4D Molecular Therapeutics (NASDAQ:FDMT) used its first Investor Day to outline its development and commercial plans for 4D-150, an investigational intravitreal gene therapy for wet age-related macular degeneration, or wet AMD. Company executives and retina specialists described the therapy as a potential one-time “backbone” treatment intended to provide continuous disease control while reducing the burden of repeat anti-VEGF injections.
David Kirn, co-founder, president and CEO, said current wet AMD care relies on episodic bolus injections despite the disease being chronic and continuous. He said the mismatch can contribute to treatment lapses, patient burden and vision loss, particularly when patients miss appointments because of illness, transportation challenges or other life events.
“Patients in the U.S. with wet AMD, the majority will lose vision,” Kirn said. “Many will still go blind.”
4D-150 program and clinical data
4D-150 uses a proprietary retinal-targeting vector designed for a single in-office intravitreal injection. According to Kirn, the therapy is intended to express aflibercept in the retina while also incorporating RNA interference targeting VEGF-C. He said the goal is to provide continuous anti-VEGF activity at the site of disease.
Arshad Khanani, a medical and surgical retina specialist at Sierra Eye Associates and a clinical investigator in the program, said repeat injections can be difficult for patients and caregivers, particularly because patients may need transportation and can spend hours at a clinic. He said real-world treatment discontinuation remains a major issue, with approximately 40% of patients dropping off therapy over time.
Carl Awh, president of Tennessee Retina, presented data from the Phase IIb PRISM study. He said 46% of treated eyes required no supplemental injections over two years, while two-thirds needed two or fewer supplemental injections. Awh said this represented a 78% reduction in treatment burden compared with an “idealized” aflibercept regimen given every eight weeks.
In a subgroup of recently diagnosed patients, Awh said two-thirds of patients required no additional injections over two years and nearly 90% required two or fewer. He characterized the results as an 87% reduction in treatment burden. He also said the study showed stable visual acuity and retinal anatomy, though he noted there was no control group in the Phase IIb trial.
Regarding safety, Awh said that among patients receiving the dose selected for Phase III development, two eyes experienced low-grade inflammation that resolved with topical therapy. He said those events occurred within the first 28 weeks and that no serious inflammation-related adverse events were reported through as long as four years of follow-up.
Two Phase III studies fully enrolled
Dhaval Desai, 4D Molecular Therapeutics’ chief development officer, said the company’s 4FRONT Phase III program consists of two nearly identical studies that are fully enrolled:
- 4FRONT-1 enrolled 523 patients in North America, all of whom were treatment-naive.
- 4FRONT-2 enrolled 531 patients globally and allowed up to 40% of participants to have received as many as four prior injections if diagnosed within the prior six months.
The primary endpoint is non-inferiority in best-corrected visual acuity at week 52 versus aflibercept 2 mg administered every eight weeks. Both study arms receive three initial loading doses. Desai said the company designed the trials with an approximately four-letter non-inferiority margin and has regulatory alignment through FDA Regenerative Medicine Advanced Therapy designation, EMA Priority Medicines designation and discussions with Japan’s PMDA.
Desai said the company expects Phase III visual-acuity results to be comparable with historical outcomes in treatment-naive wet AMD trials, where patients generally gained about six to eight letters at one year, depending on baseline vision. He declined to provide details on blinded safety findings from the ongoing trials.
Kirn said the company expects one Phase III readout in the first half of 2027 and the second in the second half of 2027. He also said the company’s cash runway extends into the second half of 2028.
Commercial strategy focuses on in-office use
Chris Simms, chief commercial and chief business officer, said 4D-150’s single intravitreal administration could allow it to fit into existing retina-clinic workflows without surgery. He said the company expects the therapy, if approved, to be reimbursed through the familiar Medicare Part B “buy-and-bill” model used for many retina treatments.
Simms estimated the global wet AMD and diabetic macular edema market at about $16 billion, with 60% of the value in the U.S. He said the company estimates approximately 600,000 U.S. wet AMD patients are currently receiving regular treatment, representing roughly 800,000 treated eyes because of bilateral disease. By 2030, the company estimates about 900,000 wet AMD eyes could be under treatment in the U.S.
The company said its market research found that 75% of retina specialists would consider prescribing 4D-150 within the first year after approval. Simms said early use would likely focus on patients with the greatest injection burden, followed by broader adoption as physicians gain confidence in real-world safety and reimbursement.
David Eichenbaum, director of research at Retina Vitreous Associates of Florida, said adoption would depend on clinical data, reimbursement confidence and the therapy’s ability to fit established practice processes. He said he would likely initially consider the therapy for high-need patients and some treatment-naive patients resembling those enrolled in clinical trials.
Company executives and participating physicians repeatedly emphasized that the eventual clinical and commercial outlook for 4D-150 remains dependent on Phase III results, regulatory review and reimbursement decisions.
About 4D Molecular Therapeutics (NASDAQ:FDMT)
4D Molecular Therapeutics, Inc is a clinical-stage biotechnology company focused on developing gene therapies for serious diseases with significant unmet medical needs. The company uses its Therapeutic Vector Evolution platform to design adeno-associated virus (AAV) vectors intended to deliver genetic medicines to specific tissues and organs.
Its pipeline has focused primarily on ophthalmology and pulmonology. Key investigational programs have included 4D-150, an intravitreal gene therapy being developed for retinal diseases such as wet age-related macular degeneration and diabetic macular edema, and 4D-710, an inhaled gene therapy designed to address the underlying cause of cystic fibrosis in patients who cannot benefit from existing CFTR modulator treatments.
