ELRIG Drug Discovery 2025

Applications of High Throughput Experimentation in Reaction Optimisation and Drug Discovery (Both Oral and Poster Presentation)

^{Date and Time: Wednesday 22nd October, 2025; 12:35 PM - 12:50 PM
Location: Auditorium 4
Presented by:  George Ballantyne, Senior Scientist HTE, Medicinal Chemistry} 

Evotec leverages automated High Throughput Experimentation (HTE) to run 96 reactions per plate, speeding up parallel synthesis and reaction optimization. This shortens Design-Make-Test-Analyse cycles significantly. The presentation highlights two case studies:

• Pd-coupling reaction optimization using plate-based HTE
• A Direct-to-Biology approach to fast-track drug discovery

High Throughput Chemistry (HTC) Combined with Direct to Biology (D2B): Integrated Processes to Fast-Track Hit Identification

^{Poster number: 119
Presented by:  Charles Gauquelin, Senior Research Scientist, High Throughput Biology and Screening}

Evotec’s High Throughput Chemistry (HTC) platform, in conjunction with its Direct to Biology (D2B) workflow, provides a fully integrated solution for rapid structure-activity relationship (SAR) exploration in early-stage drug discovery. This approach enables the microscale synthesis of large compound derivative libraries in a plate-based format, significantly reducing the time and resources typically required for compound purification.

Crude reaction mixtures, which contain target molecules, are directly screened in bioassays using Evotec’s High Throughput Screening (HTS) platforms. This direct interface between synthetic chemistry and biological evaluation facilitates a streamlined transition from chemical synthesis to functional data generation.

Evotec showcases the efficiency benefits of the fully integrated HTC-D2B platform through successful case studies, highlighting its capacity to shorten cycle time and support faster, data-driven decision-making.

Applications of High Throughput Experimentation in Reaction Optimization and Drug Discovery (Both Oral and Poster Presentation)

^{Poster number: 75
Presented by:  George Ballantyne, Senior Scientist HTE, Medicinal Chemistry} 

Accelerating drug discovery demands efficient exploration of chemical space while conserving materials and reducing timelines. High Throughput Experimentation (HTE) provides a robust solution by enabling parallel screening of reaction conditions with minimal manual input.

At Evotec, automated HTE workflows allow up to 96 reactions to run simultaneously, significantly reducing chemist intervention and speeding up optimisation. This presentation features case studies from discovery chemistry, highlighting the impact of HTE on reaction optimisation.

High Throughput Transcriptomics-Empowered Drug Discovery – A Case Study for Identifying More Disease-Relevant Hits

^{Poster number: 116 
Presented by:  Rüdiger Fritsch, VP Panomics}

High failure rates in drug discovery highlight the need for better early decisions around efficacy, safety, and mechanisms of action. Omics technologies offer a solution by providing unbiased, highly multidimensional data to guide these choices.

To address this, Evotec has developed ScreenSeq™, a scalable and cost-effective 384-well transcriptomics platform that delivers high-quality data. The proprietary platform has been applied across the discovery pipeline - from large-scale primary screens to SAR analyses and safety profiling.

ScreenSeq™ enables very precise hit selection in phenotypic screening by identifying disease signature reverting compounds, and supports hit validation and expansion. A case study involving over 20,000 compounds will illustrate its utility and diverse applications in drug discovery.

The Application of New Approach Methodologies with Machine Learning as an Integrated Safety Strategy to De-risk Drug-Induced Liver Injury in Drug Discovery

^{Poster number: 255
Presented by:  Julie Eakins, Principal Scientist, Toxicology & Innovation Efficiency}

High drug failure rates, often due to organ-specific toxicities like drug-induced liver injury (DILI), have driven the adoption of New Approach Methodologies (NAMs) in early drug discovery. These human-relevant, high-throughput assays - combined with AI and machine learning - enable earlier and more accurate toxicity and efficacy predictions.

This study used five validated NAM assays with human exposure-based thresholds to classify 139 compounds for DILI risk. While cumulative flag analysis showed moderate accuracy, integrating all assay data into an XGBoost model significantly improved predictive performance, supporting better decision-making in drug development.

From Targeting to Efficacy: Characterisation of Psychedelic-Like Compounds Acting as 5HT_2A Receptor Agonists

^{Poster number: 42
Presented by: Elisabetta Perdona}

The serotonin 5-HT_2A receptor is a key target in the central nervous system, with growing interest due to its involvement in functional selectivity, biased agonism and interactions with brain neurotransmitters. Despite their therapeutic potential in neuropsychiatric disorders, the hallucinogenic effects of psychedelic 5-HT_2A receptor agonists limit their clinical use. This study outlines a preclinical assay platform designed to identify and optimize novel 5-HT_2A agonists that retain therapeutic efficacy without inducing hallucinations. Reference compounds included serotonin, psilocin, and psilocybin, which were used to validate binding, functional activity, and behavioral outcomes.

Psilocin showed selective partial agonism at 5-HT_2A and 5-HT_2C receptors, and full antagonism at 5-HT_2B, with functional effects confirmed in human and mouse recombinant cell lines. Electrophysiological recordings demonstrated increased firing of prefrontal cortex neurons, while behavioral assays confirmed psilocybin’s hallucinogenic activity, which was blocked by a selective 5-HT_2A receptor antagonist. Together, these assays form a robust translational platform for screening non-hallucinogenic 5-HT_2A receptor agonists, supporting their development for mood disorder treatment.