In the wake of announcing a 25% cut in its workforce last month, 4D Molecular Therapeutics (4DMT) reported new 60-week findings from its ongoing phase 2 clinical study evaluating its investigational gene therapy asset 4D-150 for the treatment of diabetic macular edema (DME).
This latest data was presented during the 2025 annual meeting of the American Society of Retina Specialists (ASRS) in Long Beach, California.
First order of business: Tell me more about 4D-150.
To understand the basis for this asset, you’ll need a rundown on 4DMT’s Therapeutic Vector Evolution, a proprietary vector discovery platform.
Those details: This platform utilizes synthetic adeno-associated virus (AAV) capsid-derived sequences to create customized vectors for the clinical advancement of 4DMT’s vector delivery-based product candidates (including 4D-150).
As for how 4D-150 is delivered—that would be thanks to the 4DMT-developed-and-customized R100 intravitreal (IVT) vector.
Explain how this enables delivery.
The R100 vector leverages a multi-target transgene payload that expresses:
- Aflibercept
- A vascular endothelial growth factor (VEGF)-C inhibitory RNA interference (RNAi)
The dual payload is designed to block four angiogenic factors responsible for DME and wet age-related macular degeneration (another potential indication for which 4D-150 is undergoing clinical evaluation).
And the intended result?
Ideally, to enable a multi-year sustained delivery of anti-VEGF from the retina via a single low-dose IVT delivery to treat those aforementioned retinal diseases.
As a bonus: 4D-150 was granted Regenerative Medicine Advanced Therapy (RMAT) designation by the FDA in May 2025.
Alrighty, now let’s talk about this DME phase 2 trial.
The prospective, multicenter, randomized, active-controlled, double-masked, dose-ranging phase 2 SPECTRA trial (NCT05930561) was originally divided into two parts:
- Part 1: Patients sequentially assigned to receive one of two open-label dose levels of 4D-150
- Part 2: Patients randomized to receive either one of two 4D-150 dose levels (based on Part 1 findings) or aflibercept control
- Note: This second part was no longer required following the 32-week findings
Its primary purpose: To determine the annualized number of aflibercept injections in the study eye (measured at 52 weeks)—see here for second and other outcomes being measured.
What has interim data previously shown?
Based on just Part 1 of the study (at 32 weeks), investigators determined:
- 4D-150 was well tolerated with no intraocular inflammation (IOI) at any point
- The lowest 4D-150 dose (3E10 vg/eye) sustained:
- The greatest gain of best-corrected visual acuity (BCVA; +8.4 letters)
- A central subfield thickness (CST) reduction of -194 µm
The conclusion: 4D-150 has strong potential to treat DME (and wet AMD) as a potential backbone therapy in providing multi-year sustained vascular endothelial growth factor (VEGF) inhibition in the retina with just one injection.
And notably: The highest dose (3E10 vg/eye) has been selected for phase 3 analysis.
Now to this latest 60-week data.
Reported during last week’s ASRS meeting, 4D-150 continues to be well tolerated, with no IOI inflammation at any point (at any dose level).
Further, all patients completed a 16-week topical steroid taper on schedule, and:
- No patients required modification to their steroid regimen
- All patients are currently off steroid use
- There have been no reports of any:
- Hypotony
- Endophthalmitis
- Vasculitits
- Choroidal effusions
- Retinal artery occlusions
Zero in on that high dose.
In terms of IOP tracking: Investigators reported that patients treated with the 3E10 vg/eye dose have continued to exhibit:
- A mean IOP within normal limits
- Sustained improvement in anatomic control
- Strong treatment burden reduction and dose response (versus lower doses)
- 58% fewer injections required
What else?
A 78% reduction in supplemental injections (from Week 8 to 60) was noted for the 3E10 vg/eye dose (versus projected on-label aflibercept 2mg Q8W).
Any adverse events to report?
No serious treatment-emergent adverse events (TEAEs) were reported to date (as of the May 2, 2025, cutoff point)—including in relation to 4D-150.
See here for the full presentation details, as presented by David Almeida, MD, MBA, PhD, DABO, FRCSC, FASRS, of Erie Retina Research in Erie, Pennsylvania.
This sounds very promising. So what’s next for this gene therapy?
As we mentioned last month (when the company announced those workforce cuts and new focus on phase 3 plans), 4DMT is in the process of initiating a single phase 3 trial on 4D-150 (3E10 vg/eye): 4FRONT-1.
What to know about this trial: While no specific details are readily available on its setup yet, we do know that it’ll be focused on 4D-150’s wet AMD (not DME) indication, and interim data is expected by H2 2027.
- On the clinical data front: Check out the positive 52-week data from the phase 2b PRISM clinical trial, which evaluated 4D-150 for wet AMD (as we reported in February 2025).
What does this mean for its DME indication?
Not a thing. The FDA has deemed that the phase 3 trial will be acceptable for supporting a future Biologics License Application (BLA) submission for both 4D-150’s DME and wet AMD indications.
Stay tuned for more phase 3 details!