ZyVersa Therapeutics highlights publication of data on inflammasome inhibitors

ZyVersa Therapeutics (ZVSA) highlights data from a peer-reviewed article, The Role of NLRP3 Inflammasome in Type 2 Diabetes Mellitus and Its Macrovascular Complications, recently published in the Journal of Clinical Medicine. The article summarized data from 105 peer-reviewed publications demonstrating that the NLRP3 inflammasome is a central mediator of metabolic inflammation and a key contributor to development and progression of T2DM and its associated macrovascular complications. “Due to its substantial cardiometabolic comorbidities, diabetes is the eighth leading cause of disability and death worldwide. In 2021, global healthcare expenditures for T2DM were over $960B. These statistics stress the critical need for effective drug therapies to attenuate the development and progression of type 2 diabetes and its associated cardiometabolic comorbidities,” said Stephen Glover, ZyVersa’s CEO. “The review article published in the Journal of Clinical Medicine provides a large body of evidence that inflammasomes trigger the inflammation leading to development and progression of type 2 diabetes and associated cardiovascular comorbidities. We are excited about the potential of Inflammasome ASC Inhibitor IC 100 to effectively control the damaging inflammation leading to development and progression of type 2 diabetes and its associated cardiometabolic comorbidities. Unlike the NLRP3 inflammasome inhibitors in development, IC 100 inhibits the adaptor ASC component of multiple types of inflammasomes and their associated ASC specks. Inhibition of multiple inflammasomes is likely important to control inflammation in cardiometabolic conditions since five types of inflammasomes are activated in insulin resistance and three types in various cardiovascular diseases. Additionally, IC 100 uniquely disrupts the structure and function of ASC specks to attenuate spread and perpetuation of inflammation that leads to multi-organ cardiometabolic conditions. In Q4-2025 we are planning to initiate an IND-enabling IC 100 preclinical study in a diet induced obesity model to provide proof-of-concept of its effects on cardiometabolic conditions; results are anticipated in Q1-2026.” Inflammasomes play a central role in the development and progression of T2DM and its cardiovascular complications by linking metabolic stress to chronic inflammation. Inflammasomes are activated by metabolic stressors: hyperglycemia, saturated fatty acids, ceramides, and other endogenous danger signals. Activated inflammasomes initiate the inflammatory cascade through production of proinflammatory cytokines IL-1beta and IL-18. Active caspase-1 cleaves gasdermin D leading to programmed cell death (pyroptosis) and release of cellular contents, including proinflammatory cytokines. This leads to a severe inflammatory response that is perpetuated and spread to surrounding tissues promoting insulin resistance, endothelial dysfunction, and atherosclerotic progression. The authors concluded that targeting inflammasomes may represent a transformative strategy for attenuating the inflammatory burden in T2DM and improving long-term cardiovascular outcomes.