Attralus Announces Presentation of Clinical Data for AT-01 (Iodine (I-124) Evuzamitide), a Novel Amyloid-Specific Imaging Agent, at the 18th International Symposium on Amyloidosis

• AT-01 is a first-in-class pan-amyloid imaging agent capable of detecting diverse types of systemic amyloidosis in multiple organs
• Sensitivity in those with previously diagnosed cardiac disease was 100% in ATTR and 93% in AL
• Organ-specific changes in amyloid load can be visualized and quantified using AT-01
• A pan-amyloid removal (PAR) peptide with technetium-99m kit (^99mTc-p5+14) for SPECT/CT imaging has the potential to be an easily accessible, highly effective, and amyloid specific agent for detecting cardiac amyloidosis

SAN FRANCISCO, Sept. 08, 2022 (GLOBE NEWSWIRE) -- Attralus Inc., a clinical stage biopharmaceutical company developing transformative medicines to improve the lives of patients with systemic amyloidosis, today announced multiple data presentations from the University of Tennessee Graduate School of Medicine for AT-01 (iodine (I-124) evuzamitide), the company’s pan-amyloid binding peptide in development as an amyloid-specific imaging agent for the diagnosis and management of all types of systemic amyloidosis. These data were included in oral and poster presentations at the 18th International Symposium on Amyloidosis (ISA) taking place September 4-8, 2022, in Heidelberg, Germany.

“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 Mat Maurer, MD, Arnold and Arlene Goldstein Professor of Cardiology, Professor of Medicine at Columbia University, College of Physicians and Surgeons and Director of The Cardiac Amyloidosis Program. “There is a significant unmet need for better diagnostics, and the development of an amyloidosis-specific imaging agent has the potential to transform the process for patients. The data from AT-01 are impressive and provide hope for using one imaging agent to detect amyloid deposits in multiple organs across distinct types of amyloidosis, the potential to detect amyloid earlier in the disease process and the ability to monitor organ specific disease progression or response.”

Presentations at ISA included data related to the pan-amyloid reactivity of AT-01, final results of the Phase1/2 study of AT-01, detection of extracardiac amyloid in ATTR patients by AT-01, quantitative monitoring of amyloid load following treatment, potential differentiation between ATTR versus AL by AT-01, and a kit method for radiolabeling the PAR peptide with technetium-99m for SPECT/CT imaging.

“AT-01 has the potential to become an essential tool not only to accelerate and streamline diagnosis, but also to provide a comprehensive assessment of disease burden and a means to monitor disease progression,” said Gregory Bell, MD, Chief Medical Officer at Attralus. “Today the diagnosis of amyloidosis is a long, complex process, and many patients with systemic amyloidosis remain undiagnosed. AT-01 has the potential to be the first and only non-invasive, pan-amyloid, whole body imaging diagnostic designed to detect all types of systemic amyloidosis across key organs.”

Pan-Amyloid Reactivity Highlights

• Uptake of AT-01 was observed in key abdominothoracic organs in patients with amyloidosis evaluated.
• AT-01 is a pattern recognition peptide that binds electronegative motifs, fibrils, and highly sulfated heparan sulfate glycosaminoglycans in amyloid deposits. Peptide binding does not require a fibril-specific neo-epitope.
• AT-01 can be used to visualize, by PET/CT imaging, many types of amyloidosis, including ATTR, AL, and ALECT2, in numerous abdominothoracic organs, including the heart and kidneys.

Imaging Study Highlights

• AT-01 was detected in one or more organs in >90% of patients with systemic amyloidosis, including uptake in the heart, kidney, liver, and spleen.
• The positive percent agreement between clinical evaluation and AT-01 imaging in the heart and kidneys was 96.2% (95% CI: 80.4–99.9; n=26) and 78.6% (95% CI: 49.2–95.3; n=14), respectively.
• The negative percent agreement, assessed in healthy subjects, for the heart and kidneys was 100% and 80%, respectively (n=5).
• Cardiac uptake of the radiotracer (SUVR mean) correlated significantly with serum NT-proBNP levels in patients with AL amyloidosis (rs= 0.48, p= 0.018, n=24).

Differentiation of ATTR versus AL Amyloid Highlights

• PET/CT imaging of patients with amyloidosis using AT-01 allows for quantitative detection of pathology in major abdominothoracic organs.
• Analysis of PET/CT images from patients enrolled in the study indicated that there was significantly less amyloid (AT-01 retention) in the liver, spleen, and kidney of patients with ATTR as compared to the AL cohort (p<0.005), resulting in significantly lower heart-to-organ ratios in AL patients.
• These data suggest that an ROC analysis could be used to identify a cut-off value for discriminating ATTR amyloidosis with some confidence, which might be enhanced by addition of other clinical biomarkers.

Quantitative Changes in Amyloid Load Highlights

• In a case study of a patient with systemic AL amyloidosis, PET/CT imaging with AT-01 indicated amyloid in the heart, spleen, liver, kidneys, pancreas, and bone marrow.
• The patient received ~2 mCi AT-01and PET/CT imaging in May 2019 with repeat imaging in April 2021.
• Concurrent with the ~24% decrease in hepatic amyloid, serum alkaline phosphatase decreased 40% (~200 IU/mL to ~120 IU/mL), which is considered a hepatic organ response per ISA criteria. This occurred in the context of a hematologic response and 40% decrease in serum kappa free light chains (FLC).
• Organ-specific changes in amyloid load can be visualized and quantified using AT-01 and may play a valuable role, not only in the diagnosis of amyloidosis, but also for monitoring changes in organ-specific amyloid load.

Detection of Extracardiac Amyloid in ATTR Highlights

• Uptake of AT-01 was observed in at least one anatomic site in 19 ATTR patients (sensitivity = 0.95;95% CI:0.77,1.00; n=20).
• Extracardiac uptake of AT-01 in ATTR amyloidosis patients was observed principally in the joints, including shoulders, spinal discs, and facets (11/20); thoracic and lumbar spine (6/20); kidney (9/20); and spleen (7/20).
• Uptake in other anatomic sites including the lung, liver, muscle, pancreas, adrenal glands, and pituitary gland was also observed in the PET/CT images.
• Using PET/CT imaging of AT-01, we have shown heterogeneous and often extensive ATTR amyloid deposits in numerous extracardiac sites, commonly the joints and spine.

Kit Method for ^99mTc Highlights

• ^99mTc-p5+14 detected hepatosplenic AA amyloid, the major sites of amyloid deposition in a murine model of the disease, as well as the scant deposits in the hearts of AA mice using ex vivo SPECT/CT imaging of isolated heart.
• Micro-autoradiography studies demonstrated that ^99mTc-p5+14 effectively and specifically bound human amyloid deposits in the liver with AL and in both AL-and ATTR-containing cardiac tissue sections.
• There was significantly more uptake of the ^99mTc-p5+14 tracer than ^99mTc-PYP in the mouse heart.
• This kit method for production of ^99mTc-p5+14 would provide a facile method for generating an easily accessible, highly effective, amyloid-binding radiotracer for the detection and diagnosis of cardiac amyloidosis using gamma scintigraphy or SPECT/CT imaging.

“Systemic amyloidosis is a multi-organ disorder with variable presentation rendering rapid and accurate diagnosis challenging,” said Jonathan Wall, Ph.D., Distinguished Professor, University of Tennessee Graduate School of Medicine. “AT-01 offers the potential to diagnose and differentiate as well as quantify amyloid burden and monitor the disease over time.”

Oral Presentation Details

Abstract Title: Pan-amyloid reactivity of radioiodinated peptide ¹²⁴I-AT-01 in patients with systemic amyloidosis demonstrated by PET/CT imaging

• Presented by: Emily Martin, Ph.D., Assistant Professor, University of Tennessee Graduate School of Medicine
• Session: 3. Scientific Session: Imaging in Amyloidosis
• Date/Time: September 5, 2022, 1:25 p.m. – 3:05 p.m. CEST

Abstract Title: Results of the first-in-human PET/CT imaging study of the amyloid-reactive peptide ¹²⁴I-AT-01(¹²⁴I-p5+14) for the detection of systemic amyloidosis

• Presented by: Jonathan Wall, Ph.D., Distinguished Professor and Director of the University of Tennessee Graduate School of Medicine’s Amyloidosis and Cancer Theranostics Program
• Session: 3. Scientific Session: Imaging in Amyloidosis
• Date/Time: September 5, 2022, 1:25 p.m. – 3:05 p.m. CEST

Poster Presentation Details

• Poster P169: Differentiation of ATTR amyloidosis based on abdominothoracic organ-specific uptake of ¹²⁴I-AT-01 (¹²⁴I-p5+14) assessed by PET/CT imaging
  • Presented by: R. Eric Heidel, Ph.D., Associate Professor, University of Tennessee Graduate School of Medicine
  • Date/Time: September 6, 2022, 12:05 p.m. – 1:15 p.m. CEST
• Poster P163: A kit method for direct radiolabeling the amyloid reactive peptide p5+14 with technetium-99m (^99mTc) for the detection of cardiac amyloidosis by SPECT/CT imaging
  • Presented by: Stephen J. Kennel, Ph.D., Professor, University of Tennessee Graduate School of Medicine
  • Date/Time: September 6, 2022, 12:05 p.m. – 1:15 p.m. CEST
• Poster P164: Quantitative changes in organ-specific amyloid load in a patient with AL amyloidosis, measured by ¹²⁴I-AT-01 PET/CT imaging, correlate with serum biomarkers
  • Presented by: Alan Stuckey, C.N.M.T., Research Director, University of Tennessee Graduate School of Medicine
  • Date/Time: September 6, 2022, 12:05 p.m. – 1:15 p.m. CEST
• Poster P170: Detection of extracardiac amyloid in patients with ATTR amyloidosis by PET/CT imaging using the amyloidophilic radiotracer ¹²⁴I-AT-01 (¹²⁴I-p5+14)
  • Presented by: Jonathan Wall, Ph.D., Distinguished Professor and Director of the University of Tennessee Graduate School of Medicine’s Amyloidosis and Cancer Theranostics Program
  • Date/Time: September 6, 2022, 12:05 p.m. – 1:15 p.m. CEST

For additional information, please visit the ISA 2022 website.

About AT-01 (iodine (I-124) evuzamitide) Pan-Amyloid Diagnostic

AT-01 (iodine (I-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, 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. The same pan-amyloid removal (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. 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 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,” “first-in-class,” “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:

Luke Heagle
Real Chemistry
(910) 619-5764
lheagle@realchemistry.com