RFA-NS-27-007-Full-Announcement.html

Department of Health and Human Services

Part 1. Overview Information

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Institute of Neurological Disorders and Stroke (NINDS)

National Eye Institute (NEI)

National Heart, Lung, and Blood Institute (NHLBI)

National Institute on Aging (NIA)

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

National Institute on Drug Abuse (NIDA)

National Center for Complementary and Integrative Health (NCCIH)

National Cancer Institute (NCI)

Funding Opportunity Title

HEAL Initiative: Non-addictive Analgesic Therapeutics Development [Small Molecules and Biologics] to Treat Pain (UG3/UH3 Clinical Trial Optional)

Activity Code

UG3/UH3 Exploratory/Developmental Phased Award Cooperative Agreement

Announcement Type

Reissue of

RFA-NS-24-019

Related Notices

Check for any recent Notices of NIH Policy Changes that may impact application requirements.

Funding Opportunity Number (FON)

RFA-NS-27-007

Companion Funding Opportunity

None

Number of Applications

See Section III. 3. Additional Information on Eligibility.

Assistance Listing Number(s)

93.853, 93.395, 93.279, 93.867, 93.840, 93.233, 93.837, 93.838, 93.839, 93.273, 93.213, 93.846, 93.866, 93.865

Funding Opportunity Purpose

The purpose of this Notice of Funding Opportunity (NOFO) is to support the preclinical optimization and development of safe, effective, and non-addictive small molecule and biologic therapeutics for the treatment of pain. The goal of the program is to accelerate the advancement of promising early-stage therapeutic candidates and facilitate their readiness for Phase II clinical trials. Applicants must have a promising small molecule or biologic lead candidate for optimization, a strong biological rationale for the proposed approach, and established assays to guide the optimization process. The scope of the program includes lead optimization, early-stage development activities, IND-enabling studies, development of pharmacodynamic and/or target engagement biomarkers, preparation and submission of an Investigational New Drug (IND) application, and Phase I clinical testing. This is a milestone-driven, phased cooperative agreement program that involves active participation by NIH program staff in project planning and ongoing monitoring of research progress.

Funding Opportunity Goal(s)

To support extramural research funded by the National Institute of Neurological Disorders and Stroke (NINDS) including: basic research that explores the fundamental structure and function of the brain and the nervous system; research to understand the causes and origins of pathological conditions of the nervous system with the goal of preventing these disorders; research on the natural course of neurological disorders; improved methods of disease prevention; new methods of diagnosis and treatment; drug development; development of neural devices; clinical trials; and research training in basic, translational and clinical neuroscience.

Key Dates

Posted Date

June 16, 2026

Open Date (Earliest Submission Date)

August 21, 2026

October 21, 2026

October 21, 2026

Not Applicable

July 2027

February 19, 2027

February 19, 2027

Not Applicable

December 2027

June 21, 2027

June 21, 2027

Not Applicable

April 2028

October 20, 2027

October 20, 2027

Not Applicable

July 2028

February 22, 2028

February 22, 2028

Not Applicable

December 2028

June 20, 2028

June 20, 2028

Not Applicable

April 2029

October 20, 2028

October 20, 2028

Not Applicable

July 2029

February 20, 2029

February 20, 2029

Not Applicable

December 2029

All applications are due by 5:00 PM local time of applicant organization.

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

Due Dates for E.O. 12372

Not Applicable

Expiration Date

February 21, 2029

Required Application Instructions

It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide, except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts).

Conformance to all requirements (both in the Application Guide and the NOFO) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.

Applications that do not comply with these instructions may be delayed or not accepted for review.

Table of Contents

Part 1. Overview Information Key Dates Part 2. Full Text of Announcement Section I. Notice of Funding Opportunity Description Section II. Award Information Section III. Eligibility Information Section IV. Application and Submission Information Section V. Application Review Information Section VI. Award Administration Information Section VII. Agency Contacts Section VIII. Other Information

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Background:

The NIH HEAL Initiative: This NOFO encourages applications in support of the NIH's Helping to End Addiction Long-term (HEAL) initiative to speed scientific solutions to the national opioid public health crisis. The NIH HEAL Initiative bolsters research across NIH to (1) improve treatment for overdose, opioid misuse and addiction and (2) enhance pain management. More information about the HEAL Initiative is available at: https://heal.nih.gov/.

More than 25 million Americans suffer from chronic pain, a highly debilitating medical condition that is complex and lacks effective treatments. In recent decades, there has been an over reliance on opioids for the treatment of pain. This contributed to a significant and alarming epidemic of opioid overdose deaths and addictions. Innovative scientific solutions to develop alternative treatment options for pain are thus critically needed. As part of the mission of the HEAL Initiative, NINDS is working with other NIH Institutes and Centers to encourage the translation of basic research into new non-addictive pain treatments. This program announcement is intended to create a foundation to initiate the optimization and development of pain therapeutics and catalyze the development of partnerships between the academic and industrial sectors so that translational research in pain can flourish as a cooperative, iterative process leading to safe, effective, and non-addictive treatments for pain.

Through this Notice of Funding Opportunity (NOFO), the NIH offers researchers funding for drug discovery and development activities that can be conducted in their own laboratories. In addition, researchers have the opportunity to collaborate with NIH-funded subject-matter experts and contract research organizations (CROs) that specialize in medicinal chemistry and Good Manufacturing Practices (GMP) manufacturing, pharmacokinetics, biodistribution, protein and virus production, cell line and process development, QC release testing, toxicology, formulations development, and Phase I clinical studies.

The Program Director/Principal Investigator (PD/PI) will be responsible for conducting or leading all studies that involve disease- or target-specific assays, disease models, pharmacodynamic biomarkers and verification of the association between the therapeutic target or pathway and modulation by the therapeutic agent. A PD/PI with, for example, medicinal chemistry expertise and resources, may request funding to conduct structure-activity relationship (SAR) studies in their own lab but collaborate with contractors on in vitro ADMET, in vivo PK, drug manufacturing and IND-enabling toxicology studies. By contrast, a PD/PI with limited experience in drug discovery and development may opt to collaborate with NIH contractors for all activities not related to disease or target biology. Applicants may propose to conduct all drug discovery and development activities themselves or collaborate with NIH contractors on activities of their choice, however, it is expected that all staff be in place at the start of the grant if not utilizing NIH resources for the work.

For each project funded under this NOFO, the NIH will assemble a customized Lead Development Team (LDT). The LDT will be co-chaired by the PD/PI and a NIH subject-matter expert and will include members of the PD/PI's team, additional subject-matter experts, and NIH staff. The LDT will establish an overall strategy for the project, plan studies to be conducted by NIH contractors, and coordinate activities across different research sites.

Potential applicants are strongly encouraged to contact NIH Scientific/Research staff and participating NIH Institutes/Centers prior to preparing an application to discuss how they may best utilize NIH contract resources and whether their application fits the mission of a particular NIH IC. See also Webinar information under Section IV.7 below ("Other Submission Requirements and Information").

The NIH HEAL Initiative will require a high level of coordination and sharing between HEAL investigators. It is expected that NIH HEAL Initiative recipients will cooperate and coordinate their activities after awards are made by participating in Program Director/Principal Investigator (PD/PI) meetings, including an annual HEAL Investigators Meeting, as well as other activities.

Scope:

This program announcement is specifically focused on providing the expertise, resources and funding to expedite the preclinical translational development process necessary to advance small molecule and biologic non-addictive therapeutics for pain to Phase I clinical testing. The program supports preclinical optimization and development of small molecules and biologics leading to the assembly and submission of an IND application and the implementation of Phase I clinical testing. The scope of this program excludes basic research, and projects focused on disease mechanism or mechanistic/mechanism of action studies of the intended therapeutic. Further, development of animal models, diagnostics, rehabilitation strategies, or therapeutic devices is nonresponsive as are Phase II and Phase III clinical studies. Finally, this program is intended to provide support of the early therapeutic development process; therefore, requests that support only a single component of the process, such as GLP toxicology studies alone , or only a Phase I clinical trial, are considered non-responsive.

General Entry Criteria:

This is a two-phased program that is organized into a preparatory UG3 phase and an execution UH3 phase. Projects must enter at the UG3 phase of the program, and this phase must not exceed 2 years. Projects may enter the program at the Discovery or Development stage. All projects must have the ultimate end goal of assembling an IND application and beginning a Phase I study by the end of the project. For entry at the Discovery Stage, projects must have a promising small molecule or biologic starting point for optimization, a rigorous biological rationale for the intended approach, and scientifically sound assays to test the agent. Applications for entry at the Development stage must have identified the candidate therapeutic; no further optimization will be supported, including back-up programs. In addition, a strong package of data linking the putative therapeutic target to the proposed disease indication and supporting the hypothesis that altering the target activity will produce desirable outcomes for the disease is required. Finally, the proposed therapeutic must have in vitro and in vivo biological activity and ADMET properties appropriate for the intended clinical use.

For the UG3 phase, this NOFO encourages projects proposing the following optimization activities:

Discovery

Development Activities that fill in efficacy, in vitro non-GLP ADMET and in vivo PK gaps necessary to begin IND-enabling work

It is expected that by the end of the UG3 phase, recipients will have characterized and selected lead candidates that are ready for in vivo efficacy testing, though additional optimization may be necessary.

After successful completion of the UG3 phase, a project may proceed to the UH3 phase. Progression from the UG3 award to the UH3 award will be based on administrative review.

For the UH3 phase, the following are examples of in-scope development activities:

It is expected that at the end of the UH3 phase, recipients will have advanced their therapeutic to Phase I clinical testing.

Intellectual Property:

Since the ultimate goal of this program is to bring new pain therapeutics to the market, the creation and protection of appropriate intellectual property are significant considerations in designing research strategies and prioritizing projects for funding. Each applicant is expected to address intellectual property issues (including permission to utilize proprietary reagents or materials if applicable) related to the proposed therapeutics, with input from the institution's technology transfer officials, if applicable. Peer reviewers will be instructed to comment on the intellectual property landscape for each application. The project milestone plan may include commercialization milestones to protect and leverage intellectual property. Recipients of awards are encouraged to identify potential licensing and commercialization partners early in the therapy development process. The PD(s)/PI(s) is encouraged to work closely with technology transfer officials at their institution, if applicable, to ensure that royalty agreements, patent filings, and all other necessary intellectual property arrangements are completed in a timely manner. See Section IV.2. Other Project Information for details.

Implementation:

The program provides funding through the UG3/UH3 cooperative agreement mechanism. As a cooperative agreement, implementation will involve participation of NIH program staff in the planning and execution of the therapy-directed projects. The UG3 portion of the award is designed to support optimization research for the first 1-2 years. Based on the progress to milestones, only a limited number of projects will proceed to the UH3 phase for the remainder of the award period which will include final optimization and development leading to assembling an IND application and beginning a Phase I clinical study, either through the grant budget or through NIH contract resources outlined above.

Milestones:

Because therapeutics optimization and development are inherently high risk, it is expected that there will be significant attrition as projects progress. Annual go/no-go milestones must outline achievements necessary for the project to progress through the stages of therapeutic development and be tailored to the specific therapeutic and its intended disease indication. Proposed milestones will be used for measuring success in achieving each of the research plan key objectives. One or more milestone(s) must be used for each key objective. More details can be found in Section IV. Application and Submission Information.

Annual go/no-go milestones listed in the application will be finalized by a team consisting of the PD/PI and NIH program staff at the start of each project and updated as needed. If justified, future year milestones may be revised based on data and information obtained during the previous project period.

NIH program staff and leadership will conduct annual administrative reviews. At the end of the UG3 phase, NIH program staff and leadership will determine if the project will advance to the UH3 phase. Annual and UH3 transition administrative reviews will be based on:

Applications will be considered nonresponsive of this announcement if they include:

Non-responsive applications will be withdrawn.

Applications will be considered incomplete if they are missing any of the following:

Incomplete applications will be withdrawn. See section IV for instructions for each of these elements.

Additional Resources:

To support these projects, additional existing NIH resources may be made available to the applicant outside this grant budget and are described below. Applicants are strongly encouraged to contact NIH staff to discuss these options. These resources include, but are not limited to the following:

NINDS

NINDS has established contract support for medicinal chemistry (including synthesis/SAR, computational chemistry and in vitro ADMET), biodistribution, protein and virus production, antisense oligonucleotide production, antibody production, cell line process and development, cell banking, pharmacokinetic studies, toxicology (GLP and non-GLP) and safety testing, drug formulation and GMP manufacturing, QC release testing and Phase I clinical studies. Contractors will provide data and reports in a format suitable for inclusion in an IND application. NIH also provides access to experts in therapeutics development through consulting contracts. Applicants must contact NINDS staff (contacts provided below) in order to utilize these resources and determine how to best leverage these as part of the application. To learn more, visit the HEAL PTDP webpage: https://www.ninds.nih.gov/current-research/trans-agency-activities/ninds-role-heal-initiative/pain-therapeutics-development-program-ptdp. As appropriate, applicants are encouraged to make use of the NINDS Common Data Elements (https://www.commondataelements.ninds.nih.gov/#page=Default).

NIDA

Pursuant to the development of analgesic medications without the liability of producing OUD following chronic use, the National Institute on Drug Abuse (NIDA) offers resources to conduct and support all phases of medications development. These programs include synthesis and preclinical evaluation of potential therapeutics, clinical trial design and execution, and preparing regulatory submissions. More information can be found at: https://nida.nih.gov/about-nida/organization/divisions/division-therapeutics-medical-consequences-dtmc/research-programs#PDP Complementary Resources:

The NIH HEAL Initiative supports the following resources outside this funding opportunity that are also focused on the development of safe, effective, and non-addictive therapeutics to treat pain. Applicants that are interested in utilizing these complementary resources should contact PSPP or NCATS directly.

NINDS

PSPP: Within the NIH HEAL Initiative, NINDS created the Preclinical Screening Platform for Pain (PSPP) to identify and profile non-opioid, non-addictive therapeutics (small molecules, biologics, natural products, or devices) for pain. NIH staff assess the suitability of assets for acceptance into the PSPP on an ongoing basis. Within PSPP, lead assets are profiled for efficacy in models relevant to human pain conditions. Program staff work with the asset owner to plan the evaluation and direct the studies, which are performed by a contract facility at no cost to the PSPP participants. All evaluation is done under a defined participant agreement that outlines confidentiality and intellectual property protection. More information can be found at: https://heal.nih.gov/research/preclinical-translational/screening-platform

NCATS

Applicants are also encouraged to potentially develop collaborations with NIH National Center for Advancing Translational Sciences (NIH/NCATS) to access the state-of-the-art capabilities at the Center. If selected for a collaboration, NCATS will make available capabilities in support of HEAL initiatives. The capabilities include, screening and scalable production of relevant stem cells and quantitative high-throughput screening to identify promising compounds to be optimized by medicinal chemists. A more detailed description of the capabilities can be found at: https://ncats.nih.gov/heal/intramural-capabilities

Other considerations:

Community-Engaged Research Methods in HEAL Research Studies:

People with lived/living experience (e.g., patients, people in recovery, caregivers, families, community leaders) have important insights that can improve meaningful outcomes and uptake of research findings across the continuum of research from basic through implementation studies. The NIH HEAL Initiative strongly encourages the use of community-engaged research methods (e.g., the promotion of bi-directional communication between the researchers and the relevant community throughout the research project). Community-engaged research methods will vary with the focus and approach used in each project but should at minimum ensure that researchers are connecting with people with lived/living experience to incorporate their input throughout the conception, implementation, and dissemination of the research. See this resource for more information on community-engaged research methods: https://heal.nih.gov/resources/engagement Clinical Trial Accrual:

This NOFO will support applications that include a series of milestones for completion of the clinical trial and provide contingency plans to proactively confront potential delays or disturbances in attaining the milestones. Continuation of the award is conditional upon satisfactory progress, availability of funds, and scientific priorities of the HEAL Initiative. If, at any time, recruitment falls significantly below the projected milestones for recruitment, NIH will consider ending support and negotiating an orderly phase-out of the award. NIH retains the option of periodic external peer review of progress. NIH program staff will closely monitor progress at all stages for milestones, accrual, and safety. Please refer to the HEAL Policy for the Enrollment of Participants in Clinical Trials for additional information. .

Investigators proposing NIH-defined clinical trials may refer to the Research Methods Resources website for information about developing statistical methods and study designs.

See Section VIII. Other Information for award authorities and regulations.

Section II. Award Information

Funding Instrument

Cooperative Agreement: A financial assistance mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.2 for additional information about the substantial involvement for this NOFO.

Application Types Allowed

New

Resubmission

Revision

The OER Glossary and the How to Apply Application Guide provide details on these application types. Only those application types listed here are allowed for this NOFO.

Clinical Trial?

Optional: Accepting applications that either propose or do not propose clinical trial(s).

Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards

The NIH HEAL (Helping to End Addiction Long-term) Initiative intends to commit an estimated total of $11,000,000 to fund 3 awards in FY 2027. Awards pursuant to this funding opportunity are contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.

Award Budget

Application budgets must reflect the actual needs of the proposed project but should not include the costs of NIH contract resources requested.

Award Project Period

The UG3 phase of the grant must be at least 1 year and cannot exceed 2 years. The UH3 phase cannot exceed 4 years. The total duration may not exceed 5 years. The actual duration of individual projects will depend upon successful achievement of milestones and conditions as described in the Milestones and Implementation sections of the program overview.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this NOFO.

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

Nonprofits Other Than Institutions of Higher Education

For-Profit Organizations

Local Governments

Federal Governments

Eligible Agencies of the Federal Government

U.S. Territory or Possession

Other

Independent School Districts

Public Housing Authorities/Indian Housing Authorities

Native American Tribal Organizations (other than Federally recognized tribal governments)

Faith-based or Community-based Organizations

Regional Organizations

Foreign Organizations/International Collaborations

Non-domestic (non-U.S.) Entities (Foreign Organizations) are not eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are not allowed.

Required Registrations

Applicant Organizations Applicant organizations must complete and maintain the following registrations as described in the How to Apply- Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference the NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications for additional information.

System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code. Foreign organizations must obtain a NATO Commercial and Government Entity (NCAGE) Code (in lieu of a CAGE code) in order to register in SAM. Unique Entity Identifier (UEI)- A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.

Program Directors/Principal Investigators (PD(s)/PI(s)) All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

All PD(s)/PI(s) must be registered with ORCID. The personal profile associated with the PD(s)/PI(s) eRA Commons account must be linked to a valid ORCID ID. For more information on linking an ORCID ID to an eRA Commons personal profile see the ORCID topic in our eRA Commons online help.

Eligible Individuals (Program Director/Principal Investigator)

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with their organization to develop an application for support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the How to Apply-Application Guide.

2. Cost Sharing This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement Section 1.2 Definition of Terms.

3. Additional Information on Eligibility Number of Applications

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

The NIH will not accept duplicate or highly overlapping applications under review at the same time, per NIH Grants Policy Statement Section 2.3.7.4 Submission of Resubmission Application. This means that the NIH will not accept:

A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.

A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.

An application that has substantial overlap with another application pending appeal of initial peer review (see NIH Grants Policy Statement 2.3.9.4 Similar, Essentially Identical, or Identical Applications).

Section IV. Application and Submission Information

1. Requesting an Application Package The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this NOFO. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide except where instructed in this notice of funding opportunity to do otherwise (in this NOFO, in a policy notice, or other notice from NIH Guide for Grants and Contracts). Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Page Limitations All page limitations described in the How to Apply- Application Guide and the Table of Page Limits must be followed.

Instructions for Application Submission

The following section supplements the instructions found in the How to Apply- Application Guide and should be used for preparing an application to this NOFO.

SF424(R&R) Cover All instructions in the How to Apply - Application Guide must be followed.

SF424(R&R) Project/Performance Site Locations All instructions in the How to Apply- Application Guide must be followed.

SF424(R&R) Other Project Information

The following additional instructions apply:

Facilities & Other Resources All applicants must describe their institutions' existing or planned infrastructure for bringing the compound or biologic to practical application (e.g., licensing for further drug development, managing IP, commercializing discoveries) consistent with achieving the program goals. For a multiple-PD/PI, multiple-institution application, applicants should describe the infrastructure of each institution for bringing the technologies to practical application and for coordinating these efforts (e.g., licensing, managing intellectual property) among institutions consistent with achieving the goals of the program. Applicants must clarify how IP will be shared or otherwise managed if there are multiple PD/PIs and institutions involved in the UG3/UH3-supported work, to ensure that IP remains unencumbered.

Other Attachments:

Intellectual Property (IP) Strategy In an "Other Attachment" entitled "IP Strategy", all applicants must include an Intellectual property (IP) strategy (2 pages maximum). Applicants are encouraged to prepare this section in consultation with their institutions' technology transfer officials.

For Discovery stage projects, applicants must describe any constraints of which they are aware that could impede their use of compounds, biologics, assays, or models for research purposes and/or commercial development (e.g., certain restrictions under transfer or sharing agreements, applicants' previous or present intellectual property filings and publications, similar compounds or therapies that are under patent and/or on the market, etc.) and how these issues would be addressed. If the applicant's institution has filed pertinent patents, the applicant should indicate filing dates, the type of patent, and application status.

For Development stage projects, applicants must describe their efforts to confirm that there are unlikely to be IP or other legal constraints that could block or impede development or commercialization of the proposed therapeutic. If the applicant's institution has filed pertinent patents, the applicant should indicate filing dates, the type of patent, and application status.

SF424(R&R) Senior/Key Person Profile

R&R Budget

A budget for each year of the proposed project, including both UG3 and UH3 phases, must be included. The UG3/UH3 award is intended to support studies to be conducted by the PD/PIs and associated personnel. The UG3/UH3 budget may not support drug development activities that the applicant proposes to conduct through NIH contracts. Equipment requests are allowed but not encouraged. Equipment requests should be considered only if the equipment is absolutely necessary to the success of the project and cannot be supported by any other means. This is likely to be a subject of negotiation before an award is made. Some budget requests may be made for the PD/PI's Institution to assemble and file the IND.

It is expected that the PD/PI will dedicate at least 20% level of effort (2.4 calendar months) to managing the proposed project. It is strongly recommended that potential applicants consult NIH staff about their anticipated budget in the early stages of preparing an application.

R&R Subaward Budget

PHS 398 Cover Page Supplement

PHS 398 Research Plan All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

Specific Aims:

The Specific Aims section must include Aims delineated for both the UG3 and UH3 phases.

Research Strategy:

The Research Strategy section must include the following subsections:

Clinical Impact (Significance):

Each application generally must focus on one or more specific pain condition(s). The target patient population and intended use guide the design of the drug and of the preclinical studies, such as toxicology and formulation.

For the specific pain condition(s) proposed, briefly describe the current state of knowledge of the etiology, clinical characteristics, and current and projected prevalence of the proposed condition indication.

Biological Rationale (Significance):

Innovation:

Applications must explain how the project offers a novel approach to treating the proposed disease indication:

Testing Strategy (Approach):

In this section, applicants must elaborate on their research plans to achieve the ultimate goal of assembling an IND application and beginning a Phase I Clinical Trial by the end of the project. This can include a table indicating acceptable and ideal characteristics of the eventual lead therapeutic and a diagram of in vitro and in vivo screening funnels. Applications that fail to include activities for both the UG3 (preparatory) and UH3 (execution) phases will be considered incomplete.

Include details on efforts to ensure the experimental design is rigorous. This includes, but is not limited to justification for model systems, endpoints, minimal requirements for agent purity, route and timing of delivery, adequacy of controls and sample sizes, description of statistical analyses, inclusions of measures to reduce bias, and plans for replication, if applicable.

Milestones:

Annual milestones to be used for measuring success in achieving each of the research plan key objectives must be provided. One or more milestone(s) must be used for each key objective. Applications that fail to include milestones will be considered incomplete.

Team management (Approach):

Team building is an essential step in the development of the overall plan for therapeutics development. Because translational research is intrinsically interdisciplinary, the plan will often involve cooperation among basic researchers, experts in preclinical development, and clinicians, and may include the participation of private-sector companies and voluntary organizations.

Letters of Support:

Applicants must include letters of support from subject-matter experts, contractors, and collaborators not provided through NIH.

If applying from an academic institution, include a letter of support from the technology transfer official who will be managing intellectual property associated with this project.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply - Application Guide.

Other Plan(s):

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

A Data Management and Sharing Plan (DMS Plan) is required for any NIH-funded or conducted research that will generate scientific data. Applicants must submit the DMS Plan at the time of application using the NIH DMS Plan Format Page. The DMS Plan must address the elements in the structured format. Where the DMS Plan Format Page requires a "Yes or No" response, no additional narrative is allowed.

The NIH notices referenced below provide additional NIH guidance that should be considered in developing a strong data management and sharing plan. The list is instructive but not comprehensive.

HEAL Public Access and Data Sharing Policy:

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan.