Allergic and Inflammatory Diseases

Mast cell hyperactivation plays a causal role in various allergic and inflammatory diseases. Many of these diseases have no or very limited treatment alternatives, which are often associated with severe side effects.

With membrane intervention therapeutics, JADO introduces a new mode-of-action for the treatment of moderate to severe allergic diseases. These compounds are positioned to challenge steroids and immunosuppressive agents in the treatment of topical and systemic allergic as well as inflammatory diseases.

The incidence of allergy and inflammatory disease is rising dramatically. More than one million Americans suffer from atopic dermatitis or urticaria (hives), forty million from allergic rhinitis (hay fever) and ten million from asthma.

In the US alone, $1 billion is spent on antihistamines each year 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. Thus, there is strong demand for therapies with improved safety profiles and new modes-of-action to supplement existing therapies or to establish a new line of defense.

JADO is conducting phase IIa studies with its first-in-class allergy lead candidate, miltefosine, in therapy of dermal and systemic diseases.

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 in green). The binding of a pollen particle clusters receptors together causing more raft lipids to coalesce until the raft is formed. The protein and lipid composition of the raft is 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 modulators prevent mediator release by interfering with raft formation. In this example, the inhibitor is designed to specifically target the antibody receptor raft, preventing receptor activation. The kinase no longer recognizes the raft containing JADO’s modulators and cannot be activated. The signaling process is thereby interrupted and histamine released blocked.