Therapy Areas: Hereditary Disorders
First Patient Dosed in Phase 1 Clinical Trial of 4D-110 by Intravitreal Injection for the Treatment of Choroideremia
29 July 2020 - - The first patient has been dosed in the Phase 1 clinical trial of 4D-110, a Roche-licensed product candidate, delivered by a single intravitreal injection for Choroideremia. Choroideremia is a blinding and currently untreatable X-linked inherited retinal disease, US-based precision-guided AAV gene medicines developer 4D Molecular Therapeutics said.

The Phase 1 open-label, dose-exploration and dose-expansion study is expected to enroll up to 15 patients with Choroideremia.

The study is designed to assess the preliminary safety, tolerability and biological activity of a single intravitreal injection of 4D-110.

In addition, the clinical trial will evaluate the effect of 4D-110 on the visual function and retinal degeneration.

Affecting approximately 10,000 individuals in the United States and the European Union, Choroideremia is an X-linked, slowly-progressive, degenerative disease of the retina and choroid of the eye caused exclusively by deletions or mutations in the CHM gene, resulting in a missing or defective REP1 protein.

Choroideremia initially manifests as night-blindness and peripheral visual field defects, usually starting in the first two decades of life.

As the disease progresses, the visual field begins to constrict relatively early in the disease's progression, which hinders patients' ability to conduct daily activities and eventually leads to vision loss.

4DMT's precision-guided gene therapy approach holds promise for the treatment of Choroideremia by using a proprietary and optimized AAV vector to deliver a functional copy of the CHM gene, resulting in the production of the REP1 protein.

4D-110, which is licensed to Roche, is comprised of a CHM transgene insert and 4DMT's proprietary vector 4D-R100, a vector designed to provide targeted delivery via intravitreal administration and to efficiently transduce all layers of the retina.

4DMT is a clinical-stage precision gene medicines company harnessing the power of directed evolution to unlock the full potential of gene therapy for rare and large market diseases in lysosomal storage diseases, ophthalmology, neuromuscular diseases, and cystic fibrosis.

4DMT's proprietary Therapeutic Vector Evolution platform enables a "disease first" approach to product discovery and development, thereby empowering customization of AAV vectors to target specific tissue types associated with the underlying disease.

These proprietary and optimized AAV vectors are designed to provide targeted delivery by routine clinical routes, efficient transduction, reduced immunogenicity, and resistance to pre-existing antibodies -- attributes that could enable the development of gene therapies that overcome known limitations of conventional AAV vectors.

4DMT vectors are designed to exhibit improved therapeutic profiles that enable the company to pursue previously untreatable patient populations and to address a broad range of rare and large market disease markets.