**Author Listing - Lead/ Submitting Author (we will be communicating with this individual): Name, Institution, City and State where the work was done. Co-authors will be added in a separate section.**
Jonathan S. Wall, University of Tennessee Graduate School of Medicine, Knoxville, TN

**Main Body of the Abstract**
Background: Cell-mediated clearance of amyloid deposits is the most promising method for reversing pathology and improving organ function. Several opsonizing antibodies have been generated for AL or ATTR amyloidosis. However, in addition ot AL and ATTR, a pan-amyloid-reactive antibody could benefit patients with rare types of amyloidosis for which no treatments are being developed.  AT-02 is a humanized IgG1 fusion protein incorporating two amyloid-reactive peptides. Here we further characterize AT-02 in support of its clinical evaluation as an immunotherapeutic for systemic amyloidosis.
Methods:  The reactivity of AT-02 was characterized using ELISA. Amyloid targeting in vivo was assessed using the human AL amyloidoma mouse model and monitored by optical imaging. The stability of AT-02 in human serum was evaluated using a heparin-binding bioactivity assay. Lastly, AT-02 activity was tested in an rVl6WIL fibril elongation assay.
Results: The binding of AT-02 to amyloid in vitro is governed exclusively by the pan-amyloid peptide moieties. When injected into mice bearing a 20 mg human AL amyloidoma, AT-02 accumulated rapidly in the amyloid mass and remained visible in the lesion for at least 7 days post-injection (Fig. 1). AT-02 was found capable of inhibiting rVl6WIL fibril elongation in a dose-dependent manner, and the peptides retained bioactivity for at least 9 days when exposed to human serum at 37°C.
Conclusion:  AT-02 is a novel pan-amyloid reactive antibody capable of rapid amyloid targeting and prolonged retention in vivo. It has good serum stability characteristics and can inhibit fibril elongation, further supporting its clinical evaluation in patients.



**Author Listing - Lead/ Submitting Author (we will be communicating with this individual): Name, Institution, City and State where the work was done. Co-authors will be added in a separate section.**
Jonathan S. Wall, University of Tennessee Graduate School of Medicine, Knoxville, TN

**Main Body of the Abstract**
**Background:** Cell-mediated clearance of amyloid deposits is the most promising method for reversing pathology and improving organ function. Several opsonizing antibodies have been generated for AL or ATTR amyloidosis. However, in addition ot AL and ATTR, a pan-amyloid-reactive antibody could benefit patients with rare types of amyloidosis for which no treatments are being developed.  AT-02 is a humanized IgG1 fusion protein incorporating two amyloid-reactive peptides. Here we further characterize AT-02 in support of its clinical evaluation as an immunotherapeutic for systemic amyloidosis.
**Methods:**  The reactivity of AT-02 was characterized using ELISA. Amyloid targeting _in vivo_ was assessed using the human AL amyloidoma mouse model and monitored by optical imaging. The stability of AT-02 in human serum was evaluated using a heparin-binding bioactivity assay. Lastly, AT-02 activity was tested in an rVl6WIL fibril elongation assay.
**Results**: The binding of AT-02 to amyloid _in vitro_ is governed exclusively by the pan-amyloid peptide moieties. When injected into mice bearing a 20 mg human AL amyloidoma, AT-02 accumulated rapidly in the amyloid mass and remained visible in the lesion for at least 7 days post-injection (Fig. 1). AT-02 was found capable of inhibiting rVl6WIL fibril elongation in a dose-dependent manner, and the peptides retained bioactivity for at least 9 days when exposed to human serum at 37°C.
**Conclusion:**  AT-02 is a novel pan-amyloid reactive antibody capable of rapid amyloid targeting and prolonged retention _in vivo_. It has good serum stability characteristics and can inhibit fibril elongation, further supporting its clinical evaluation in patients.



Characterization of the Peptide-Antibody Fusion, AT-02 – Studies to Support its Use as an Immunotherapy in Patients with Amyloidosis OA6 (#253)

We invite you to attend the XIX International Symposium on Amyloidosis to be held in Rochester, MN.

This symposium is organized as a hybrid meeting (with the focus on in-person) held from Sunday, May 26 through Thursday, May 30, 2024.

Together with the ISA Board and members of Mayo Clinic, a very attractive scientific hybrid program is being planned. The program will cover a variety of types of systemic amyloidosis: ATTR (hereditary and wild-type), AL (light-chain), AA and less frequent forms. There will be key lectures, specific symposia including those company sponsored, oral presentations and poster sessions of accepted abstracts.

COURSE DESCRIPTION
This program will provide a comprehensive review of state-of-the-art education in systemic amyloidosis: basic science, pathophysiology, diagnosis, current and emerging treatments. Scientific presentations will include competitive oral and poster abstracts. The rapid evolution of scientific discovery and expanding treatment options has created tremendous interest in the field and this meeting will fill and important gap in educating scientists and clinicians.