Technetium(99mTc)Methylenediphosphonate

AT-01 is a first-in-class pan-amyloid imaging agent capable of detecting diverse types of systemic amyloidosis in multiple organs.AT-01 demonstrated to be highly accurate, with 100% sensitivity for detection of cardiac amyloid, across three independent investigator-initiated studies.Attralus-Sponsored Test-Retest repeatability study demonstrates excellent repeatability and supports the potential use of AT-01 imaging to monitor disease progression in patients with cardiac amyloidosis.AT-01 may be more sensitive than 99m-Tc pyrophosphate bone scintigraphy (Tc99-PYP) for detecting transthyretin cardiac amyloidosis in patients with hereditary ATTR-CA.AT-01 uptake in cardiac amyloidosis shows moderate and statistically significant correlations with traditional measures of cardiac structure and function.AT-01 has the potential to play a valuable role for diagnosing cardiac amyloidosis and for monitoring changes in organ-specific amyloid load. SAN FRANCISCO, Oct. 02, 2023 (GLOBE NEWSWIRE) -- Attralus, Inc., a clinical stage biopharmaceutical company developing transformative medicines to improve the lives of patients with systemic amyloidosis, announced eight data presentations (from an Attralus sponsored trial and from four investigator-initiated trials) related to the use of 124I-evuzamitide (AT-01), the company’s pan-amyloid binding imaging agent in development for the diagnosis and management of all types of systemic amyloidosis. These data were included in oral and poster presentations at the 28th Annual Scientific Session of the American Society of Nuclear Cardiology (ASNC) taking place September 29-October 1, 2023, in Toronto, Canada. “AT-01 has the potential to become an essential tool not only to streamline diagnosis, but also to provide a comprehensive assessment of disease burden and a means to monitor disease progression,” said Gregory Bell, M.D., Chief Medical Officer at Attralus. “We are impressed by the consistency of results across multiple studies and institutions. AT-01 has the potential to be the first and only non-invasive, pan-amyloid, whole body imaging diagnostic agent designed to detect all types of systemic amyloidosis across key organs.” “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. 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 and the ability to monitor organ specific disease progression or response.” “Despite recent progress in diagnosis, ATTR patients continue to go undiagnosed or are diagnosed late in their disease. A delayed diagnosis leads directly to poorer outcomes for patients. Bone Scintigraphy with Tc99-PYP imaging is the current standard for a non-biopsy diagnosis for cardiac ATTR, but in the seminal study, its utility was only ‘70% sensitive’,” said Mat Maurer, M.D., Arnold and Arlene Goldstein Professor of Cardiology at Columbia University Irving Medical Center. “In our study, we were able to demonstrate cardiac uptake with AT-01 in hereditary ATTR patients who were negative with the standard imaging, Tc99-PYP, for non-biopsy diagnosis of cardiac ATTR, implying that I124 Evuzamitide is a more sensitive diagnostic. The data from AT-01 are encouraging as an imaging agent that could directly detect amyloid deposits and diagnose patients earlier in their disease. This could be invaluable for patients and would be a welcome addition to our practice for more prompt and accurate diagnosis.” Oral Presentation Details Abstract Title: 124I-evuzamitide PET/MR Unveils Hypertrophic Cardiomyopathy in a Patient with Renal AL Amyloidosis Presented by: Jessica Cardin, Ph.D. and Ahmad Masri, M.D., Assistant Professor of Medicine, Division of Cardiovascular Medicine, Knight Cardiovascular Institute at OHSU Oregon Health & Science UniversityDate/Time: September 30, 2023, 9:55 a.m. – 9:59 a.m. EDTSession: 204 – Rapid-Fire Cases: Amyloidosis and Technology, Tracers, Instrumentation, SoftwareHighlights: AT-01 PET/MR case report Abstract Title: I-124 Evuzamitide PET/CT is More Sensitive than Tc-99m Pyrophosphate for the Diagnosis of Hereditary Transthyretin Cardiac Amyloidosis Presented by: Dia A. Smiley, D.O. and Mathew S. Maurer, M.D., Arnold and Arlene Goldstein Professor of Cardiology at Columbia University Irving Medical CenterDate/Time: October 1, 2023, 8:00 a.m. EDTSession: 301 – Controversies in Cardiac AmyloidosisHighlights: Ten hereditary ATTR patients with negative Tc99-PYP scans were included in the analysis.All subjects with known cardiac amyloidosis had positive AT-01 uptake.Cardiac Uptake of AT-01 was observed in eight out of ten hereditary ATTR patients who had a negative Tc99-PYP scan, the current standard for non-biopsy diagnosis of cardiac ATTR, suggesting AT-01 is more sensitive than Tc99-PYP for detection of cardiac amyloid. Of these eight, five patients were confirmed positive via a cardiac biopsy and three were diagnosed through other imaging and genetic testing. Poster Presentation DetailsPoster 216-04: Iodine-124-Evuzamitide PET/CT in Systemic Amyloidosis: Safety Evaluation & Reproducibility of Cardiac Uptake Quantitation Presented by: Gregory Bell, M.D., Attralus, Inc.Date/Time: September 30, 2023, 3:15 p.m. - 4:15 p.m. EDTHighlights: 33 systemic amyloidosis patients were enrolled and received ≥1 dose of AT-01, and 27 received two doses of AT-01 (image-evaluable population).There were no TEAEs related to AT-01 administration, and no TEAEs occurred on the day of dosing.Semiquantitative assessments of AT-01 cardiac uptake demonstrated high levels of intra- and inter-rater consistency.Interclass Coefficient Correlation (ICC) values in the heart were >0.95; Cardiac repeatability coefficients using SUV peak are consistent with other PET/CT tracers.These findings support the potential use of this novel imaging agent to monitor disease progression in patients with cardiac amyloidosis. Poster 216-13: First-in-Human Cardiac and Whole-Body 124I-evuzamitide (AT-01) PET/MRI in Systemic Amyloidosis Presented by: Ahmad Masri, M.D., Assistant Professor of Medicine, Division of Cardiovascular Medicine, Knight Cardiovascular Institute at OHSU Oregon Health & Science UniversityDate/Time: September 30, 2023, 3:15 p.m. – 4:15 p.m. EDTHighlights: 50 subjects were enrolled in this study, including 36 cardiac amyloidosis patients and 14 controls. Controls included patients with high LVH, HCM and systemic amyloidosis patients without cardiac amyloid. Cardiac amyloidosis was ruled out in control population.In this population of patients diagnosed with or suspected to have cardiac amyloidosis, AT-01 PET/MRI had a 100% sensitivity and specificity for the diagnosis of cardiac amyloidosis.Mean myocardial to LV blood pool SUV ≥1.45 yielded a 100% sensitivity and specificity for the diagnosis of cardiac amyloidosis.AT-01 PET/MRI is feasible and provides comprehensive diagnostic evaluation and organ survey of patients suspected to have or diagnosed with systemic amyloidosis. Poster 216-14. Relationship Between Myocardial 124I-evuzamitide Uptake and Cardiac Structure and Function: A Cardiac PET/MRI Study Presented by: Ahmad Masri, M.D., Assistant Professor of Medicine, Division of Cardiovascular Medicine, Knight Cardiovascular Institute at OHSU Oregon Health & Science UniversityDate/Time: September 30, 2023, 3:15 p.m. – 4:15 p.m. EDTHighlights: 50 subjects were enrolled in this study, including 36 cardiac amyloidosis patients and 14 controls.AT-01 was safe without any serious adverse events and no tracer-related adverse events.There were moderate and significant correlations of AT-01 uptake with measures of cardiac structure and function on CMR.In this high-risk group of suspected cardiac amyloidosis, an ECV cut-off of 39% yielded a higher diagnostic performance than a cut-off of 30%.ECV and AT-01 mean myocardial SUVR had a moderate and statistically significant correlation coefficient of 0.6.AT-01 cardiac PET/MRI provides comprehensive diagnostic evaluation of cardiac structure, function, and surrogates for amyloid load. Poster 216-16. Quantitative Assessment of Changes in Cardiac and Extracardiac Amyloid Load in Patients with AL and ATTR Amyloidosis, Measured By PET/CT Imaging Using the Pan-Amyloid Reactive Radiotracer Iodine (124I) Evuzamitide Presented by: Alan Stuckey, C.N.M.T., University of Tennessee Graduate School of MedicineDate/Time: September 30, 2023, 3:15 p.m. – 4:15 p.m. EDTHighlights: The study has enrolled 19 patients (AL (n=9) and ATTR (n=10)) who had positive cardiac uptake of AT-01 in a previous phase 1 for the purpose of evaluating longitudinal change in uptake over time.The mean time between imaging sessions was 3.0±0.9 years.In patients with ATTR amyloidosis (n=10) on silencers or stabilizer therapy, cardiac amyloid assessed by AT-01 uptake changed by -2.4%±21.4% (range –24.7% to +49.5%). Despite therapy, only 1 out of 10 cardiac ATTR patients had a decrease of ≥25% after a mean of 3 years.In patients with AL (n=9) who were in hematologic remission, cardiac amyloid changed by 1.5%±37.6% (range -24.7% to +92.7%). Despite being in heme remission, only 1 out of 10 cardiac AL patients had a decrease of ≥25%.In contrast, in AL patients the liver and splenic decreased dramatically, -25.5%±25.3% and -16.6%±49.9%, respectively.Significant correlations were observed between echocardiography parameters, serum NTproBNP and cardiac SUVR mean measurements.Changes in cardiac amyloid load, based on differential uptake of radiotracer, can be quantified using AT-01 PET/CT imaging and may be useful for monitoring changes in organ-specific amyloid load. Poster 216-23. Comparing Novel Quantitative 124I-Evuzamitide PET/CT Metrics to Diagnose Cardiac Amyloidosis Presented by: Olivier F. Clerc, M.D., MPH, Researcher, Brigham and Women's HospitalDate/Time: September 30, 2023, 3:15 p.m. – 4:15 p.m. EDTHighlights: This study included 43 participants: 12 with light-chain (AL) cardiomyopathy (CMP),12 with wild-type transthyretin (ATTRwt) CMP and 20 controls.CMP participants underwent PET/CT with both radiotracers AT-01 and 18F-florbetapir.In CMP participants, median age was 74 years (IQR 69 – 78) and 92% were male.Median AT-01 left ventricular percentage of injected dose (LV %ID) was 0.17 (IQR 0.07 – 0.45) in AL-CMP, 0.44 (0.35 – 0.75) in ATTRwt-CMP, and 0.00 (0.00 – 0.01) in controls (p<0.001).High LV %ID perfectly discriminated CMP from controls.In ATTRwt-CMP, LV %ID was higher with AT-01 (p=0.002) than with 18F-florbetapir.AT-01 LV %ID had intermediate to strong correlations with interventricular septal thickness (ρ=0.80) and LV strain (ρ=0.55) on echocardiography, as well as with LV mass index (ρ=0.82) and extracellular volume (ρ=0.55, all p≤0.02) on MRI.AT-01 detects amyloid CMP and accurately discriminates it from controls, with higher uptake than 18F-florbetapir in ATTRwt-CMP.Correlations with cardiac structural and functional metrics imply valid amyloid quantification. Poster 216-25 - I-124 Evuzamitide PET/CT is More Sensitive than Tc-99m Pyrophosphate for the Diagnosis of Hereditary Transthyretin Cardiac Amyloidosis Presented by: Dia A. Smiley, D.O. and Mathew S. Maurer, M.D., Arnold and Arlene Goldstein Professor of Cardiology at Columbia University Irving Medical CenterDate/Time: September 30, 2023, 3:15 p.m. - 4:15 p.m. EDTHighlights: Same findings as oral presentation in Session 301 - Controversies in Cardiac Amyloidosis. For additional information, please visit the ASNC 2023 https://www.asnc.org/asnc2023. 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 initial clinical trials, AT-01 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 obtained exclusive rights to commercialize AT-01 under a commercial license agreement with the University of Tennessee Research Foundation. Similar PAR-peptide technology is utilized in AT-02 and AT-04, two of the company’s therapeutic candidates. 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. Amyloid Light Chain (AL) is caused by a bone marrow disorder in which the light chain proteins become misfolded and accumulate as amyloid fibrils, in the heart, kidneys, liver, nerves and other organs. AL is progressive, debilitating, and often fatal. There is a significant unmet need for new therapies and diagnostics in systemic amyloidosis, especially AL. About Attralus Attralus 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 universal 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 San Francisco. 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

近日，远大医药全球创新放射性核素偶联药物TLX101中国IND申请获受理，用于治疗多形性胶质母细胞瘤（GBM）。无独有偶，恒瑞医药镥[177Lu]氧奥曲肽注射液也收到了《药物临床试验批准通知书》，将于近期开展临床试验，用于治疗不可切除或转移性、进展性、分化良好（G1及G2）、生长抑素受体阳性的成人胃肠胰神经内分泌瘤（GEP-NETs）的临床研究。核素药物消息不断，以上两款一旦获批上市，或将打破我国核药市场的双寡头竞争格局。（中国同辐市场规模占比40.4%，东诚药业市场规模占比21.6%，其他药企仅占38%。）随着远大医药、恒瑞医药的强势入局，百亿核素药市场或迎新霸主，谁将力压群雄？强势入局，远大医药核药管线分析远大医药的TLX101是一种基于放射性核素-小分子偶联技术用于治疗多形性胶质母细胞瘤的治疗型放射性药物。该产品可自由通过血脑屏障进入大脑，并靶向胶质母细胞瘤过度表达的L型氨基酸转运蛋白1（LAT-1）精准辐射癌细胞，促使其凋亡以达到治疗效果。目前，TLX101已在美国及欧洲获得孤儿药认定，在欧洲和澳洲开展的I/II期临床试验也在顺利进行中，其海外II期临床研究早前已顺利完成首例患者给药。除了TLX101外，核药抗肿瘤诊疗板块也是远大医药的重点布局领域之一。围绕肿瘤诊疗一体化的治疗理念，远大核药抗肿瘤诊疗板块目前已储备13款创新产品（其中三款产品的IND申请已获得国家药监局受理），涵盖68Ga、177Lu、131I、90Y、89Zr、99mTc在内的6种核素，覆盖了肝癌、前列腺癌、脑癌等在内的8个癌种；在产品种类方面，涵盖诊断和治疗两类核素药物，为患者提供多适应症治疗选择、多手段且诊疗一体化的全球领先的抗肿瘤方案。双寡头竞争格局，核药市场生变？根据Frost&Sullivan数据，2022-2027年预计中国放射性药物行业市场规模将提高，CAGR达到21.4%，市场规模于2023年达到78.1亿元。截至2021年，全球市场中，中国市场占比仅为6%，北美市场达到40%。2017年，中国核药人均支出为3.2元，而美国人均支出为56.5元，是中国的17.66倍。与发达国家相比，中国放射性药物使用率较低，市场还有超10倍空间。图1 国内核药市场规模及增速图片来源：西南证券百亿规模待爆发，但我国核药市场目前已形成寡头竞争格局。根据Frost&Sullivan的数据统计，中国同辐（原子高科母公司）的市场规模占比达40.4%，位居全国第一，产品品种类型丰富，远超其余竞争对手。现阶段天津赛德和北京智博高科的产品品种较为单一，唯有东诚药业在市场占有率和品种种类方面奋力追赶。随着核药市场的进一步扩大，双寡头有望分享行业快速扩容的红利。图2 国内核药市场规模占比图片来源：Frost&Sullivan、新三板智库报告除了上述公司，近期国内制药巨头恒瑞也开始进入核药领域。2023年1月，恒瑞发布公告，宣布子公司天津恒瑞收到国家药品监督管理局核准签发的关于镥[177Lu]氧奥曲肽注射液的《药物临床试验批准通知书》，将于近期开展临床试验，用于治疗不可切除或转移性、进展性、分化良好（G1及G2）、生长抑素受体阳性的成人胃肠胰神经内分泌瘤（GEP-NETs）的临床研究。该款药物的临床试验获批，也标志着恒瑞医药正式切入了核素药物领域。核药研发方向畅想从产品类型上看，核药产品主要分为诊断用核药及治疗用核药，当前诊断性核药占主导地位。2020年，全球核药中诊断核药占主要市场，规模达到77.15亿美元，占比83.4%；治疗性核药受限于上游核素产能，以及较为严格的审批流程和使用条件，仅占比16.6%。图3 2017年国内同位素医疗应用市场分布图片来源：德邦证券长远来看，治疗用核素药物的前景更加广阔，日益受到重视。近10年来，由于放射性核素标记技术的进步、新的放射性核素的制备以及单克隆抗体技术的成熟，我国放射性核素治疗领域发展迅速，涌现出诸如云克注射液等过亿品种。未来，随着治疗性核药审批流程的不断优化，临床应用范围的持续扩大，核药诊疗一体化的推进，治疗性核药预计将表现出更高的弹性。据远大医药CEO周超预计，到2030年治疗性核药在全球核药占比中有望达到60%。尽管与美国相比，核医学人均支出差异巨大，但中国核素治疗总数保持增长态势，I131、Sr90/Y90、Tc99m是主要应用的治疗核素，这些核素对应症状分别为甲亢及甲状腺癌治疗、敷贴器治疗、类风湿性关节炎治疗，分别占比43.5%/25.5%/18.6%。图4 2019年分核素治疗情况图片来源：德邦证券小结2021年，国家发布针对核技术在医疗卫生应用领域的纲领性文件《医用同位素中长期发展规划（2021–2035年）》及《放射性体内诊断药物非临床研究技术指导原则》等规范政策，对于中国提升医用同位素相关产业能力水平，推动和规范中国放射性体内诊断药物的研发，保障健康中国战略具有重要的意义。随着社会经济的发展、居民消费水平增加以及核医学的发展空间，预计未来我国放射性药物市场有望继续保持较快发展。参考文献：1.远大医药官网2.西南证券报告《东诚药业（002675）2019年年报点评》3.新三板智库报告《寻找新三板精选层标的专题报告（七十）》4.德邦证券《东诚药业（002675.SZ）：多元业务布局的高成长核药龙头企业》声明：本内容为作者独立观点，不代表药智网立场。如需转载，请务必注明文章作者和来源。对本文有异议或投诉，请联系maxuelian@yaozh.com。责任编辑 | 八角转载开白 | 马老师 18996384680（同微信） 阅读原文，是昨天最受欢迎的文章哦