EyePoint's Q3 2025: Contradictions Emerge on DME Trial Endpoints, Enrollment Timing, and Design

Business Commentary:

• Clinical Program Progress and Market Positioning:
• EyePoint Pharmaceuticals completed enrollment of the LUCIA trial, the second Phase III trial for DURAVYU in wet AMD in July, and both trials were enrolled in just 7 months.
• Top line data for DURAVYU in wet AMD is expected in mid-2026, positioning it as the first to file and potentially the first to market among all current investigational sustained delivery programs.

• The company's focus on reducing treatment burden and its differentiated multi-target MOA with DURAVYU are expected to address unmet needs in wet AMD and DME markets.

• Financial Strength and Operational Cash Runway:

• EyePoint ended September 2025 with over $200 million in cash and equivalents and closed a $172 million follow-on offering in October, extending its cash runway into Q4 2027.

• The strong financial position supports the company's Phase III wet AMD data anticipated in 2026 and the advancement of the Phase III DME program.

• DURAVYU's Multi-Target MOA and Innovation Potential:

• Preclinical data shows that DURAVYU's active drug, vorolanib, inhibits both VEGF-mediated vascular permeability and interleukin-6-mediated inflammation, offering a unique multi-target MOA.

• This multi-mechanism of action has the potential to be particularly effective in treating multifactorial diseases such as wet AMD and DME, supporting EyePoint's confidence in its clinical programs.

• Phase III DME Program and Market Access Strategy:

• EyePoint's Phase III DME program, consisting of two non-inferiority trials, is expected to be the only Phase III program enrolling patients in 2026 for this indication.
• The company plans to leverage its existing Phase III clinical trial infrastructure and strong investigator relationships to achieve rapid enrollment, positioning DURAVYU as a potential market leader in DME treatment.
  

Contradiction Point 1

Endpoints for DME Studies

It involves the choice of endpoints for the DME studies, which is critical for the design and validity of the clinical trials.

Have you considered using a single endpoint for DME studies, and why do you believe the blended endpoint is the best approach? - Unknown Analyst (TD Cowen)

2025Q3: We decided against a single endpoint for its trials. The blended endpoint reduces missing data and accounts for vision recovery during follow-up evaluations. - Jay Duker(CEO)

How does the FDA view blended vs. single time-point endpoints, and what is the post-approval launch timeline? - Yigal Dov Nochomovitz (Citigroup)

2025Q2: The blended endpoint was strongly suggested by the FDA for reducing variability and risk of missing endpoints. It's common in recent studies. - Jay Duker(CEO)

Contradiction Point 2

Trial Enrollment Timing and Rapid Enrollment

It reflects differing expectations and actual timelines for completing trial enrollment, which impacts the company's product development timeline and potential market entry.

Are you on track to complete Phase 3 enrollment earlier than expected? - Jennifer Kim (Cantor)

2025Q3: We are still guiding to full enrollment in both trials in the second half of this year. However, completion of enrollment in the LUGANO trial could potentially be achieved in the second quarter of this year due to rapid enrollment. - Jay Duker(CEO)

What caused the rapid enrollment in your Phase 3 wet AMD trials? - Tessa Romero (JPMorgan)

2025Q1: We are planning a single Phase 3 study comparing our drug to the standard of care. The primary endpoint will be BCVA. We are proposing this clinical plan to the FDA soon this summer, aiming for efficiency in our program. - Ramiro Ribeiro(CMO)

Contradiction Point 3

DME Trial Enrollment Strategy

The company's approach to enrolling patients in the DME trial appears to have shifted, which could impact the efficiency and outcome of the trial.

How are you structuring enrollment criteria to maximize DME market reach compared to competitors in the long-acting TKI space? - Unknown Analyst (Citi)

2025Q3: EyePoint will enroll both treatment-naive and previously treated DME patients. Aflibercept on label will be the control arm. Each trial will enroll approximately 240 patients, leveraging existing infrastructure and investigator relationships for rapid enrollment. - Jay Duker(President and CEO)

With the study 50% enrolled, can you characterize the recruited patient population and how they differ from W2? Regarding DME's development plan, particularly Phase III, how do you plan to address the standard of care baseline? - Yatin Suneja (Guggenheim Securities, LLC, Research Division)

2024Q4: We currently have multiple options for the DME Phase III trial, with the potential to design a study that is both efficient and reduces the need for loading doses. We do not plan to enroll patients who have received prior treatment. - Jay Duker(President and CEO)

Contradiction Point 4

Single versus Blended Endpoint in DME Trials

It highlights a change in the company's approach to trial endpoints, which could impact data interpretation, statistical power, and regulatory approval.

Have you considered using a single endpoint for DME studies, and why do you believe a blended endpoint is the best approach? - Unknown Analyst (TD Cowen)

2025Q3: We are still believing that a blended endpoint may actually be more appropriate in the DME space, given the variability of vision outcomes in DME patients. - Jay Duker(CEO)

What are your expectations for the upcoming FDA meeting on the DME program? - Tessa Romero (JPMorgan)

2025Q1: We have a lot of confidence in a single endpoint. The biology of the disease is one thing that gives us comfort. The vision loss in DME patients is caused by the leakage of fluid into the retina, which is a very consistent phenomenon. - Ramiro Ribeiro(CMO)

Contradiction Point 5

Phase III Trial Design and Endpoint Strategy

The company has shifted its approach to endpoint strategy in its Phase III trials, which could affect the interpretability and comparability of trial results.

Given the FDA's recent approval of a single endpoint, have you considered using a single endpoint for the DME studies and why do you believe a blended endpoint is the optimal approach? - Unknown Analyst (TD Cowen)

2025Q3: EyePoint decided against a single endpoint for its trials. The blended endpoint reduces missing data and accounts for vision recovery during follow-up evaluations. This approach decreases variability and increases study power, and EyePoint has the FDA's green light for this method. - Jay Duker(President and CEO)

Are there plans to conduct long-term post-marketing studies for DURAVYU? What valuable information from these studies would further differentiate it in the wet AMD market? - Unknown Analyst (Jefferies)

2024Q4: We believe our noninferiority testing approach can be executed efficiently, and we expect to be able to demonstrate noninferiority and potentially superiority in these studies. - Ramiro Ribeiro(Chief Medical Officer)