4D Molecular Therapeutics recently announced positive 2-year data from the phase 2b PRISM clinical trial evaluating 4D-150 in the treatment of wet age-related macular degeneration (AMD).
These findings were presented during the American Society of Retina Specialists (ASRS) 2026 annual meeting in Montréal, Canada, earlier this month.
Give me some background on 4D-150.
First: It helps to know about 4DMT’s Therapeutic Vector Evolution.
- What it is: a proprietary platform that uses synthetic adeno-associated virus (AAV) capsid–derived sequences to create customized vectors (such as R100, below) for advancing vector delivery–based product candidates, including 4D-150.
Then: There’s the customized R100 intravitreal (IVT) vector.
- What it does: utilizes a dual transgene payload—aflibercept and a VEGF-C–inhibitory RNAi—to block four angiogenic factors driving wet AMD in order to deliver 4D-150.
How, exactly?
4D-150 is formulated to offer a multi-year, sustained, and low-dose IVT delivery of anti-VEGF from the retina.
Its clinical performance thus far:
- Check out this 52-week wet AMD data from the phase 2b PRISM trial
- See here findings from a 60-week phase 2 analysis on its second proposed indication: diabetic macular edema (DME)
- The gene therapy has also received FDA Regenerative Medicine Advanced Therapy (RMAT) designation for DME
Before we get into this new data, wasn’t 4DMT just in the news?
Indeed. Earlier this year the company reported that patient enrollment was completed in its first phase 3 clinical trial, 4FRONT-1 (NCT06864988), based in North America.
Note: This is the first registrational trial on 4D-150 in the company’s planned wet AMD phase 3 clinical program, which also includes the global 4FRONT-2 study (NCT07064759).
Let’s move on to the PRISM study.
The phase 1/2a and 2b PRISM study comprises multiple steps:
- Phase 1/2a: safety, proof of concept study featuring a cohort of patients with severe, recalcitrant wet AMD (n=24)
- Phase 2b: assessment of clinical activity in a broader population (n=30)
- Phase 2b subgroup: Patients recently diagnosed (within 6 months) with wet AMD (n=15)
The trial’s phase 2b portion(NCT05197270) enrolled 45 wet AMD patients at two dose levels (3E10 [n=30] and 1E10 [n=15] vg/eye) of a single 4D-150 injection.
Findings?
The 2-year data demonstrated consistent improvements in key markers, such as:
- Maintenance of best-corrected visual acuity (BCVA)
- Control of central subfield thickness (CST) as measured by optical coherence tomography (OCT)
- Durable and clinically meaningful reduction in treatment burden:
- Overall cohort: 78% overall treatment burden reduction (2.7 mean supplemental injections per patients vs. 12.0 injections projected with on-label aflibercept 2 mg dosed every 8 weeks [Q8W])
- Recently diagnosed subgroup: 87% overall treatment burden reduction (1.6 mean supplemental injections per patients vs. 12.0 injections projected with on-label aflibercept 2 mg Q8W)
Moreover: The dose response maintained throughout the 2 years highlights the efficacy of the phase 3 dose.
How did it perform in terms of safety?
Safety data was based on the phase 3 dose (3E10 vg/eye) in the overall PRISM phase 1/2a and 2b clinical trial (n=71), and demonstrated that 4D-150 continues to be well tolerated.
Within approximately the first 6 months (28 weeks) post-4D-150 dosing:
- 2.8% (2 of 71) of patients had treatment-related 1+ (mild) intraocular inflammation (IOI), as measured by the SUN/NEI scales, which were transient 1+ vitreous cells noted at a single timepoint.
Following the first 28 weeks post-4D-150 dosing:
- There were no new cases of inflammation with 2 to more than 4 years of follow-up on all patients as of the data cutoff (May 18, 2026).
Moreover: No 4D-150-related adverse events like hypotony, endophthalmitis, vasculitis, occlusive/non-occlusive retinal vasculitis, or choroidal effusions have been observed to date.
And what did 4DMT have to say about this performance? the company?
Referencing the intense injection schedule many wet AMD patients undergo to manage the disease, Carl Awh, MD, FASRS, who practices at Tennessee Retina and presented the data, highlighted:
“The 2-year PRISM results demonstrate the potential of a single IVT administration of 4D-150 to provide long-term anti-VEGF and sustained disease control. Reducing treatment burden will undoubtedly improve our ability to preserve vision over the long term for our patients.”
When can we expect an update on 4D-150?
Topline data from the 4FRONT-1 and 4FRONT-2 phase 3 clinical trials are expected in H1 2027 and H2 2027, respectively.
In terms of DME: 4DMT plans to initiate a global phase 3 trial in Q3 2026, and 2-year data from the phase 2 SPECTRA trial (NCT05930561) is expected H2 2026.