Rat: minimal to mild thymus and mesenteric lymph node depletion, not reversed after recovery
“Effects on thyroid gland (follicular call atrophy), thymus and mesenteric lymph node (minimal to mild depletion) did not resolve at the end of the recovery period in the 3-month study.”
“Notably, brain exposure was measurable (brain/plasma AUC ≈ 0.6), supporting blood–brain barrier penetration adequate for the treatment of paediatric low-grade gliomas. Tovorafenib also demonstrates a reversible affinity for melanin-rich tissues, including pigmented skin, the uveal tract or substantia nigra.”
Limited exposure margins: toxicities at or below clinical exposure
“The data suggest that, although the non-clinical findings are indicative of potential toxicities, the exposure margins relative to the proposed clinical doses are limited.”