Sci-B-Vac™ is SciGen's lead product. It is one of the most potent hepatitis B vaccines in the world. Hepatitis B The hepatitis B virus (HBV) is the major cause of liver disease worldwide. The World Health Organization estimates that 2 billion people (one-third of the world's population) have been infected by HBV. Of these, approximately 400 million people have chronic infections that put them at high risk of ultimately developing cirrhosis and cancer of the liver and the death of liver tissue. In the Asia Pacific region alone, the WHO estimates that 250 million people have chronic HBV infections. Specific treatments for viral hepatitis exist, but prevention of disease by vaccination is the only effective medical measure for controlling the spread of the disease and decreasing illness and death due to hepatitis. As 80% of primary liver cancers are known to be caused by HBV infection, the Centers for Disease Control and Prevention in the USA has designated the hepatitis B vaccine as the first anti-cancer vaccine.

Vaccines in general
Two types of recombinant hepatitis B vaccines are currently available:

• A yeast-derived vaccine, made by inserting into yeast cells DNA that codes for only the small surface protein of HBV (one of three surface proteins).
• Sci-B-Vac™, a mammalian cell vaccine made by inserting into Chinese hamster ovary (CHO) cells DNA coding for the three surface proteins of HBV.

Sci-B-Vac™
Sci-B-Vac™ is a third generation recombinant hepatitis B vaccine produced by Chinese hamster ovary cells in the laboratory. Sci-B-Vac™ contains immunogenic regions of the three surface proteins of HBV.

Results to date show that the two additional protein segments in Sci-B-Vac ™ appear to:

• increase the production of antibodies to combat HBV
• increase the production of a type of antibody that promotes the clearance of HBV and prevents the HBV from binding to liver cells
• stimulate the cellular response of the immune system
• overcome the lack of genetic response to small surface antigen alone

Sci-B-Vac™ has been tested thoroughly for safety and efficacy in over 3,500 individuals.

Clinical efficacy of Sci-B-Vac™

• Sci-B-Vac™ has a faster onset of action (earlier seroconversion and seroprotection after the first and second doses).
• Sci-B-Vac™ achieved protection in 98% of vaccinated people following three injections at the recommended dose of 10 mcg in adults.
• People vaccinated with Sci-B-Vac™ recorded higher levels of anti-HBV antibodies compared with subjects given yeast derived vaccines.
• Sci-B-Vac™ is highly immunogenic and effective at low doses.
• Sci-B-Vac™ (20 mcg) has been shown to offer protection to non-responders to conventional yeast derived vaccines.
• Sci-B-Vac™ has been shown to be safe and effective in over 3500 subjects (Asians and Caucasians).

Higher levels of HBV antibodies are induced with Sci-B-Vac™ compared with conventional vaccines. Sci-B-Vac™ has enhanced immunogenicity because it incorporates regions of all three HBV surface proteins compared to one in the yeast-derived vaccines currently available.

Sci-B-Vac™ in special groups
The enhanced immune response to Sci-B-Vac™ may confer additional advantage in the following groups:

• immunosuppressed and dialysis patients;
• patients who are non-responsive to yeast vaccines because of genetic makeup or age.

It has been reported that patients who received vaccines against only the small surface protein have mutations of HBV that differ slightly in this protein and so escape the immune system. The presence of components from the three HBV surface proteins in Sci-B-Vac™ is likely to eliminate or reduce the generation of these vaccine-escaping HBV mutants.

“Sci-B-Vac™, is indeed a unique hepatitis B vaccine which has repeatedly been shown to be highly immunogenic and safe in neonates, babies and adults alike. While conventional yeast derived vaccines contain only one of the three hepatitis B virus envelope proteins, Sci-B-Vac™ contains two additional proteins - namely pre-S1and pre-S2 which significantly enhance the immune response against potential encounter with the virus. This enhanced immunogenicity is manifested by a very rapid generation of high titer, neutralizing antibodies against the hepatitis B virus which appear in the majority of vaccinees already after the first (out of three) injections. Further more, in comparison with conventional yeast derived vaccines, Sci-B-Vac™ has been shown to be more immunogenic in special risk groups such as vaccinees with overweight, immune suppressed individuals ie patients receiving hemodialysis , healthcare workers as well as nonresponders to conventional hepatitis B vaccines. These features make Sci-B-Vac™ one of the most potent hepatitis B vaccines in the world.”
Daniel Shouval MD, Dean of the Medical School at Hebrew University; Professor of Medicine, Faculty of Medicine Hadassah University Hospital and Head of the Liver Disease Group at Hadassah Hospital.

The world market for Hepatitis B Vaccines
Worldwide sales of hepatitis B vaccines are estimated to be US$1.2 billion. Significant growth in this market is expected with rising awareness of the disease and increased public health expenditure to prevent and fight its spread. In Asia, Africa and Eastern Europe , vaccination is managed largely through the public health systems. In more developed economies, such as Japan , the US and Western Europe , private-sector growth is driving this market. The trend to immunize against hepatitis B is increasing with changes in travel patterns.

Investigating the therapeutic potential of Sci-B-Vac™
SciGen is one of few companies investigating the potential of highly immunogenic vaccines such as Sci-B-Vac™ for therapeutic treatment of hepatitis B. In December 2004, SciGen announced the signing of a collaborative agreement with Intercell AG for the development of a new therapeutic HBV vaccine.

A therapeutic HBV vaccine that provides a cure for HBV would significantly reduce the burden of the disease and meet a high medical demand in an attractive market. Currently there is no therapeutic vaccine against hepatitis B. Pre-clinical studies on our therapeutic vaccine are ongoing and clinical trials are expected.

The proposed therapeutic vaccine combines Sci-B-Vac™ with Intercell's novel synthetic immunizer, IC 31™, as an adjuvant that induces the type of immune response needed to overcome the infection. If the new concept can be proven in animals and then human studies, Sci-B-Vac™ may be the first therapeutic vaccine to take a significant share of the Hepatitis B treatment market.

Worldwide rights and SciGen Manufacturing Facility
In February 2005, SciGen entered the European market as a consequence of acquiring worldwide rights to Sci-B-Vac™. SciGen entered into an agreement with Berna Biotech AG to be exclusive distributor for Sci-B-Vac™ in Western Europe.

In order to meet rising demands, SciGen has established a manufacturing facility in Israel with a capacity of 12 million doses and has a contract manufacturing facility through Shreya Biotech in India with a capacity of 15 million doses. Both facilities will be Good Manufacturing Practice (GMP) compliant and will meet all requirements of the European Medicines Evaluation Agency (EMEA) and other regulatory agencies, such as the Therapeutic Goods Administration in Australia and the US Food and Drugs Administration.