NIH – Partnerships for Countermeasures Against Select Pathogens (R01)

NIAID supports extramural research focused on understanding, controlling and preventing diseases caused by virtually all infectious agents. In response to threats presented by emerging infectious diseases, the NIAID Division of Microbiology and Infectious Diseases (DMID) has established research programs to facilitate development of countermeasures for certain pathogens. The purpose of this FOA is to solicit research applications for projects focused on preclinical development of lead candidate therapeutics or vaccines (or related countermeasures) that address select NIAID Emerging Infectious Diseases/Pathogens, as defined below.

For the purpose of this FOA, “lead candidate” is defined as a candidate product, or a collection of optimized products (e.g. lead candidate series), for which proof-of-concept data have been obtained and “preclinical development” is defined as all activities beyond lead candidate identification. Examples of supported research areas include: lead optimization; efficacy testing, safety evaluation; stability testing; manufacturing; development of broad spectrum platforms and/or production technologies; optimization of products or technologies; process development; scale-up; production of quantities sufficient for preclinical regulatory requirements; and IND-enabling activities required for initiation of Phase I clinical trials. Priority will be given to projects that address the greatest public health concerns.

Background

NIH and other DHHS agencies support development of countermeasures to protect the public from infectious diseases. In 2002, the NIH initiated development of strategic plans to counter threats presented by emerging infectious diseases. As a component of these plans, NIAID was assigned responsibility for research leading to and development of candidate countermeasures against a growing list of emerging pathogens. NIAID established the Partnerships program to support discovery, preclinical research, product development and eventual commercialization of candidate products that address specific pathogens/agents. This FOA reflects current priorities outlined in the NIAID Strategic Plan for Biodefense Research, the HHS Public Health Emergency Medical Countermeasures Enterprise (PHEMCE) Strategy and Implementation Plan, the National Strategy for Combating Antibiotic-Resistant Bacteria (CARB), the National Action Plan for Combating Multi-drug Resistant Tuberculosis, the HHS 2010 Medical Countermeasure Review, and Homeland Security Presidential Directive 18: Medical Countermeasures against Weapons of Mass Destruction.

Research Goals, Objectives, and Scope

The objective of this FOA is to support milestone-driven preclinical research that will advance the development and/or production of lead candidate therapeutics or vaccines (or related products) for select Emerging Infectious Diseases/Pathogens described below. Each application must propose a research and development project whose goal is to advance an already identified lead candidate. Proposed projects are not required to result in a “final” product, nor is it necessary to propose completion of the product development process up to the point of readiness for clinical trials or validation within the time frame of the project. Applications that would significantly advance a candidate product toward clinical or field usefulness are responsive and encouraged. Required industrial participation on applications from academic institutions (see below) will facilitate appropriate and validated product development activities. Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) are strongly encouraged to obtain expertise in the areas of product development planning and target product profile development in general, and regulatory matters in particular. Expertise needed to fulfill project objectives may be retained as defined effort or may be included as periodic consultation on specific issues.

Descriptions of supported countermeasure development activities and targeted pathogen categories are presented below:

Therapeutics

This FOA will support preclinical development of therapeutics against select NIAID Emerging Infectious Diseases/Pathogens (antimicrobial-resistant bacteria and emerging viral pathogens; see below), including immune-based and host-targeted forms, with emphasis on broad-spectrum therapeutics and those targeting pathogens for which no standard clinical treatment exists or for which drug resistance poses a significant public health concern. Therapeutics of interest include small molecules, biopharmaceuticals, nucleic acids, or peptides to be used as monotherapy or in combination, or as adjunctive therapy, with other drugs. Projects must initiate with a single candidate therapeutic or lead candidate series. For projects initiating with a lead series, down-selection to a single lead candidate must be accomplished within the first two years of the project period.

Immune-based therapeutic projects may focus on broad-spectrum or pathogen-specific immunotherapeutics. Of particular interest are immunotherapeutics that would enable prevention of infection or intoxication in the face of an immediate threat, protection of immunocompromised individuals, or post-exposure treatment to suppress infection and disease. NIAID encourages development of immunotherapeutics that directly affect pathogens and/or therapeutic approaches to stimulate non-specific immunity. Passive treatments may be especially valuable during the acute emergence of infectious diseases and may complement the use of antimicrobial drugs or vaccination programs to optimize protection.

Host-targeted therapeutic projects must focus on a host-encoded function required for infection, replication, spread and/or pathogenesis by one or more pathogens. Host-targeted therapeutic candidates that act primarily by stimulating the host immune response through direct regulation of interferon expression will be considered non-responsive. For host-targeted intervention projects, applicants must clearly define the specific required host-pathogen interaction(s) for development of the corresponding targeted therapeutic(s). NIAID encourages development of therapeutics that target specific host functions/pathways that are required for infection and pathogenesis by unrelated pathogens. Of particular importance for novel host-targeted therapeutics is consideration of proposed work that directly addresses the clinical and regulatory pathway to product registration and potential hurdles such as demonstration of pathogen susceptibility and therapeutic efficacy using non-standard in vitro assays and in vivo disease models, as well as potential toxicity issues.

Applications for development of a broad spectrum anti-infective against multiple targeted Emerging Infectious Diseases/Pathogens are encouraged. A broad-spectrum therapeutic is defined as a therapeutic agent that targets a common, invariable, or essential component of different strains or classes of microbes, or one that targets a host function required for infection and/or disease.

Each therapeutic development project supported by this FOA must focus on a previously-identified, well-characterized lead candidate (or lead candidate series) that targets one or more pathogen(s) from either of the following select pathogen categories:

Antimicrobial-Resistant Bacteria/Fungi

This initiative will support development of new or improved therapeutics for select pathogens for which drug resistance poses a significant public health concern. Responsive applications must target at least one pathogen listed in the Centers for Disease Control and Prevention’s Antibiotic Resistance Threats in the United States, 2013 report. Projects focused on drug-resistant Mycobacterium tuberculosis are limited to development and/or evaluation of therapeutic entities that are not currently licensed for another indication (that is, projects focused on repurposed drugs are excluded). Antibacterial categories supported by this FOA include, but are not limited to, narrow-spectrum drugs, broad-spectrum drugs, innovative therapeutic approaches/strategies, drugs targeting novel mechanisms, or adjunctive therapeutics.

Emerging Viral Pathogens

This initiative will support development of new or improved therapeutics for emerging viral pathogens of public health concern. Responsive applications must target at least one viral pathogen on the NIAID Emerging Infectious Diseases/Pathogens list (https://www.niaid.nih.gov/research/emerging-infectious-diseases-pathogens). Antiviral categories supported by this FOA include, but are not limited to, broad-spectrum antivirals, immunotherapeutics, or host-targeted therapeutics.

Therapeutics projects supported by this FOA may include, but are not limited to, one or more of the following preclinical activities:

  • Lead optimization; medicinal chemistry; structure/activity relationships;
  • Synthesizing, purifying, and testing lead candidates for efficacy and toxicity in in vitro assays and preclinical in vivo model systems;
  • Performing preliminary pharmacokinetic (PK) and pharmacodynamics (PD) analyses on lead candidates;
  • Preclinical testing for efficacy and safety in animals;
  • Testing and validation of efficacy in in vitro or in vivo models (e.g., rodents, nonhuman primates);
  • Optimization of dose, dosing interval, and route of delivery in preclinical evaluation or in animal models;
  • Methods to modify existing drugs/therapeutics to improve economy of production, half-life in vivo, target affinity, neutralization potency, microbial clearance rates, or tissue accessibility; or to decrease adverse side effects of administration;
  • Evaluation of the potential for the emergence of drug/therapeutic resistance in model systems;
  • Assessing bioavailability and mechanism of action;
  • Process development for the manufacturing of a therapeutic, including QA/QC, methods for product recovery, characterization, purification, identity, stability etc.;
  • GLP or cGMP production to generate sufficient product to conduct pre-clinical and for future Phase I clinical studies; and
  • Performing required benchmarks for successful submission and review of an IND application by the FDA.

Vaccines

Vaccines are the most effective method of protecting the public against infectious diseases. This FOA will support development of candidate vaccines (including immunoprophylactics) against emerging pathogens, focusing on multivalent/universal forms or vaccines targeting specific pathogens (see below). Development of candidate vaccines should initiate with previously-identified, well-characterized immunogens. Projects are expected to include proof-of-concept in animal models, preclinical evaluation, and if warranted, scale-up production under GMP to provide sufficient quantities for pre-clinical FDA-required animal studies and early clinical evaluations.

Projects must focus on development of a lead candidate vaccine aligned with one of the following categories:

Multivalent/Universal Vaccines

Multivalent or universal vaccines are defined as broad-spectrum vaccines that provide protection against a group of taxonomically-related pathogens, or two or more unrelated pathogens. Vaccines characterized by broad-spectrum activity in this class include cross-protective forms, which induce an immune response against constant components of two or more microbes, and multiple component forms, which include elements that protect against microbes that are different, and may or may not be related. Examples of this vaccine category include, but are not limited to, a universal influenza vaccine or a multivalent vaccine that protects against multiple flaviviruses.

Vaccines Against Antimicrobial-Resistant Bacteria/Fungi

This initiative will support development of candidate vaccines targeting select bacterial/fungal pathogens for which drug resistance poses a significant public health concern. Responsive applications must target at least one pathogen listed in the Centers for Disease Control and Prevention’s Antibiotic Resistance Threats in the United States, 2013 report. Note that NIAID currently supports development of candidate vaccines against Mycobacterium tuberculosis under RFA-AI-16-079 (Partnerships for Development of Vaccines to Prevent Mycobacterium tuberculosis Infection and/or Tuberculosis Disease (R01)). Accordingly, this FOA will not support projects focused on development of a vaccine against Mycobacterium tuberculosis.

Vaccines Against Select Emerging Viruses

This initiative will support development of candidate vaccines targeting emerging viral pathogens of public health concern. Responsive applications must target at least one viral pathogen listed in the World Health Organization Priority Diseases Needing R&D Actions, 2017 revision (http://www.who.int/csr/research-and-development/list_of_pathogens/en/).

For all vaccine projects, approaches should consider the ultimate potential of a candidate vaccine to quickly induce safe and protective responses in a diverse civilian population. Vaccine projects may include, but are not limited to, one or more of the following product development activities:

  • Lead vaccine candidate optimization;
  • Evaluation of safety, toxicity and immunogenicity in animals;
  • Evaluation of efficacy in challenge models where appropriate animal models are available;
  • Optimization of dose and route of delivery in preclinical evaluation;
  • Optimization of production methodology including process development;
  • Scale up and production of candidate vaccines including cGMP production;
  • Process development for the production of vaccine components, including Quality Assurance (QA)/Quality Control (QC), methods for product recovery, characterization, purification, identity, stability, etc.;
  • Manufacturing under GLP or cGMP to provide quantities sufficient for preclinical and early clinical evaluation;
  • Performing preclinical testing for safety, toxicity, and efficacy in animal models and other benchmarks required for successful submission and review of an Investigational New Drug (IND) application by the Food and Drug Administration (FDA);
  • Optimization of delivery platforms, antigen and adjuvant combinations/formulations;
  • Advanced development of non-needle vaccine delivery systems, such as transdermal, oral, or nasal delivery; and
  • Advanced development of formulation methodologies that obviate the need for cold-storage of the resulting product and/or extend shelf-life.
Industrial Participation

All projects submitted by academic institutions to this FOA must include substantive investment by at least one industry participant. For the purpose of this FOA, “industry” is defined as a large or small, domestic or foreign, pharmaceutical, biotechnology, bioengineering, or chemical company, or a related non-profit entity with an established track record in product development, and “substantive investment” is defined as a significant commitment of one or more resources to the project including, but not limited to: project and product development guidance/support (consultation), personnel, in kind contributions of materials and/or reagents (i.e. chemical libraries, innovative biotechnology platforms, scale up of cGMP chemical synthesis or production, etc.), provision of animal or other laboratory models for evaluation, subcontracts, data management resources, regulatory support, or alterations/renovations of facilities or provision of equipment to address biohazard concerns. For projects with consultation-only investment, the industrial partner must commit a specific level of effort (concomitant to stage of preclinical and/or product development activities) that is included in the requested budget. Support for industrial partner activities may be included in the project budget. There is no requirement for an academic participant on applications submitted by industrial organizations.

Applications including the following will be considered non-responsive and will not be reviewed:

  • Projects lacking appropriate proof-of-concept data supporting the candidate therapeutic or vaccine.
  • Projects from academic institutes that lack substantive investment by at least one industry participant.
  • Projects focused on development of a therapeutic that acts primarily by stimulating the host immune response to infection through direct regulation of interferon expression.
  • Projects focused on repurposing a licensed drug as a therapeutic for Mycobacterium spp.
  • Projects focused on development of a vaccine against Mycobacterium tuberculosis.
  • Clinical trials (all phases).
  • Projects on AIDS or HIV.

Deadline:  December 12, 2017 (letters of intent); January 12, 2018 (full proposals)

URL:  https://grants.nih.gov/grants/guide/rfa-files/RFA-AI-17-026.html