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Industry leaders reveal how high throughput screening is changing in R&D

Top 10 Drug Discovery Trends at the Top 20 Pharma

Industry leaders reveal how high throughput screening is changing in R&D

What do you think are the major trends in drug discovery R&D? Biologics are booming. Small screens are better than large ones. Biochemical assays have the highest success rate. Think again.

That is not what PerkinElmer found in a comprehensive survey of leaders at the top 20 Pharma, ranked for R&D spending. In fact, all three of the above assumptions are wrong.

“To lead in product development and partner with customers in solving everyday challenges, we gather information regularly about current practices and future trends,” said Volker Eckelt, PhD, Senior Strategy Leader, PerkinElmer Life Sciences.

Dr. Eckelt conducted 23 hour-long, 1:1 interviews over five months in 2020 to gather market insights on how the top 20 Pharma are increasing productivity, efficiency, and speed of drug discovery in the short and long-term.

A PerkinElmer White Paper offers a detailed look at the findings. Here, we summarize the top 10 survey findings on drug discovery trends for the top 20 Pharma leaders in R&D.

Top 10 trends in pre-clinical drug discovery at top 20 Pharma

1. Target-based screening is the preferred approach to high-throughput screening.
It is an ongoing debate. Which high throughput screening (HTS) approach is the most productive in finding hits for drug development: target-based or phenotypic? By a 3:1 margin, PerkinElmer found top Pharma screens for a specific target.

2. Small molecules are making a comeback.
These simple, stable compounds, used to treat various conditions, are the focus for 78% of preclinical research. For the minority of companies working with large molecules and biologics, most said they were in a phase of clinical research.

3. Oncology is the top therapeutic area of interest, today and tomorrow.
COVID-19 has generated a wave of interest and activity, which is expected to last for several years. However, leaders predict continued focus on traditional top therapeutic areas: oncology, CNS, cardiovascular, and metabolics.

4. Screening targets are across the board.
Arguably the most important investment in drug discovery, this critical decision is highly diversified, based on a project’s therapeutic area. Enzymes, kinases, GPCRS, and PPI lead the pack with activity levels exceeding 90%.

5. Screening models are going to get a lot more complex.
The top 20 Pharma are moving away from proteins in biochemical assays and overexpressed targets in simple cell lines toward more physiologically relevant assays using primary cells, cocultures, 3-D cell systems, or organoids. The hope is that complex models, which offer a more accurate reflection of disease biology, will provide better predictive data on the likelihood for later success.

6. Big screens are still very popular.
Large screens are still in use by leading Pharma. Full decks up to 1.4M are run roughly once a month. The top five companies may run more than 20 screening campaigns a year. The caveat here is that subsets are often the first step. Subsequent, larger screens are used when something looks promising.

7. Outsourcing is filling internal gaps when it comes to screening.
More and more Pharma look to global CROs to conduct routine screening. When faced with COVID-19 operating restrictions, staffing shortages, or training issues, R&D teams worldwide used CROs to maintain HTS productivity.

8. Multi-parameter, complex HTS platforms will be leveraged for decision-making.
Top Pharma see multiple platforms as the way to maximize hit finding, confirm targets, or conduct secondary screening. Today’s top choices (i.e., enzymatic assays, binding/immunoassays) will decrease somewhat in popularity to make room for cellular target engagement (CETSA), Label-free techniques like surface plasmon resonance (SPR), and HT FACS/Flow for primary blood cells.

9. More robust data analysis is needed.
More sophisticated HTS platforms and models will drive a need for more sophisticated data analysis. Those using off-the-shelf or homemade solutions are expected to re-evaluate data analysis in search of more flexible, customizable, integrated systems that can support big data, multi-parameter analysis in the cloud.

10. Target invalidation is the major reason for project failure.
According to survey participants, target invalidation is behind three out of four project failures. These pre-clinical projects never reach lead optimization because of a lack of confidence or an invalidated scientific hypothesis.

What is the driving force behind these trends?

Physiological relevance was a central theme across all areas of discussion. “People want to get as close as possible to the biology,” said Dr. Eckelt. “But they have limitations in their framework, which means material limitations to the current screen, or in all cases with patient-derived sets.”

Getting closer to real biology, however, must happen in the real world. Pharma companies must improve productivity and efficiency amidst rising R&D costs. Therefore, new technologies and innovative solutions cannot require intensive training or expensive instrumentation. PerkinElmer can bring novel reagents, high content screening and analysis, and seamless data integration into pre-clinical drug development.

“If we understand customers’ needs, we can bring our core competencies to fill the gaps,” said Dr.Eckelt. “Through collaboration and true partnerships, PerkinElmer can get customers up to date with these needed technologies and approaches in a cost-efficient way because we have validated products as well as custom-tailored solutions.”

For a more detailed overview of PerkinElmer’s survey of drug development trends among top 20 Pharma, get the full white paper.

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