High-throughput screening (HTS) has revolutionised early-stage drug discovery. It enables teams to screen hundreds of thousands of compounds at speed, helping to identify and generate leads, before high-cost pre-clinical studies. But despite its scale, HTS often hits a wall. Compounds can look undeniably promising in vitro, however, they can underperform or fail completely, down the line during in vivo studies. The root issue? A lack of biological context. This can cause drug development to be extremely costly and time-consuming, with the average cost for developing a drug being $2.6 billion and taking 10-15 years to get to market [1, 2]. As drug discovery teams face growing pressure to de-risk pipelines earlier, and avoid costly downstream failures, there’s a growing need for methods that combine HTS efficiency with physiological relevance, without sacrificing throughput.
HTS remains a vital tool in early drug discovery, particularly through two dominant strategies: biochemical (target-based) assays and cell-based phenotypic screens. Biochemical assays allow researchers to assess compound activity against defined molecular targets with high precision. They are designed to detect direct interactions such as enzyme inhibition, receptor binding, or modulation of specific signalling components, and their strength lies in target specificity, quantifiability, and scalability [3.]. When the underlying disease mechanism is well understood, target-based assays offer a streamlined path from screen to lead optimisation, however, the lack of biological context can lead to downstream failure, when tested in more complex environments.
Cell-based models, on the other hand, offer a way of identifying phenotypic effects, adding another layer of biological relevance. They offer the ability to measure compound effects on more complex cellular behaviours within a living cellular context [4]. Both approaches benefit from automation, cost-efficiency, and clear readouts, making them ideal for large-scale compound libraries.
For all their advantages, however, traditional HTS models often fall short when it comes to biological complexity. Isolated targets may not reflect the broader context of human physiology, and even cellular systems fail to capture whole-organism interactions [5].
Despite advances in HTS technologies, a persistent challenge in drug discovery remains: the translational gap. Promising hits identified in biochemical or cell-based assays often fail to demonstrate efficacy or safety in animal models or human trials. This gap stems largely from the lack of systemic context in early-stage models. While these platforms are excellent for understanding molecular interactions or cellular phenotypes, they rarely capture the complex interactions between tissues, organs, and metabolic processes that define disease progression in living organisms [6].
For example, a compound may show potency in isolated cells but be rendered ineffective in vivo due to poor absorption, rapid metabolism, or unintended effects on other systems. This is especially true for diseases involving ageing, neurodegeneration, or metabolic dysfunction, where whole-organism dynamics are crucial. As a result, pharmaceutical teams are often forced to rely on costly, time-consuming in vivo studies later in the pipeline to validate findings, by which point major resources have already been committed.
This disconnect can cause high attrition rates and inflates R&D timelines. The ideal solution would be a screening platform that offers both biological relevance and scalability, enabling earlier identification of candidates with true translational potential, before committing to resource-intensive downstream development.
The nematode Caenorhabditis elegans (C. elegans) has long been a valuable tool in biological research. As one of the first multicellular organisms to have its genome fully sequenced, it has contributed significantly to our understanding of development, neurobiology, and ageing. With a short lifecycle, transparent body, and a fully mapped nervous system, C. elegans offers a rare combination of genetic tractability, experimental speed, and whole-organism insight.
Importantly, around 60–80% of human disease genes have homologues in C. elegans, making it a powerful model for exploring conserved pathways in areas such as neurodegeneration, metabolic dysfunction, mitochondrial disorders, and lifespan regulation [7]. The worm’s simplicity does not come at the expense of biological relevance. It has a nervous system, a well-characterised muscle system that shares features with more complex animals, a digestive tract, and complex behavioural outputs that can be quantified in response to drug exposure.
Historically, however, the C. elegans model has been underutilised in drug discovery pipelines, largely due to perceived limitations in throughput and automation. However, their ability to thrive in liquid culture, paired with recent technological advances, has now made scalable, phenotypic screening in C. elegans not only possible but practical, opening new doors for early-stage in vivo testing [8].
At Magnitude Biosciences, we’ve harnessed the well-established biological advantages of C. elegans to develop a high-throughput screening (HTS) platform tailored for the demands of modern drug discovery. VivoScanTM , our liquid-based C. elegans screening system, enables the efficient testing of large compound libraries at scale, providing whole-organism, functional readouts that go beyond what traditional cell-based or biochemical assays can offer.
By introducing in vivo screening earlier in the pipeline, our platform helps teams identify promising targets and compounds with greater biological context, improving the chances of translational success. Positive hits from VivoScanTM can be prioritised with higher confidence before moving into mammalian models, reducing risk, cost, and time in early-stage development. Because C. elegans is a non-protected species under most regulatory frameworks, this approach also avoids the ethical and logistical challenges associated with vertebrate studies.
Our HTS workflow provides lifespan and healthspan data captured across multiple timepoints, enabling you to monitor treatment effects dynamically over the worm’s lifecycle. This makes it possible to detect both acute and long-term compound effects, further enhancing decision-making during hit selection. For teams looking for lead optimisation, our proprietary WormGazer™ platform adds another level of resolution. WormGazer™ uses advanced imaging and analysis tools to quantify healthspan, locomotion, and cognitive-like behaviours over time, revealing the biological impacts of candidate compounds.
Together, our platforms offer a scalable, biologically rich, and cost-effective solution to streamline early-stage discovery and improve the likelihood of identifying translatable drug candidates faster and with greater confidence.
Why wait for in vivo testing when early whole-organism screening can give you invaluable insight from the first hurdle? VivoScanTM delivers scalable, biologically rich data, capturing the systemic effects missed by traditional screens. If you’re looking for truly translatable discovery data, at scale, the worm is the way to go.
References
Sign up to our newsletter today, to get access to the latest company and industry news
© 2025 Magnitude Biosciences Ltd. All rights reserved.