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Since our founding, Incyte scientists have focused on exploring the wide-reaching impacts of the
immune system. Our research in this area has led us to
discover and develop new treatments for patients with cancer and certain autoimmune diseases,
including dermatologic conditions.
As we follow the science, important mechanisms, including the JAK-STAT pathway, have been shown to
play a key role in our development of new medicines for immune-mediated diseases.
About JAK, the JAK-STAT Pathway and Its Role in Immune-Mediated Diseases
The JAK-STAT pathway plays an integral role in regulating cytokines and mediating inflammatory
response. However, when the JAK-STAT pathway becomes dysregulated, or overly active, diseases can
occur. Dysregulation of the pathway has been associated with increased growth of blood vessels that
feed cancer, enhanced survival of cancer and suppression of the immune system.
The JAK-STAT pathway is a chain of interactions between proteins in a cell with three key parts:
Janus kinases (JAKs), signal transducer and activator of transcription proteins (STATs) and
receptors (which bind the chemical signals). This pathway takes information from chemical signals
outside the cell into the cell center (or nucleus), which activates genes to ultimately change the
function or activity of the cell.
Cytokines are small proteins that are important in controlling the growth and activity of other
immune and blood cells. When released, cytokines signal the immune system to become activated and
protect the body from foreign pathogens.
For example, overactive JAK pathway signaling is a key driver of a group of rare blood cancers called
myeloproliferative neoplasms (MPNs), as well as other serious conditions affecting the immune system
such as graft-versus-host disease (GVHD), which can occur after an allogeneic stem cell transplant.
GVHD is associated with significant morbidity and mortality and can lead to a variety of skin
conditions and immune disorders.
Understanding the JAK-STAT Pathway
Since 2002, our understanding of inflammation and autoimmunity, including the JAK-STAT pathway, has
led to important scientific discoveries and new treatment approaches in oncology and inflammation and autoimmunity,
Our first approved therapy was a JAK1/JAK2 inhibitor discovered by Incyte scientists. After years of
innovative research and testing, it is now approved globally to treat two types of
MPNs—polycythemia vera and myelofibrosis—and patients with steroid-refractory acute GVHD
or chronic GVHD.
“At Incyte, we always let the science guide us. Over the last 20 years, our understanding of
the key pathways has deepened and our research has expanded. One area of focus has been uncovering
potential applications for JAK inhibition that address significant unmet patient needs beyond our
initial discoveries in oncology,” said Dash Dhanak, Ph.D., Executive Vice President and Chief
Our decades-long experience and exploration of the JAK-STAT pathway also led us to develop a topical
treatment for atopic dermatitis—a chronic, immune-mediated skin disease that is the most
common type of eczema—as well as vitiligo—a chronic autoimmune disease characterized by
depigmentation of skin.
At Incyte, we are committed to finding solutions for some of the most critical unmet medical needs.
Looking ahead, I believe this is just the beginning. The potential to explore
the development of innovative medicines for immune-mediated conditions is exciting, and I am
especially encouraged by our ongoing clinical trials exploring the potential of JAK inhibition to
treat several dermatologic conditions that currently have limited treatment options, including
hidradenitis suppurativa, chronic hand eczema and prurigo nodularis.
Steven Stein, M.D., Chief Medical Officer
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Innovating for Tomorrow
A Day in the Life—Dija Atta