viruses increased the risk for overall mortality.2 As demonstrated in this study, viral infections are a significant cause of disease, including extended or repeat hospitalizations, and mortality in the months following the transplant. Too often, the high risk of infection in the first year after transplant results in patients and their families deciding against having a potentially curative transplant.

Our goal is to develop safe and effective therapies to treat and protect these patients from the dangers of life-threatening infections so they can remain on the path to recovery.

Adenovirus causes upper respiratory and gastrointestinal infections in individuals with a functional immune system. However, in people with a weakened immune system, such as patients who have undergone a transplant, adenovirus can lead to life-threatening infections, including pneumonia and hepatitis. Disseminated untreated adenovirus disease can be associated with a mortality rate of 50 to 80 percent in patients who are undergoing stem cell transplant. Currently, no therapies are approved for the treatment of adenovirus.4
CMV is a member of the herpesvirus family and remains a significant cause of viral infections in transplant recipients. A majority of adults have evidence of a prior infection with CMV, which establishes a dormant or latent infection that cannot be cleared; most individuals have an immune system that is able to prevent CMV from reactivating and causing disease.9 In individuals with weakened immune systems—such as transplant recipients—CMV commonly reactivates during the first weeks following the transplant. This can lead to infection of the lungs or other organ systems and can increase the risk of other viral, bacterial and fungal infections.
The majority of adults have been infected with BK virus, which can reactivate and cause severe complications in stem cell transplant and solid organ transplant recipients, and other immunocompromised individuals. After a kidney transplant, BK virus can lead to the loss of the transplanted kidney.6 In patients who have received a stem cell transplant, BK virus can cause significant infections of the bladder and kidney.
Smallpox is estimated to have killed more than one billion people worldwide prior to its eradication, declared by the World Health Organization in 1980 following a global vaccination campaign. Smallpox stocks remain for research purposes in the U.S. and Russia; however, undeclared stocks are suspected to exist. Routine smallpox vaccination programs were discontinued after the global eradication, and with no antiviral agent approved for the treatment of smallpox, the U.S. population may be susceptible to a bioterror attack. Chimerix is working with the Biomedical Advanced Research and Development Authority (BARDA) to develop a medical countermeasure to treat potential smallpox outbreaks in the event of bioterror attacks or accidental release.10

Brincidofovir (CMX001) was originally selected for development based on its activity against poxviruses in vitro and in animal models. In 2003, Chimerix began a partnership with the U.S. National Institute of Asthma and Infectious Diseases (NIAID) to complete the initial work needed to begin human testing. By 2011, the collaboration with NIAID had completed the early development work and a new partnership with the U.S. Biomedical Advanced Research and Development Authority (BARDA) began, with the goal of developing brincidofovir as a medical countermeasure against smallpox.
Norovirus is a common viral infection that causes up to 685 million cases and approximately 200,000 deaths annually worldwide, according to the U.S. Centers for Disease Control and Prevention (CDC).11,12,13 Norovirus results in $4.2 billion in direct healthcare costs and $60.3 billion in societal costs per year globally, with two thirds of these costs resulting from infection in children under five years of age.14 Norovirus is the most cited reason for seeking emergency hospital treatment among adults with acute gastroenteritis.8 Gastroenteritis is characterized by inflammation of the stomach and large intestine, and subsequently results in cramping, nausea, vomiting and diarrhea in those infected. More than 60 percent of norovirus outbreaks in the United States occur in healthcare facilities.15 For most people, norovirus illness lasts less than three days. However, in immunocompromised people, norovirus infection can become chronic and persist for weeks to years; in these patients, it can lead to severe dehydration, hospitalization and even death.8 Among stem cell transplant and solid organ transplant recipients, approximately 15 to 20 percent are diagnosed with norovirus within the first year after transplant.16 Currently there are no therapies approved for the prevention or treatment of norovirus

Technology that Inspires Drug Development

We believe it is possible to treat or prevent life-threatening viral infections caused by adenovirus, CMV and BK virus in vulnerable stem cell transplant recipients. Our proprietary lipid conjugate technology has led us to two product candidates currently showing great potential: brincidofovir (CMX001) and CMX157, which was licensed to ContraVir Pharmaceuticals. Brincidofovir, a clinical-stage lipid conjugate nucleotide analog, has demonstrated broad-spectrum antiviral activity against the most important dsDNA viruses that affect humans, including adenovirus, the virus that causes smallpox (Variola) and cytomegalovirus.

Chimerix also conducts targeted screening of its Chemical Library for other compounds active against viruses with unmet medical need. Recent success in screening and preclinical development has resulted in a clinical candidate for prevention and treatment of norovirus.

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