Funding Opportunities

The National Center for Advancing Translational Sciences (NCATS) at the National Institutes of Health (NIH), is transforming the translational science process so that new treatments and cures for disease can be delivered to patients faster. NCATS strives to develop innovations to reduce, remove or bypass costly and time-consuming bottlenecks in the translational research pipeline in an effort to speed the delivery of new drugs, diagnostics and medical devices to patients. High throughput screening emerged toward the end of the last century and plays a critical role in the discovery and ultimately development of small molecule treatments today. However, significant numbers of human diseases are caused by currently undruggable proteins or mechanisms, meaning that they cannot readily be treated via current conventional target-based approaches using small molecules and biologics. A significant number of human disease conditions are considered untreatable as they are caused by pathologies for which we lack drug development options, such as protein misfolding, proteins with hidden active sites, defective protein-protein interactions or where the targets are “other cellular entities” (e.g., RNAs and metabolites, among others). In order to address these issues, NCATS invites applications for exploratory and early-stage projects that focus on currently undruggable target classes within intractable human diseases. Research Objectives and Scope This Notice of Funding Opportunity (NOFO) solicits applications for exploratory and early-stage projects that focus on undruggable target classes within intractable human diseases. Applicants will identify a human disease relevant undruggable target class and develop a method or agent that is selective for one or more targets within that target class. Projects proposed in response to this NOFO must address targets traditionally considered undruggable and perform preclinical proof of concept studies to further the development of methods and/or agents selective for undruggable target classes in intractable human disease. For the purposes of this NOFO, a druggable target is a target that can be engaged with high affinity through ‘conventional’ means - conventional referring to small molecules (typically produced through fully synthetic or semisynthetic methods) and biologics (typically produced in a living system) , which reversibly bind to a target as either an inhibitor, activator, agonist, or antagonist, to achieve a level of target occupancy that elicits an effect on the biology associated with the bound target. An undruggable target is considered to be a target that cannot be engaged with high affinity through conventional means, and includes targets such as intrinsically disordered proteins, RNA, organelles, and metabolites, among others. An intractable disease is considered to be any disease or class of diseases that is not easily treated, relieved, or cured, or is unable to be treated, relieved, or cured through currently available therapies. Projects should identify gaps preventing or slowing the development of treatments for diseases associated with undruggable targets and propose a preclinical method or agent that addresses the identified gap. Projects submitted in response to this NOFO are expected to identify an undruggable target class relevant to an intractable human disease (or diseases) and develop a method and/or agent that is selective for a target (or targets) within that undruggable target class. Projects that address multiple classes of undruggable targets and/or groups of intractable diseases are encouraged. The proposed project should serve as a use case that demonstrates modulation of a traditionally undruggable target, but that also serves as a proof of concept for a larger study and/or technology development that could be applied to the undruggable target class as a whole. Topics of Low Programmatic Priority - Projects that focus on (1) well established methods, such as small molecule development or gene therapy, (2) a target or group of targets that are considered druggable (such as receptors, enzymes, transporters etc.) or (3) disease(s) with significant numbers of existing effective treatments will be considered low programmatic priority. An application on a low programmatic priority topic may be deprioritized for funding despite scoring better than an application not in one of these low programmatic priority areas. Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with their organization to develop an application for support. Early-stage investigators are encouraged to apply.