Participating Organization(s)	National Institutes of Health (NIH)
Components of Participating Organizations	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Funding Opportunity Title	Lead Optimization and Pre-Clinical Development of Therapeutic Candidates for Diseases of Interest to the NIDDK (R43/R44)
Activity Code	R43/R44 Small Business Innovation Research (SBIR) Grant - Phase I, Phase II, and Fast-Track
Announcement Type	New
Related Notices	January 24, 2017 - This PA has been reissued as PA-17-130. October 4, 2016 - Notice to Inform the Applicant Community that NIDDK Will Not Accept Clinical Trial Applications in Response to Current Small Business Announcements. See Notice NOT-DK-16-030. NOT-OD-16-004 - NIH & AHRQ Announce Upcoming Changes to Policies, Instructions and Forms for 2016 Grant Applications (November 18, 2015) NOT-OD-16-006 - Simplification of the Vertebrate Animals Section of NIH Grant Applications and Contract Proposals (November 18, 2015) NOT-OD-16-011 - Implementing Rigor and Transparency in NIH & AHRQ Research Grant Applications (November 18, 2015) June 3, 2014 - Notice NOT-14-074 supersedes instructions in Section III.3 regarding applications that are essentially the same. May 12, 2014 ( NOT-OD-14-089) - Updated Grant Application Forms (FORMS-C) Now Available for SBIR/STTR Funding Opportunities. Forms-C applications are required for due dates on or after August 5, 2014.
Funding Opportunity Announcement (FOA) Number	PA-14-055
Companion Funding Opportunity	PA-FY-054, STTR R41/R42- Phase I, Phase II, and Fast Track
Number of Applications	See Section III. 3. Additional Information on Eligibility.
Catalog of Federal Domestic Assistance (CFDA) Number(s)	93.847
Funding Opportunity Purpose	The goal of this Funding Opportunity Announcement (FOA) is to support lead optimization and preclinical development of new therapies for diseases within the mission of the NIDDK. Phase I supports preliminary steps in the process for lead optimization or preclinical development of therapeutics. Phase II supports lead optimization and preclinical development of lead candidates and projects must be sufficiently advanced such that an Investigational New Drug (IND) or Investigational Device Exemption (IDE) application to the Food and Drug Administration (FDA) can be submitted by the end of a Phase II or IIB project. Applications are expected to have defined Milestones and Timelines detailing how the project will move forward with identified key Go / No Go decision points. This FOA is not intended to support earlier stages of work to generate assays, conduct screens for small molecules or biologic agents, or those primarily focused on early-stage validation of targets. The program scope excludes clinical research, basic research, and studies of disease mechanism. Applications for which the primary outcome is the development of a diagnostic or biomarker are not appropriate; however, applications which propose the co-development of a companion diagnostic or biomarker to a new therapy are appropriate.

Posted Date	January 2, 2014
Open Date (Earliest Submission Date)	March 5, 2014
Letter of Intent Due Date(s)	Not Applicable
Application Due Date(s)	Standard dates apply, 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.
AIDS Application Due Date(s)	Not Applicable
Scientific Merit Review	Standard dates apply
Advisory Council Review	Standard dates apply
Earliest Start Date	Standard dates apply
Expiration Date	January 8, 2017
Due Dates for E.O. 12372	Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the SF424 (R&R) SBIR/STTR Application Guide except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) 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.

Part 1. Overview Information
Part 2. Full Text of the Announcement
Section I. 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

Recent significant advances in genetics, the basic understanding of physiology, and the pathogenesis of disease coupled with technological advances in areas such as bioinformatics, chemical biology, synthetic chemistry, and protein engineering have provided a rich knowledge base and strong toolbox to identify and pursue new drug targets with the goal of generating new molecular therapies for the treatment of diseases. As part of its mission to reduce the burden of disease, NIDDK is committed to encouraging the translation of these discoveries into new treatments. The goal of this FOA is to support milestone-driven projects focused on the optimization and preclinical testing of candidate therapeutics for diseases within the mission of the NIDDK. All proposed studies must be directed at the most efficient route to regulatory submission, and therefore this program excludes basic research, studies of disease mechanism, or clinical studies.

Prospective applicants are strongly encouraged to discuss the relevance of proposed projects to the mission of the NIDDK with program staff before preparing an application. The NIDDK is exclusively interested in disease-focused translational research relevant to its mission which includes obesity, diabetes, diabetic complications, endocrine diseases, liver and digestive diseases, nutrition, kidney and urological diseases, hematology, and inborn errors of metabolism. For additional information on disease areas of interest to the NIDDK, please see http://www2.niddk.nih.gov/Research/.

The process of identifying and validating drug targets, small molecule chemical scaffolds, or biologics for the treatment of human disease begins with a hypothesis and can be viewed as progressing along a continuum of increasing confidence leading to widespread acceptance of its use in patient populations. This FOA is intended to support only later-stage efforts in lead optimization and pre-clinical development. For the purposes of this FOA, these stages are defined as:

Clinical target validation: Is defined as studies conducted in human patient populations to fully understand the efficacy and safety profiles of a compound and its associated target. True validation of a target may take decades of post-regulatory approval data accumulation.

Lead optimization and pre-clinical development: Are processes by which additional alterations to a pre-therapeutic lead may be made in conjunction with pre-clinical assessments of its in vivo pharmacokinetics, efficacy, and safety. The goal is to generate a lead clinical candidate and associated data packet which strongly supports regulatory approval for the initiation of clinical target validation.

Early-stage pharmacological target validation: Is a process of pre-clinical hypothesis testing to generate data that, over time, increases confidence that pharmacological manipulation of a target may be clinically efficacious and safe. This process occurs prior to clinical testing of a new compound but should include the use of human-derived data, tissues, cells, and systems.

Target identification: The generation of scientific evidence that a target is exploitable and involved in some significant way with a disease process.

This FOA is intended to stimulate research and development activities around lead optimization and pre-clinical development to a point where there is sufficient scientific evidence to justify filing of regulatory approval. It is not intended to support target identification or early-stage pharmacological or clinical target validation

This funding opportunity announcement is intended to support lead optimization and pre-clinical development activities around agents with the potential to treat diseases within the mission of the NIDDK.

The following are types of applications that are not appropriate for this FOA:

• Applications for which pre-therapeutic lead molecules or biologics have not yet been identified (e.g. assay development projects, screening of compound libraries, fractionation of natural products, target identification efforts);
• The development of novel tools, models, or technologies without an integrated plan for their use in lead optimization or pre-clinical development;
• Research focused primarily on understanding normal biology or disease processes;
• Clinical studies or interventional clinical trials;
• Agents for which the primary indication falls outside of the mission of the NIDDK.

The primary purpose of Phase I is to conduct key studies in support of Phase II applications, which are expected support projects that proceed through IND- or IDE-enabling studies.

Particular areas of interest appropriate for Phase I applications include, but are not limited to:

• Generation of key proof-of-concept data for a pre-therapeutic lead agent in established models of pre-clinical efficacy to justify extensive pre-clinical development activities in Phase II;
• Conducting a limited exploration of the structure activity/function relationship around a potential pre-clinical agent to demonstrate feasibility of an extensive lead optimization campaign in Phase II.

Phase I projects must result in one or more identified pre-clinical therapeutic leads with supporting efficacy data (e.g. animal models, ex vivo human tissues, iPSC-derived organoids, well justified in vitro target/pathway engagement) for a disease within the mission of the NIDDK to be considered for a Phase II award. Preliminary data should demonstrate rigor in the evaluation of candidate therapeutics entering Phase II, including, when possible, preliminary assessments of drug-like characteristics. It is expected that Phase II applications are focused on the generation and/or testing of potential therapeutic agents along a pathway headed towards regulatory filing.

Particular areas of interest appropriate for Phase II applications include, but are not limited to:

• Medicinal chemistry efforts leveraging existing structure activity relationships of a chemical scaffold to optimize a lead pre-clinical candidate, including characterization of efficacy as well as absorption, distribution, metabolism, excretion, and toxicity properties;
• Protein engineering to produce a lead clinical candidate molecule that modulate the activity of key regulators of tissue and organ regeneration;
• Pharmacological testing of novel pre-clinical lead candidates in state of the art efficacy models as well as the evaluation of novel models to better predict the efficacy of compounds (e.g. next-generation animal models, interconnected human organoid systems);
• The finalization of a novel nanoparticle formulation, such as one incorporating multiple agents, and demonstration of its potential to significantly enhance the therapeutic efficacy of the molecule(s) being studied.

Phase II applications may, and Phase IIB applications must, include pre-clinical studies which specifically generate data to support regulatory filing, and applicants are encourage to have had discussions with regulatory agencies prior to submission.

Particular areas of interest appropriate for Phase II or IIB applications include, but are not limited to:

• Scale-up GMP manufacturing of a small molecule pre-clinical lead and GLP IND-enabling pharmacological and toxicological testing;
• IDE-enabling toxicological studies of a nanoparticle based formulation of an existing medication to enhance tissue-specific uptake and target accessibility.

Applicants should refer to Section IV.2 for additional application instructions.

Applications may propose interaction with experts involved in NIDDK-funded existing research consortia, such as the Beta Cell Biology Consortium (www.betacell.org), the Nuclear Receptor Signaling Atlas (www.nursa.org), the Diabetic Complications Consortium (www.diacomp.org), the Mouse Metabolic Phenotyping Centers (www.mmpc.org), the Intestinal Stem Cell Consortium (iscc.coh.org), or the GenitoUrinary Development Molecular Anatomy Project (www.gudmap.org). If applicable, applicants should include letters of collaboration from experts detailing the nature of the collaboration.

Applicants are encouraged to take advantage of the resources provided by the National Center for Advancing Translational Sciences' Clinical Translational Science Awards (CTSAs) program, (http://www.ncats.nih.gov/research/cts/ctsa/ctsa.html) to leverage resources for therapeutic discovery in areas described in this FOA. CTSA resources include, for example, core facilities, super computer centers, biostatistics, bioinformatics, community engagement network, tissue repositories, and animal models. For more information about resources available at individual CTSAs, please contact the Program Officials listed at http://www.ncats.nih.gov/research/cts/ctsa/contact/contact.html .

Applicants that have not yet identified pre-therapeutic lead candidates as starting points should consider the Molecular Libraries Program (http://mli.nih.gov/mli/) and the following FOAs: Development of Assays for High-Throughput screening for use in Probe and Pre-therapeutic Discovery (R01) https://grants.nih.gov/grants/guide/pa-files/pa-10-213.html ; Solicitation of Assays for High Throughput Screening (HTS) to Discover Chemical Probes (R01) (https://grants.nih.gov/grants/guide/pa-files/PAR-12-058.html ); Early-Stage Pharmacological Validation of Novel Targets and Accompanying Pre-Therapeutic Leads for Diseases of Interest to the NIDDK (R01) (https://grants.nih.gov/grants/guide/pa-files/PAR-13-007.html ).

Funding Instrument	Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.
Application Types Allowed	New (Phase I, Fast-Track) Renewal (Phase II) Resubmission (all phases) Phase IIB Competing Renewal (Phase IIB) Revision The OER Glossary and the SF424 (R&R) SBIR/STTR Application Guide provide details on these application types.
Funds Available and Anticipated Number of Awards	The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.
Award Budget	According to statutory guidelines, total funding support (direct costs, indirect costs, fee) normally may not exceed $150,000 for Phase I awards and $1,000,000 for Phase II awards. With appropriate justification from the applicant, Congress will allow awards to exceed these amounts by up to 50% ($225,000 for Phase I and $1,500,000 for Phase II). Applicants are strongly encouraged to contact NIH program officials prior to submitting any application in excess of the guidelines. In all cases, applicants should propose a budget that is reasonable and appropriate for completion of the research project. Phase IIB budgets must be submitted in accordance with participating IC-specific budget limitations described in the current SBIR/STTR Program Descriptions and Research Topics of the NIH, CDC and FDA.
Award Project Period	According to statutory guidelines, award periods may not exceed 1 year for Phase I and 2 years for Phase II. Applicants are encouraged to propose a project duration period that is reasonable and appropriate for completion of the research project.

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

Only United States small business concerns (SBCs) are eligible to submit applications for this opportunity. A small business concern is one that, at the time of award of Phase I and Phase II, meets all of the following criteria:

1. Is organized for profit, with a place of business located in the United States, which operates primarily within the United States or which makes a significant contribution to the United States economy through payment of taxes or use of American products, materials or labor;

2. Is in the legal form of an individual proprietorship, partnership, limited liability company, corporation, joint venture, association, trust or cooperative, except that where the form is a joint venture, there must be less than 50 percent participation by foreign business entities in the joint venture;

3. (i) SBIR and STTR. Be a concern which is more than 50% directly owned and controlled by one or more individuals (who are citizens or permanent resident aliens of the United States), other business concerns (each of which is more than 50% directly owned and controlled by individuals who are citizens or permanent resident aliens of the United States), or any combination of these; OR

(ii) SBIR-only. Be a concern which is more than 50% owned by multiple venture capital operating companies, hedge funds, private equity firms, or any combination of these. No single venture capital operating company, hedge fund, or private equity firm may own more than 50% of the concern; OR

(iii) SBIR and STTR. Be a joint venture in which each entity to the joint venture must meet the requirements set forth in paragraph 3 (i) or 3 (ii) of this section. A joint venture that includes one or more concerns that meet the requirements of paragraph (ii) of this section must comply with 121.705(b) concerning registration and proposal requirements.

4. Has, including its affiliates, not more than 500 employees.

If the concern is more than 50% owned by multiple venture capital operating companies, hedge funds, private equity firms, or any combination of these falls under 3 (ii) or 3 (iii) above, see Section IV. Application and Submission Information for additional instructions regarding required application certification.

If an Employee Stock Ownership Plan owns all or part of the concern, each stock trustee and plan member is considered an owner.

If a trust owns all or part of the concern, each trustee and trust beneficiary is considered an owner.

Definitions:

• Hedge fund has the meaning given that term in section 13(h)(2) of the Bank Holding Company Act of 1956 (12 U.S.C. 1851(h)(2)). The hedge fund must have a place of business located in the United States and be created or organized in the United States, or under the law of the United States or of any State.
• Portfolio company means any company that is owned in whole or part by a venture capital operating company, hedge fund, or private equity firm.
• Private equity firm has the meaning given the term private equity fund in section 13(h)(2) of the Bank Holding Company Act of 1956 (12 U.S.C. 1851(h)(2)). The private equity firm must have a place of business located in the United States and be created or organized in the United States, or under the law of the United States or of any State.
• Venture capital operating company means an entity described in 121.103(b)(5)(i), (v), or (vi). The venture capital operating company must have a place of business located in the United States and be created or organized in the United States, or under the law of the United States or of any State.

SBCs must also meet the other regulatory requirements found in 13 C.F.R. Part 121. Business concerns, other than investment companies licensed, or state development companies qualifying under the Small Business Investment Act of 1958, 15 U.S.C. 661, et seq., are affiliates of one another when either directly or indirectly, (a) one concern controls or has the power to control the other; or (b) a third-party/parties controls or has the power to control both. Business concerns include, but are not limited to, any individual (sole proprietorship) partnership, corporation, joint venture, association, or cooperative. The SF424 (R&R) SBIR/STTR Application Guide should be referenced for detailed eligibility information.

Small business concerns that are more than 50% owned by multiple venture capital operating companies, hedge funds, private equity firms, or any combination of these are NOT eligible to apply to the NIH STTR program.

Phase I to Phase II Transition Rate Benchmark

In accordance with guidance from the SBA, the HHS SBIR/STTR Program is implementing the Phase I to Phase II Transition Rate benchmark required by the SBIR/STTR Reauthorization Act of 2011. This Transition Rate requirement applies to SBIR and STTR Phase I applicants that have received more than 20 Phase I awards over the past 5 fiscal years, excluding the most recently-completed fiscal year. For these companies, the benchmark establishes a minimum number of Phase II awards the company must have received for a given number of Phase I awards received during the 5-year time period in order to be eligible to receive a new Phase I award. This requirement does not apply to companies that have received 20 or fewer Phase I awards over the 5 year period.

Companies that apply for a Phase I award and do not meet or exceed the benchmark rate will not be eligible for a Phase I award for a period of one year from the date of the application submission. The Transition Rate is calculated as the total number of SBIR and STTR Phase II awards a company received during the past 5 fiscal years divided by the total number of SBIR and STTR Phase I awards it received during the past 5 fiscal years excluding the most recently-completed year. The benchmark minimum Transition Rate is 0.25.

SBA calculates individual company Phase I to Phase II Transition Rates daily using SBIR and STTR award information across all federal agencies. For those companies that have received more than 20 Phase I awards over the past 5 years, SBA posts the company transition rates on the Company Registry at SBIR.gov. Information on the Phase I to Phase II Transition Rate requirement is available at SBIR.gov.

Applicants to this FOA that may have received more than 20 Phase I awards across all federal SBIR/STTR agencies over the past five (5) years should, prior to application preparation, verify that their company’s Transition Rate on the Company Registry at SBIR.gov meets or exceeds the minimum benchmark rate of 0.25.

Non-domestic (non-U.S.) Entities (Foreign Institutions) 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, may be allowed.

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) 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. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM, SBA Company registry, and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) (formerly CCR) 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.
• SBA Company Registry New requirement. See Section IV. Application and Submission Information, SF424(R&R) Other Project Information Component for instructions on how to register and how to attach proof of registration to your application package. Applicants must have a DUNS number to complete this registration. SBA Company registration is NOT required before SAM, Grants.gov or eRA Commons registration.
• eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account and should work with their organizational officials to either create a new account or to affiliate an existing account with the applicant organization’s eRA Commons account. 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.

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 his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

Under the SBIR program, for both Phase I and Phase II, the primary employment of the PD/PI must be with the small business concern at the time of award and during the conduct of the proposed project. For projects with multiple PDs/PIs, at least one must meet the primary employment requirement. Occasionally, deviations from this requirement may occur.

The SF424 (R&R) SBIR/STTR Application Guide should be referenced for specific details on eligibility requirements. For institutions/organizations proposing multiple PDs/PIs, see Multiple Principal Investigators section of the SF424 (R&R) SBIR/STTR Application Guide.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

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

NIH will not accept similar grant applications with essentially the same research focus from the same applicant organization. This includes derivative or multiple applications that propose to develop a single product, process, or service that, with non-substantive modifications, can be applied to a variety of purposes. Applicants may not simultaneously submit identical/essentially identical applications under both this funding opportunity and any other HHS funding opportunity, including the SBIR and STTR Parent announcements.

NIH will not accept any application that is essentially the same as one already reviewed within the past thirty-seven months (as described in the NIH Grants Policy Statement), except for submission:

• To an RFA of an application that was submitted previously as an investigator-initiated application but not paid;
• Of an investigator-initiated application that was originally submitted to an RFA but not paid; or
• Of an application with a changed grant activity code.

A Phase I awardee may submit a Phase II application either before or after expiration of the Phase I budget period, unless the awardee elects to submit a Phase I and Phase II application concurrently under the Fast-Track procedure. To maintain eligibility to seek Phase II support, a Phase I awardee should submit a Phase II application within the first six due dates following the expiration of the Phase I budget period.

In Phase I, normally, a minimum of two-thirds or 67% of the research or analytical effort must be carried out by the small business concern. The total amount of all consultant and contractual arrangements to third parties for portions of the scientific and technical effort generally may not exceed 33% of the total amount requested (direct, F&A/indirect, and fee).

In Phase II, normally, a minimum of one-half or 50% of the research or analytical effort must be carried out by the small business concern. The total amount of consultant and contractual arrangements to third parties for portions of the scientific and technical effort generally may not exceed 50% of the total Phase II amount requested (direct, F&A/indirect, and fee).

A small business concern may subcontract a portion of its SBIR or STTR award to a Federal laboratory within the limits above. A Federal laboratory, as defined in 15 U.S.C. 3703, means any laboratory, any federally funded research and development center, or any center established under 15 U.S.C. 3705 & 3707 that is owned, leased, or otherwise used by a Federal agency and funded by the Federal Government, whether operated by the Government or by a contractor.

The basis for determining the percentage of work to be performed by each of the cooperative parties in Phase I or Phase II will be the total of the requested costs attributable to each party, unless otherwise described and justified in Consortium/Contractual Arrangements of the PHS 398 Research Plan component of SF424 (R&R) application forms.

Additional details are contained in the SF424 (R&R) SBIR/STTR Application Guide.

Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the Apply for Grant Electronically button in this FOA or following the directions provided at Grants.gov.

It is critical that applicants follow the instructions in the SF424 (R&R) SBIR/STTR Application Guide, except where instructed in this funding opportunity announcement to do otherwise. 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.

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

All page limitations described in the SF424 (R&R) SBIR/STTR Application Guide and the Table of Page Limits must be followed.

The forms package associated with this FOA includes all applicable components, required and optional. Please note that some components marked optional in the application package are required for submission of applications for this FOA. Follow all instructions in the SF424 (R&R) SBIR/STTR Application Guide to ensure you complete all appropriate optional components.

Instructions for Application Submission

The following section supplements the instructions found in the SF 424 (R&R) SBIR/STTR Application Guide and should be used for preparing an application to this FOA.

All instructions in the SF424 (R&R) SBIR/STTR Application Guide must be followed.

All instructions in the SF424 (R&R) SBIR/STTR Application Guide must be followed.

All instructions in the SF424 (R&R) SBIR/STTR Application Guide must be followed.

Other Attachments:

1. SBA Company registry

All applicants to the SBIR and STTR programs are required to register at the SBA Company Registry prior to application submission and attach proof of registration. Completed registrations will receive a unique SBC Control ID and .pdf file. If applicants have previously registered, you are still required to attach proof of registration. The SBA Company Registry recommends verification with SAM, but a SAM account is not required to complete the registration. In order to be verified with SAM, your email address must match one of the contacts in SAM. If you are unsure what is listed in SAM for your company, you may verify the information on the SAM site. Confirmation of your company's DUNS is necessary to verify your email address in SAM. Follow these steps listed below to register and attach proof of registration to your application.

a. Navigate to the SBA Company Registry.

b. If you are a previous SBIR/STTR awardee from any agency, search for your small business by Company Name, EIN/Tax ID, DUNS, or Existing SBIR/STTR Contract/Grant Number in the search fields provided. Identify your company and click Proceed to Registration .

c. If you are a first time applicant, click the "New to the SBIR Program?" link on lower right of registry screen.

d. Fill out the required information on the Basic Information and Eligibility Statement screens.

e. Press Complete Registration on the lower right of the Eligibility Statement screen and follow all instructions.

f. Download and save your SBA registry PDF locally. The name will be in the format of SBC_123456789.pdf, where SBC_123456789 (9 digit number) is your firm’s SBC Control ID. DO NOT CHANGE OR ALTER THE FILE NAME. Changing the file name may cause delays in the processing of your application.

g. When you are completing the application package, attach this SBA registry PDF as a separate file by clicking "Add Attachments" located to the right of the Other Attachments field on the Research and Related Other Project Information form.

For questions and for technical assistance concerning the SBA Company Registry, please contact the SBA at http://sbir.gov/feedback?type=reg.

2. SBIR Application Certification for small business concerns majority-owned by multiple venture capital operating companies, hedge funds, or private equity firms

Applicant small business concerns that are majority-owned by multiple venture capital operating companies, hedge funds, or private equity firms (e.g. majority VCOC-owned) are required to submit a Certification at time of their application submission per the SBIR Policy Directive. Follow the instructions below.

Applicants small business concerns who are more than 50% directly owned and controlled by one or more individuals (who are citizens or permanent resident aliens of the United States), other business concerns (each of which is more than 50% directly owned and controlled by individuals who are citizens or permanent resident aliens of the United States), or any combination of these (i.e. NOT majority VCOC-owned) should NOT fill out this certification and should NOT attach it their application package.

a. Download the SBIR Application VCOC Certification.pdf at the NIH SBIR Forms webpage.

b. Answer the 3 questions and check the certification boxes.

c. The authorized business official must sign the certification.

d. Save the certification using the original file name. The file must be named SBIR Application VCOC Certification.pdf . DO NOT CHANGE OR ALTER THE FILE NAME. Changing the file name may cause delays in the processing of your application.

e. When you are completing the application package, attach this certification as a separate file by clicking "Add Attachments" located to the right of Other Attachments field on the Research and Related Other Project Information form.

All instructions in the SF424 (R&R) SBIR/STTR Application Guide must be followed.

All instructions in the SF424 (R&R) SBIR/STTR Application Guide must be followed.

All instructions in the SF424 (R&R) SBIR/STTR Application Guide must be followed.

All instructions in the SF424 (R&R) SBIR/STTR Application Guide must be followed.

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

Research Strategy:

Justification of Target, Disease, and pre-Therapeutic

Applications must include a strong justification for the selection and appropriateness to the mission of the NIDDK of both the target and small molecule chemical scaffold or biologic as well as a discussion of the relevant prior art, intellectual property, and competitive landscape.

Technical Prerequisites for Phase II/IIB Applications

Phase I applications are not required to have these pre-requisites in place and may in fact propose to use the Phase I period to generate data and validate assays.

1. Pre-therapeutic lead candidate(s). Applications which propose to conduct lead optimization should discuss the starting points for optimization approaches (e.g. medicinal chemistry, protein engineering, microbial engineering). Applications must include an in-depth description of their initial candidate agent as well as a detailed plan for the generation and/or synthesis of refined derivatives. Preliminary data should include:

• Demonstration of a reproducible response within the assays proposed for further optimization and target validation;
• Analytical data showing appropriate quality, identity, and suitability of the agent;
• Preliminary data around analogs of the lead candidate to indicate sufficient structure activity / function relationships to justify additional rounds of lead optimization.

The submission of applications with back-up agents is encouraged to increase the overall likelihood of a successful project.

2. Assays. The application should provide a sound rationale for the choice of established in vitro and / or in vivo assays that will be used to support lead candidate optimization and / or pre-clinical development. Assays should be presented within the context of a testing flow diagram for testing newly derived agents and should be of sufficient throughput to support testing based on their position in the flow diagram.

It is acceptable to include the co-development of new assays (e.g. next-generation animal models, interconnected human organoids) that do not meet the requirements above, but it is expected that this co-development will incorporate benchmarking against more established assays.

3. Emerging technologies. The emergence of truly novel therapeutics may necessitate new approaches. The co-development of these technologies, tools, and models in direct support of lead optimization and / or pre-clinical development efforts within an application is appropriate. If proposing such co-development, applicants must include a section discussing why the development of these technologies is necessary to advance lead clinical candidates for a disease relevant to the mission of the NIDDK and provide preliminary data that the approach is feasible.

Milestones and Timeline

Applicants are required to include project performance and timeline objectives as a component of the Research Strategy. Applications must include proposed milestones at the end of Phase I (for Phase I and Fast-Track applications) and annually in Phase II to be within program scope. Applications lacking the Milestones and Timeline section will be deemed incomplete. This section should be limited to 1 page and should include:

• A clear description of all interim objectives to be achieved during the course of the project and how they relate to the overall goal of advancing the pre-clinical agent towards clinical trials;
• A detailed schedule or timeline for the anticipated attainment of each milestone and the objective of extending both target and molecule validation;
• Clearly delineated Go / No Go decision points;
• Succinct plans for the future development of the resulting therapeutic.

Resource Sharing Plans

Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) SBIR/STTR Application Guide.

Appendix

Do not use the Appendix to circumvent page limits. The instructions for the Appendix of the Research Plan are described in the SF424 (R&R) Application Guide.

Note that Phase I SBIR/STTR Appendix materials are not permitted.

Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) SBIR/STTR Application Guide.

This initiative is not subject to intergovernmental review.

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

Applications must be submitted electronically following the instructions described in the SF424 (R&R) SBIR/STTR Application Instructions. Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management (SAM). Additional information may be found in the SF424 (R&R) SBIR/STTR Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review, NIH. Applications that are incomplete will not be reviewed.

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-13-030.

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Significance

Does the project address an important problem or a critical barrier to progress in the field? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field? Does the proposed project have commercial potential to lead to a marketable product, process or service? (In the case of Phase II, Fast-Track, and Phase II Competing Renewals, does the Commercialization Plan demonstrate a high probability of commercialization?)

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Innovation

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangement?

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

Phase II Applications

For Phase II Applications, how well did the applicant demonstrate progress toward meeting the Phase I objectives, demonstrating feasibility, and providing a solid foundation for the proposed Phase II activity?

Phase I/Phase II Fast-Track Applications

For Phase I/Phase II Fast-Track Applications, reviewers will consider the following:

1. Does the Phase I application specify clear, appropriate, measurable goals (milestones) that should be achieved prior to initiating Phase II?

2. To what extent was the applicant able to obtain letters of interest, additional funding commitments, and/or resources from the private sector or non-SBIR/STTR funding sources that would enhance the likelihood for commercialization?

Protections for Human Subjects

For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

Inclusion of Women, Minorities, and Children

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of children to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

Phase IIB Competing Renewals

For Phase IIB Applications, the committee will consider the progress made in the last funding period.

Revisions

For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

Select Agent Research

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Resource Sharing Plans

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genome Wide Association Studies (GWAS).

Budget and Period of Support

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the Center for Scientific Review , in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

• May undergo a committee process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
• Will receive a written critique.

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications. Following initial peer review, recommended applications will receive a second level of review by the National Diabetes and Digestive and Kidney Diseases Advisory Council (NDDKAC). The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Any application awarded in response to this FOA will be subject to the DUNS, SAM Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants website.

The Office of Inspector General Hotline accepts tips from all sources about potential fraud, waste, abuse and mismanagement in Department of Health & Human Services programs. The reporting individual should indicate that the fraud, waste and/or abuse concerns an SBIR/STTR grant or contract, if relevant. Report Fraud.

Cooperative Agreement Terms and Conditions of Award

Not Applicable

NIH requires that SBIR/STTR grantees submit the following reports within 90 days of the end of the grant budget period unless the grantee is under an extension.

• Final Progress Report (requirements have recently changed - please see the NOT-OD-12-152)
• Final Invention Statement and Certification (HHS 568)
• Annual Invention Utilization Reports
• Federal Financial Report (FFR) replaced the Final Cash Transaction Report (PSC 272)
• Phase II Data Collection Requirement for Government Tech-Net Database

Failure to submit timely final reports may affect future funding to the organization or awards with the same PD/PI.

For details about each specific required report, see the section on Award Guidelines, Reporting Requirements, and Other Considerations, in the SF424 (R&R) SBIR/STTR Application Guide.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact Center Telephone: 800-518-4726
Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone: 301-945-7573
TTY: 301-451-5936
Email: [email protected]

eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application , documenting system problems that threaten submission by the due date, post submission issues)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

Web ticketing system: https://public.era.nih.gov/commonshelp
TTY: 301-451-5939
Email: [email protected]

SBA Company Registry (Questions regarding required registration at the SBA Company Registry and for technical questions or issues)

Website to Email: http://sbir.gov/feedback?type=reg.

Guillermo Arreaza-Rubin, M.D.
Division of Diabetes, Endocrinology and Metabolic Diseases
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-4724
Email: mailto:[email protected]

Aaron C. Pawlyk, Ph.D.
Division of Diabetes, Endocrinology and Metabolic Diseases
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-451-7299
Email: [email protected]

Marva Moxey-Mims, M.D.
Division of Kidney, Urologic, and Hematologic Diseases
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-7717
Email: [email protected]

Christine Densmore, M.S.
Division of Digestive Diseases and Nutrition
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-402-8714
Email: [email protected]

Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).

Todd Le
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-7794
Email: [email protected]

Florence Danshes
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-8861
Email: [email protected]

Pamela Love
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-435-6198
Email: [email protected]

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.

The SBIR Program is mandated by the Small Business Innovation Development Act of 1982 (P.L. 97-219), reauthorizing legislation (P.L. 99-443) P.L. 102-564, and P.L. 112-81 (SBIR/STTR Reauthorization Act of 2011). The basic design of the NIH SBIR Program is in accordance with the Small Business Administration (SBA) SBIR Policy Directive.