Remaining challenges in developing a glaucoma neuroprotection drug • Standard of care constraints: Withdrawing IOP - lowering drops is unethical, so new therapies must demonstrate neuroprotection on top of existing treatments • Multifactorial disease: Glaucoma optic neuropathy involves multiple pathogenic pathways, often requiring a polymedicine approach. Combining dual mechanisms in a single therapy could address this complexity • Drug delivery challenges: Neuroprotection targets are mostly intracellular, making retinal ganglion cell delivery of small molecules difficult. Durability is critical, as frequent dosing is impractical; quarterly delivery is preferred over daily drops • Adherence and treatment burden: Less frequent dosing improves adherence, but achieving durable, effective concentrations in the retina remains a key challenge 12 Therapeutic innovation is needed to overcome these challenges — a therapy that can combine multiple mechanisms of action, target retinal ganglion cells directly, and provide long - term durability