PROJECT SUMMARY/ABSTRACT
Maternal mortality and AIDS are among the leading causes of death in reproductive-age women globally due to
unintended pregnancy and the disproportionate burden of HIV infection. While effective prevention methods
exist, only 21% of women have access to modern contraceptives and adherence to HIV PrEP regimen is poor
in many HIV-endemic regions. Multipurpose prevention technologies (MPT) aim to synchronize contraceptive
delivery with HIV PrEP, offering a patient-centered approach to provide dual coverage to sexually active women
in a single product. A long-acting unified delivery product that can be administered in a discreet manner could
reduce stigma around contraceptives and HIV PrEP, thereby improving uptake and adherence to combination
prevention products. Our goal is to develop a long-acting delivery implant of etonogestrel (ENG) and islatravir
(ISL) drugamer with an unprecedented 2-year release duration for pregnancy and HIV prevention that eliminates
further need of adherence. A new subcutaneous nanofluidic multipurpose implant (NanoMPI) will be brought
together with a new polymeric prodrug technology termed “drugamer”, to achieve this innovative product
candidate that delivers ultra-long acting ENG+ISL drug dosing durations. The NanoMPI leverages a nanofluidic
membrane with nanochannels and a single drugamer reservoir to achieve zero-order release kinetics through
passive diffusion without pumping mechanisms, permitting discreet, user-independent dosing. Key product
attributes will include drug stabilization on the multi-year timeframe, minimized early- and late-stage burst release
and pharmacokinetic (PK) tailing, zero-order drug release kinetics tailored to the individual drug PK/PD
(pharmacodynamic) requirements, user-independent dosing, and retrievability. The project is structured around
3 specific aims: 1) to develop optimized ENG-ISL drugamer formulations that stabilize the drugs and exhibit the
desired zero order release profiles, in concert with the optimization of the NanoMPI device for 2-year sustained
release; 2) to assess pharmacokinetics, tolerability, and safety of the lead ENG-ISL NanoMPI device for 2 years
in pigtail macaques; and 3) to evaluate contraception and HIV PrEP efficacy of ENG-ISL NanoMPI in pigtail
macaques via repeated low-dose vaginal challenge and develop a PK/PD model. We will use a milestone-driven
research approach to advance the ENG-ISL NanoMPI technology towards the ultimate goal of clinical translation,
leveraging the interdisciplinary team’s experience in drugamer technology, drug delivery, pre-clinical and clinical
HIV prevention studies, and hormonal contraceptive and antiretroviral pharmacology. Importantly, the NanoMPI
addresses user preferences for a dual prevention product, discretion and longer dosing duration. Successful
completion will generate a versatile MPT platform that could be adopted for other drug combinations and
preventative strategies.