CDX-2101

Hepatitis B Therapeutic Vaccine Program

We have an IND-ready clinical program for the therapeutic treatment of Hepatitis B infection, a novel advance in the treatment of this difficult infectious disease. Hepatitis B virus (HBV) is one of the world's most prevalent causes of disease and death (World Health Organization). About one third of the world’s population has serological evidence of past or present infection, with over 350 million people who are chronic carriers of the virus. Many of these long-term carriers will suffer from chronic hepatitis, cirrhosis and/or liver cancer; about 65 million of them will die from hepatitis B-related conditions. Each year, over 1 million people die due to the consequences of chronic HBV infection, the majority from cirrhosis and primary hepatocellular carcinoma.

In the US alone, approximately 300,000 people are infected with HBV annually, with 1.25 million Americans living with chronic hepatitis B infection. In Europe, a similar prevalence of 1.2 million chronically infected people has been estimated. In Japan, the prevalent chronic hepatitis B population is approximately 1 million. Prophylactic Hepatitis B vaccines have been on the market since 1981 and their use has resulted in a 60% decline in the number of new Hepatitis B infections in the US between 1985 and 1997.

However, hepatitis B infection continues to be a significant problem in Asia, where the incidence of infection exceeds 300 million people. To date there is no therapeutic HBV immunotherapy, and the treatments available are only maintenance therapies without the hope of long-term protection or cure. In addition, such nucleoside analog treatments Epivir (lamivudine), Hepsera (adefovir dipivoxil) and Baraclude (entecavir) have serious side-effect profiles that make the treatment regimen very difficult to tolerate.

Currently, there are prophylactic hepatitis B vaccines on the market (e.g. Engerix-B/GSK). These vaccines are composed of hepatitis B surface antigen, and although successful as a prophylactic vaccine, Engerix-B has been shown to be ineffective in a therapeutic setting. This is because although the hepatitis B surface antigen induces strong antibody responses, which can block viral infection, it induces ineffective cellular immune responses. By contrast, CDX-2101 is composed of hepatitis B core antigen (HBcAg) which is expressed by infected hepatocytes, and thus serves as a key target for efficacious cell-mediated responses against hepatitis B.

CDX-2101 is a viral-like particle (VLP) comprising 240 modified HBcAg protein subunits, which have been engineered to improve stability, remove the DNA-binding C-terminus, and to inactivate a dominant epitope recognized by HBcAg-specific antibodies from infected individuals. Celldex has completed a full pre-clinical research program that demonstrates the effectiveness of our CDX-2101 vaccine in animal models, and has developed a clinical development plan to take this program into human patients. We have manufactured >200 GMP doses of our vaccine / adjuvant product, and are currently exploring corporate partnerships to initiate clinical trials on CDX-2101 in Asia to validate our rationale. We see this as a tremendous scientific breakthrough, and expect that the success of such a product as a therapeutic could potentially bring tremendous benefit to millions of patients.