4DMT refocuses pipeline to prioritize 4D-150 trials in wet AMD and DME

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Clinical-stage genetic medicines company 4D Molecular Therapeutics (4DMT) has announced a strategically focused pipeline in addition to updated Phase 3 4FRONT program plans, initial 4FRONT guidance, and resulting updated cash runway guidance.

“4DMT was founded to address the challenges posed by traditional AAVs and to bring genetic medicines to market to transform outcomes for millions of patients. Over 10 years we created a diverse pipeline to bring this vision closer to reality with seven named product candidates across three therapeutic areas utilizing 3 novel, clinically validated vectors,” said David Kirn, MD, cofounder and CEO of 4DMT, in the release. “We have prioritized 2 product candidates with the strongest clinical proof of concept and high potential to impact the most patients to fulfill our mission. In addition, our ongoing regulatory interactions support an efficient path to Biologics License Applications (BLA) for 4D-150 in both wet age-related macular degeneration (wet AMD) and diabetic macular edema (DME).”

The company listed updates and upcoming milestones for its 4D-150 programs in the release. 4D-150 is a potential backbone therapy that is designed to provide multi-year sustained delivery of anti-VEGF (aflibercept and anti-VEGF-C) to be targeted to the retina with a single, well-tolerated intravitreal injection. Currently, 4DMT is assessing 4D-150 for wet AMD and DME. For wet AMD, the company has an ongoing Phase 1/2 PRISM clinical trial currently in long-term follow-up, with 52-week interim data from the Phase 2b cohort to be presented at Angiogenesis, Exudation, and Degeneration 2025 on February 8, 2025. Further data discussions will occur via corporate webcast on February 10, 2025.

Additionally, the Phase 3 4FRONT program has aligned trial designs and CMC plans with the US FDA under RMAT designation and European Medicines Agency under PRIME designation. 4FRONT-1 and 4FRONT-2 are on target to initiate in Q1 and Q3 2025 respectively. The clinical trial design for both trials has a primary endpoint of best corrected visual acuity (BCVA) noninferiority of 4D-150 3E10 vg/eye to aflibercept 2mg Q8W. Target enrollment is listed as 400 patients per trial. 52-week topline data from both trials is expected in H2 2027.

As for 4D-150 for DME, the ongoing SPECTRA Part 1 follow-up continues, with positive 32-week interim data also announced in January 2025. The trial found that 4D-150 continues to be well tolerated with no intraocular inflammation observed at any timepoint or dose level. The 3E10 vg/eye dosage demonstrated a sustained gain of BCVA of +8.4 letters and reduction of CST of -194 from baseline through week 32. The single Phase 3 clinical trial was found as acceptable for the basis of a BLA submission for 4D-150 in DME as based on data from the SPECTRA and PRISM trials to date.

However, 4DMT will be reducing capital allocation for its 4D-175 program for geographic atrophy, which is preclinical with open IND. Additionally, the company will terminate its early-stage rare disease clinical programs evaluating 4D-110 for choroideremia and 4D-125 for X-linked retinitis pigmentosa. 4DMT will not be investing additional capital into new preclinical product candidates at this time, the release stated. The company will now expect its current cash to fund operations into 2028, including full execution and topline 52-week data from 4FRONT-1 and 4FRONT-2 Phase 3 clinical trials in wet AMD and ongoing early-stage development for DME.

Reference:

1. 4DMT Focuses Pipeline to Prioritize 4D-150 in Wet AMD & DME and 4D-710 in CF and Extends Cash Runway. Accessed January 13, 2025. https://ir.4dmoleculartherapeutics.com/news-releases/news-release-details/4dmt-focuses-pipeline-prioritize-4d-150-wet-amd-dme-and-4d-710