Science Pool

The Covid-19 worldwide pandemic unveiled extraordinary resources within the scientific and pharmaceutical community delivering vaccines and therapeutic drug candidates within timelines never seen before. While the pandemic hit suddenly and the number of cases increased exponentially, the AMR crisis remained silent. Nevertheless, it is progressing and the emergency and spread of multidrug resistance is putting our existing antibiotic arsenal under increasing threat.

Is AMR our next pandemic?

Possibly, if we continue to consider antibiotics as fire-extinguishers: and only create novel therapeutics once we are face to face with the fire.

Innovation and collaboration are key in the preparedness, together with expertise and operational excellence. Evotec, with more than 200 scientists dedicated to antibacterial drug R&D, is at the forefront of AMR research and innovation. With infectious disease platforms spanning from in vitro biology to in vivo pharmacology and medicinal chemistry and benefiting from HTS platforms, ADME and toxicology expertise.

Innovative thinking and creativity to discover novel antibacterial compounds begins with designing a strategy to discover novel active compounds. By changing the paradigm in phenotypic screening and developing the Vivo Mimetic Media (VMM) concept for discovering novel Gram-negative antibacterials, Evotec has validated five alternative bacterial culture media that better mimic the conditions bacteria are facing during infections. These VMM conditions are affecting the physiology of growing bacteria by altering permeability (porins, efflux pumps and outer membrane) but mainly unveiling new targets and mechanisms of action (MoAs).

The cornerstone of innovation in antibacterial drug discovery is the application of machine learning to optimise chemical matter. By combining biological data, medicinal chemistry expertise and a deep learning approach, Evotec has enabled the prediction of antibacterial activities against 15 bacterial strains and provided de novo design of compounds, 76% of which were accurately predicted for their activity.

Validation of active compounds in appropriate pharmacodynamic models is crucial, while innovative approaches are needed for tailored design and improved readouts. By using luminescent or fluorescent bacteria, infection models with higher complexity have been developed to evaluate the spread of infection in real time and most importantly, measure the distribution of the active compound fluorescently labelled to the site of infection.

Innovation through collaboration and partnership is at the forefront of Evotec’s unique business model. Through a highly strategic partnership between Evotec, Resolute Therapeutics and CARB-X, a new antibacterial drug class termed TriBe is being advanced in the preclinical pipeline, with the objective to bring a candidate for the treatment of cUTI, cIAI and lung infections to clinical phase I. The TriBE series have unique properties with nanomolar bacterial topoisomerase inhibitors binding via the GyrB/ParE subunits, very broad bacterial spectrum, low potential to select for resistance, favourable PK and in vivo efficacy in multiple models of infection have been demonstrated.

While a consensus exists on the real and clear need for new antibacterials and approaches, the challenges are numerous and complex. Innovative thinking, creativity and novel approaches (target and technology) underpin anti-infective drug discovery at Evotec, enabling the redesigning of antibacterial discovery infrastructure to ensuring an integrated approach and foster collaboration, partnership, training and cross-interaction.

WATCH OUR WEBCAST TO LEARN MORE

Date: July 24th-29th, 2022

Venue: Renaissance Tuscany Il Ciocco, Lucca | Barga, Italy

Attendees: Alastair Parkes, Stephane Vandenbeele, Guiseppe D'Angelo, Florian Marro

Evotec will be sponsoring the New Antibacterial Discovery and Development Conference, as well as showcasing its research on-site in Italy.

Our scientific program

Presentation

Using Probabilistic Approaches and AI/ML to advance antibacterial drug discovery projects

Alastair Parkes, VP Head of Department III, Medicinal Chemistry

Wednesday, 27 July | 11.30 am - 11.50am

Poster Presentation

Intracellular Staphylococcus aureus replicative dynamics monitoring under antibiotics challenges: highlighting persisters.

Florian C. Marro, Research Associate, Mass Spectrometry & Phenomics

Poster Sessions are scheduled 4:30 pm - 6:00 pm from 25-28 July 2022.

If you wish to meet with us in Italy, get in touch via the form below, we will be happy to arrange a meeting.

Learn more about the GRC - New Antibacterial Discovery and Development.

Don't miss our educational webinar. In-house expert, Ellenia Bordini, will cover various early stage "alternative approaches" for the evaluation of metabolites in human and preclinical species, and how these can be used to direct preclinical safety testing for regulatory submission. 

Take a Ride on the Evotec "Data-Driven R&D Autobahn to Cures"

5 Virtual Sessions over 5 Days

Date: 6 - 10 November 2021 Online | 9 - 11 November 2021 Fiera Milano

Location: Virtual

• Learn how Evotec is using data and science across treatment modalities to accelerate innovation in the area of precision medicine to deliver enhanced speed, lower cost, and predictive efficacy

• Find out about our efforts in AI/ML in the design and development of both small molecules and antibodies, the importance of  biomarker development, targeting RNA, and our approaches to target validation

Day 1:
Drug Discovery in Evotec Multiverse: Knowledge-driven Integrated R&D

Presented by: Adam Davenport, Tim James and Christophe Boldron
When | Monday 6 December @ 11am EST | 8am PST | 4pm GMT | 5pm CET

Day 2:
The Importance of Precision Medicine: How Biomarkers Optimise Translation from Bench to Bedside and Back

Presented by: Elizabeth van der Kam, Christoph Schaab
When |Tuesday 7 December @ 11am EST | 8am PST | 4pm GMT | 5pm CET

Day 3:
The Early Bird Catches the Helix: Expanding the Druggable Target Space to RNA

Presented by: Steffen Grimm, Hilary Brooks
When | Wednesday 8 December @ 11am EST | 8am PST | 4pm GMT | 5pm CET

Day 4:
Do Firefighters cause Fires? Establishing Real Disease Associations through Target Validation

Presented by: Hauke Cornils, Susan Boyce
When |Thursday 9 December @ 11am EST | 8am PST | 4pm GMT | 5pm CET

Day 5:
Translate your Idea into Product: AI-Driven Antibody Discovery at Evotec

Presented by: Barbara Bachler-Konetzki, Randal Ketchem, Maria Pilla
When | Friday 10 December @ 11am EST | 8am PST | 4pm GMT | 5pm CET

Each session will take approx. 45 min including Q&A. You will need to register for each day separately to reserve your seat.

RESERVE YOUR SEAT

This article forms a book chapter in Artificial Intelligence in Drug Design.

In this review article, we provide the latest insights into de novo design approaches based on  artificial intelligence (AI) algorithms with a specific focus on ligand-based methods.

It includes:

• a background to de novo design approaches developed prior to the use of AI
• an overview of AI and commonly employed neural network architectures used in ligand based de novo design
• a list of more than 100 deep generative models reported in the literature from 2017-2020
• current applications of deep generative approaches in the drug discovery context
• an insight into future applications of deep generative models in de novo drug design 

LEARN MORE

Date: 18th November 2021

Venue: Virtual

Attendee: Dr Alastair Parkes, Group Leader at Evotec will be presenting on "Novel LpxA inhibitors targeting Pseudomonas aeruginosa"

Learn More About the EADA Conference

Date: 15th-16th November 2021

Location: ENS Campus Gerland, Lyon, France

Attendee: Antoine Alam, VP Virology will be presenting on "CD40 agonists boost IFN-induced signaling pathway and subsequent anti-HBV response in vitro and in vivo"

Huge Watson, Virology Clinical Development will be presenting a poster entitled "Household clustering suggests a novel chemoprophylaxis trial design for an arboviral disease"

Francesca Bernardini, VP In Vitro Biology, Sébastien Coyne, Group Leader In Vitro Biology, Kara Carter, Virology Entrepreneur in Residence, Lilia Boucinha, Team Leader, Bioinformatics

Learn More About I4ID

Transient Receptor Potential Melastatin 5 (TRPM5) is an intracellular calcium-activated cation-selective ion channel which is expressed in a variety of cells and tissues. Dysfunction of the TRPM5 channel has been linked to a number of pathological conditions including diabetes, inflammatory responses, enteric infections and parasitic infections. Identifying sufficiently selective agonists or positive modulators of the TRPM5 channel has, to date, proved challenging which has limited its potential as a drug target.   

In this publication, we focus on:

• the development of a high throughput screen using a fluorescent membrane potential assay for primary hit identification screening and selectivity assessment of TRPM5 channel positive modulators 
• use of medium and high throughput electrophysiology assays (QPatch HTX and SyncroPatch 384PE) as follow-up screens to confirm activity and selectivity of identified hits
• the SyncroPatch 384PE assay for structure-activity relationship (SAR) expansion of the identified chemical series

LEARN MORE

Fireside Chat at BIO-Europe 2021

Evotec Chief Scientific Officer, Dr Cord Dohrmann, talks to Dr Hubert Birner, Managing Partner at TVM Capital Life Sciences, about how Evotec has built an impressive and innovative platform.

WATCH NOW