# Post-exposure immunotherapy for ricin exposure

> **NIH NIH R44** · ZABBIO, INC. · 2021 · $788,841

## Abstract

PROJECT SUMMARY
 Ricin is a category B toxin due to its ease of acquisition, dissemination, and the high potential
for morbidity and mortality after exposure. Ricin is naturally produced by the castor bean plant,
Ricinus communis, which is cultivated on industrial levels worldwide. Ricin constitutes up to 5% of the
total dry weight of the castor bean and can be extracted using several simple enrichment steps. Ricin
in semi-purified or purified form is extremely toxic to humans following injection, inhalation, or
ingestion and has been used as an agent of bioterrorism. Ricin was previously weaponized by the
United States, the former Soviet Union, Iraq and likely other countries, has been used in
assassinations and was recently detected in a number of U.S. government facilities. There are
currently no methods of preventing or treating ricin exposure – this represents a major unmet
need for protection of civilians and military forces.
 The Mapp team, in collaboration with Dr. Nicholas Mantis (Wadsworth Center, Albany, NY)
and Dr. Chad Roy (Tulane National Primate Research Center, Covington, LA), has identified a
number of highly potent anti-ricin monoclonal antibodies (mAbs). These mAbs, either in their original
fully murine state, when chimerized with human constant regions, or when fully humanized, have
demonstrated protection of mice when administered prior to and after ricin challenge. Further, one of
these mAbs, humanized PB10 (hPB10), has been shown to protect non-human primates (NHPs) from
aerosol challenge therapeutically – this is the first demonstration of protection of NHPs by a
therapeutic against a lethal aerosol challenge. We have now generated evidence that a mAb cocktail
consisting of one RTA and one RTB mAb may provide improved potency and extend the therapeutic
window. The in vitro and in vivo potency of the mAb cocktails we have tested is superior to any
individual mAb previously described, which is consistent with the combination of mAbs functioning at
different steps in the intoxication process. Anti-RTB mAbs interfere with ricin attachment to target
cells, while anti-RTA mAbs are proposed to block ricin intracellular trafficking.
The Specific Aims to advance a ricin medical countermeasure to the clinic are: 1) Engineer, produce,
and down-select from the panel of RTA/RTB mAbs; 2) Humanize the lead RTA/RTB mAb cocktail and
manufacture to support Aim #3; 3) Determine the prophylactic and therapeutic efficacy of the lead
RTA/RTB combination in the rhesus macaque aerosol challenge model. These data combined with
the Chemistry, Manufacturing and Control (CMC) information will form the basis of a pre-
Investigational New Drug (IND) meeting with the FDA to solicit guidance on continued development of
the product.

## Key facts

- **NIH application ID:** 10236557
- **Project number:** 5R44AI141282-04
- **Recipient organization:** ZABBIO, INC.
- **Principal Investigator:** Miles Burke Brennan
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $788,841
- **Award type:** 5
- **Project period:** 2018-06-29 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10236557

## Citation

> US National Institutes of Health, RePORTER application 10236557, Post-exposure immunotherapy for ricin exposure (5R44AI141282-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10236557. Licensed CC0.

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