Data Presented at the 47th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy Demonstrate That INCB9471 is a Potent, Selective Inhibitor of the HIV-1 Virus with Excellent Pharmacokinetics Suitable for Once-Daily Dosing
INCB9471 is a novel, orally available CCR5 antagonist that is a member of a new class of drugs to treat HIV/AIDS. Data presented at ICAAC suggest that INCB9471:
-- is a potent and highly selective inhibitor of the HIV-1 virus;
-- offers an improved pharmacokinetic profile that may provide clinically relevant advantages over other CCR5 antagonists including once daily dosing with or without ritonavir;
-- is synergistic with existing HIV therapies including nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase, protease inhibitors, and the HIV fusion inhibitor, T20; and,
-- is not associated with rapid development of resistance to the HIV-1 virus in in vitro studies.
INCB9471, which is being developed as a once-daily treatment for HIV, has been studied at 100 mg, 200 mg and 300 mg once-daily doses in a Phase IIa 14-day trial in which the compound provided potent and prolonged antiviral effects in HIV patients with R5-tropic virus. In this initial Phase IIa trial, INCB9471 was well-tolerated at all three doses. The compound is currently being evaluated in several drug interaction trials to support the initiation of two Phase IIb six-month trials in treatment-experienced HIV patients.
Below are summaries of the four presented posters which can also be accessed at the following link under the event - Incyte Corporation at 47th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC): http://investor.incyte.com/phoenix.zhtml?c=69764&p=irol-calendar.
Poster Number 751
INCB9471 Is a Non-Competitive Small Molecule Antagonist of CCR5
The potency of INCB9471 in blocking CCR5 ligand binding is similar to that of other CCR5 antagonists however; saturation binding assays suggest that INCB9471 may have a different binding site than maraviroc, the recently approved CCR5 antagonist, which may be of significance in the context of overcoming drug resistant HIV-1 strains.
Poster Number 818
INCB9471 Is a Potent Inhibitor of R5-HIV-1 Infection In Vitro
In in vitro studies, INCB9471 demonstrates synergistic or additive effects, rather than antagonistic effects, when combined with the four major classes of antiretroviral agents. Additionally, experiments designed to study development of resistance to INCB9471 demonstrate that de novo mutations that result in resistance to INCB9471 do not appear rapidly in cell culture.
Poster Number H-1034
Single- and Multiple-Dose Pharmacokinetics of INCB9471, a Potent Antagonist of CCR5 Co-Receptor
In these two studies, INCB9471 exhibited rapid absorption and slow elimination (terminal elimination half-life of 60 hours) compatible with QD dosing without ritonavir. The pharmacokinetics were linear in both the single- and multiple-dose. In the multiple-dose escalation trial, accumulation of INCB9471 was also linear and well-behaved. INCB9471 was safe and well tolerated at all doses e.g., for single doses up to 300 mg and for repeat doses up to 200 mg once-daily.
Poster Number H-1035
Effect of Ritonavir (RTV) on the Pharmacokinetics of INCB9471, a Potent Antagonist of CCR5 Co-Receptor
The primary objective of this clinical trial was to evaluate the effect of RTV when co-administered with INCB9471. In the study, the RTV 100mg BID, significantly altered the single-dose pharmacokinetic profile of INCB9471 by: reducing clearance by 93%, increasing AUC by 14-fold, and increasing t1/2 from 39 to 286h. Cmax increased by only 55%, implying that RTV had a greater effect on systemic clearance than on bioavailability. The repeat-dose pharmacokinetic results were consistent with the single-dose data. The data support the use of reduced doses of INCB9471 in the presence of ritonavir to achieve nearly constant blood levels of INCB9471 with once daily dosing. INCB9471 was safe and well tolerated when co-administered with RTV for 10 days.
Incyte Corporation (NASDAQ:INCY) is a Wilmington, Delaware-based drug discovery and development company focused on developing proprietary small molecule drugs to treat serious unmet medical needs. Incyte has a pipeline with programs in HIV, diabetes, oncology and inflammation. For additional information on Incyte, visit the Company's web site at www.incyte.com
Forward Looking Statements
Except for the historical information contained herein, the matters set forth in this press release, including statements with respect to the potential for INCB9471 to be combined with other once-daily antiviral therapies and to provide clinically relevant advantages over other CCR5 antagonists in development, the potential for CCR5 antagonists as a new class of drugs to treat HIV/AIDS, expectations regarding the initiation Phase IIb studies of INCB9471, and the efficacy and potential benefits of INCB9471, are all forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. These forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially, including the high degree of risk associated with drug development and clinical trials, results of further research and development, the impact of competition and of technological advances and the ability of Incyte to compete against parties with greater financial or other resources, Incyte's ability to enroll a sufficient number of patients for its clinical trials, and other risks detailed from time to time in Incyte's filings with the Securities and Exchange Commission, including its Quarterly Report on Form 10-Q for the quarter ended June 30, 2007. Incyte disclaims any intent or obligation to update these forward-looking statements.
Pamela M. Murphy
Vice President, Investor Relations/
Posted: September 2007