Department of Health and Human Services
July 18, 2014
July 18, 2014
SBIR / 2014
May 07, 2017 (closing in 711 days)
NOTE: The Solicitations and topics listed on this site are copies from the various SBIR agency solicitations and are not necessarily the latest and most up-to-date. For this reason, you should use the agency link listed below which will take you directly to the appropriate agency server where you can read the official version of this solicitation and download the appropriate forms and rules.
The official link for this solicitation is: http://grants.nih.gov/grants/guide/pa-files/PAR-14-289.html
This Funding Opportunity Announcement (FOA) is part of a suite of complementary programs to encourage the translation of research discoveries into new treatments for disorders
that fall under the NINDS mission.
The NINDS Cooperative Research to Enable and Advance Translational Enterprises for Biotechnology Products and Biologics (CREATE Bio) program is dedicated to biotechnology product- and biologics- based therapies, which broadly include modalities such as peptides, proteins, oligonucleotides, gene therapies, and cell therapies. The program includes two tracks: the Discovery Track (see PAR-14-287) supports lead optimization in order to obtain a candidate appropriate for entering the Development Track, and the Development Track supports IND-enabling studies for the candidate, as well as early-phase clinical trials.
For the NINDS CREATE Bio Development Track FOA, at entry, the project should have an identified candidate that has undergone rigorous preclinical testing and has sufficient bioactivity, stability, manufacturability, bioavailability, in vivo efficacy and/or target engagement, and is considered state-of-the-art for the disease (see entry criteria for details). At the end of the funding period, projects are expected to achieve filing of an Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA), at a minimum, by the end of the funding period. For more advanced projects, a small, early-phase clinical study may also be proposed when feasible, but is not required (see 'Scope' for more details). The Development Track has two phases, Phase I and Phase II. While the U44 Phase I supports the preparatory activities needed before launching IND-enabling studies (such as manufacturing for IND-enabling toxicology and verification of such manufactured material for its activities), the U44 Phase II phase supports the IND-enabling studies (e.g., GLP toxicology, biodistribution, immunogenicity evaluations), and early-phase clinical trials.
Projects are funded via a U44 cooperative agreement mechanism, which involves NINDS Program staff's participation in developing the project plan, monitoring research progress, and appropriate go/no-go decision-making. NINDS staff will also provide assistance to academic investigators in helping them to distinguish activities that fall under the Phase I versus Phase II of a Development project. The expectations of the program are in line with those of industry in regards to advancing therapeutic agents through the developmental pipeline.
For more information about other NINDS Translational Programs visit the website http://www.ninds.nih.gov/funding/areas/translational_research/index.htm and for more information specifically about the CREATE Bio Program visit the website (http://www.ninds.nih.gov/funding/areas/translational_research/CREATE-Bio.htm). Applicants are strongly advised to read through the CREATE Program Announcement Frequently Asked Questions (FAQs) and examples at the website (http://www.ninds.nih.gov/funding/areas/translational_research/CREATE-FAQ.htm). For this funding opportunity announcement phase I clinical testing, studies or trials refer to the common phases of a clinical trial. U44 Phase I and II refer to the project phases of the SBIR program.
Projects must focus on a single disorder that falls within the NINDS mission.
The CREATE Bio FOAs focus on biotechnology products and biologics, which broadly include modalities such as peptides, proteins, oligonucleotides, gene therapies, and cell therapies. Applicants should contact NINDS Scientific/Research staff regarding small peptide derivatives, natural products, molecules with complex structures, or combination products, to determine the fit for the FOA.
Applicants are not required to have received and completed a prior NINDS CREATE Bio Discovery Track award to be eligible to apply to the NINDS CREATE Bio Development Track. Applicants are encouraged to talk to Scientific/Research staff about the stage of their activity and receive advice as to which program is the best fit. Applicants cannot simultaneously submit both a Discovery and Development Track application on the same agent and disease.
Only the most promising agents that have undergone rigorous preclinical testing and are considered state-of-the-art for the disease of interest will be considered for advancement to IND-enabling studies. To be eligible for this Development Track FOA, applicants must have a candidate with the final structure for human testing that minimally satisfies all of the following:
(1) Optimization is finished and final characterization of the candidate, such as structure/identity, selectivity, stability, manufacturability, and other modality-specific characteristics are complete.
(2) For a candidate with sufficient purity, its minimal effective dose, optimal effective dose, time and duration of treatment, have been determined in relevant in vivo assays using clinically relevant functional and/or anatomical outcome measures, and/or in vivo target engagement assays. [This normally should have been done using the clinically intended route of administration and special formulations if proposed (such as slow release, liposomes, nanoparticles, etc.), unless justified to use other routes of administration in which case the dose-response must have been reliably bridged by pharmacokinetics measurements]. The in vivo study results should also include assessment of pharmacokinetics, bioavailability at the relevant site of action, and pharmacokinetics-pharmacodynamics relationship. In particular for CNS disorders, there needs to be rigorous evidence that the agent is blood-brain-barrier penetrant (unless the agent is proposed to be delivered directly to the CNS) and available at an effective dose or evidence that the agent can act in the periphery. Key studies should be sufficiently powered and controlled with experimental and statistical rigor to lend a high degree of confidence in the results, with sufficient information available about study design, execution, analysis, and interpretation.
(3) Feasibility for production and reproducible production of the candidate.
U44 Phase I Scope
Examples of studies that can be proposed during this Phase include, but are not limited to:
The length of Phase I can be brief depending on the maturity of the project at entry. Funding for Phase I cannot exceed two years.
U44 Phase II Scope
The Phase II will support IND-enabling development activities. For more advanced projects, a small, early-phase clinical trial (see definitions below) can also be supported when feasible during the Phase II. It should be noted that in this FOA clinical trials are only supported for projects where the preclinical activities are conducted under this funding mechanism and have transitioned from the Phase I. Applicants seeking support only to conduct early stage clinical trials should consider applying for an NINDS Exploratory Clinical Trials R01, through PAR-13-281, which provides additional flexibility in budget and time, as well as the option of including a clinical trial.
In-scope preclinical development activities for Phase II include, but are not limited to:
In-scope small, early-phase clinical trials include:
In-scope activities for clinical trial preparatory activities (only if clinical trials are proposed), which may be performed concurrently with IND-enabling preclinical studies during Phase II include, but are not limited to:
Within scope clinical trial activities during Phase II include, but are not limited to:
Examples of Activities Inappropriate for this FOA include:
Because therapy development is an inherently high-risk process, it is anticipated that there may be significant attrition as projects move through the therapy development process. Milestones are goals that are quantifiable for measuring success that can be used for go/no-go decision-making for the project, and should have quantitative criteria associated with them (see Section IV.2 for details).
Prior to funding an application, NINDS Program staff will contact the applicant to discuss the proposed milestones and any changes suggested by the NINDS review panel or NINDS Program staff. A final set of milestones will be specified in the Notice of Award.
Progress towards achievement of the final set of milestones will be evaluated by NINDS Program staff. NINDS Program staff may consult as necessary with independent consultants with relevant expertise. If justified, future year milestones may be revised based on data and information obtained during the previous project period. If, based on the progress report, a funded project does not meet the milestones, funding for the project may be discontinued. In addition to milestones, the decision regarding continued funding will also be based on the overall robustness of the entire data package that adequately allows an interpretation of the results (regardless if they have been captured in the milestones), overall progress, NINDS portfolio balance and program priorities, competitive landscape, and availability of funds.
Since the primary focus of the Development Track is to determine the safety and toxicology of the product that will move into humans, applicants should keep in mind that the efficacious dose levels should, ideally, be non-overlapping with a dose(s) resulting in significant toxicity and reflect the fact that one has to carefully assess toxicity in relationship to efficacy. NINDS intends to only move forward agents that are both efficacious and safe. Although the primary goals of the Development Track are to assess safety and toxicology, lack of evidence of robust efficacy in the dose range where the candidate is safe can also be a consideration for discontinuation.
NINDS emphasizes the importance of the robustness and reproducibility of experimental results. In some cases, conducting additional critical experiments will be important for NINDS to have confidence in making a funding decision. Therefore, NINDS Program staff, in consultation with the PD/PI, may add experiments that need to be conducted prior to or during the award as an additional milestone(s). In most cases, these studies will be supported by additional funds from NINDS.
U44 Phase I/II transition
An administrative review will be conducted by NINDS Program staff to decide whether a project will be considered for transition from the Phase I to the Phase II. Phase II eligible projects must have a candidate that has been manufactured with satisfactory purity and stability, verified to have activity in vivo and/or in vitro as necessary, have bioavailability with a proper formulation, and have a good preliminary safety profile. Specifically, projects entering the Phase II must satisfy the following:
Transition to Small, Early-Phase Clinical Trial
Clinical Trial preparatory activities may be performed concurrently with IND-enabling preclinical Phase II activities with approval of NINDS staff. General criteria for starting clinical preparatory activities, if applicable, will be based on:
Prior to commencement of the clinical trial (defined as first subject signature on an informed consent form), the applicant must provide sufficient documentation to NINDS for review. On scientific or clinical grounds, NINDS may require inclusion of additional procedures beyond those required by the FDA. Therefore, approval must be received from NINDS prior to commencement of the clinical trial.
General criteria for starting a clinical trial:
Since the goal of this program is to generate therapeutics which will be eligible for FDA approval, adherence to compliance and quality criteria is required.
Since the ultimate goal of the CREATE Bio program is to bring new therapies to the market/patients, the program strongly encourages the awardees and/or their collaborators to obtain and retain any IP developed around the therapy during the project period (see instructions on attachment of letters to address IP issues in Section IV). Recipients of awards are encouraged to identify and foster relationships with potential licensing and commercialization partners early in the therapy development process. PDs/PIs are expected to work closely with their institutional technology transfer officials to ensure that royalty agreements, patent filings, and all other necessary IP arrangements are completed in a timely manner and that commercialization plans are developed and updated over the course of the project. For rare or ultra-rare diseases where commercialization may be challenging, applicants are encouraged to discuss alternative strategies with NINDS Scientific/Research staff to get further guidance.
As an U44 cooperative agreement, implementation will involve the participation of NINDS Program staff in the planning and execution of the therapy-directed projects. Applicants are strongly encouraged to consult with NINDS Scientific/Research staff when planning an application. Early contact provides an opportunity for NINDS Scientific/Research staff to provide further guidance on program scope, goals, developing appropriate milestones, and budget. Applicants should contact NINDS Scientific/Research staff at least 12 weeks before a receipt date.