Science Pool

Machine Learning (ML) is becoming critical for the design and development of therapeutics. Just-Evotec Biologics has created a Humanoid Antibody Library for the discovery of biopharmaceuticals that is the first step towards leveraging artificial intelligence and ML. 

In this publication we describe how we have started the validation of the library by isolating antibodies against a target of pandemic concern, SARS-CoV-2.

We successfully identified a panel of human monoclonal antibodies that are novel, diverse, and pharmacologically active. These first-generation antibodies exhibited neutralization of SARS-CoV-2 viral infectivity across multiple strains and indicated high developability potential.

These results demonstrate the applicability of our platform for effective therapeutic antibody discovery.

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Continuous biomanufacturing is reducing the cost of goods of biopharmaceuticals. Achieving continuous manufacturing requires expertise in equipment design.

Download the highlights of Andrea Isby's presentation at Repligen's DSP Workshop in Estonia from May 23rd, 2024 to learn more. 

Download the presentation

High-throughput screening methodologies have accelerated downstream development for monoclonal antibodies by enabling parallelized evaluation of chromatographic resins across a range of conditions. However, scientists must now interpret results in a meaningful and consistent way.

Learn how Just - Evotec Biologics' Downstream Data Browser automates visualization of high-throughput datasets, fits response surface statistical models, standardizes report results from a high-throughput screening method and facilitates comparison across molecules allowing the accelerated development of continuous biomanufacturing processes.

Read our poster to learn more

4’-Phosphopantetheinyl transferase (PptT) is a crucial enzyme for the survival and virulence of Mycobacterium tuberculosis (Mtb), making it an attractive target for tuberculosis treatment. In recent research, our collaborators at University of North Carolina (UNC ); Weill Cornell Medical College, Texas Agricultural and Mechanical University (TAMU) explored ways to replace the amidinourea moiety in the previously known PptT inhibitor AU 8918.  These findings hold promise for developing new drugs to combat mycobacterial infections.

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Evotec and Sanofi scientists, together with TBAlliance and Tuberculosis Drug Accelerator  (TBDA) partners, have been involved in the discovery of  sequanamycins, a class of compounds that combat drug-resistant tuberculosis. The original compound , the SEQ-503 was a macrolide from the Sanofi Natural Product patrimony, discovered in 1962 in Vitry-sur Seine and named after sequana, the seine goddess in the Gallo-Roman religion. Optimization of SEQ-503 has given rise to SEQ9 with a remarkable efficacy against Mycobacterium tuberculosis (Mtb).

Key findings:

• Sequanamycins overcome Mtb’s inherent macrolide resistance.
• Lead compound   SEQ-9 is bactericidal when combined with other TB drugs.

Promising prospects for TB clinical candidates!

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We are honoured to be part of the TBDA consortium and would like to congratulate our colleagues on the release of their new publication

Interested in learning more?

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Evotec specializes in antifungal drug discovery with a focus on WHO and CDC priority human pathogens such as Aspergillus fumigatus, Candida spp, and Cryptococcus neoformans. Their track record in late-stage drug discovery is proven, aided by a range of established in vivo models of fungal infection that facilitate seamless progression from in vitro to in vivo studies.

Their expertise encompasses various areas, including in vitro compound characterization, invasive and localized in vivo fungal infection models, PK/PD mathematical modeling, and custom assay development tailored to individual project needs. They conduct comprehensive antifungal susceptibility testing to industry standards and offer specialized modalities such as combination testing to determine synergy or antagonism.

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A recent publication in Nature Medicine further validates Just – Evotec Biologics’ J.MD^TM Molecular Design suite. 

Children under the age of 5 years account for more than 75% of deaths attributable to malaria. The World Health Organization (WHO) has recommended the vaccine Morsquirix for paediatric use, but it has modest efficacy. Monoclonal antibodies and other complementary strategies are critically important in efforts to eradicate this disease. 
 
A multi-disciplinary team of scientists from multiple organizations collaborated on a project to select and engineer a potent and long-lasting antibody drug with anti-malaria activity. Key to this mission was to develop an antibody with developability properties amenable for cost-effective manufacturing and dosing in paediatric populations. 
 
Scientists from Just – Evotec Biologics played a crucial role in the project. They helped with the lead candidate selection by ranking a panel of human-derived potential antibody candidates for developability using Just - Evotec Biologics’ in silico Abacus tool. Abacus is a component of our J.MD^TM Molecular Design suite of tools for antibody research and development. Once the team had selected a lead and backup candidates, Just - Evotec Biologics scientists designed optimized variants of the candidate antibodies with greatly improved developability properties informed by stability violations found with the Abacus tool. 
 
Scientists used stable pools to express the optimized designs and generate material for biophysical characterization and activity assays. This enabled the final lead selection of AB000224 and AB007088 for advancement as a clinical lead and backup. The team engineered the variable domains of both antibodies to enable low-cost manufacturing at scale for distribution to paediatric populations. 
 
Just-Evotec Biologics scientists identified the best-producing clonal cell line, expressing the candidate molecule in continuous-perfusion bioreactors at twice the original titre. They advanced the candidate into production following good manufacturing practices. The material generated from this production run is being used to support studies for clinical development of an antimalaria drug suitable for use in paediatric populations living in Low to Middle Income Countries. 

Learn more in the following article published in the prestigious journal, Nature Medicine. 

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Antimicrobial resistance (AMR) is one of the biggest health threats worldwide. Key to countering AMR is the development of novel anti-infective drugs. The limitations of animal models and clinical trial design have emphasised the importance of nonclinical pharmacokinetics/pharmacodynamics (PK/PD) platforms which provide a detailed understanding of the relationship between the fate of the antimicrobial compound in the body (PK) and the impact of exposure to the compound on the target microbes (PD). This allows us to optimise dosing regimens to maximise the efficacy of antimicrobial compounds (microbial killing) while minimising toxicity and the risk of the emergence of AMR.

What is the HFIM?

The HFIM is a system of pumps, tubing and microfibers that mimics the body, allowing in vitro assessment of anti-infective compounds under more relevant conditions. It consists of a central reservoir and tubing used as a circulating system, and a hollow fibre cartridge with thousands of permeable capillaries. The extra capillary space (ECS) outside the fibres within the cartridge contains the target organism. During operation, the drug-infused growth medium in the central reservoir is continuously pumped to the hollow fibre cartridge, rapidly passing through the capillaries into the ECS. This continuous flow ensures that nutrients, oxygen, and test compounds are continuously refreshed while waste products are removed. To simulate drug clearance, fresh medium is added to the central reservoir effectively diluting the drug from the system. Accordingly, this balance of drug supply/clearance can effectively simulate the drug’s PK profile.

Why choose the HFIM as PK/PD model?

It is the most capable in vitro system for PK/PD determination for anti-infective compounds, against bacteria and fungi. It is a dynamic model capable of simulating almost any given concentration-time profile for one or more compounds, even if they have very different half-lives.. The Hollow Fibre Infection Model is not limited by in vivo model availability, compatibility of PK profiles, dosing or sampling frequency, or study duration, which is extremely important for understanding PK/PD relationships and the risk of AMR over clinically relevant treatment times. Various cartridges with fibres manufactured from different materials are available to optimise the HFIM for microbial growth and compound performance.

In conclusion, the HFIM is a versatile in vitro PK/PD platform which can accelerate the development of antibacterial and antifungal compounds, contributing to the fight against AMR. 

If you’d like to learn more about the uses of the Hollow Fibre Infection Model you can download our white paper here

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Learn more about the Evotec's EvostrAln^TM, a comprehensive collection of diverse human pathogenic bacteria and fungi:

• ESKAPE pathogens
• Strains from the WHO priority pathogen lists
• Highly characterised and fully sequenced with defined MoR