- AT-04 demonstrates potent binding and promotes phagocytosis in ATTR and AL amyloidosis
- AT-04 binds potently to Aβ, tau, and α–synuclein, common amyloid pathologies in CNS disorders such as Alzheimer’s
SAN FRANCISCO, Calif. – September 7, 2022 – Attralus, Inc., a clinical stage biopharmaceutical company developing transformative medicines to improve the lives of patients with systemic amyloidosis, today announced encouraging preclinical data for AT-04, one of the Company’s pan-amyloid removal therapeutic candidates. The data was included in a poster presentation at the 18th International Symposium on Amyloidosis (ISA) taking place September 4-8, 2022, in Heidelberg, Germany.
AT-04, a peptibody, is a fusion of the Company’s pan-amyloid removal (PAR) peptide technology with the Fc component of an IgG1 antibody. This is based on the same pan-amyloid peptide technology as is utilized in AT-01 (iodine (I-124) evuzamitide), the Company’s diagnostic imaging agent currently preparing to enter Phase 3 trials. The latest preclinical data for AT-04 demonstrate potent binding to multiple types of systemic amyloid, as well as Aβ, tau, and α-synuclein aggregates, amyloid pathologies common in neurodegenerative disorders. This binding of AT-04 to amyloid can induce phagocytosis, which is anticipated to lead to clearance of amyloid from the body. While most therapies in development for neurodegenerative amyloid pathologies target individual forms of amyloid, such as Aβ, tau or α-synuclein, AT-04 could potentially target all forms of amyloid in each patient.
“We are encouraged to see that AT-04, much like AT-01 and AT-02, potently binds to all types of amyloid, including Aβ, tau, and α-synuclein, amyloid common to neurodegenerative disorders such as Alzheimer’s,” said Gregory Bell, MD, Chief Medical Officer at Attralus. “We are excited to further explore the potential of AT-04 in CNS disorders.”
- The humanized peptibody, AT-04, specifically binds systemic and cerebral amyloid with high potency.
- The potency of AT-04 binding (EC50) to AL amyloid-like fibrils and human AL and ATTR amyloid extracts ranged between 0.5 –1.8 nM.
- Binding to fibrillar aggregates of Aβ, tau, and α-synuclein was saturable and similarly potent (0.5 –7 nM EC50).
- Pan-amyloid reactivity of AT-04 was further demonstrated immunohistochemically with specific binding to AL amyloid in the heart, liver, and kidney, cardiac ATTR amyloid, as well as perivascular and core Aβ plaques in the brain from a patient with Alzheimer’s disease.
- Phagocytosis of AL amyloid-like fibrils, AL and ATTR extracts by activated human THP-1 cells was significantly enhanced by AT-04 in a dose-dependent manner as compared to a control IgG.
- Phagocytosis was further significantly enhanced in the presence of 20% human serum as a source of complement.
- When injected IV into mice with systemic AA amyloidosis, 125I-AT-04 accumulated rapidly in hepatosplenic (10-20% ID/g), renal (5-10% ID/g) and cardiac (~4%ID/g) amyloid deposits within 1 h post injection.
- Specific localization 124I-AT-04 with amyloid was confirmed by microautoradiography.
- AT-04 could serve as a potent opsonin to facilitate the macrophage-mediated phagocytosis of amyloid.
“While AT-04 is based on our PAR-peptide technology, it is unique in its small molecular size. When compared to monoclonal antibodies currently in development for Alzheimer’s disease, it is considerably smaller,” said Jonathan Wall, Ph.D., Distinguished Professor, University of Tennessee Graduate School of Medicine. “When we consider both its smaller size and its potent binding to amyloid within the brain, AT-04 may be a compelling candidate for CNS diseases.”
Poster Presentation Details
Poster P282: Preclinical characterization of AT-04, a pan-amyloid-binding Fc domain-peptide fusion, to serve as an opsonin for macrophage-mediated clearance of amyloid deposits
- Presented by: Steve Foster, M.S., Research Associate, University of Tennessee Graduate School of Medicine
- Date/Time: September 7, 2022, 12:05 p.m. – 1:20 p.m. CEST
For additional information, please visit the ISA 2022 website.
About AT-04 PAR Therapeutic
AT-04 is a fusion of our pan-amyloid removal (PAR) peptide technology with the Fc component of an IgG1 antibody. The PAR-peptide mediates binding to all types of amyloid and the Fc stimulates the immune system to remove amyloid. The same PAR-peptide technology is utilized in AT-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-04. Words such as “developing,” “first and only,” “potential,” “unique,” “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.