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**DEN-181** is an investigational, antigen-specific tolerizing immunotherapy for anti-citrullinated protein antibody-positive rheumatoid arthritis. It is a subcutaneous liposomal fixed-dose product containing a type II collagen 259-273 self-peptide and calcitriol. The collagen peptide is intended to promote antigen-specific regulation of autoreactive T-cell responses, while calcitriol provides tolerogenic dendritic-cell conditioning through vitamin D receptor signaling and NF-kappa-B pathway suppression. In a randomized placebo-controlled Phase I study in HLA-DRB1*04:01- or *01:01-positive ACPA-positive rheumatoid arthritis patients receiving methotrexate, single-dose DEN-181 was generally well tolerated and produced exploratory antigen-specific immunomodulatory signals. ([anzctr.org.au](https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=373425))
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