Case Study: Zebrafish Models Reduce Preclinical Costs by 60%

Exploring how zebrafish screening transformed cardiomyopathy drug development, reducing costs and accelerating timelines

Background

A small biotech company dedicated to developing therapies for genetic cardiomyopathies faced significant hurdles in its preclinical drug development process. Their initial approach involved screening a library of 300 commercial compounds targeting heart-related pathways. The primary screening was conducted using human cardiomyocytes in two models: Dilated Cardiomyopathy (DCM, failure in heart relaxation) and Hypertrophic Cardiomyopathy (HCM, failure in heart contraction). This process led to the identification of 20 promising hits.

However, leaping from in vitro assays directly to mammalian models, such as rodents, often resulted in low success rates during clinical trials. Traditional murine models incurred high costs and extended timelines, prompting the company to seek a more efficient strategy to streamline drug development and reduce expenditures.

Challenges

• High Costs: Screening 20 hits in custom rodent models would cost over $1.5 million.
• Prolonged Timelines: Rodent screening would take more than 24 months due to the extended breeding and growth periods needed to reach the necessary sample size (minimum 10 animals per compound).
• Lack of relevant genetic models: Few CROs offered appropriate HCM and DCM genetic models to test the efficacy of potential therapies before first-in-human trials.

Solution

ZeClinics implemented a comprehensive zebrafish-based approach to bridge the gap between in vitro assays and costly mammalian models. The solution involved three key steps:

1. Custom Disease Model Generation

We developed tailored zebrafish genetic models targeting key genes involved in Dilated Cardiomyopathy (DCM) and Hypertrophic Cardiomyopathy (HCM). Using advanced CRISPR/Cas9 technology, we created models that closely mimic human pathophysiology, ensuring biological relevance. Our Knockout Builder Solutions include:

• Gene editing strategy design & validation
• Embryo microinjection
• Founder screening
• Line establishment

2. Model Characterization and Validation

Before drug screening, we thoroughly characterized and validated the zebrafish models to ensure they accurately represented the cardiomyopathy phenotypes. Using our ZeCardio platform, we automatically evaluated key cardiovascular parameters such as:

• Heartbeat frequency
• Ejection fraction
• Arrhythmias
• Heart chamber area
• Cardiac arrest

3. High-Throughput Drug Screening

Once validated, we conducted high-throughput drug screening of the 20 compounds identified from in vitro assays using the ZeCardio platform. This rapid process enabled us to evaluate the efficacy of the compounds within just a few months, leading to the identification of 5 promising candidates for further testing.

By integrating zebrafish early in the screening process, we provided actionable data that significantly reduced the number of compounds moving on to costly rodent models.

Results

The integration of zebrafish into their drug discovery pipeline produced substantial benefits:

Faster Screening

Zebrafish enabled rapid, high-throughput screening, compressing models generation and the evaluation of 20 compounds in just 7 months. By running zebrafish screenings in parallel with the early development stages of rodent models, the company was able to narrow the number of compounds tested in mice from 20 to 5. This approach shortened the overall preclinical timeline from 24 months to 14 months, accelerating the drug development process by over 40%.

Reduced R&D Costs

By leveraging zebrafish as a first step in screening, the company significantly cut down on the number of costly rodent experiments, reducing overall preclinical screening costs to $600,000. This resulted in a 60% reduction in costs, translating to $900,000 in savings that could be reallocated to other R&D initiatives.

Optimized Candidate Selection

Zebrafish models provided critical whole-organism insights early in the screening process. When combined with data from rodent models, this synergy led to a more robust preclinical assessment, enhancing the predictive value for clinical outcomes and reducing clinical trial failures. Prioritizing only the most promising candidates for rodent testing streamlined the company’s workflow, optimizing time and resources while boosting overall success rates.

Conclusion

This case exemplifies how integrating zebrafish models can transform drug discovery, especially in areas where traditional models may fall short. By adopting this innovative approach, the biotech company not only achieved substantial cost savings but also improved its capacity to bring effective therapies to market.

By Miriam Martínez

Miriam is a Human Biologist with a strong background in neuropharmacology and a passion for bridging science and innovation. After earning a master’s degree in the Pharmaceutical and Biotech Industry, she completed her PhD in Biomedicine at Pompeu Fabra University (Barcelona), where her research focused on the behavioral analysis of animal models for neurophenotypical characterization. Following her doctoral studies, Miriam transitioned into the healthcare marketing and communication sector, where she played a key role in developing impactful marketing strategies and educational campaigns for leading pharmaceutical brands. She now leverages her scientific expertise, strategic thinking, and creative communication skills in her current role at ZeClinics.