75 microgram remains quite a significant increase when we...

75 microgram remains quite a significant increase when we consider the trial was originally approved for the following;
low = 3 microgram,
mid = 10 microgram
high = 30 microgram

Yes, Rohan described the potential 75 microgram dose as a “very high” dose.

Compare these doses with those used by ProQR in their studies in Leber congenital amaurosis (LCA).

When ProQR initially planned their Phase 1 trial, they were going to test 3 dose levels of sepofarsen– a low dose of 160/80 micrograms (loading followed by maintenance dose), a medium dose of 320/160 and a high dose of 500/270. Ultimately they seem to have run with just the “low’ and “medium doses”.

Of the 5 patients who received the medium dose of 320/160 micrograms, all developed cataracts in the treated eye, 4 were considered to have serious adverse events and one developed macular edema. In the low dose group of 160/80 micrograms, 2 of 5 patients had serious adverse events.

A decision was made to discontinue the 320/160 microgram dose.

It was planned to use the 160/80 microgram dose in the pivotal Phase 2/3 trial, although a second arm dosed at 80/40 micrograms was ultimately included.

Neither the 80/40 nor 160/80 microgram doses demonstrated efficacy better than placebo in the pivotal trial. While Pro QR deemed sepofarsen to be “generally well tolerated” in the pivotal trial, they still reported observation of cataracts, cystoid macular edema and retinal thinning.

https://www.nature.com/articles/s41591-022-01755-w

https://www.proqr.com/press-release...-trial-of-sepofarsen-in-cep290-mediated-lca10