In this poster we focus on:
While the public has taken note of RNA-based medicine only with the advent of mRNA-based Corona virus vaccines, biopharmaceutical research and development has been working on mRNA-based medicine for almost two decades. Evotec also expanded the druggable target space to RNA and in the last years added considerable know-how in RNA-based medicine.
RNA is used by cells in multiple ways: mRNA is conveying genetic information from DNA to the ribosomes which also are made from RNA (ribosomal RNA), where another RNA species (tRNA) is transporting amino acids to the ribosomal apparatus so that a protein can be synthesized. In addition to mRNA, there are also shorter RNA molecules being used in the cell for the regulation of genes and entire genetic cascades.
This provides for plenty of potential interventions: antisense (ASO) and short interfering RNA (siRNA) can up or down regulate an RNA target, e.g., to block the translation of an unwanted or diseased protein or to suppress or stimulate the expression of genes. RNA can be targeted with (complementary) RNA, but it is also possible to alter or block the translation, re-locate or initiate RNA, degradation, etc. by small molecules interfering with the three-dimensional structure of RNAs or protein-RNA-complexes.
During our recent Innovation Week, Evotec experts Steffen Grimm, Group Leader, Hit ID & Biophysics, and Hilary Brooks, Senior Research Scientist, In Vitro Pharmacology, hosted a session called "The early bird catches the helix: Expanding the druggable target space to RNA".
In the session, they discussed how to:
RNA as Therapeutics
Using RNA as therapeutics is not trivial. Nucleic acids introduced from outside may trigger adverse reactions by the innate immune system. A lot of knowledge is necessary to ensure delivery, avoid degradation and inflammation and to fine-tune the stability and function of the molecules. RNA may also have off-target effects. To ensure efficacy and safety, monitoring these early on needs to be incorporated into the developmental workflow. High quality synthetic RNA is costly to make, therefore a scaleable process and the relevant analytics must be established early in the process to accompany both the discovery and development stages of research with quality test material; Eventually producing GMP grade RNA at a commercial scale (several hundred grams) for human administration.
Evotec already has integrated all capabilities under one roof, allowing for the complete preclinical data set, reduced transition times and efficient communication to the regulators. For antisense oligonucleotide therapy, efficient hit sequences that knock down target expression can be selected in a matter of weeks. Toxicity profiling is a priority to establishing final leads and, subsequently, project-specific dose, duration and delivery will be established using optimized backbone chemistry. Using its in-silico capabilities as well as iPSCs, animal models, transcriptomics, etc. Evotec is able to predict toxicity and efficacy, and de-risk unwanted immune stimulation as well as off-target effects. For manufacturing, Evotec is discovery-capable and already building medium-scale capacity (up to 50g) which will be ready by 2023.
For inhibiting the translational machinery, Evotec has established an RNA small molecule targeting platform and established in various case studies, molecules binding to RNA, and demonstrating a significant effect in vitro without affecting cell viability. Evotec’s capabilities also allow the creation of a representation of the 3-dimensional structure of the target complex and its interaction with the compounds.
Evotec’s experienced team of scientists with proven drug discovery and development expertise already have a track record of driving RNA targeting projects forward. Its integrated medicinal and computational chemistry capabilities, combined with bioinformatics, structural biology, pharmacology, and drug safety expertise allows for the identification and characterization of RNA target species and their modulation by different modalities. Partner projects can be driven all the way from target identification to IND and beyond. Evotec therefore is a low-risk outsourcing partner and a company continually investing in its platform to the benefit of the customer.
Tags: Oncology, Blog, Videos & Webinars, Hit & Target ID/Validation, In vitro Biology, IND Enabling Studies/Preclinical Development, In vivo Pharmacology
The NADase SARM1 (sterile alpha and TIR motif containing 1) is a key executioner of axon degeneration and there is great interest in developing SARM1 enzyme inhibitors as candidate therapies for multiple neurodegenerative diseases.
Through a combined approach of X-ray crystallography and cryo-EM we uncovered the molecular mechanism of SARM1 inhibition by a compound (DSRM-3716), demonstrating that it undergoes a base-exchange reaction with the nicotinamide moiety of NAD+, and that the transferase product is the bona fide inhibitor. Further more we reveal the activated state of SARM1 for the first time.
Tags: Neuroscience, Medicinal Chemistry, Articles & Whitepapers, Structural Biology & Protein Science
Date: 15-18 November 2022
Location: Austria Center Vienna, Austria | Hybrid
Join Evotec at the Tides Europe 2022 in Autria!
If you wish to meet with us in Vienna, get in touch via the form below, we will be happy to arrange a meeting.
Date: 9-12 May 2022
Location: Hynes Convention Center, Boston, US | Hybrid
Join Evotec at the Tides USA in Boston!
If you wish to meet with us in Boston, get in touch via the form below, we will be happy to arrange a meeting.
Date: 5-6 May 2022
Location: Novotel London West, London, UK
Attending: Lynsey Haskayne
If you wish to meet with us in London, get in touch via the form below, we will be happy to arrange a meeting.
Date: 1-3 November, 2022
Venue: Messe Frankfurt, Germany
Evotec will be exhibiting at CPhI Frankfurt at booth # 90J11, Hall 9.0
Our team, including Partnering, Drug Development and Procurement experts, will be happy to meet you in Frankfurt to explain how our fully integrated R&D and all-modalities platform can help advancing your projects seamlessly along the drug discovery and development process.
Our Partnering experts: Margit Wissenbach, Jim Beaumont, Nick Johnson, David Straight and Nigel Shipston
Our Drug Development experts: Ciriaco Maraschiello, Elisabetta Verardo, Jerome Dauvergne, Paolo Gatti, Emanuela Del Vesco, Pascale Clement and Paola Tocchetti
Our Procurement experts: Alessio Rodari, Claudio Bismara and Sara Trevisan
To request a meeting, get in touch via the form below, we will be happy to arrange a meeting.
Date: 29-30 Novomber, 2022
Venue: Strasbourg Convention Centre, Strasbourg, France
Attendees: Frederic Somny
If you wish to meet with us in Strasbourg, get in touch via the form below, we will be happy to arrange a meeting.
Date: 18-19 October, 2022
Venue: Mercure Hotel MOA, Berlin, Germany
Attendees: Florian Tegeler, Erik Schliep, Carla Tameling
Evotec will be sponsoring Bio IT World – Europe, as well as showcasing its research in Berlin.
Our scientific program
EVOpanHunter: path to precision medicine
Erik Schliep, Head of Productmanagement EVOpanHunter
If you wish to meet with us in Berlin, get in touch via the form below, we will be happy to arrange a meeting.
Learn more about Bio IT World.
Date: 18-21 September, 2022
Venue: The Maastricht Expositie en Congres Centrum, Maastricht, The Netherlands
Attendees: Michela Pecoraro, Marco Pergher, Jim Beaumont, Rob Brown, Tim Potter, Daniel Gliesche & Alicia Rosell-Hidalgo
Evotec will be exhibiting and showcasing their research at the XVIth International Congress of Toxicology along with our ADME-Tox Cyprotex experts.
Booth Number: 35
If you wish to meet with us in Maastricht, come at booth 35 or get in touch via the form below, we will be happy to arrange a meeting.
Learn more about the XVIth International Congress of Toxicology.