# Predictive assessment of acute and chronic cardiotoxicity using combinatorially matured hPSC-CMs

> **NIH NIH R44** · CURI BIO INC · 2021 · $750,000

## Abstract

PROJECT SUMMARY
Nearly 90% of drugs under development fail to reach the market. Many of these failures occur due to
cardiotoxicity. In a few notable cases, some drugs pass pre-clinical screens and clinical trials, only to be removed
from the market once toxic effects are discovered in large patient populations. These failures represent a
tremendous source of waste and constitute a significant part of the ~$2 billion cost of bringing a single drug to
market. Consequently, the FDA now mandates that all drugs undergo in vitro cardiotoxicity testing before being
tested in humans. This has led to a significant and growing market for tools and technologies that enable earlier
detection of toxic effects before exposure to patients. However, current screening methods fall short of predicting
how a drug will behave in the body; indeed there is a pressing need for more predictive model systems. Further,
most screens focus on acute toxicity and do not test for longer-term structural toxicity which is typically only
caught after a patient is exposed to the drug over long treatments. Human induced pluripotent stem cell-derived
cardiomyocytes (hPSC-CMs) are an attractive model for in vitro preclinical toxicity screening; they are relatively
easy to maintain, are derived from human tissue, and have the potential to reduce the need for animal
experimentation. However, at present, hPSC-CM based assays do not properly replicate the function of the
human heart. These cells exhibit phenotypes similar to that of fetal tissue and do not respond as expected to
drugs of known effect; in some cases, known bad-actor drugs fail to induce toxicity in hPSC-CMs, while others
only show effects when exposed to supra-physiological doses of the drug in question. The drug discovery
industry and its regulators realize the potential of hPSC-CMs for early cardiotoxicity screening, but also
understand that—at present—there are significant limitations to their use in the drug development process. Thus,
it is clear that the production of mature cardiac tissues that accurately recapitulate in vivo drug responses
represents a significant opportunity for reducing cost and waste in drug development. NanoSurface Biomedical,
Inc., aims to apply bioengineering approaches to enhance the maturity and predictive power of hPSC-CM cells
for highly predictive drug-induced cardiotoxicity screening. We hypothesize that these cells will give more
predictive results in in vitro cardiotoxicity detection for both acute and chronic toxicity mechanisms. We will first
focus on applying these stimuli and validating their ability to predict toxicity (Phase 1). After this validation, we
will characterize the phenotypes of these cells and use them in a variety of assays targeted toward understanding
a wide variety of specific toxicity mechanisms that are very difficult to screen in the laboratory (Phase 2). We will
use these data to understand the role that cell maturity plays in toxicity detection and create a ...

## Key facts

- **NIH application ID:** 10274730
- **Project number:** 4R44HL151094-02
- **Recipient organization:** CURI BIO INC
- **Principal Investigator:** Nicholas Andrew Geisse
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $750,000
- **Award type:** 4N
- **Project period:** 2020-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10274730

## Citation

> US National Institutes of Health, RePORTER application 10274730, Predictive assessment of acute and chronic cardiotoxicity using combinatorially matured hPSC-CMs (4R44HL151094-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10274730. Licensed CC0.

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