Replies to post #192598 on Biotech Values

[DewDiligence]

AAVL—Another possibility re retinal thickness increasing is that the treatment isn't fully working and the condition is worsening, even if VA doesn't correlate with that deterioration. What makes you think it’s a safety issue, and to be clear, you're saying its a problem with the standard subretinal injection, not the vector/promoter is causing the increase, or bit or both, or something else?

The retinal-thickness data could be caused by any of the above factors or a combination. I’m not guessing what the cause is; rather, I’m saying AAVL needs to do more work so that they know the answer to these questions.

If subretinal problem,...how does that correlate with any other programs at AGTC/ONCE that are subretinal?

Good question. My inclination here is that each company’s subretinal program be evaluated on its own merits rather than inferring that subretinal injection per se is unworkable.

The Ph2b is that next trial, or you expect another one on top of Ph2b for some reason?

My view is that AVA-101 is not ready for a large phase-2b until AAVL better understands the phase-2a dataset, particularly with respect to retinal thickness. Whether AAVL will, in fact, proceed directly to phase-2b is a different question (hence my reference to Zebra’s Law as a likely driver of this decision).

…why you think 7.5-letter improvement on top of previous improvements from SOC is needed?

It’s an arbitrary figure, but I wanted to be quantitative to show the rough magnitude of the shortfall; 2.5 letters is clearly not enough, IMO.

Agree on the rescue-injection figures. Too many.

I should point out that this is more of a commercially relevant endpoint than a regulatory one. To my knowledge, no major regulatory body has approved a drug for a retinal disease based on a frequency-of-treatment primary endpoint. Regards, Dew

[GrthzGd]

Having verified safety, I wonder if AAVL will address retinal thickening and reducing the number of rescue injections in Phase IIb with dosage increases. Possibly more letter improvements also.