At Evotec, we offer a uniquely integrated and industrial-scale platform for tuberculosis (TB) drug discovery, designed to accelerate the journey from concept to clinic. Our global infrastructure, combined with deep scientific expertise, enables us to deliver high-impact solutions across the entire R&D continuum.

Evotec’s proprietary and partner-accessible compound libraries encompass hundreds of thousands of structurally diverse, drug-like molecules, including natural products, focused anti-infective subsets, and novel scaffolds. These libraries are continuously enriched through medicinal chemistry innovation and strategic collaborations, ensuring relevance to evolving resistance mechanisms and pathogen biology. For in silico approaches Evotec uses commercial libraries as well as bespoke de novo designed virtual libraries, employing generative AI tools. 

As with other pathogens, phenotypic screening is often the most effective hit-finding strategy for TB. We apply advanced screening technologies using virulent Mycobacterium tuberculosis (M.tb) in BSL-3 facilities. These platforms support high-throughput and miniaturized assays, enabling robust hit identification and expansion. With a wide range of readouts - including CFU, luminescence, and fluorescence - we ensure precise and reliable data from the earliest stages of discovery.

Besides phenotypic screening Evotec also applies a variety of alternative hit-finding approaches. Target-based biochemical, biophysical and fragment-based screening are complemented by in silico approaches. Ligand and structure based virtual screening can be performed using commercial and AI-designed virtual libraries to widen the chemical space explored. Once potential hits are identified early synthesis or purchase and testing to establish true activity, ideally in virulent M.tb, is performed. 

Evotec’s hit triage strategy is tailored to the unique challenges of TB and infectious diseases. It integrates:

• Structure-activity relationship (SAR) analysis including purchase and testing of close analogues to guide early medicinal chemistry
• Microbiological profiling including evaluating minimum inhibitory (MIC) and bactericidal (MBC) concentrations, time-kill kinetics, and the effects of inoculum and serum. Our studies cover replicating, non-replicating, and intracellular M.tb.
• Mode-of-action (MoA) studies using genetic and biochemical tools
• Resistance profiling through mutant generation and whole-genome sequencing
• In vitro ADME and early DMPK profiling to assess developability

Confirmed hit series with demonstrated potential are then progressed into the next phases of drug discovery.

From hit-to-lead through lead optimization to IND-enabling studies, Evotec offers seamless progression. Efficient Design-Decide-Make-Test-Learn (D2MTL) cycles quickly generate data to inform predictive model building. Integrated capabilities in in vitro and in vivo ADME and toxicology supplement primary potency and selectivity testing. Gap analyses help define goals for multi-parameter optimization. Human and AI-supported designs are triaged and prioritized to ensure fast optimization towards candidate quality molecules. Our TB-specific in vivo models, including acute and chronic infection models as well as relapsing mouse models including with mice that develop necrotic granulomas, are complemented by the Hollow Fibre Infection Model (HFIM), which supports PK/PD and resistance studies. Mathematical modeling and simulation further guide dose and regimen selection, ensuring a smooth transition from preclinical to clinical development.

With a proven track record in TB drug discovery and a team of globally recognized experts, Evotec stands as a trusted partner in the fight against tuberculosis. We combine innovation, flexibility, and scientific excellence to deliver results - on time and at scale.  Evotec’s platform is not only scientifically rigorous but also highly adaptable - capable of supporting bespoke project designs aligned with partner goals and pathogen-specific challenges.