4D Molecular Therapeutics (FDMT) 3rd Annual Guggenheim Healthcare Innovation Conference summary

Platform and opportunity

• Directed evolution produces tissue-targeted vectors; proprietary R100 is designed to target retinal cells while limiting transduction of other cells.

• 4D-150 combines R100 with an aflibercept payload, delivered by a low-dose intravitreal injection for long-term retinal expression.

• The global anti-VEGF category is valued at $16B and growing; wet AMD remains a chronic disease treated with episodic injections.

• The proposed treatment profile is continuous disease control from one injection, with potential vision preservation and reduced treatment burden; current anti-VEGF dosing may be monthly to every two or three months.

Clinical evidence and safety

• In recently diagnosed PRISM patients, two-year data showed maintained vision and controlled CST, with an average 1.66 supplemental injections versus 12 on-label EYLEA injections at Q8 dosing.

• PRISM results represented an 87% treatment-burden reduction; 66% of patients were supplement-free through two years.

• Among 71 patients treated at the phase III dose, two mild, transient inflammation cases resolved with topical prophylactic steroid; no related serious adverse events or specified severe ocular events were seen.

• Initial real-world uptake is expected to focus on patients with higher disease burden, with broader use potentially following evidence of safety and reimbursement confidence over time.

• 4D-150 is intended to provide steady VEGF control rather than incremental dosing extensions; occasional supplemental treatment may still be needed, and continuous control may reduce fluid fluctuations.

Phase III program and milestones

• 4FRONT-1 is a North American non-inferiority trial with 523 patients; enrollment finished ~4 months ahead of schedule, and top-line results are expected in Q2 2027.

• Global 4FRONT-2 includes U.S., European, South American and Asian sites; top-line results are expected in H2 2027.

• 4FRONT-1 compares 4D-150 with on-label aflibercept; its 52-week primary endpoint is vision non-inferiority, using a 4.5-letter margin in the U.S.

• Enrollment criteria include VEGF responsiveness; retreatment criteria are designed to protect the primary endpoint, with intervention planned if patients lose vision.

• Recently diagnosed patients showed the strongest PRISM treatment-burden reduction; 4FRONT-2 allows up to six months of prior treatment to meet European requirements, with no major outcome difference expected between trials.