Iodine (124I) evuzamitide

124I-evuzamitide (AT-01) is one of the first investigational diagnostic imaging agents to receive Breakthrough Therapy Designation (BTD) from the US Food and Drug Administration (FDA), and the only diagnostic imaging agent that has received BTD for cardiac amyloidosis.124I-evuzamitide received orphan drug designations as a diagnostic for the management of ATTR and AL amyloidosis by both the US FDA and the European Commission.A Phase 3 study for 124I-evuzamitide in patients with suspected cardiac amyloidosis is anticipated to begin in the first half of 2025. BURLINGAME, Calif., Aug. 05, 2024 (GLOBE NEWSWIRE) -- Attralus, Inc., a clinical stage biopharmaceutical company developing transformative products to improve the lives of patients with systemic amyloidosis, today announced that its investigational diagnostic imaging agent drug, 124I-evuzamitide (AT-01), has been granted Breakthrough Therapy Designation (BTD) by the U.S. Food and Drug Administration (FDA) for positron emission tomography (PET) imaging in patients with suspected or known cardiac amyloidosis. FDA granted BTD for 124I-evuzamitide (AT-01) based on clinical data from Attralus-sponsored and investigator-initiated studies evaluating the use of 124I-evuzamitide in patients with cardiac amyloidosis, representing experience in more than 200 trial participants. BTD is a program used by the FDA to expedite the development and review of a product when: (1) intended to treat or diagnose a serious or a life-threatening condition; and (2) when preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapies on one or more clinically significant endpoints. BTD products are eligible for more intensive guidance from FDA to expedite development, including an organizational commitment by FDA and eligibility for Biologics License Application (BLA) rolling and priority review. “We are highly encouraged by FDA’s decision to grant Breakthrough Therapy Designation to 124I-evuzamitide (AT-01), recognizing its potential as an innovative diagnostic agent for patients with systemic amyloidosis” said Gregory Bell, M.D., Chief Medical Officer, Attralus. “There are no FDA approved diagnostic imaging agents for cardiac amyloidosis. The diagnosis of cardiac amyloidosis is a challenging and time-consuming process for patients, with many going years without an accurate diagnosis, and losing critical time in the process. We remain committed to bringing 124I-evuzamitide to the market as quickly as possible and look forward to working more closely with FDA to bring 124I-evuzamitide to patients.” About Systemic Amyloidosis Systemic 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. The majority of systemic amyloidosis patients have cardiac involvement, including the two most common forms, with ~95% of ATTR and 75% of AL patients having cardiac involvement. Other rare types of systemic amyloidosis such as AA, AApoAI, AApoAIV also have cardiac involvement. Cardiac amyloidosis is significantly underdiagnosed due to low awareness, non- specific symptoms, and lack of disease-specific diagnostics. There remains a significant unmet need for better diagnostics that may be able to more accurately diagnose patients earlier in the disease process. About 124I-evuzamitide (AT-01) Pan-Amyloid Diagnostic124I-evuzamitide (AT-01) is the first non-invasive pan-amyloid PET imaging agent specifically designed for systemic amyloidosis. 124I-evuzamitide utilizes the company’s pan-amyloid binding peptide labeled with iodine-124 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 ATTR and AL, in major organs such as the heart, kidney, liver, and spleen. Orphan drug designations have been granted to 124I-evuzamitide as a diagnostic for the management of ATTR and AL amyloidosis by both the Food and Drug Administration (FDA) and the European Commission. About Attralus Attralus is a clinical stage biopharmaceutical company focused on creating transformative products 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

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