uniQure Announces New Preclinical Data in Hemophilia A and Fabry Disease in Oral Presentations at the 22nd ASGCT Annual Meeting
LEXINGTON, Mass. and AMSTERDAM, the Netherlands, May 02, 2019 (GLOBE NEWSWIRE) -- uniQure N.V. (NASDAQ: QURE), a leading gene therapy company advancing transformative therapies for patients with severe medical needs, will present today new preclinical data on its gene therapy candidates AMT-180 for the treatment of hemophilia A and AMT-190 for the treatment of Fabry disease. These data will be featured today in back-to-back oral presentations at the 22nd American Society for Gene and Cell Therapy (ASGCT) Annual Meeting in Washington D.C.
AMT-190 for Fabry Disease
Fabry disease is an X-linked genetic disorder resulting from a deficiency of a-galactosidase A (a-gal or GLA). The current standard of care for Fabry disease is bi-weekly infusions of enzyme replacement therapy, a treatment that has shown not to be effective in many patients due to poor targeting of target organs such as the kidney and heart. In addition, a significant number of patients develop antibodies to the enzyme, a-gal or GLA.
AMT-190 is a novel AAV5 gene therapy approach for Fabry disease that comprises a recombinant AAV5 vector incorporating a proprietary, exclusively licensed, modified NAGA (ModNAGA) variant. AMT-190 provides expression of ModNAGA, which shows a high structural resemblance to a-gal. This approach may have several advantages over a-gal therapies, including higher stability in blood, better biodistribution in the target organs, secondary toxic metabolite reduction and improved cross-correction of neighboring cells. ModNAGA is also effective in the presence of a-gal antibodies.
Data from in vitro and in vivo studies show that AMT-190 has the potential to become a one-time treatment option that improves upon the enzyme replacement standard of care with more efficient uptake in the kidney and heart and an improved immunogenicity profile.
AMT-190 Preclinical Data Findings
Proof-of-concept for AMT-190 was established through multiple studies in wild-type and Fabry mice. The oral presentation at ASGCT features the following data:
Preclinical in vitro studies demonstrated that the expression of ModNAGA results in GLA activity in cells and suggest that uptake of ModNAGA is mediated by the Mannose-6-phosephase (M6P) receptor.
In vivo studies in wild-type mice show that a single intravenous administration of AMT-190 resulted in a ten- to twenty-fold higher GLA activity in the plasma compared to the control group, suggesting that AMT-190 has the potential to provide therapeutically relevant GLA activity in plasma and in target organs.
These results were underscored by a study in GLA knock-out mice, demonstrating significantly increased GLA activity in plasma and significantly reduced Lyso-Gb3 in the target organs after a single dose of AMT-190. In silico and in vitro studies also show that the modifications introduced into NAGA pose a very low immunogenicity risk.
“These data show that AMT-190 has the potential to be a differentiated, one-time treatment option that could be used by all Fabry patients,” added Dr. van Deventer. “We will continue to advance our preclinical research toward our goal of developing a best-in-class gene therapy for Fabry disease.”