Cortecs International establishes collaboration with Cambridge University.

LONDON--(BUSINESS WIRE)--July 24, 1996--Cortecs International (NASDAQ:DLVRY / LSE:COR / ASX: CRI) today announced that Cortecs and the University of Cambridge (the "University") will collaborate on the development of a novel system for the production and delivery of microbial antigens which has resulted from research at the University's Department of Pathology.

Under the agreement, the University has licensed exclusively to Cortecs the commercialization rights to the human medical applications of the technology and the two parties have agreed to collaborate on their development.

Cortecs has been working in the field of oral mucosal vaccines research for about ten years and has synergistic technologies and patentable products to which the Cambridge system could be applied. Initially, the collaborative program will address chronic infectious disease targets; however, the technology will also be used to explore the potential for the manufacture of antigens and their delivery for the management of certain autoimmune diseases and for the manufacture and delivery of chemo-therapeutics.

Researchers at the University, partly in collaboration with the University of Ghent, Belgium, have been working with a specially modified bacterium called Lactococcus lactis. Different strains of this bacterium are used for the manufacture of fermented diary products. The Cambridge team has developed techniques which will enable this innocuous organism to manufacture antigens which would not normally be produced by this bacterium. The researchers can also control whether the antigens are located in the body of the organism, on its surface or are secreted from the bacterium itself. A benefit of this lactococcal system is that with some protein antigens, up to 25 percent for the total soluble cell protein becomes the protein of choice.

As these organisms are of optimum size to be taken up into the immune system which lines the gastrointestinal tract, this technology presents a method for both manufacturing antigens for oral vaccination and delivery of the antigen within or on the surface of the Lactococcus. The system also can be used as a discovery vehicle for novel antigens, in particular from Gram-positive organisms.

Dr. Michael Flynn, President of Cortecs stated, "Through collaborations such as this one with Cambridge University, Cortecs has created a growing collaborative network of research centers with synergistic technologies. It may be possible to commercialize these by linking them with Cortecs' oral delivery systems. A number of bacteria have been explored for their potential to be used as manufacturing and delivery vehicles but we believe that Lactococcus lactis has potentially very significant advantages in terms of safety and suitability as a delivery vehicle. We are very pleased to have this new collaboration with Cambridge University which will create a platform for our next generation of products as well as directly contributing to a number of our existing programs."

Dr. Richard Le Page and Dr. Jeremy Wells of the University of Cambridge, Department of Pathology, added, "It is the synergy between Cortecs' expertise in mucosal delivery systems and our technology which we find especially exciting. We are pleased that the collaboration with Cortecs will allow us to accelerate a program of work which has previously received outstanding support for a number of years from the Biotechnology and Biological Research Council ("BBSRC"). This initial backing has enabled us to develop the basic technology to the point at which collaboration with Cortecs will enable us to apply the lactococcal technology to human health care. The European Union (EU) has also been concerned to foster novel industrial applications for lactic acid bacteria."

"Safe Harbor" Statement under the Private Securities Litigation Reform Act of 1995: Some or all of the statements in this release that relate to future plans, expectations, events, performance and the like are forward-looking statements, as defined in the Private Securities Litigation Reform Act of 1995. Actual results or events could differ materially from those described in the forward-looking statements due to a variety of factors, including those set forth in the company's filings with the Securities and Exchange Commission.

Cortecs is a British-based company quoted on the London Stock Exchange, the Australian Stock Exchange and on NASDAQ. The company specializes in the development of new pharmaceutical delivery systems and point-of-care rapaid diagnostics which provide the opportunity to advance the management of serious diseases such as:

- Osteoporosis - Oral Calcitonin - an oral therapy for the prevention of bone breakdown. In Phase II; Osteosal - a rapid doctors' office test in collaboration with Osteometer to detect increased bone breakdown indicating the risk of the disease osteoporosis and also to monitor the adequacy of therapy. In development.

- Helicobacter Pylori - Helisal(TM) - a rapid doctors' office whole blood test for the detection of Helicobacter pylori in the market and a rapid saliva test in development; Oral Therapeutic Vaccine in development to stimulate immunity; Oral Therapeutic in research to improve eradication results.

- Diabetes - Oral Insulin - human tests planned in 1996; Glycosal - a rapid doctors' office test in collaboration with Exocell to assist in the management and identification of diabetics. In development.

- Cystic Fibrosis - Pseudostat - oral therapeutic antigens to treat and prevent lung infection with Pseudomonas aeruginosa. Now entering Phase II trials.

- Influenza - Flustat - an oral vaccine against influenza. Entering human trials in 1996.

- Thrush - Moniliastat - an oral therapeutic vaccine against vaginal thrush. Enters human trials in 1996.

- Diarrhoea - Adept - an oral system to treat diarrhoea without antibiotics. Entering Phase II trials.

- Male Hormone Deficiency - Halo Testosterone - an oral male hormone replacement therapy in development to treat male hypogonadism. Entering human trials in 1996.

Cortecs also markets a range of ethical and OTC medicines and diagnostic products.

NOTE: Press releases and other Cortecs International Limited information are available on the Cortecs International Limited web site: http://www.cortecs.com.

Background Information on Lactococcus Lactis

Lactococcus lactis belongs to a group of bacteria known as the lactic acid bacteria, some of which play a major role in the fermentation and preservation of food products. Related members of this group of bacteria colonize tissue surfaces in the mouth, intestines and vagina. The group at the University of Cambridge, Department of Pathology realized several years ago that, suitably developed, a lactic acid bacterium might offer a harmless means of delivering antigens and biologically active peptides across mucosal surfaces. Recent results have provided support for this approach.

Under a program of research funded by the Biotechnology and Biological Research Council ("BBSRC"), members of the Cambridge group have subsequently greatly extended our basis knowledge of the rules governing gene expression in lactococci and have applied their understanding to the production of molecules of medical significance in lactococci.

Working with laboratory mice, the group has shown that lactococci (which are non-colonizing and non-invasive) can deliver antigen to the immune system when given intra-nasally or orally. In work partly funded by the Wellcome Trust, lactococci expressing a model antigen (a harmless part of the tetanus toxin) have proved able to elicit protective levels of immunity. In collaboration with scientists from the University of Ghent, the group has manipulated the lactococci so that they can co-delivery both an antigen and a biologically active peptide known as a cytokine. Cytokines are small protein molecules which play a vital role in the regulation of immune responses. When these co-expressor strains of lactococci were given orally or intra-nasally to mice, the Cambridge group could detect enhanced immune responses in the mice.

Other bacterial delivery vehicles, which might be used in principle to deliver Cytokines to augment immune responses or for therapeutic purposes, suffer from the disadvantage that the best-known of these bacteria (such as the typhoid or tuberculosis vaccine bacteria) colonize the body for prolonged periods of time. Hence, neither the quantity of cytokine administered nor the timing of its delivery can be controlled.

In addition to the mucosal delivery of antigens and biologically active polypeptides, Lactococcus lactis has recently proved to be an exceptionally useful platform for the study of antigens derived from a number of pathogenic Gram-positive bacteria. Although responsible for a significant proportion of cases of bacterial disease, the study of these bacteria has lagged behind that of their cousins, the Gram-negative bacteria, which have proved to be more susceptible to genetic manipulation.

The genes for some disease-causing or disease-associated molecules from Gram-positive bacteria are unstable in E. coli -- the workhorse organism of microbial geneticists -- and their products often cannot be properly formed. Lactococcus lactis is, however, able to reproduce these molecules faithfully. The Cambridge groups' expertise in lactococcal genetics is, therefore, unlocking novel approaches to the investigation of Gram-positive bacterial virulence factors, and use of the lactococcal system is expected to reveal novel molecular targets for therapy and prevention of microbial disease.

The innocuity of the lactococci also makes them suitable for the oral delivery of molecules which have been shown in studies in various laboratories to possess the capacity of down-regulating established immune responses. Although the feasibility of achieving immuno-modulation by administering antigens in lactococci remains to be tested, the fact that lactococci are normally ingested as part of the diet implies that these tests will not be complicated by toxicity, and that the production of suitable antigens in lactococci could lead relatively quickly to tests in human volunteers.

CONTACT: Cortecs International

Dr. Michael Flynn, 011-44-181-568-7071

or

Buchanan Communications

Zena Bates, 011-44-171-489-1441

or

Kehoe, White, Savage & Co. Inc.

John P. Kehoe/Van Negris, 212/888-1616