NExT Proposal Instructions
Please note that a NExT proposal is NOT a grant application. Rather, a NExT proposal is an application to gain access to scientific capabilities and resources available to the NCI with the goal of moving promising anti-cancer concepts and novel agents into clinical testing. Applications to the NExT Program are evaluated for scientific merit, feasibility, novelty, clinical need, and alignment with NCI mission. Special consideration will be given to applications that address unmet needs in oncology, including approaches to exploit “undruggable” drug targets, orphan malignancies, and pediatric cancers.
NExT Program Data Reporting Guideline (NEW)
Rigor, minimization of bias, and transparency of reporting are important for the evaluation of the NExT application, contributing to a successful collaboration, and ultimately drug development. Several reporting guidelines have been applied in the scientific community, but given the broad scope of drug discovery and development, no single set of criteria can apply to all studies. For this reason, the NExT Program suggests that the applicants consider the items listed in the following guideline in their study design, addressing the items that are appropriate — specifically those in bold font — when describing preliminary studies performed in support of their applications.
|• Rationale for the selected models (animal and/or cell), clinical applications, and endpoints|
|• Adequacy of experimental controls|
|• Choice of route and schedule of intervention dosing|
|• Justification for sample size, including statistical power calculation (discussion of effect of size in relation to potential clinical impact)|
|• Appropriate statistical methods for analysis and interpretation of data|
|• Authenticity of cell models via recent sequence analysis (such as short tandem repeat) to ensure that cell lines utilized in the described/anticipated studies are consistent with the original data in the repository (http://bioinformatics.istge.it/hypercldb/)|
|• Methods of blinding (allocation concealment and blinded assessment of outcome)|
|• Strategies for randomization and/or stratification|
|• Reporting data missing due to attrition or exclusion|
|• Reporting all results (negative and positive)|
|• Independent validation and replication, if available|
|• Relevant literature in support of/in disagreement with the results|
|• Robustness and reproducibility of the observed results|
|• Evidence of a dose (concentration) response relationship that is target dependent|
Clearly indicate in the body of the proposal what you would like the NCI to provide in the form of resources in response to this application.
Please Note: Applicants who are requesting early discovery resources should be aware that such resourcing is done via the NCI’s Chemical Biology Consortium (CBC). Applicants whose projects are approved will be invited to join the CBC and are expected to become signatories to the CBC Participants Agreement. If you are submitting an early discovery NExT Program application, you are expected to have read and understood the referenced agreement and to have contacted your institution’s or company’s Technology Transfer Office to make certain that your organization is willing to accept the terms of this agreement.
Applicants may also apply for access to the NExT Diversity Library for their screening activities. These applications will also undergo the evaluation process.
The “NExT Concept Application” for both discovery and development projects includes 5 sections as described in detail below; additional material can be uploaded as an appendix. Please use the NExT Concept Application Template, also available when the cycle opens, in proposalCENTRAL; follow PHS 398 font guidelines, i.e. Arial, Helvetica, Palatino Linotype or Georgia typeface, 11 point or larger; and convert all documents to PDF files, and please make sure all PDF files are not password protected, before submission.
Required Documents for Discovery and
1. NExT Concept Application
The concept application document should not exceed 5 pages and should outline the scientific nature and rationale of the proposed project and should include the following:
Background: 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 target, targeted cellular pathways, and molecular mechanism of action, if known. Please be concise and specific; it is not necessary to address cancer incidence.
Hypothesis: Include a clear statement of the hypothesis(es) to be tested and define the objectives of the proposal. Specifically, address the scientific merit of your proposal by evaluating whether your hypothesis is supported by the field. Provide evidence to validate the target and/or the approach for pharmacological 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; manuscripts and supporting material can be uploaded as an appendix. Include an assessment of safety and therapeutic index. When available, include information on the competitive landscape and comparator efficacy studies.
Research Strategy and Specific Request: Clearly describe the intended research strategy defining the specific activities requested from the NCI with 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 as necessary 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 early-stage drug discovery projects, describe the proposed screening strategy, readiness of the primary assay, and any supporting secondary assays available, including structure-based, virtual, and selectivity assays. Supporting data can be uploaded as an appendix. For new molecular entities, describe the development status of the compound and optimization strategy (for guidance, please refer to the NExT Stage Gates). Indicate whether the compound has undergone medicinal chemistry optimization; if not, describe the proposed strategy. Describe available enzymatic, cell-based, and ADME assays, and where appropriate, access to a structure-based drug design platform; include a description of validated disease animal models (e.g., GEMMs). Specify the expected resources or expertise required from the NCI to facilitate advancement of the agent into first-in-human studies.
Examples of resources that can be provided by the NCI for discovery projects include, but are not limited to:
- Target validation; applicant should specify what needs to be done to increase the confidence in mechanism (e.g., transgenics, knock-out studies, RNAi, chemical probes).
- Exploratory screen development and high-throughput screening (HTS) assay optimization.
- HTS and hit validation; requests should address general attributes of the HTS selected (format, scalability, performance).
- Medicinal chemistry optimization: if agent is available, provide assessment of the quality and/or the potential and strategy to obtain quality leads, including patent position and potential for analog development. Specify clinical benefits of your new molecular entity compared to existing therapy in terms of efficacy and side effects, as well as the therapeutic gap you aim to address.
- Evaluation of functional activity, potency, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy.
- Biomarker development; applicant should address the utility of the biomarker in the clinical setting.
For late-stage drug discovery projects, describe the current compound optimization status and strategy for further development (refer to the NExT Stage Gates for guidance). Indicate whether the compound has undergone medicinal chemistry optimization. Indicate whether any formulation work has been performed or describe the proposed formulation strategy. Describe available PK/PD assays and clinical readiness of the assays. Include an evaluation of functional activity, potency, and PK/PD relationship, with an emphasis on therapeutic index if available; supporting data can be uploaded as an appendix.
Please also indicate whether you have had meetings with the FDA. Specify the expected resources from the NCI and the role of the applicant’s institute and collaborators in the project. Examples of resources that can be provided by NCI include, but are not limited to:
- Definition or optimization of dose and schedule for in vivo activity
- Development of pharmacology assays
- Conduct of pharmacology studies with a pre-determined assay
- Acquisition of bulk substance (GMP and non-GMP)
- Scale-up production from lab-scale to clinical-trials lot scale
- Development of suitable formulations
- Development of analytical methods for bulk substances
- Production of dosage forms
- Stability assurance of dosage forms
- Range-finding initial toxicology
- IND-directed toxicology, with correlative pharmacology and histopathology
- Planning of clinical trials
- Regulatory affairs, so that FDA requirements are likely to be satisfied by participating investigators seeking to test new molecular entities in the clinic
- IND filing advice
For clinical drug development projects (Phase 0/I/II), provide a summary of all pertinent preclinical and clinical efficacy, toxicology, PK, and PD data, including studies of agent combinations. Describe the development plans for the agent, including the clinical trial design and objectives if known (e.g., primary and secondary study objectives, endpoints, patient population, eligibility criteria, estimated sample size, treatment arms/regimens, statistical endpoints, correlative studies, and patient samples required to perform correlative studies). For combination trials, include details about the originator of the agents (investigational/marketed) and rationale for conducting the study, indicating possible advantages over single agents/current therapies. If available, please upload the Investigator’s Brochure as an appendix.
Justification: Provide a statement to indicate whether your proposal adequately addresses unmet needs in oncology, including orphan or rare malignancies, pediatric cancers, “incurable” cancers, or cancers not commonly addressed by the pharmaceutical industry. Specify how the proposed compound or approach will advance clinical practice and improve current therapy. For imaging agents, provide an explanation of why the imaging represents a particularly innovative or promising approach to the prevention, detection, diagnosis, or treatment of cancer.
Uniqueness: Include a statement about how the proposed agent or therapy differs from standard therapies in practice or under clinical evaluation. If available, provide comparator efficacy and safety data for your investigational agent (biologic, vaccine, or new molecular entity) or cell therapy approach. 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 NExT Program.
Intellectual Property (IP) Information: The applicant should include a list of any patents issued or pending with respect to either the agent or to any non-commercially available technology/material required for the development of the agent. In the event that an application requires the use of non-commercially available technology/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 NExT application must include the information described below signed by an authorized staff member overseeing IP and/or technology transfer at the applicant’s institution. This verifies that he/she has reviewed the NExT request and that the technology is or is not eligible for consideration by the NExT Program. If the technology is found not to be eligible for use as outlined in the NExT application, and it is central to the investigator’s proposal, submission to the NExT Program is not encouraged.
The following information is requested:
- Details of all the following rights which 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 NExT 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 NExT 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 NExT 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 institutions’ business related to the project proposal
- Details of all the following rights which your institution owns and that are used in the project (the “institution’s IP”):
Current and Pending Support: Please provide a list of current and pending funding sources. For applicants in academia, this would include current grants from both government and non-government sources, and any research resources provided directly from their institution. Individuals working directly for the government should provide an annual budget for their laboratory and any additional outside funding sources.
Principal Investigator Biosketch: The principle investigator biosketch should follow the NIH standard format. In the list of PI publications, please highlight any that are directly related to proposed project by preceding them with a double asterisk (**).
Questionnaire for Biologics: If submitting a project involving the discovery or development of biologics, please complete the appropriate NCI Biological Resources Branch (BRB) Questionnaire and include it in the appendices of the application.
Additional Documentation as Appropriate: If appropriate, additional information can be submitted, including a letter of commitment for any proposals containing a clinical component and any preliminary or supporting data (use appendices upload buttons).
Clinical Letter of Commitment: All investigators requesting production of clinical-grade material and/or IND-directed toxicology studies must provide a letter of commitment from their institute. This letter is intended to ensure the reviewers and the NCI that the products and data produced by the NExT Program have a clinical outlet, and as such, the letter should indicate that the institution is committed to the filing of an IND and conduct of a clinical trial once NExT Program activities are completed. The letter of commitment should be signed by the head of the cancer center or the director of clinical research at the institution(s) at which the clinical trial will occur, or other party with obvious authority to commit the institution to conducting a clinical trial. If neither the signatory nor the applicant is a practicing medical oncologist, the letter of commitment should also contain the signature and contact information of the clinician who will be the principle investigator of the clinical trial. It may also be helpful for the applicant to include a supplemental letter from this clinician indicating that he or she is willing to undertake the trial.
Other Appendices: Appendices should be limited to papers in press and preliminary data. Please do not include PDF files of PowerPoint presentations or entire RO1 grant applications.
Applications should be submitted according to the published NExT submission deadlines.