ZyVersa Therapeutics Announces Peer-Reviewed Publication Demonstrating That Inflammasome ASC Inhibitor IC 100 Protects Against Stroke-Related Cardiovascular Injury and Dysfunction in Preclinical Trial
ZyVersa Therapeutics (NASDAQ: ZVSA) has published new data showing their Inflammasome ASC Inhibitor IC 100 protects against stroke-related cardiovascular injury in preclinical trials. The study, conducted on mice and zebrafish hearts, demonstrated that IC 100 blocked AIM2 inflammasome activation and cell death in the heart, improving cardiac function post-stroke. Key findings showed that IC 100 significantly reduced inflammasome proteins and cardiac inflammation when administered 30 minutes post-stroke. The company plans to progress IC 100's development into phase 1 around mid-2025, targeting obesity-related cardiovascular diseases, which have seen deaths triple between 1999 and 2020.
ZyVersa Therapeutics (NASDAQ: ZVSA) ha pubblicato nuovi dati che mostrano come il loro Inibitore dell'Inflammasoma ASC IC 100 protegga dalle lesioni cardiovascolari associate all'ictus in studi preclinici. Lo studio, condotto su cuori di topo e zebrafish, ha dimostrato che IC 100 blocca l'attivazione dell'inflammasoma AIM2 e la morte cellulare nel cuore, migliorando la funzione cardiaca dopo l'ictus. Le principali scoperte hanno mostrato che IC 100 riduce significativamente le proteine dell'inflammasoma e l'infiammazione cardiaca quando somministrato 30 minuti dopo l'ictus. L'azienda prevede di far progredire lo sviluppo di IC 100 nella fase 1 verso metà del 2025, mirando alle malattie cardiovascolari correlate all'obesità, le cui morti sono triplicate tra il 1999 e il 2020.
ZyVersa Therapeutics (NASDAQ: ZVSA) ha publicado nuevos datos que muestran cómo su Inhibidor del Inflamasoma ASC IC 100 protege contra las lesiones cardiovasculares relacionadas con el accidente cerebrovascular en ensayos preclínicos. El estudio, realizado en corazones de ratones y peces cebra, demostró que IC 100 bloquea la activación del inflamasoma AIM2 y la muerte celular en el corazón, mejorando la función cardíaca tras el accidente cerebrovascular. Los hallazgos clave mostraron que IC 100 redujo significativamente las proteínas del inflamasoma y la inflamación cardíaca cuando se administró 30 minutos después del accidente cerebrovascular. La empresa planea avanzar en el desarrollo de IC 100 hacia la fase 1 alrededor de mediados de 2025, enfocándose en las enfermedades cardiovasculares relacionadas con la obesidad, que han visto triplicar las muertes entre 1999 y 2020.
ZyVersa Therapeutics (NASDAQ: ZVSA)는 그들의 Inflammasome ASC 억제제 IC 100이 전임상 시험에서 뇌졸중 관련 심혈관 손상으로부터 보호한다는 새로운 데이터를 발표했습니다. 쥐와 제브라피쉬의 심장을 대상으로 한 연구에서 IC 100은 AIM2 inflammasome의 활성화와 심장 세포 사멸을 차단하여 뇌졸중 후 심장 기능을 개선하는 것으로 나타났습니다. 주요 발견에 따르면, IC 100은 뇌졸중 발생 후 30분에 투여했을 때 inflammasome 단백질과 심장 염증을 크게 줄였습니다. 이 회사는 2025년 중반에 1상으로의 개발을 진행할 계획이며, 1999년과 2020년 사이 3배 증가한 비만 관련 심혈관 질환을 목표로 하고 있습니다.
ZyVersa Therapeutics (NASDAQ: ZVSA) a publié de nouvelles données montrant que leur inhibiteur de l'inflammasome ASC IC 100 protège contre les lésions cardiovasculaires liées aux AVC lors d'essais précliniques. L'étude, réalisée sur des cœurs de souris et de poisson zèbre, a démontré que IC 100 bloquait l'activation de l'inflammasome AIM2 et la mort cellulaire dans le cœur, améliorant ainsi la fonction cardiaque après un AVC. Les principales conclusions ont montré qu'IC 100 réduisait significativement les protéines de l'inflammasome et l'inflammation cardiaque lorsqu'il était administré 30 minutes après un AVC. La société prévoit de faire progresser le développement d'IC 100 vers la phase 1 autour de mi-2025, en visant les maladies cardiovasculaires liées à l'obésité, qui ont vu leur taux de mortalité tripler entre 1999 et 2020.
ZyVersa Therapeutics (NASDAQ: ZVSA) hat neue Daten veröffentlicht, die zeigen, dass ihr ASC-Inhibitor IC 100 im Bereich präklinischer Studien vor kardiovaskulären Verletzungen im Zusammenhang mit Schlaganfällen schützt. Die Studie an Herzen von Mäusen und Zebrafischen zeigte, dass IC 100 die Aktivierung des AIM2-Inflammasoms und den Zelltod im Herzen blockierte und somit die Herzfunktion nach einem Schlaganfall verbesserte. Wesentliche Erkenntnisse zeigten, dass IC 100 die Inflammasom-Proteine und die Herzentzündung signifikant verringerte, wenn es 30 Minuten nach dem Schlaganfall verabreicht wurde. Das Unternehmen plant, die Entwicklung von IC 100 in Phase 1 Mitte 2025 voranzutreiben, wobei das Augenmerk auf kardiovaskulären Erkrankungen liegt, die mit Fettleibigkeit in Zusammenhang stehen und deren Todesfälle zwischen 1999 und 2020 dreifach gestiegen sind.
- Preclinical data shows IC 100 effectively reduces cardiac inflammation and improves heart function
- Company has clear timeline for Phase 1 trials starting mid-2025
- IC 100 demonstrates unique mechanism targeting multiple inflammasomes versus competitors' NLRP3 inhibitors
- Product is still in preclinical stage, far from commercialization
- Will require significant time and resources to complete clinical trials
- Success in animal studies may not translate to human trials
Insights
The preclinical data for IC 100 demonstrates promising potential in addressing a significant unmet medical need. The study reveals that IC 100 effectively blocks AIM2 inflammasome activation and reduces cardiac inflammation post-stroke, which could be particularly valuable given that 795,000 people suffer strokes annually in the US.
The unique mechanism of IC 100 targeting ASC to inhibit multiple inflammasomes, rather than just NLRP3, represents a potential competitive advantage. However, investors should note that the data is still preclinical and the planned Phase 1 trial in mid-2025 indicates a long runway to potential commercialization. The large addressable market of obesity-related cardiovascular disease, which has seen a tripling in deaths between 1999-2020, presents a significant commercial opportunity if clinical trials prove successful.
While the preclinical results are encouraging, several market considerations warrant attention. The cardiovascular disease space is highly competitive, with numerous established treatments and competing developmental programs. ZyVersa's market cap of
The planned Phase 1 timeline in mid-2025 indicates substantial capital requirements ahead. Investors should monitor the company's cash position and potential dilution risks. The broad applicability of IC 100 across multiple inflammasome-mediated conditions could provide multiple shots on goal, but successful clinical translation and commercialization remain distant milestones requiring substantial resources.
- Strokes affect 795,000 people annually in the US. Obesity, a top risk factor for strokes, is associated with around one out of five strokes.
- Cardiac complications following a stroke are a leading cause of mortality and morbidity, second only to acute neurological injury.
- The pathomechanism underlying cardiac dysfunction following a stroke includes a surge of catecholamines, such as epinephrine, which induces inflammasome activation triggering a systemic inflammatory response.
- The published data showed that following a stroke, Inflammasome ASC Inhibitor IC 100 blocked AIM2 inflammasome activation and cell death (pyroptosis) in the heart and improved cardiac function.
- Data from this article support ZyVersa’s development of Inflammasome ASC Inhibitor IC 100 for obesity and its associated cardiovascular comorbidities.
WESTON, Fla., Nov. 20, 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 newly published data demonstrating that stroke-related cardiovascular injury and dysfunction is induced by AIM2 inflammasome activation and pyroptosis in the heart, which can be blocked by Inflammasome ASC Inhibitor IC 100.
“These data demonstrate the potential for IC 100 to attenuate stroke-related cardiovascular disease which is common in patients living with obesity. According to the American Heart Association, obesity-related cardiovascular disease deaths tripled between 1999 and 2020, and this is expected to continue to increase without effective therapeutic options,” said Stephen C. Glover, ZyVersa’s Co-founder, Chairman, CEO and President. “We are excited about the potential of IC 100 to effectively control the inflammation that drives stroke-related cardiovascular injury and dysfunction. Unlike the NLRP3 inhibitors in development, IC 100 targets ASC to inhibit activation of multiple inflammasomes, including AIM2, which triggered the systemic inflammatory response affecting the heart after stroke in this study. More importantly, IC 100 uniquely disrupts the function of ASC specks to attenuate chronic, systemic inflammation leading to comorbidities. We look forward to progressing IC 100’s development program into phase 1 around mid-2025.
This study was published in the peer-reviewed journal, Translational Stroke Research, by acclaimed inflammasome researchers from the University of Miami Miller School of Medicine and inventors of IC 100. In the publication titled, Catecholamine‑Induced Inflammasome Activation in the Heart Following Photothrombotic Stroke, the researchers report data from studies conducted in a mouse model of photothrombotic stroke (PTS) and in excised zebrafish hearts.
Key Findings
- PTS in mice results in activation of the AIM2 inflammasome in the heart resulting in significant increases in IL-1β and ASC oligomerization into ASC specks contributing to a systemic inflammatory response affecting the heart after stroke.
- Treatment with IC 100 (30 mg/kg) at 30 minutes post-PTS significantly reduced the levels of inflammasome proteins and IL-1β in the heart thus reducing cardiac inflammation.
- Epinephrine-treated zebrafish hearts demonstrated a shortened action potential duration (SAPD) which was attenuated by IC 100. SAPD can cause irregular heart rhythm and reduced cardiac efficiency commonly seen in strokes and heart failure.
“These findings indicate that stroke initiates a catecholamine surge that induces inflammasome activation and pyroptosis in the heart that is blocked by IC 100, thus providing a framework for the development of therapeutics for stroke-related cardiovascular injury,” stated author Dr. Robert W. Keane, Professor, Physiology and Biophysics, Neurological Surgery and Microbiology, and Immunology, University of Miami Miller School of Medicine.
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
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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 Cashmere
Chief Commercial Officer
kcashmere@zyversa.com
786-251-9641
FAQ
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