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Chimerix's PIM Conjugate Technology Reduces Risk of Nephrotoxicity for CMX001 and CMX157
Date:11/16/2010

rganic Anion Transporter 1 (hOAT1) and hOAT3, which are both linked to kidney excretion of endogenous substances and certain drugs.  Researchers noted that net uptake of CMX001 and CMX157 was not enhanced in OAT-expressing cells.  These data provide evidence that CMX001 and CMX157 are not substrates of human OAT1 and OAT3 and therefore have a low potential to cause OAT-mediated nephrotoxicity.  In contrast, uptake of cidofovir and tenofovir was enhanced in in vitro cells expressing OAT1, consistent with previous literature reports.  

"Nephrotoxicity is a serious and potentially life-threatening adverse effect associated with the antiviral agents cidofovir and tenofovir.  Through the application of our proprietary PIM Conjugate Technology we are able to dramatically alter drug distribution and thereby potentially avoid nephrotoxicity," said George Painter, Ph.D., Chief Scientific Officer of Chimerix.  "Our animal and clinical studies of CMX001 and CMX157, in which both compounds have demonstrated a positive safety profile, are consistent with our in vitro observations that CMX001 and CMX157 are not metabolized in the kidney.  Furthermore, these data are consistent with, and provide a mechanistic explanation for, data presented at the recent ICAAC meeting that CMX001 was well tolerated in 46 patients with compromised renal function."

Chimerix is developing CMX001 for dual-use as a broad-spectrum antiviral for the treatment of life-threatening viruses in immunocompromised transplant and cancer patients and as a medical countermeasure in the event of a smallpox release.  CMX001 is currently in Phase 2 clinical trials for the prophylaxis and treatment of human cytomegalovirus infection. CMX157 is currently in Phase 1 clinical testing for the treatment of HIV infections.

Cidofovir and tenofovir are polar, acyclic nucleoside phosphonates that are FDA-approved as Vistide® (cidofovir injection) f
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SOURCE Chimerix, Inc.
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