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

This Funding Opportunity Announcement (FOA) encourages the translation of research discoveries into new treatments for disorders that fall under the mission of NIAAA. The goal is to advance the commercialization of small molecules, natural products or biologics that have shown therapeutic potential for alcohol use disorder or alcohol-related diseases in preclinical testing, by supporting efforts to achieve IND approval. For application to the FOA, at entry, the project should have an identified candidate that has undergone rigorous preclinical testing and has sufficient bioactivity, stability, manufacturability, bioavailability, in vivo efficacy and/or target engagement, and is considered state-of-the-art for the disease (see entry criteria for details). Projects are expected to achieve filing of an Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) by the end of the funding period. This FOA for an STTR UT2 cooperative agreement is structured as a Fast-Track, requiring both Phase I and Phase II components. In Fast-Track, the milestones of Phase I must be completed before the Phase II funding will be released. While the UT2 Phase I supports the preparatory activities needed before launching IND-enabling studies (such as manufacturing for IND-enabling toxicology and verification of such manufactured material for its activities), the UT2 Phase II phase supports the IND-enabling studies (e.g., GLP toxicology, biodistribution, immunogenicity evaluations).

Projects are funded via a UT2 cooperative agreement mechanism, which involves NIAAA Program staff's participation in developing the project plan, monitoring research progress, and appropriate go/no-go decision-making. The expectations of the program are in line with those of industry in regards to advancing therapeutic agents through the developmental pipeline.

For this funding opportunity announcement, UT2 Phase I and II refer to the project phases of the STTR program, and are not to be confused with phase I of clinical trials, which may be proposed, but are not required..

This FOA seeks applications that propose to advance the following classes of therapeutics beyond pre-clinical development by preparing to seek regulatory approval for future trials: small molecules, natural products, and biologics, which broadly include peptides, proteins, oligonucleotides, gene therapies, and cell therapies. Applicants are strongly encouraged contact NIAAA Scientific/Research staff regarding the agent under development, to determine the fit for the FOA.

Entry Criteria

Only the most promising agents that have undergone rigorous preclinical testing and are considered state-of-the-art for the disease of interest will be considered for advancement to IND-enabling studies. To be eligible for this FOA, applicants must have a candidate with the final structure for human testing that minimally satisfies all of the following:

(1) Optimization is finished and final characterization of the candidate, such as structure/identity, selectivity, stability, manufacturability, and other modality-specific characteristics is complete.

(2) For a candidate with sufficient purity, its minimal effective dose, optimal effective dose, time and duration of treatment, have been determined in relevant in vivo assays using clinically relevant functional and/or anatomical outcome measures, and/or in vivo target engagement assays. [This normally should have been done using the clinically intended route of administration and special formulations if proposed (such as slow release, liposomes, nanoparticles, etc.), unless justified to use other routes of administration in which case the dose-response must have been reliably bridged by pharmacokinetics measurements]. The in vivo study results should also include assessment of pharmacokinetics, bioavailability at the relevant site of action, and pharmacokinetics-pharmacodynamics relationship. In particular for CNS-active agents, there needs to be rigorous evidence that the agent is blood-brain-barrier penetrant (unless the agent is proposed to be delivered directly to the CNS) and available at an effective dose or evidence that the agent can act in the periphery. Key studies should be sufficiently powered and controlled with experimental and statistical rigor to lend a high degree of confidence in the results, with sufficient information available about study design, execution, analysis, and interpretation.

(3) Feasibility for production and reproducible production of the candidate.

UT2 Phase I Scope

Examples of studies that can be proposed during this Phase include, but are not limited to:

• Chemistry, Manufacturing, and Control (CMC) activities (e.g., master and working banks development, purification development, CMC analytical development, formulation development, scale-up manufacturing or cGMP manufacturing) for IND-enabling pharmacology/toxicology tests
• Pharmacokinetic evaluations in species relevant for toxicology or human dose-prediction
• If needed for certain therapeutic modalities, final characterization and definitive verification of in vitro and in vivo activities such as preclinical target engagement and/or efficacy studies, using the final manufactured material (using final cGMP process depending on regulatory requirement) intended for IND-enabling toxicology studies
• Preliminary safety such as safety pharmacology and/or dose-range finding toxicology
• Optimizing and/or validation of appropriate assays for pharmacokinetics, bioactivity (potency), target engagement markers or other assays to monitor safety to be used in human trials

The length of Phase I can be brief depending on the maturity of the project at entry.

UT2 Phase II Scope

The Phase II will support IND-enabling development activities. For more advanced projects, a small early phase clinical trial can also be supported when feasible during the Phase II. Applications seeking to support only early stage clinical trials are not appropriate for this FOA.

Preclinical development activities appropriate for Phase II include, but are not limited to:

• IND-enabling toxicology, with toxicokinetics, if applicable
• Tumorigenicity evaluations particularly for gene therapies and cell therapies, if applicable
• Immunogenicity evaluations, if applicable
• Biodistribution studies, if applicable
• Large animal study to assess biocompatibility of means of clinical delivery of the candidate, if applicable
• Validation of appropriate assays such as for target engagement markers to enable human use
• IND and other regulatory submissions

Small, early-phase clinical trials that are appropriate include:

• Population: patients with indicated disease, or healthy volunteers
• Total subjects =50
• Design is single dose or single ascending dose treatment, and may be placebo-controlled or open-label studies; multiple ascending dose may be requested only if agent has a short half-life
• Outcomes are safety, pharmacokinetics and pharmacodynamics/target engagement/target modulation. Note that clinical efficacy outcome data may be collected to prepare for Phase 2 clinical studies, but efficacy cannot be the primary objective of the study
• The duration of the clinical trial, from initiation at first informed consent signature to the completion of data analysis, should rarely exceed 2 years

Activities that are appropriate for clinical trial preparatory activities (only if clinical trials are proposed), which may be performed concurrently with IND-enabling preclinical studies during Phase II include, but are not limited to:

• Manufacturing of cGMP (current Good Manufacturing Practices) material for the small, early-phase clinical trial if not done already in Phase I
• Development and validation of biochemical assays required for clinical trials if not already complete (e.g., pharmacokinetic, pharmacodynamic, and/or immunogenicity assays)
• Preparation of clinical trial protocol, Investigator's brochure
• Preparation of documents required to support a clinical trial (e.g., case report Fforms, pharmacy manual, study coordinator manual, monitoring plan)

Clinical trial activities that are appropriate during Phase II include, but are not limited to:

Patient/subject recruitment and enrollment

Site monitoring

Data collection and quality assurance

Statistical analysis

Safety reviews

Examples of Activities Inappropriate for this FOA include:

• Animal model development
• Basic research and studies of disease mechanisms
• Early research such as identifying and validating targets and generation of preliminary agents that are not suitable for human testing
• Development of risk, detection, diagnostic, prognostic, efficacy prediction biomarkers. (NIAAA recognizes that target engagement markers developed under the Phase I may evolve into predictive markers for treatment trials, but it is not the intent of this FOA to develop predictive biomarkers.)
• Activities already performed utilizing other private or public funds to advance the agent
• Performance of a clinical trial with the objective of demonstrating clinical efficacy or clinical proof-of-concept

Because therapy development is an inherently high-risk process, it is anticipated that there may be significant attrition as projects move through the therapy development process. Milestones are goals that are quantifiable for measuring success that can be used for go/no-go decision-making for the project, and should have quantitative criteria associated with them (see Section IV.2 for details).

Since the primary focus of IND-enabling research is to determine the safety and toxicology of the product that will move into humans, applicants should keep in mind that the efficacious dose levels should, ideally, be non-overlapping with a dose(s) resulting in significant toxicity and reflect the fact that one has to carefully assess toxicity in relationship to efficacy. NIAAA intends to only move forward agents that are both efficacious and safe. Although the primary goals are to assess safety and toxicology, lack of evidence of robust efficacy in the dose range where the candidate is safe can also be a consideration for discontinuation.

UT2 Phase I/II transition

An administrative review will be conducted by NIAAA Program staff to decide whether a project will be considered for transition from the Phase I to the Phase II. Phase II eligible projects must have a candidate that has been manufactured with satisfactory purity and stability, verified to have activity in vivo and/or in vitro as necessary, have bioavailability with a proper formulation, and have a good preliminary safety profile. Specifically, projects entering the Phase II must satisfy the following:

• For certain therapeutic modalities, the final manufactured material for IND-enabling toxicology studies needs to have final characterization and definitive verification for in vitro and in vivo activities. In these cases, these studies should have been satisfactorily completed prior to the Phase II
• Have bioavailability with a proper formulation; addressed blood-brain-barrier penetrant issues if it is a CNS target
• Pharmacokinetics and pharmacokinetics-pharmacodynamics relationships are known and allow feasible dose for human testing
• Preliminary toxicology studies in animal models have been completed; any safety concerns raised based on these studies can be addressed
• Evidence that IND-enabling preclinical testing plans and study protocols have been reviewed by the FDA and input received in the context of pre-submission interaction with the agency (e.g., Pre-IND meeting with FDA)
• Transition to Small, Early-Phase Clinical Trial
• Clinical Trial preparatory activities may be performed concurrently with IND-enabling preclinical Phase II activities with approval of NIAAA staff. General criteria for starting clinical preparatory activities, if applicable, will be based on:
• Meeting previous milestone criteria during Phase I and Phase II
• Progress in IND-enabling studies
• Assessment that submission of an IND appears feasible on a timeline allowable within the grant
• Prior to commencement of the clinical trial (defined as first subject signature on an informed consent form), the applicant must provide sufficient documentation to NIAAA for review. On scientific or clinical grounds, NIAAA may require inclusion of additional procedures beyond those required by the FDA. Therefore, approval must be received from NIAAA prior to commencement of the clinical trial.
• General criteria for starting a clinical trial:
• Successful achievement of the defined milestones for the preclinical portions of the Phase II period;
• Successful completion of any clinical preparatory milestones
• Submission of an IND with a "may proceed" letter or email from the FDA
• Submission of the clinical protocol and supporting documents to the NIAAA
• Agreement with NIAAA staff on updated timeline, milestones and budget for clinical trial
• NIAAA approval of protocol and safety monitoring plan

Since the goal of this program is to generate therapeutics which will be eligible for FDA approval, adherence to compliance and quality criteria is required.

• It is expected that all IND-enabling nonclinical studies will be performed in a manner consistent with Good Laboratory Practices (GLP).
• Investigational products should be produced under current Good Manufacturing Practices (cGMP). Bioassays such as pharmacokinetics, pharmacodynamics or immunogenicity should, when possible, be performed under GLP guidelines.
• All clinical trials must be performed following Good Clinical Practices (GCP) and be in accord with NIAAA Policy.
• Investigational products should be produced under current Good Manufacturing Practices (cGMP). Bioassays such as pharmacokinetics, pharmacodynamics or immunogenicity should, when possible, be performed under GLP guidelines.

Since the ultimate goal of the SBIR/STTR program is to bring new therapies to the market/patients, the program strongly encourages the awardees and/or their collaborators to obtain and retain any IP developed around the therapy during the project period (see instructions on attachment of letters to address IP issues in Section IV.2). Awardees are encouraged to identify and foster relationships with potential licensing and commercialization partners early in the therapy development process. PDs/PIs are expected to work closely with their institutional technology transfer officials to ensure that royalty agreements, patent filings, and all other necessary IP arrangements are completed in a timely manner and that commercialization plans are developed and updated over the course of the project. For rare or ultra-rare diseases where commercialization may be challenging, applicants are encouraged to discuss alternative strategies with NIAAA Scientific/Research staff to get further guidance.

As an UT2 cooperative agreement, implementation will involve the participation of NIAAA Program staff in the planning and execution of the therapy-directed projects. Applicants are strongly encouraged to consult with NIAAA Scientific/Research staff when planning an application. Early contact provides an opportunity for NIAAA Scientific/Research staff to provide further guidance on program scope, goals, developing appropriate milestones, and budget. Applicants should contact NIAAA Scientific/Research staff at least 8 weeks before the due date.

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.

Phase II to Phase III Commercialization Benchmark

In accordance with guidance from the SBA, HHS, including NIH, SBIR/STTR Programs are implementing the Phase II to Phase III Commercialization Rate benchmark for Phase I applicants, as required by the SBIR/STTR Reauthorization Act of 2011. The Commercialization Rate Benchmark was published in a Federal Register notice on August 8, 2013 (78 FR 48537).

This requirement applies to companies that have received more than 15 Phase II awards from all agencies over the past 10 years, excluding the two most recently-completed Fiscal Years. Companies that meet this criterion must show an average of at least $100,000 in revenues and/or investments per Phase II award or at least 0.15 (15%) patents per Phase II award resulting from these awards. This requirement does not apply to companies that have received 15 or fewer Phase II awards over the 10 year period, excluding the two most recently-completed Fiscal Years.

Information on the Phase II to Phase III Commercialization Benchmark is available at SBIR.gov.

Applicants to this FOA that may have received more than 15 Phase II awards across all federal SBIR/STTR agencies over the past ten (10) years should, prior to application preparation, verify that their company’s Commercialization Benchmark on the Company Registry at SBIR.gov meets or exceeds the benchmark rate listed above.

Applicants that fail this benchmark will be notified by SBA annually and will not be eligible to receive New Phase I, Fast-track or Direct Phase II awards for a period of one year.

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. 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.

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.

For the STTR program, the PD(s)/PI(s) may be employed with the SBC or the single, partnering non-profit research institution as long as s/he has a formal appointment with or commitment to the applicant SBC, which is characterized by an official relationship between the SBC and that individual. Each PD/PI must commit a minimum of 10% effort to the project and the PD/PI must have a formal appointment with or commitment to the applicant small business concern, which is characterized by an official relationship between the small business concern and that individual. Such a relationship does not necessarily involve a salary or other form of remuneration.

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.

The NIH will not accept duplicate or highly overlapping applications under review at the same time. 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 NOT-OD-11-101).

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 or IIB support, a Phase I awardee should submit a Phase II application, and a Phase II awardee should submit a Phase IIB application, within the first six due dates following the expiration of the Phase I or II budget period, respectively.

In Phase I and Phase II, at least 40% of the research or analytical effort must be performed by the small business concern and at least 30% of the research or analytical effort must be performed by the single, partnering research institution. The basis for determining the percentage of work to be performed by each of the cooperative parties will be the total of direct and F&A/indirect costs attributable to each party, unless otherwise described and justified in Consortium/Contractual Arrangements of the PHS 398 Research Plan component of the SF424 (R&R) application forms.

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, including Supplemental Grant Application Instructions 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.

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

Dr. Abraham P. Bautista
Telephone: 301-443-9737
Fax: 301-443-6077
Email: [email protected]

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

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, with the following additional instructions:

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. Intellectual property (IP) strategy

Applicants are encouraged to prepare this section of the application in consultation with their institution's technology transfer officials, if applicable.

Applicants should describe the IP landscape surrounding their therapy. Applicants should describe any known constraints that could impede the development of their therapy (e.g., certain restrictions under transfer or sharing agreements, applicants' previous or present IP filings and publications, similar therapies that are under patent protection and/or on the market, etc.) and how these issues could be addressed. If the applicant proposes using an agent(s) whose IP is not owned by the applicant's institution, either an investigational therapeutic, FDA-approved therapeutic, or other licensed product, the applicant should address any questions of freedom to operate consistent with achieving the goals of the program. Applicants should include a letter (see Letters of Support) from the entity who owns the IP indicating whether they will provide the agent(s), if there are any limitations on the studies that can be performed with that agent(s), agreement about public disclosure of results (including negative results), and whether there is an agreement already in place.

If patents pertinent to the therapy being developed under this application have been filed, the applicant should indicate the details of filing dates, what type of patents are filed, and application status, and associated United States Patent and Trademark Office (USPTO) database links, if applicable.

Applicants should discuss future IP filing plans. For a multiple PD/PI, multi-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 IP) among the institutions. Applicants should clarify how IP will be shared or otherwise managed if there are multiple PD/PIs and institutions involved, as appropriate and consistent with achieving the goals of the program.

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) 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:

Specific Aims: The Specific Aims section should include separate Aims delineated for each of the phases. A scientific hypothesis is not required.

Research Strategy: The Research Strategy section should include the following subsections:

A. Significance: Clinical Impact and Feasibility
B. Supporting Data for Entry
C. Detailed Plans for Approach (Including Milestones and Timelines)
D. Team Management

A. Significance

Describe the proposed Target Product Profile, how it affects clinical practice with consideration of existing treatments and therapeutic development efforts underway in academia and industry, including all therapeutic classes

Clinical Impact and Feasibility: Each application should focus on only one disorder or disease, even if the therapeutics proposed for development show activity in models for more than one disorder. This is because the target patient population and intended use guide the design of the therapy and the path for an IND, and the preclinical IND-enabling studies. Levels of tolerated toxicities may also differ between different disorders especially if the proposed treatment is chronic versus acute.

• Describe the current state of knowledge of the etiology, clinical characteristics, and prevalence of the proposed disease indication.
• Briefly discuss available treatments (if any), their limitations, and how the proposed project would provide an advantage over all existing therapies, regardless of therapeutic class (i.e., discussion only on within class comparisons is not sufficient).
• If the therapy is an improvement over an earlier generation agent(s) that has not been marketed, discuss what advantages the new agent has. Include results from previous clinical trials with related agents.
• Discuss how the proposed project relates to therapy development efforts underway in academia and industry, regardless of therapeutic class. What are the distinct advantages to the new, proposed therapy considering other investigational agents that might be entering the clinical pipeline soon?
• Provide a Target Product Profile (TPP) based on the FDA guidance (see guidance and example at http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm080593.pdf) that shows the ultimate goals of the proposed therapy development effort, such as disease indication and stage, patient population, delivery mode and dosing regimen, treatment duration, and standards for clinical efficacy. Explain the rationale behind the minimally acceptable and ideal parameters for the clinical population.
• Briefly outline the plans for the first clinical proof-of-concept study that aligns with the proposed TPP and comment on feasibility of conducting the trial(s).

B. Supporting Data for Entry

The Supporting Data for Entry section contains, but is not limited to, comprehensive data to justify that the application meets the entry criteria, as well as data that demonstrate the feasibility of conducting studies to address the specific aims, for example:

(1) Describe what is known about the candidate such as structure/identity, selectivity/specificity, bioactivity, stability, bioavailability, and other modality- specific characteristics.

• Show structure/identity such as cell identity for cell therapies, purity, aggregation, epitope mapping, glycosylation, or other post-translational modification for proteins
• Demonstrate selectivity/specificity
• Describe bioactivities of the candidate in vitro (e.g., binding affinities, IC50 in relevant in vitro model). Show evidence that the candidate modulates the targets or pathway in vitro.

(2) Present data showing the minimal effective dose, optimal effective dose, time and duration of treatment. These should have been determined in relevant in vivo assays using clinically relevant functional and/or anatomical outcome measures, and/or in vivo target engagement assays, using a candidate that is sufficiently pure. [This normally should have been done using the clinically intended route of administration and special formulations if proposed (such as slow release, liposomes, nanoparticles, etc.), unless justified to use other routes of administration in which case the dose-response must have been reliably bridged by pharmacokinetics measurements]. Present data on pharmacokinetics, CNS penetration (if applicable), and pharmacokinetics-pharmacodynamics relationship. NIAAA encourages discussion of rigor, control of bias, and transparency of reporting in order to ensure robustness and reproducibility of the observed results.

• Explain the choice of models or assays, primary, secondary and exploratory endpoints, and how they are clinically relevant. If multiple models have been employed, outline the pros and cons of each model and why one model may be more robust than another. Explain which model(s) is the one most frequently employed in IND-enabling studies to seek approval from the FDA.
• Describe power analyses and associated assumptions for the determination of sample size, statistical handling of the data such as criteria for data inclusion or exclusion, and describe the procedures of how blinding and randomization were conducted, and whether independent replication was employed in these studies.
• Describe bioavailability; include data and analyses performed to demonstrate the candidate can penetrate the blood-brain-barrier, if required for efficacy.
• When interpreting the results, consider alternative interpretations of the experimental data, relevant literature in support of or in disagreement with the results, and include discussion of effect size in relation to potential clinical impact.
• Applicants should explain what key data, if any, has been reproduced, by the applicants or by independent investigators.

(3) Discuss feasibility of production and reproducibility of production of the candidate.

C. Detailed Plans for Approach (Including Milestones and Timelines)

In this section applicants should elaborate on their research plans. Describe milestones to be used for measuring success in achieving each of the research plan’s objectives. One or more milestone should be used for each objective. For each milestone provide details on methods, assumptions, experimental designs, and data analysis plans (if the results are quantitatively measured). Specify the quantitative criteria for measuring success and the rationale for the quantitative criteria. Quantitative criteria should be robust and be consistent with the state-of-the-art in the field. Most of the time the quantitative criteria for success in the milestones will also be used for making go/no-go decisions and this should be specified. Specify the timeline for each milestone. There should be at least one milestone proposed for completion at the end of each year.

Plans could include but are not limited to:

• Describe experimental designs, delineated for Phase I and Phase II. If the studies proposed are planned to be done in a Contract Research Organization (CRO), Contract Manufacturing Organizations (CMO), list the name(s) of the CRO(s) for the activities.
• Present a plan for the Phase I for the preparatory work for IND-enabling studies such as CMC activities, preliminary safety studies, validation of target engagement assays to support future human clinical trials, final characterization of the manufactured material intended for preclinical IND-enabling toxicology studies, etc.
• Present a plan for how the Phase II preclinical studies that are consistent with or per regulatory guidance will be achieved. These include IND-enabling toxicology, tumorigenicity evaluations as needed, immunogenicity evaluations as needed, biodistribution studies as needed, large animal study to assess biocompatibility of means of clinical delivery of the candidate, validation of appropriate assays for target engagement markers to enable human use, etc.
• For critical preclinical studies, like definitive verification of the activities of the candidate (if needed) in preclinical efficacy studies, and/or pharmacokinetics-pharmacodynamics studies, provide the following:
• The choice of models, assays, and clinically-relevant endpoints (primary, secondary, and exploratory when applicable) for these studies;
• Information on study design, power analyses and associated assumptions for sample size estimation (e.g., what is considered a minimal change predictive of clinically meaningful change, variance known in the in vivo assay described in supporting data, expected treatment effect size), and detailed procedures of how blinding and randomization will be done;
• Data handling rules such as criteria for inclusion and exclusion of data;
• Plans for data analysis and interpretation;
• Outline any differences between how these analyses will be performed and those used to develop the Entry Criteria (outlined above) for the candidate. Provide a rationale for any changes.

Early-Phase Clinical Trial Synopsis

If requesting funding to conduct the first-in-human study, provide a brief synopsis that includes the following:

• Planned population (e.g, adult, pediatric, newly diagnosed, advanced disease, subtype and/or screened for molecular/cellular target)
• Objectives
• Study design
• Route of administration and determination of dose levels
• Safety assessments
• Pharmacokinetics and pharmacodynamics assessments, with attention to demonstration of CNS penetration (if appropriate) and target engagement or modulation
• Correlative or surrogate analyses designed to assess target engagement (e.g, using blood, urine, saliva, cerebral spinal fluid (CSF), or imaging measures)
• Safety management plan (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-038.html.

It is understood that at the time of application, some of the above may be limited or even unavailable, but an effort should be made to predict trial design when possible. Since details of the trial may change in the course of therapeutic development, the overview might not reflect/include the final details of the protocol that will be implemented.

Summarize milestones and timelines in a Gantt chart.

D. Team Management Plan

NIAAA strongly encourages applicants to form multidisciplinary teams that consist of preclinical and clinical scientists, CMC experts, regulatory experts, statisticians, and other academic/industry experts relevant to the therapeutic modality. This multidisciplinary team should be able to define a desired TPP, to design the details of the plans and experiments, and to execute the research strategy. Describe how the team will work together (e.g., data generation, reporting of data and integrated review across teams with various disciplines, decision-making, participate meetings with NIAAA, communication etc.) over the course of the project. Indicate the willingness of the PD(s)/PI(s) and key personnel to operate under the cooperative agreement terms and conditions outlined in Section VI.2 of the FOA.

Letters of Support: Applicants should include letters of support from consultants, contractors, and collaborators.

• If research will be performed at more than one institution, include a letter of support from each institution clarifying how intellectual property will be shared or otherwise managed across the institutions.
• If collaborating with a private entity, include a letter of support that addresses any agreement to provide agent(s), any limits on the studies that can be performed with said agent(s), any limitations on sharing of data (including negative results), and whether a licensing agreement(s) is in place. This letter should come from a high official within the private entity who has authority to speak on these issues.

Resource Sharing Plans: Individuals are required to comply with the instructions for the Resource Sharing Plans 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, with the following modifications:

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

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

Commercialization Plan: All applicants are expected to describe a realistic plan (extending beyond the UT2 Phase II), which outlines how and when full commercialization can be accomplished. The full commercialization of the product/technology should be carried out with non-SBIR/STTR funds.

The following subsections with the headings should be included within the Commercialization Plan, in addition to the requirements listed in the SF424 Application Guide:

1) Statement of Need

Applicants must provide a concise Statement of Need . This statement is expected to provide answers to the questions listed below:

• What is the perceived Valley of Death for the product/technology under development?
• To what extent would a possible award under this FOA advance the product or technology far enough to attract sufficient, independent third-party financing and/or strategic partnerships to carry out full commercialization?

2) SBIR/STTR Commercialization History

Applicants should provide an SBIR/STTR Commercialization History that addresses the questions listed below. The following questions should be addressed for all SBIR/STTR awards received from any Federal agency:

• Has the company gone through any name changes within the past five years? If so, then all previous company names should be listed in the application.
• Is the company a subsidiary or a spin-off? If so, then the name of the parent company should be provided.
• What percentage of the company’s revenue was derived from SBIR/STTR funding during each of the past 5 years, including both Phase I and Phase II awards? Applicants should report a percentage value for each year individually.
• What is the total number of SBIR/STTR Phase II awards that the company has received from the Federal government? For each award, companies should provide the award number, the award amount, project duration, and the name of the awarding agency.
• What are the total revenues that have been generated to date as a result of the commercialization of the SBIR/STTR projects funded within the past 5 years?

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. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues.

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 and compliance with application instructions by the Center for Scientific Review, NIH. Applications that are incomplete or non-compliant will not be reviewed.

In order to expedite review, applicants are requested to notify the NIAAA Referral Office by email at [email protected] when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.

Applicants are required to follow our Post Submission Application Materials policy.

Important Update: See NOT-OD-16-006 and NOT-OD-16-011 for updated review language for applications for due dates on or after January 25, 2016.

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.

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?)

If the project is successful according to the proposed Target Product Profile, how does it affect clinical practice with consideration of existing treatments and therapeutic development efforts underway in academia and industry, including all therapeutic classes?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those 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?

Have researchers with preclinical and clinical expertise, necessary statistical expertise, and experts in relevant therapeutic modality development been included in the conception, design, and proposed implementation of the project?

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?

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?

Regarding the Section on Supporting Data for Entry:

Is there a complete description of the candidate such as structure/identity, selectivity/specificity, stability, manufacturability, and other modality-specific characteristics? Does this candidate represent a competitive, state of the art agent that should be moved forward to IND-enabling studies?

Have the minimal effective dose, optimal effective dose, time and duration of treatment been determined using in vivo assays? Were these conducted using clinically relevant functional and/or anatomical outcome measures, and/or in vivo target engagement assays, using a candidate that is sufficiently pure? Did the application address bioavailability, blood-brain-barrier penetration issues if it is a CNS target, and pharmacokinetics-pharmacodynamics relationship? What is the robustness of the unpublished and published data used in support of the application? For key experiments, did the application include the following?

• The choice of models or assays, primary, secondary and exploratory endpoints, and how they are clinically relevant.
• Power analyses and associated assumptions for the determination of sample size, statistical handling of the data such as criteria for data inclusion or exclusion, and procedures of how blinding and randomization were conducted, and whether independent replication was employed in these studies.
• Alternative interpretations of the experimental data, relevant literature in support of or in disagreement with the results, and discussion of effect size in relation to potential clinical impact, when interpreting the results.
• Key data, if any, that have been reproduced, by the applicants or independently?

Regarding the Section on Detailed Plans for Approach (Including Milestones and Timelines):

Are the plans necessary and sufficient to achieve the Specific Aims?

For key preclinical experiments (if needed for final verification), do the proposed analyses include the following?

• A primary endpoint and/or other endpoints and an explanation as to why they were chosen
• Appropriate controls
• An explanation of assumptions and supporting data for power analyses
• A description of planned data analyses and data handling rules such as criteria for data inclusion or exclusion
• A detailed description of the procedures of how blinding and randomization will be implemented

Are the therapy development plan and activities in the Phase II appropriate for enabling final toxicology and safety studies, consistent with the desired TPP?

Are the milestones robust and associated with clear, quantitative criteria for success that allow go/no-go decisions? If a criterion is not to be used for go/no-go decisions, is it justifiable?
Are the timelines proposed for achieving the milestones realistic and inclusive of necessary steps, but also efficient without adding unnecessary steps?

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.

Market, Customer, and Competition

How compelling is the value proposition, and to what extent does the application demonstrate a substantial market-pull for the technology under development?

How well has the applicant described the market niche(s) for the product/ technology, and how urgent is the unmet need(s) being addressed?

To what extent has the applicant identified realistic, market-based milestones that can be achieved over the next five years?

How well has the applicant demonstrated an understanding of the competitive environment in which they plan to sell their product?

To what extent has the applicant identified their customers and demonstrated a clear understanding of their needs?

How well has the company addressed potential hurdles that may delay or prevent acceptance of their product?

How reasonable are the applicant's plans for generating a revenue stream, and how realistic are the revenue projections?

Company

How well can the applicant SBC sustain itself and grow as a business?

To what extent do the prior experience and qualifications of the project team members lend confidence that the team will be successful in commercializing the proposed product/technology? For example, how successful have the PD(s)/PI(s) been in commercializing other SBIR/STTR supported technologies and discoveries in the past?

To what extent will the applicant's business alliances and/or corporate partnerships help in facilitating commercialization? For example, will third-party investors play an active role in facilitating the commercialization of the product/technology, and if so to what extent?

If the SBC has received previous SBIR/STTR funding from ANY Federal agency, then how successful is the company’s track record in commercializing prior SBIR/STTR projects?

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?

Not Applicable

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?

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.

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.

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.

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.

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.

Not Applicable

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.

Intellectual Property (IP)

How strong is the applicant's intellectual property (IP) portfolio/position (pertinent to the proposed project), and to what extent does the company have a reasonable strategy to protect its IP going forward?

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).

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) /Genomic Data Sharing Plan.

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 NIAAA, 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 submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Council on Alcohol Abuse and Alcoholism . 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.

Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

Prior to funding an application, NIAAA Program staff will contact the applicant to discuss the proposed milestones and any changes suggested by the NIAAA review panel or NIAAA Program staff. A final set of milestones will be specified in the Notice of Award.

Progress towards achievement of the final set of milestones will be evaluated by NIAAA Program staff. NIAAA Program staff may consult as necessary with independent consultants with relevant expertise. If justified, future year milestones may be revised based on data and information obtained during the previous project period. If, based on the progress report, a funded project does not meet the milestones, funding for the project may be discontinued. In addition to milestones, the decision regarding continued funding will also be based on the overall robustness of the entire data package that adequately allows an interpretation of the results (regardless if they have been captured in the milestones), overall progress, NIAAA portfolio balance and program priorities, competitive landscape, and availability of funds.

NIAAA emphasizes the importance of the robustness and reproducibility of experimental results. In some cases, conducting additional critical experiments will be important for NIAAA to have confidence in making a funding decision. Therefore, NIAAA Program staff, in consultation with the PD/PI, may add experiments that need to be conducted prior to or during the award as an additional milestone(s). In some cases, these studies will be supported by additional funds from NIAAA.

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.

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

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the UT2 cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the purpose of NIH is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

The PD(s)/PI(s) will have primary responsibility for:

• The PD(s)/PI(s) will have primary responsibility for defining objectives and approaches, and for planning, conducting, analyzing, interpreting, drawing conclusions on their studies, publishing and sharing the results.
• Awardees are responsible for developing and proposing rigorous milestones that will be achieved during the project period.
• Awardees will retain custody of and have all rights to the data and therapy developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.
• Awardees are responsible for pursuing patent protection.
• Awardees are responsible for providing progress reports with completeness that include experimental design with rigor, including assumptions for the design of the experiments, the results of the investigations, interpretations of the results, and for concluding whether milestones have been met or not. In cases when NIAAA Program staff request raw data, awardees agree to provide the data.
• Awardees agree to participate at least once a year in progress meetings (teleconferences) that are organized by NIAAA staff.
• Regarding meetings and interactions with regulatory agencies, awardees agree to communicate meeting dates and agenda to the NIAAA Program staff and invite their participation.
• Awardees agree to communicate study reports from CROs, meeting minutes (and associated data packages if applicable), letters and other forms of communications with FDA, Recombinant DNA Advisory Committee (RAC), and other authorities.

NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

• Each project will have the support of one or more Project Scientists from NIAAA Program staff who are assigned an administrative role for the alcohol-related disorder being studied and have expertise in medications development.
• The NIAAA Project Scientists will have substantial scientific/programmatic involvement during the conduct of this activity, through technical assistance, advice, and coordination above and beyond normal program stewardship for grants.
• NIAAA Project Scientist(s) provides input on the milestones and makes decisions regarding their finalization.
• NIAAA Project Scientist(s) will be responsible for assessing the progress of the project towards the specified milestones, and for recommending if further funds should be released to the project.
• NIAAA Project Scientist(s), in consultation with the PDs/PIs, may add critical experiments that need to be conducted prior to or during the award as an additional milestone(s). In most cases, these studies will be supported by additional funds from NIAAA.
• NIAAA Program Scientist(s) participates in meetings together with PDs/PIs with regulatory agencies related to the funded project.
• Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.
• NIAAA leadership will make decisions on project continuation based on Program staff recommendations, programmatic prioritizations and budget considerations. NIAAA Program staff may consult as necessary with independent consultants with relevant expertise. If justified, future year milestones may be revised based on data and information obtained during the previous year. If, based on the progress report, a funded project does not meet the milestones, funding for the project may be discontinued. In addition to milestones, the decision regarding continued funding will also be based on the overall robustness of the entire data package that adequately allows an interpretation of the results (regardless if they have been captured in the milestones), overall progress, NIAAA portfolio balance and program priorities, competitive landscape, and availability of funds.

Areas of Joint Responsibility include:

Clarifying, negotiating and finalizing the milestones and timelines.

Dispute Resolution

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: one designee chosen by the grantee and his collaborators, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16. Final decisions made by NIAAA regarding a discontinuation are not appealable

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. When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

• 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 Part III. Section 5, "SBIR/STTR Award Guidelines, Reporting Requirements, and Other Considerations, in the Supplement Grant Applications For All Competing Applications and Progress Reports.

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)
Email: [email protected] (preferred method of contact)
Telephone: 301-945-7573

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)
Finding Help Online: https://grants.nih.gov/support/index.html
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

Joanne B Fertig, Ph.D.
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-443-8774
Email: [email protected]

Ranga Srinivas, Ph. D.
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-451-2067
Email: [email protected] .

Judy Fox
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-443-4704
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 Part 75.

The STTR Program is mandated by the Small Business Reauthorization Act of 1997 (P.L. 105-135), and reauthorizing legislation, P.L. 107-50 and P.L. 112-81 (SBIR/STTR Reauthorization Act of 2011). The basic design of the NIH STTR Program is in accordance with the Small Business Administration (SBA) STTR Policy Directive.