The present invention relates to polypeptides, particularly fusion protein variants comprising interleukin-37 (IL-37) and related therapeutics and compositions thereof. More particularly, the invention relates to fusion proteins comprising a mutant IL-37 polypeptide and an Fc region of an antibody. The biophysical stability such as thermal stability of said fusion proteins can be improved compared to a reference IL-37 construct, such as a wild-type IL-37 polypeptide or a mutant variant of an IL-37 polypeptide. It also relates to the fusion polypeptide variants and compositions for use in treating inflammatory diseases or conditions. In addition, the present invention relates to nucleic acid molecules encoding such fusion proteins, and vectors and host cells comprising such nucleic acid molecules.