DAta | National Center for Advancing Translational Sciences

ID	Title	Body
488	TRND Projects	TRND projects are selected based on their potential to move forward into human trials and transform patient care for rare and neglected diseases. Each project has the potential for success and ability to teach important lessons about rare and neglected disease drug development. Browse preclinical active projects and completed projects, or learn more about clinical research studies, drug repurposing screening for rare and neglected diseases, and gene therapy platform for rare diseases.
487	Updates to Prior TRND Proposals	TRND may accept updates one year after a proposal is initially deferred or declined. Updates may require: A summary letter, not to exceed two pages. Explain how the proposal has been modified and strengthened. If the prior proposal received a detailed evaluation by TRND, respond to any comments and recommendations, and address any disagreements. An amended proposal. The amended proposal should follow the current “Proposal Instructions” governing required documents and page limits.
486	TRND Project Implementation and Conduct	TRND researchers conduct projects using a milestone-driven, team-based operational model. Upon selection for collaboration, TRND scientists perform an initial gap analysis to determine the scope of work. A joint scientific team forms based on the project’s specific needs, and a formal project plan and collaboration agreement governs the tasks to be completed. A TRND project team lead oversees day-to-day operations and project plan execution. Projects failing to meet critical milestones or timelines are subject to discontinuation. Project Team For each project, TRND staff assemble a scientific project team, led by a TRND manager. In consultation with the collaborating investigator, the project team develops and defines the following elements: Project plan Timeline Milestones and deliverables “Go/no-go” decision points Project Plan TRND leadership approve the project plan, and any changes to the plan must be approved by TRND leadership. A joint research committee may make recommendations to TRND leadership regarding project termination, if necessary. Project Termination If a project fails to meet its timeline, milestones or deliverables — or with a recommendation from the joint research committee — TRND staff will terminate a project. Whenever possible, the collaborating investigators receive guidance on how to move the project forward.
485	Intellectual Property and TRND	Applicants/institutions retain any intellectual property (IP) generated prior to the initiation of a TRND collaboration as background IP. The potential for development of new, multi-party IP will depend on the stage at which the project begins collaboration with TRND. However, all TRND program collaborators should anticipate joint IP development with NCATS employees. Inventorship of any new, multi-party IP created from the TRND collaboration will be determined according to U.S. patent law and governed under the collaborative agreements executed at the outset of the partnership. To ensure sufficient freedom to operate on the agent proposed in the application, the applicant must provide a clear description of the relevant patent space and status of the IP. This includes a list of any patents issued or pending with respect to either the agent to be developed or to any commercially unavailable technology or material required for the development of the proposed agent. In the event that a project requires the use of commercially unavailable technology or equipment that is patented by a third party, the applicant must provide documentation that the patent holder does not object to the applicant’s use in support of the proposed TRND project. Each TRND application must include the information described below, signed by an authorized staff member overseeing IP and/or technology transfer at the applicant’s institution or company. This verifies that the request has been reviewed and that the technology is eligible for consideration by the TRND program. If technology central to the proposal is found to be ineligible for use as outlined in the TRND application, submission to the program is not encouraged. Required Information The following information will be required: Description of the patent space/freedom to operate around the proposed agent. This is especially important for, though not limited to, lead optimization projects likely to require significant medicinal chemistry support. Details of all the following rights that are owned by the applicant institution and that will be used in the project (the “institution’s IP”): Patents and patent applications Significant know-how Registered trademarks, applications for registered trademarks and other marks Registered designs, applications for registered designs and significant other designs Significant copyright works and other IP rights Details of all employees, consultants and other parties involved in the development of the institution’s IP related to the TRND project submission. If there are contributors from outside the institution, describe their role in development. A complete list and brief description of all agreements with third parties related to the TRND project submission: Granting rights to those third parties under the institution’s IP Granting rights under third-party IP to the institution A complete list and brief description of all confidentiality agreements with third parties related to the TRND project proposal. Details of any: Claims made by third parties against the institution related to the project proposal that the institution has infringed a third party’s IP rights Circumstances where a third party has or may have infringed the institution’s IP or other IP used in the institution’s business related to the project proposal
484	Considerations for TRND Collaborators	TRND supports projects across phases of development that include preclinical and Investigational New Drug (IND) application-enabling studies. Individual projects can begin at various stages, depending on the treatment type. TRND does not support direct entry into clinical testing. TRND projects typically represent one of the following general stages or types: Lead Optimization: In this stage, researchers aim to identify and develop a potent, specific development candidate. These early-stage candidates must include: Clear structure-activity relationships in at least two structurally distinct chemical series or a well-defined biological lead; Reproducible activity in primary and orthogonal assays; Efficacy in an accepted animal model (or, when not available, cellular model) of the disease; Initial indications of favorable absorption, distribution, metabolism and excretion properties; and Favorable head-to-head comparisons to the prior art. New Molecular Entity or New Biologic Entity: This type of project involves an advanced lead molecule, requiring completion of IND-enabling studies. At minimum, the selected candidate molecule will include clear efficacy data, good drug metabolism and pharmacokinetic properties, and initial non-Good Laboratory Practice safety studies demonstrating no gross toxicities. Development candidates may require completion of IND-enabling pharmacokinetics, pharmacodynamics, toxicology or formulation studies. Gene or Cell-Based Therapy: Gene or cell-based therapies use technologies to deliver genes or living, intact cells to patients to treat or prevent certain diseases. TRND only considers late-stage gene or cell-based therapy projects at this time. At minimum, these projects should have an identified delivery vector, a selected curative gene construct and a validated animal disease model(s). Repurposing: A repurposing candidate represents a drug previously approved by the Food and Drug Administration to treat another disease that has been shown to also be effective in an animal model (or, when not available, cellular model) of a rare condition or neglected tropical disease. Relying heavily on the previous indication data package, a repurposing candidate will be more advanced, in need of formulation, dose-finding, disease-specific toxicology or other studies to enable clinical testing. Platform Technology: Through these projects, investigators seek to develop a therapeutic candidate directed toward a specific rare condition or neglected tropical disease, but the technology represents a platform with the potential to address a wider range of additional disorders and that can enable more efficient future development of other therapeutics. Both early- and later-stage projects are considered, as described above.
483	How to Request a TRND Collaboration	TRND is accepting new proposals to collaborate. Proposals are due Sept. 30. Interested investigators should contact program staff to initiate the process. Please email askTDB@nih.gov(link sends e-mail) for further information.Prospective collaborators are encouraged to connect with NCATS for timely notification when program updates are announced.General Proposal ProcessProposals for collaborative research are assessed for scientific merit, program balance, availability of resources and technical feasibility. Steps include:Pre-screening with TRND staff to confirm eligibility. This “letter of intent” process consists of submission of a summary abstract of the proposed project and a telephone discussion with TRND staff.Eligible investigators submit a full proposal package. This package includes a formal written proposal and specified supporting documents.TRND staff assess proposals. Select proposals may receive additional input from staff in other NIH Institutes and Centers and from external drug development experts. Additional supporting data may be requested by TRND through a due diligence process. ConfidentialityAs with any research or contract proposal submitted to NIH, proposals submitted to the TRND program are considered confidential and do not constitute public disclosure.
482	Work with TRND	The TRND program is accepting new proposals to collaborate. Proposals are due Sept. 30.Review How to Request a Collaboration to begin the process. By collaborating with TRND, partners with promising new therapeutic candidates benefit from the significant rare and neglected disease preclinical development expertise of TRND scientists. No funds are awarded through TRND. In general, the program leverages internal resources and preclinical and regulatory expertise to support the development of promising, well-validated therapeutic candidates from as early as lead compound optimization through submission of an Investigational New Drug application to the Food and Drug Administration.Interested investigators undergo initial pre-screening to assess overall fit for the TRND program prior to submitting a formal proposal. Full proposals are rigorously assessed by TRND staff, with additional input from staff in other NIH Institutes and Centers and from external drug development experts. When a collaboration is initiated, TRND forms a project team and a project plan is developed, including a timeline, milestones, deliverables and “go/no-go” decision points.Learn more about working with TRND:How to Request a Collaboration: Overview of general proposal process and detailed instructions for interested investigatorsConsiderations for Collaborators: Minimal data requirements and scope limitationsIntellectual Property: How TRND handles background versus new intellectual property created during the projectProject Implementation and Conduct: Project management, oversight and governanceUpdates to Prior Proposals: How to amend a prior proposal and what needs to be achieved in the interim
481	TRND Resources	Internal Resources As part of the NIH Intramural Research Program, the TRND program also has access to shared resources on the NIH campus in Bethesda, Maryland, including small and large animal facilities and the NIH Clinical Center, the world’s largest facility dedicated to clinical research. External Resources The external TRND network includes organizations across the rare diseases patient community and, through close collaboration with the Food and Drug Administration, regulatory experts. In situations where TRND internal resources are insufficient to generate key materials or data, such as Good Manufacturing Practice production and multi-species Good Laboratory Practice toxicology studies, NCATS leverages its government contracting capability to work with expert contract research organizations.
480	TRND Expertise	The TRND program supports a world-class, in-house team of drug development experts and project managers with experience and knowledge across the spectrum of drug discovery and development. TRND staff are capable of providing any and all of the following expertise, as needed: Medicinal chemistry optimization Evaluation of functional activity, potency, pharmacokinetics, pharmacodynamics and efficacy Biomarker development Definition or optimization of dose and schedule for in vivo activity Development of pharmacology assays Conduct of pharmacology studies with pre-determined assays Acquisition of bulk substance (Good Manufacturing Practice [GMP] and non-GMP) Development of suitable formulations Development of analytical methods for bulk substances Production of dosage forms Stability assurance for dosage forms Range-finding initial toxicity IND-directed Good Laboratory Practice toxicology, with correlative pharmacology and histopathology Planning of clinical trials Regulatory support to increase the likelihood of satisfying Food and Drug Administration requirements IND filing support
479	TRND Scientific Capabilities	Scientific CapabilitiesThe program leverages both internal capabilities and external contract resources to advance projects most efficiently. TRND is not a grant program. TRND provides in-kind resources to push forward preclinical drug development. TRND ExpertiseThe TRND program supports a world-class, in-house team of drug development experts and project managers with experience and knowledge across the field of drug discovery and development. TRND staff can provide the following expertise, as needed:• Medicinal chemistry optimization• Evaluation of functional activity, potency, pharmacokinetics, pharmacodynamics and efficacy• Biomarker development• Definition or optimization of dose and schedule for in vivo activity• Development of pharmacology assays• Conduct of pharmacology studies with pre-determined assays• Acquisition of bulk substance (Good Manufacturing Practice [GMP] and non-GMP)• Development of suitable formulations• Development of analytical methods for bulk substances• Production of dosage forms• Stability assurance for dosage forms• Range-finding initial toxicity• Investigational New Drug (IND)–directed Good Laboratory Practice toxicology, with correlative pharmacology and histopathology• Planning of clinical trials• Regulatory support to increase the likelihood of satisfying U.S. Food and Drug Administration requirements• IND filing support

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