Inflammation is now understood as a cause, not just a symptom of many disease states.

“Regulated”, intermittent or short-term inflammation is the body’s healthy, natural response to stress and pathogens (e.g., infection, virus, bacteria, cellular and tissue damage).  Its role is to assist in killing pathogens, protect the body against further injury, and facilitate the healing process. In a healthy person, once the immune system has cleared the infection or resolved the injury, the inflammatory response shuts off and normal functioning is returned.
 
“Dysregulated”, chronic inflammation or long-term inflammation is an unhealthy response and the primary contributing factor in a broad spectrum of diseases including arthritis, cardiovascular disease, asthma, and neurodegenerative and other central nervous systems diseases, among others.  It is estimated that approximately 5 to 7 percent of the Western population suffers from one or more chronic inflammatory diseases; many more have a disease condition made worse by chronic low-grade inflammation. 

Despite billions of dollars in R&D spending over the past three decades, there still does not exist a safe and effective treatment for (dysregulated) inflammation-based disease, in part because key aspects of the inflammatory process were not well understood until relatively recently

The Next Class
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Chronic inflammation is driven primarily by the dysregulated, excessive production of a pro-inflammatory protein called: Interleukin 1-beta (“IL-1β”).  Discovered in the 1970s by Olatec’s co-Chief Scientific Officer and Scientific Advisory Board Chair, Dr. Charles Dinarello, IL-1β is the primary pro-inflammatory messenger signal, or “cytokine”, involved in chronic inflammation.  When too much IL-1β is produced, the body’s immune system begins to attack healthy cells, leading to a wide range of inflammation-based diseases. 
 
IL-1β is processed and released from immune cells following the formation of an intracellular structure called an “NLRP3 inflammasome” that exists throughout the body.  The NLRP3 is a cytosolic receptor member of the nucleotide-binding and oligomerization domain NOD-like receptor (NLR) family. This primary inflammasome forms in response to injury or other disturbances detected by the immune system, sending messenger signals (such as IL-1β) to immune cells to tell them to respond. If the disturbances cannot be cleared, such as in the case of amyloid plaques in Alzheimer's, cholesterol crystals in atherosclerosis, uric acid crystals in gouty arthritis, asbestos crystals etc., these molecular machines continue to fire, resulting in progression of disease from the sustained inflammation.

Breakthrough Technology
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The active pharmaceutical ingredient, dapansutrile (also referred to by laboratory code OLT1177®), is a small non-lipophilic molecule that selectively inhibits the NLRP3 inflammasome which in turn prevents the activation of caspase-1 and the maturation of pro‑interleukin‑1b(pro-IL‑1β) and pro-interleukin-18 (pro‑IL‑18) to their active inflammatory forms IL‑1β and IL‑18, respectively.  Demonstrating selectivity for the NLRP3 inflammasome, dapansutrile does not inhibit the synthesis of the IL-1β precursor, nor does it have an effect on the NLRC4 and AIM2 inflammasomes. Additionally, dapansutrile has no direct effects on cyclooxygenase-1 (COX-1) or COX-2 and does not bind to opioid receptor.

Dapansutrile is being developed clinically for acute and chronic non-infectious inflammatory diseases that are known to be responsive to IL-1β neutralization treatment via biologics which includes, acute gouty arthritis flares, inflammation-mediated cardiac dysfunction and Schnitzler’s syndrome.  

The effect of dapansutrile has been evaluated in numerous animal models of inflammation including: arthritis, Cardiovascular Disease, asthma, and neurodegenerative and other Central Nervous Systems diseases, among others.