Forecast for Expanding the Target Landscape by Drugging the Undruggable (R21 Clinical Trial Not Allowed)

forecasted

The National Center for Advancing Translational Sciences, with other NIH Institutes and Centers (ICs), intends to publish a Notice of Funding Opportunity (NOFO) to solicit applications for research on undruggable target classes within intractable human disease. 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. This NOFO is intended to jumpstart research that demonstrates innovative strategies to modulate targets that cannot be addressed by established therapeutic types, furthering the development of methods and/or agents selective for undruggable target classes. 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. 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. 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 development of conventional therapies. Applications are not being solicited at this time. Notice is being provided to allow potential applicants sufficient time to develop meaningful collaborations and responsive projects. This NOFO will utilize the R21 activity code. Investigators with expertise and insights into this area of translational science are encouraged to begin to consider applying for this new NOFO. In addition, collaborative investigations combining expertise in translational science, drug development and drug discovery will be encouraged and these investigators should also begin considering applying for this application.