AA amyloidosis

Data demonstrate that extracellular ASC specks, independent of IL-1β, govern the pathogenesis and extent of amyloid A (AA) amyloidosis, which is characterized by deposition of insoluble amyloid fibrils in tissues and organs disrupting their structure and function.Extracellular ASC interacts with serum amyloid A (SAA) released by the liver during inflammation, forming a scaffold that accelerates SAA aggregation into amyloid fibrils, which are deposited in tissues and organs.Amyloid A amyloidosis occurs in a heterogeneous spectrum of chronic inflammatory conditions such as rheumatoid arthritis, Crohn’s disease, and inflammatory bowel disease.ZyVersa is developing Inflammasome ASC Inhibitor IC 100, which inhibits intra- and extracellular ASC and specks associated with multiple types of inflammasomes to attenuate damaging inflammation and its perpetuation and spread to surrounding tissues. WESTON, Fla., Aug. 07, 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 data published in the peer-reviewed journal, EMBO Molecular Medicine, demonstrating that extracellular ASC has a crucial role in aggregation and deposition of amyloid A fibrils leading to associated chronic inflammatory conditions. “This research highlighting the role of extracellular ASC specks, independent of IL-1β, in the pathogenesis of chronic conditions associated with amyloid A amyloidosis reinforces our selection of ASC as a target for our inflammasome inhibitor IC 100,” stated Stephen C. Glover, ZyVersa’s Co-founder, Chairman, CEO, and President. “This paper provides one more piece of evidence that inhibiting extracellular ASC specks associated with multiple types of inflammasomes has potential to control damaging inflammation associated with a broad range of inflammatory diseases.” The paper titled, The ASC inflammasome adapter governs SAA-derived protein aggregation in inflammatory amyloidosis, summarizes data from in vitro and in vivo research investigating the role of ASC in inflammation-associated amyloidosis. Following is a summary of key findings: ASC colocalized tightly with SAA in human AA amyloidosis.ASC specks accelerated SAA fibril formation.Splenic amyloid load was decreased in a Pycard knock-out mouse model of AA Amyloidosis which lacks ASC.Treatment with anti-ASCPYD antibodies decreased amyloid loads in wild-type mice suffering from AA amyloidosis. “Our findings might have therapeutic implications that advance the fields of protein misfolding disorders (PMDs) and chronic inflammatory diseases in general as ASC could be a target of disease-modifying therapies that aim to reduce amyloid deposition and pathology in various proteinopathies,” concluded the authors. 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

AT-02, the company’s lead pan-amyloid removal therapeutic candidate, is currently being evaluated in a Phase 1 three-part trial and a Phase 2 open label extension trial in ATTR and AL amyloidosis patients to support its use as an immunotherapy in patients with systemic amyloidosis.AT-02 binds amyloid in mouse models within one day of injection and remains present in the amyloid 10 days after injection.AT-01, the first pan-amyloid diagnostic imaging agent, demonstrated high levels of sensitivity and specificity for detection of cardiac amyloid.AT-01 uptake in cardiac amyloid was significantly correlated with measures of cardiac structure, cardiac function, disease staging, cardiac biomarkers, and quality of life measures.AT-05 cardiac uptake was observed in ATTR and AL patients with no cardiac uptake in healthy subjects. BURLINGAME, Calif., May 30, 2024 (GLOBE NEWSWIRE) -- Attralus, Inc., a clinical stage biopharmaceutical company developing transformative medicines to improve the lives of patients with systemic amyloidosis, announced 11 data presentations (from four investigator-initiated trials), including two oral presentations related to the use of 124I-evuzamitide (AT-01), the company’s pan-amyloid binding imaging agent in development for the diagnosis of cardiac amyloidosis. The company also announced two presentations from AT-02, including highly encouraging preclinical data for AT-02, the company’s lead pan-amyloid removal therapeutic candidate in an oral presentation. In addition, data were presented from an investigator-initiated trial on 99tc-evuzamitide (AT-05) for the diagnosis of cardiac amyloid, and preclinical data were presented for AT-06, a CAR-macrophage therapy for systemic amyloidosis. In total, 16 abstracts were presented related to Attralus’ pan-amyloid pipeline including three oral and 13 poster presentations at the XIX International Symposium on Amyloidosis (ISA) held in Rochester, MN. on May 26-30, 2024. “Diagnosis is a challenging and time-consuming process for systemic amyloidosis patients, with many going years without an accurate diagnosis, and losing critical time in the process,” said Ahmad Masri, M.D., Assistant Professor of Medicine and the Director of Cardiac Amyloidosis and Hypertrophic Cardiomyopathy Centers at Oregon Healthy & Science University. “In our study, we were able to learn important disease characteristics about our patients that we cannot learn from any currently available imaging agent. Quantitative measures of AT-01 cardiac uptake showed correlations with standard measures of cardiac structure and function. The AT-01 data we generated provide an impressive road map to detecting and quantifying amyloid deposits in multiple organs across different types of amyloidosis, with the potential to detect amyloid earlier in the disease process.” “Current approved therapies for systemic amyloidosis target precursor protein production, reducing the formation of new amyloid, but there is a significant unmet need for new therapies that can remove the existing toxic amyloid fibrils that cause organ damage and mortality,” said Jonathan Wall, Ph.D., Distinguished Professor from the University of Tennessee Graduate School of Medicine. “The preclinical data from AT-02 that we presented demonstrate rapid and persistent binding of AT-02 to amyloid in both AL amyloidoma and AA animal models. These data provide a highly encouraging foundation for a disease modifying treatment approach for systemic amyloidosis using AT-02, which has the potential to improve outcomes for patients.” Oral Presentation Details Abstract Title: Characterization of the Peptide-Antibody Fusion, AT-02- Studies to Support its Use as an Immunotherapy in Patients with Amyloidosis Date: May 27, 2024, 10:55-11:05 a.m. CDTPresenter: Jonathan Wall, Ph.D., University of Tennessee Graduate School of Medicine Highlights AT-02 binds rapidly and specifically to amyloid in the liver, spleen, and heart in an AA mouse model.After a single IV injection, AT-02 can be seen in the liver, spleen, and heart amyloid 7 days after injection.AT-02 binds human AL amyloid in a mouse within one day of injection and remains present in the amyloid 10 days after injection.AT-02 enhances phagocytosis of ATTRwt amyloid extract at sub-nanomolar concentrations.Binding of AT-02 to synthetic AL amyloid fibrils is not inhibited by free light chains.AT-02 is stable and retains its bioactivity after nine days in human serum. Abstract Title: Changes in Organ-Specific Amyloid Load Assessed by Serial PET/CT Imaging of Iodine (124I) Evuzamitide – Correlation with Serum Biomarkers Date: May 28, 2024, 8:45-8:55 a.m. CDTPresenter: Emily Martin, Ph.D., University of Tennessee Graduate School of Medicine Highlights 19 cardiac amyloidosis patients underwent repeat imaging with 124I-evuzamitide (AT-01) PET/CT approximately three years after their initial scan.All ATTR patients were on a silencer or stabilizer (or both) during the period between AT-01 scans.All AL patients were in some form of hematologic remission with most not on therapy.The cardiac SUVR mean remained stable in 78% of AL patients, decreased in 11% and increased in 11%. However, the splenic and hepatic SUVR decreased dramatically in a few patients.The change in cardiac SUVR from baseline to repeat imaging correlated significantly with the change in serum NT-proBNP in the whole population. Abstract Title: First-in-Human Cardiac and Whole-Body 124I-evuzamitide (AT-01) PET/MRI in Systemic Amyloidosis Date: May 28, 2024, 9:05-9:15 a.m. CDTPresenter: Morris Kim, M.D., Oregon Health and Science University Highlights In this population of 50 patients (34 cardiac amyloidosis and 16 controls) diagnosed with or suspected to have cardiac amyloidosis, 124I-evuzamitide PET/MRI uptake was detected in all patients with cardiac amyloid and in none of the control patients.In this single center study in select patients, a simple measure of mean myocardial to LV blood pool SUV ratio ≥1.45 yielded a 100% sensitivity and specificity for the diagnosis of cardiac amyloidosis.124I-evuzamitide PET/MRI provided novel information of the distribution of amyloid in the heart, kidney, spleen, liver and lung.124I-evuzamitide PET/MRI provided comprehensive diagnostic evaluation and organ survey of patients suspected to have or diagnosed with systemic amyloidosis. Poster Presentations Poster PC143: Clinical Trial Design of AT-02 Phase 2 Open-Label Extension Study in Systemic Amyloidosis Date: May 29, 2024: 2:45-3:45 p.m. CDTPresenter: Mazen Hanna, M.D., Cleveland Clinic Poster PB115: Uptake of Iodine (124I) Evuzamitide in Patients with AL and ATTR Amyloidosis and Correlation with Echocardiographic Parameters Date: May 28, 2024, 2:45-3:45 p.m. CDTPresenter: Robert Heidel, Ph.D., University of Tennessee Graduate School of Medicine Poster PB120: Automatic quantification of AL and ATTR amyloidosis disease burden using 124I-evuzamitide, a novel radiotracer Date: May 28, 2024, 2:45-3:45 p.m. CDTPresenter: Zhiyang Wei, M.D., Harvard University Poster PB122: Relationship Between Myocardial Amyloid Load Measured by 124I-evuzamitide and Prognostic Staging Systems in Transthyretin Amyloid Cardiomyopathy Date: May 28, 2024, 2:45-3:45 p.m. CDTPresenter: Morris Kim, M.D., Oregon Health and Science University Poster PB123: Relationship Between Myocardial 124I-evuzamitide Uptake and Extracellular Volume Fraction: A Cardiac PET/MRI Study Date: May 28, 2024, 2:45-3:45 p.m. CDTPresenter: Morris Kim, M.D., Oregon Health and Science University Poster PB126: Characterizing Renal Involvement in Light Chain Amyloidosis on 124I-evuzamitide PET/MRI Imaging Date: May 28, 2024, 2:45-3:45 p.m. CDTPresenter: Bryton Davis, M.D., Oregon Health and Science University Poster PB127: Utilizing 124I-Evuzamitide PET/MRI to Elucidate the Relationship between Renal Dysfunction and Amyloid Deposition in Transthyretin Amyloid Cardiomyopathy Date: May 28, 2024, 2:45-3:45 p.m. CDTPresenter: Bryton Davis, M.D., Oregon Health and Science University Poster PB135: Quantitative Uptake of 124I-Evuzamitide on PET Correlates with Markers of Transthyretin Cardiac Amyloidosis, Quality of Life, and Functional Status Date: May 28, 2024, 2:45-3:45 p.m. CDTPresenter: Dia Smiley, D.O., Columbia University Poster PB141: Cardiac Involvement in Rare Forms of Amyloidosis Assessed Using 124I-Evuzamitide PET/CT Date: May 28, 2024, 2:45-3:45 p.m. CDTPresenter: Olivier Clerc, M.D., M.P.H., Brigham and Women’s Hospital Poster PB142: Temporal Changes in Cardiac Amyloid Burden Assessed Using 124I-Evuzamitide PET/CT Date: May 28, 2024, 2:45-3:45 p.m. CDTPresenter: Olivier Clerc, M.D., M.P.H., Brigham and Women’s Hospital Poster PB109: Preliminary Evaluation of 99mTc-Labeled Peptide p5+14 (AT-05) for the Detection of Cardiopulmonary Amyloidosis Using SPECT/CT and Planar Gamma Scintigraphic Imaging Date: May 28, 2024, 2:45-3:45 p.m. CDTPresenter: Jonathan Wall, Ph.D., University of Tennessee Graduate School of Medicine Poster PB114: Early Development and Pre-Clinical Evaluation of a Fluorine-18 Labeled Peptide, p5+14, for the Detection of Amyloid Cardiomyopathy by PET/CT Imaging Date: May 28, 2024, 2:45-3:45 p.m. CDTPresenter: Eric Webster, University of Tennessee Graduate School of Medicine Poster PA40: Temporal Changes in the Renal Cytokine Profile in Response to AA Amyloidosis Induce Macrophage Infiltration Enabling Host-Mediated Targeting of Therapeutic Chimeric Antigen Receptor Macrophages (CARM) Date: May 27, 2024, 2:45-3:45 p.m. CDTPresenter: Manasi Balachandran, Ph.D., University of Tennessee Graduate School of Medicine For additional information, please visit the ISA 2024 website. To view posters and presentations, visit the Attralus website. About Systemic AmyloidosisSystemic amyloidosis encompasses a diverse group of rare diseases that occur due to accumulation of toxic amyloid deposits in tissues and organs, a consequence of aberrant protein misfolding events. These diseases are progressive, debilitating and often fatal. Systemic amyloidosis is significantly underdiagnosed due to low awareness, lack of specific symptoms, and no current disease-specific diagnostics. There are approximately 17 different types of systemic amyloidosis, which combined represent over 500,000 patients in the United States, the European Union and Japan. The two most common forms of systemic amyloidosis are transthyretin-associated amyloidosis (ATTR) and immunoglobulin light-chain-associated (AL) amyloidosis. While currently approved treatments slow disease progression by targeting precursor proteins, there is a significant unmet need for new therapies that can remove toxic amyloid deposits across all amyloid types and improve organ function and patient quality of life. About AT-02, Pan-Amyloid Removal TherapeuticAT-02 is the company’s lead pan-amyloid removal (PAR) therapeutic candidate for systemic amyloidosis. AT-02 is a humanized IgG1 monoclonal antibody genetically fused with the company’s proprietary pan-amyloid binding peptide, enabling binding to multiple types of amyloid deposits. The Fc region of the antibody stimulates the immune system to remove amyloid deposits that are bound by AT-02. AT-02 uses a similar pan-amyloid peptide to 124I-evuzamitide, the company’s diagnostic agent, which has been shown in multiple clinical trials to selectively bind to amyloid deposits in the heart, liver, kidney, and other organs in multiple types of amyloidosis. As a result, the company expects AT-02 to bind specifically to amyloid in systemic amyloidosis patients. Preclinical data have shown the ability of AT-02 to bind to multiple amyloid types in major organs, induce macrophage mediated phagocytosis, and remove amyloid. AT-02 is currently being evaluated in a Phase 1 three-part trial and a Phase 2 open label extension trial in ATTR and AL amyloidosis patients. About 124I-evuzamitide (AT-01) Pan-Amyloid Diagnostic124I-evuzamitide (AT-01) utilizes the company’s pan-amyloid binding peptide as an amyloid-specific imaging agent to image all types of systemic amyloidosis by PET/CT imaging. In clinical trials, 124I-evuzamitide has been shown to detect multiple types of amyloid deposits, including AL and ATTR, in major organs such as the heart, kidney, liver, and spleen. Attralus has a special protocol assessment (SPA) in place with the FDA to conduct a single pivotal Phase 3 trial for 124I-evuzamitide. About AT-05, Pan-Amyloid DiagnosticAT-05 uses the same pan amyloid binding peptide as 124I-evuzamitide but is labelled with technetium-99m (Tc-99m, 99mTc). AT-05 is designed to be used with single-photon emission computerized tomography (SPECT) to be more accessible to community cardiologists, and thereby support broader screening in addition to diagnosis. AT-05 is currently in a Phase 1 clinical trial. About AT-06AT-06 is an additional therapeutic candidate that incorporates differentiated technology to treat all types of systemic amyloidosis. AT-06 incorporates the PAR-peptide into a CAR-M, which is an alternative approach to enabling the immune system to remove amyloid deposits. About AttralusAttralus is a clinical stage biopharmaceutical company focused on creating transformative medicines to improve the lives of patients with systemic amyloidosis. The company’s proprietary pan-amyloid removal (PAR) therapeutics are designed to directly bind to and remove toxic amyloid in organs and tissues. By targeting the disease-causing pathology in systemic amyloidosis diseases, PAR therapeutics have the potential to treat and reverse disease in patients with all types and stages of systemic amyloidosis. Attralus was founded by scientific experts in the field of amyloidosis and the company is headquartered in Burlingame, CA. Forward-Looking Statements This press release contains forward-looking statements, including statements related to the efficacy, continued development, and potential of AT-01. Words such as “developing,” “potential,” “shown” and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon Attralus’ current expectations. Forward-looking statements involve risks and uncertainties. Attralus’ actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties. Attralus expressly disclaims any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in Attralus’ expectations with regard thereto or any change in events, conditions, or circumstances on which any such statements are based. Contact:Krishna Gorti, M.D. FRCSCorporate Developmentkgorti@attralus.com

Google’s DeepMind unit has used artificial intelligence (AI) to catalogue millions of ‘missense’ mutations in human DNA that could be related to the development of genetic diseases. Developed by DeepMind researchers as an extension of its AlphaFold database, the AlphaMissense AI tool has classified the effects of 71 million missense mutations and categorised 89% of them as either ‘likely’ or ‘unlikely’ to be linked to human diseases. The AlphaFold database was originally released in 2021 and is freely used by researchers worldwide to predict the three-dimensional structures of the human proteome. Around 350 million people worldwide are living with rare disorders, approximately 80% of which are genetic in origin, including AA amyloidosis, Adrenoleukodystrophy and Ehlers-Danlos syndrome. Missense variants, which are genetic mutations affecting the structure and function of human proteins, can lead to diseases such as cystic fibrosis, sickle-cell anaemia or cancer. In previous studies, scientists have only been able to categorise around 0.1% of missense mutations, and only 6% of them have been studied. On average, a person carries over 9,000 missense variants, therefore, classifying them is important to understanding what can develop to diseases. By utilising the AlphaMissense catalogue, which is also freely-available, and the AlphaFold database, research into molecular biology could be accelerated by understanding how harmful missense mutations can cause disease, potentially forming the basis of research into diagnostics and treatments. DeepMind’s research scientists, Žiga Avsec and Jun Cheng, wrote: “With millions of possible mutations and limited experimental data, it’s largely still a mystery which ones could give rise to disease.” They added: “Experiments to uncover disease-causing mutations are expensive and laborious – every protein is unique, and each experiment has to be designed separately, which can take months. “By using AI predictions, researchers can get a preview of results for thousands of proteins at a time, which can help to prioritise resources and accelerate more complex studies."