HIV/AIDSremainsaformidableglobalepidemic,with~37millionpeopleinfected(including~1.1millionin the US) and about one million AIDS-related deaths in 2017 (UNAIDS, CDC). Despite the efficacy of modern combination anti-retroviral therapy (cART), side effects and drug resistance remain serious obstacles to achieving optimal care, and poor adherence is a key factor in treatment failure. Thus, there is continued demand for well-tolerated HIV inhibitors with novel mechanisms of action and stronger barriers to resistance. HIVspecialistsareespeciallyenthusiasticaboutthepotentialoflong-actingtherapiestominimizesideeffects, enhance efficacy, and delay resistance through improved compliance. Navigen has identified a novel, protease-resistantD-peptideHIVentryinhibitor,CPT31,withthesedesiredcharacteristicsandhasadvancedit throughpreclinicaldevelopment.CPT31addressesmanyofthelimitationsofcurrentcARTandhasprovento be well tolerated and highly efficacious for both indications in non-human primates (NHPs), making it an ideal candidate for both therapy and PrEP. Additionally, CPT31?s PK makes it amenable to monthly and perhaps quarterly dosing (with depot formulation). In this grant application, we will partner with Johns Hopkins University to conduct a Phase Ia/Ib safety, tolerability, pharmacokinetics, and pharmacodynamics study of CPT31. The study will include three stages: 1) single ascending dose (SAD) in healthy volunteers, 2) multiple ascendingdose(MAD)inhealthyvolunteers,and3)MADinHIVpositivepatientsclassifiedasGroup1under the FDA guidance for industry. This study will enable Navigen to determine whether CPT31 has the characteristicsthatwarrantcontinuedclinicalstudiesandfurtherinvestment.

Public Health Relevance

Despite the efficacy of modern combination anti-retroviral therapy (cART) for HIV, side effects and drug resistance remain serious obstacles to achieving optimal care. Navigen?s novel, protease-resistant D-peptide HIVentryinhibitor,CPT31,addressesmanyofthelimitationsofcurrentcARTandiswell-toleratedandhighly efficacious in non-human primates. In this grant application, we will partner with Johns Hopkins University to conductaPhaseIa/Ibsafety,tolerability,pharmacokinetics,andpharmacodynamicsstudyofCPT31.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Small Business Innovation Research (SBIR) Cooperative Agreements - Phase II (U44)
Project #
2U44AI095172-08
Application #
9785192
Study Section
Special Emphasis Panel (ZAI1)
Program Officer
Lacourciere, Gerard
Project Start
2011-08-10
Project End
2022-03-31
Budget Start
2019-04-25
Budget End
2020-03-31
Support Year
8
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Navigen, Inc.
Department
Type
DUNS #
792046224
City
Salt Lake City
State
UT
Country
United States
Zip Code
84108