The following transcript has been edited for clarity.
Hi, I'm Diana V. Do, MD, with Retinal Physician. Today, I’m at Innovate Retina 2026, where I’m joined by a retina leader, Veeral Sheth, MD, MBA. Tell us about your presentation on intravitreal gene therapy.
Veeral Sheth, MD: Today I gave an update on the 4D-150 gene therapy program (4D Molecular Therapeutics), which, as you know, is a unique program, from how it’s constructed to how it’s delivered, which is as an intravitreal therapy. We’ve got updated data for neovascular age-related macular degeneration (AMD) going back now 2 years, which is fantastic because we really think that these treatments are durable. They’re going to reduce treatment burden for our patients. And so we want to see that over a longer period of time. So now we have 2-year data from the phase 1/2 PRISM program that shows us really nice results in terms of central subfield thickness (CST) and best-corrected visual acuity (BCVA) stability, but also the ability to reduce the treatment burden: fewer injections, less supplemental treatments for patients over time.
Dr. Do: On average, do these patients even need any supplemental injections? Or is it one and done?
Dr. Sheth: That’s a good question. I hesitate to say “one and done,” because we know that there's always going to be patients that just have higher disease activity and might need treatments. What we saw was, we broke it down into different groups. So if you look at the really difficult-to-treat patients—let’s call them recalcitrant patients—even they benefited. They had a treatment burden reduction—22% of those patients in 2 years didn’t receive any injections. Now these are patients that were getting almost monthly treatments before they entered the trial. And close to 59% of those patients needed 2 or fewer supplemental treatments in 2 years.
Now you look at the more recently diagnosed patients—patients that are just kind of walking into clinic—they had a significant treatment burden reduction. So 66% of those didn't need any supplemental treatments at 2 years and close to 90% needed 2 or fewer injections in 2 years. It’s incredible; life-changing for those patients.
Dr. Do: That is incredible data. What about safety? Does an intravitreal injection of a gene therapy vector need any immunosuppression?
Dr. Sheth: Great question. The answer is yes, we think so. In this trial in particular, and in the phase 3 study, for example, we’re going to be giving patients 20 weeks of topical steroids right out the gate. The hope is that we can blunt any inflammation and then taper those drops down over the course of 20 weeks. And then hopefully at that point, no more drops for those patients.
Dr. Do: We’re going to be excited to hear more about the phase 3 as it enrolls and congratulations again on doing this research. RP
