AHR antagonism with KYN-101

A novel AHR antagonist, KYN-101 that is potent and selective inhibitor has been developed by Ikena Oncology, formerly known as Kyn Therapeutics. KYN-101 has an IC₅₀ of 22 nM in the human HepG2 DRE-luciferase reporter assay and 23 nM in the murine Hepa1 Cyp-luc assay. For efficacy studies with B16-F10 melanoma model, C57Bl/6 female mice were inoculated intradermally in the hind flank with B16^IDO tumor cells at 2 × 10⁵ cells/mouse in a 50 μL injection volume. Seven days after cell inoculation, animals were randomized into 4 groups. Animals were dosed with vehicle, KYN-101, anti-PD1, or a combination of anti-PD1 and KYN-101. KYN-101 (10 mg/kg) and vehicle control (0.5% MC) were administered PO daily (QD) for a total of 12 doses. Anti-PD1 (250 μg/mouse) and Rat IgG control (in 1X PBS) were administered IP Q3D for a total of 4 doses. Tumor and body weight measurements were taken three times per week. Tumor volumes were calculated, percent inhibition of tumor growth and survival with KYN-101 as a single agent or in combination with anti-PD1 compared to vehicle control were determined. For the CT26 colorectal cancer model, Balb/C female mice were inoculated subcutaneously in the hind flank with CT26 tumor cells at 5 × 10⁵ cells/mouse in a 100 μL injection volume. Four days after cell inoculation, animals were randomized into 4 groups based on body weight. Animals were dosed with vehicle, KYN-101, anti-PD1, or a combination of anti-PD1 and KYN-101. KYN-101 (3 or 10 mg/kg) and vehicle control (0.5% MC) were administered PO daily (QD). Anti-PD1 (10 mg/kg) and Rat IgG control (in 1X PBS) were administered IP BIW for a total of 5 doses. Tumor and body weight measurements were taken three times per week. Tumor volumes were calculated and percent inhibition of tumor growth with KYN-101 as a single agent or in combination with anti-PD1 compared to vehicle control were determined.