4D Molecular Therapeutics’ one-time gene therapy reduced the need for annual injections in patients with age-related blindness in a mid-stage trial.
The company on Wednesday reported updated Phase 1/2 data for its lead candidate, 4D-150, finding that 70% of treated patients in a broad Phase 2b population did not need an annualized injection of Regeneron’s Eylea. In that 30-patient group, 4DMT reported an 89% reduction in annualized injections through 52 weeks and said that 80% of patients received zero or one injection.
The findings were even more pronounced in a 15-person cohort of patients who were recently diagnosed with wet age-related macular degeneration.
4DMT reported similar data in a Phase 1/2 population with more severe patients, including an 83% reduction in annual injections. More than half of patients had zero or one injection through 52 weeks and 44% were injection-free.
In an interview, CEO David Kirn said the results are substantial evidence that its intravitreal injection — meaning it’s injected directly into the eye — is just as effective as other anti-VEGF candidates that require subretinal shots. Intravitreal injections are easier to perform than subretinal, which require surgery.
“We’re thrilled to say we now have that,” he said. Though regulators only ask for data through 52 weeks, Kirn expects the effects of the therapy to be durable for five or more years.
Investors were evidently less thrilled, with the company’s shares down 22% after the market opened Thursday.
The injection did not lead to any new side effects and fit the safety profile of other anti-VEGF options, according to the California biotech. Roughly 3% of patients experienced intraocular inflammation, and all but one patient completed their steroid prophylaxis taper on time.
All eyes are now on the company’s pivotal trials set for 2025. The first, a US-based study, is set to begin in the first quarter of next year. Kirn said that “we’re all aligned with FDA already.” He added that the company is “almost there” with European regulators and is hashing out final study details. That study would launch three or four months after the US one, Kirn said.
Equipped with $578 million at the end of June, Kirn said there are no plans for a follow-on offering, a staple action for today’s public biotechs following positive readouts.
“But we’ll be opportunistic and smart about how we build the business,” he said, adding that the company’s current runway extends through the first Phase 3 readout.
Kirn also believes the company will have enough money to continue to advance earlier-stage candidates while prioritizing late-stage development of 4D-150. It has two other clinical-stage ophthalmology candidates in the pipeline, plus one that’s received IND clearance. 4DMT also has one clinical-stage candidate apiece for its pulmonary and cardiology wings.
“We’re very rapidly shifting from a diversified company to what we hope to be the leader in large-market ophthalmology for genetic medicine,” Kirn said.