Dalazatide is a synthetic peptide inhibitor of Kv1.3 potassium channels that was originally isolated from the sea anemone Stichodactyla helianthus. Autoreactive T cells in autoimmune diseases are effector memory T (TEM) cells that express high levels of Kv1.3 channels when activated and depend on this channel to function. These T cells are involved in the pathogenesis of the disease. Inhibition of the Kv1.3 channels on these T cells has become an important strategy for the treatment of autoimmune disorders. Kv1.3 is detected in diseased tissue from patients with a variety of autoimmune diseases including psoriasis, psoriatic arthritis, inflammatory bowel disease, multiple sclerosis, and rheumatoid arthritis. We see that in patients with active autoimmune disease they have increased numbers of TEM cells that express proinflammatory molecules that contribute to the disease. This suggests that by blocking the Kv1.3 channel, we should be able to intervene in the inflammatory process and reverse the underlying disease.
The foundation for KPI's technology is built on a clinically validated and immune sparing therapeutic platform. This platform is based upon a new class of patent protected drugs which target the Kv1.3 potassium channel. This channel is required by effector memory T cells (TEM) which, as data suggests, are centrally involved in many autoimmune diseases. KPI is developing potent and specific Kv1.3 blockers (including dalazatide) that deactivate these TEM cells. Dalazatide's mechanism is more targeted and immune sparing than existing therapies because dalazatide does not broadly block the beneficial action of signaling cytokines or other cells (e.g. B cells or central memory T cells) needed for normal immune function.
KPI is focused on initiating proof of concept studies in myositis (including dermatomyositis and inclusion-body myositis) along with cutaneous lupus. In addition, we have interests in exploring other T cell mediated diseases including mycosis fungoides.
Dalazatide is being studied as a potential treatment for multiple autoimmune diseases. KPI has completed three Phase one clinical studies. The drug has been well tolerated and the program is ready to continue through the development process. We have completed a study in patients with psoriasis. In this trial we demonstrated that dalazatide was successful at reducing inflammatory cytokines involved in autoimmune process; this reduction resulted in an improvement in the disease itself (link to poster). In 2017 we plan to conduct proof of concept trials in myositis and cutaneous lupus as well as to continue our research initiatives in other T cell mediated diseases.