Tunable pH releasable linkers for intravitreal uses Highly Confidential 17 X CP2 Linker Drug CO 2 X Drug CO 2 CP2 X CP2 Linker Drug X Drug Class 1: Cyclization - Release Class 2: Eliminative Release CP2 • Neutral - pH self - immolative linker for IVT ‒ The vitreal environment has near - neutral pH and low enzyme levels; therefore, we deploy neutral - pH – responsive self - immolative linkers. • Release - rate control - SAR demonstrates broad tunability of the linker release half - life (t ₁ / ₂ ) via: 1. Electronic effects: introducing electron - withdrawing or electron - donating groups to shift local pK ₐ and modulate fragmentation. 2. Sterics : using differently hindered groups to accelerate or slow the self - immolation cascade. • Dosing objective ‒ Kinetics can be engineered to support the desired injection interval • Payload specific ‒ The linkers are selected for NLRP3 inhibitors and IOP - lowering agents