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Chimerix's Brincidofovir (CMX001) Data Accepted for Three Presentations at 27th International Conference on Antiviral Research

DURHAM, N.C., May 6, 2014 (GLOBE NEWSWIRE) -- Chimerix, Inc. (Nasdaq:CMRX), a biopharmaceutical company developing novel, oral antivirals in areas of high unmet medical need, today announced three presentations on its investigational broad-spectrum antiviral brincidofovir (BCV, CMX001) at the 27th International Conference on Antiviral Research (ICAR) being held May 12-16, 2014 at the Raleigh Convention Center in Raleigh, NC.

The presentations will summarize in vitro studies that advance understanding of brincidofovir's activity and resistance profile. The Phase 3 trial of brincidofovir, SUPPRESS, is currently enrolling adult allogeneic hematopoietic cell transplant (HCT) recipients to determine the safety and efficacy of brincidofovir for the prevention of cytomegalovirus (CMV) infection in HCT recipients. Brincidofovir is also being evaluated in an open-label pilot trial for the treatment of adenovirus (AdV) infection in immunocompromised patients.

The ICAR presentations suggest that: 1) BCV-resistance to AdV may be relatively slow to develop in the clinic; 2) acyclovir (ACV) co-administration with BCV will not have a negative effect on the utility activity of BCV against CMV in the clinical setting; and 3) enhanced uptake of BCV and production of the active antiviral helps explain the improved activity/safety profile of BCV versus cidofovir (CDV).

  • In Vitro Selection of Brincidofovir-Resistant and Cidofovir-Resistant Human Adenovirus (AdV). (Poster Session 1 on Tuesday, May 13)

    This is the first report of viral resistance to brincidofovir selected from AdV grown in cell culture. The first mutation detected in AdV polymerase resulted in a two-to-three-fold decrease in antiviral activity compared to wild-type virus; emergence of a second mutation led to an overall four-to-eight-fold decrease in activity. These data suggest that BCV-resistant AdV may be relatively slow to develop in the clinic and may require multiple mutations for moderate levels of viral resistance (less than 10-fold) compared to wild-type virus.
  • Brincidofovir (BCV, CMX001) and Acyclovir (ACV) Are Additive Against Cytomegalovirus (CMV) In Vitro. (Poster Session 1 on Tuesday, May 13)

    ACV is a commonly administered antiviral in transplant recipients for the prevention of herpes simplex virus reactivation. BCV is in development for the prevention of CMV reactivation in HCT recipients. BCV and ACV together demonstrated no antagonistic effects and modest additive antiviral activity against CMV in vitro, suggesting ACV co-administration with BCV would not have a negative effect on the activity of BCV against CMV in the clinical setting, an important finding in patients often administered many anti-infective medications in the post-transplant period.
  • Brincidofovir (BCV, CMX001) Delivers High Intracellular Concentrations of Cidofovir Diphosphate (CDV-PP). (Poster Session II on Wednesday, May 14)

    BCV shares the in vitro broad-spectrum antiviral activity of CDV against all five families of double-stranded DNA (dsDNA) viruses that cause disease in humans. Both compounds are converted to the active antiviral CDV-PP within cells, but BCV is 50-500 fold more potent in in vitro assays. Cell-lines commonly used in viral assays were incubated with the same concentration of BCV and CDV, with much higher levels of the active antiviral (160 to 450-fold) CDV-PP detected inside the cells exposed to BCV. Improved intracellular transfer of the circulating molecule and subsequent delivery of CDV to the intracellular space where viral replication takes place results in the 50 to more than 500-fold improvement in in vitro potency of BCV relative to CDV against dsDNA viruses. In addition to improved efficacy, BCV may provide an improved safety profile through lower plasma concentrations of CDV, a compound noted for its renal toxicity due to preferential uptake by human organic anion transporters (hOATs) and resulting high concentration in the proximal renal tubules. The significantly improved safety profile of BCV versus CDV is partly attributable to the inability of hOATs to recognize BCV. The combination of low BCV doses/plasma exposure leading to high intracellular active drug levels and inability of hOATs to concentrate BCV in kidneys helps explain the favorable renal safety profile for BCV versus CDV.

About Brincidofovir (CMX001)

Chimerix's lead product candidate, brincidofovir, has the potential to be the first broad-spectrum antiviral for the prevention and treatment of clinically significant infections caused by DNA viruses. Brincidofovir is an oral nucleotide analog that has shown broad-spectrum in vitro antiviral activity against all five families of DNA viruses that affect humans, including viruses in the herpesvirus family and adenoviruses (AdV). Brincidofovir has shown no evidence of kidney or bone marrow toxicity in nearly 900 patients exposed to date. Building on the positive Phase 2 results in CMV prevention, Chimerix initiated the Phase 3 SUPPRESS trial in 2013. If positive, data from SUPPRESS will support Chimerix's initial regulatory submission for brincidofovir for the prevention of CMV infection in adult HCT recipients. Chimerix recently initiated a Phase 3 trial in AdV, an often-fatal viral infection with no approved treatment; enrollment is ongoing for the pilot portion of that trial. Chimerix is also working with BARDA to develop brincidofovir as a medical countermeasure against smallpox. Brincidofovir has received Fast Track designation from the FDA for CMV, AdV, and smallpox.

About Cytomegalovirus (CMV)

CMV is a member of the herpes virus family and remains the most common cause of fatal infections in HCT recipients. Two-thirds of adults have been exposed to CMV, generally in childhood, with lifelong viral latency established following the initial infection. In immunocompromised individuals such as transplant recipients, CMV often reactivates during the post-transplant period when the immune system is weak. CMV itself is immunosuppressive and reactivation of the virus can predispose a patient to other opportunistic infections. No therapies are approved for the prevention of CMV in HCT recipients.

About Adenovirus (AdV)

AdV causes upper respiratory infections including the common cold in individuals with intact immune systems, but is often rapidly fatal in patients with compromised immune responses. AdV is most common during the post-transplant period when the immune system is weak. No therapies are approved for the treatment of AdV.

About Chimerix

Chimerix is a biopharmaceutical company dedicated to developing and commercializing novel, oral antivirals in areas of high unmet medical need. Chimerix's proprietary technology has given rise to two clinical-stage nucleotide analog lipid-conjugates, brincidofovir and CMX157, both of which have demonstrated the potential for enhanced activity and safety in convenient, orally administered dosing regimens. Chimerix is currently enrolling SUPPRESS, a Phase 3 study of brincidofovir for the prevention of CMV, and the pilot portion of a Phase 3 study of brincidofovir treatment for adenovirus infection. Chimerix is also working with BARDA to develop brincidofovir as a medical countermeasure against smallpox. Chimerix's second product candidate, CMX157, was licensed to Merck in July 2012 for the treatment of HIV infections. For further information, please visit Chimerix's website, www.chimerix.com.

Forward-Looking Statements

Statements contained in this press release regarding matters that are not historical facts are "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Risks are described more fully in Chimerix's filings with the Securities and Exchange Commission, including without limitation its most recent Quarterly Report on Form 10-Q, its most recently filed Current Reports on Form 8-K and other documents subsequently filed with or furnished to the Securities and Exchange Commission. All forward-looking statements contained in this press release speak only as of the date on which they were made. Chimerix undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.

CONTACT: Joseph T. Schepers Executive Director, Investor Relations and Corporate Communications ir@chimerix.com 919-287-4125Source:Chimerix, Inc.