Ho: First in human clinical evaluation of 10E8.4/iMab, a potent and broad bispecific antibody against HIV
OVERVIEW
Protection against HIV infection by the infrequent, passive administration of a potent HIV-neutralizing antibody
could be a better alternative to current pre-exposure prophylaxis regimens which are based on daily dosing
with antiviral drugs. This option requires that the chosen antibody possesses suitable antiviral breadth,
potency, and pharmacokinetic properties.
Background: Prior
in vitro
and preclinical studies at the Aaron Diamond AIDS Research Center (ADARC),
performed with Foundation funding, identified 10E8.4/iMab as a potent and broad bispecific antibody
against HIV. It neutralized a global panel of 118 HIV-1 pseudotyped viruses with a geometic mean IC50 of
0.001 μg/mL. An earlier variant of 10E8.4/iMab also potently neutralized 98% of viruses in a second panel of
200 HIV-1 isolates belonging to clade C, the dominant subtype accounting for 50% of new infections worldwide,
and the most prevalent clade in sub-Saharan Africa. 10E8.4/iMab also reduced virus load substantially in
HIV-1-infected humanized mice, and an earlier variant of 10E8.4/iMab provided complete protection when
administered prior to systemic HIV challenge.
The activities under this award will advance 10E8.4/iMab into clinical development in order to further evaluate
its potential as a novel prophylactic agent against HIV-1. Investigators at ADARC will conduct a first-in-human
clinical trial evaluating the safety, pharmacokinetics, and antiviral activity of 10E8.4/iMab. A dose escalation
study will be conducted in a phased approach and will evaluate IV administration in HIV-negative participants,
IV administration in HIV-positive participants with viremia, and subcutaneous administration in HIV-negative
subjects. In addition, a master cell bank of an earlier variant of 10E8.4/iMab, known as 10E8.2/iMab, will be
generated as a back-up molecule for potential GMP manufacture.
The grant is led by David D. Ho at the Aaron Diamond AIDS Research Center.
RESEARCH OBJECTIVES
1. Phase 1 clinical trial to determine the safety, tolerability, pharmacokinetics and antiviral activity of 10E8.4/iMab for HIV-1 prevention
2. 10E8.2/iMab master cell bank creation for potential GMP manufacture