Biodistribution : Several literature reports indicate that LNP-formulated RNAs can distribute rather nonspecifically to several organs such as spleen, heart, kidney, lung and brain. In line with this, results from the newly transmitted study 185350, indicate a broader biodistribution pattern with low and measurable radioactivity in the ovaries and testes. Given the current absence of toxicity in the DART data, the absence of toxicological findings in gonads in the repeat-dose studies and that the radioactivity in the gonads were low (below 0,1% of total dose), the current data does not indicate it to be a safety concern. The relative high dose used in the rats (500x margin to human dose based on weight) also supports a low risk from distribution to the gonads in humans.

Concentrations of mRNA-1647 were quantifiable in the majority of tissues examined at the first time point collected (2 hours post-dose) and peak concentrations were reached between 2- and 24-hours post-dose in tissues with exposures above that of plasma. Besides injection site [muscle] and lymph nodes [proximal and distal], increased mRNA concentrations (compared to plasma levels) were found in the spleen and eye. Both tissues were examined in the frame of the toxicological studies conducted with mRNA-1273 final vaccine formulation. Low levels of mRNA could be detected in all examined tissues except the kidney. This included heart, lung, testis and also brain tissues, indicating that the mRNA/LNP platform crossed the blood/brain barrier, although to very low levels (2-4% of the plasma level). Liver distribution of mRNA-1647 is also evident in this study, consistent with the literature reports that liver is a common target organ of LNPs