- AT-02 demonstrates amyloid reduction from the heart, kidney, liver, and spleen
- AT-02 induces in vivo macrophage-mediated phagocytosis of amyloid fibrils
- AT-02 binds potently to multiple types of amyloid including ATTR, AL, and ALECT2
SAN FRANCISCO, Calif. – September 6, 2022 – Attralus, Inc., a clinical stage biopharmaceutical company developing transformative medicines to improve the lives of patients with systemic amyloidosis, today announced highly encouraging preclinical data for AT-02, the company’s lead pan-amyloid removal (PAR) therapeutic candidate. The data was included in an oral presentation at the 18th International Symposium on Amyloidosis (ISA) taking place September 4-8, 2022, in Heidelberg, Germany.
“There is a significant unmet need in systemic amyloidosis to remove deposited toxic amyloid fibrils,” said Professor Ashutosh Wechalekar, MBBS, MD, FRCP, FRCPath, DM, University College London. “The pan-amyloid removal data from AT-02 indicates that this molecule has the potential to be game changing. The reduction of cardiac amyloid deposits by 50% in a systemic amyloidosis progressive animal model is unprecedented. We look forward to upcoming human clinical trials to further evaluate this promising agent in this critical area currently lacking therapeutics.”
In in vitro studies, AT-02 was shown to have subnanomolar binding potency to ATTR and AL amyloid and to opsonize amyloid extracts promoting macrophage-mediated phagocytosis of the amyloid. In vivo preclinical data for AT-02 demonstrated significant reduction in amyloid in mouse models of human AL amyloidoma and systemic AA amyloidosis. Treatment of mice with progressive systemic AA amyloidosis with AT-02 decreased local cardiac amyloid by ~50% and significantly reduced renal and hepatic amyloid load and organ impairment.
“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 from patients which cause organ damage and mortality,” said Gregory Bell, MD, Chief Medical Officer at Attralus. “The in vivo preclinical data from AT-02 demonstrates the potential to remove existing tissue amyloid, in key organs. 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. We look forward to initiating clinical studies with AT-02.”
- The humanized IgG1-peptide fusion, AT-02, specifically binds to many types of amyloid, including ATTR and AL, with subnanomolar potency.
- Immunohistochemical analyses revealed specific reactivity with ATTR, AL, and ALECT2 amyloid deposits in heart, kidney, and spleen.
- AT-02 co-localized with cardiac amyloid deposits in a novel murine model of AL amyloidosis following intravenous administration.
- Binding of AT-02 to human amyloid extracts promoted phagocytosis of amyloid by activated human macrophage (THP-1) cells, which was further enhanced by complement.
- Pretreatment of human ALlamyloid extract with AT-02 significantly enhanced in vivo phagocytosis and clearance of amyloid in mice.
- Treatment of mice with progressive systemic AA amyloidosis with AT-02 decreased local cardiac amyloid by ~50% and significantly reduced renal and hepatic amyloid load and organ impairment.
“Systemic amyloidosis is a diverse group of rare diseases that in all cases present with a buildup of toxic amyloid within the body,” said Jonathan Wall, Ph.D., Distinguished Professor, University of Tennessee Graduate School of Medicine. “Early preclinical therapy studies indicate that AT-02 has the potential to remove tissue amyloid and reduce organ impairment.”
Oral Presentation Details
Abstract Title: Preclinical characterization of AT-02, a pan-amyloid-binding immunoglobulin-peptide fusion protein capable of inducing enhanced phagocytosis of amyloid
- 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: Scientific Session: Basic Research – New Treatment Targets and Biomarkers
- Date/Time: September 6, 2022, 10:30 a.m. – 12:05 p.m. CEST
For additional information, please visit the ISA 2022 website.
About AT-02 PAR Therapeutic
AT-02 is a fusion of our pan-amyloid removal (PAR) peptide technology with an IgG1 antibody. The proprietary peptide binds to all types of amyloid and delivers the antibody to the site of disease to stimulate the immune system to remove amyloid. A similar PAR-peptide technology is utilized inAT-01 (iodine (I-124) evuzamitide).
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.
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.
This press release contains forward-looking statements, including statements related to the efficacy, continued development, and potential of AT-02. Words such as “novel,” “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.