Tildrakizumab

Tildrakizumab (SCH 900222) is a humanized anti-IL-23 (p19 subunit) monoclonal antibody. IL-23 is a critical cytokine to maintain the Th17 cell phenotype. Tildrakizumab has high-affinity for single-chain IL-23 (Kd: 136 pM). Tildrakizumab is effective against moderate to severe plaque psoriasis.

Tildrakizumab inhibits IL-23-induced STAT3 signaling in HeLa cells expressed the human IL-23Rα and IL-12Rβ1 receptors, with an IC₅₀ of 23 pM^[2].
Tildrakizumab reduces IL-23’s affinity for IL-23Rα through a negative allosteric modulation^[2].

Tildrakizumab (100 mg/kg, s.c., every 2 weeks up to 9 months) is well tolerated in cynomolgus monkeys (toxicity studies)^[3].

References:
[1]. Papp K, et al. Tildrakizumab (MK-3222), an anti-interleukin-23p19 monoclonal antibody, improves psoriasis in a phase IIb randomized placebo-controlled trial. Br J Dermatol. 2015 Oct;173(4):930-9.
[2]. Zhou L, et al. A non-clinical comparative study of IL-23 antibodies in psoriasis. MAbs. 2021 Jan-Dec;13(1):1964420.
[3]. Santostefano M, et al. Nonclinical safety of tildrakizumab, a humanized anti-IL-23p19 monoclonal antibody, in nonhuman primates. Regul Toxicol Pharmacol. 2019 Nov;108:104476.