Repeat PET/CT Imaging of Patients With Systemic Amyloidosis Using Amyloid Reactive Peptide 124I-AT-01 (124I-p5+14, Iodine-124I-evuzamitide) to Measure Changes in Organ-specific Amyloid Load

The goal of this research study is to determine whether changes in organ-specific uptake of 124I- AT-01 can be measured by PET/CT imaging and further, whether these values correlate with changes in a subject's disease status and thereby enable monitoring of disease response over time in terms of organ-specific amyloid load.

Start Date07 Dec 2022

Sponsor / Collaborator

University of Tennessee

NCT05635045 / RecruitingPhase 2IIT

A Follow-Up Study to Monitor Therapeutic Response in Transthyretin Cardiac Amyloidosis Using Amyloid Reactive Peptide 124I-evuzamitide (AT01) PET/CT

This is a single center, prospective cohort study that is evaluating the ability of 124I-evuzamitide PET scanning to detect potential therapeutic changes in subjects under treatment for ATTR after one year has elapsed since their original 124I-evuzamitide PET scan.
Ten previously scanned subjects will re-consent to undergo another 124I-evuzamitide PET scan. Demographic, clinical and phenotypic data will be collected to characterize potential changes since their previous scans.

Start Date08 Jul 2022

Sponsor / Collaborator

Columbia University

[+1]

NCT05235269 / Active, not recruitingPhase 2

A Multicenter, Open-label, Single-arm, Phase 2 Study to Evaluate Safety and Organ Uptake Quantitation Repeatability of 124I AT-01 Using Positron Emission Tomography/X-ray Computed Tomography (PET/CT) in Subjects With Systemic Amyloidosis

This study is designed to assess the repeatability of organ-specific quantitation of radiotracer uptake following Positron Emission Tomography/Computed Tomography (PET/CT) imaging of AT- 01 in subjects with amyloid light chain (AL) or amyloid transthyretin (ATTR) systemic amyloidosis.

Start Date30 Nov 2021

Sponsor / Collaborator

Attralus, Inc.Startup

100 Clinical Results associated with Iodine (124I) evuzamitide

100 Translational Medicine associated with Iodine (124I) evuzamitide

100 Patents (Medical) associated with Iodine (124I) evuzamitide

Literatures (Medical) associated with Iodine (124I) evuzamitide

01 Nov 2023·JACC. Cardiovascular imaging

Cardiac Amyloid Detection by PET/CT Imaging of Iodine (124I) Evuzamitide (124I-p5+14)

Article

Author: Guthrie, Spencer ; Williams, Angela D ; Stuckey, Alan ; Richey, Tina ; Foster, James S ; Ramchandren, Radhakrishnan ; Martin, Emily B ; Powell, Dustin ; Kennel, Stephen J ; Whittle, Bryan ; Wall, Jonathan S ; Lands, Ronald ; Heidel, R Eric

BACKGROUND:

The noninvasive detection of cardiac amyloid, as well as deposits in other vital organs, is critical for early diagnosis and quantitative disease monitoring. Positron emission tomography is an intrinsically quantitative imaging modality suitable for high-resolution amyloid detection.

OBJECTIVES:

This study sought to evaluate the safety and efficacy of a novel amyloid-reactive peptide, designated p5+14, labeled with iodine-124 (¹²⁴I), in patients with diverse types of systemic amyloidosis.

METHODS:

In a single-site, open label phase 1/2 study (NCT03678259), the safety, biodistribution, and sensitivity of a single intravenous infusion of ¹²⁴I-evuzamitide was assessed in patients with systemic amyloidosis (n = 50), asymptomatic transthyretin sequence variant carriers (n = 2), and healthy volunteers (n = 5). Subjects were administered 1.4 ± 0.2 mg of ¹²⁴I-evuzamitide (71.5 ± 12.4 MBq) and positron emission tomography/x-ray computed tomography images acquired at 5.2 hours (Q25-Q75: 4.9-5.4 hours) postinfusion. Images were assessed visually and semi-quantitatively for positive uptake of radiotracer in the heart and other major organs.

RESULTS:

Uptake of ¹²⁴I-evuzamitide in the heart and other abdominothoracic organs was consistent with the patient's clinical presentation and the type of amyloidosis. The patient- and cardiac-associated sensitivity for imaging and clinical observations was 93.6% (95% CI: 82.8%-97.8%) and 96.2% (95% CI: 81.8%-99.8%), respectively. Semi-quantitative uptake of the radiotracer correlated significantly with serum N-terminal pro-B-type natriuretic peptide measurements in patients with light chain-associated amyloidosis. Cardiac uptake was not observed in any healthy volunteers. The agent was well tolerated, with 1 drug-related adverse event and no deaths.

CONCLUSIONS:

¹²⁴I-evuzamitide is an amyloid-binding radiotracer capable of detecting cardiac amyloid in patients with high sensitivity.

01 Nov 2023·JACC. Cardiovascular imaging

Cardiac Amyloid Quantification Using 124I-Evuzamitide (124I-P5+14) Versus 18F-Florbetapir

Article

Author: Dorbala, Sharmila ; Clerc, Olivier F ; Falk, Rodney H ; Di Carli, Marcelo F ; Bianchi, Giada ; Neri, Jocelyn Canseco ; Cuddy, Sarah A M ; Chemburkar, Vaidehi ; Vijayakumar, Shilpa ; Kijewski, Marie Foley ; Robertson, Matthew

BACKGROUND:

Cardiac amyloid quantification could advance early diagnosis of amyloid cardiomyopathy (CMP) and treatment monitoring. However, current imaging tools are based on indirect measurements. ¹²⁴I-evuzamitide is a novel pan-amyloid radiotracer binding to amyloid deposits from multiple amyloidogenic proteins. Its ability to quantify cardiac amyloid has not yet been investigated.

OBJECTIVES:

The objectives of this pilot study were to quantify myocardial ¹²⁴I-evuzamitide uptake and to compare its diagnostic value to ¹⁸F-florbetapir in participants with amyloid CMP and control subjects.

METHODS:

This study included 46 participants: 12 with light-chain (AL) CMP, 12 with wild-type transthyretin (ATTRwt) CMP, 2 with hereditary amyloidosis, and 20 control subjects. All amyloidosis participants underwent positron emission tomography/computed tomography with ¹²⁴I-evuzamitide and ¹⁸F-florbetapir. Control subjects underwent ¹²⁴I-evuzamitide (n = 10) or ¹⁸F-florbetapir (n = 8) positron emission tomography/computed tomography. Left ventricular percent injected dose (LV% ID) was measured as mean activity concentration × myocardial volume/injected activity. High LV %ID was defined using Youden's index.

RESULTS:

In CMP participants, median age was 74 years and 92% were men. ¹²⁴I-evuzamitide LV %ID differed across groups: median AL-CMP 1.48 (IQR: 1.12-1.89), ATTRwt-CMP 2.12 (IQR: 1.66-2.47), and control subjects 0.00 (IQR: 0.00-0.01; overall P < 0.001). High LV %ID perfectly discriminated CMP from control subjects. Discrimination performance was similar for ¹⁸F-florbetapir LV %ID. Notably, for ATTRwt-CMP, LV %ID was higher with ¹²⁴I-evuzamitide than ¹⁸F-florbetapir (P = 0.002). ¹²⁴I-evuzamitide LV %ID was correlated with interventricular septum thickness (Spearman's ρ = 0.78) and LV global longitudinal strain (ρ = 0.54) from echocardiography, and with LV mass index (ρ = 0.82) and extracellular volume (ρ = 0.51) from cardiac magnetic resonance.

CONCLUSIONS:

¹²⁴I-evuzamitide demonstrates uptake by cardiac amyloid and accurately discriminates amyloid CMP from control subjects. In AL-CMP, discrimination performance is similar to ¹⁸F-florbetapir. In ATTRwt-CMP, performance may be better with ¹²⁴I-evuzamitide. Moderate-to-strong correlations of ¹²⁴I-evuzamitide uptake with cardiac structural and functional metrics suggest valid amyloid quantification. Hence, ¹²⁴I-evuzamitide is a promising novel radiotracer to detect and quantify cardiac amyloid.

Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis

Longitudinal PET/CT imaging with iodine ( ¹²⁴ I) evuzamitide reveals organ response to plasma cell immunotherapy in a patient with AL amyloidosis

Article

Author: Guthrie, Spencer ; Martin, Emily B ; Wall, Jonathan S ; Stuckey, Alan ; Raj, Renju ; Kennel, Stephen J ; Powell, Dustin ; Whittle, Bryan ; Lands, Ronald

News (Medical) associated with Iodine (124I) evuzamitide

30 May 2024

·www.globenewswire.com

Attralus Presents New Data on Its Pan-Amyloid Therapeutic and Diagnostic Candidates at the XIX International Symposium on Amyloidosis (ISA)

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

Phase 2Clinical ResultPhase 3Phase 1

06 Feb 2024

·www.globenewswire.com

Attralus Closes $56 Million Financing

- Proceeds intended to advance clinical pipeline of transformational pan-amyloid removal (PAR) therapeutic candidates- Financing led by Alpha Wave Global and also included Bristol Myers Squibb (BMY) SAN FRANCISCO, Feb. 06, 2024 (GLOBE NEWSWIRE) -- Attralus, Inc., a clinical-stage biopharmaceutical company developing transformative medicines to improve the lives of patients with systemic amyloidosis, today announced that it has closed a $56 million financing. The financing round was led by new investor Alpha Wave Ventures and also included Bristol Myers Squibb (BMY). Existing investors also participated including founding investor venBio Partners, Surveyor Capital (a Citadel company), Vivo Capital, Logos Capital and Sarissa Capital Management. “This financing by a world-class syndicate of investors with deep expertise and experience in the life sciences space reflects the recognition of the strong potential of our pipeline of innovative pan-amyloid removal (PAR) therapeutic candidates to bring a new treatment approach to patients with systemic amyloidosis with potential to reverse the disease pathology,” said Mark Timney, CEO of Attralus. “With this support, we plan to accelerate our clinical development strategy to advance our portfolio programs.” Attralus intends to use the proceeds from the financing to advance the Phase 1/2 development of Attralus’ lead PAR therapeutic product, AT-02, in ATTR and AL amyloidosis. The financing proceeds are also expected to support the clinical development of the pan-amyloid diagnostic imaging agent I-124-Evuzamitide (AT-01) and AT-05 as well as the preclinical development of PAR therapeutic candidates for the treatment of neurodegenerative diseases. “We are thrilled to support Attralus in its vision to build a leading Systemic Amyloidosis company and the company’s approach of targeting removal of existing amyloid deposits, going beyond current treatments that slow progression but do not remove amyloid from organs” said Chris Dimitropoulos, Managing Director of Healthcare Investments at Alpha Wave Global. “We look forward to supporting Attralus as it progresses its programs and Attralus looks towards its next phase of growth.” 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 I-124-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 an open label phase 1 / 2 clinical trial in ATTR and AL amyloidosis patients. About I-124-Evuzamitide, Pan-Amyloid Diagnostic (Also known as AT-01)I-124-Evuzamitide (iodine-124 Evuzamitide) 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, I-124-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 I-124-Evuzamitide. About AT-05, Pan-Amyloid DiagnosticAT-05, uses the same pan amyloid binding peptide as I-124 -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 Neurodegeneration ProgramAttralus is developing the next generation of therapies for neurodegenerative diseases by simultaneously targeting multiple proteinopathies. Patients suffering from neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Lewy Body diseases, often have multiple proteinopathies. The company’s research is aiming to capitalize on this by binding to multiple misfolded protein aggregates including Aβ, Tau, and α-Synuclein. Attralus’ pan-amyloid product candidates provide an opportunity for therapeutics that can simultaneously target multiple proteinopathies in individual patients unlike approved therapies that target a single proteinopathy. The company is also exploring a blood brain barrier shuttle to potentially improve brain penetration. 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 San Francisco. About Alpha Wave Alpha Wave is a global investment company with three main verticals: private equity, private credit, and public markets. It is led by Rick Gerson, Navroz Udwadia, and Ryan Khoury. Its flagship global private equity fund, Alpha Wave Ventures, aims to invest in best-in-class growth-stage companies and endeavors to be helpful long-term partners to the founders and management teams. Alpha Wave has offices in New York, Miami, London, Monaco, Madrid, Abu Dhabi, Tel Aviv, Bangalore, Jakarta, and Sydney. For more information, please visit www.alphawaveglobal.com. Forward-Looking StatementsThis press release contains forward-looking statements, including statements related to the efficacy, continued development, and potential of the Company’s product candidates. Words such as “developing,” “aiming,” “advance,” “will,” “potential,” “intends,” “expected,” “plan,” “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, MD FRCSCorporate Development(212) 489-4351kgorti@attralus.com

Phase 3Phase 1

07 Nov 2023

·www.globenewswire.com

Attralus Announces Publication of Two Studies Evaluating Iodine (124I) Evuzamitide (AT-01) using PET/CT in the Journal of American College of Cardiology (JACC CV Imaging)

124I-evuzamitide shown to be highly accurate for detection of cardiac amyloid across two independent investigator-initiated studies.124I-evuzamitide detects multiple types of systemic amyloidosis.124I-evuzamitide may be more sensitive than standard diagnostics, with cardiac uptake shown in ATTR patients who had negative 99mTc-PYP scans.Moderate-to-strong correlations were observed with 124I-evuzamitide uptake and structural and functional cardiac imaging measures, health related quality of life (HRQoL), and cardiac biomarkers. SAN FRANCISCO, Nov. 07, 2023 (GLOBE NEWSWIRE) -- Attralus, Inc., a clinical stage biopharmaceutical company developing transformative medicines to improve the lives of patients with systemic amyloidosis, today announced the publication of results from two Attralus-funded investigator-initiated studies of 124I-evuzamitide, the company’s investigational pan-amyloid radiotracer under development for the diagnosis and management of systemic amyloidosis. The manuscripts from Brigham and Women’s Hospital (BWH) and from the University of Tennessee Graduate School of Medicine were published in the Journal of American College of Cardiology – Cardiovascular Imaging (JACC CV Imaging). The manuscripts, entitled “Cardiac Amyloid Quantification Using 124I-Evuzamitide (124I-P5+14) Versus 18F-Florbetapir” and “Cardiac Amyloid Detection by PET/CT Imaging of Iodine (124I) Evuzamitide (124I-p5+14): A Phase 1/2 Study,” have been published online. These two manuscripts were also accompanied by an editorial entitled “Shining a Radiant Light on Cardiac Amyloidosis with Novel 124I-Evuzamitide PET Imaging.” All three articles can be found online here. The key data reported in the publications show PET/CT imaging of patients with diverse types of systemic amyloidosis with visually appreciable uptake in the heart with high sensitivity and other organs suspected of amyloid involvement and highlighted that 124I-evuzamitide imaging may detect cardiac amyloid prior to clinical manifestation. Furthermore, 124I-evuzamitide was shown to accurately discriminate amyloid cardiomyopathy (CMP) from controls. In patients with ATTRwt-CMP, performance may be better with 124I-evuzamitide, as evidenced by significantly higher uptake than 18F-florbetapir, and higher uptake than in AL patients aligning with literature that ATTR patients have a higher cardiac amyloid load. Moderate-to-strong correlations between 124I-evuzamitide uptake and cardiac structural and functional measures utilizing echocardiography and cardiac magnetic resonance imaging, health related quality of life (HRQoL) metrics, and cardiac biomarkers were observed. The results also support the potential of 124I-evuzamitide as a pan-amyloid imaging agent, with positive cardiac uptake also seen in AApoAIV, AApoA1 and ALys amyloidosis patients. Infusion of 124I-evuzamitide was generally safe and well tolerated in these studies. These studies suggest that 124I-evuzamitide is a promising novel radiotracer to detect and quantify cardiac amyloid in multiple types of amyloidosis. Furthermore, the authors from BWH study stated that the ability of 124I-evuzamitide to specifically bind to amyloid deposits is promising for the ongoing Phase I trial investigating a monoclonal antibody fusion protein incorporating a similar amyloid-binding peptide, which targets amyloid deposits to trigger their removal. “Cardiac amyloidosis is an underdiagnosed condition. Despite recent improvements, diagnosis continues to be a challenge. There is an unmet need for more sensitive and specific diagnostics” said Professor Sharmila Dorbala MD, MPH, Harvard Medical School, Cardiovascular Medicine, and lead author of the BWH study. “In our study, I-124 evuzamitide perfectly discriminated between healthy subjects and both AL and ATTR cardiac amyloidosis patients. In ATTR patients, myocardial uptake was significantly higher with I-124 evuzamitide than with F18-florbetapir, suggesting that diagnostic performance may be better with I-124 evuzamitide. Although not evaluated in this study, direct amyloid quantification with I-124 evuzamitide may be useful for diagnosis of early disease and for monitoring disease progression or response to treatment. We were particularly encouraged by the moderate to strong correlations between amyloid quantitation by I-124 evuzamitide and health-related quality of life metrics, cardiac biomarkers, and standard imaging measures of structure and function.” “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. “The iodine-124 evuzamitide radiotracer has the potential to be an invaluable tool to both detect early cardiac and extracardiac deposits and to quantify amyloid burden.” Summary of Published ResultsBWH studyThis pilot study enrolled 26 patients with systemic amyloidosis (12 AL, 12 ATTR and 2 other types) and 12 healthy volunteers (HVs). Eight additional HVs were included in the publication from a 18F-florbetapir study to compare the accuracy of 18F- florbetapir to 124I-evuzamitide. The BWH study is the first to systematically evaluate myocardial uptake of 124I-evuzamitide compared to standard imaging modalities, clinical metrics, and HRQoL parameters in a cohort of participants with amyloid CMP, and the first to compare it to 18F- florbetapir. The study evaluated the quantitative myocardial uptake of 124I-evuzamitide and measured correlations between 124I-evuzamitide and clinical markers of amyloid CMP. All patients received an IV infusion of 1 mCi of 124I-evuzamitide and images were acquired at 5 hours post injection. Quantitative uptake of 124I-evuzamitide perfectly discriminated all cases of known AL-CMP and ATTRwt-CMP from controls, using measures of left ventricular % injected dose (LV %ID), cardiac amyloid activity (CAA), and target to background ratio (TBR).When comparing radiotracers, 124I-evuzamitide consistently showed higher myocardial uptake in patients with ATTRwt amyloidosis, suggesting that it may perform better in these patients. The performance was similar to 18F- florbetapir in AL Amyloidosis.Furthermore, among AL and ATTRwt participants, 124I-evuzamitide LV %ID was moderately to strongly correlated with indirect metrics of amyloid burden, both structural and functional (interventricular septum thickness, LV mass index, MCF, GLS, ECV), assessed using standard echocardiographic and MRI techniques, suggesting valid amyloid burden quantitation.Cardiac uptake of 124I-evuzamitide strongly correlated with cardiac-related serum biomarkers (NT-proBNP and troponin), and moderately to strongly correlated with clinical and HRQoL measures, suggesting meaningfulness to patients. The results also include a case in which an ATTRwt patient showed positive cardiac uptake of 124I-evuzamitide, a negative 99mTc-PYP scan, with an amyloid positive cardiac biopsy, suggesting 124I-evuzamitide may be more sensitive than 99mTc-PYP.No cardiac uptake was observed in HVs. The results suggest that 124I-evuzamitide can accurately detect and quantify cardiac amyloid burden. With further validation, quantitative 124I-evuzamitide uptake may be particularly useful to diagnose early disease or to monitor disease progression or response to therapy in subjects with cardiac amyloidosis. UT studyThe first in human Phase 1/2 trial evaluated the ability of 124I-evuzamitide to detect amyloid deposits by PET/CT imaging in patients with diverse forms of systemic amyloidosis. The trial enrolled 50 systemic amyloidosis pts (23 AL, 20 ATTR and 7 other types) and 5 HVs. All patients received an IV infusion of <2 mg of 124I-evuzamitide (≤2 mCi of I-124) and images were acquired at ~5 hours post injection. Efficacy endpoints included patient- and organ-based sensitivity of 124I-evuzamitide uptake in the heart, liver, spleen, and kidney. Cardiac uptake of the radiotracer was observed in 100% of patients with ATTR in whom clinical evidence supported a diagnosis of amyloid CMP.Positive cardiac PET/CT imaging was observed in six patients with a diagnosis of ATTR amyloidosis but no clinical evidence of cardiac involvement, with negative 99mTc-PYP imaging and normal serum NTproBNP levels. At least one of these subjects had a confirmatory cardiac biopsy confirming ATTR amyloidosis in the heart.Of the major abdominothoracic organs, the sensitivity (positive percent agreement) between clinical findings and 124I-evuzamitide imaging was strongest for the heart (96.2%; 95% CI: 80.4-99.9; n=25/26). PET/CT imaging of 124I-evuzamitide in patients with ATTR and AL amyloidosis exhibited diverse anatomic uptake involving e.g., the lung, liver, kidney, pancreas, spheroid joints, spine, and abdominal fat, consistent with the systemic nature of these diseases, and with previously published autopsy findings. These data suggest that 124I-evuzamitide imaging can detect not only cardiac amyloidosis, but also extracardiac disease.No cardiac uptake was observed in HVs. The data from this first-in-human study supports the overall safety and efficacy of 124I-evuzamitide for detecting cardiac amyloidosis, as well as systemic amyloid deposits. 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. Systemic amyloidosis is significantly underdiagnosed due to low awareness, lack of specific symptoms, and no current disease-specific diagnostics. The two most common forms of systemic amyloidosis are immunoglobulin light-chain-associated (AL) amyloidosis and transthyretin-associated amyloidosis (ATTR). There is a significant unmet need for new therapies and diagnostics in systemic amyloidosis. About I-124-EVUZAMITIDE Pan-Amyloid Diagnostic (Also known as AT-01)I-124-EVUZAMITIDE (iodine-124 Evuzamitide) 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, I-124-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 obtained exclusive rights to commercialize I-124-EVUZAMITIDE under a commercial license agreement with the University of Tennessee Research Foundation. The same PAR-peptide technology is utilized in AT-02 and AT-04, two of the company’s therapeutic candidates. 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 the Company’s product candidates. Words such as “novel,” “developing,” “first and only,” “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, MD FRCSCorporate Development‍(212) 489-4351kgorti@attralus.com

Clinical ResultLicense out/inPhase 1

100 Deals associated with Iodine (124I) evuzamitide

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Indication	Highest Phase	Country/Location	Organization	Date
Amyloidosis, Hereditary, Transthyretin-Related	Phase 2	US	Attralus, Inc.Startup	08 Jul 2022
Transthyretin cardiac amyloidosis	Phase 2	US	Attralus, Inc.Startup	08 Jul 2022
Systemic amyloidosis	Phase 2	US	Attralus, Inc.Startup	30 Nov 2021

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ASH2023	Not Applicable	Immunoglobulin Light-Chain Amyloidosis First line	20	Evuzamitide (AL amyloidosis)	cmcpaqjunz(lmwrxgwjca) = fmgxppidtn lublrxzxhz (aiqnobinkw )	-	09 Dec 2023
NCT03678259 (Literature) Manual	Phase 1/2	Systemic amyloidosis	57	Iodine (124I) evuzamitide	cbqiksfxva(dexjkjdwuw) = circezziwr qekmwvgecc (oazgsrynpv, 82.8 - 97.8) View more	Positive	07 Nov 2023
NCT03678259 (ESC2020)	Phase 1	Senile cardiac amyloidosis	22	124I-p5+14 peptide	hobywafamb(kxhzhdalwh) = ayunpnwasv hmjjzferip (lxbuvjurdr )	-	29 Aug 2020

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