The number of approvals for new drugs and biologics has fallen steadily in recent years, despite increasing R&D expenditure. Cost effective and innovative approaches to drug discovery and development have therefore become particularly important to ensure shareholder value. Improvements to the lead generation process are a key initiative for company’s aiming to avoid expensive compound failures in the latter stages of the drug discovery process.

‘Accelerating Lead Generation: Emerging technologies and strategies’ is a report that provides an in-depth examination of state-of-the-art technologies for lead generation. This report assesses the potential of new and emerging technologies for improving the quality of drug candidates entering clinical research, and reviews the benefits associated with different approaches to lead generation, including high throughput screening, fragment based drug discovery and virtual screening. The lead generation strategies adopted by leading pharma companies are evaluated to provide strategic recommendations for success, and the trends that are shaping the future acceleration of lead generation are identified.

Key Findings

Truly novel molecules are far more likely to be identified during the optimization process through the manipulation of structures than through screening. Methods include forming a new ring structure within a compound (or opening one out), the replacement of functional groups with bioisosteres and scaffold-hopping. Emerging methods for scaffold hopping based on force fields are growing in popularity.

Virtual screening and fragment-based drug discovery will complement HTS-generated data rather than replacing it. The low cost of virtual screening and its potential for improving library design means that large screens can be carried out in the earliest stages of drug discovery. Conversely, it is best to apply fragment-based drug discovery to targets for which quality structural information is readily available.

New technologies that replace fluorescence-based or radioligand displacement assays are growing in throughput and are being rapidly introduced across the industry. Innovations that improve the throughput and sensitivity of label-free technologies are either introducing them to drug discovery as secondary assays, or promoting secondary assay technologies to primary versions.

Improved methods for handling data, multiplexing assays, and using primary cells, 3D cell culture or stem cell derived populations will increase the physiological relevance of data collected. Novel in vivo models, such as zebrafish and whole animal imaging may also provide additional data.

Use this report to...

• Analyse the potential of emerging technologies for improving the quality of drug candidates and understand how such innovations can improve the ability of fragment based drug discovery and virtual screening to identify new lead compounds.

• Explore recent developments in high throughput screening with this report’s analysis of innovations in biological assay development, including improvements in in vitro assays, cell-based assay technology and in-vivo methods for lead generation.

• Examine the role of ADME and toxicology in accelerating lead generation with this report’s analysis of innovations in the assessment of ADME characteristics and toxicology at the lead generation stage.

• Evaluate the lead generation strategies of major companies with this report’s case study analysis of Bayer, Boehringer Ingelheim, Millennium Pharmaceuticals (Takeda), and understand the importance of R&D models, academia collaborations and technological innovations to lead generation success.

Explore issues including...

The need for innovation. In response to declining R&D productivity, companies are aiming to address the areas that are most likely to lead to the failure of a new compound. The overall likelihood of a project progressing from Phase 1 to approval is roughly 20%, although in some therapeutic areas this may be as low as 8%. Failure in the late stages of drug development remains a real problem for the industry.

Emerging assay technologies. Novel assays are required to improve the output of HTS (high throughput screening). Key areas of innovation include the development of label-free assay technologies and the increasing use of cell-based assays/high content assays.

The early identification of ADME and toxicology issues. Primary HTS focuses on compound potency rather than any of the other numerous attributes required for a drug to succeed in the clinic. These include cell permeability, solubility, plasma protein binding, pharmacokinetics, bioavailability and predicted metabolism, as well as target specificity and toxicology.

Discover...

• What has driven interest in the improvement of lead generation in recent years?
• Which are the key technologies in the drive to improve lead generation and identify the most suitable lead series for further optimization?
• What are the most promising areas of innovation in lead generation?
• What strategies are the leading pharma companies adopting in order to measure key endpoints for lead generation in a high throughput, parallel and cost effective fashion?
• How can companies take a truly novel approach to lead generation through the use of innovative new technology?