B. Riley Names 4D Molecular Therapeutics a Top Biotech Pick

B. Riley Securities has reaffirmed 4D Molecular Therapeutics (NASDAQ: FDMT) as one of its year-end top biotech picks, maintaining a Buy rating and $37 price target after the company advanced its lead gene-therapy candidate, 4D-150, into another Phase 3 trial.

The latest analyst view comes as 4D Molecular Therapeutics expands 4D-150 beyond wet age-related macular degeneration (wet AMD) into diabetic macular edema (DME). The company recently began enrolling patients in the 4SIGHT Phase 3 trial, adding another major retinal-disease opportunity to an already advanced clinical program.

For investors, the story is less about a conventional biotech revenue stream and more about whether 4D-150 can demonstrate durable efficacy, reduce the burden of repeated eye injections and ultimately succeed in late-stage clinical trials.

Why B. Riley Is Highlighting 4D Molecular Therapeutics

B. Riley's thesis centers on 4D-150, an intravitreal gene therapy designed to provide sustained production of anti-VEGF proteins inside the retina following a single injection.

Anti-VEGF drugs are already an important part of treating retinal diseases, but many patients require repeated injections. 4DMT is developing 4D-150 as a potential longer-duration treatment intended to reduce that treatment burden. The company says the therapy is designed to provide multi-year, potentially lifelong, delivery of anti-VEGF biologics.

B. Riley argues that the potential reduction in injection frequency is a key differentiator. Its analysis estimates that, over five years, patients could require approximately 34 intravitreal procedures with standard aflibercept treatment, compared with roughly 18–23 with Eylea HD or Vabysmo, 21 with Kodiak Sciences' Zenkuda and potentially 8–12 with 4D-150 under its modeled treatment schedules. Those figures are B. Riley's estimates, not clinical outcomes established for 4D-150.

The distinction matters because the Phase 3 trials still have to establish whether the therapy can deliver the expected benefit at scale.

4D-150 Enters Phase 3 for Diabetic Macular Edema

A major recent catalyst was the launch of the 4SIGHT Phase 3 trial in DME.

4DMT announced on September 28 that the first patients had been enrolled in the global study, which is planned to include 514 treatment-naïve DME patients. The randomized, double-masked trial compares 4D-150 with aflibercept 2 mg administered every eight weeks.

The primary objective is to determine whether 4D-150 is non-inferior to aflibercept on the change in best-corrected visual acuity at Week 52. The study will also examine treatment burden, including the number of supplemental injections required.

DME is a complication of diabetic retinopathy in which fluid accumulates in the macula and can impair vision. Current anti-VEGF treatment can involve injections every four to 12 weeks, making adherence and treatment frequency important clinical issues.

Two-Year SPECTRA Data Add to the Investment Case

The Phase 3 expansion follows updated two-year data from the SPECTRA trial.

Among the nine patients receiving the Phase 3 dose of 4D-150, the company reported a mean gain of 10.8 letters in best-corrected visual acuity and a mean reduction in central subfield thickness of 176 micrometers. The company also reported no intraocular inflammation or ocular serious adverse events in the 22-patient safety population at the data cutoff.

After three aflibercept loading doses, patients averaged 5.2 supplemental injections, which 4DMT calculated as a 61% reduction in treatment burden compared with 13 projected injections under an on-label aflibercept schedule. Under the criteria planned for the larger 4SIGHT trial, the company retrospectively estimated a 75% reduction. It explicitly noted that the latter is a retrospective estimate and that actual 4SIGHT results may differ.

The small sample size is an important limitation. Results from nine patients at the Phase 3 dose cannot establish whether the same efficacy and treatment-burden profile will be reproduced in a much larger randomized trial.

Wet AMD Remains the Bigger Near-Term Catalyst

DME is now the second Phase 3 indication for 4D-150, but wet AMD remains central to the company's development strategy.

4DMT has completed enrollment in both 4FRONT Phase 3 trials. The company reported that 4FRONT-1 enrolled 523 patients, with topline results expected in the second quarter of 2027. 4FRONT-2 completed enrollment with more than 500 patients expected to be randomized, with topline results anticipated in the second half of 2027.

That creates several potentially important clinical milestones across 2027.

The wet-AMD trials compare 4D-150 with aflibercept and are designed to test whether a single administration can provide comparable vision outcomes while reducing treatment burden.

Financial Position Gives 4DMT Time to Execute

Unlike many early-stage biotechnology companies, 4DMT has built a substantial cash position while moving its lead program into late-stage trials.

As of June 30, 2026, the company had $430.6 million in cash, cash equivalents and marketable securities. During the second quarter, it reported $3.8 million in collaboration and license revenue and a net loss of $72.9 million. Research and development spending was $68.3 million for the quarter, reflecting the cost of advancing 4D-150 through Phase 3.

The company also secured a credit facility of up to $200 million from Hercules Capital, initially drawing $20 million. Management said its existing resources were expected to fund the current operating plan into the second half of 2028.

That financial runway is relevant because Phase 3 development is expensive, and the company needs sufficient capital to reach important clinical readouts without excessive near-term financing pressure.

B. Riley's Valuation Assumptions

B. Riley's $37 price target is based on its own valuation model rather than a guaranteed future stock price.

The brokerage uses a sum-of-the-parts discounted cash-flow framework and estimates risk-adjusted peak global sales of approximately $1.44 billion for 4D-150, including about $599 million from wet AMD and $338 million from DME. These are analyst assumptions about a future commercial outcome and should not be treated as company revenue guidance.

The company's commercial opportunity depends heavily on successful Phase 3 trials, regulatory approvals and eventual adoption against established retinal therapies.

Key Risks for Investors

The biggest risk remains clinical.

4D-150 is still an investigational therapy. 4DMT explicitly states that its product candidates have not been approved for marketing by the FDA or other regulatory authorities, and clinical results could differ materially from earlier-stage data.

There is also execution risk. The company is running multiple late-stage trials simultaneously, which increases research and development spending. Its first-half 2026 net loss reached $141.7 million, compared with $102.6 million during the same period in 2025.

Investors should also consider competition. Existing treatments such as Eylea HD and Vabysmo already serve the retinal market, while other long-acting approaches are also being developed.

What Investors Should Watch Next

The most important catalysts are now clearly tied to clinical execution.

Investors should monitor the progress of the 4SIGHT DME Phase 3 trial, further updates from the 4FRONT wet-AMD program and the company's October 21 investor day. The first major wet-AMD Phase 3 topline data are expected in 2027.

The key question will be whether the promising early evidence around durability and lower injection frequency translates into statistically robust results in larger controlled studies.

B. Riley's decision to retain 4D Molecular Therapeutics as a top biotech pick reflects the brokerage's assessment of that potential. For investors, however, the $37 target ultimately depends on clinical, regulatory and commercial assumptions that remain unproven.

Conclusion

4D Molecular Therapeutics has moved into an important stage of its development, with 4D-150 now being tested in Phase 3 for both wet AMD and diabetic macular edema. B. Riley Securities has maintained its Buy rating, $37 price target and year-end top-pick designation, citing the therapy's potential durability and the expanding clinical opportunity.

The investment case now hinges on execution. Upcoming Phase 3 data, treatment-burden results, safety findings, regulatory progress and the company's cash position will be more important than any single analyst target.

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