Background

PRX012 is a humanized monoclonal IgG1 antibody to an N-terminal epitope on Aβ. The company reports a 70 picomolar affinity for Aβ fibrils, or about 10-fold greater binding avidity than aducanumab. The antibody is given by subcutaneous injection.

According to preclinical data presented at conferences, PRX012 binds plaque in mouse and human brain tissue preparations, and mediates microglial phagocytosis of Aβ1-42 fibrils from these tissues. It reportedly blocks binding of soluble Aβ oligomers to rat neurons (CTAD 2020 poster).

The antibody does not bind to synthetic pyroglutamate-modified Aβ42, yet it still promoted microglial clearance of this form from plaques in brain tissue (Aug 2021 conference news; AAIC 2021 poster; Tam et al., 2021).

At the April 2023 AD/PD conference in Gothenburg, additional preclinical data showed PRX012 bound Aβ protofibrils with 20-fold higher affinity than lecanemab, and cleared pyroglutamate-modified Aβ42 from brain tissue with three to eight times the potency of donanemab (April 2023 conference news; slides).

Findings

No trials are registered but, according to company information, PRX012 began a single-ascending-dose Phase 1 study in March 2022 (press release). Approximately 50 healthy controls and AD patients will receive a single subcutaneous injection at up to six dose levels, to determine safety, tolerability, immunogenicity, and pharmacokinetics. In April 2023, the company announced it was partnering with a U.S. national drug store chain to accelerate enrollment in an ongoing multiple-ascending-dose study (press release). In January 2024, the company claimed that amyloid reduction was seen following six months of treatment with 70 mg PRX012, with ARIA-E frequency similar to placebo (press release). Doses of up to 400 mg injected once a month are being tested. Top-line data is expected in 2024.

In April 2022, PRX012 received Fast Track designation from the U.S. FDA (press release).