Ho: First in human clinical evaluation of 10E8.4/iMab, a potent and broad bispecific antibody against HIV
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.
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.
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