Chimerix's CMX157 Shows Potential to Treat Multi-Drug-Resistant HIV and Improve the Activity and Toxicity Profile of Tenofovir
RESEARCH TRIANGLE PARK, N.C., July 28 /PRNewswire/ -- Chimerix,
Inc., a biopharmaceutical company developing orally-available
antiviral therapeutics, today announced the publication of research
results demonstrating the potential of CMX157 (hexadecyloxypropyl
tenofovir) to effectively suppress replication of human
immunodeficiency virus (HIV) that cannot be treated with currently
available nucleoside/nucleotide reverse transcriptase inhibitors
(NRTIs), including tenofovir disoproxil fumarate (Viread®), due
to the development of multi-drug resistance. Earlier this year,
Chimerix initiated a dose-escalating Phase 1 clinical trial of
CMX-157 to evaluate drug safety, tolerability and
In these preclinical studies, CMX157 was highly active against
all major subtypes of HIV, including strains that fail to respond
to all currently available NRTIs. HIV strains with pan-NRTI
resistance were sensitive to CMX157, and no antagonistic
interactions were observed between CMX157 and any currently
approved antiretroviral. The in vitro efficacy of CMX157 was
increased approximately 300-fold relative to tenofovir. This
improvement in potency was attributable to the significantly
increased intracellular uptake of CMX157, resulting in
approximately 34-fold higher levels of the active antiviral in
cells treated with CMX157 as compared to tenofovir. No toxicities
were seen with CMX157, even at concentrations 100-fold above the
EC50 of HIV mutants highly resistant to current therapies.
The article, "Development of Hexadecyloxypropyl Tenofovir
(CMX157) for the Treatment of Wild-Type and
Nucleoside/Nucleotide-Resistant HIV" appears in the July 2010 issue
of the journal Antimicrobial Agents and Chemotherapy.
"CMX157 has the potential to address three issues with
tenofovir: loss of efficacy against multi-nucleoside resistant HIV,
renal toxicity and slow uptake by target cells," said Randall
Lanier, Ph.D., the paper's lead author and Senior Director of
Virology at Chimerix. "In addition, the ability of CMX157 to
directly intercalate the envelope of HIV virions may lead to an
important application as a topical microbicide."
"As a promising clinical stage antiretroviral with significant
potential as a powerful new treatment option for HIV patients,
CMX157 may lead to a new set of combination therapies," said George
Painter, Ph.D., Chief Scientific Officer and Chairman of the Board
of Chimerix. "Chimerix is actively exploring the best ways to match
the unique properties of this drug with the needs of the global HIV
CMX157 is a new chemical entity created by applying Chimerix's
PIM (Phospholipid Intramembrane Microfluidization) Conjugate
Technology to chemically modify tenofovir, marketed as the prodrug
Viread®, an antiviral agent approved for the treatment of HIV
and chronic hepatitis B. Chimerix's PIM Conjugate Technology
improves the absorption and distribution profile of tenofovir,
effectively decreasing potential toxicity while increasing
antiviral efficacy. The compound is currently in Phase 1 clinical
testing in the United States.
Chimerix is developing novel antiviral therapeutics with the
potential to transform patient care in multiple settings, including
transplant, oncology, acute care and global health. The company's
lead candidate, CMX001, is in Phase 1 and Phase 2 clinical studies
in immunocompromised transplant and cancer patients for the
treatment of life-threatening viruses, such as BK virus,
cytomegalovirus and adenovirus. CMX001 is also being developed as a
biodefense countermeasure in the event of a smallpox release.
Chimerix has advanced a second antiviral compound, CMX157, into
Phase 1 clinical studies as a potent nucleoside analogue against
multi-drug resistant HIV infections. Led by a world-class antiviral
drug development team, Chimerix is also leveraging the company's
extensive chemical library to pursue new treatments for hepatitis C
virus, malaria and other global public health needs.
Privately-held, Chimerix has received financing from Sanderling
Ventures, Canaan Partners, Alta Partners, Asset Management Company
and Frazier Healthcare Ventures, as well as significant funding
from the National Institute of Allergy and Infectious Diseases. For
additional information on Chimerix, please visit http://www.chimerix.com/.
Source: Chimerix, Inc.
CONTACT: Kenneth I. Moch, Chief Executive Officer of Chimerix,
+1-919-313-2961; or Karen L. Bergman, +1-650-575-1509, or Susan M.
Pietropaolo, +1-201-923-2049, both of BCC Partners for Chimerix, Inc.
Web Site: http://www.chimerix-inc.com/
Posted: July 2010