caspase 1

NEW YORK--( BUSINESS WIRE )--Olatec Therapeutics, Inc. (Olatec), a leader in the developing class of selective NLRP3 inhibitors, today announced that Cure Parkinson’s granted an award to initiate a Phase 2 clinical trial investigating the potential of oral dapansutrile to slow or stop the progression of Parkinson’s disease. Parkinson’s is a complex neurodegenerative disease, which as reported by Cure Parkinson’s, is the fastest growing neurological condition in the world. The symptoms of Parkinson’s are treated with a range of medications, but despite decades of research, currently there remains a serious unmet need for a treatment to slow, stop or reverse the progression of this disease. The movement-associated symptoms of Parkinson’s are mainly caused by the loss of dopamine-producing nerve cells (dopaminergic neurons) in the mid-brain called the substantia nigra which controls movement. This loss of dopaminergic neurons is associated with accumulation of a protein known as α-synuclein within neurons, which is thought to disrupt their function. There is growing scientific literature suggesting that inflammation contributes to the damage and loss of neurons in the brain in Parkinson’s patients. In particular, there is evidence that the NLRP3 inflammasome is activated within the inflammatory cells of the brain, called microglia, and this activation may be triggered by abnormal aggregates of α-synuclein protein. Treatment with dapansutrile has the potential to arrest this cyclical process of cell damage thereby slowing the progression of the disease. This investigator-initiated study entitled “Anti-inflammatory Intervention with Dapansutrile (OLT1177 ® ) for Parkinson’s Disease Modification (DAPA-PD): A Randomised Double-Blind Placebo-Controlled Phase II Trial” is targeting to commence in mid-2024, subject to completion of all contractual agreements and regulatory authorizations. The trial will seek to enroll 36 participants with early Parkinson’s disease. Treatment duration will be six months with placebo control, followed by an optional, six month open-label phase. This single center study will be conducted at the John van Geest Centre for Brain Repair, Department of Clinical Neurosciences at the University of Cambridge in the UK. Dr. Caroline H. Williams-Gray, who leads the Cambridge Parkinson’s Disease Research Clinic, is the Principal Investigator. When asked about the study, Dr. Caroline Williams-Gray, said: “There is a pressing need for a specific treatment, such as dapansutrile, which targets the most relevant aspects of the immune activation pathway in Parkinson’s without causing general immunosuppression and leading to unwanted side effects. In this trial, we aim to determine dapansutrile’s safety and tolerability in patients with Parkinson’s, and to establish whether treatment with dapansutrile can reduce inflammation in both the brain and periphery in Parkinson’s. We will also investigate whether this results in a positive effect on clinical symptoms and disease progression.” Olatec’s Founder and CEO, Damaris Skouras commented: “The grant from Cure Parkinson’s and our collaboration with Dr. Williams-Gray at the University of Cambridge provides the possibility to advance dapansutrile in its first CNS indication as a potential disease modifying treatment for Parkinson’s.” About Parkinson’s Disease Over 9 million people worldwide are living with Parkinson’s disease ( mdabstracts.org , 2020). Currently, there are no therapeutics that can alter Parkinson’s disease progression. Patients initially present with complaints of changes in movement, walking and speech; worsening physical symptoms are accompanied by the development of cognitive decline as well as a range of other non-motor symptoms including mood disturbance, bladder and bowel dysfunction, sleep problems and difficulties with blood pressure control. Medications such as levodopa can improve movement symptoms but are unable to control the wide range of non-motor symptoms that affect people with Parkinson’s disease, and do not alter disease progression. About Scientific Rationale for NLRP3 in Parkinson’s Disease The movement-associated symptoms of Parkinson’s are mainly caused by the loss of dopamine-producing nerve cells (dopaminergic neurons) in an area of the midbrain called the substantia nigra which controls movement. This loss of dopaminergic neurons is associated with accumulation of a protein known as α-synuclein within neurons, which is thought to disrupt their function. Once around half of the dopaminergic neurons in the substantia nigra are lost, typically the clinical symptoms of Parkinson’s manifest, including slowness of movement, muscle stiffness and tremor. Parkinson’s can also cause a wide range of non-movement related symptoms including anxiety, sleep disturbance, gut symptoms, cognitive problems and dementia. There is growing scientific literature suggesting that inflammation contributes to the damage and loss of neurons in the brain in Parkinson’s. In particular, there is evidence that a complex of proteins called the NLRP3 inflammasome is activated within the inflammatory cells of the brain, called microglia, and this activation may be triggered by abnormal aggregates of α-synuclein protein. Activation of the NLRP3 inflammasome causes microglia to produce inflammatory molecules which are damaging to dopaminergic neurons, and may promote further α-synuclein aggregation, thus leading to a cyclical process of cell damage. Olatec believes that treatment with dapansutrile has the potential to inhibit the NLRP3 dependent neuroinflammatory process and in so doing arrest this cyclical process of cell damage thereby slowing the progression of the disease. About Dr. Caroline Williams-Gray, Principal Investigator Dr. Caroline Williams-Gray is a leading clinician scientist specializing in Parkinson’s disease and movement disorders. She studied medicine at Cambridge University and Oxford Clinical School, graduating in 2001, and gained her PhD from Cambridge University in 2008, thereafter training in neurology in Cambridge, Norwich and Queen Square, London. Dr. Williams-Gray leads the Cambridge Parkinson’s Disease Research Clinic. Dr. Williams-Gray’s work focuses on the theory that the immune system is a significant player in mediating the clinical variability of Parkinson’s disease and its progression; and in particular that peripheral immune activation plays a critical role through exacerbating microglial activation and neuronal damage in the brain. About Cure Parkinson’s Cure Parkinson’s, a UK-registered foundation, funds, facilitates and encourages research aiming to find a cure for Parkinson’s, with urgency, for people currently living with Parkinson’s. It was founded in 2005 by people living with Parkinson’s, who set out to find a cure. It focuses on research projects investigating disease-modifying therapies, with the potential to slow, stop or reverse the progression of Parkinson’s. Cure Parkinson’s partners with Van Andel Institute (VAI) and the John Black Charitable Foundation (JBCF) to fund an International Linked Clinical Trials (iLCT) initiative aiming to develop new, potentially disease-modifying Parkinson’s therapies. Together, they have directly funded, or secured funding from donors and fundraisers, for over £75 million supporting clinical trials searching for a cure for Parkinson’s and have pledged a total of USD $6.75 million to Parkinson’s research, over three years. Under its iLCT program, Cure Parkinson’s supports clinical trials based on a drug prioritization process conducted by a committee of world-leading experts. Over the last decade, the iLCT program has completed 13 trials and currently has 16 ongoing studies investigating 15 molecules. About Dapansutrile Dapansutrile (lab code: OLT1177 ® ) is an investigational small molecule, new chemical entity that specifically binds to and blocks NLRP3 (nucleotide-binding and oligomerization domain [NOD]‑, leucine rich repeat-, pyrin domain-containing 3), the sensor molecule integral in the formation of the NLRP3 inflammasome. Inflammasomes are multiprotein complexes involved in intracellular surveillance of danger signals that trigger an intense inflammatory response, via generation of bioactive IL-1β and IL-18 through caspase-1 activation. Dapansutrile has been shown to prevent the formation of the NLRP3 inflammasome, which in turn inhibits the production of IL-1β and IL‑18. Dapansutrile has been well tolerated and shown to improve clinical outcomes in patients with acute gout flare (see The Lancet Rheumatology ) and heart failure (see Journal of Cardiovascular Pharmacology ). Dapansutrile has also been observed to have anti-inflammatory properties and other promising activity in a broad spectrum of over 20 preclinical animal models including arthritis, asthma, acute myocardial infarction (AMI), heart failure, contact dermatitis, multiple sclerosis, melanoma, pancreatic and breast cancers, spinal cord injury (SCI), Parkinson’s and Alzheimer’s disease. For a complete list of Olatec’s original publications on dapansutrile in various preclinical and clinical disease areas, please refer to Olatec’s publication page, here . About Olatec Therapeutics, Inc. Olatec is a privately held, clinical-stage biopharmaceutical company developing a platform of oral NLRP3 inhibitors to treat and prevent a broad spectrum of acute and chronic inflammatory diseases known to be mediated by IL-1. Clinical trials include gout and diseases of aging such as type 2 diabetes, heart failure and cancer (see list of clinical trials to-date, here ). In addition to the lead compound, dapansutrile, Olatec’s platform of proprietary compounds includes approximately 40 analogues (OLT Analogues) being screened as viable drug candidates. A portfolio of intellectual property registrations protecting Olatec’s compounds consists of over 150 patents granted. Olatec’s drug development team is comprised of experienced management and international experts in translational medicine with unparalleled expertise in inflammation and immunology and has been involved in the discovery and development of first-line inflammation treatments in the market today. For more information, please visit http://www.olatec.com Disclaimer & Forward-looking Statement This press release is not an offer to sell and is not soliciting an offer to buy any equity interests in the Company. The information contained herein is being provided for information purposes only. The Company makes no express or implied representation or warranty as to the completeness of this information. Any forward-looking statements contained in this release are based on assumptions made by Olatec at the time this Press Release was prepared. Any forward-looking statement contained in this Press Release is subject to known and unknown risks, uncertainties and other factors that may be materially different from those contemplated in such forward-looking statements. All information with respect to industry data has been obtained from sources believed to be reliable and current, but the accuracy thereof cannot be guaranteed by the Company. Olatec does not undertake any obligation to update or revise the forward-looking statements contained in this Press Release to reflect events or circumstances occurring after the date this Press Release was prepared, or to reflect the occurrence of unanticipated events.

Insulin resistance (IR), a common feature of childhood obesity which affects 15 million children and adolescents, is the main driver of obesity-related metabolic complications such as Type 2 diabetes, hypertension, and premature heart disease.This study demonstrated that NLRP3 inflammasome activation was highest in obese children with the worst metabolic profile (higher serum glucose levels, a late insulin response to glucose tolerance tests, adverse serum lipid profiles, and higher oxidative stress (based on ROS levels).ZyVersa is developing Inflammasome ASC Inhibitor IC 100 which inhibits NLRP3 and other types of inflammasomes and their associated ASC specks to attenuate initiation and perpetuation of damaging inflammation. WESTON, Fla., Jan. 31, 2024 (GLOBE NEWSWIRE) -- ZyVersa Therapeutics (Nasdaq: ZVSA, or “ZyVersa”), a clinical-stage specialty biopharmaceutical company developing first-in-class drugs for treatment of renal and inflammatory diseases, highlights an article published in the peer-reviewed Journal of Translational Medicine supporting that NLRP3 activation is associated with a pathologic inflammatory response in obese children with insulin resistance and increased risk of developing metabolic complications. Inflammation and oxidative stress, which are closely related pathophysiological processes, one of which can be easily induced by the other, are key drivers for developing metabolic complications, such as type 2 diabetes and cardiovascular disease, in this population. In the paper titled, “Altered insulin secretion dynamics relate to oxidative stress and inflammasome activation in children with obesity and insulin resistance,” the authors conducted a case-controlled study of 132 children who were either lean or obese. The obese group was segmented into those with or without insulin resistance, and those with insulin resistance were segmented into those with an early and late insulin response to glucose as determined by an oral glucose tolerance test (OGTT). The researchers reported the following key findings in Children with obesity, insulin resistance, and increased risk of metabolic complications: Higher levels of NLRP3 and its effector proteins (active IL-1β, caspase-1, and gasdermin D) in peripheral blood mononuclear cells (PBMCs) and serum compared to the other groups studied, indicative of NLRP3 activation and an inflammatory response.Higher levels of uric acid versus the other groups, a well-known trigger of NLRP3 activation.Increased levels of oxidative stress and oxidative damage versus the other groups. The authors concluded, “It is insulin response to an OGTT that identifies children with obesity suffering oxidative stress, and inflammasome activation more specifically. Uric acid could be mediating this pathological inflammatory response by activating NLRP3 in peripheral blood mononuclear cells.” To read the article, Click Here. “Childhood obesity, which has increased more than 8-fold over the last 40 years, is an alarming health problem today due to the increased risk for developing type 2 diabetes, early heart disease, and other co-morbidities,” commented Stephen C. Glover, ZyVersa’s Co-founder, Chairman, CEO, and President. “The research published in the Journal of Translational Medicine points to a significant role for inflammasome-mediated inflammation and oxidative stress in development of metabolic complications in obese children. ZyVersa is developing Inflammasome ASC Inhibitor IC 100 designed to inhibit NLRP3 and other types of inflammasomes and their associated ASC specks to attenuate initiation and perpetuation of inflammation, which may have therapeutic potential to alleviate metabolic complications of childhood obesity with early intervention.” To review a white paper summarizing the mechanism of action and preclinical data for IC 100, Click Here. 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, 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. 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 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. 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 and IR Contact:Karen CashmereChief Commercial Officerkcashmere@zyversa.com786-251-9641 Media ContactsTiberend Strategic Advisors, Inc.Casey McDonaldcmcdonald@tiberend.com646-577-8520 Dave Schemeliadschemelia@tiberend.com609-468-9325

Atherosclerosis, an inflammatory disease characterized by buildup of cholesterol, lipids, and other substances (plaque) in arteries leading to heart attack and stroke, is accelerated in patients with diabetes. The study published in Diabetes demonstrates that AIM2 and NLRP3 inflammasome activation leads to development of atherosclerotic lesions in diabetic mice. ZyVersa is developing Inflammasome ASC Inhibitor IC 100, which inhibits multiple inflammasome pathways (including NLRP3 and AIM2) to attenuate initiation and perpetuation of damaging inflammation that is pathogenic in numerous diseases. WESTON, Fla., Dec. 06, 2023 (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 publication of an article in the peer-reviewed journal, Diabetes, demonstrating that AIM2 and NLRP3 inflammasome activation contributes to development of atherosclerosis in two different animal models of type 1 diabetes. In the paper titled, “Hematopoietic NLRP3 and AIM2 inflammasomes promote diabetes-accelerated atherosclerosis, but increased necrosis is independent of pyroptosis,” the authors studied mouse models of type 1 diabetes and atherosclerosis. Following are key findings reported in the paper: Diabetic animals demonstrated activation of inflammasome pathways, based on increased levels of plasma IL-1β and IL-18, and elevated levels of cleaved caspase- 1 in the peritoneal cavity fluid. Each of the two different type 1 diabetes models exhibited similar levels of plasma IL- 1β and IL-18 and similar aortic lesion sizes and severity. Diabetic mice deficient in NLRP3 and/or AIM2 had reduced aortic lesion size compared to diabetic controls, indicating that NLRP3 and AIM2 inflammasome activation contributes to atherosclerotic lesion development. Results are consistent with other animal model studies showing deficiencies in essential inflammasome components, such as NLRP3, AIM2, ASC, and caspase-1, appear to protect against atherosclerosis. To read the article, Click Here. “The research published in Diabetes reinforces that inhibition of multiple types of inflammasomes, not just NLRP3, may be required to effectively control inflammation in diseases, such as atherosclerosis, in which activation of more than one type of inflammasome is pathogenic,” commented Stephen C. Glover, ZyVersa’s Co-founder, Chairman, CEO and President. “ZyVersa’s Inflammasome ASC inhibitor IC 100 is designed to inhibit formation of multiple types of inflammasomes and their associated ASC specks to attenuate initiation and perpetuation of damaging inflammation contributing to numerous diseases.” To review a white paper summarizing the mechanism of action and preclinical data for IC 100, Click Here. 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, 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 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. 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 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 . 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. Corporate and IR Contact: Karen Cashmere Chief Commercial Officer kcashmere@zyversa.com 786-251-9641 Media Contacts Tiberend Strategic Advisors, Inc. Casey McDonald cmcdonald@tiberend.com 646-577-8520 Dave Schemelia dschemelia@tiberend.com 609-468-9325