Ocular Therapeutix (OCUL) Corporate presentation summary

Regulatory framework for single trial approval

• FDA Modernization Act of 1997 and subsequent guidance allow approval based on one adequate and well-controlled trial plus confirmatory evidence.

• Recent FDA guidance clarifies the substantial evidence standard can be met with a single pivotal trial and supporting data.

• Special Protocol Assessment (SPA) agreements ensure trial design and endpoints are pre-approved by FDA, supporting regulatory acceptance.

Prevalence and acceptance of single trial approvals

• Single trial approvals are increasingly common, with over 40% of recent non-orphan CDER approvals based on a single pivotal trial.

• Majority of recent CDER approvals for novel drugs in 2024 and 2025 relied on a single pivotal trial.

Evidentiary standards and trial design

• Adequate and well-controlled trials must align with FDA protocols and meet regulatory definitions under 21 CFR § 314.

• SPA agreements confirm FDA concurrence on critical trial elements, increasing the likelihood of approval if endpoints are met.

• FDA Division of Ophthalmology considers p-values ≤ 0.001 as highly supportive for single trial approval.