Why We Experience Inflammation
Our immune system evolved primarily to protect us from infections, which were historically a leading cause of illness and death. Today, as people live longer, the immune system can become chronically activated, triggering persistent, low-grade inflammation. Over time, this can contribute to inflammatory and autoimmune diseases, as well as tissue degeneration in the brain and body.
Systemic inflammation can affect many organs and tissues, including the musculoskeletal system, lungs, kidneys, gut, skin and eyes. By blocking the initiation and progression of harmful inflammation, we aim to address both the symptoms and the underlying drivers of diseases that affect many people.
Growing evidence also supports a pivotal role for chronic inflammation in the onset and progression of neurodegenerative diseases such as Parkinson’s and Alzheimer’s. Dysfunction of immune cells in the brain, including microglia and astrocytes, can impair the clearance of harmful proteins, such as amyloid, and may contribute to the destruction of cells essential for healthy brain function.
Target X and complement factor B, or FB, have been identified as key drivers of these inflammatory processes and are implicated in a broad range of diseases. At Sitala, we are discovering and developing potent, potentially best-in-class small molecule Target X antagonists and FB inhibitors designed to stop harmful inflammation before it gets out of control.
The Science of Harmful Inflammation
The immune system uses multiple coordinated mechanisms to fight infection and clear debris from the body. Immune cells communicate through soluble “messenger” molecules that recruit additional immune cells to sites of inflammation. This response is normally short-lived, with natural mechanisms that switch off inflammation and restore tissue balance once the threat has passed.
In chronic autoimmune and inflammatory diseases, these inflammatory signals can become overwhelming and difficult to control, causing tissue damage that may extend beyond the original site of inflammation to organs such as the skin, eyes and lungs.
Sitala’s strategy combines a broad approach to dampen the production of inflammatory messenger molecules with a more targeted approach designed to prevent these molecules from activating immune cells.
Complement
The complement cascade is an essential part of the innate immune system, continuously surveying the body for foreign substances, tissue debris and pathogens that need to be removed. When complement is activated, it marks target surfaces for clearance and generates small messenger proteins, such as C3a and C5a, that recruit immune cells to the affected tissue.
Once a threat is detected, complement activation is rapidly amplified. This produces inflammatory mediators that attract and activate additional immune cells. Activated factor B is a key driver of this amplification process. In some cases, the cascade also forms the membrane attack complex, or MAC, which can puncture cell membranes and cause direct cell death, further fueling inflammation and tissue damage.
Sitala is developing oral small molecule medicines designed to precisely block complement amplification or dampen inflammatory signaling to immune cells. By intervening early in this process, we aim to prevent the long-term consequences of harmful inflammation and slow or stop damage to organs such as the lungs, eyes and skin.
Complement-Driven Autoinflammatory Diseases
Complement-driven diseases are broad and diverse. In some conditions, autoantibodies bind inappropriately to cell surfaces, activating complement and damaging cell membranes. This can disrupt nerve function in certain neuropathies or trigger localized skin inflammation that can progress into severe, painful blistering disease.
Tissue damage can also activate complement, creating a vicious cycle of inflammation and further injury. A small initial trigger can therefore be amplified into a much larger downstream effect. These mechanisms are implicated in lung disease and a range of autoimmune and inflammatory conditions.
In other diseases, inherited genetic traits can over activate complement or impair the body’s ability to control it. This can drive inflammation in organs that are particularly vulnerable to complement dysregulation, including the kidney and eye.
Discover more about our science
Select Publications
Factor B & Complement
Paroxysmal nocturnal hemoglobinuria (PNH)
Immunoglobulin A Nephropathy (IgAN)
Collaborating with Sitala offers the opportunity to be part of cutting-edge science with the potential to transform the lives of patients worldwide. We welcome partnering interest from academia, biotech and pharma, as well as career enquiries from motivated individuals who want to work in a dynamic, fast-moving small-team environment.