Drug discoverers have wrestled with the problem of attrition for over a decade. Yet today, about 60% of candidate drugs still fail in clinical trials due to poor efficacy. Luckily, this old problem is finally being tackled by new solutions. Novel approaches are now enabling more reliable efficacy predictions early in the drug discovery pipeline, helping to prioritize only the very best compounds from the outset. As we discuss in our new eBook, these advances offer multiple advantages over conventional methods to improve the success of your drug discovery programs.
Read on to learn how you can overcome the challenges posed by conventional approaches, to help drive the success of your programs and the development of essential new drugs for patients.
What are the challenges hindering drug discovery success?
Drug discovery is well-known for being a highly complex, multi-step process involving substantial investment and years of research and development. Consequently, efficacy failure during late-stage clinical development can be significantly costly for pharmaceutical and biotech companies. This is because they receive no return on their investment and lose that part of their portfolio development, which can negatively impact their market share. What’s more, for smaller companies with fewer assets, failure could mean complete shutdown of the business.
Avoiding costly clinical failure is therefore a key goal for drug developers. One technique that is routinely used to predict efficacy involves assessing target engagement, i.e., measuring whether the compound binds to the intended target. However, the current high rate of efficacy failure indicates that conventional assessments of target engagement are not as effective as they should be—and can even hinder the success of your programs.
For instance, early lead generation involves high-throughput screening (HTS) of >100,000 compounds against the target. At this stage, it’s imperative to quickly and reliably discard inactive compounds and prioritize only those that are true hit compounds. However, conventional target engagement assays can easily generate false positive results, which are likely to cause costly efficacy failures at later stages.
But this isn’t the only problem. Identifying these false positives can be difficult and labor-intensive, potentially causing delays to your project. What’s more, traditional target engagement assays used in later lead optimization are typically time-consuming and costly. All of this means it can be difficult to ensure the quality of the compounds you progress while staying within your project’s time and budget constraints.
Fortunately, a novel tool can now help you overcome these challenges.
How a new approach is overcoming key challenges in drug discovery
An innovative target engagement assay that enables you to quickly and reliably identify efficacious compounds from a stage as early as lead generation is now available. The Cellular Thermal Shift Assay (CETSA) assesses target engagement directly in live intact cells, lysates and even tissues, offering you more physiologically relevant data compared to traditional assays. This enables you to prioritize only the very best compounds and reduce the risk of late-stage efficacy failure, while also expediting your programs and ensuring you stay within budget.
Reducing the risk of false positives in lead generation
The three CETSA formats offer you flexibility to apply the assay to any stage of drug discovery. The CETSA HT format, for example, enables rapid primary screening of >100,000 compounds. Importantly, the reliability of the data radically reduces the risk of generating false positives to prevent efficacy failure. Since the proof-of-concept study just three years ago, other studies have shown how CETSA HT can enhance primary screening during lead generation, for example by efficiently identifying inhibitors of two important oncology targets.
Speeding up timelines and keeping projects on track
Once you have set up CETSA, you can use the same assay repeatedly without investing any more time in assay development, helping you to speed up your timelines by 6-12 months compared to conventional assays. What’s more, the CETSA EC50 values give you a consistent reference point that can facilitate translational studies as your compounds move from lead generation into lead optimization. Indeed, a recent study has shown how CETSA can enhance lead optimization by reliably assessing target engagement in in vivo animal experiments. CETSA can also be used to strengthen target validation and inform structure-activity relationships to ensure your projects hit key milestones.
Why not seize the opportunity to succeed with CETSA?
CETSA is designed to help overcome some of the biggest challenges you face in your drug discovery programs. The ability to quickly generate more robust, relevant target engagement data early in the pipeline enables you to ‘fail faster’ and confidently prioritize only the very best compounds. CETSA can also reduce false positives to avoid late-stage efficacy failures, expedite your project timelines, and ensure you stay within budget. So why not seize this opportunity to enhance the success of your programs and ensure patients get the treatments they need?
Download your free copy of our new eBook to find out how CETSA can help overcome the key challenges you face in drug discovery: