31 May 2019 - - US-based AAV gene therapy products developer 4D Molecular Therapeutics, Inc has released new preclinical data with its novel vector, 4D-C102, broadly for neuromuscular diseases and specifically for the product candidate incorporating 4D-C102 for Fabry Disease, 4D-310, the company said.
The data was highlighted in a poster presentation at the 6thInternational Update on Fabry Disease held May 26 to 28, 2019 in Prague, Czech Republic.
The data presented demonstrated superior transduction of 4DMT's novel vector, 4D-C102, in human cardiomyocytes in vitro as compared to AAV1, AAV8 and AAV9; dose dependent GLA expression and function after administration of 4D-310, that incorporates the 4D-C102 vector, in vitro in Fabry patient fibroblasts; and superior delivery of the 4D-C102 vector in non-human primate cardiac tissue in vivo as compared to AAV8 and AAV9.
Fabry disease is a rare, X-linked, monogenic disorder caused by mutations in the GLA gene that results in storage and accumulation of lipids and leads to debilitating effects on a range of organs and systems, including the heart.
Current enzyme replacement therapy partially clears accumulated lipids from the endothelial cells of affected organs; however, clearance in other cell types, including cardiomyocytes, appears incomplete.
As a result, heart disease is the most common cause of mortality in these patients. 4DMT's Fabry product candidate, 4D-310, aims to preferentially express the GLA enzyme in cardiomyocytes, in addition to other tissues including kidney and liver, to directly address the cause of Fabry-related heart disease.
4DMT is focused on the discovery and development of targeted, customised and proprietary next-generation AAV gene therapy products for use in patients with severe genetic diseases with high unmet medical need.
The company's discovery platform, termed Therapeutic Vector Evolution, empowers it to create customised gene delivery vehicles that can be designed to deliver genes specifically to any tissue or organ in the body, by optimal clinical routes of administration, at lower doses and with resistance to pre-existing antibodies.
4DMT believes the product candidates it has in development may enable it to treat both rare genetic diseases and complex large market diseases. 4DMT is creating a diverse and deep product pipeline through its own internal 4DMT products, as well as partnered programs.
The company is advancing the field of targeted and optimized AAV vector technology by deploying principles of evolution and natural selection to create vectors that are designed to efficiently and selectively target the desired cells within the diseased human organ via clinically optimal routes of administration, at manageable doses and with resistance to pre-existing antibodies in the population.
4DMT's Therapeutic Vector Evolution platform can deploy over 35 unique and proprietary AAV libraries comprised of an estimated 1bn vector capsid sequences.
After defining the target product profile, and the associated target vector profile, 4DMT then applies proprietary methods to identify lead vectors from within our AAV libraries.
The result is a customised, novel, and proprietary pharmaceutical-grade product candidate designed for targeted therapeutic gene delivery and efficacy in humans.