Alzheimer's disease: illustration of the amyloid-beta 40 peptide (and others) accumulating to form amyloid fibrils that build up dense amyloid plaques.
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U.S. biopharma Attralus this week reported promising findings at a scientific meeting in Germany for its therapies targeting systemic amyloidosis, a diverse group of debilitating diseases involving the build-up of amyloid in vital organs.  

The findings, presented at this year’s International Symposium on Amyloidosis in Heidelberg, cover clinical and preclinical studies with several agents in the Californian company’s portfolio, including AT-01, AT-02, CAR-M and AT-04.

Attralus is developing novel pan-amyloid removal (PAR) therapeutics that bind to and remove the disease-causing amyloid and improve the diagnosis of systemic amyloidosis.

Clinical data showed that 124I-AT-01 (iodine evuzamitide), which is in development as a radiotracer for the diagnosis of systemic amyloidosis, could detect cardiac amyloidosis among people previously diagnosed with cardiac disease.

AT-01, which is most advanced in the company’s pipeline, had 100% sensitivity in those with ATTR amyloidosis, which is caused by abnormal versions of the blood protein transthyretin and 93% in those with AL amyloidosis, in which abnormal light-chain proteins gather in organs and tissue.

Organ-specific changes in amyloid load could also be visualized and quantified using AT-01, which is under a commercial license agreement with the University of Tennessee Research Foundation.

“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.

The same PAR-peptide technology in AT-01 is used in its therapeutic candidates AT-02, a fusion of this with an IgG1 antibody.  and AT-04, a fusion with the Fc component of an IgG1 antibody.

Pre-clinical findings revealed that amyloid reduction with AT-02 from the heart, kidney, liver, and spleen.

AT-02 induced in vivo macrophage-mediated phagocytosis of amyloid fibrils and bound potently to multiple types of amyloid including ATTR, AL, and ALECT2, a novel form of amyloidosis derived from leukocyte chemotactic factor.

AT-04 meanwhile showed potent binding and promoted phagocytosis in ATTR and AL amyloidosis. The investigational drug bound potently to Aβ, tau, and α–synuclein, which are common amyloid pathologies in disorders of the central nervous system such as Alzheimer’s disease.

In an oral presentation at the meeting, there were further positive preclinical findings with CAR-M, a proprietary peptide formed from a fusion of Attralus’s pan-amyloid reactive p5 peptide and human chimeric antigen receptor-macrophages.

The investigational agent binds to all types of amyloid and delivers the CAR-M to disease site to stimulate the immune system to remove amyloid, and could serve as an adjunct to anti-amyloid monoclonal antibodies for the enhanced clearance of tissue amyloid.

The presented results showed that human CAR-M cells could be generated with the pan-amyloid reactive p5 peptide as the target amyloid recognition element.

“We have seen the innovations in CAR-T and CAR-M approaches to the treatment of cancers. We were eager to see if the same concept could be used to promote phagocytosis of amyloid,” said Jonathan Wall, PhD, distinguished professor at the University of Tennessee Graduate School of Medicine.

“We are enthusiastic about our ability to leverage the PAR technology in new and innovative ways, in this case cell therapy.”

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