Hunter-Fleming / EtxB (just parking):
HF 1020 (the non-enterotoxic B-subunit of Escherichia coli heat-labile enterotoxin (EtxB)
Potential Therapeutic Indications:
Allergic conditions such as asthma, hay fever (allergic rhinitis) and atopic dermatitis; auto-immune disorders such as rheumatoid arthritis, Type I diabetes; adjuvant for improved vaccine efficacy
Owner:
University of Bristol
Licensee:
Hunter-Fleming
Patent Situation:
One patent (PCT/GB96/01614) covering use of EtxB and related moieties in the treatment and prevention of auto immune disease, transplant rejection and vaccinations, filed 1995, in national phases in US, EPA, New Zealand, China, Norway, Hungary, Czechoslovakia, Japan, Canada and Korea. Granted in USA, New Zealand and Singapore.
Patent (PCT/GB99/00070) on the use of EtxB and related moieties in the prevention and treatment of allergic disease, filed 1998, in national phases in USA, EPA, UK Japan, Australia, Canada and New Zealand.
Patent (PCT/GB99/00290) covering the use of an EtxB-related moiety (StxB) as an immunomodulator filed 1998, in national phases in EPA, Australia, Canada and New Zealand.
Patent (PCT/GB99/01461): on the use of EtxB and related moieties as a vaccine adjuvant, filed 1998, national phases in USA, EPO, EA, Australia, Canada, New Zealand, Brazil, Japan, India, Yugoslavia, Singapore, Poland, Norway, Mexico, Korea, Hungary, Finland, Czechoslovakia.
Patent (PCT/GB99/02970): covering agents which bind to EtxB co-receptors in the treatment and prevention of auto-immune disease, transplant rejection, vaccination and allergy, filed 1998, in national phase in USA, EPO, EA, Australia, Canada, New Zealand, Brazil, Japan, India, Yugoslavia, Singapore, Poland, Norway, Mexico, Korea, Hungary, Finland, Czechoslovakia.
Pharmacological Properties:
• EtxB down-regulates inflammation by altering T-cell differentiation with concomitant induction of regulatory T-cells that control the inflammatory response.
• EtxB modulates activation of antigen-presenting cells with alterations in cytokine production and antigen presentation.
• EtxB boosts serum IgG1 and the mucosal IgA antibody levels to co-administered antigens.
• EtxB is active by sub-cutaneous injections and when given intra-nasally or orally
• EtxB has an excellent safety profile
Development Status:
Production process (to Good Manufacturing Practice, GMP) underway, Master Cell Bank (MCB) has been laid down and scale up is underway. GMP material expected 2003. Out-licensing of adjuvant use in process.
Mechanism of Action:
In a number of disorders, such as rheumatoid arthritis or Type 1 diabetes, (auto-immune disorders), the immune system behaves inappropriately, leading to attacks on tissues of the body itself. Similarly, exaggerated responses to outside antigens can lead to allergic reactions such as hay fever, asthma or atopic dermatitis.
Hunter-Fleming is working on the use of a bacterial protein, EtxB, that triggers naturally occurring regulatory systems within the immune system that can block damaging immune reactions. This would provide a completely different approach to treating and preventing auto-immune disorders and allergic reactions as well as providing vaccine adjuvant activity (boosting the efficacy of a vaccine).
Efficacy data havebeen generated in mouse models of asthma (the OVA/alum model), type I diabetes (the NOD mouse) and arthritis (collagen-induced arthritis in the DBA/1 mouse). In addition the adjuvant activity of EtxB has been proven for use with antigens from viruses (herpes simplex virus), bacteria (Streptococci) and parasites (malaria).
EtxB induces "regulatory T-cell" activation, by binding to, and cross-linking, cell surface receptors, principally the glycolipid GM1-ganglioside. This receptor interaction modulates cytokine production, activates B-lymphocytes and directly modulates T-lymphocyte function. The result of altering the microenvironment within local lymphoid tissues in this way is to activate regulatory T cells, which then migrate to areas of inflammation where they have suppressive effects.
The core EtxB technology is backed by identification of a peptide with EtxB-like properties This is expected to lead to a development pipeline for the technology... |
