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Failing Faster To Succeed Sooner in Drug Discovery

A picture of medicines.
Credit: Anshu A / Unsplash.
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Read time: 8 minutes

Developing drugs is no easy feat. Behind every newly approved, safe and efficacious therapeutic are years of work through pre-clinical and clinical testing. Failures in the late stages of this pipeline are incredibly costly, both for developers and patients that eagerly await life-saving treatments. The current landscape of drug development, therefore, places great emphasis on approaches to help novel candidates “fail faster” so that they can ultimately “succeed sooner”. 

 

Revvity, a global health science solutions company, supports scientists in this quest. Its portfolio of products centers around utilizing genomic insights to accelerate therapeutic discovery, whether that be through cell line engineering, screening or basic research.

 

This week, Revvity announced its newly established Scientific Centre of Excellence in Cambridge, where scientists can outsource their research needs to Revvity experts. The site features a range of laboratories, home to translational multi-omics technologies that can support biomarker identification, imaging, prediction, screening, detection and diagnosis, informatics and other healthcare research efforts. 

 

Technology Networks recently had the pleasure of visiting the Scientific Centre of Excellence. We spoke with Dr. Chris Lowe, head of technology and innovation at Revvity, and Dr. Michelle Fraser, business unit manager in base editing at Revvity, to learn first-hand about Revvity’s motivations for launching the center, the scale of the company’s growing technology portfolio and how customers are utilizing Revvity’s services.

 

Molly Campbell (MC): Revvity’s portfolio of products supports customers with a variety of needs across healthcare research. Can you highlight key products that are accelerating novel drug development?


Chris Lowe (CL): Revvity strategically partners with customers to help them address unmet needs when developing novel drugs, starting from early steps in the workflow for target identification, lead identification and optimization, to pre-clinical. This collaboration drives speed to market and increases productivity and success rate. Our solutions support every step of the discovery workflow, from basic research to data analysis.


Target identification and confirmation:

In cases where isolation of high-quality nucleic acids from patient material or model system is required, Revvity’s Chemagic instrument and kits are the optimal automation solution. Our Dharmacon Edit-R CRISPR-Cas9 reagents deliver gene editing techniques like knock-outs and knock-ins to accelerate detection of novel molecular pathways. Additionally, we provide a wide selection of pre-made, edited cell lines and expert genome engineering services, as well as antibodies for cell characterization with imaging or flow cytometry.


Lead identification and improvement for their target:

For studying everything from large endogenous protein complexes to very small molecules, serum and plasma to crude cell lysates and purified reagents, we offer no-wash, reliable and easy-to-use immunoassays such as Alpha Technologies and HTRF, alongside configurable plate readers – including EnVision Nexus – with high sensitivity at high throughput.


For cell counting and health, image cytometers like Cellaca and Celligo give our customers increased control of their samples and data generated from their cell-based assays. When detailed profiling using molecular, morphological, and kinetic readouts is requested, our cellular high-content imaging solutions – such as Operetta CLS and Opera Phenix Plus in combination with the PhenoVue suite reagents – enable both target-based and phenotypic screening.


Furthermore, from cellular screening to high-throughput screening, custom explorer G3-integrated workstations provide innovative, application-focused automation to improve labs’ efficiency. Partnered with data handling and analysis, Signals VitroVivo unites assay development, up to ultra-high-throughput production assays, high-content screening and in vivo studies, so that our customers can search across all assays and screening data in a single platform.


Pre-clinical candidate evaluation and validation:


Revvity’s ImmuSignature assay is designed to quickly tell a customer if their drug will react adversely with the human immune system. This information has immense value as, accessed early in the pre-clinical process, it can help customers make informed decisions before investing a wealth of time and resources.

 

Additionally, our screening services provide information of what genes interact with a candidate drug. Knowing this genetic information helps determine how the drug is working in the body (mechanism of action) and what other drugs may work to complement the activity for a potential combination therapy or would likely be adverse (work against the drug), providing insight into possible safety concerns.

 

In vivo imaging provides understanding of early disease-related biological changes, allows for visualization and tracking of disease progression and helps evaluate efficacy and safety of drug candidates in model organisms. Here is where our IVIS platform, Quantum GX2 microCT and Vega ultrasound system play a key role, alongside their corresponding reagents.

 

MC: Revvity also offer services in the diagnostic space. Can you tell us more about these and how they help in our strive towards personalized medicine


CL: Revvity provides a portfolio of technologies and methods to improve the detection and management of health conditions. Our comprehensive solutions for laboratories and clinics enable reliable testing and the discovery of new biomarkers and therapies. For example, we offer innovative, end-to-end workflows for biomarker identification and characterization, as well as applications that enable labs to translate insights into decisions rapidly and efficiently. Adaptable and scalable solutions allow labs to minimize errors, reduce hands-on time and increase throughput and reproducibility. Flexible modules, based on your testing and throughput requirements, can be used to meet labs’ current and future needs.


Personalized medicine requires a rapid and accurate understanding of an individual’s genetic code to provide the most effective treatment for that individual. Specifically in our Centre of Excellence in Cambridge, we develop cell-line-derived molecular reference standards that mimic patient materials while maintaining genomic complexity. This provides a renewable and reliable source of genomic reference material for easy implementation into any quality control workflow from sample prep to downstream analysis to ensure consistency in end-to-end workflow validation and routine monitoring of performance.


Additionally, our global service laboratory Revvity Omics provides high-complexity clinical omics testing, including whole-genome sequencing. We are proud of the fact that, to date, Revvity Omics has touched the lives of more than 350 million patients.

MC: Why has Revvity opened the Scientific Centre of Excellence for Genomic Insight, and why was Cambridge the location of choice?


CL: From its Scientific Centre of Excellence for Genomic Insight in Cambridge, Revvity is able to contribute to the UK’s economy and life sciences industry by harnessing the wealth of talent in the local ecosystem to develop breakthrough solutions for unsolved health challenges.


Cambridge is not only a UK but a global scientific powerhouse, so our Centre of Excellence is strategically located and boasts top expertise and specialized capabilities to help our customers accelerate time to market for therapeutic discovery.


The site is easily accessible from the major UK and European Biotech clusters, putting us at the heart of our customer base. Cambridge is the biotech location in the UK with 15 science and business parks, and is less than 80 miles from both London and Oxford, which together form the UK’s life science golden triangle. 

Within 20 miles of Cambridge there are 608 life sciences companies (Cambridge Cluster Insights - Cambridge Ahead), not to mention the University of Cambridge, one of the top 3 universities in the world and ranked in second place globally for research in 2023  – behind Oxford University in first place, and Imperial College London in tenth place.


MC: The center includes a demonstration laboratory where Revvity product experts can train scientists on how to use the products in their particular research work. What inspired you to include the laboratory in the planning of the site?


CL: We aim to continually bring our technologies and expertise closer to our customers and potential customers and have a number of demonstration labs around the world to materialize this commitment.

 

We understand that deciding on what instruments are most appropriate for a specific lab is a significant decision, considering the investment involved. It is equally important to ensure that the scientists who are going to use the equipment are able to extract the maximum value from the investment. By providing hands-on evaluation and training in our demonstration labs, scientists can experience the value we can add to their research and see how we can help them accelerate discovery first-hand.

 

MC: For readers that may be unfamiliar, can you discuss Revvity’s work with the Pin-point™ base editing system? What is base-editing, why is it garnering excitement and how does it differ to CRISPR-based editing?


Michelle Fraser (MF): The Pin-point base editing system is part of Revvity’s cell and gene therapy portfolio aimed at improving the specificity, efficacy and safety of cell and gene therapies.


The system and underlying base editing technology is designed to enable highly efficient and precise single and multiplex (multi-gene) editing without unintended impact on cell viability or functionality. Compared to traditional CRISPR technologies, which create double-stranded breaks in the DNA, this newer editing system uses a modified Cas enzyme that only nicks one strand of the DNA. This allows for a more controlled approach to gene disruption and base correction.


With the help of the Pin-point™ base editing technology, researchers are working on the development of universal cell lines for novel therapies to treat cancer and immune-mediated diseases which, among other things, contribute to improving the affordability of cell and gene therapies worldwide.


Base editing offers precise modifications to DNA to deliver gene or cell therapy approaches with greater safety profiles. Whilst the original CRISPR/Cas system was revolutionary, base editing is a gentler method to modify the genome, potentially making the therapy safer. Additionally, Revvity’s base editing system has been shown to enable knock-out of immune response-causing proteins and knock-in a targeted CAR (chimeric antigen receptor) creating an anti-tumor CAR-T cell in a single editing reaction.


MC: What are the key bottlenecks presented to you by your customers in the drug development space?


CL: Drug discovery is a lengthy and costly process, with declining productivity in recent decades. From the first steps of target identification in the lab to post-market surveillance, the entire process can take 15 years and cost more than $1 billion.


As part of this complex drug development process, there are a number of potential bottlenecks that our customers need to overcome, including the difficulties involved in gaining a deeper understanding of early target identification and validation, the availability of validated assay kits, access to innovative tools for novel modalities – such as protein degradation or cell and gene therapy –  and the time to market. Revvity is uniquely positioned as strategic partner to provide complete workflows and services that may transform customers’ research by streamlined parallelized processes and solutions.

 

MC: Revvity says that the words “can’t be done” are a call to action. Can you explain what this means to Revvity as a company philosophy, but also how it is considered in the day-to-day work of Revvity scientists?


CL: These words truly embody the force that drives our work and supports our purpose: to expand the boundaries of human potential through science. Whether it be within newborn screening, autoimmune disease or by helping pharma and biotech customers with novel tools and capabilities, we are in a unique position to address some of the greater health challenges in the world. Responding to those challenges that come directly from our customers is what propels our constant innovation and guides our day-to-day work.


The courage, tenacity and endless curiosity of our talented teams drive us to think in unconventional ways, pivot when needed and embrace the risks and opportunities that come with the unknown.


This philosophy manifests in our day-to-day work at the Centre of Excellence in Cambridge, as our scientists seek to design experimental solutions to our customers’ scientific challenges and questions, with the aim of improving the translation of genomic insights into actions that help accelerate the time to market for therapeutic discovery.


Whether that is designing a series of screens with novel assay readouts to unravel a biological question or developing a molecular reference standard to replicate a new patient relevant format we work collaboratively to exploit the wealth of knowledge and expertise across Revvity. By doing so, we deliver solutions that enable customers to diagnose diseases earlier, develop new treatments and cures sooner, forge new pathways faster and to do it all with the highest level of quality.


Dr. Chris Lowe, Head of Technology & Innovation at Revvity, and Dr. Michelle Fraser, Business Unit Manager of base editing at Revvity, were speaking to Molly Campbell, Senior Science Writer for Technology Networks.