4D Molecular Therapeutics Announces FDA Fast Track Designation Granted to 4D-125 for the Treatment of X-linked Retinitis Pigmentosa

4D Molecular Therapeutics recently announced the  US FDA has granted Fast Track Designation for 4D-125 for treatment of patients with inherited retinal dystrophies due to defects in the RPGR gene, including X-linked Retinitis Pigmentosa (XLRP). 4D-125 is a targeted and evolved R100-based product candidate, which was invented at 4DMT for efficient intravitreal delivery, and is designed to deliver a functional copy of the RPGR gene to photoreceptors in the retina.

“Patients living with XLRP currently have no approved treatments, and they suffer from progressive vision loss and blindness that reduces their quality of life and independence,” said Robert Kim, MD, Senior Vice President and Ophthalmology Therapeutic Area Head of 4DMT. “Fast Track Designation is a landmark event for the program and underscores the potential of 4D-125 to address a significant unmet need for those living with XLRP.”

The FDA’s Fast Track process is designed to accelerate the development and review of treatments for serious and life-threatening diseases where no treatment exists or where the treatment in discovery may provide advantages over what is currently available. A drug candidate that receives Fast Track designation is eligible for more frequent communication with the FDA throughout the drug development process and a rolling and/or priority review of its marketing application if relevant criteria are met.

4D-125 is 4DMT’s targeted and evolved R100-based product candidate for XLRP and is designed to deliver a functional copy of the RPGR gene to photoreceptors in the retina. 4DMT is currently enrolling patients in an on-going Phase 1/2 clinical trial. The study employed a standard 3+3 dose-escalation design, followed by dose expansion. In dose-escalation, patients were enrolled in one of two dose cohorts: 3E11 vg/eye and 1E12 vg/eye. The dose expansion phase of the study is enrolling patients at the 1E12 vg/eye dose. The primary objectives of this trial are to evaluate the safety and maximum tolerated dose of 4D-125. Secondary endpoints include assessments of clinical activity, including both visual function and anatomical endpoints.

XLRP is a rare inherited X-linked recessive genetic disorder that causes progressive vision loss and blindness in boys and young men. There are currently no approved therapies for XLRP. Seventy percent of cases are caused by mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene. The estimated worldwide prevalence of XLRP due to RPGR variants is approximately one in 25,600 people, which represents approximately 24,000 patients in the US, and France, Germany, Italy, Spain and the UK (together, EU-5). It is characterized by dysfunction and degeneration of photoreceptors in the retina. Symptoms of XLRP are initially characterized by night blindness, followed by loss of peripheral visual field, decreasing visual acuity and eventually blindness.

4DMT is a clinical-stage company harnessing the power of directed evolution for targeted gene therapies. 4DMT seeks to unlock the full potential of gene therapy using its platform, Therapeutic Vector Evolution, which combines the power of directed evolution with approximately one billion synthetic capsid sequences to invent evolved vectors for use in targeted gene therapy products. The company is initially focused in three therapeutic areas: ophthalmology, cardiology and pulmonology. The 4DMT targeted and evolved vectors are invented with the goal of being delivered through clinically routine, well-tolerated and minimally invasive routes of administration, transducing diseased cells in target tissues efficiently, having reduced immunogenicity and, where relevant, having resistance to pre-existing antibodies. 4DMT is currently advancing five product candidates in development: 4D-310 for Fabry disease, 4D-125 for XLRP, 4D-150 for wet AMD, 4D-110 for choroideremia and 4D-710 for cystic fibrosis.

4D-310, 4D-150, 4D-125 and 4D-110 are in clinical trials and have not yet been approved for marketing by the US FDA or any other regulatory authority. No representation is made as to the safety or effectiveness of 4D-310, 4D-150, 4D-125 or 4D-110 for the therapeutic use for which they are being studied. 4D Molecular Therapeutics, 4DMT, Therapeutic Vector Evolution, and the 4DMT logo are trademarks of 4DMT.