Allergic Diseases

Mast cell hyperactivation plays a causal role in many allergic and inflammatory diseases. Many of these diseases have no or very limited treatment alternatives with severe side effects.

With RAFT intervention therapeutics, JADO introduces a new mode-of-action for the treatment of moderate to severe cases of allergic diseases. These compounds are positioned to replace steroids and immunosuppressive agents, such as Cyclosporin® and Tacrolimus®, in topical allergy treatment, and immunosuppressants in systemic treatment of moderate to severe allergy.

The incidence of allergy and asthma is rising dramatically. More than one million Americans suffer from atopic dermatitis or urticaria (hives), forty million from allergic rhinitis (hay fever) and 10 million from asthma. In the US alone, $1 billion is spent on antihistamines and the global asthma/COPD market is approximately $13 billion. Many of the currently available therapies are inadequate and the patients’ quality of life is severely reduced. There is a strong demand for therapies with improved profiles and new modes-of-action to supplement existing therapies or to establish a new line of defense against allergic diseases.

JADO is conducting phase II studies for its first-in-class allergy therapeutic, TF002, for topical treatment of cutaneous mastocytosis and atopic dermatitis. A systemic version of the compound is also being investigated.

RAFT Intervention Targeting Upstream Allergic Events Allergens such as pollen and dust mites bind to specific antibody receptors on the surface of mast cells and other immune cells. These receptors have an affinity for RAFT lipids (shown here in green). The binding of a pollen particle clusters these receptors together causing more RAFT lipids to coalesce until the RAFT is activated. The protein and lipid composition of the RAFT is very specific for the receptor and this is recognized by other proteins, such as kinases, which are subsequently attracted to the RAFT by virtue of their own lipid anchors. The kinase itself becomes activated in the RAFT and carries forward the signaling process initiated by the pollen particle. This signaling event results in the release of immune mediators, such as histamine, from mast-cells. In diseases such as asthma and allergy, there is excess histamine release causing airway hyper-responsiveness or skin inflammation. JADO’s RAFT modulator compounds prevent mediator release by interfering in the first stage of RAFT formation. These inhibitors are designed to specifically target the antibody receptor RAFT, but once incorporated, they prevent the RAFT from becoming active. The kinase no longer recognizes the RAFT with JADO’s modulators in it and hence cannot become activated. The signaling process is thereby interrupted and histamine no longer released.