Zyversa Therapeutics Inc (ZVSA) News & EventsZVSANews & EventsZyversa Therapeutics Inc

ZyVersa Therapeutics Showcases Release of Data on Inflammasome Inhibitors

ZyVersa Therapeutics 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.

ZyVersa Therapeutics Showcases Lipidomic Findings in Alport Syndrome and Diabetic Kidney Disease

ZyVersa Therapeutics highlights key data from a recently published study, Lipidomics Unveils Critical Lipid Pathway Shifts in Alport Syndrome, designed to elucidate how disrupted lipid metabolism contributes to lipotoxicity and progressive kidney damage in AS. To contextualize the lipidomic alterations observed in AS, a comparator group of patients with diabetic kidney disease was included since lipotoxicity in this population has been extensively characterized and recognized as a central driver of podocyte injury and chronic kidney damage. The researchers found that although both AS and DKD share lipotoxicity as a core mechanism, there were some distinct lipid alterations in AS when compared with DKD reflecting differences in metabolic pathways. AS demonstrated more pronounced changes in the lipid classes evaluated, indicating increased cellular stress. Lipid alterations in both AS and DKD were intricately linked to impaired ABCA1 lipid transport out of kidney cells and the underlying renal injury processes of lipotoxicity, inflammation, and mitochondrial dysfunction. The study concluded that drugs that mediate renal lipid efflux to attenuate lipotoxicity have potential to mitigate renal disease progression. "The relationship between lipotoxicity and kidney damage has been well established in chronic kidney diseases including AS, FSGS, and DKD. The authors of this paper expanded on this by identifying the specific lipid alterations that contribute to the lipotoxicity and kidney damage in in AS in comparison to lipid alterations in DKD," commented Stephen Glover, CEO. "Their data reinforce that impaired efflux of cholesterol and other lipids are key contributors to renal lipotoxicity, and the need for drug therapies, such as Cholesterol Efflux Mediator VAR 200, to restore lipid homeostasis and preserve kidney function. Currently, over 130,000 patients with kidney disease progress to renal failure each year in the US, and more than 800,000 patients are living with renal failure requiring dialysis or transplant to sustain life. We are hopeful that attenuating lipotoxicity with Cholesterol Efflux Mediator VAR 200 can help to reduce these statistics and improve patients' quality of life. We are looking forward to the preliminary results from our Phase 2a VAR 200 clinical trial in patients with DKD around year's end."

ZyVersa Therapeutics highlights data on role of lipotoxicity in DKD

ZyVersa Therapeutics highlights key data on the role of lipotoxicity in the development and progression of DKD from a review article, Targeting lipid metabolic reprogramming to alleviate diabetic kidney disease: molecular insights and therapeutic strategies, recently published in Frontiers in Immunology. This article, which summarized 172 papers, demonstrated that under diabetic conditions, kidney cells undergo significant lipid metabolic abnormalities resulting in accumulation of lipids that trigger inflammation and fibrosis leading to DKD progression. Metabolic issues associated with diabetes, especially insulin resistance and high blood glucose, lead to abnormal lipid metabolism resulting in kidney lipid accumulation, inflammation, and fibrosis. Multiple impaired pathways contribute to lipid accumulation: Insulin resistance increases release of free fatty acids and uptake by kidney cells; Activation of fatty acid synthesis pathways leads to excessive lipid production; Impaired cholesterol efflux resulting from reduced function of cholesterol transporters, ABCA1 and ABCG1, leads to cholesterol and lipid accumulation; Impaired fatty acid oxidation, reduces ability to break down and use stored lipids. Of the above pathways, impaired cholesterol efflux is a key factor in DKD pathology. It exacerbates lipid accumulation, especially in podocytes, the key component of the kidney's filtration system, causing structural damage and impaired filtration resulting in protein leaking into the urine, DKD progression, and ultimately kidney failure, if the lipotoxicity is not addressed. Lipid overload can trigger an inflammasome-induced inflammatory response in kidney cells. Free fatty acids activate inflammasomes initiating an inflammatory cascade via release of IL-1beta. Inflammasome activation also induces upregulation of lipid synthesis-related genes while inhibiting expression of lipid efflux transporters like ABCA1, further increasing lipid accumulation. This creates a vicious cycle, causing continuous decline in renal function and ultimately causes irreversible damage. Currently, no drugs specifically target kidney lipotoxicity.