ZyVersa Publishes Data Supporting IC 100 for Chronic Inflammation Control

Research has shown that extracellular ASC specks play a significant role in the pathogenesis and progression of amyloid A (AA) amyloidosis. This condition is marked by the accumulation of insoluble amyloid fibrils in tissues and organs, impairing their structural and functional integrity. The interaction between extracellular ASC and serum amyloid A (SAA)—a protein produced by the liver during inflammation—forms a scaffold that accelerates the aggregation of SAA into amyloid fibrils, which then deposit in various tissues and organs.

AA amyloidosis manifests across a diverse array of chronic inflammatory conditions, including rheumatoid arthritis, Crohn’s disease, and inflammatory bowel disease. ZyVersa Therapeutics, Inc. is developing a drug named Inflammasome ASC Inhibitor IC 100, which targets both intra- and extracellular ASC specks associated with multiple types of inflammasomes. The goal is to mitigate harmful inflammation, preventing its spread to surrounding tissues.

ZyVersa Therapeutics, a clinical-stage biopharmaceutical company focused on inflammatory and renal diseases, recently released data published in EMBO Molecular Medicine. The findings underscore that extracellular ASC significantly influences the formation and deposition of amyloid A fibrils, which are linked with chronic inflammatory diseases. Stephen C. Glover, Co-Founder, Chairman, CEO, and President of ZyVersa, highlighted the importance of targeting extracellular ASC specks to control inflammation related to a wide range of inflammatory diseases.

The publication, titled "The ASC inflammasome adapter governs SAA-derived protein aggregation in inflammatory amyloidosis," provides insights from both in vitro and in vivo studies on the role of ASC in inflammation-associated amyloidosis. Key findings include:

1. A close colocalization of ASC with SAA in human AA amyloidosis.
2. Acceleration of SAA fibril formation by ASC specks.
3. Reduction of splenic amyloid load in a Pycard knock-out mouse model lacking ASC.
4. Decreased amyloid loads in wild-type mice treated with anti-ASCPYD antibodies.

The study’s authors suggest that these findings could pave the way for therapies aimed at reducing amyloid deposition and pathology in various protein misfolding disorders and chronic inflammatory diseases by targeting ASC.

IC 100, ZyVersa's innovative humanized IgG4 monoclonal antibody, inhibits the inflammasome adaptor protein ASC. It is designed to reduce both the initiation and continuation of the inflammatory response by binding to a specific region of ASC found in multiple types of inflammasomes, such as NLRP1, NLRP2, NLRP3, NLRC4, AIM2, and Pyrin. Intracellularly, IC 100 prevents the formation of inflammasomes by binding to ASC monomers, thereby inhibiting early activation of IL-1β. It also binds to ASC in extracellular ASC specks, further blocking IL-1β activation and reducing the perpetuation of inflammatory responses. By curbing cytokine activation, IC 100 also diminishes the adaptive immune response.

ZyVersa Therapeutics is leveraging advanced technologies to develop groundbreaking drugs for inflammatory and kidney diseases with significant unmet needs. The company is well-positioned in the emerging inflammasome space with its distinctive monoclonal antibody, IC 100, and in kidney disease with its phase 2 Cholesterol Efflux Mediator VAR 200. IC 100 is primarily aimed at treating obesity and its related metabolic issues, while VAR 200 targets focal segmental glomerulosclerosis (FSGS). Each drug offers potential for a range of indications, addressing a market worth over $100 billion.