Post-Event Report

Post Event Report – Discovery Week Online 2021

By Oliver Picken |
01 October 2021
This year’s Discovery Week: Online brought together over 800 discovery leaders to further innovation in drug discovery.

This year’s Discovery Week: Online brought together over 800 discovery leaders to enable innovation in discovery on target, chemistry biology and medicinal chemistry. Building on the success of our 2020 online event, the event engaged with peers and selected leading providers in an exciting and interactive networking environment. Driven by the current focus on delivering interactivity, the programme included over 20 hours of valuable networking sessions, roundtable discussions, panel discussions and workshops.  
 

Key Topics   

Discovery Week: Online took place over four days, with each having a thematic focus.  

Day One: On Target Discovery, Phenotyping Discovery, and Animal Modelling 

The event began with a series of presentations and case studies about identifying and validating novel targets, phenotypic based discovery and Screening Approaches, animal and disease modelling, and organoid based discovery. Additionally, discussion groups gathered to talk about the latest developments in functional genomics in target discovery and available methods to characterise compound target interaction on a molecular level via SPR, MST, ITC, and TSA. Some of our most popular presentations included Thierry Dorval’s (HCS – Group Leader, Biotechnology Chemical-Biology, Servier) “Phenotypic Compound Profiling Through High Content Approaches”, Laura Rosenberg’s (Associate Director Target Validation, AstraZeneca) “Delivering Novel Target Biology At Scale” and Steve Rees’s, (Vice-President of Discovery Biology, AstraZeneca) “Identification And Validation of Novel Drug Targets”.  

Day Two: Targeted Protein Degradation and PROTAC 

The second day focused on new modalities and targeting challenging areas and possibilities for targeting currently undruggable proteomes. In the afternoon, several interactive sessions were held. Workshops on molecular glue for new drug development as well as ubiquitin ligases and targeted protein degradation proved particularly popular. Highlights included the following presentations; Ian Churcher’s (Chief Scientific Officer, Amphista Therapeutics Limited) “Next Generation Protein Degradation Beyond The Usual E3 Ligases”, Ryan Pott’s (Executive Director & Head of Induced Proximity Platform, Amgen) “Induced Proximity Medicines For Targeted Degradation Of Proteins And RNAs” and Eric Fischer’s (Associate Professor of Biological Chemistry and Molecular Pharmacology, Co-Director DFCI Center for Protein Degradation, “Dana-Farber Cancer Institute, Harvard Medical School) “Structural Insight Of Molecular Glues, E3 Ligands And PROTACs”. 

Day Three: Medicinal Chemistry and Optimisation of HITs 

Day three centred around integrating technologies in the optimisation of HITs, featuring presentations on covalent inhibitors and protein degradation. In addition, several interactive roundtable sessions explored molecular drug design and medicinal chemistry, new chemical modalities, and challenging targets, how to choose the suitable modalities and covalent inhibitor design and discovery. Werngard Czechtizky’s (Chair of Global Chemistry & Head of Medicinal Chemistry, AstraZeneca) presentation on Covalent Inhibitors Design And Discovery was particularly insightful, so much so that we have created a condensed version here. 

Day Four: Computational Drug Design 

Our final day wrapped up the event with several presentations on computation drug design. This year, advances in AI were a key topic, with industry leaders highlighting exciting new use cases and approaches for novel drug design. Furthermore, day four’s Digitising Drug Discovery Labs discussion group received a great deal of interest due to the increasing competitive advantage smart lab technology provides for pharma companies. Presentations including Rolf Jautelat’s (Vice President Medicinal Chemistry, Bayer AG) “Digital Transformation: Delivering Value to Drug Discovery” and Alexander Hillisch’s (Vice President, Head Of Computational Molecular Design, Bayer Ag) Compound Library Expansion And The Computational Design Of Macrocyclic Compounds To Address Difficult Drug Targets proved to be especially insightful. 

Opportunities for knowledge Sharing & Networking 

Attendees of this year’s discovery week: online were given a glimpse of the future of drug discovery. This event brought together industry leaders who shared cutting edge information on new modalities such as protein degradation, RNA based therapeutics and case studies on the identification and Validation of Novel Targets, as well as the latest updates on the integration of screening approaches in phenotypic and genomics-based discovery, organoid discovery, organ-on-a-chip, and 3D modelling, and novel RNA drug targets.  

Discovery week provided a unique opportunity to learn about DNA encoded libraries, protein-protein interactions, AI/ML in drug design and new modalities such as Protein Degradation and Covalent Inhibitors. Additionally, this year there was an increased focus on innovative tools, including AI in ADME, big data management, model management, artificial intelligence, machine learning in drug design and AI in chemical synthesis, AI-enabled target ID capabilities and lead identification/optimisation.  

Networking is also an essential aspect of discovery week, allowing attendees to engage in interactive discussions, including the Integration Of DEL, Covalent Inhibitors and Protein Degradation Technologies in optimising HITs. 

Market Trends and Challenges  

The global drug discovery market is expected to grow considerably in the coming decades, with a predicted revenue of $83.2 billion by 2027. The critical drivers influencing the growth in the global drug discovery market is an ageing population and technological advancement. As a result, biopharmaceutical companies are rapidly progressing in various disciplines, including genomics, machine learning and AI in data analytics, drug design, and targeting.  

Drug Discovery and AI  

In attempts to address the concerns associated with rising capital requirements in drug discovery and prevent late-stage failure of drug development programs, stakeholders in the pharmaceutical industry are exploring several options. One example is the implementation of Artificial Intelligence (AI) based tools to aid drug development operations with available chemical and biological data. Currently, a new drug takes an average of 12-15 years and $1.6 billion to make it to market. AI can speed up this process by predicting how likely a compound is to work against certain illnesses. Researchers can use those predictions to focus on only a few dozen compounds rather than thousands, increasing the pace of testing and increasing the likelihood of yielding a positive result. 

Targeted Protein Degradation  

Most disease-causing proteins are not amenable to modulation by conventional pharmacological methods. However, in recent years an alternative therapeutic strategy known as targeted protein degradation has emerged with the potential to inhibit these “undruggable” proteins. Targeted protein degradation is revolutionising drug development and has the true potential to produce next-generation therapeutics for various diseases. This area will help accelerate innovation and attract further investment and major collaboration partners in the pharmaceutical industry.  

Increasing Adoption of Personalised Drugs to Drive Organoids Market  

Traditional drug discovery methods are inadequate and less relevant to the pace of the growing life science research and development. Organoids are, therefore, expected to generate a significant revenue share in the market for drug discovery applications. The increasing failure rate in human preclinical trials is luring academics and researchers to explore organoid models for toxicology and regenerative mediation research. Organoids are proving to be an appropriate alternative to animal testing models and are increasingly likely to be used as a substitute.   

Conclusion  

Drug discovery remains an extraordinarily complex, lengthy, and costly process with high attrition rates. There is no assurance of success by the time a drug goes through clinical trials after over a decade in development. With the costs of bringing a drug to market now over $1 billion, Pharma continues to face increased pressures to develop new therapies, reduce costs and avoid late-stage failure. Leading experts are currently debating how to meet these challenges. As a result, the obstacles are decreasing as advancements, and technological innovations enable new methods and speeding up processes and the future looks bright for drug discovery.  

Speaker Biographies

Werngard Czechtizky – Chair of Global Chemistry & Head of Medicinal Chemistry, AstraZeneca 

Werngard Czechtizky is Chair of AZ Global Chemistry Leadership and Head of Medicinal Chemistry, Respiratory and Immunology at AstraZeneca, Sweden. She has studied at the Technical University of Graz, Austria, received a PhD from ETH Zürich and a postdoctoral training at Harvard University. She has been working at Aventis, then Sanofi in Germany, before joining AZ in 2017. 

 

Jane Wiener – Senior Director & Head of Chemistry, Lundbeck 

Jake Wiener is Senior Director of Medicinal Chemistry at Lundbeck La Jolla Research Center, overseeing the chemistry and chemical biology teams in their pursuit of developing first in class therapies. Prior to joining Lundbeck, Jake was Senior Director at Abide Therapeutics where he led multiple project teams designing inhibitors for serine hydrolase targets. With over 16 years in drug discovery, beginning at Janssen before moving to Abide and Lundbeck, Jake has worked on an array of target classes for various therapeutic areas, including infectious diseases, immunology, and CNS (Central Nervous System). Jake received his Ph.D. in organic chemistry from the California Institute of Technology where he worked with Professor David W. C. MacMillan. 

 

Gianni Chessari – Vice President & Head of Medicinal Chemistry, Astex Pharmaceuticals 

At Astex, Gianni has served as Head of Modelling before being appointed as Head of Medicinal Chemistry in 2019. Gianni has extensive experience of fragment-based and structure-based drug design and has contributed to the discovery of a number of small molecule drug candidates that have entered into human clinical trials. Gianni obtained his degree in Chemistry from the University of Catania (Italy), his PhD in Chemistry from the University of Sheffield (UK) and he carried out postdoctoral research at the Institute Pasteur (France) and at the Institute of Cancer Research (UK). Gianni has authored more than 70 publications and patents. 

 

Istvan Enyedy – Director Computational Chemistry, Black Diamond Therapeutics 

In the past 21 years Istvan J Enyedy has been involved in new target evaluation, hit finding, and hit-to-lead optimization projects for several types of target classes using both ligand and structure-based methods. He is co-author on more than 50 publications and 14 patents/applications. He received his PhD in 1998 at Catholic University of America, Washington DC, and did postdoctoral training in Dr. Shaomeng Wang’s group at Georgetown University Medical Center, Washington DC. Between 2001 and 2008 he worked at Bayer Pharmaceuticals, West Haven CT and Novartis Institutes for Biomedical Research and Biogen in Cambridge MA. Since February 2020 he has been working at Black Diamond Therapeutics in Cambridge MA. After obtaining a PhD in organic chemistry at the University of Exeter under the supervision of Professor Stan Roberts, Phil moved to the States in 1990 to first work as a post doc with Professor Carl Johnson at Wayne State University and then Professor Phil Garner at CWRU. 

 

Phil Cox – Senior Principal Research Scientist, AbbVie  

Phil began his industrial career in 1997 with Oxford Asymmetry International (now Evotec) where he was a Project Leader in the Discovery Services Division working on multiple collaborations in both the Pharmaceutical and Agrochemical sectors. Phil then moved to Pharmacia, Skokie, where he was a member of the Parallel Medicinal Chemistry Group before transferring to Ann Arbor as part of the Pfizer acquisition in 2003. In 2007, Phil moved to Abbott Labs (now AbbVie Inc.) where he is currently a Senior Principal Research Scientist and fragment-based drug discovery chemistry group leader. Phil is an inventor on numerous patents spanning multiple therapeutic areas and has published articles in the areas of property-based design, fragment-based drug discovery, and compound file management. 

 

Friedrich Rippmann – Director of Global Computational Chemistry & Biology, Merck 

Friedrich Rippmann is Director of Computational Chemistry & Biology at Merck in Darmstadt, Germany. Previously he was head of Bio- and Chemoinformatics at Merck, with responsibility for groups in Germany, France, and Switzerland. He was also responsible for the set-up of bioinformatics and protein crystallography in Darmstadt. In his academic career he worked at the National Institute for Medical Research, MRC London, and at the German Cancer Research Center in Heidelberg, Germany. Several major software developments originated in his group, among them RELIBASE, a comprehensive database of protein-ligand complexes; and more recently DoGSite Scorer, a druggability prediction server; TRAPP, a webtool for analysis of transient binding pockets in proteins; and a panel of methods for selective kinase inhibitor generation. Currently he is working on digitizing many aspects of the early discovery research, including the integration into coherent workflows. Machine Learning, especially Deep Learning, and other aspects of Artificial Intelligence are central to this. Two recent press releases highlight his commitment to making latest AI technologies available to Merck’s drug discovery process. 

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Commentary
Covalent inhibitors have progressed significantly since they were discovered in the 18th century and are now experiencing a resurgence.
12 October 2021

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