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

• ¹²⁴I-evuzamitide proven to be extremely correct for detection of cardiac amyloid throughout two unbiased investigator-initiated research.

• ¹²⁴I-evuzamitide detects multiple kinds of systemic amyloidosis.

  

• ¹²⁴I-evuzamitide could also be extra delicate than customary diagnostics, with cardiac uptake proven in ATTR sufferers who had unfavorable ^99mTc-PYP scans.

• Moderate-to-strong correlations have been noticed with ¹²⁴I-evuzamitide uptake and structural and practical cardiac imaging measures, well being associated high quality of life (HRQoL), and cardiac biomarkers.

SAN FRANCISCO, Nov. 07, 2023 (GLOBE NEWSWIRE) — Attralus, Inc., a scientific stage biopharmaceutical firm growing transformative medicines to enhance the lives of sufferers with systemic amyloidosis, at the moment introduced the publication of outcomes from two Attralus-funded investigator-initiated research of ¹²⁴I-evuzamitide, the corporate’s investigational pan-amyloid radiotracer underneath improvement for the prognosis and administration of systemic amyloidosis. The manuscripts from Brigham and Women’s Hospital (BWH) and from the University of Tennessee Graduate School of Medicine have been printed within 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 printed on-line. These two manuscripts have been additionally accompanied by an editorial entitled “Shining a Radiant Light on Cardiac Amyloidosis with Novel ¹²⁴I-Evuzamitide PET Imaging.” All three articles could be discovered on-line here.

The key knowledge reported within the publications present PET/CT imaging of sufferers with numerous kinds of systemic amyloidosis with visually considerable uptake within the coronary heart with excessive sensitivity and different organs suspected of amyloid involvement and highlighted that ¹²⁴I-evuzamitide imaging could detect cardiac amyloid previous to scientific manifestation.

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Furthermore, ¹²⁴I-evuzamitide was proven to precisely discriminate amyloid cardiomyopathy (CMP) from controls. In sufferers with ATTRwt-CMP, efficiency could also be higher with ¹²⁴I-evuzamitide, as evidenced by considerably increased uptake than ¹⁸F-florbetapir, and better uptake than in AL sufferers aligning with literature that ATTR sufferers have the next cardiac amyloid load. Moderate-to-strong correlations between ¹²⁴I-evuzamitide uptake and cardiac structural and practical measures using echocardiography and cardiac magnetic resonance imaging, well being associated high quality of life (HRQoL) metrics, and cardiac biomarkers have been noticed. The outcomes additionally assist the potential of ¹²⁴I-evuzamitide as a pan-amyloid imaging agent, with constructive cardiac uptake additionally seen in AApoAIV, AApoA1 and ALys amyloidosis sufferers. Infusion of ¹²⁴I-evuzamitide was usually secure and properly tolerated in these research.

These research counsel that ¹²⁴I-evuzamitide is a promising novel radiotracer to detect and quantify cardiac amyloid in a number of kinds of amyloidosis. Furthermore, the authors from BWH examine acknowledged that the power of ¹²⁴I-evuzamitide to particularly bind to amyloid deposits is promising for the continuing Phase I trial investigating a monoclonal antibody fusion protein incorporating an identical amyloid-binding peptide, which targets amyloid deposits to set off their removing.

“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” mentioned Professor Sharmila Dorbala MD, MPH, Harvard Medical School, Cardiovascular Medicine, and lead writer of the BWH examine. “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,” mentioned 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 Results
BWH examine
This pilot examine enrolled 26 sufferers with systemic amyloidosis (12 AL, 12 ATTR and a couple of different sorts) and 12 wholesome volunteers (HVs). Eight extra HVs have been included within the publication from a ¹⁸F-florbetapir examine to match the accuracy of ¹⁸F- florbetapir to ¹²⁴I-evuzamitide. The BWH examine is the primary to systematically consider myocardial uptake of ¹²⁴I-evuzamitide in comparison with customary imaging modalities, scientific metrics, and HRQoL parameters in a cohort of individuals with amyloid CMP, and the primary to match it to ¹⁸F- florbetapir. The examine evaluated the quantitative myocardial uptake of ¹²⁴I-evuzamitide and measured correlations between ¹²⁴I-evuzamitide and scientific markers of amyloid CMP. All sufferers acquired an IV infusion of 1 mCi of ¹²⁴I-evuzamitide and pictures have been acquired at 5 hours put up injection.

• Quantitative uptake of ¹²⁴I-evuzamitide completely discriminated all instances of recognized AL-CMP and ATTRwt-CMP from controls, utilizing measures of left ventricular % injected dose (LV %ID), cardiac amyloid exercise (CAA), and goal to background ratio (TBR).

• When evaluating radiotracers, ¹²⁴I-evuzamitide constantly confirmed increased myocardial uptake in sufferers with ATTRwt amyloidosis, suggesting that it might carry out higher in these sufferers. The efficiency was much like ¹⁸F- florbetapir in AL Amyloidosis.

• Furthermore, amongst AL and ATTRwt individuals, ¹²⁴I-evuzamitide LV %ID was reasonably to strongly correlated with oblique metrics of amyloid burden, each structural and practical (interventricular septum thickness, LV mass index, MCF, GLS, ECV), assessed utilizing customary echocardiographic and MRI strategies, suggesting legitimate amyloid burden quantitation.

• Cardiac uptake of ¹²⁴I-evuzamitide strongly correlated with cardiac-related serum biomarkers (NT-proBNP and troponin), and reasonably to strongly correlated with scientific and HRQoL measures, suggesting meaningfulness to sufferers.

• The outcomes additionally embody a case through which an ATTRwt affected person confirmed constructive cardiac uptake of ¹²⁴I-evuzamitide, a unfavorable ^99mTc-PYP scan, with an amyloid constructive cardiac biopsy, suggesting ¹²⁴I-evuzamitide could also be extra delicate than ^99mTc-PYP.

• No cardiac uptake was noticed in HVs.

The outcomes counsel that ¹²⁴I-evuzamitide can precisely detect and quantify cardiac amyloid burden. With additional validation, quantitative ¹²⁴I-evuzamitide uptake could also be significantly helpful to diagnose early illness or to watch illness development or response to remedy in topics with cardiac amyloidosis.

UT examine
The first in human Phase 1/2 trial evaluated the power of ¹²⁴I-evuzamitide to detect amyloid deposits by PET/CT imaging in sufferers with numerous types of systemic amyloidosis. The trial enrolled 50 systemic amyloidosis pts (23 AL, 20 ATTR and seven different sorts) and 5 HVs. All sufferers acquired an IV infusion of <2 mg of ¹²⁴I-evuzamitide (≤2 mCi of I-124) and pictures have been acquired at ~5 hours put up injection. Efficacy endpoints included patient- and organ-based sensitivity of ¹²⁴I-evuzamitide uptake within the coronary heart, liver, spleen, and kidney.

• Cardiac uptake of the radiotracer was noticed in 100% of sufferers with ATTR in whom scientific proof supported a prognosis of amyloid CMP.

• Positive cardiac PET/CT imaging was noticed in six sufferers with a prognosis of ATTR amyloidosis however no scientific proof of cardiac involvement, with unfavorable ^99mTc-PYP imaging and regular serum NTproBNP ranges. At least one among these topics had a confirmatory cardiac biopsy confirming ATTR amyloidosis within the coronary heart.

• Of the foremost abdominothoracic organs, the sensitivity (constructive % settlement) between scientific findings and ¹²⁴I-evuzamitide imaging was strongest for the center (96.2%; 95% CI: 80.4-99.9; n=25/26). PET/CT imaging of ¹²⁴I-evuzamitide in sufferers with ATTR and AL amyloidosis exhibited numerous anatomic uptake involving e.g., the lung, liver, kidney, pancreas, spheroid joints, backbone, and belly fats, in step with the systemic nature of those illnesses, and with beforehand printed post-mortem findings. These knowledge counsel that ¹²⁴I-evuzamitide imaging can detect not solely cardiac amyloidosis, but in addition extracardiac illness.

• No cardiac uptake was noticed in HVs.

The knowledge from this first-in-human examine helps the general security and efficacy of ¹²⁴I-evuzamitide for detecting cardiac amyloidosis, in addition to systemic amyloid deposits.

About Systemic Amyloidosis 
Systemic amyloidosis encompasses a various group of uncommon illnesses that happen on account of accumulation of poisonous amyloid deposits in tissues and organs, a consequence of aberrant protein misfolding occasions. These illnesses are progressive, debilitating and sometimes deadly. Systemic amyloidosis is considerably underdiagnosed on account of low consciousness, lack of particular signs, and no present disease-specific diagnostics. The two most typical types of systemic amyloidosis are immunoglobulin light-chain-associated (AL) amyloidosis and transthyretin-associated amyloidosis (ATTR). There is a major unmet want for brand spanking new therapies and diagnostics in systemic amyloidosis.

About I-124-EVUZAMITIDE Pan-Amyloid Diagnostic (Also often known as AT-01)
I-124-EVUZAMITIDE (iodine-124 Evuzamitide) makes use of the corporate’s pan-amyloid binding peptide as an amyloid-specific imaging agent to picture all kinds of systemic amyloidosis by PET/CT imaging. In preliminary scientific trials, I-124-EVUZAMITIDE has been proven to detect a number of kinds of amyloid deposits, together with AL and ATTR, in main organs resembling the center, kidney, liver and spleen. Attralus obtained unique rights to commercialize I-124-EVUZAMITIDE underneath a business license settlement with the University of Tennessee Research Foundation. The similar PAR-peptide expertise is utilized in AT-02 and AT-04, two of the corporate’s therapeutic candidates.

About Attralus  
Attralus is a scientific stage biopharmaceutical firm targeted on creating transformative medicines to enhance the lives of sufferers with systemic amyloidosis. The firm’s proprietary pan-amyloid removing (PAR) therapeutics are designed to instantly bind to and take away poisonous amyloid in organs and tissues. By focusing on the common disease-causing pathology in systemic amyloidosis illnesses, PAR therapeutics have the potential to deal with and reverse illness in sufferers with all sorts and levels of systemic amyloidosis. Attralus was based by scientific consultants within the area of amyloidosis and the corporate is headquartered in San Francisco.

Forward-Looking Statements 
This press launch incorporates forward-looking statements, together with statements associated to the efficacy, continued improvement, and potential of the Company’s product candidates. Words resembling “novel,” “developing,” “first and only,” “potential,” “shown” and comparable expressions are meant to establish forward-looking statements. These forward-looking statements are based mostly upon Attralus’ present expectations. Forward-looking statements contain dangers and uncertainties. Attralus’ precise outcomes and the timing of occasions might differ materially from these anticipated in such forward-looking statements on account of these dangers and uncertainties. Attralus expressly disclaims any obligation or endeavor to launch publicly any updates or revisions to any forward-looking statements contained herein to replicate any change in Attralus’ expectations with regard thereto or any change in occasions, situations, or circumstances on which any such statements are based mostly.

Contact:
Krishna Gorti, MD FRCS
Corporate Development
‍(212) 489-4351
[email protected]