Resources at the National Institute of Health

(Neil Buckholtz, National Institute on Aging)

For overview of NIH funding opportunities, please see TABLE 1.

NIA’s Alzheimer’s disease translational research initiative – multiple programs/grants available for different stages of drug discovery (see FIG. 2)

  • Many programs available to projects in both academia and the small business community
  • Assay development, screening, hit-to-lead development – PAS 10-151 (R21)
  • Lead selection and optimization – PA 10-205 (U01)
  • IND-enabling toxicology – contract service with SRI International
  • Clinical development
    • AD pilot clinical trials – PAR-11-100 (R01)
    • AD cooperative study – U01
    • Investigator initiated clinical trials (up to phase III) – R01

Preclinical drug development program U01 (PA 10-205) – facilitates preclinical drug development and testing necessary for an IND submission

  • Provides support for:
    • Proof of concept of efficacy in animal models relevant to AD
    • Medicinal chemistry and formulation
    • PK/PD profiling
    • GMP synthesis
    • Initial toxicological evaluation.
  • Milestone-driven – requirement for quantitative milestones to guide GO/NO-GO decisions on an annual basis

Drug discovery for nervous system disorders (PAR-10-001, PAR-10-002; R01 and R21 mechanisms)

  • Participating institutes: NIMH, NIA, NINDS, NIDA, NIAAA
  • Objective to stimulate preclinical research in the discovery, design, development and testing of novel compounds aimed at prevention or treatment of nervous system disorders.
  • Novel targets encouraged.
  • Projects designed for target identification are not covered.

Mechanisms and review of applications

  • Mechanisms:
    • R21 (PAS 10-151; PAR 10-002) – 2 year projects; 275K direct costs for the entire project
    • R01 (PAR 10-001) – 3-5 year projects; modular budget 250K per year (as high as 499K per year with detailed justification)
    • U01 (PA 10-205) – 3-5 year projects; non-modular budget
  • Review:
    • R21s and R01s are reviewed by the Center for Scientific Review group, Drug Discovery for the Nervous System (directed by Dr. Mary Custer)
    • U01s are reviewed at NIA’s review office by a special emphasis panel, Drug Development (directed by Dr. Alexander Prasadanian)

Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) programs are another avenue for submitting funding applications.

Trans-NIH support for translational research

  • Roadmap initiatives/programs:
    • MLSCN: Molecular Libraries Screening Centers Network
    • RAID: Rapid Access to Intervention Development
    • CTSA: Clinical and Translational Science Awards
    • TRND: Therapeutics for Rare and Neglected Diseases
  • Blueprint:
    • Grand Challenge: Neurotherapeutics/NeuroRx

NIH Rapid Access to Interventional Development (RAID) program – X01 resource access award (PAR-09-027)

  • NIH Roadmap Initiative program to address trans-NIH programmatic needs
  • Open to domestic and foreign academic and non-profit institutions, SBIR-eligible businesses, NIH Intramural programs
  • Applications are accepted for therapies for all diseases.
  • Makes available, on a competitive basis, certain critical resources needed for the development of new therapeutic agents.
    • Approved projects are provided access to the expertise and contract resources of NCI and NHLBI programs
  • IP retained by principal investigator.
  • Small molecules, peptides, oligonucleotides, natural products, gene vectors, monoclonal antibodies and recombinant proteins are eligible for development.
  • Does not provide lead optimization or animal efficacy services.
  • For identified leads, resources include:
    • Synthesis
    • Scale-up production
    • Development of analytical methods
    • Development of suitable formulations
    • Isolation and purification of natural products
    • Pharmacokinetic/ADME studies including bioanalytical method development
    • Range-finding initial toxicology
    • IND-directed toxicology
    • Manufacture of clinical trial supplies
    • Product development planning and advice in IND preparation
  • No identified leads, resources include:
    • Recombinant proteins and monoclonal antibodies:
      • Pharmacokinetic/ADME studies including bioanalytical method development
      • Range-finding initial toxicology
      • IND-directed toxicology
      • Product development planning and advice in IND preparation
    • Small molecules, natural products, peptides, oligonucleotides, and gene vectors:
      • Synthesis
      • Development of analytical methods
      • Isolation and purification of natural products
      • Preliminary Pharmacokinetic/ADME studies, including bioanalytical method development
      • Preliminary toxicology
  • Application and review process
    • Three receipts per year: January, May and September.
    • 25 page maximum research plan.
    • Programmatic assessment of responsiveness.
    • CSR review (Special Emphasis Panel).
    • Preliminary cost estimate prepared by NIH.
    • Investigator seminar, if warranted.
    • Preparation of tasks, timeline, milestones, and costs by NIH.
    • Funding decisions by co-sponsoring Institutes
    • Independent Product Development Plans available
  • Project management
    • Projects typically completed over two years.
    • Monthly progress meetings and reports.
    • Meetings at decision points.
    • Reports and material and sent to PI.
  • Administrative supplements
    • In vitro or in vivo efficacy studies
      • New agent in same model
      • Same agent in new model
      • Not model development or clinical support
    • Studies completed by PI or collaborator/contractor
      • 50K direct costs
      • One year award
      • Five page request

How to decide which funding opportunity is best for your project

  • Investigators should send a brief summary of your prospective project to the appropriate program officer(s).
  • Program staff will set up a teleconference and discuss the best funding venue(s) at the NIA or refer the investigator to another IC, a trans-NIH funding opportunity (i.e. RAID), or a non-federal funding agency (i.e. ADDF).
  • If the project is mature enough to enter the U01 program (optimized leads are in place or a lead has been selected), program staff will request preliminary milestones and budget and will work with the investigator to formulate the quantitative milestones for the application.

New NIH center – National Center for Advancing Translational Science (NCATS)

  • Approved December 2010, to be enacted by October 2011
  • Many translational programs (e.g. CTSA, RAID, MLSCN, TRND) will be centralized in the new center, but programs associated with individual institutes will stay with the institutes.

(Rebecca Farkas, National Institute on Neurological Disorders and Stroke)

For overview of NIH funding opportunities, please see TABLE 1.

Office of Translational Research (OTR) at NINDS

  • Mission is to facilitate preclinical discovery and development of new therapeutic interventions for neurological disorders

Cooperative Program in Translational Research (U)

  • Must have preclinical proof-of-concept to apply
  • IND/IDE by the end of 5-year project period
  • Cooperative agreement mechanism (U)
    • Projects have annual milestones
    • Significant NIH staff involvement
  • Reviewed by therapy development experts
  • Currently 25 U01, 2 U54, 4 U44 (SBIR) Agreements
  • 6 filed INDs and 5 clinical trials

Exploratory/Developmental Projects in Translational Research (R21)

  • “Get ready” for Cooperative Program
  • Support for preclinical development tasks
    • Creation, validation of screening assays
    • Development of animal models
    • Identification of candidate therapeutics
    • Proof-of-principle animal efficacy testing
  • 3 receipt dates per year, special review panel
  • $275,000 in direct costs over 2 years

Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) programs

  • Facilitate small business development of neurotherapeutics, diagnostics, and tools for neuroscience research
  • Congressionally mandated set-aside program (2.8% of the NINDS budget)
  • Broad Scope: Can support bench research, translational research, and early stage clinical trials
  • Two Phases that should lead to commercialization of a product:
    • Phase I: Feasibility Study
    • Phase II: Full Research Study
  • Specific eligibility requirements

Molecular Libraries and Imaging Roadmap Program

  • Develop assays to identify small molecule interactions via high-throughput screening of compound libraries
  • Chemically optimize active compounds as molecular probes

NIH Rapid Access to Interventional Development (RAID)

  • IND-enabling studies
  • All diseases
  • Access to government expertise and contract resources
    • Production, bulk supply, GMP manufacturing
    • Pharmacokinetic/ADME studies
    • IND-directed toxicology, and more
  • 6 successful IND submissions and 4 clinical trials to date

Blueprint Neurotherapeutics Network

  • Provide researchers with a “virtual pharma” to develop new drugs for nervous system disorders
  • Combines strengths of academia and industry
    • Investigator-initiated drug starting points
    • Industry-standard services: medicinal chemistry, PK/tox, Phase I clinical trials
    • Industry expertise and guidance on committees
  • Develops licensing opportunities: investigator retains IP
  • Entry requirements:
    • Probe compound(s)
    • Primary screening assay
    • Secondary assays for biological validation
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