Why Target Dysregulated Inflammation?
​
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 cancer, atherosclerosis, heart failure, type 2 diabetes, Alzheimer’s disease, arthritis, 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.  (Note: dapansutrile targets the root cause of chronic or dysregulated 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
​
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-1βis 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.  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
​
Dapansutrile inhibits the NLRP3 inflammasome and in turn prevents the activation and secretion of IL-1β.  In other words, dapansutrile is the ‘off-switch’ to inflammation, along with the chronic diseases that accompany it. 
​
A potent and selective anti-inflammatory, OLT1177™ dapansutrile, in addition to certain of the Company’s platform drug candidates, is a modulator of interleukin (IL)-1 in the innate immunity pathway, via inhibition of the NLRP3 inflammasome.  Dapansutrile’s novel mechanism of action inhibits the maturation of pro-IL-1β and pro-IL-18. 
 
In all clinical trials to date, the pharmacology of dapansutrile has translated into a remarkably clean safety profile and has shown early clinical benefit in its Phase 2 trials, allowing the targeting of a wide breadth of inflammatory and other diseases mediated by excessive caspase-1 activation and overproduction of IL-1β.