ELRIG´s Advances in Cell Based Profiling in Drug Discovery 2022

The fourth ELRIG meeting on Advances in Cell Based Profiling in Drug Discovery was held on May 10-12 at the AstraZeneca R&D site in Gothenburg. The interactive 3-day event hosted leading scientists from academia, industry and the vendor community to discuss current and future formats for cell based assays. Building on the success from last time, the third day of the meeting, organized by key academic chemical biology infrastructures in the Nordic countries. Our ambition was to create an open and inspiring environment for networking between biologists and chemists, discussing the latest advancements and best practices in cell assay profiling and their application for target identification, target validation and compound optimisation purposes.

Cell based assays are utilized at all stages of drug discovery to explore disease mechanisms and to identify novel molecular therapeutics. To achieve this the field is continuously looking for improvements in cell reagents, assay formats, and readouts to ensure disease-relevant contexts, aiming at improving translation to human physiology. Implementation of cell assays with improved translatability is much needed for improving success rates in drug discovery, but we are struggling with restrictions in cell availability and assay costs, considerations that are holding back their broader implementation. This meeting will explore these challenges and look into how cell profiling efforts must be adapted to emerging drug modalities, in this case with a special focus on therapeutic oligonucleotides and other modalities that affect protein levels rather than their activities.

The meeting program was developed around five key focus areas:

Enabling Advanced Cell Models in Profiling
This session explores how to embrace individual diversity and variability in drug discovery through the use of advanced cell models. Topics will flow from the relevance of diverse genetic backgrounds in generating disease models, through advances in long-term provision of these cells and possibilities for miniaturisation, to the use of multiparametric and multidimensional readouts   for better biological interpretation of data.

Towards a complete temporal and spatial understanding of cellular responses
Positive demonstration of target engagement and translation to expected biomarkers of treatment response are known to correlate with successful progression of clinical studies. Here we explore case studies that looks broadly at treatment response – from interaction with intended molecular target to a map of disease-relevant cell responses – and the potential heterogeneity of such responses between cell models.

Designing cell profiling support for therapeutic OLIGO discovery
Seasoned drug discoverers are well versed when it comes to designing panels of assays for optimization of small molecule-based drugs and therapeutic antibodies. With the entrance of new clinically validated drug modalities, such as antisense oligonucleotides, these screening cascades must be re-built to suit the needs. This session is dedicated to sharing successful examples of cell profiling performed in the field of therapeutic oligonucleotides.

The rise of high throughput protein MS in cellular profiling
Modern drug modalities such as antisense oligonucleotides and PROTACs function by removing target proteins of interest, adding significantly to the repertoire of tools available for disease modulation. Complementing antibody-based approaches for assessing impact on endogenous protein levels, this session will explore recent advances in high throughput applications of protein mass spectrometry.

Using Biology for Fingerprinting Compounds (Nordic Chemical Biology infrastructures)
Small molecule profiling or “drug fingerprinting” is defined by systematic testing of well-characterized chemical libraries across disease models to uncover biological mechanisms fundamental to health and disease. This session will explore this interesting interplay between chemistry and biology and includes talks on functional fragments as well as image-based fingerprinting using high-content imaging.

There will be ample opportunity for networking with scientists and researchers from the pharmaceutical, academic and vendor communities throughout the 3- day conference. The program also includes poster viewing sessions, poster snapshot presentation opportunities for select high quality posters and a tour of the Amazing Journey at AstraZeneca.