NLRP3 Inhibition
NLRP3 represents a unique opportunity to address a fundamental driver of chronic inflammation while preserving the body’s ability to fight infection.
NLRP3 is activated when the body senses damage, or danger signals such as cholesterol crystals in cardiovascular disease, or misfolded proteins in neurologic disease. When NLRP3 activity becomes chronic, it can cause and accelerate disease.
NLRP3 is an attractive therapeutic target because, when it is inhibited, reductions in the inflammatory activity of IL-1β, IL-18, and IL-6 are observed. This breadth of activity is not possible with antibody therapy against any one component of this pathway. Importantly NRLP3 inhibition does not prevent the activation of other pathways that detect and drive the natural responses to infection.
NLRP3 Inflammasome Activity
Importantly NLRP3 inhibition does not prevent the activation of other pathways that detect and drive the natural responses to infection. To date, we have not observed an increased rate of infections or serious infections among participants treated with ruvonoflast compared with placebo in our completed placebo-controlled clinical trials.
In clinical trials, ruvonoflast has demonstrated reductions in pro-inflammatory molecules downstream of NLRP3, including IL-1β, IL-18, IL-6, fibrinogen, Lp(a), and hsCRP. Separately, canakinumab, which inhibits IL-1β, has demonstrated a similar reduction in these pro-inflammatory molecules, with the exception of IL-18.
From the beginning, we have invented and engineered our potent, oral NLRP3 inhibitors to be active beyond the circulation to reach the tissues where chronic inflammation causes disease – the arterial wall, the heart, skeletal muscles and the brain.
In CANTOS, a large clinical trial of more than ten thousand patients with cardiovascular disease, canakinumab reduced major adverse cardiovascular events such as heart attack and stroke by 15% in all patients, and by 25% in patients achieving meaningful reductions in inflammation (hsCRP < 2 mg/L). Because canakinumab blocks IL-1β, a node responding to infectious stimuli, a higher rate of serious and fatal infections was observed in patients treated with canakinumab in this study.
Our scientific founder, Dr. Watt, has been working on developing therapeutics to inhibit NLRP3 for over two decades. Founded on his insights, Rezera has been a leader in the science of NLRP3 inhibition, developing a deep understanding of this complex biological pathway and the molecular properties required to create differentiated oral inhibitors.