# Development of PTLS-209 for treatment for giardiasis

> **NIH NIH R44** · PRIMETIME LIFE SCIENCES, LLC · 2022 · $300,000

## Abstract

Project Summary:
This project focuses on the development of treatment to combat giardiasis resistance to standard care drugs.
Giardia lamblia is a highly infective waterborne parasite that causes severe diarrhea. Current antigiardiasis drugs
fail in about 20% of cases, and they all have undesirable side effects. Additionally, drug-resistant G. lamblia
strains can be readily raised in the laboratory, increasing the risk of this category B bioterrorism organism.
Chronic infection of giardiasis and lack of treatment in developing countries lead to malnutrition, growth
retardation in children, and death. Thus, the prevalence of giardiasis impacts global health profoundly, and the
World Health Organization has included giardiasis in its Neglected Diseases Initiative.
Our collaborators and NCATS/NIH investigators identified fumagillin as a lead compound through screening an
approved drug library. Fumagillin kills Giardia trophozoites in vitro with high potency via MetAP2 inhibition. It has
also shown excellent efficacy in an in vivo mouse model; however, it has two liabilities: heat and humidity
instability, as well as potential toxicity in humans. These liabilities hamper the further development of fumagillin.
We addressed these issues during our lead optimization process and identified PTLS-209, which has high
potency for MetAP2, low bioavailability, improved efficacy, and enhanced stability. Thus, PTLS-209 has the ideal
attributes to be an effective and safe intestinal targeting drug for treating giardiasis, particularly drug-resistant
giardiasis.
The arsenal of drugs available for treating giardiasis belongs to only a few chemical classes, primarily
nitroimidazoles, thiazolides, and benzimidazoles. G. lamblia drug resistance already exists for each of these
classes of compounds. None of the currently used drugs to treat giardiasis act on the MetAP2 enzyme. Thus,
PTLS-209, a fumagillin analog, will not be subject to the current drug resistance mechanisms that result in
treatment failures.
PTLS-209 has an excellent safety profile, while other analogs of the fumagillin class, beloranib, ZGN-1061, and
ZGN-1258, have shown adverse effects in preclinical studies and clinical trials. Note that these analogs were
administered subcutaneously, whereas PTLS-209 is administered orally and has a very low oral bioavailability
in mice (which may be the cause of its low toxicity). In order to mitigate the risks early, we have adopted the “Fail
Early, Fail Cheap” approach. We propose two critical tests to evaluate these toxicity concerns in our SBIR Phase
I portion of the Fast-Track application. Once we meet our Phase I milestones, we will continue IND-enabling
studies to ensure that PTLS-209 has all the attributes to be a successful treatment for giardiasis and will file an
IND application.

## Key facts

- **NIH application ID:** 10483491
- **Project number:** 1R44AI165220-01A1
- **Recipient organization:** PRIMETIME LIFE SCIENCES, LLC
- **Principal Investigator:** Janak K Padia
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $300,000
- **Award type:** 1
- **Project period:** 2022-07-12 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10483491

## Citation

> US National Institutes of Health, RePORTER application 10483491, Development of PTLS-209 for treatment for giardiasis (1R44AI165220-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10483491. Licensed CC0.

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