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In addition to the two clinical trials in Acute Kidney Injury (AKI) indication, QPI-1002 (formerly also called DGFi) is tested in a Phase I/II clinical trial for prevention of delayed graft function in patients undergoing deceased donor kidney transplantation. The multi-center, two-part Phase I/II clinical trial in DGF is expected to enroll up to 204 adult kidney transplant recipients. The first part of the study is a dose-escalation design to evaluate the safety and tolerability of a single intravenous injection of QPI-1002 in renal transplant patients at high risk to develop DGF. The second part of the study will evaluate safety and potential clinical activity of a selected dose of QPI-1002 in the same patient population. Patients will be enrolled in clinical sites in the United States. DGF represents Quark’s second indication being evaluated for the systemically administered dug candidate in human clinical trials.
The initiation of patient dosing with QPI-1002 in DGF is an important milestone for Quark. The siRNA drug candidate is based on Quark’s proprietary concept of temporary and reversible inhibition of p53 for therapeutic purposes, first described by Quark scientists and collaborators from University of Illinois, Chicago in 1999 in Science magazine (Science. 1999 Sep 10; 285). QPI-1002 reflects Quark’s success in developing products originating from conceptually novel internal developments. These accomplishments further validate Quark’s ability to advance innovative product candidates from discovery into the clinic.
The investigational drug candidate QPI-1002 is a siRNA designed to temporarily inhibit the expression of the pro-apoptotic gene, p53 to protect normal cells from acute injury. Preclinical studies have shown that p53-targeted siRNA can be effective in protecting kidneys from injury due to cold ischemia or lack of oxygen during organ preservation and storage between removal from the donor and implantation QPI-1002 is a chemically modified siRNA discovered by Quark and protected by a host of patents and patent applications of Quark and with structure covered under licenses from Silence Therapeutics and from Alnylam Pharmaceuticals. QPI-1002 was the first systemically administered siRNA in a human clinical study.
DGF is one of the most common complications during the immediate postoperative period in renal transplantation and affects 25-40% of the deceased donor renal transplants in the United States and Europe. DGF in renal transplantation results most often from ischemia-reperfusion injury that occurs when the blood flow is re-established to the transplanted kidney initiating a chain of events that can lead to severe renal damage upon transplantation. Post-kidney transplant DGF is associated with longer hospital stays and higher rates of graft rejection, which in turn decreases the survival of the transplanted kidney (graft survival). Currently there is no marketed drug therapy or preventive therapy for DGF. DGF is designated by FDA and EMEA as indication for orphan drug development.
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