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Review
. 2021 Jan;20(1):64-81.
doi: 10.1038/s41573-020-0087-3. Epub 2020 Nov 16.

Improving target assessment in biomedical research: the GOT-IT recommendations

Christoph H Emmerich  1 , Lorena Martinez Gamboa  2   3 , Martine C J Hofmann  4 , Marc Bonin-Andresen  2 , Olga Arbach  2   5 , Pascal Schendel  2 , Björn Gerlach  6 , Katja Hempel  7 , Anton Bespalov  6   8 , Ulrich Dirnagl  2   3 , Michael J Parnham  4   9
Affiliations
Review

Improving target assessment in biomedical research: the GOT-IT recommendations

Christoph H Emmerich et al. Nat Rev Drug Discov. 2021 Jan.

Abstract

Academic research plays a key role in identifying new drug targets, including understanding target biology and links between targets and disease states. To lead to new drugs, however, research must progress from purely academic exploration to the initiation of efforts to identify and test a drug candidate in clinical trials, which are typically conducted by the biopharma industry. This transition can be facilitated by a timely focus on target assessment aspects such as target-related safety issues, druggability and assayability, as well as the potential for target modulation to achieve differentiation from established therapies. Here, we present recommendations from the GOT-IT working group, which have been designed to support academic scientists and funders of translational research in identifying and prioritizing target assessment activities and in defining a critical path to reach scientific goals as well as goals related to licensing, partnering with industry or initiating clinical development programmes. Based on sets of guiding questions for different areas of target assessment, the GOT-IT framework is intended to stimulate academic scientists' awareness of factors that make translational research more robust and efficient, and to facilitate academia-industry collaboration.

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Conflict of interest statement

M.J.P. is a member of the Scientific Advisory Boards of EpiEndo Pharmaceuticals, Cyclone Therapeutics and aidCURE GmbH. A.B. is an employee and/or shareholder of PAASP GmbH, PAASP US LLC, EXCIVA GmbH, Synventa LLC and RITEC Pharma. The other authors declare no competing financial interests.

Figures

Fig. 1
Fig. 1. Defining the critical path of target assessment.
a | Different target assessment aspects and requirements are grouped into assessment blocks, which can be arranged into a project-specific critical path according to project needs, timelines and available resources. The order of assessment blocks is project-specific and some assessment blocks can run in parallel, might not be relevant or do not apply due to indication-specific characteristics. b | The identification and arrangement of all project-relevant assessment blocks is facilitated by answering a set of critical path questions at the beginning of a project (step 1). As a next step, sets of experimental approach questions help to define specific activities for each selected assessment block (step 2) to identify key experiments to increase confidence in the target of interest. Requirements to ensure data quality/robustness also need to be checked after new assessment block-specific tasks have been identified, especially for decision-enabling processes. For this, a detailed set of data quality questions has been created (step 3). If all milestone requirements and go criteria are fulfilled, a go decision is appropriate and the next assessment block can be addressed (step 4).
Fig. 2
Fig. 2. Workflow of the target assessment process according to the GOT-IT recommendations.
Steps 1–7: the steps of the GOT-IT (Guidelines On Target Assessment for Innovative Therapeutics) workflow to define a project-specific critical path. The dotted arrow indicates an important data feedback mechanism, highlighting the recurrent nature of the data review exercise for each assessment block after a certain set of information has been collected. The design of studies and experiments as well as the definition of goals and expectations, specifying the direction of a translational project, can be facilitated by completing a target assessment project plan at the beginning of a project (see Supplementary Table 2 for a template).
Fig. 3
Fig. 3. Position of the GOT-IT recommendations in the drug discovery value chain.
The GOT-IT (Guidelines On Target Assessment for Innovative Therapeutics) recommendations cover and raise awareness for experimental, technical or translational/commercial activities within the drug discovery value chain that assess the potential therapeutic benefit of a molecular drug target (green areas). Guidance is also provided to support selection and prioritization of the most promising drug targets, up to the point where the first hit compounds are identified using available screening assays (light green areas). The GOT-IT recommendations do not address chemical and compound-related aspects, including hit/lead compound optimization, absorption, distribution, metabolism and excretion (ADME) studies, intellectual property and freedom-to-operate aspects of the compound, its physicochemical properties, drug–drug interactions, compound safety and so on, which are also critical for the success for drug development but are beyond the scope of this article (light blue areas). HTS, high-throughput screening.
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