This is NOT a grant application and, if successful, funds will not be transferred to your institution to support your project. Instead, this is an application to access the scientific capabilities and resources of NCI with the goal of moving promising cancer preventive agents into clinical testing. If successful, you will partner with NCI through a drug development pipeline. Depending on the drug development stage of your agent, your agent will be optimized and tested in appropriate task(s) increments with the goal of filing an IND with the US Food and Drug Administration (FDA) and entering your agent into clinical testing.
- Applications to PREVENT are evaluated for scientific merit, potential prevention efficacy, study feasibility, toxicity and pharmokinetic (PK) concerns, clinical need and opportunity, and alignment with NCI mission.
- Applications must be submitted in an Adobe Acrobat® PDF file format to: NCIPREVENT@mail.nih.gov
- Clearly indicate in the body of the proposal what resources you would like NCI to provide in response to this application.
The submission deadline is September 8, 2020.
The concept application document should be prepared using the PREVENT Concept Application form. Applications that do not conform to this requirement may be returned without review. Applications should outline the scientific nature and rationale of the proposed project and should include:
A. Background and Rationale
Provide a summary of the field sufficient to allow an appropriate understanding of the scientific and medical context from which the opportunity emerges. Describe the targeted high-risk cohorts (i.e. individuals with an increased likelihood of developing certain types of cancer, such as current or former smokers, individuals with hereditary breast and ovarian cancer syndrome, Lynch syndrome, or familial adenomatous polyposis, etc.), target cancers, targeted molecules and/or pathways, and molecular mechanism of action, if known. Please be concise and specific; it is not necessary to address cancer incidence.
B. Hypothesis and Research Objectives
Include a clear statement of the hypothesis or hypotheses to be tested and define the objectives of your proposal. Specifically, address the scientific merit of your proposal by providing supporting evidence from the field. Provide evidence to validate the target or approach for pharmacological or immunological intervention based on in vitro, in vivo, or clinical studies from your research or the literature. Provide a summary of the key experiments you have conducted to date and preliminary data that are crucial to support your proposed research. Manuscripts (published or in press) and supporting material can be included as an appendix (see the list of allowable appendix materials below). Include an assessment of the safety and therapeutic index, if known. When available, include information on the competitive landscape and comparator efficacy studies.
C. Research Strategy
Clearly describe the intended research strategy, defining the specific activities requested from NCI for the proposal; if the research activities necessary to move the concept forward to the clinic are not established or clear, please indicate this. Include specific details to demonstrate that the project has been well thought out (for example, if requesting assistance in the development of a pharmacodynamic assay, include a description of the analyte to be measured, strategy for biospecimen acquisition, assay platform, etc.). Address the feasibility of the proposed research strategy.
For preclinical drug development projects, describe the proposed development strategy, readiness of the primary assays, animal models for in vivo studies, biomarker analysis, and any supporting secondary assays, including structure-based, virtual, and selectivity assays. Supporting data can be included as an appendix (see the list of allowable appendix materials below). If specific animal models are to be proposed, clearly indicate that animals of both sexes will be used in accordance with NIH guidelines unless studies in a single sex are justified (e.g., ovarian or prostate cancer models), provide the estimated number of animals required for the proposed research, and describe at minimum the following properties of the proposed animal models: (1) whether the proposed models recapitulate the target human disease(s), (2) whether the models are known to develop consistent tumor burden within a reasonable timeframe, and (3) whether the models are known to produce data predictive of cancer preventive efficacy vs. non-efficacy in humans.
If the research involves the use of marketed drugs for new indications (drug repurposing), describe (1) whether new molecular mechanism(s) of action are proposed, (2) if new dosage, scheduling, and/or an alternate route of administration need to be established, (3) if new or previously unknown safety concerns are emerging from post-marketing surveillance, and (4) how the clinical translation is envisioned.
For new molecular entities, describe the development status of the compound and optimization strategy (for guidance, please refer to the PREVENT Stage Gates, at https://prevention.cancer.gov/major-programs/prevent-cancer-preclinical). Indicate whether the compound has undergone medicinal chemistry optimization; if not, describe the proposed strategy. Describe available enzymatic, cell-based, and absorption, distribution, metabolism, and excretion (ADME) assays. Where appropriate, also describe access to a structure-based drug design platform, available pharmokinetic (PK) and pharmacokinetic/pharmacodynamic (PK/PD) assays, and clinical readiness of the assays. Include an evaluation of functional activity, potency, and the PK/PD relationship, with an emphasis on therapeutic index, if available; supporting data can be included as an appendix (see the list of allowable appendix materials). Please also indicate whether you have had meetings with the FDA (see the list of allowable appendix materials).For immunopreventive agent development projects (e.g., preventive vaccines), describe the proposed development strategies, including the characteristics of the proposed immunomodulatory agent(s) or strategies, readiness of pertinent immune response monitoring assays, the availability of appropriate preclinical animal model(s) with key information as requested above for preclinical drug development projects, and primary and secondary study endpoints as envisioned. Describe immunological and/or molecular biomarkers deemed useful for the research. Supporting methods and data can be included as an appendix (see the list of allowable appendix materials).
D. Specific Work Request
Specify the technical expertise and resources required to implement the proposed research and to facilitate advancement of the agent into first-in-human studies, and which of these are expected to be provided by NCI. Examples of resources that can be provided by NCI include, but are not limited to:
- In vitro and in vivo efficacy studies and preclinical pharmacology
- Various carcinogen-induced and genetically engineered animal models of cancer
- Identification and evaluation of intermediate biomarkers
- PK and PK/PD modeling to evaluate efficacy and optimize dosing regimen
- Characterization of immune responses to vaccines and immunomodulatory agents
- Formulation optimization for enhanced bioavailability and clinical usefulness
- Analytical method development for investigational agents in bulk form and in biological fluids and tissues
- Scale-up cGMP and non-cGMP production of an investigational agent
- Stability testing for bulk and formulated material
- Preclinical investigational new drug (IND)-directed GLP toxicology studies
- Regulatory support
- Other resources to support drug development
Provide a statement to indicate whether your proposal adequately addresses unmet needs in cancer prevention. Include in the statement how the proposed agent or intervention differs from existing cancer preventative interventions. Specify how the proposed agent or approach will advance clinical practice. Address the novelty of the concept with respect to the target and approach, and indicate the likelihood of the concept advancing into the clinic without the assistance of the NCI PREVENT program.
1. Intellectual Property (IP) Information
The applicant should include a list of any patents issued or pending, either with respect to the agent or to any non-commercially available technology or material required for development of the agent. If an application requires the use of non-commercially available 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 with the proposed project.
Each PREVENT application must include the information described below signed by an authorized staff member overseeing IP and/or technology transfer at the applicant’s institution. The signature verifies that the staff member has reviewed the PREVENT request and determined that the technology is or is not eligible for consideration by the PREVENT program. If the technology is found not to be eligible for use as outlined in the PREVENT application, and it is central to the applicant’s proposal, submission to the PREVENT program is not encouraged.
2. The following information is requested
Details of all the following rights that your institution owns and that are used in the project (the "institution's IP"):
- Patents and patent applications
- Registered trademarks, applications for registered trademarks, and other marks
- Registered designs, applications for registered designs, and significant other designs
- Significant know-how
- 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 PREVENT project submission. (Are there contributors outside the institution and, if so, what was their role in development?)
- A complete list and brief description of all agreements with third parties related to the PREVENT project submission:
- Granting rights to those third parties under the institution's IP
- Granting rights under the third-party IP to the institution
- A complete list and brief description of all confidentiality agreements with third parties related to the PREVENT 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
G. Principal Investigator Biosketch
The principal investigator (PI) biosketch should follow standard NIH format. In the list of PI publications, please highlight any that are directly related to the proposed project by preceding them with a double asterisk (**).
H. Additional Documentation as Appropriate
Additional information that is relevant and crucial to support the proposed concept can be submitted as an appendix (see the list of allowable appendix materials below). Applications with appendix materials that are not specifically listed below may be withdrawn and not reviewed.
Allowable Appendix Materials
- Articles (published or in press) that describe relevant data
- Supplementary materials and methods describing animal models and experimental protocols in detail that cannot be accommodated in the main body of the application, but are integral to the proposed concept
- Supplementary data (figures with legends and tables with footnotes) that cannot be accommodated in the main body of the application, but are integral to support the proposed concept
- For applications proposing clinical trial support (for example, CGMP synthesis, IND-enabling preclinical studies, etc.):
- Clinical trial protocols that are approved by the applicant’s relevant institutional review board (IRB)
- Pre-IND meeting minutes, if appropriate
Please do not include PDF files of PowerPoint presentations or entire RO1 grant applications.