Science Pool

Autotaxin (ATX) is a secreted glycoprotein that hydrolyzes lysophosphatidylcholine (LPC) to lysophosphatidic acid (LPA). LPA signalling directly modulates tumour cell function and contributes to the development of the fibrotic tumour microenvironment, resulting in reduced host immunity and impaired response to therapy.

iOnctura, a clinical-stage oncology company, based in Switzerland (Genève), targeting core resistance and relapse mechanisms at the tumor-stroma-immune interface, has developed a potent and orally available autotaxin inhibitor, IOA-289, as a novel treatment for pancreatic cancer and other highly fibrotic tumours.

The first Phase I clinical study in healthy volunteers has been successfully completed. Evotec is very proud to have actively contributed in conducting the trial and analyzing the results that led to the achievement of this exciting goal.

Read the poster presented by iOnctura at the ESMO Immuno-Oncology Congress held in December 2021 to learn more about IOA-289 and its activity as autotaxin inhibitor. IOA-289 was also presented by iOnctura at the recently held AACR Annual Meeting in New Orleans.

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Evotec sample management team is responsible for the long-term storage and distribution of Evotec and partners compound collections.

In 2019, Evotec decided to invest in acoustic tubes technology in order to support future customer need and plan for potential transfer of our libraries into acoustic tubes. In parallel to this decision, Evotec sample management decided to initiate an internal project to evaluate the impact of acoustic tubes usage on compound integrity.

This poster highlights and describes the experiments performed, which substantiate and validate the use of acoustic tubes.

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In this poster we focus on:

• Development of robust feeder-free 3D differentiation protocol to reduce iNK cells
• Transnational validation of iNK functionality with freshly isolated CLL patient tumor cells
• Enhances CLL patient tumor cell killing with CAR19 iNK
• EVOcells Oncology programs

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Chikungunya virus, which is transmitted by mosquitoes, can cause disabling chronic arthritis. There are currently no medicines for prophylaxis of Chikungunya, or other viruses transmitted by Aedes mosquitoes, such as Dengue and Zika. Potential therapeutics have been identified, but to perform a successful chemoprophylaxis trial during a short Chikungunya outbreak requires an identified at-risk population. We examined the potential for application of a household transmission model, as used in testing prophylactic drugs against respiratory viruses, included influenza and COVID-19.

In this poster we:

• Set out the evidence for multiple Chikungunya infections occurring per household
• Describe how we are validating the secondary household infection rate
• Show how this could be used in future clinical trials to demonstrate prophylactic efficacy against chikungunya virus infection and other Aedes-mosquito-borne viruses

Read our poster to learn more about our research!

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Reactive metabolites play a role in drug-induced toxicity. Early stage in vitro screening for electrophilic reactive metabolite formation involves the use of trapping agents such as glutathione (GSH) in the presence of a drug metabolising system.

In this poster, we focus on:

• the use of an alternative GSH trapping method using combined stable labelled GSH (GSH-¹³C₂,¹⁵N) with unlabelled GSH
• the advantages of the stable labelled GSH method over common approaches for the detection of GSH conjugation such as GSH neutral loss post acquisition
• analytical conditions including the HPLC and mass spectrometric methods 
• validation data for a set of literature compounds

Read our poster to learn more about our research!

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Lipophilicity is an essential physicochemical property used to predict compound behaviour with respect to pharmacokinetics, pharmacodynamics and safety. 

In this poster, we focus on:

• the use of the chromatographic hydropobicity index (CHI) as an alternative to LogD for lipophilicity determination
• the use of LC Time-of-Flight mass spectrometry for CHI determination and its advantages with respect to reduced inference from impurities, decreased compound requirements and improved throughput
• applicability of CHI for large scale screening projects
• the presentation of the reproducibility and robustness of the method along with comparison with literature values

Read our poster to learn more about our research!

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Cardiotoxic drugs can display acute alteration in the mechanical function of the myocardium (functional changes) or morphological damage to cardiomyocytes and/or loss of viability (structural changes).   

In this poster, we focus on:

• the detection of functional cardiomyocyte changes through monitoring of calcium transients using human iPSC-derived cardiomyocytes
• the analysis of structural morphology using high content imaging (calcium homeostasis and mitochondrial function) as well as cellular ATP in human iPSC-derived cardiomyocytes
• the presentation of a strategy for understanding cardiotoxicity risk for novel compounds enabling in vitro to in vivo translation at an early stage in preclinical screening.

Read our poster to learn more about our research!

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