title: Turning mirror-image oligonucleotides into drugs: the evolution of Spiegelmer(®) therapeutics.
abstract: Spiegelmers are synthetic target-binding oligonucleotides built from non-natural l-nucleotides. Like aptamers, Spiegelmers fold into distinct shapes that bind the targets with high affinity and selectivity. Furthermore, the mirror-image configuration confers plasma stability and immunological passivity. Various Spiegelmers against pharmacologically attractive targets were shown to be efficacious in animal models. Three Spiegelmer candidates: emapticap pegol (NOX-E36; anti-CCL2), olaptesed pegol (NOX-A12; anti-CXCL12) and lexaptepid pegol (NOX-H94; anti-hepcidin), underwent regulatory safety studies, demonstrated good safety profiles in healthy volunteers and were taken into Phase IIa studies in patients. Proof-of-concept for emapticap pegol has recently been demonstrated in diabetic nephropathy patients. Furthermore, promising interim Phase IIa data of olaptesed pegol and lexapteptid pegol also suggest efficacy in the respective patient populations.
authors.affiliation: NOXXON Pharma AG, Max-Dohrn-Strasse 8-10, 10589 Berlin, Germany. Electronic address: avater@noxxon.com.
authors.forename: Axel
authors.initials: A
authors.lastname: Vater
authors.affiliation: NOXXON Pharma AG, Max-Dohrn-Strasse 8-10, 10589 Berlin, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Klussmann
mesh_terms: D000818:Animals; D052157:Aptamers, Nucleotide / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D016568:Drugs, Generic; D006801:Humans
chemical_list: D052157:Aptamers, Nucleotide; D016568:Drugs, Generic