CTSA ReFRAME Call for Proposals

Scripps Research Translational Institute and drug discovery affiliate Calibr-Skaggs invite proposals for collaborative drug repurposing screens. This translational endeavor aims to partner clinical proficiencies throughout the Clinical and Translational Science Awards (CTSA) network with drug discovery resources. CTSA-affiliated researchers and clinicians who have identified potential drug targets, pathways or screening approaches and are interested in accelerated translation into patients through drug repurposing are encouraged to respond. Working closely with Calibr-Skaggs scientists to develop an innovative assay or idea, investigators will have an opportunity to screen a best-in-class drug repurposing collection containing nearly all small molecules in any phase of clinical development. The program will give CTSA investigators access to small molecule screening capabilities and associated support, including assay optimization and miniaturization, hit identification and triaging, hit characterization, medicinal chemistry and in vivo pharmacology. Seeking synergy, a clear ability to execute on potential direct repurposing opportunities will be a key factor in selecting collaborative screens, in addition to innovation, enablement, and impact.

Repurposing, Focused Rescue, and Accelerated Medchem (ReFRAME) is a screen-ready collection of approximately 12,000 clinical compounds created with financial support from the Gates Foundation. This unique drug repurposing library contains not only FDA-approved drugs, but also investigational new drugs (INDs) that are or were in any phase of clinical development, including >1000 non-commercially available compounds with undisclosed structures manually determined using broad competitive intelligence resources. The scale and comprehensiveness of ReFRAME—the first collection built by systematically querying all available clinical data and obtaining compounds through purchase (~57%) or resynthesis (~43%) without regard to mechanism of action, availability, patent status or cost—represent a far greater reach than typical FDA-approved drug libraries. 

This call for proposals is designed to accelerate drug discovery and facilitate the translation of unique biology discovered in the laboratory or clinic into new medicines for patients. Teaming up with scientists and clinicians throughout the CTSA consortium, Calibr-Skaggs and the Scripps Research Translational Institute envision collaborative ReFRAME screens to identify repurposed drug candidates that can be quickly evaluated in patients in clinical trials. Applicants do not need to have previous knowledge or experience in high-throughput screening, and responses do not need to include a specific plan for adapting biological insights into high-throughput screens. Calibr-Skaggs’ staff has expertise ranging from assay development to medicinal chemistry, allowing support and execution of activities throughout the screening campaign, such as assay design and optimization leading up to the screen and hit triaging after the screen. 

Applicants should use the attached template to submit a brief proposal. Submissions will be competitively reviewed by a committee of scientists at the Scripps Research Translational Institute and Calibr-Skaggs and prioritized based on unmet medical need, scientific merit/feasibility, and the ability to follow up clinically if a repurposing opportunity is identified. Once a screen has been selected for the program, Calibr-Skaggs scientists will work directly with the CTSA investigator to develop a workplan to optimize the assay for screening (as needed) and execute the screen. Calibr-Skaggs has efficient mechanisms for bringing screen-ready assays in-house or providing the library to investigators in a ready-to-use format for screening at their preferred site. Sharing will be subject to a standard collaboration and MTA template that has been developed for ReFRAME. In addition to providing compounds for primary screening and hit confirmation assays, Calibr-Skaggs will be available to assist as needed with pre-screening assay optimization and miniaturization, developing hit triage workflow, resynthesis of confirmed hits, and engaging in discussions on the merits of direct repurposing versus accelerated medicinal chemistry.  

Calibr-Skaggs is a non-profit drug discovery institute established in 2012 with the mission of filling a translational gap between innovative biological research in academia and drug discovery activities in biotech and pharma. In 2018 Calibr-Skaggs became an operating division of Scripps Research, creating the unique opportunity for the Scripps Research Translational Institute to serve as an accelerated drug discovery hub amongst the CTSA network. In addition to the one-of-a-kind ReFRAME drug repurposing library, Calibr-Skaggs has broad drug discovery capabilities, including state-of-the-art robotics and high-throughput screening facilities, on-site medicinal chemistry, in vivo pharmacology resources, and a core strength in cell-based screening. By partnering with the broader CTSA network, the hope is to create a powerful platform for the identification of novel therapies coupled with direct translation to patients, all within the non-profit sector. 

Learn more about Calibr-Skaggs.