# Repurposing the EMD-Serono "mini-library" for Cryptosporidium drug development

> **NIH NIH R21** · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · 2020 · $230,252

## Abstract

PROJECT SUMMARY
Cryptosporidiosis is amongst the most important causes of life-threatening diarrhea in children globally, causes
incurable diarrhea in AIDS and transplant patients, and is the most common cause of waterborne diarrheal
outbreaks in the United States. Almost all human cases of cryptosporidiosis are due to infection of the small
intestinal epithelium with one of two species of Cryptosporidium parasites, C. parvum and C. hominis.
Nitazoxanide, the only approved drug, is efficacious in otherwise healthy adults, but unfortunately, has limited
efficacy (~56%) in children and is equivalent to a placebo in AIDS patients. The goal of this project is to address
the need for new anti-Cryptosporidium drugs via an exciting collaboration between the German pharmaceutical
company EMD-Serono, an academic Cryptosporidium biologist, an academic medicinal chemist with extensive
prior industry experience, and an academic biologist (also with extensive industry experience) whose laboratory
specializes in in vitro and in vivo drug pharmacology. The developmental cascade to accomplish this is guided
by an ideal target product profile for a drug effective in all affected patient populations; the methods bring together
novel in vitro assays and a highly immunocompromised mouse model of cryptosporidiosis with well-established
pharmacology and medicinal chemistry approaches. The R21 phase will deliver two lead compounds with anti-
Cryptosporidium efficacy in a chronic mouse model of infection, along with knowledge of key compound
characteristics and potential safety concerns. The open access EMD-Serono “mini-library” has already been
screened and three promising Cryptosporidium growth inhibitors were identified that are suitable for follow-up.
A second EMD-Serono mini-library will be screened to identify additional potential starting points. Validated
Cryptosporidium growth inhibitors will then be prioritized using 1) assays to assess if compounds are cidal or
static, selective, and active against C. hominis, and 2) existing EMD-Serono pharmacokinetic and safety data
and available EMD-Serono analogs for structure-activity relationship (SAR) studies. After prioritization and
testing available analogs in vitro, mouse pharmacokinetic studies and efficacy studies will be performed. If the
progression milestones are met, the R33 phase will result in optimization of one lead chemical series for potency
and safety. The other series will be held in backup. For this, cyclic rounds of chemical synthesis will be combined
with in vitro Cryptosporidium assays, in vitro ADME studies, mouse PK studies, and the chronic mouse model of
cryptosporidiosis. Success would yield an optimized clinical candidate that is ready to be advanced to testing in
large animal diarrhea models and regulatory toxicology studies. Given the dire need for new cryptosporidiosis
drugs, the public health impact of success could be extremely significant.

## Key facts

- **NIH application ID:** 9868261
- **Project number:** 5R21AI141184-02
- **Recipient organization:** UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
- **Principal Investigator:** David Griggs
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $230,252
- **Award type:** 5
- **Project period:** 2019-02-08 → 2021-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9868261

## Citation

> US National Institutes of Health, RePORTER application 9868261, Repurposing the EMD-Serono "mini-library" for Cryptosporidium drug development (5R21AI141184-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9868261. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*