Chronic Viral Infections

Hepatitis C Virus (HCV) and associated liver injuries is a primary direction for Zylacta. There is a critical and unmet need in a growing population of non-responders to current hepatitis C therapy. Uncontrolled apoptosis and oxidative stress in the liver caused by HCV results in cellular injury, which in turn initiates an inflammatory response. The net result of this development is liver destruction through hepatocyte death, and if left unmanaged, the damagebecomes chronic and progresses to fibrosis. Fibrosis is still a 'silent' process and often diagnosed only through check-ups of liver enzymes or a liver biopsy. Continued fibrosis leads to cirrhosis with outcomes such as end stage liver disease, hepatic failure, or hepatocellular carcinoma. Zylacta's approach to treat HCV is rooted in a different philosophy than that of treatments offered by other pharmaceutical companies. Zylacta's lead compounds, Zl016 and Zl056, act by mobilizing the patient’s immune system to fight HCV and other viral infections, rather than acting directly on the viruses.

Case studies

Chronic Liver Desease (CLV)

The World Health Organization reported approximately 1.4 million deaths due to chronic liver disease (CLD) in 2008. Most importantly, the US CDC now lists CLD as one of the top ten causes of death in the US, where cirrhosis and associated complications cause 25-30,000 deaths per annum. Chronic liver disease arises through a variety of factors, the most common being chronic viral infections, metabolic disorders, and excessive consumption of alcohol. The treatment of liver disease should focus on the modulation of liver apoptosis and reduction of oxidation, as indicated by elevated levels of TNF-α and γ-glutamyl transpeptidase (GGT). However, regulating liver apoptosis is a challenge. Apoptosis of HCV infected hepatocytes needs to be improved with the concurrent inhibition of enhanced apoptosis of normal hepatocytes, as well as eliminating liver inflammation in NAFD/NASH disease. In parallel, high levels of GGT should be reduced as well. Only through such a comprehensive approach can the practical management of chronic liver disease be achieved. Zylacta’s glycopeptide compounds, including the lead glycopeptide ZL016, are ideally suited to specifically target hepatic fibrosis, necrosis, and cirrhosis. ZL016 inhibits both TNF alpha and FAS antigen killing pathways, reduces liver transaminases ALT, AST, and transpeptidase GGT activities, NF-κB expression, inhibits proinflammatory reaction of macrophages.

Managing Oxidative Stress

In a growing number of worldwide epidemiological studies, elevated levels of serum γ-glutamyl transpeptidase (GGT) emerged as a major risk factor of all cause mortality. GGT plays a central role in the homeostasis of the body’s major antioxidant glutathione, and is considered to be a sensitive marker of systemic oxidative stress. Oxidative injury in various tissues is the final and universal stage of the pathogenesis of many chronic degenerative diseases. Several recent studies (UK, Germany, Austria’s ‘Vorarlberg Health Monitoring and Promotion Program, US (Framingham Heart Study)) ,working with a pool of over a million subjects from unselected populations or cohorts with ascertained disease, have shown the role of elevated GGT in the clinical evolution of cardiac and cerebrovascular diseases, independently from the occurrence of hepatic disease, alcohol consumption, and established traditional risk factors in multivariable analyses. Zylacta’s clinical observations showed that its leads ZL016 and ZL056 consistently reduce the level of serum γ-glutamyl transpeptidase in patients. Thus, Zylacta’s novel glyco[D]peptide™ compounds could occupy an important niche in the emerging wellness and preventive care market.

Clinical observations