APOA1

124I-evuzamitide (AT-01) PET/CT, the first pan-amyloid diagnostic imaging agent, demonstrated 100% sensitivity and specificity for the diagnosis of cardiac amyloidosis in patients suspected or diagnosed with cardiac amyloidosis in ATTR, AL, and other rare types of systemic amyloidosis.124I-evuzamitide PET/CT demonstrated uptake in multiple organs with amyloid deposition utilizing cutoffs from automated quantification in patients with AL and ATTR amyloidosis.Phase 3 – REVEAL study with 124I-evuzamitide in patients with suspected cardiac amyloidosis is ongoing by Brigham and Women’s Hospital, Boston, MA.AT-05 (99mTc-p5+14), a radiotracer, designed for SPECT imaging, demonstrated high levels of sensitivity and specificity for detection of cardiac amyloid in AL and ATTR patients. NAPLES, Fla., April 01, 2025 (GLOBE NEWSWIRE) -- Attralus, Inc., a clinical stage biopharmaceutical company developing transformative medicines and diagnostics to improve the lives of patients with systemic amyloidosis, announced three poster presentations (from four investigator-initiated trials), on the use of 124I-evuzamitide, the company’s pan-amyloid binding imaging agent in development for the diagnosis of cardiac amyloidosis, and one poster presentation of encouraging new clinical data from the University of Tennessee Graduate School of Medicine from an investigator-initiated trial on AT-05 (99mTc-p5+14) for the diagnosis of cardiac amyloid, at the 2025 American College of Cardiology (ACC) Annual Scientific Session held in Chicago, IL on March 29-April 1, 2025. “Diagnosing patients early remains one of the biggest unmet needs for systemic amyloidosis patients, with many going years without an accurate diagnosis. Current diagnostic methods may not accurately detect early infiltration of amyloid deposits,” said Ahmad Masri, M.D., Assistant Professor of Medicine and the Director of Cardiac Amyloidosis and Hypertrophic Cardiomyopathy Centers at Oregon Health & Science University. “In our study, in 97 patients, we were able to show high levels of sensitivity and specificity for detection of cardiac amyloid in ATTR, AL, and other rare types of systemic amyloidosis patients, including in very early patients. We have been impressed by our results to date and are very much looking forward to the results of the ongoing Phase 3 REVEAL study in suspected cardiac amyloidosis patients. We are excited by the potential of 124I-evuzamitide to become a new standard of care for diagnosing systemic amyloidosis.” “Detection and quantification of amyloid burden in the heart is an unmet clinical need for patients with diverse types of systemic amyloidosis,” said Jonathan Wall, Ph.D., Distinguished Professor, University of Tennessee Graduate School of Medicine. “AT-05 is a promising new reagent candidate for the facile detection of ATTR and AL cardiac amyloid using gamma imaging and may serve as a useful tool for the early detection of amyloidosis by community cardiologists, having the potential to be an invaluable tool to both detect early cardiac and extracardiac deposits.” Poster Presentations – Poster 905-21: DIAGNOSTIC PERFORMANCE OF CARDIAC AND WHOLE-BODY 124I-EVUZAMITIDE (AT-01) PET/MRI IN SYSTEMIC AMYLOIDOSIS - Ahmad Masri Date: March 29, 2025, 11:18 – 11:25 a.m. CDTPresenter: Ahmad Masri, M.D., Oregon Health and Science UniversityHighlights This study included 97 patients (57 had cardiac transthyretin amyloidosis, 20 had cardiac light chain amyloidosis, 3 had ApoA1 or ApoA4, 8 had systemic amyloidosis but no cardiac involvement, and 17 had no evidence of systemic amyloidosis).124I-evuzamitide PET/MRI demonstrated 100% sensitivity and specificity in detecting cardiac amyloidosis. No false positive or false negative cases were observed.124I-evuzamitide PET/MRI demonstrated uptake in multiple organs with amyloid deposition, including the kidneys, liver, spleen and lungs. Poster 997-13: RELIABILITY OF 124I-EVUZAMITIDE IMAGING AND QUANTITATIVE AGREEMENT IN PATIENTS WITH AL AND ATTR SYSTEMIC AMYLOIDOSIS Date: March 31, 2025, 10:00 – 10:07 a.m. CDTPresenter: Spencer Guthrie, MPH, Attralus, Inc.Highlights Twenty-seven (n=27) patients were included (64% AL, and 36% with ATTR amyloidosis).Subjects received 1 mCi of 124I-evuzamitide by IV infusion and were scanned with PET/CT on Day 1 and Week 6 to determine reliability and repeatability of quantitative measures across the heart, kidneys and other organs.Using automated quantification methods, for cardiac uptake, the SUV mean and %ID mean yielded excellent reliability (ICC=0.95) and bias of 1 with 95% upper and lower LOA of 0.81 and 1.23, indicating that ~20% change in the 124I-evuzamitide cardiac uptake represents a real change. The mean features provided reliable analytics (ICC ≥0.9) with good agreement for every organ measured. Poster 997-19: AUTOMATED QUANTIFICATION OF AL AND ATTR SYSTEMIC AMYLOID BURDEN USING 124I-EVUZAMITIDE, A NOVEL PAN-AMYLOID RADIOTRACER Date: March 31, 2025, 10:36 – 10:43 a.m. CDTPresenter: Spencer Guthrie, MPH, Attralus, Inc.Highlights This study included 95 CA patients (n=37 AL-CA and n=58 ATTR-CA) and 16 healthy volunteers, pooled from four independent clinical studies. The 3-dimensional volumes of the liver, spleen, kidneys, pancreas, and adrenals were segmented in the CT data using an automated trained deep learning algorithm.124I-evuzamitide uptake was observed: in the liver in 15 of the n=37 (41%) AL patients and 5 of the n=58 (9%) ATTR patients; in the spleen in 22 (59%) AL and 9 (16%) ATTR patients; in the kidney in 18 (49%) AL and 3 (5%) ATTR patients; in the pancreas in 25 (68%) AL and 18 (31%) ATTR patients.This new radiotracer candidate affords a novel noninvasive approach to characterize cardiac and extracardiac organ amyloid burden, including in organs that have been less characterized such as the pancreas and adrenals. Poster PB123: DETECTION OF CARDIAC AMYLOIDOSIS, AND MORE, USING SPECT/CT IMAGING OF TECHNETIUM-99M-LABELED PEPTIDE p5+14 (AT-05) Date: March 31, 2025, 9:36 – 9:43 a.m. CDTPresenter: Jonathan Wall, Ph.D.., University of Tennessee Graduate School of MedicineHighlights This study includes 18 cardiac amyloidosis patients and 5 healthy controls.Subjects were administered a single IV injection of 99mTc-p5+14 (<22 mCi). SPECT/CT and planar images were acquired at 1 h and 3 h post injection.No cardiac uptake of 99mTc-p5+14 was seen in healthy subjects.Cardiac uptake was observed in both planar and SPECT/CT images acquired at 1 h and 3 h post injection.Comparison of 99mTc-p5+14 and 99mTc-PYP in the same ATTR patient suggests that the myocardium uptake-to-blood pool ratio is 3-fold higher for the peptide tracer at 1 h post injection.Extracardiac uptake of radiotracer was also observed in the lungs of patients with ATTR and the liver, spleen, salivary glands, lung, and tongue in AL patients. For additional information, please visit the ACC.2025 website.To view posters and presentations, visit the Attralus website. About 124I-evuzamitide (AT-01) Pan-Amyloid Diagnostic124I-evuzamitide 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 radiotracer to detect all types of systemic amyloidosis by PET/CT imaging. In clinical trials, 124I-evuzamitide has been observed 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 Phase 3 REVEAL StudyResearch with 124I-EVuzamitide to Elucidate Cardiac AmyLoidosis (REVEAL) study is an ongoing Phase 3 clinical trial of the investigational diagnostic imaging agent 124I-evuzamitide in patients with suspected cardiac amyloidosis by Brigham and Women’s Hospital in Boston, MA. The trial is designed to determine the sensitivity and specificity of 124I-evuzamitide imaging to diagnose cardiac amyloidosis. 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 of systemic amyloidosis. AT-05 is currently in a Phase 1 clinical trial. 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 Attralus Attralus is a clinical stage biopharmaceutical company focused on creating transformative medicines and diagnostics 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 Naples, FL. Forward-Looking Statements This press release contains forward-looking statements, including statements related to the efficacy, continued development, and potential of 124I-evuzamitide and AT-05. 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

Dive Brief:An RNA drug developed by Eli Lilly sharply reduced blood levels of a protein particle that scientists and drugmakers increasingly see as important to assessing heart disease risk, alongside cholesterol and triglycerides.Treatment with a high dose of Lillys drug, called lepodisiran, reduced levels of this particle, lipoprotein(a), by about 94% over a four-month period. People enrolled in the companys Phase 2 study who received one of two lower lepodisiran doses also had reduced lipoprotein(a) levels, but the declines werent as large.Around 14% of study participants given the high lepodisiran dose experienced treatment-emergent adverse events, but none were serious or led them to drop out of the trial, Lilly said. One patient on a lower dose died as a result of complications from chronic coronary disease.Dive Insight:LDL cholesterol and triglycerides are well known for their link to elevated cardiovascular risk. So too are the treatments, like statins, that can be used to tamp down high levels of either lipid.While genetic and epidemiological studies have shown a similar link between lipoprotein(a) and heart disease, there are no treatments available that can reduce levels of the protein particle, which seem tied to genetics.Pharmaceutical companies like Lilly aim to fill the gap. Lepodisiran works by whats known as RNA interference, a biologic process drugmakers have harnessed to silence the expression of certain genes. These therapies degrade the transitional nucleic acid cells use to construct apolipoprotein(a), an essential building block for Lp(a) particles.Novartis and Amgen previously showed drugs that work this way can dramatically reduce Lp(a) levels. Both companies, as well as Lilly, are now running large Phase 3 trials designed to prove that Lp(a)-lowering translates to a cardioprotective benefit.How well they do remains an open question. How much lipoprotein(a) reduction is necessary to produce clinical benefits remains uncertain and has been debated, wrote the authors of a paper publishing Lillys results in The New England Journal of Medicine on Sunday. The data were also presented at the American College of Cardiologys annual conference.Novartis will likely be first to provide an answer. The company had expected a readout of data from its late-stage study this year, but now anticipates results will be available in 2026. Amgen could also have data from its trial in 2026, but likely later in the year.If these studies are successful, Lp(a)-lowering therapies could become a third pillar for managing heart disease risk in the 20% or so of Americans who are estimated to have elevated levels of the protein.In addition to lepodisiran, Lilly is advancing an oral drug called muvalaplin that targets Lp(a) and is exploring gene editing approaches to treatment with Verve Therapeutics. Merck & Co., meanwhile, recently paid $200 million to China-based Jiangsu Hengrui Pharmaceutical to license a competing oral medicine. '

iStock, Alona Horkova BMO Capital Markets analysts said the results potentially position lepodisiran as “one of the most durable assets in development to date” in the competitive Lp(a) space, where drugs are designed to lower the risk of cardiovascular events such as heart attack and stroke. Eli Lilly ’s investigational siRNA therapeutic lepodisiran can elicit up to a nearly 94% reduction in lipoprotein(a) levels, according to data from the Phase II ALPACA study presented over the weekend at the American College of Cardiology 2025 Scientific Sessions. “We view these results positively amongst the competitive Lp(a) space, potentially positioning lepodisiran as one of the most durable assets in development to date,” analysts at BMO Capital Markets said in an investor note on Sunday. ALPACA is a randomized, double-blinded and placebo-controlled trial that enrolled 320 patients with elevated Lp(a) levels, which can increase risk of cardiovascular events such as heart attack or stroke. Patients in the treatment group were given one of three doses—16 mg, 96 mg or 400 mg—at baseline and after 180 days. Change in serum Lp(a) levels were measured from day 60 to 180. The results, which were simultaneously published in The New England Journal of Medicine , showed that the 400-mg dose cut Lp(a) levels by 93.9%. Meanwhile, the 96-mg and 16-mg doses led to a 75.2% and 40.8% reduction in Lp(a), respectively. Lepodisiran also hit a key secondary endpoint, producing a 94.8% decrease in average Lp(a) levels from day 30 to 360 for its 400-mg dose. Lp(a) concentrations remained 91% below baseline at 360 days and 74.2% below baseline at 540 days. The BMO analysts were particularly encouraged by these data, which they believe are suggestive of a durable treatment effect. Lilly’s ALPACA data also “show the feasibility of [once every six months] dosing” for lepodisiran, which could be “a clear differentiator” in the Lp(a) space. For instance, Ionis and Novartis’s pelacarsen, an antisense oligonucleotide, is given monthly . Meanwhile, Amgen’s siRNA silencer olpasiran is injected subcutaneously once every 12 weeks . Despite the potential step forward in dosing regimen, BMO believes that Lilly, and pharma at large, still needs to develop the market further for lepodisiran. “While efficacy is obvious, we believe Lp(a) diagnostic testing needs to improve significantly to start to shape a commercial market for the drug.” Lepodisiran is an siRNA molecule that targets the mRNA that encodes for apolipoprotein(a), an important structural component of Lp(a). In November 2023, Phase I data supported this mechanism of action, showing that a 608-mg dose could elicit a 94% Lp(a) reduction at 48 weeks. Lilly is running the Phase III ACCLAIM-Lp(a) program to test the effect of lepodisiran on cardiovascular events in adults with heightened Lp(a). The trial is currently enrolling. Aside from lepodisiran, Lilly’s cardiovascular portfolio also includes the oral pill muvalaplin, which in November 2024 reduced Lp(a) by nearly 86% at 12 weeks for a 240-mg dose. At the time, Lilly said that it would discuss the next steps for muvalaplin with the FDA, building toward the potential first oral Lp(a)-lowering therapy.