作者: Elizabeth Hartnett, M ; Yuan, Huijun ; Chou, Tsung-Han ; Porciatti, Vittorio ; Keane, Robert W ; Chen, Shaoyi ; Benny, Merline ; Wu, Shu ; Dalton Dietrich, W ; Duncan, Matthew R ; de Rivero Vaccari, Juan Pablo ; Schmidt, Augusto F ; Young, Karen ; Park, Kevin K

AbstractBackgroundRetinopathy of prematurity (ROP), which often presents with bronchopulmonary dysplasia (BPD), is among the most common morbidities affecting extremely premature infants and is a leading cause of severe vision impairment in children worldwide. Activations of the inflammasome cascade and microglia have been implicated in playing a role in the development of both ROP and BPD. Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) is pivotal in inflammasome assembly. Utilizing mouse models of both oxygen-induced retinopathy (OIR) and BPD, this study was designed to test the hypothesis that hyperoxia induces ASC speck formation, which leads to microglial activation and retinopathy, and that inhibition of ASC speck formation by a humanized monoclonal antibody, IC100, directed against ASC, will ameliorate microglial activation and abnormal retinal vascular formation.MethodsWe first tested ASC speck formation in the retina of ASC-citrine reporter mice expressing ASC fusion protein with a C-terminal citrine (fluorescent GFP isoform) using a BPD model that causes both lung and eye injury by exposing newborn mice to room air (RA) or 85% O2 from postnatal day (P) 1 to P14. The retinas were dissected on P14 and retinal flat mounts were used to detect vascular endothelium with AF-594-conjugated isolectin B4 (IB4) and citrine-tagged ASC specks. To assess the effects of IC100 on an OIR model, newborn ASC citrine reporter mice and wildtype mice (C57BL/6 J) were exposed to RA from P1 to P6, then 75% O2 from P7 to P11, and then to RA from P12 to P18. At P12 mice were randomized to the following groups: RA with placebo PBS (RA-PBS), O2 with PBS (O2-PBS), O2 + IC100 intravitreal injection (O2-IC100-IVT), and O2 + IC100 intraperitoneal injection (O2-IC100-IP). Retinal vascularization was evaluated by flat mount staining with IB4. Microglial activation was detected by immunofluorescence staining for allograft inflammatory factor 1 (AIF-1) and CD206. Retinal structure was analyzed on H&E-stained sections, and function was analyzed by pattern electroretinography (PERG). RNA-sequencing (RNA-seq) of the retinas was performed to determine the transcriptional effects of IC100 treatment in OIR.ResultsASC specks were significantly increased in the retinas by hyperoxia exposure and colocalized with the abnormal vasculature in both BPD and OIR models, and this was associated with increased microglial activation. Treatment with IC100-IVT or IC100-IP significantly reduced vaso-obliteration and intravitreal neovascularization. IC100-IVT treatment also reduced retinal microglial activation, restored retinal structure, and improved retinal function. RNA-seq showed that IC100 treatment corrected the induction of genes associated with angiogenesis, leukocyte migration, and VEGF signaling caused by O2. IC100 also corrected the suppression of genes associated with cell junction assembly, neuron projection, and neuron recognition caused by O2.ConclusionThese data demonstrate the crucial role of ASC in the pathogenesis of OIR and the efficacy of a humanized therapeutic anti-ASC antibody in treating OIR mice. Thus, this anti-ASC antibody may potentially be considered in diseases associated with oxygen stresses and retinopathy, such as ROP.

2024-01-01·Alzheimer's & Dementia: Translational Research & Clinical Interventions

Association of region‐specific hippocampal reduction of neurogranin with inflammasome proteins in post mortem brains of Alzheimer's disease

Article

作者: Zetterberg, Henrik ; Gultekin, Sakir Humayun ; Brzostowicki, Daniel ; Dallmeier, Julian ; Kvartsberg, Hlin ; Rundek, Tatjana ; Blennow, Kaj ; Gober, Ryan ; Keane, Robert W ; de Rivero Vaccari, Juan Pablo ; Davis, David A ; Sun, Xiaoyan ; Vontell, Regina T ; Barreda, Ayled ; Bramlett, Helen M ; Dietrich, W Dalton

AbstractINTRODUCTIONNeurogranin (Ng) is considered a biomarker for synaptic dysfunction in Alzheimer's disease (AD). In contrast, the inflammasome complex has been shown to exacerbate AD pathology.METHODSWe investigated the protein expression, morphological differences of Ng, and correlated Ng to hyperphosphorylated tau in the post mortem brains of 17 AD cases and 17 age‐ and sex‐matched controls. In addition, we correlated the Ng expression with two different epitopes of apoptosis‐associated speck‐like protein containing a caspase recruitment domain (ASC).RESULTSWe show a reduction of Ng immunopositive neurons and morphological differences in AD compared to controls. Ng immunostaining was negatively correlated with neurofibrillary tangles, humanized anti‐ASC (IC100) positive neurons and anti‐ASC positive microglia, in AD.DISCUSSIONThe finding of a negative correlation between Ng and ASC speck protein expression in post mortem brains of AD suggests that the activation of inflammasome/ASC speck pathway may play an important role in synaptic degeneration in AD.Highlights

We show the role that neurogranin plays on post‐synaptic signaling in specific hippocampal regions.

We demonstrate that there could be clinical implications of using neurogranin as a biomarker for dementia.

We describe the loss of plasticity and neuronal scaffolding proteins in the present of AD pathology.

We show the response of neuroinflammation when tau proteins phosphorylate in hippocampal neurons.

We show that there is a potential therapeutic target for the inflammasome, and future studies may show that IC100, a humanized monoclonal antibody directed against ASC, may slow the progression of neurodegeneration.

2023-07-01·Brain Pathology

Identification of inflammasome signaling proteins in neurons and microglia in early and intermediate stages of Alzheimer's disease

Article

作者: Bramlett, Helen M. ; Gultekin, Sakir Humayun ; Keane, Robert W. ; de Rivero Vaccari, Juan Pablo ; Sun, Xiaoyan ; Vontell, Regina T. ; Dietrich, W. Dalton

AbstractAlzheimer's disease (AD) is a progressive neurodegenerative disease that destroys memory and cognitive function. Inflammasome activation has been suggested to play a critical role in the neuroinflammatory response in AD progression, but the cell‐type expression of inflammasome proteins in the brain has not been fully characterized. In this study, we used samples from the hippocampus formation, the subiculum, and the entorhinal cortex brain from 17 donors with low‐level AD pathology and 17 intermediate AD donors to assess the expression of inflammasome proteins. We performed analysis of hippocampal thickness, β‐amyloid plaques, and hyperphosphorylated tau to ascertain the cellular pathological changes that occur between low and intermediate AD pathology. Next, we determined changes in the cells that express the inflammasome sensor proteins NOD‐like receptor proteins (NLRP) 1 and 3, and caspase‐1. In addition, we stained section with IC100, a humanized monoclonal antibody directed against the inflammasome adaptor protein apoptosis‐associated speck‐like protein containing a caspase recruitment domain (ASC), and a commercially available anti‐ASC antibody. Our results indicate that hippocampal cortical thickness did not significantly change between low and intermediate AD pathology, but there was an increase in pTau and β‐amyloid clusters in intermediate AD cases. NLRP3 was identified mainly in microglial populations, whereas NLRP1 was seen in neuronal cytoplasmic regions. There was a significant increase of ASC in neurons labeled by IC100, whereas microglia in the hippocampus and subiculum were labeled with the commercial anti‐ASC antibody. Caspase‐1 was present in the parenchyma in the CA regions where amyloid and pTau were identified. Together, our results indicate increased inflammasome protein expression in the early pathological stages of AD, that IC100 identifies neurons in early stages of AD and that ASC expression correlates with Aβ and pTau in postmortem AD brains.

项与 IC-100 相关的新闻（医药）

2024-11-14

·GlobeNewswire-Health Care

ZyVersa Therapeutics Reports Third Quarter, 2024 Financial Results and Provides Business Update

KEY BUSINESS HIGHLIGHTS Phase 2a clinical trial for Cholesterol Efflux Mediator™ VAR 200 in patients with diabetic kidney disease expected to begin Q1-2025.New Obesity, Metabolic & Inflammatory Disease Scientific Advisory Board (SAB) was formed in October 2024 to support development of Inflammasome ASC Inhibitor IC 100 for obesity with metabolic complications.Two obesity proof-of-concept studies with IC 100 in diet-induced obesity (DIO) mouse models are planned, which will include assessment of various metabolic parameters. At least one of the studies is targeted to begin Q4-2024.IC 100 Investigational New Drug (IND) submission is planned for Q2-2025, and once cleared, will be followed by initiation of a Phase 1 clinical trial in healthy overweight subjects at risk for certain metabolic complications (Q2/Q3-2025), with safety data expected H2-2025.Raised approximately $3.9 million from the beginning of Q3-2024 to present. WESTON, Fla., Nov. 14, 2024 (GLOBE NEWSWIRE) -- ZyVersa Therapeutics, Inc. (Nasdaq: ZVSA, or “ZyVersa”), a clinical-stage specialty biopharmaceutical company developing first-in-class drugs for the treatment of renal and inflammatory diseases with high unmet medical needs, reports financial results for the quarter ended September 30, 2024, and provides business update. “We are pleased to announce the progress that ZyVersa has made toward achieving our key near-term development milestones,” stated Stephen C. Glover, ZyVersa’s Co-founder, Chairman, CEO, and President. “Our Phase 2a clinical trial with Cholesterol Efflux Mediator™ VAR 200 in diabetic kidney disease is expected to begin Q1-2025, with an initial data read-out around mid-year 2025. In preparation for an IND submission for Inflammasome ASC Inhibitor IC 100 and a subsequent Phase 1 trial in healthy overweight subjects at risk for certain metabolic complications, we are initiating two proof-of-concept studies with IC 100 in obesity DIO models. At least one of the studies is expected to begin in Q4-2024. One study will evaluate IC 100 as monotherapy compared to semaglutide, and the other will evaluate IC 100 in combination with semaglutide. Our newly formed Obesity, Metabolic & Inflammatory Disease SAB has been instrumental in designing these two studies to optimize the parameters to be evaluated. We are pleased with the level of scientific evidence from our preclinical program and published third party data that support the potential of IC 100 to control the damaging obesity-driven inflammation and its associated comorbidities. Unlike NLRP3 inhibitors in development for obesity with metabolic complications, IC 100 targets ASC to inhibit multiple inflammasomes, including NLRP3 and AIM2 associated with obesity. More importantly, IC 100 uniquely disrupts the function of ASC specks to attenuate chronic, systemic inflammation leading to obesity comorbidities. We are excited about the promise of our two lead compounds in development to improve health and transform lives. We believe our near-term milestone achievement will be a key inflection point for ZyVersa that will drive shareholder value.” BUSINESS UPDATE CHOLESTEROL EFFLUX MEDIATOR™ VAR 200 FOR RENAL DISEASE Phase 2a clinical trial in diabetic kidney disease planned to begin Q1-2025. All necessary regulatory preparation has been completed by ZyVersa, our CRO, George Clinical, and our two clinical sites who are gearing up for site initiation and patient recruitment in the new year. INFLAMMASOME ASC INHIBITOR IC 100 FOR OBESITY WITH METABOLIC COMPLICATIONS IC 100 IND submission planned for Q2-2025, to be followed by initiation of a Phase 1 clinical trial in healthy overweight patients at risk for certain metabolic complications. Safety data expected before year end 2025. New Obesity, Metabolic & Inflammatory Disease SAB established to provide expert advice on IC 100’s obesity clinical program. SAB comprised of five top tier experts in the areas of obesity and metabolic diseases, and four world-renowned inflammasome experts and inventors of IC 100 from University of Miami Miller School of Medicine who have provided advisory support for IC 100 since its license. Two IC 100 obesity proof-of-concept studies in DIO mouse models designed with expert advice from SAB. One will evaluate IC 100 monotherapy in comparison to semaglutide, and the other will evaluate IC 100 in combination with semaglutide.At least one of the DIO model studies is planned to begin Q4-2024.Data read-outs expected within six months of initiation. IC 100 GLP toxicology studies are anticipated to begin Q4-2024/Q1-2025 THIRD QUARTER FINANCIAL RESULTS Net losses were approximately $2.4 million for the three months ended September 30, 2024, with an improvement of approximately $0.5 million or 17.3% compared to a net loss of approximately $2.9 million for the three months ended September 30, 2023. Based on its current operating plan, ZyVersa expects its cash of approximately $0.1 million as of September 30, 2024, will be sufficient to fund its operating expenses and capital expenditure requirements on a month-to-month basis. ZyVersa will need additional financing to support its continuing operations and to meet its stated milestones. ZyVersa will seek to fund its operations and clinical activity through public or private equity or debt financings or other sources, which may include government grants, collaborations with third parties or outstanding warrant exercises. Research and development expenses were approximately $0.4 million for the three months ended September 30, 2024, a decrease of approximately $0.2 million or 35.3% from the three months ended September 30, 2023. The decrease is primarily attributable to a decrease of approximately $0.2 million in the costs of manufacturing, pre-clinical costs for IC 100, and clinical costs for VAR 200. General and administrative expenses were approximately $1.8 million for the three months ended September 30, 2024, a decrease of approximately $0.4 million or 17.7% from the three months ended September 30, 2023. The decrease is attributable to an approximate $0.1 million decrease in professional fees due to reduced fees of public auditors and legal counsel, an approximate $0.2 million decrease in director and officer insurance due to reduced costs in the second year of being a public company, and an approximate $0.1 million decrease in stock-based compensation as a result of options becoming fully amortized in 2024. About ZyVersa Therapeutics, Inc. ZyVersa (Nasdaq: ZVSA) is a clinical stage specialty biopharmaceutical company leveraging advanced proprietary technologies to develop first-in-class drugs for patients with inflammatory or kidney diseases with high unmet medical needs. We are well positioned in the rapidly emerging inflammasome space with a highly differentiated monoclonal antibody, Inflammasome ASC Inhibitor IC 100, and in kidney disease with phase 2 Cholesterol Efflux Mediator™ VAR 200. The lead indication for IC 100 is obesity and its associated metabolic complications, and for VAR 200, focal segmental glomerulosclerosis (FSGS). Each therapeutic area offers a “pipeline within a product,” with potential for numerous indications. The total accessible market is over $100 billion. For more information, please visit www.zyversa.com. Cautionary Statement Regarding Forward-Looking Statements Certain statements contained in this press release regarding matters that are not historical facts, are forward-looking statements within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended, and the Private Securities Litigation Reform Act of 1995. These include statements regarding management’s intentions, plans, beliefs, expectations, or forecasts for the future, and, therefore, you are cautioned not to place undue reliance on them. No forward-looking statement can be guaranteed, and actual results may differ materially from those projected. ZyVersa uses words such as “anticipates,” “believes,” “plans,” “expects,” “projects,” “future,” “intends,” “may,” “will,” “should,” “could,” “estimates,” “predicts,” “potential,” “continue,” “guidance,” and similar expressions to identify these forward-looking statements that are intended to be covered by the safe-harbor provisions. Such forward-looking statements are based on ZyVersa’s expectations and involve risks and uncertainties; consequently, actual results may differ materially from those expressed or implied in the statements due to a number of factors, including ZyVersa’s plans to develop and commercialize its product candidates, the timing of initiation of ZyVersa’s planned preclinical and clinical trials; the timing of the availability of data from ZyVersa’s preclinical and clinical trials; the timing of any planned investigational new drug application or new drug application; ZyVersa’s plans to research, develop, and commercialize its current and future product candidates; the clinical utility, potential benefits and market acceptance of ZyVersa’s product candidates; ZyVersa’s commercialization, marketing and manufacturing capabilities and strategy; ZyVersa’s ability to protect its intellectual property position; and ZyVersa’s estimates regarding future revenue, expenses, capital requirements and need for additional financing, as well as ZyVersa’s ability to successfully complete any such financing. New factors emerge from time-to-time, and it is not possible for ZyVersa to predict all such factors, nor can ZyVersa assess the impact of each such factor on the business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any forward-looking statements. Forward-looking statements included in this press release are based on information available to ZyVersa as of the date of this press release. ZyVersa disclaims any obligation to update such forward-looking statements to reflect events or circumstances after the date of this press release, except as required by applicable law. This press release does not constitute an offer to sell, or the solicitation of an offer to buy, any securities. Corporate, Media, IR Contact Karen CashmereChief Commercial Officerkcashmere@zyversa.com786-251-9641 ZYVERSA THERAPEUTICS, INC.CONDENSED CONSOLIDATED BALANCE SHEETS September 30, December 31, 2024 2023 (Unaudited) Assets Current Assets: Cash$122,921 $3,137,674 Prepaid expenses and other current assets 267,494 215,459 Total Current Assets 390,415 3,353,133 Equipment, net - 6,933 In-process research and development 18,647,903 18,647,903 Vendor deposit 178,476 98,476 Deferred offering costs 207,130 - Operating lease right-of-use asset - 7,839 Total Assets$19,423,924 $22,114,284 Liabilities and Stockholders' Equity Current Liabilities: Accounts payable$9,284,631 $8,431,583 Accrued expenses and other current liabilities 2,257,372 1,754,533 Operating lease liability - 8,656 Total Current Liabilities 11,542,003 10,194,772 Deferred tax liability 854,621 844,914 Total Liabilities 12,396,624 11,039,686 Stockholders' Equity: Preferred stock, $0.0001 par value, 1,000,000 shares authorized: Series A preferred stock, 8,635 shares designated, 50 shares issued and outstanding as of September 30, 2024 and December 31, 2023, respectively - - Series B preferred stock, 5,062 shares designated, 5,062 shares issued and outstanding as of September 30, 2024 and December 31, 2023 1 1 Common stock, $0.0001 par value, 250,000,000 shares authorized; 1,074,203 and 405,212 shares issued at September 30, 2024 and December 31, 2023, respectively, and 1,074,196 and 402,205 shares outstanding as of September 30, 2024 and December 31, 2023, respectively 107 40 Additional paid-in-capital 118,245,220 114,300,849 Accumulated deficit (111,210,860) (103,219,124) Treasury stock, at cost, 7 shares at September 30, 2024 and December 31, 2023, respectively (7,168) (7,168) Total Stockholders' Equity 7,027,300 11,074,598 Total Liabilities and Stockholders' Equity$19,423,924 $22,114,284 ZYVERSA THERAPEUTICS, INC.CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS(Unaudited) For the Three Months Ended For the Nine Months Ended September 30, September 30, 2024 2023 2024 2023Operating Expenses: Research and development$436,043 $673,943 $1,658,030 $2,950,462 General and administrative 1,833,578 2,228,735 6,192,205 9,694,097 Impairment of in-process research and development - - - 69,280,171 Impairment of goodwill - - - 11,895,033 Total Operating Expenses 2,269,621 2,902,678 7,850,235 93,819,763 Loss From Operations (2,269,621) (2,902,678) (7,850,235) (93,819,763) Other Income (Expense): Interest (income) expense 131,635 210 131,794 (555) Pre-Tax Net Loss (2,401,256) (2,902,888) (7,982,029) (93,819,208) Income tax (provision) benefit - 485 (9,707) 8,859,762 Net Loss (2,401,256) (2,902,403) (7,991,736) (84,959,446) Deemed dividend to preferred stockholders - (32,373) - (7,948,209) Net Loss Attributable to Common Stockholders$(2,401,256) $(2,934,776) $(7,991,736) $(92,907,655) Net Loss Per Share - Basic and Diluted$(2.43) $(30.18) $(9.79) $(1,591.46) Weighted Average Number of Common Shares Outstanding - Basic and Diluted 988,378 97,252 816,293 58,379

临床2期财报临床1期

2024-07-25

·GlobeNewswire-Health Care

ZyVersa Therapeutics Selects Obesity and Related Metabolic Complications as Lead Indication for Inflammasome ASC Inhibitor IC 100

WESTON, Fla., July 25, 2024 (GLOBE NEWSWIRE) -- ZyVersa Therapeutics, Inc. (Nasdaq: ZVSA, or “ZyVersa”), a clinical stage specialty biopharmaceutical company developing first-in-class drugs for treatment of inflammatory and renal diseases, announces that obesity and its related metabolic complications has been selected as the lead indication for Inflammasome ASC Inhibitor IC 100. “Obesity, a well-established risk factor for an array of different metabolic disorders, including insulin resistance, type 2 Diabetes, hypertension, cardiovascular disease, and cancer, has reached pandemic proportions, affecting up to two-thirds of the adult population in developed countries,” stated Stephen C. Glover, ZyVersa’s Co-founder, Chairman, CEO and President. “Published research demonstrating that inflammasome activation in fat tissue triggers cell death and systemic release of proinflammatory IL-1β, and ASC specks, which can perpetuate and spread inflammation leading to metabolic disturbances associated with obesity provides support for Inflammasome ASC Inhibitor IC 100 as a potential therapeutic option. We are excited about progressing our development program in this area of high unmet needs.” Following is the rationale behind selection of obesity and related metabolic complications, and an overview of the development program. Why Obesity and Related Metabolic Complications as an Indication? Large Growing Market: The global obesity drug market reached nearly $24 billion in 2023, more than a sevenfold growth in just three years, and it is forecasted by IQVIA t to reach up to $131 Billion by 2028 (24 – 27% CAGR).Significant Health and Economic Impact: Obesity, which now affects over 40% of Americans (CDC), is associated with multiple chronic medical conditions, including type 2 diabetes, heart disease, and some forms of cancer, at an annual cost and economic impact exceeding 1.4 trillion in the United States including healthcare expenditures, loss of productivity (Milken Institute).Need for Alternative Mechanisms of Action to Complement GLP-1 agonists: While GLIP-1 drugs deliver meaningful weight loss, improve glucose control, and help to mitigate cardiovascular disease, they do not address the chronic tissue inflammation observed in adipose tissue, liver, muscle, and pancreatic islet cells that has emerged as a key feature of obesity. This chronic tissue inflammation, termed, “immunometabolism,” leads to insulin resistance, beta cell dysfunction, and development of type 2 diabetes and long-term inflammatory complications including microvascular disease (retinopathy, nephropathy, and neuropathy), macrovascular disease (stroke, myocardial infarction, and peripheral arterial disease), heart failure, and nonalcoholic fatty liver disease. As such, anti-inflammatory drugs have potential to provide additional benefits in obesity management (Immunity. 2022 Jan 11;55(1):31-55). Rationale for Inflammasome Inhibitors as a Treatment for Obesity and Related Metabolic Complications Inflammasomes, which are activated by nutrients, such as glucose and free fatty acids, trigger activation and stimulation of downstream inflammatory pathways, leading to chronic inflammation in obesity (Front Endocrinol (Lausanne). 2023 Aug 31;14:1232171). Nutrient overload triggers inflammasome-induced inflammation in the brain’s hypothalamus, causing increased appetite and food intake, increasing the number and size of fat cells associated with weight gain and obesity.The fat cells become hypoxic, resulting in cell death and macrophage recruitment. This leads to inflammasome activation, death of inflamed cells, and systemic release of proinflammatory cytokines, such as IL-1β, and ASC specks, spreading inflammation throughout the body. If unresolved, sustained inflammation leads to the metabolic complications of obesity. Why Inflammasome ASC Inhibitor IC 100? Multiple types of inflammasomes, not just NLRP3, are activated in obesity and related metabolic complications (NLRP1, NLRP3, NLRC4, and AIM2). Because IC 100 targets the inflammasome ASC component, it inhibits each of these inflammasomes, including NLRP3, with potential to better attenuate the damaging inflammation associated with obesity and its complications (Immunology. 2021 Aug;163(4):348-362).Inflammation is spread and perpetuated by systemic release of proinflammatory IL-1β and ASC specks during death of inflamed cells, leading to obesity-related complications. IC 100 disrupts the structure and function of ASC specks, thereby attenuating spread and perpetuation of inflammation (Transl Res. 2022 Jul 3:S1931-5244(22)00150-5). ZyVersa believes that inflammasome ASC Inhibitor IC 100 administered concurrently with GLIP-1 agonists will lead to incremental weight loss, and more importantly, attenuate the chronic tissue inflammation not addressed by GLIP-1 agonists to reduce the long-term micro- and macrovascular inflammatory complications. Inflammasome ASC Inhibitor IC 100 Development Plans for Obesity and Related Complications IC 100’s preclinical program is nearing completion, with a planned Investigational New Drug (IND) submission Q4-2024, and Phase 1 clinical trial initiation shortly thereafter.Preclinical scientific collaboration to assess IC 100 as a potential treatment for atherosclerosis, a common obesity-related metabolic complication, is expected to conclude H2-2024.Preclinical scientific collaboration with University of Miami Miller School of Medicine to assess IC 100 as a potential treatment for obesity and metabolic syndrome is expected to begin H2-2024, with a second study looking at concomitant treatment with IC 100 and a GLIP-1 agonist to begin shortly thereafter.ZyVersa has recruited six top-tiered experts in obesity and related metabolic complications for a scientific advisory board to guide clinical development plans for IC 100, which will be announced in the next few weeks. About Inflammasome ASC Inhibitor IC 100 IC 100 is a novel humanized IgG4 monoclonal antibody that inhibits the inflammasome adaptor protein ASC. IC 100 was designed to attenuate both initiation and perpetuation of the inflammatory response. It does so by binding to a specific region of the ASC component of multiple types of inflammasomes, including NLRP1, NLRP2, NLRP3, NLRC4, AIM2, and Pyrin. Intracellularly, IC 100 binds to ASC monomers, inhibiting inflammasome formation, thereby blocking activation of IL-1β early in the inflammatory cascade. IC 100 also binds to ASC in ASC Specks, both intracellularly and extracellularly, further blocking activation of IL-1β and the perpetuation of the inflammatory response that is pathogenic in inflammatory diseases. Because active cytokines amplify adaptive immunity through various mechanisms, IC 100, by attenuating cytokine activation, also attenuates the adaptive immune response. The lead indication for IC 100 is obesity and its associated metabolic complications. To review a white paper summarizing the mechanism of action and preclinical data for IC 100, Click Here. About ZyVersa Therapeutics, Inc. ZyVersa (Nasdaq: ZVSA) is a clinical stage specialty biopharmaceutical company leveraging advanced proprietary technologies to develop first-in-class drugs for patients with inflammatory or kidney diseases with high unmet medical needs. We are well positioned in the rapidly emerging inflammasome space with a highly differentiated monoclonal antibody, Inflammasome ASC Inhibitor IC 100, and in kidney disease with phase 2 Cholesterol Efflux MediatorTM VAR 200. The lead indication for IC 100 is obesity and its associated metabolic complications, and for VAR 200, focal segmental glomerulosclerosis (FSGS). Each therapeutic area offers a “pipeline within a product,” with potential for numerous indications. The total accessible market is over $100 billion. For more information, please visit www.zyversa.com. Cautionary Statement Regarding Forward-Looking Statements Certain statements contained in this press release regarding matters that are not historical facts, are forward-looking statements within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended, and the Private Securities Litigation Reform Act of 1995. These include statements regarding management’s intentions, plans, beliefs, expectations, or forecasts for the future, and, therefore, you are cautioned not to place undue reliance on them. No forward-looking statement can be guaranteed, and actual results may differ materially from those projected. ZyVersa Therapeutics, Inc (“ZyVersa”) uses words such as “anticipates,” “believes,” “plans,” “expects,” “projects,” “future,” “intends,” “may,” “will,” “should,” “could,” “estimates,” “predicts,” “potential,” “continue,” “guidance,” and similar expressions to identify these forward-looking statements that are intended to be covered by the safe-harbor provisions. Such forward-looking statements are based on ZyVersa’s expectations and involve risks and uncertainties; consequently, actual results may differ materially from those expressed or implied in the statements due to a number of factors, including ZyVersa’s plans to develop and commercialize its product candidates, the timing of initiation of ZyVersa’s planned preclinical and clinical trials; the timing of the availability of data from ZyVersa’s preclinical and clinical trials; the timing of any planned investigational new drug application or new drug application; ZyVersa’s plans to research, develop, and commercialize its current and future product candidates; the clinical utility, potential benefits and market acceptance of ZyVersa’s product candidates; ZyVersa’s commercialization, marketing and manufacturing capabilities and strategy; ZyVersa’s ability to protect its intellectual property position; and ZyVersa’s estimates regarding future revenue, expenses, capital requirements and need for additional financing. New factors emerge from time-to-time, and it is not possible for ZyVersa to predict all such factors, nor can ZyVersa assess the impact of each such factor on the business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any forward-looking statements. Forward-looking statements included in this press release are based on information available to ZyVersa as of the date of this press release. ZyVersa disclaims any obligation to update such forward-looking statements to reflect events or circumstances after the date of this press release, except as required by applicable law. This press release does not constitute an offer to sell, or the solicitation of an offer to buy, any securities. Corporate, Media, and IR Contact:Karen CashmereChief Commercial Officerkcashmere@zyversa.com786-251-9641

临床1期临床2期

2024-04-07

·GlobeNewswire-Health Care

ZyVersa Therapeutics Highlights Published Data Demonstrating NLRP3 Inflammasome Inhibition Has Potential to Decrease Atherosclerotic Lesions in Patients with Diabetes

Atherosclerosis (AS) and its sequelae are the most common cause of death in diabetic patients and one of the reasons why diabetes has entered the top 10 causes of death worldwide. The published data show that inhibiting the NLRP3 inflammasome pathway significantly reduces atherosclerotic lesions and improves hyperglycemic-induced plaque instability. ZyVersa is developing IC 100, a monoclonal antibody targeting inflammasome ASC and ASC specks from multiple types of inflammasomes, including NLRP3, to block initiation and perpetuation of damaging inflammation that promotes atherosclerosis and its progression, among numerous other inflammatory diseases. April 04, 2024 -- ZyVersa Therapeutics, Inc. (Nasdaq: ZVSA or “ZyVersa”), a clinical stage specialty biopharmaceutical company developing first-in-class drugs for treatment of inflammatory and renal diseases, highlights data from a peer-reviewed article published in Biochemical and Biophysical Research Communications. This article demonstrates that NLRP3 inhibition results in improved glucose tolerance and markedly smaller and more stable atherosclerotic lesions in a diabetic mouse model. In the paper titled, “High glucose levels accelerate atherosclerosis via NLRP3-IL/ MAPK/ NF-κB-related inflammation pathways,” the authors evaluated serum and coronary artery tissues from patients with coronary artery disease (CAD), with and without diabetes and they conducted a study in diabetic mouse models. Key findings include: Patients with comorbid CAD and diabetes had higher serum levels and expression of NLRP3 in their coronary arteries, and increased serum levels of IL-1β and IL-6 than those with CAD only. Diabetic mouse models showed a significantly higher atherosclerotic plaque/vessel area ratio than non-diabetic mice, which was markedly reduced with NLRP3 inhibition and the resulting reduction in levels of proinflammatory cytokines and inflammation. The authors concluded, “Our research offers new understanding of the pathological mechanisms of diabetes-accelerated AS and provide a novel and promising target for treating diabetes-accelerated AS.” To review the publication, Click Here. “We are excited about the data published in Biochemical and Biophysical Research Communications demonstrating that inhibiting inflammasome NLPR3 pathways has potential to attenuate the development and progression of AS in patients with diabetes, a leading cause of morbidity and mortality,” commented Stephen C. Glover, ZyVersa’s Co-founder, Chairman, CEO, and President. “We look forward to seeing our preclinical data with Inflammasome ASC Inhibitor IC 100 in an animal model of atherosclerosis in the first half of this year. We believe that by inhibiting multiple types of inflammasomes and disrupting the structure and function of their associated ASC specks to attenuate initiation and perpetuation of inflammation, that IC 100 has promise to effectively control AS development and progression.” To review a white paper summarizing the mechanism of action and preclinical data for IC 100, Click Here. IC 100 is a novel humanized IgG4 monoclonal antibody that inhibits the inflammasome adaptor protein ASC. IC 100 was designed to attenuate both initiation and perpetuation of the inflammatory response. It does so by binding to a specific region of the ASC component of multiple types of inflammasomes, including NLRP1, NLRP2, NLRP3, NLRC4, AIM2, and Pyrin. Intracellularly, IC 100 binds to ASC monomers, inhibiting inflammasome formation, thereby blocking activation of IL-1β early in the inflammatory cascade. IC 100 also binds to ASC in ASC Specks, both intracellularly and extracellularly, further blocking activation of IL-1β and the perpetuation of the inflammatory response that is pathogenic in inflammatory diseases. Because active cytokines amplify adaptive immunity through various mechanisms, IC 100, by attenuating cytokine activation, also attenuates the adaptive immune response. ZyVersa (Nasdaq: ZVSA) is a clinical stage specialty biopharmaceutical company leveraging advanced, proprietary technologies to develop first-in-class drugs for patients with renal and inflammatory diseases who have significant unmet medical needs. The Company is currently advancing a therapeutic development pipeline with multiple programs built around its two proprietary technologies – Cholesterol Efflux Mediator™ VAR 200 for treatment of kidney diseases, and Inflammasome ASC Inhibitor IC 100, targeting damaging inflammation associated with numerous CNS and other inflammatory diseases. For more information, please visit www.zyversa.com. The content above comes from the network. if any infringement, please contact us to modify.