In the second presentation on nonclinical ophthalmology studies, Dr. Milton focuses primarily on in vivo gene therapies. Gene therapies for ocular diseases typically use AAVs delivered intravitreally or subretinally. Cell therapies can be encapsulated in a device for intravitreal implantation, but this approach has had limited success.

Key CMC considerations include dose concentration, low endotoxin levels, minimal empty capsids, minimal particulate matter, and ensuring the transgene is compatible with the viral vector delivery system. The FDA has published guidance for inherited retinal diseases that can also be applied to other ocular diseases. The overall non-clinical plan should be lean, follow the 3Rs guidelines, and avoid excessive caution.

Dr. Milton also presents a case study evaluating an AAV8 vector carrying the RLBP1 transgene, which highlights the key considerations for nonclinical studies.