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The following is an excerpt from a press release from uniQure. Read the press release in its entirety here.


uniQure N.V., a gene therapy company, presented new preclinical data on its gene therapy candidates for the treatment of hemophilia A and for the treatment of Fabry disease during back-to-back oral presentations at the 22nd聽American Society for Gene and Cell Therapy Annual Meeting in Washington, D.C.

AMT-180 for Hemophilia A

Hemophilia A is an X-linked bleeding disorder resulting from a deficiency in coagulation Factor VIII that serves as a cofactor for Factor IX in the activation of the coagulation cascade. About 30 percent of the hemophilia A patient population develops inhibitors to Factor VIII over the course of the disease.

AMT-180 comprises a recombinant AAV5 vector incorporating a proprietary modified Factor IX hat, when activated through normal mechanisms, induces thrombin generation independently of Factor VIII.

Data from multiple in vitro and in vivo studies show that a single intravenous administration of AMT-180 results in dose-dependent, therapeutically meaningful Factor VIII-independent activity as measured by thrombin generation and one-stage clotting assay. AMT-180 is a differentiated approach that is suggested to be hepatocyte-friendly and non-thrombogenic based on the studies conducted to date and is expected to reduce and potentially prevent bleedings in hemophilia A patients with and without inhibitors.

AMT-180 Preclinical Data Findings

Proof-of-concept for AMT-180 was established through studies across two different animal models. The oral presentation at ASGCT features the following data:

  • Preclinical studies in FVIII-depleted human plasma show that AMT-180 induced clinically relevant thrombin activation, and up to 29% of Factor VIII-independent activity, in plasma with and without inhibitors.
  • The mechanistic proof-of-concept of AMT-180 was demonstrated in a hemophilia A mouse model, where a single intravenous administration of AMT-180 resulted in sustained, dose-dependent hemostatic effect as measured by one-stage clotting assay.
  • The studies further demonstrate that AMT-180 shows activation kinetics similar to native FIX and is not hyperactive.
  • A pilot study in non-human primates demonstrated that a single administration of AMT-180 resulted in sufficient FIX protein expression that translates to clinically relevant Factor VIII-independent activity in humans. No elevation of coagulation activation markers or signs of thrombi formation were observed.

鈥淒ata from these preclinical studies show the exciting potential of AMT-180 to provide clinically meaningful Factor VIII-independent activity after a one-time administration.鈥 stated Sander van Deventer, M.D., Ph.D., chief scientific officer at uniQure. 鈥淲e are particularly encouraged by the broad potential of AMT-180 in treating both patients with and without inhibitors, and the unique approach of AMT-180 that potentially circumvents durability issues because of its hepatocyte-friendly profile.鈥

 

Read the press release in its entirety here.聽

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