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|Gilead Announces Findings from New Preclinical Study Evaluating Novel Class of HIV Capsid Inhibitors|
– Findings Support Continued Investigation of Inhibitor Class as Part of a Long-Acting Antiretroviral HIV Treatment Strategy –
“Capsid inhibition is a previously unexplored target for antiviral
therapy and we are pleased to share these preclinical results showing
the potential role of this class of therapy as a novel, long-acting
injectable for HIV treatment and prevention in the future,” said
The preclinical study found that GS-CA1, an exemplified member of a novel class of CAIs, is a highly potent inhibitor of HIV-1 replication in human peripheral blood mononuclear cells (PBMCs) (EC50 = 140 pM) and displays similar potency against multiple HIV-1 clinical isolates from all major clades. The study also found that the identified CAIs bind to a broadly conserved site at the interface of two adjacent monomers within a capsid hexamer and accelerate capsid assembly in vitro.
The identified CAIs maintained full activity in vitro against HIV-1 mutants resistant to licensed antiretrovirals (ARVs) and selected for HIV capsid variants L56I, M66I, Q67H or N74D with an attenuated in vitro replication phenotype. Preclinical mechanistic studies revealed a dual mode of action targeting both the late-stage virion maturation and post-entry capsid functions. GS-CA1 showed high in vitro metabolic stability and displayed an extended-release preclinical pharmacokinetic profile following a single subcutaneous administration that maintained target plasma concentrations for over 10 weeks.
Gilead plans to evaluate a selected development candidate in Investigational New Drug (IND)-enabling toxicology studies and begin Phase 1 clinical trials in 2018.
GS-CA1 is an investigational therapy and has not been determined to be safe or efficacious.
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. In addition, we may
be unable to begin Phase 1 clinical trials in the currently anticipated
timelines. In addition, we may observe unfavorable results from
additional studies involving proprietary CAIs, including GS-CA1. In
addition, Gilead may make a strategic decision to discontinue
development of GS-CA1 and other proprietary investigational CAIs if, for
example, Gilead believes commercialization will be difficult relative to
other opportunities in its pipeline. As a result, GS-CA1 and other
proprietary investigational CAIs may never be successfully
commercialized. These risks, uncertainties and other factors could cause
actual results to differ materially from those referred to in the
forward-looking statements. The reader is cautioned not to rely on these
forward-looking statements. These and other risks are described in
detail in Gilead’s Quarterly Report on Form 10-Q for the quarter ended
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