4D Molecular Therapeutics announced FDA clearance of the Investigational New Drug Application (IND) for 4D-150, an R100 vector-based intravitreal genetic medicine, for the treatment of patients with Diabetic Macular Edema (DME). The Phase 2 SPECTRA clinical trial will assess 4D-150 in patients with DME. The study design consists of a Dose Confirmation stage followed by a masked Dose Expansion stage, in which patients will be randomized to receive a single intravitreal injection at one of two dose levels of 4D-150 or aflibercept in a 1:1:1 ratio (n=54 patients).

The doses to be evaluated in DME are anticipated to be between 6E9 to 3E10 vg/eye. The IND clearance enables the initiation of SPECTRA clinical study sites, and 4DMT expects to begin enrollment in the third quarter of 2023. Initial Cohort 1 data (n=5) from the Phase 1 portion of the Phase 1/2 PRISM clinical trial with 4D-150 for wet age-related macular degeneration (wet AMD) demonstrated a reduction in annualized anti-VEGF injection rate by over 95%, further validating the potential of intravitreal R100 vector for other large market eye diseases such as geographic atrophy.

On January 9, 2023, 4DMT disclosed that the Company had initiated the randomized Phase 2 portion of the Phase 1/2 PRISM clinical trial for 4D-150 in patients with wet AMD. This portion of the trial is now enrolling patients. In addition, the Company intends to present interim data for dose Cohorts 1, 2, & 3 (n=15) at the 2023 ARVO Annual Meeting taking place April 23-27, 2023; at the time of the ARVO data presentation, all patients are predicted to have at least six months of follow-up following 4D-150 treatment.

4D-150 is comprised of targeted and evolved intravitreal vector, R100, and a payload that expresses both aflibercept and a VEGF-C RNAi. R100 was invented at 4DMT through proprietary Therapeutic Vector Evolution platform; created this platform utilizing principles of directed evolution, a Nobel Prize-winning technology. This dual transgene payload inhibits 4 angiogenic factors: VEGF A, B, C and PlGF.

4D-150 is designed for a single low dose intravitreal delivery. Wet AMD is a highly prevalent disease with an estimated incidence rate of 200,000 new patients per year in the United States, according to published data. Wet AMD is a type of macular degeneration where abnormal blood vessels (choroidal neovascularization or CNV) grow into the macula, the central area of the retina.

As a consequence, CNV causes swelling and edema of the retina, bleeding and scarring, and causes visual distortion and reduced acuity. The proliferation and leakage of abnormal blood vessels is stimulated by VEGF. This process distorts and can potentially destroy central vision and may progress to blindness without treatment.

DME is a highly prevalent disease with significant unmet medical need. It is estimated that there are approximately one million individuals with DME in the United States according to published data. DME is characterized by swelling in the macula due to leakage from blood vessels.

This can lead to blurred vision. DME is typically treated with intravitreal anti-VEGF agents administered approximately every 4-12 weeks.