ELRIG’s Drug Discovery Digital has begun. In addition to world-class scientific talks, a bustling virtual exhibition provides the opportunity to connect directly with experts to hear about the latest technologies that could aid your research efforts. You’ll also be able to pick up a few tips and tricks you can take back to your lab and might even find a technology that could unlock the full potential of your research and lead to a major breakthrough!
ELRIG’s Platinum Sponsors provide some invaluable insights into the challenges facing drug discovery today, the technologies that could overcome them and reveal what you can expect from the exhibition.
Q: WHAT ARE THE MAIN CHALLENGES YOU SEE DRUG DEVELOPERS FACING TODAY?
Paul Morrill, Chief Business Officer, bit.bio:The development of new drugs has not kept up with progress in biology. Despite significant scientific breakthroughs and technological advances, today drugs are more likely to fail in clinical development than they were 40 years ago. Differences between human biology and models used for drug discovery, such as mice, are an important contributor to the problem. In fact, one of the biggest challenges to R&D productivity remains the lack of valid human screening and disease models.
Peter Banks, Scientific Director, BioTek Instruments: The main challenges that researchers face are somewhat indication- and therapy-dependent, but in general, the biggest obstacle we see in the industry is the high attrition of drug candidates in clinical trials, which lead to untenable R&D costs, and, in the worst cases, can force smaller organisations to close. The two main causes of this attrition are lack of clinical efficacy and safety, so it’s clear that we need better ways to predict these earlier in the pipeline.
Miles Rackliff, European Sales and Marketing Director, Curiox Biosystems: For me, the length of the research and discovery process and late stage failures continue to be the main challenges. Developing a deeper understanding with reliable, accurate and reproducible data throughout the discovery process is fundamental in reducing late stage attrition. How internal teams and external partners work together is evolving and a shared understanding of innovation, success and failure is increasingly powerful in helping to shape the future with new exciting and increasingly invaluable relationships. If COVID-19 has taught us one thing it is the power of working together that collaboration can bring.
Stina Lundgren, Principal Project Advisor, Pelago Bioscience: Bringing a compound through the entire drug discovery and development value chain is associated with a lot of risk due to high costs, long lead times and the use of many different methods and assays. And the risks increase the further into the process you are. The high attrition rate in drug development is often attributed to lack of efficacy in the proof of concept studies or off-target induced toxicities. A main reason for the efficacy failures is insufficient target engagement at the intended site of action and incomplete understanding of the mode of action of the compound.
Q: WHAT TECHNOLOGIES ARE AVAILABLE TODAY TO SUPPORT DRUG DISCOVERY AND DEVELOPMENT EFFORTS?
Peter Banks: A range of technologies have been developed over the last five years to reduce attrition and achieve better therapies. One area of focus has been on more physiologically relevant cell models used in early drug discovery. The belief here is that in vitro models that more closely resemble human physiology will provide a more accurate indication of efficacy ahead of clinical trials. This has led to the development of 3D cell culture technologies and methods that use aggregates of cells, often human primary or differentiated stem cells into tissue or organ-like structures associated with the indications of a disease. Assays associated with these 3D models tend to quantify specific phenotypes of the cell aggregate which often are best analysed by quantitative automated microscopy. BioTek’s Cytation Cell Imaging MultiMode Reader platform has been designed with this in mind. Together with Gen5 Image Prime image analysis software, the platform provides a comprehensive tool for quantitative assays particular to 3D cell culture methods.
Miles Rackliff: The effective analysis of biological change and response starts with the quality of the sample. Consistency in sample processing workflows, minimising sample manipulation and cell stress results in better data. By eliminating the centrifuge, Curiox customers continue to improve workflows and results for cytometry, bead-based immunoassays, and single cell genomics. We have a range of solutions for staining and processing just a few, to hundreds of samples on the benchtop. The technology is called the Laminar Wash technology, which is proven to increase cell retention, viability and provide cleaner samples over centrifuge-wash methods. Much more efficient and cost effective, the Laminar Wash systems can process from a single cell to 10 million cells per well. With rare populations or very small sample volumes, it is becoming invaluable in many laboratories. I’d also like to mention the importance of biosafety. Already an established platform for work in infectious diseases, the Laminar Wash systems do not produce centrifugal aerosols, eliminate the practice of ‘microplate flicking’ and are designed for use in biosafety cabinets. This has been crucial for our COVID research partners as well as being good laboratory practice.
Stina Lundgren: The patented Cellular Thermal Shift Assay (CETSA) was developed to enable target engagement quantification of a compound with its protein target in a physiologically relevant setting. CETSA is a label-free method that assesses the thermal stability of proteins in living cells and tissue – based on denaturation and aggregation as a result of heating. CETSA is available in two formats with different applications in drug discovery: CETSA Navigate, which is used from early target validation, on to lead generation and through to late preclinical development, and CETSA Explore, which is used in diverse applications such as selectivity and specificity studies, mechanism-of-action analysis and phenotypic target deconvolution.
Paul Morrill: Human induced pluripotent stem cells (iPSCs) provide an excellent source of starting material. However, classical differentiation methodologies have been challenging, fraught with inconsistent and complex protocols that are difficult to reproduce and scale.
bit.bio is actively innovating on a transformative technology and platform – both in the form of developing new medicine and therapies for use in patients, as well as developing cells of the utmost quality for use by the greater research community, including academics, pharma and biotech. We are taking aspects of artificial intelligence and combining it with the deep knowledge that we have in iPSC reprogramming to develop a new way of accessing a range of primary cell types. By doing so, we are placing disease-relevant human cells within the context of driving translational experiments at the earliest stages of drug development.
Q: IN YOUR VIEW, WHAT ARE THE MOST EXCITING APPLICATIONSAND BENEFITS OF THE TECHNOLOGY HIGHLIGHTED IN QUESTION 2?
Stina Lundgren: CETSA Navigate, has revolutionized the measurement of target engagement, which previously relied on traditional biophysical assays. Moving forward CETSA HT will be used for unlocking new chemistry and for tackling undruggable targets by identifying high quality binders.
With CETSA Explore it is possible to study the direct consequences of a drug on both its intended and off-targets, as well as the immediate signalling cascade perturbed by the addition of a compound. As the assay can be carried out in the live cells protein targets and pathways that would otherwise not be identified using traditional methods, can be identified.
In five years CETSA will be an established platform for studying compound-protein interactions enabling more efficient identification and optimisation of high-quality drug candidates.
Miles Rackliff:It’s always about the biology and the cells! No matter what the disease, enabling better cell retention, consistency of sample quality and removing workflow bottle necks continues to be key for our customers. The benefits of improved workflow and results were initially adopted for bead immunoassays, flow and mass cytometry. More recently these advantages, especially of high cell retention and reduced background have been seized upon by single cell genomic scientists across a diverse range of applications. We are proud to be able to bring the consistency and quality in sample preparation to difficult analyses where it has been very much needed.
Paul Morrill: Our proprietary reprogramming technology, opti-ox, can generate cells with high consistency and functionality at scale. From human iPSCs, including patient-derived iPSCs, or those carrying disease-specific mutations, these cells provide biologically relevant in vitro human models for research and high throughput screening. The technology platform also enables the consistent manufacture of homogenous and mature human iPSC-derived functional cells within days, offering access to the highest quality cellular models with simple protocols. Our human glutamatergic neurons, for example, are already able to shed new light on diseases such as autism and provide an unprecedented opportunity to drive human translational experiments.
Over the next 5-10 years, bit.bio will be rapidly expanding its repertoire of human cell types and disease models. We plan to launch a total of 10 products by the end of 2021. Our focus is on CNS, muscle and cells for toxicology with associated disease models, all of which are in demand within the industry.
Human skeletal myocytes generated by MYOD1-driven reprogramming of stem cells using opti-ox technology.
Peter Banks: Many of our customers are applying 3D cell culture methods with our Cytation platform for cancer biology applications. This includes the use of co-cultures aggregated into spheroids encased in Matrigel, where the model replicates cancer metastasis. The co-culture spheroid typically is comprised of both cancerous and normal cells to represent a tumour, while the Matrigel represents surrounding tissue. The invadopodia in the Matrigel can then be quantified by imaging and represents a measure of metastasis. Perhaps more exciting is immune-oncology applications involving 3D cell culture and Cytation where adoptive immunotherapy approaches can be used in conjunction with the Cytation platform to monitor and quantify immune cell-mediated cytotoxicity assays involving 3D structures. These cell therapies offer great promise for not only leukemias, but also for solid tumours in the future.
Q: WHY IS IT IMPORTANT TO ATTEND VIRTUAL EVENTS? WHAT ARE THE BENEFITS OF SPEAKING WITH VENDORS AND VISITING THEIR BOOTHS AT THESE EVENTS?
Miles Rackliff: I would just like to say a very big WELCOME! The usual/real life exhibition stand with an army of smiling salespeople can be daunting at the best of times no matter what cookies, pens, even ice cream and coffee is served. Now online, you’ll be able to learn about the technology with new animated videos, access data posters, ask the technical questions with confidence and learn why sample preparation is going centrifuge free… We will have freebies of course and look out for our “The new working-lab survival kit and “Biology At Its Best” T-Shirt competition”.
On Thursday at 15th at 15:05 in the CRUK track, we have an application workshop highlighting the use of the Laminar Wash technology. Here, we will share and discuss data and simple steps to transform your workflow to go centrifuge-free for both cell and bead assays.
One Friday 16th at 11:35am Curiox Biosystems hosts “Biology at its best for all modalities” where three global companies will detail their benefits of going centrifuge free in different modalities. 30 minutes will change the way you work forever: Discovery oncology: Charles River-Improved cell recovery from low sample volumes for immunophenotyping in TILs and whole blood. Single cell genomics. Curiox et al-Standardising sample prep and increasing cell retention for single cell proteogenomic analysis. Cell gene therapy-Analytical development and Q.C: AdiCet Bio- Improving workflow and consistency for Gamma delta (γδ) T cell products. Hope to see you there!
Peter Banks: In this age of COVID-19, it is challenging to widely communicate new and exciting scientific progress in the short term, like we do at our favourite conferences. Virtual conferences provide a venue for this in these difficult times where scientists can learn about product advances and new applications developed with them in mind, with a focus on cancer biology as well as other areas of drug discovery and development.
Stina Lundgren: Virtual events are a great way to cross the geographical chasm and exchange knowledge between scientists in both academia and the industry across the globe. We at Pelago Bioscience are convinced that the CETSA method will create substantial value and accelerate the drug discovery process by providing actionable data from physiologically relevant environments. At our booth, we can provide scientists with information about CETSA and general drug discovery advise. We want such discussions because it is through those that we advance our understanding and get better at generating value for our clients and collaborators.
Abbey Crawford, Senior Marketing Manager bit.bio: The world has changed and the way we work has been transformed. Virtual conferences are now the new normal and provide a great networking platform. If attendees visit out booth, they can discover our full offering in one place and get to speak to one of our experts to gain full insight into how we can best help them overcome challenges in their laboratory.
This article first appeared on the ELRIG website