Four Posters Highlight Unique Mechanism and Broad-Spectrum
Antibacterial Activity of ACH-702
Unique Elvucitabine Activity Profile and 48-Week Phase 2 Results
Featured in Oral Presentation
NEW HAVEN, Conn., Oct. 27, 2008 (GLOBE NEWSWIRE) -- Achillion Pharmaceuticals today announced the presentation of data from its antibacterial and HIV programs at the 48th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC)/ Infectious Diseases Society of America (IDSA) 46th annual meeting, held October 25-28, 2008, in Washington, D.C.
Data from Achillion's antibacterial program was highlighted in four abstracts, which demonstrate the potent antibacterial activity and dual-targeting mode-of-action of its isothiazoloquinolone (ITQ) analogs, including lead candidate ACH-702, particularly against gram-positive pathogens.
"These abstracts build the case that ACH-702 possesses strong bactericidal activity, particularly against gram-positive pathogens such as S. aureus," said Milind Deshpande, Ph.D., Executive Vice President of Research and Chief Scientific Officer. "The compound's activity against drug-resistant bacteria, including both laboratory and clinical MRSA strains with multiple mutations, demonstrates its potential utility in combating these serious and difficult-to-treat infections."
* The abstract, "Dual Targeting of Gyrase and Topoisomerase IV
by ACH-702 and Mutation Analysis in Staphylococcus aureus,"
described the dual-enzyme targeting mode-of-action of ACH-702.
In vitro, ACH-702 expressed significant inhibitory activity
against the target enzymes gyrase and topoisomerase, which are
responsible for drug-resistant mutations, and assays confirmed
that the candidate inhibits DNA synthesis.
* The abstract, "In Vitro and In Vivo Antibacterial Activities
of ACH-702 against Gram-positive Pathogens," details the
broad-spectrum activity displayed by ACH-702, particularly
against gram-positive bacteria, including those resistant to
methicillin, vancomycin, and quinolones. ACH-702 also
demonstrated activity against gram-negative bacteria, and
exhibited in vivo efficacy for S. aureus in animal models of
infection.
* The abstract, "Optimization of the Anti-MRSA Activity of
3-Animomethylpyrrolidine-Substituted Isothiazoloquinolones,"
detailed the optimization of ITQ substitution patterns for
anti-MRSA activity, which created a series of ITQ analogs.
These analogs were highly active against S. aureus and E. coli,
validating that optimizing these substitution patterns may lead
to exceptionally potent ITQ compounds against MRSA infection.
* The abstract, "Bactericidal Activity of ACH-702 against
Non-dividing Staphylococci," examined the antibiotic activity
of ACH-702 against non-dividing bacteria, because in many
clinical infections, pathogens are often in environments not
conducive to growth. In this study, ACH-702 retained dose-
dependent bactericidal activity against the non-dividing
pathogens, which is in contrast to other antibiotic
comparators, which showed little or no killing of non-dividing
cells.
"The antibacterial market represents an enormous opportunity which Achillion hopes to capture in the long-term with measured investment into our development programs," said Michael Kishbauch, President and CEO. "Given the evolving regulatory climate for antibacterials, we recently completed a pre-IND consultation with FDA on the most appropriate therapeutic applications and clinical development program for ACH-702. We received guidance on a path toward regulatory approval for topical administration of ACH-702, but we will work with another FDA group, the Division of Special Pathogen and Transplant Products (DSPTP), to seek additional guidance on the systemic administration of the candidate. We are currently assessing our development plans for ACH-702, and will update investors once we make a decision on how best to allocate resources toward the program's advancement."
In addition, on Sunday, October 26, 2008, Edwin DeJesus, M.D., an investigator from the Orlando Immunology Center Orlando, FL, gave an oral presentation of previously reported 48-week safety and efficacy results from Achillion's Phase 2 trial of elvucitabine in treatment naive HIV-1 infected patients. The results demonstrated that elvucitabine had a substantial anti-viral effect and a safety profile similar to 3TC (lamivudine).
About ACH-702
ACH-702, Achillion's lead antibacterial candidate, is an internally discovered compound for the treatment of serious nosocomial (hospital-based) bacterial infections. ACH-702 has a novel target profile against bacterial DNA replication enzymes and potent broad-spectrum bactericidal activity, characteristics that indicate it may play an important role in the fight against drug-resistant bacteria. In preclinical studies, ACH-702 has demonstrated potent antibacterial activity against a number of medically relevant bacteria, including drug-resistant strains such as MRSA and vancomycin-resistant enterococci (VRE). In late-stage preclinical studies, ACH-702 demonstrated acceptable pharmacokinetic and safety profiles. Potent antibacterial activity has been demonstrated against both sensitive and drug-resistant strains in well established preclinical infection models.
About Elvucitabine
Elvucitabine, Achillion's HIV product candidate, is an L-cytosine nucleoside analog reverse transcriptase inhibitor (NRTI) that has demonstrated potent antiviral activity against HIV, including strains resistant to other NRTIs in vitro. NRTIs are the predominant class of drugs for use in HIV combination therapy and are frequently prescribed given their established potency, favorable short and long-term safety profile and fewer and less severe adverse side effects. Clinical and pre-clinical data collected to date indicate that elvucitabine can be dosed as a 10 mg pill once daily and may be used in combination therapy. In addition, the L-nucleoside configuration of the compound may provide protection against mitochondrial toxicity, a serious side effect often seen with D-nucleosides. Finally, elvucitabine has been demonstrated to have a longer half-life than other approved NRTIs, providing a potential barrier to the emergence of drug resistance in patients who are less than perfectly compliant.
About Achillion
Achillion is an innovative pharmaceutical company dedicated to bringing important new treatments to patients with infectious disease. The company's proven discovery and development teams have advanced multiple product candidates with novel mechanisms of action. Achillion is focused on solutions for the most challenging problems in infectious disease -- HIV, hepatitis and resistant bacterial infections. For more information on Achillion Pharmaceuticals, please visit the company's web site at www.achillion.com or call Achillion at 1-203-624-7000. ACHN-G
This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including statements with respect to the timing, completion and success of Achillion's preclinical studies and clinical trials of Achillion's drug candidates. Among the factors that could cause actual results to differ materially from those indicated by such forward-looking statements are: unexpected regulatory actions or delays; uncertainties relating to results of clinical trials, including additional data relating to ongoing clinical trials; Achillion's ability to obtain additional funding required to conduct its research, development and commercialization activities; Achillion's ability to enter into successful collaboration arrangements; Achillion's ability to obtain shareholder approval for its private placement financing, and Achillion's dependence on its collaboration with Gilead Sciences. These and other risks are described in the reports filed by Achillion with the U.S. Securities and Exchange Commission, including its Annual Report on Form 10-K for the year ended December 31, 2007.