Approval Path Set: SOL-1 Stands Alone – and SOL-R is Now Playing Offense

Research evidence excerpt

Approval Path Set: SOL-1 Stands Alone – and SOL-R is Now Playing Offense

a single Phase 3 superiority trial evaluating Q12M Axpaxli

vs sham in NPDR (dosed at randomization and Week 48), with an ordinal ≥2-step diabetic

retinopathy severity score (DRSS) primary endpoint assessed at Week 56. This simplifies

the diabetic retinopathy strategy and aligns with mgmt’s market research indicating retina

specialists strongly prefer a once-yearly regimen in DR. Mgmt cited four rationales for the

streamlining the program: (1) strong SOL-1 and HELIOS-1 results; (2) SOL-1 demonstrating

durability up to 12 months; (3) Q12M as the preferred regimen in DR per physician market

research; (4) HELIOS-3 supporting global regulatory objectives (uses sham comparator

instead of ranibizumab 0.3 mg, which isn’t approved globally). The shift away from the second

ranibizumab-comparator study (HELIOS-2, which had an SPA but had not yet initiated) should

reduce development complexity while preserving the potential for a broad DR label, including

non-center-involved DME. OCUL does plan to initiate HELIOS-2 at some point and could

occur after HELIOS-3 has completed enrollment (our view). Mgmt indicated HELIOS-3 is

seeing strong demand for patient enrollment.

• Commercial positioning and labeling strategy are well-advanced. The Investor Day

provided meaningful color on OCUL's commercial readiness and the potential label profile

for Axpaxli. Mgmt highlighted that Axpaxli’s potential superiority label positions it in "a class

of one" relative to current therapies, all of which were approved on non-inferiority designs.

The commercial team framed the $15B global branded anti-VEGF market as one defined

by marginal durability improvements: Vabysmo generated ~$4.4B in WW revenue within