PAP-1 is a preclinical small molecule kv1.3 calcium channel blocker that appears to act only on effector memory T cells.

Allergy drugs firm Circassia acquired worldwide development and commercialization rights to a preclinical-stage topical candidate for the treatment of psoriasis and atopic dermatitis from Airmid. PAP-1 is a small molecule Kv1.3 calcium channel blocker derived from the medicinal plant Ruta graveolens, which the firms claim acts on effector memory T cells but leaves naive and central memory T cells intact. Preclinical studies have also demonstrated the activity of topically applied PAP-1 in psoriasis and atopic dermatitis models.

“PAP-1 is an ideal strategic fit with Circassia’s focus on immune-based therapeutics, and we intend to advance this novel treatment into the clinic as quickly as possible,” comments Rod Hafner, Ph.D., Circassia’s vp for R&D. 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.”

With operations in the U.K. and Canada, Circassia is focused on developing T-cell vaccines based on its ToleroMune® technology for the treatment of allergies. The firm is also broadening its pipeline into other therapeutic areas that hinge on control of the immune system, including organ transplant rejection and autoimmune diseases, with initial work focused on rheumatoid arthritis.  

A number of ToleroMune allergy vaccines are in clinical development. The lead cat allergy candidate is being prepared for Phase III evaluation in Europe. Just last week Circassia reported positive data from a large-scale Canadian Phase II study evaluating the ToleroMune cat allergy treatment. In November 2010 positive data was reported from a Phase II trial with the house dust mite allergy candidate, and the final Phase II study with a ragweed allergy ToleroMune therapy was initiated.  Data from a Phase II grass allergy candidate is expected during 2011. During August 2010 Circassia out-licensed its ToleroTrans organ transplant antirejection technology to Oxford Immunotec.

Based in Redwood City, CA, Airmid is focused on developing potassium ion-channel blockers as potential treatments for autoimmune diseases including multiple sclerosis, psoriasis, diabetes, and rheumatoid arthritis. In addition to PAP-1, Airmid is developing another peptide-based Kv1.3 blocker, ShK-186. Derived from a naturally occurring component of the venom of the sea anemone, Stichodactyla helianthus, ShK-186 is in preclinical development as a potential injectable drug for treatment of multiple sclerosis.

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