Regulus have published their preclinical work on RGLS4326
for ADPKD in Nature. There’s no mention that I could see of the mouse tox that
led to the clinical hold. I was interested to note that RGLS4326 uses a mixture
of cEt, 2’-F and 2’O-Me modifications.
One interesting aspect is the preferential distribution of
RGLS4326 to the kidney (8 to 13x the exposure in liver) which I think is unusual
for an oligo. If they can figure out why, this would enable a unique kidney targeting
I’ve pasted the discussion section below and highlighted the
passage that affirms what got me interested in Regulus in the first place - the
potential to normalise gene expression in complex diseases.