CREATE BIO

CREATE BIO program logo

CREATE BIO program overview diagram


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 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.


CREATE Bio Discovery Track and Development Track

 

Discovery

Development

Purpose

It supports the optimization of therapeutic lead(s) showing convincing proof-of-concept. At the end of the funding period, projects that successfully advance through support from this program will have identified an optimized candidate, which has sufficient bioactivity, stability, manufacturability, bioavailability, in vivo efficacy and/or target engagement, and other favorable properties that are consistent with the desired clinical application, and will be ready for entry into the CREATE Bio Development track for further development to enable filing for an IND.

It supports IND-enabling studies for the candidate and early-phase clinical trials. At the end of the funding period, a successful project should have an IND application submitted to the U.S. Food and Drug Administration (FDA), at a minimum.  The program supports early-phase clinical trials, but these are not required components of proposed projects.

Entry Criteria

(1) There must be a clear and convincing demonstration of proof-of-concept (e.g., clear dose-response relationship). The therapeutic leads should show either in vivo efficacy using clinically relevant outcome measures (e.g., anatomical, and functional when possible), and/or in vivo target engagement (measurement of target binding or proximal downstream effects) at the clinically intended site of action, using sufficient experimental and statistical rigor.  If an established animal model exists for the disease, demonstration of in vivo efficacy is the minimal requirement. 

(2) Applicants must have one or more therapeutic leads from which a candidate can potentially be derived.  For a therapeutic lead, a few final design characteristics may still need to be optimized. See Scope section for examples. The leads must have been sufficiently profiled so that all the essential key parameters to be optimized to fulfill criteria for a candidate can be quantitatively specified and prioritized. Critically, the preliminary findings need to be at a stage where IND-enabling studies are feasible at the end of the 4 years of funding.  Bioactive agents where little is known about their profile or where too many parameters (e.g., three or more) need to be optimized may not be advanced enough yet to enter the program.  

Note: NINDS recognizes that, depending on the type of agent and how it was identified and characterized, projects will enter at different stages, where certain required properties may have been optimized (repurposing a marketed therapy for a new indication is an extreme example).

(3) For key in vitro and in vivo assays proposed to optimize the leads, applicants must have pre-existing data demonstrating that the assays are suitable for the proposed purpose and available in either the applicant's or collaborator's laboratories.  Appropriate controls should be employed and efforts should be taken to demonstrate dynamic detection range and acceptable variability so the feasibility of conducting the proposed studies can be adequately assessed.

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.

Grant mechanism

Projects are funded up to 4 years through the U01 or SBIR U44 cooperative agreement award mechanism

Projects are funded up to 5 years through UH2/UH3 or SBIR U44 cooperative agreement award mechanism