4D Molecular Therapeutics Presents Interim Results from the Ongoing 4D-125 Phase 1/2 Clinical Trial in Patients with Advanced X-Linked Retinitis Pigmentosa
October 10, 2021 at 03:50 pm EDT
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4D Molecular Therapeutics, Inc. announced interim safety and clinical activity data from the Phase 1/2 clinical trial of intravitreal 4D-125 in patients with advanced X-linked retinitis pigmentosa (XLRP). The interim data were presented in a late-breaking presentation at the American Society of Retina Specialists (ASRS) 39th Annual Meeting. The data described are from the first-in-human, on-going Phase 1/2 dose escalation and dose expansion clinical trial assessing intravitreal 4D-125, 4DMT’s targeted and evolved R100-based product candidate for XLRP. As of the data cutoff date (September 1, 2021), eight patients with clinically advanced XLRP due to RPGR gene mutation had been enrolled. A standard 3+3 dose escalation design was used, followed by a dose expansion cohort. Patients were enrolled in one of three dose cohorts: dose-escalation cohort 1 (3E11 vg/eye; n=3), dose-escalation cohort 2 (1E12 vg/eye n=3) and the dose expansion cohort (1E12vg/eye; n=2 to date). Patients enrolled in the dose escalation cohorts of the first-in-human clinical trial had clinically-advanced XLRP, with patients having limited or no measurable remaining photoreceptor area or retinal sensitivity. As of the data cutoff date, two dose escalation patients (n=1 at 3E11 vg/eye; n=1 at 1E12 vg/eye) were evaluable for clinical activity defined as having both measurable ellipsoid-zone area (EZ Area) by spectral domain optical coherence tomography (SD-OCT) and retinal sensitivity by microperimetry in both the treated and untreated control eye with at least six months follow-up; dose expansion cohort patients (n=2) had not yet reached six months follow-up but are expected to be evaluable with sufficient follow up. On-going enrollment in the dose expansion cohort is expected to enroll patients with less advanced disease than those enrolled in dose escalation, and who the company expects to be evaluable for clinical activity based on central reading center confirmation at screening. Interim Safety Data Summary: 4D-125 was well-tolerated in all eight XLRP patients, including in five patients at the top dose level of 1E12 vg/eye; No dose-limiting toxicities or serious adverse events were observed; No chronic inflammation was observed; and Transient, grade 1+ anterior chamber and/or vitreous cells were observed in two of the eight patients at a single protocol-defined assessment timepoint (SUN1 & NEI2 grading scales): One patient had grade 1+ vitreous and anterior chamber cells; One additional patient had grade 1+ vitreous chamber cells. Interim Clinical Activity Summary: Patient 3 (3E11 vg/eye cohort – 9 months follow-up): Decreases from baseline EZ Area were -12.4% in the treated eye compared to -16.2% in the untreated control eye (~23% lower relative progression rate). An increase in mean retinal sensitivity was demonstrated, with an increase of +1.65 dB in the treated eye from baseline compared to +0.25 dB in the untreated control eye. The number of loci gaining greater than = 7 dB sensitivity were six in the treated eye compared to one in the untreated control eye; Patient 5 (1E12 vg/eye cohort – 6 months follow-up): Decreases from baseline EZ Area were -20.2% in the treated eye compared to -28.7% in the untreated control eye (~30% lower relative progression rate). An increase in mean retinal sensitivity was demonstrated, with an increase of +0.90 dB in the treated eye from baseline compared to +0.10* dB in the untreated control eye. The number of loci gaining greater than = 7 dB sensitivity were three in the treated eye compared to zero in the untreated control eye.
4D Molecular Therapeutics, Inc. is a clinical-stage genetic medicines company focused on unlocking the full potential of genetic medicines to treat diseases in ophthalmology and pulmonology. The Company has a portfolio of genetic medicine product candidates, with five product candidates in clinical trials in seven patient populations: 4D-150 for the treatment of wet age-related macular degeneration (wet AMD) and diabetic macular edema (DME), 4D-710 for the treatment of cystic fibrosis lung disease (both in modulator ineligible and eligible populations), 4D-310 for the treatment of Fabry disease cardiomyopathy, 4D-125 for the treatment of X-linked retinitis pigmentosa (XLRP), and 4D-110 for the treatment of choroideremia. In addition, it has two product candidates in preclinical development: 4D-175 for geographic atrophy (GA) and 4D-725 for alpha-1 antitrypsin deficiency lung disease.