Circassia

The global allergy market is currently underserved, despite the huge numbers of sufferers. Estimates suggest that allergies affect 25% of the population in the US and Europe, and this figure is growing at 2.5% per annum. Despite this, traditional allergy treatments have a number of drawbacks, either simply providing short-term relief from symptoms, or requiring extended periods of therapy under expert supervision due to potential serious and even life-threatening adverse reactions.

In contrast, clinical experience with Circassia's ToleroMune® T-cell allergy treatments shows that the company's unique technology has the potential to treat sufferers with short, simple and well tolerated courses of treatment. This compares favourably with current immunotherapies, for which patients must often endure several years of carefully supervised treatment.

Circassia’s ToleroMune® T-cell technology identifies short peptide sequences, typically 10 to 20 amino acids long, from the allergen proteins that are responsible for causing allergic reactions in sufferers. These peptides are selected for their ability to bind promiscuously to multiple Major Histocompatibility Class II (MHC Class II) molecules on the surface of antigen presenting cells. Circassia's ToleroMune® technology selects an optimal peptide mixture to ensure broad coverage across the multiple different MHC class II alleles in the population.

Unlike traditional immunotherapies, Circassia’s peptide vaccines are short sequences of amino acids that can be chemically synthesised and readily standardised. Administration of these epitopes induces regulatory T-cells, which down regulate the T cell, B cell and mast cell components of the allergic response to the allergens from which the peptide was originally derived. This leads to the development of tolerance. As the peptides selected by Circassia’s ToleroMune® technology are linear they do not contain B-cell epitopes, which are present in whole allergens and cause the cross-linking of IgE on the surface of mast cells that is associated with itchy eyes, runny nose and, in some cases, asthmatic responses that allergic individuals suffer on exposure to allergens. Cross-linking of IgE can also cause anaphylactic-type reactions. As a result Circassia’s approach offers the potential of effective allergy treatments without the need for dose escalation or the serious adverse reactions associated with traditional immunotherapies.

Circassia's ToleroMune® cat allergy T-cell allergy treatment utilises seven specific epitopes derived from cat dander. The allergy treatment has achieved phase II clinical validation, and clinical studies have identified the optimal dosing regime for Phase III clinical testing. The encouraging data from phase II clinical trials show that the ToleroMune® T-cell allergy treatment can significantly reduce patients’ symptoms while proving extremely well tolerated. As a consequence Circassia is rapidly progressing its cat allergy programme into late-stage development and it entered Phase III development in October 2012. The allergy treatment has also undergone phase II testing in patients with cat allergies and asthma as many sufferers have both conditions.

Ragweed is an important allergen, particularly in the USA, and Circassia has an active programme developing a T-cell allergy treatment to treat those with allergies to this common plant. The Company has licensed a series of patents on the sequence of the major ragweed allergen and has identified a number of T-cell epitopes that form the base of its treatment. Circassia began the first phase II clinical trial with the allergy treatment in April 2009, reported positive results in February 2010, and is currently conducting a further large-scale study of the T-cell allergy treatment.

House dust mites are responsible for a significant proportion of allergies. Circassia has applied its ToleroMune® technology to the field and identified the optimal mix of epitopes for its T-cell allergy treatment candidate. This allergy treatment has successful completed the initial stage of phase II testing.

While grass is potentially responsible for the largest number of allergies, it is a complicated area to address because of the many different species that can cause reactions in patients. Circassia’s T-cell allergy treatment includes epitopes from the key grasses responsible for allergies. The Company’s ToleroMune® T-cell allergy treatment has completed GMP manufacture, undergone pre-clinical testing and moved into phase II clinical testing in 2010.

Circassia’s unique T-cell allergy treatment technology offers a range of technical advantages that complement the benefits offered to patients. By drawing on well-established synthetic chemistry rather than the techniques for purifying whole allergens used by many immunotherapies, Circassia has been able to establish the scale-up and production processes required to meet modern regulatory standards for pharmaceutical products. As a result, Circassia’s allergy treatments are well placed to advance rapidly through the final stages of development.

Clinical progress

• Impressive efficacy without the complexity and significant safety issues associated with traditional immunotherapies
• Extensive clinical experience gained in hundreds of subjects
• Phase II clinical validation complete
• Formal regulatory pathway established
• Optimal short dosing regimens identified for late-stage development
• Single standardised doses: no need for dose escalation

Technical progress

• Low risk approach: next generation improvement of proven immunotherapies
• Strong intellectual property protection
• Low complexity GMP manufacture established
• Fully-characterised products controlled using established analytical methods

Autoimmune diseases arise when the immune system produces inappropriate responses to specific cells within the body. Many conditions are considered to have an autoimmune component, and Circassia is currently focused on two such diseases: psoriasis and rheumatoid arthritis. These conditions affect large numbers of people, with over 125 million affected by psoriasis and up to 1% of the population suffering from rheumatoid arthritis. There are a range of treatments for these chronic diseases, which can include corticosteroids and biological therapies, but no cure is currently available.

Circassia has initiated a development program to apply its ToleroMune® technology to the treatment of rheumatoid arthritis. The Company is working in collaboration with McMaster University in Canada, and is currently researching a range of T-cell epitopes to identify those with the potential to act as an immunotherapy.

Circassia is developing the novel molecule PAP-1 for the topical treatment of psoriasis. Results from research in atopic dermatitis and psoriasis models show that by specifically targeting effector memory T-cells and leaving other components of the immune system intact, PAP-1 has the potential to offer the efficacy of topical steroids while avoiding their side-effects.