IC 100 / ZyVersa - LARVOL DELTA

ZyVersa Therapeutics Reports Second Quarter 2025 Financial Results and Highlights Key Near-term Value-building Milestones (GlobeNewswire) - "In preparation for filing an IND for IC 100, a diet-induced obesity (DIO) mouse model study is expected to be initiated in partnership with University of Miami Miller School of Medicine Q4-2025....Following IND clearance, a phase 1 trial will be initiated with IC 100 in healthy overweight people (BMI: 27 - 30) at risk of cardiometabolic conditions..."

IND • Preclinical • Obesity

ZyVersa Therapeutics Highlights Published Study Reinforcing That Microglia-driven Inflammation Is Pivotal in Development of Parkinson’s and Alzheimer’s Diseases (GlobeNewswire) - "Our data showed that microglial inflammation was driven by activation of NLRP1 inflammasomes triggered by ASC specks and alpha-synuclein aggregates. Inflammasome ASC Inhibitor IC 100 inhibited NLRP1 inflammasome activation, thereby reducing the levels and spread of toxic phosphorylated alpha-synuclein."

Preclinical • Alzheimer's Disease • Parkinson's Disease

ZyVersa Therapeutics Reports First Quarter 2025 Financial Results and Highlights Pipeline Progress (ZyVersa Press Release) - "First patient expected to start therapy by end of Q2-2025 in Phase 2a proof-of concept clinical trial for Cholesterol Efflux Mediator VAR 200 in patients with diabetic kidney disease (DKD). Obesity-associated cardiometabolic preclinical proof-of-concept study with Inflammasome ASC Inhibitor IC 100 planned to begin by end of Q2-2025. Investigational New Drug Application (IND) for IC 100 anticipated to be submitted H2-2025, followed by initiation of a Phase 1 clinical trial in healthy overweight subjects at risk of cardiometabolic diseases. Groundbreaking data demonstrating IC 100 blocks microglial inflammasome activation and reduces neurotoxic alpha-synuclein accumulation — both key contributors to neurodegeneration and Parkinson’s disease (PD) progression, Invited MJFF grant request submitted for funding PD animal model proof-of-concept studies; response expected in June 2025. Raised approximately $2.0 million in Q1-2025."

Financing • IND • New P1 trial • New P2 trial • Preclinical • Cardiovascular • Obesity • Parkinson's Disease • Renal Disease

ZyVersa Unveils Groundbreaking Potential of Inflammasome Inhibitors in Combination with GLP-1 Agonists to Address Unmet Medical Needs of People Living with Obesity; Provides R&D Update (GlobeNewswire) - "ZyVersa has outlined a comprehensive development plan for IC 100, with key milestones anticipated over the next 12 months: H1-2025: Initiate preclinical study in diet-induced obesity (DIO) mouse model to evaluate IC 100's efficacy as monotherapy and in combination with semaglutide. H2-2025: Submit an Investigational New Drug (IND) application for IC 100; H1-2026: Commence Phase 1 clinical trials in overweight subjects (BMI 27–30) with cardiometabolic risk factors to assess safety and biomarkers of cardiometabolic risk."

IND • New P1 trial • Preclinical • Obesity

ZyVersa Therapeutics Announces Published Data Showing Inflammasome ASC Inhibitor IC 100 Decreases Microglial Inflammasome Activation and Alpha-Synuclein That Contribute to Neurodegeneration in Parkinson’s Disease (GlobeNewswire) - "ASC specks from PD patient brains triggered inflammasome activation and cell death in human microglia. This was blocked by IC 100. Preformed alpha-synuclein fibrils from brains of PD patients significantly increased total and phosphorylated alpha-synuclein and ASC specks in microglia, triggering inflammasome activation that was inhibited by IC 100. IC 100 altered the cellular distribution and decreased levels of phosphorylated alpha-synuclein, indicating improved clearance of pathogenic alphaαα-synuclein."

Preclinical • Parkinson's Disease

ZyVersa Therapeutics CEO Issues Shareholder Letter Announcing Transformative R&D Trends for Inflammasome Inhibitors, and Provides Update on Inflammasome ASC Inhibitor IC 100’s Development Status (GlobeNewswire) - "Proof-of-concept study with IC 100 in diet-induced obesity (DIO) mouse model is planned to begin H1-2025. Study will evaluate the effects of IC 100 on changes in inflammatory and cardiometabolic biomarkers, including insulin resistance which can lead to type 2 diabetes, as well as changes in body weight and body composition in comparison to semaglutide and when administered concurrently with semaglutide. We expect a preliminary read-out in H2-2025...Preclinical study funded by The Michael J. Fox Foundation (MJFF) to evaluate the potential of IC 100 as a treatment for Parkinson’s disease has been completed and a manuscript has been accepted for publication. Stay tuned for an announcement of the published data when available; Invited MJFF grant request for funding of a second IC 100 proof-of-concept preclinical study in Parkinson’s disease animal model has been submitted; response expected in June 2025."

Preclinical • Obesity • Parkinson's Disease

Inflammasome ASC Inhibitor IC 100 (GlobeNewswire) - "In preparation for filing an IND for IC 100, planned for second half of 2025, we will initiate two diet-induced obesity (DIO) mouse model studies, with the first planned to begin in H1-2025. The studies will evaluate the effects of IC 100 on body weight, body composition, and changes in metabolic and inflammatory parameters in comparison to semaglutide (study 1), and the effects of IC 100 administered concurrently with semaglutide on those same endpoints (study 2). We expect a preliminary read-out of study 1 by end of second half 2025....Following IND clearance, a phase 1 trial will be initiated with IC 100 in healthy overweight people (BMI: 27 – 30) to evaluate the safety of 3 different doses of IC 100, and to get a signal on the degree of weight loss that can be expected with each dose. Results are anticipated in the first half of 2026."

IND • New P1 trial • P1 data • Preclinical • Obesity

ZyVersa Therapeutics Highlights Data Demonstrating Inflammasome Inhibition Reduces Neuroinflammation and Pathological Brain Deposition of Amyloid Beta in Alzheimer’s Disease Mouse Model (GlobeNewswire) - "Initial Aβ deposition directly triggers NLRP3 activation and neuroinflammation in AD mouse model, which was attenuated by NLRP3 inhibition. NLRP3 inhibition significantly increased degradation and elimination of Aβ in microglia via a process called phagocytosis. Increased microglia phagocytosis with NLRP3 inhibition was attributed to increased microglial metabolic activity: (1) NLRP3 inhibition increased glutamine utilization and α-ketoglutarate (αKG) levels; (2) αKG triggered phagocytic gene transcription, and this cellular reprogramming enhanced uptake and degradation of Aβ by microglia. Data demonstrate an additional role for NLRP3 inhibition. In addition to attenuating damaging neuroinflammation, NLRP3 Inhibition increased mitochondrial and metabolic function, leading increased degradation and elimination of Aβ in microglia to attenuate progression of AD."

Preclinical • Alzheimer's Disease

ZyVersa Therapeutics Highlights Data Demonstrating NLRP3 Inflammasome Inhibition Reduces Inflammation, Improves Heart Function, and Restores Glucose Homeostasis and Insulin Sensitivity in Obese Animal Model of Heart Failure (HFpEF) and Type 2 Diabetes (GlobeNewswire) - "'We look forward to initiating two IC 100 preclinical studies in diet-induced obesity mouse models in the first half of this year. The first study will compare the effects of IC 100 to semaglutide, and the second will assess the effects of IC 100 administered concurrently with semaglutide.'...Key Findings: Attenuated circulating levels of pro-inflammatory cytokine, IL-18, and lowered macrophage infiltration into the heart leading to a substantial reduction in cardiac inflammation. Reduced cardiac hypertrophy and fibrosis, and improved cardiac diastolic function. Reduced fat mass, adipocyte size, and macrophage infiltration into visceral adipose tissue associated with obesity and metabolic disease. Improved glucose homeostasis and insulin sensitivity."

New trial • Preclinical • Obesity

ZyVersa Therapeutics Announces Peer-Reviewed Article Supporting the Therapeutic Potential of Targeting ASC Specks During Progression of Alzheimer’s Disease (GlobeNewswire) - "ZyVersa Therapeutics, Inc...is pleased to announce that world renowned inflammasome researchers and inventors of ZyVersa’s Inflammasome ASC Inhibitor IC 100 have published a scientific paper in the peer-reviewed journal, Alzheimer’s & Dementia: Translational Research & Clinical Interventions....In the paper titled, “Association of region-specific hippocampal reduction of neurogranin with inflammasome proteins in postmortem brains of Alzheimer’s disease,” the researchers demonstrated that loss of plasticity and neuronal scaffolding proteins, part of the neurodegenerative process leading to memory and learning deficits in AD, is associated with recruitment of ASC molecules and formation of inflammasome complexes in both neurons and microglia."

Clinical • Alzheimer's Disease • CNS Disorders

ZyVersa Therapeutics Announces Research Published in the Peer-Reviewed Journal Diabetes Reinforcing IC 100’s Rationale for Inhibiting ASC to Attenuate Damaging Inflammation Associated with Serious Conditions Such as Obesity-related Heart Disease (BioSpace) - "ZyVersa Therapeutics, Inc...announces a publication in the peer-reviewed journal, Diabetes, demonstrating the role of ASC in myocardial fibrosis induced by obesity....They also studied an animal model of obesity, with and without induced myocardial injury. Data indicate that: Activated NLRP3 inflammasomes leading to increased levels of proinflammatory IL-1β and IL-18 contribute to obesity-related myocardial fibrosis in obese humans and mice. Inflammasome ASC localized in the heart’s mitochondria participates in NLRP3 inflammasome formation and activation based on mouse data. Inhibition of NLRP3 activation or removal of IL-1β and IL-18 abated the adverse effects on cardiac fibrosis and function in mice. The authors concluded that these results provide new evidence for the involvement of mitochondria-localized ASC in obesity-induced cardiac fibrosis."

Preclinical • Cardiovascular • Metabolic Disorders • Obesity

ZyVersa Therapeutics Announces Research Published in Frontiers in Immunology Reinforcing IC 100’s Rationale for Inhibiting Multiple Inflammasomes to Control Inflammation in Various Inflammatory Diseases (GlobeNewswire) - "ZyVersa Therapeutics, Inc...announces publication of a paper in the peer-reviewed journal, Frontiers in Immunology, highlighting potential limitations of NLRP3 inhibition in attenuating CNS Inflammation associated with activation of multiple inflammasome pathways. This paper supports ZyVersa’s rationale for targeting inflammasome ASC with IC 100 to inhibit multiple inflammasome pathways, not just NLRP3, to control inflammation in various inflammatory diseases. In the paper...the authors conducted studies in various human cell lines and in an animal model of ALS. Data demonstrate that NLRP3 inhibition alone is insufficient to attenuate proinflammatory cytokine release and inflammatory cell death associated with activation of multiple inflammasome pathways. Likewise, NLRP3 inhibition alone did not ameliorate spinal cord inflammation in an ALS model."

Preclinical • Amyotrophic Lateral Sclerosis • CNS Disorders

ZyVersa Therapeutics and University of Miami Awarded a Grant from The Michael J. Fox Foundation to Determine if Inhibition of Microglial Inflammasome Activation with IC 100 Blocks Neuroinflammation Driving Parkinson's Disease Pathology (PRNewswire) - "ZyVersa Therapeutics...is honored to receive a grant from The Michael J. Fox Foundation for Parkinson's Research (MJFF) to determine if IC 100 inhibition of inflammasomes and ASC specks blocks microglial-mediated inflammation in a PD model. The research will be conducted at the University of Miami Miller School of Medicine in the labs of IC 100 inventors....'We are grateful to The Michael J. Fox Foundation for funding this research,' says Dr. Robert Keane.' This project will be the first to determine if α-synuclein preformed fibrils (PFF) and ASC specks trigger microglial inflammasome activation, causing them to shift to a detrimental phenotype and whether inflammasome inhibition with IC 100 prevents this shift by inhibiting ASC speck formation.'...'MJFF continues to fund therapeutic research to improve the lives of people with Parkinson's disease.'"

Financing • CNS Disorders

Ultrastructural and proapoptotic-like effects of kaempferol in Giardia duodenalis trophozoites and bioinformatics prediction of its potential protein target. (PubMed, Mem Inst Oswaldo Cruz) - "KPF exerted a proapoptotic effect on G. duodenalis trophozoites involving partial interruption of DNA synthesis without oxidative stress or structure damage to chromatin and cytoskeletal structures. GdAldRed is a likely target underlying its antigiardial activity."

Journal • Infectious Disease

Differences In Anthropometric Measures Between Critical Limb Threatening Ischaemia And Intermittent Claudication In Patients Undergoing Aorto Bifemoral Bypass. (PubMed, Rev Port Cir Cardiotorac Vasc) - "CLTI patients had lower anthropometric measures of obesity, when compared to IC patients. These results could be explained by the fact that CLTI patients with severe atherosclerotic disease are in a state of chronic inflammation, with consequent cardiometabolic demands and catabolism."

Clinical • Journal • Atherosclerosis • Cardiovascular • Diabetes • Dyslipidemia • Genetic Disorders • Hypertension • Immunology • Inflammation • Metabolic Disorders • Obesity • Peripheral Arterial Disease

Assessment of developmental neurotoxicity induced by chemical mixtures using an adverse outcome pathway concept. (PubMed, Environ Health) - "Our findings suggest that the use of human iPSC-derived mixed neuronal/glial cultures applied to a battery of assays anchored to key events of an AOP network represents a valuable approach to identify mixtures of chemicals with potential to cause learning and memory impairment in children."

Adverse events • Journal • Alzheimer's Disease • Autism Spectrum Disorder • CNS Disorders • Cognitive Disorders • Genetic Disorders

Comparison of Intraocular Pressure Measurements Between Reichert Tono-Vera Tonometer and Goldmann Tonometry (clinicaltrials.gov) - P=N/A; N=100; Not yet recruiting; Sponsor: Reichert, Inc.; Trial completion date: Aug 2020 ➔ Dec 2020; Initiation date: May 2020 ➔ Oct 2020; Trial primary completion date: Aug 2020 ➔ Dec 2020

Trial completion date • Trial initiation date • Trial primary completion date • Glaucoma • Ophthalmology

Agreement and repeatability of Icare ic100 tonometer. (PubMed, Indian J Ophthalmol) - "Icare ic100 showed good repeatability with RC and CV of 2.67 and 4.89, respectively. Icare ic100 rebound tonometer can measure IOP with relatively small measurement error and can provide a reliable and repeatable reading in comparison with GAT across a wide pressure range without hampering corneal health."

Journal • Ophthalmology

Determining the Optimal Normalization Factor of Different Target Arteries for ex vivo Vascular Function Experiments: A New Standardized Procedure. (PubMed, J Vasc Res) - "The IC1/IC100 ratio (also referred to as factor k), a value that is believed to be constant for a defined vessel type in one species, was calculated by a novel mathematical approach. Here, we present an easy-to-use toolbox for the systematic and computer-based calculation of factor k and simplified optimal pre-stretching of any vascular segments for wire myography experiments."

Journal • Preclinical

Comparison of the Icare ic100 rebound tonometer and the Goldmann applanation tonometer in 1000 eyes. (PubMed, Ophthalmic Res) - "Conclusions The Icare ic100 tonometer consistently under-estimated IOP compared to GAT, irrespective of CCT ranges and other subgroup analyses. The mean difference of -4.2mmHg can have significant implications, particularly in the management of glaucoma patients."

Journal • Glaucoma • Ophthalmology

Evaluation of the Effectiveness of Crotoxin as an Antiseptic against Candida spp. Biofilms. (PubMed, Toxins (Basel)) - "Candida spp biofilm formation was more sensitive to both CTX and CTX-containing mouthwash (IC100 = 12 μg/mL) when compared to nystatin (IC100 > 47 μg/mL). Moreover, significant membrane permeabilization at concentrations of 1.5 and 47 µg/mL was observed. Native CTX was less cytotoxic to HaCaT cells than CTX-containing mouthwash or nystatin between 24 and 48 h. These preliminary findings highlight the potential use of CTX in the treatment of oral candidiasis caused by resistant strains."

Journal • Candidiasis

Development of multi-specific humanized llama antibodies blocking SARS-CoV-2/ACE2 interaction with high affinity and avidity. (PubMed, Emerg Microbes Infect) - "Importantly, our current bi-specific antibody shows potent S/ACE2 blocking (KD - 0.25 nM, IC100 ∼ 36.7 nM, IC95 ∼ 12.2 nM, IC50 ∼ 1 nM) which is significantly better than individual monoclonal VHH-Fcs. No abstract available"

Journal • Immunology • Novel Coronavirus Disease

IC100: a novel anti-ASC monoclonal antibody improves functional outcomes in an animal model of multiple sclerosis. (PubMed, J Neuroinflammation) - "These data indicate that IC100 suppresses the immune-inflammatory response that drives EAE development and progression, thereby identifying ASC as a promising target for the treatment of MS as well as other neurological diseases with a neuroinflammatory component."

Journal • Preclinical

Journal of Neuroinflammation article shows ZyVersa's inflammasome inhibitor, IC 100, improves functional outcomes in an animal model of multiple sclerosis (PRNewswire) - "ZyVersa Therapeutics, Inc...is pleased to announce that the Journal of Neuroinflammation has published data showing that inflammasome inhibitor, IC 100, attenuates the inflammatory response causing neuronal damage in multiple sclerosis (MS), and that it improves functional outcomes. Data were collected in the EAE (experimental autoimmune encephalomyelitis) mouse model of multiple sclerosis (MS), which exhibits the key pathological features found in humans."

Preclinical • CNS Disorders • Multiple Sclerosis

Comparison of Intraocular Pressure Measurements Between Reichert Tono-Vera Tonometer and Goldmann Tonometry (clinicaltrials.gov) - P=N/A; N=100; Not yet recruiting; Sponsor: Reichert, Inc.

New trial