HT942526ALSRPTIA_GG.pdf

This program announcement must be read in conjunction with the General Application Instructions, version CD26_01.

Program Announcement for the Defense Health Agency

Amyotrophic Lateral Sclerosis Research Program Therapeutic Idea Award

Funding Opportunity Number: HT942526ALSRPTIA

Pre-Application Due: June 24, 2026

Application Due: September 30, 2026 https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01

FY26 Amyotrophic Lateral Sclerosis Therapeutic Idea Award 2

Content Before You Begin 3

Basic Information Summarizes the funding opportunity, funding details, submission deadlines and review dates

Eligibility Details eligibility factors for the applicant organization and Principal Investigator

Program Description Describes the program mission and intent of the Therapeutic Idea Award; provides key award information and considerations; and outlines funding details

Application Contents Presents the two-step application process and instructions for preparing a pre-application and full application

Submission Requirements Provides locations for application packages, instructions for submitting pre-applications and full applications, and describes application verification

Application Review Information Outlines the processes for application compliance review, pre-application and full application selection/notification, and risk assessment. Also, details the review criteria for pre-application screening and both tiers of the CDMRP application review process – Peer Review and Programmatic Review

Federal Award Notices Outlines what a successful applicant can expect if recommended for funding

Post-Award Requirements References policy requirements for funded research; outlines reporting requirements and restrictions related to Principal Investigator changes and institutional award transfers

Other Information Outlines criteria for administrative actions including application rejection, modification, withdrawal and withhold

Appendix 1 Includes a checklist for all full application components to facilitate application submission

Appendix 2 Acronym List

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Before You Begin

• Active SAM.gov, eBRAP.org and Grants.gov registrations are required for application submission. User registration for each of these websites can take several weeks or longer.

Each applicant must ensure their registrations are active and up to date prior to application preparation.

• Read this funding opportunity announcement in the order it is written before beginning to prepare application materials. It is the responsibility of the applicant to determine whether the proposed research meets the intent of this funding opportunity and that all parties meet eligibility requirements.

• To support application preparation, additional resources are available including an application process FAQ, a Guide for Intragovernmental & Intramural Applicants and a CDMRP Video Series detailing the application process.

Who to Contact for Support

This document uses internal links; you can go back to where you were by pressing the Alt + left arrow keys (Windows) or command + left arrow keys (Macintosh) on your keyboard.

Click to be taken to additional guidance and instructions within the General Application Instructions (GAI).

eBRAP Help Desk

301-682-5507 help@eBRAP.org

Questions regarding funding opportunity submission requirements, as well as technical assistance related to pre-application or intramural application submission.

Grants.gov Support Center

800-518-4726 International: 1-606-545-5035 support@grants.gov

Questions regarding Grants.gov registration and Workspace.

https://sam.gov/ https://ebrap.org/eBRAP/public/index.htm https://grants.gov/register https://cdmrp.health.mil/#:%7E:text=Frequently%20Asked%20Questions%20%C2%BB https://cdmrp.health.mil/#:%7E:text=Guide%20for%20Intragovernmental%20%26%20Intramural%20Applicants https://ebrap.org/eBRAP/public/Program.htm#:%7E:text=Journey%20of%20an,Tier%20Review%20Process mailto:help@eBRAP.org mailto:support@grants.gov https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01

Section Shortcuts Basic Information | Eligibility | Program Description | Application Contents and Format | Submission Requirements Application Review Information | Federal Award Notices | Post-Award Requirements | Other Information

FY26 Amyotrophic Lateral Sclerosis Therapeutic Idea Award 4

1. Basic Information About the Funding Opportunity

Summary: The fiscal year 2026 (FY26) Amyotrophic Lateral Sclerosis Research Program (ALSRP) Therapeutic Idea Award (TIA) supports new, innovative, high-risk, high-gain ideas aimed at amyotrophic lateral sclerosis (ALS) drug or therapy discovery. The studies supported by this award mechanism are expected to be hypothesis-driven and generate preliminary data for future avenues of therapeutic investigation.

Distinctive Features: Potential impact and innovation are important features of the TIA.

Applications may demonstrate the ability to achieve interpretable results in the absence of preliminary data supporting the hypothesis. While the inclusion of preliminary data is not prohibited, the strength of the application should rely on the approach.

Funding Details: The Congressionally Directed Medical Research Programs (CDMRP) expects to allot roughly $10.08 million (M) to fund approximately 12 Therapeutic Idea Award applications with total cost caps of $840,000 per award. The maximum period of performance is two years. It is anticipated that awards made from this FY26 funding opportunity will be funded with FY26 funds, which will expire for use on September 30, 2032. Awards supported with FY26 funds will be made no later than September 30, 2027.

Submission and Review Dates and Times

• Pre-Application (Preproposal) Submission Deadline: 5:00 p.m. Eastern Time (ET), June 24, 2026

• Invitation to Submit an Application: August 3, 2026

• Application Submission Deadline: 11:59 p.m. ET, September 30, 2026

• End of Application Verification Period: 5:00 p.m. ET, October 6, 2026

• Peer Review: November 2026

• Programmatic Review: January 2027 Announcement Type: Initial Funding Opportunity Number: HT942526ALSRPTIA Assistance Listing Number: 12.420

Basic Information | Eligibility | Program Description | Application Contents and Format | Submission Requirements Application Review Information | Federal Award Notices | Post-Award Requirements | Other Information

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2. Eligibility Information

2.1. Eligible Applicants

2.1.1. Organization

Extramural and intramural U.S. Department of War (DOW) organizations are eligible to apply, including foreign and domestic organizations, for-profit and nonprofit organizations, and public or private entities.

2.1.2. Principal Investigator

Independent investigators affiliated with an eligible organization are eligible to be named Principal Investigator (PI) on the application, regardless of ethnicity, nationality or citizenship status. An investigator may be named as PI on no more than three FY26 ALSRP applications across all award mechanisms, in any combination.

For titles outside of academia that may not be analogous to traditional hierarchies, investigators at or above an independent scientist level may be named by their organization as the PI on the application.

2.2. Cost Sharing

Cost sharing is not an eligibility requirement.

2.3. Other

Awards are made to eligible organizations, not to individuals. Refer to the GAI for additional recipient qualification requirements.

https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01#_Content_Form_Full_App_Submission:%7E:text=pre%2Dapplication%20submission.-,Extramural%20Organization%3A,-A%20foreign%20or https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01#_Definition_List:%7E:text=Intramural%20DOW%20Organization%3A%20A%20subset%20of%20intragovernmental%20organizations%3B%20refers%20specifically%20to%20DOW%20organizations%2C%20including%20DOW%20laboratories%2C%20DOW%20military%20treatment%20facilities%2C%20and/or%20DOW%20activities%20embedded%20within%20a%20civilian%20medical%20center https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01#_Recipient_Qualification_Restriction_Info:%7E:text=APPENDIX%201-,RECIPIENT%20QUALIFICATION%20AND%20RESTRICTION%20INFORMATION,-A.%C2%A0%C2%A0%C2%A0%C2%A0%C2%A0%C2%A0%C2%A0%C2%A0

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3. Program Description

The Defense Health Agency Contracting Activity (DHACA) is soliciting applications to this funding opportunity using delegated authority provided by United States Code, Title 10, Section 4001 (10 USC 4001). The CDMRP is the program office managing this FY26 funding opportunity as part of the Amyotrophic Lateral Sclerosis Research Program (ALSRP). The CDMRP is located within the Defense Health Agency Research and Development (DHA R&D), which is a part of the Department of Defense, DOD, herein referred to using the secondary title Department of War, DOW. Congress initiated the ALSRP in 2007 to provide support for research of high potential impact and exceptional scientific merit. Appropriations for the ALSRP from FY07 through FY25 totaled $309.4M. The FY26 appropriation is $40.0M.

The Vision of the FY26 ALSRP is to improve outcomes and find cures for people with ALS. The Mission is to fund and accelerate research that translates science into effective ALS treatments.

The program will prioritize applications that support the vision and mission of the FY26 ALSRP.

3.1. Award History

The ALSRP Therapeutic Idea Award mechanism was first offered in FY10. Since then, 769 Therapeutic Idea Award applications were received, and 179 were recommended for funding.

3.2. Intent of the Therapeutic Idea Award

The FY26 ALSRP Therapeutic Idea Award (TIA) supports new, innovative, high-risk, high-gain ideas aimed at Amyotrophic Lateral Sclerosis (ALS) drug or therapy discovery. The studies supported by this award mechanism are expected to be hypothesis-driven and generate preliminary data for future avenues of therapeutic investigation.

The FY26 ALSRP TIA welcomes medical device studies as well as investigational drug studies.

Projects that focus primarily on pathophysiology of ALS without development of a therapy or device are outside the scope of this funding opportunity.

Applications may demonstrate the ability to achieve interpretable results in the absence of preliminary data supporting the hypothesis. While the inclusion of preliminary data is not prohibited, the strength of the application should rely on the approach.

3.2.1. Key Elements for the TIA

The key elements of this award mechanism are:

• Innovation: The proposed project should represent the exploration of a highly innovative, untested, potentially high-gain concept, theory, paradigm, and/or method(s) that may lead to future therapeutics for ALS.

• Impact: Research submitted for consideration for the FY26 TIA may address a specific ALS subtype and does not have to broadly apply to all patients. Research should be non-incremental and pioneer transformative results that could lay the foundation for a new direction in the field of ALS therapy development. Incremental advancement of ongoing research does not meet the intent of this funding opportunity.

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• Strong Scientific Rationale: Projects must include a well-formulated, testable hypothesis based on strong scientific rationale that holds translational potential to improve ALS treatment and/or advance a novel treatment modality.

• Biomarkers: Applicants are required to include rational development of a biomarker(s) to measure biological effects of the study compound or modality for eventual clinical trials.

○ Biomarkers should be specific to the therapeutic strategy’s biological mechanism and may include:

Target engagement biomarkers Objective pharmacodynamic biomarkers to measure the biological effect of the investigational therapeutic Predictive/cohort-selective biomarkers to identify patients (including individual, subgroup, or pre-symptomatic gene carriers) likely to benefit

○ Applications focused solely on developing diagnosis, prognosis, or disease progression biomarkers, without a clear link to therapeutic development, will not be supported.

Researchers pursuing such studies are encouraged to apply for the Clinical Outcomes and Biomarkers Award (HT942525ALSRPCOBA).

Applicants are encouraged to consult the following resources for additional information regarding biomarker types, qualifications, and use in ALS clinical trials:

• “National Institute of Neurological Disorders and Stroke (NINDS) Biomarker Program,”

National Institutes of Health (NIH) https://www.ninds.nih.gov/current-research/focus-tools-topics/focus-biomarkers-research

• “U.S. Food and Drug Administration (FDA) Biomarker Qualification Program,” FDA, https://www.fda.gov/drugs/drug-development-tool-ddt-qualification-programs/biomarker-qualification-program.

• FDA-NIH Biomarker Working Group, BEST (Biomarkers, EndpointS, and other Tools) Resource (U.S. Food and Drug Administration, 2016+), https://www.ncbi.nlm.nih.gov/books/NBK326791/.

• FDA Center for Drug Evaluation and Research, Amyotrophic Lateral Sclerosis: Developing Drugs for Treatment Guidance for Industry (FDA, 2019), https://www.fda.gov/regulatory-information/search-fda-guidance-documents/amyotrophic-lateral-sclerosis-developing-drugs-treatment-guidance-industry.

• Leonard H van den Berg et al, “Revised Airlie House Consensus Guidelines for Design and Implementation of ALS Clinical Trials,” Neurology 92, no. 14 (2019): e1610-e1623, https://pubmed.ncbi.nlm.nih.gov/30850440/.

• Nick S. Verber et al, “Biomarkers in Motor Neuron Disease: A State of the Art Review,” Frontiers in Neurology 10 (2019): 291, https://www.frontiersin.org/articles/10.3389/fneur.2019.00291/full.

• Michael Benatar et al, “ALS Biomarkers for Therapy Development: State of the Field and Future Directions,” Muscle Nerve 53, no. 2 (2016): 169-182, https://doi.org/10.1002/mus.24979.

Expected Outcomes: Projects should strive to produce the type and amount of data needed to apply for the next stage of therapy development, i.e., ALSRP Therapeutic Development Award or other mechanisms for ALS therapeutic advancement.

https://www.ninds.nih.gov/current-research/focus-tools-topics/focus-biomarkers-research https://www.ninds.nih.gov/current-research/focus-tools-topics/focus-biomarkers-research https://www.fda.gov/drugs/drug-development-tool-ddt-qualification-programs/biomarker-qualification-program https://www.fda.gov/drugs/drug-development-tool-ddt-qualification-programs/biomarker-qualification-program https://www.ncbi.nlm.nih.gov/books/NBK326791/ https://www.fda.gov/regulatory-information/search-fda-guidance-documents/amyotrophic-lateral-sclerosis-developing-drugs-treatment-guidance-industry https://www.fda.gov/regulatory-information/search-fda-guidance-documents/amyotrophic-lateral-sclerosis-developing-drugs-treatment-guidance-industry https://www.fda.gov/regulatory-information/search-fda-guidance-documents/amyotrophic-lateral-sclerosis-developing-drugs-treatment-guidance-industry https://pubmed.ncbi.nlm.nih.gov/30850440/ https://www.frontiersin.org/articles/10.3389/fneur.2019.00291/full https://doi.org/10.1002/mus.24979

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3.2.2. Other Important Considerations for the TIA

The ALSRP aims to improve the health, care, and well-being of military Service Members, Veterans, their families, and the American public affected by ALS. Evidence from scientific research suggests a mutually inclusive relationship between ALS and military service, with a higher rate of incidence in the Veteran population, without any known reasons for this incidence.

Knowledge, information, products, or technologies gained from the proposed research should advance research that is of significance to Service Members, Veterans, and/or their Families.

In accordance with the National Defense Authorization Act for Fiscal Year 2026, Section 732, the CDMRP does not support the conduct of painful research (U.S. Department of Agriculture pain category D or E) involving domestic cats or dogs, except for studies relating to military or service animals.

Standards for Preclinical Study Design: All projects should adhere to a core set of standards for rigorous study design and reporting to maximize the reproducibility and translational potential of preclinical research. All projects should adhere to a core set of standards for rigorous study design and reporting to maximize the reproducibility and translational potential of clinical and preclinical research, such as those described in the STROBE, CONSORT, SPIRIT and ARRIVE

2.0 guidelines. Projects that include research on animal models are required to submit Attachment 9, Animal Research Plan, as part of the application package to describe how these standards will be addressed.

Guidelines for the Use of ALS Animal Models: Many factors must be considered in the design of studies using animal models of ALS. A number of investigators and organizations have published guidelines and recommendations for the design of ALS animal model studies.

Applicants are strongly encouraged to become familiar with the concepts presented in the articles listed below and to incorporate recommendations contained therein in their study designs. While most of the recommendations pertain to the SOD1-G93A transgenic mouse model, many general concepts for using animal models for ALS research are also described.

• Albert C. Ludolph et al, “Guidelines for Preclinical Animal Research in ALS/MND: A

Consensus Meeting,” Amyotrophic Lateral Sclerosis 11 (2010): 38-45.

https://dx.doi.org/10.3109/17482960903545334

• Sean Scott et al, “Design, Power, and Interpretation of Studies in the Standard Murine Model of ALS,” Amyotrophic Lateral Sclerosis 9 (2008): 4-15.

https://dx.doi.org/10.1080/17482960701856300

• Albert C. Ludolph et al, “Guidelines for the Preclinical in vivo Evaluation of Pharmacological Active Drugs for ALS/MND: Report on the 142nd ENMC International Workshop,” Amyotrophic Lateral Sclerosis 8 (2007): 217-223.

https://dx.doi.org/10.1080/17482960701292837

Clinical trials are not allowed within this funding opportunity.

For biomarker development efforts proposing to use large datasets for training predictive models, a discussion of mechanisms for addressing rigor in model design, training, and assessment should be provided. Depending upon the context, this might include algorithmic designs to avoid overfitting, saliency analysis, feature attribution, node ablation, or other alternate strategies.

Precision medicine approaches based on results from long-read sequencing and epigenetic profiling are strongly encouraged.

https://www.strobe-statement.org/ https://www.nature.com/articles/s41591-025-03635-5#:%7E:text=SPIRIT%20and%20CONSORT%20are%20evidence,relevant%20empirical%20evidence%20where%20possible https://www.nature.com/articles/s41591-025-03668-w?fromPaywallRec=false https://arriveguidelines.org/arrive-guidelines https://arriveguidelines.org/arrive-guidelines https://dx.doi.org/10.3109/17482960903545334 https://dx.doi.org/10.1080/17482960701856300 https://dx.doi.org/10.1080/17482960701292837 https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01#_Definition_List:%7E:text=or%20hardware%20procurement.-,Clinical%20Trial%3A,-As%20defined%20in

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Applications from investigators within the DOW and applications involving multidisciplinary collaborations among academia, industry, the DOW, the U.S. Department of Veterans Affairs (VA) and other federal government agencies are encouraged. These relationships can leverage knowledge, infrastructure and access to unique clinical populations that the collaborators bring to the research effort, ultimately advancing research that is of significance to Service Members, Veterans, their Families and the American public. If the proposed research relies on access to unique resources or databases, the application must describe the access at the time of submission and include a plan for maintaining access as needed throughout the proposed research.

3.3. Funding Instrument

The funding instrument for awards made under the program announcement will be grants

(31 USC 6304).

3.4. Funding Details

Period of Performance: The maximum period of performance is two years.

Cost Cap: The application’s total costs budgeted for the entire period of performance should not exceed $840,000. If indirect cost rates have been negotiated, indirect costs are to be budgeted in accordance with the organization’s negotiated rate. Collaborating organizations should budget associated indirect costs in accordance with each organization’s negotiated rate.

All direct and indirect costs of any subaward or contract must be included in the direct costs of the primary award.

The applicant may request the entire maximum funding amount for a project that may have a period of performance less than the maximum two years.

The appropriateness of the budget for the proposed research will be assessed during peer review.

Direct Cost Restrictions: For this award mechanism, direct costs:

May be requested for (not all-inclusive):

• Travel in support of multi-institutional collaborations.

• Costs for one investigator to travel to one scientific/technical meeting per year. The intent of travel to scientific/technical meetings should be to present project information or disseminate project results from the ALSRP Therapeutic Idea Award.

Must not be requested for:

• Costs for travel to scientific/technical meeting(s) beyond the limits stated above.

https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01#_Recipient_Qualification_Restriction_Info:%7E:text=Period%20of%20Performance%3A%20The%20time%20interval%20between%20the%20start%20of%20a%20federal%20award%20and%20the%20planned%20end%20date.

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4. Application Contents and Format

4.1. Application Overview

Application submission is a two-step process requiring both a pre-application submitted via the Electronic Biomedical Research Application Portal (eBRAP) and a full application submitted through eBRAP or Grants.gov. Depending on the submission portal, certain aspects of the application will differ.

Intramural DOD organizations submitting a full application should follow instructions for submission through eBRAP.

Extramural organizations submitting a full application must follow instructions for submission through Grants.gov.

4.2. Pre-Application Components

Pre-application submissions must include the following components.

Upload documents as individual PDF files unless otherwise noted. Files must comply with the formatting guidelines listed in the GAI.

• Preproposal Narrative (three-page limit): The Preproposal Narrative page limit applies to text and non-text elements (e.g., figures, tables, graphs, photographs, diagrams, chemical structures, drawings) used to describe the project. Inclusion of URLs that provide additional information to expand the Preproposal Narrative and could confer an unfair competitive advantage is prohibited and may result in administrative withdrawal of the pre-application.

The Preproposal Narrative should include the following:

○ Innovation: Describe how the project explores a highly innovative, untested, potentially high-gain concept, theory, paradigm, and/or method that may lead to future therapeutics for ALS. Innovative uses or investigations of previously developed resources are acceptable. Research that is an incremental advance upon published data is not considered innovative.

○ Impact: State explicitly how the proposed work will have an impact on the development of therapeutics for ALS and on patient populations. Outline, in general terms, how the proposed research may lay the foundation for a new direction in ALS therapy development and the next steps to transition the study outcomes to therapeutic application(s).

○ Research Strategy and Feasibility: Explain the rationale for selecting the specific target(s) for investigation. Concisely state the project’s objectives and specific aims.

Describe how the proposed experiments demonstrate the testability of the hypothesis.

Describe the high-risk/high-gain nature of the testable hypothesis to be investigated. If animal models are to be used, describe the selected model and its relevance to the hypothesis. Explain the feasibility of the study leading to a therapy for ALS.

○ Biomarker Rationale: Describe the proposed biomarker, the proposed contexts of use, and the biological rationale for the proposed biomarker, including feasibility and regulatory considerations for eventual use in ALS clinical trials. Describe the extent to which study results will be used to steer the therapeutic development process.

https://ebrap.org/eBRAP/public/index.htm https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01#Appendix2:%7E:text=APPENDIX%202.%0AFORMATTING%20GUIDELINES https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01#_Full_App_Submission_Grants:%7E:text=IV.%C2%A0%C2%A0%C2%A0%C2%A0%C2%A0%C2%A0%C2%A0%20FULL%20APPLICATION%20SUBMISSION%20THROUGH%20GRANTS.GOV https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01#_Full_App_Submission_eBRAP:%7E:text=V.%C2%A0%C2%A0%C2%A0%C2%A0%C2%A0%C2%A0%C2%A0%C2%A0%C2%A0%20FULL%20APPLICATION%20SUBMISSION%20THROUGH%20eBRAP

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• Pre-Application Supporting Documentation: The items to be included as supporting documentation for the pre-application must be uploaded as individual files and are limited to the following:

○ References Cited (one-page limit): List the references cited (including URLs if available) in the Preproposal Narrative using a standard reference format that includes the full citation (i.e., author[s], year published, reference title, and reference source, including volume, chapter, page numbers, and publisher, as appropriate).

○ List of Abbreviations, Acronyms and Symbols: Provide a list of abbreviations, acronyms, and symbols used in the Preproposal Narrative.

○ Key Personnel Biographical Sketches: All biographical sketches should be uploaded as a single combined file. Biographical sketches should be used to demonstrate background and expertise through education, positions, publications, and previous work accomplished.

4.3. Full Application Components

Applicants must receive an invitation to submit a full application. Uninvited full application submissions will be rejected.

Each application submission must include the completed full application package for this program announcement. See Appendix 1 for a checklist of the full application components.

(a) SF424 Research & Related Application for Federal Assistance Form (Grants.gov submissions only):

IMPORTANT: When completing the SF424 R&R, enter the eBRAP log number assigned during pre-application submission into Block 4a – Federal Identifier.

(b) Attachments:

Each attachment of the full application components must be uploaded as an individual file in the format specified and in accordance with the formatting guidelines in the GAI.

○ Attachment 1: Project Narrative (12-page limit): Upload as

“ProjectNarrative.pdf”.

Describe the proposed project in detail using the outline below.

Innovation: Describe how the project may introduce a new paradigm, challenge current paradigms, introduce novel concepts or agents, or exhibit other uniquely creative qualities that may lead to potential therapeutics for ALS. For hypothesis-generating research that may be high-risk, clearly describe the potential gain and anticipated advancements in ALS therapeutic development. This may include a description of novel applications or investigations of a previously developed resource.

Scientific Rationale: Present the scientific rationale behind the proposed work.

State the specific aims of the study. Explain how the novel idea is supported by sound logical reasoning and strong scientific rationale. Cite relevant published literature and, if applicable, any preliminary data (preliminary data are not required; if preliminary data are provided, the details should include statistical analysis).

Applicants from outside the ALS research field are encouraged to include collaborators with the necessary relevant expertise, such as experience with ALS model systems, endpoints and pathogenic findings.

https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01#_Recipient_Qualification_Restriction_Info:%7E:text=APPENDIX%202.%0AFORMATTING%20GUIDELINES https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01#_Recipient_Qualification_Restriction_Info:%7E:text=(a)%C2%A0%C2%A0%C2%A0%C2%A0%C2%A0%C2%A0%20SF424%20(R%26R)%20%E2%80%93%20Application%20for%20Federal%20Assistance%20Form https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01#_Recipient_Qualification_Restriction_Info:%7E:text=%C2%B7-,Project%20Narrative%3A,-Attach%20as%20%E2%80%9CProjectNarrative https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01#_Content_Form_Full_App_Submission:%7E:text=eBRAP%20User%20Name-,Biographical%20Sketch,-%3A%20This%20file

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Study Personnel Description: Describe the composition of the study team in enough detail to determine whether the team includes relevant subject matter expertise to accomplish the proposed work. Include the roles of individuals named in the organizational chart along with any external consultants or advisors who will provide critical guidance and input to the study team (e.g., statistician, biomarker interpretation expert, patient advocate/community partner). Early-career investigators or applicants from outside the ALS research field are encouraged to include collaborators with the necessary relevant expertise, such as experience with ALS model systems, endpoints and pathogenic findings, as part of the research team.

Hypothesis or Objective: State the hypothesis(es) to be tested or the objective(s) to be reached.

Research Strategy and Feasibility: Describe the experimental design, methods, and analyses (including appropriate controls) in sufficient detail for analysis.

Explain how the proposed tools or models are suited to, and will be used for, preclinical testing or development of therapeutics, as opposed to basic pathophysiology research.

Include qualitative milestones and control measures to assess the study’s success and ensure progress toward the stated objectives.

Applications involving artificial intelligence should include details regarding the specific platforms and approaches that will be implemented.

If applicable, discuss how well any animal studies consider the published guidelines for working with ALS animal models and are designed to achieve the objectives, including the relevance of the model and endpoints/outcome measures to be used.

Address potential problem areas and present alternative methods and approaches. Because the TIA mechanism is designed to support high risk/high gain research, hypotheses may prove incorrect, but the proposed experiments must be feasible and designed to adequately test the hypotheses. The “risk” should not be whether the experiments will work, but rather whether the novel therapeutic hypothesis is valid. Consult appropriate guidelines to ensure relevant aspects of rigorous and reproducible research are adequately planned for and, ultimately, reported.

Next Steps: Describe the next steps to transition the study outcomes into further therapeutic application(s). Include how the project will produce the type and amount of data needed to apply for the next stage, i.e., ALSRP Therapeutic Development Award or other mechanisms to continue the advancement of the ALS therapeutic.

Biomarker: Briefly introduce the biomarker and its Contexts of Use. Additional details of the marker effort should be provided in Attachment 8, Biomarker Statement.

If the proposed research involves access to military and/or VA patient populations and/or DOW or VA resources or databases, describe the access at the time of submission and include a plan for maintaining access as needed throughout the proposed research. Also include a plan for obtaining any required data sharing, memorandum of understanding or other agreements required to access and publish data. Refer to the GAI, Appendix 4, for additional considerations.

https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01#_Use_Of_DOW_Dept_Veterans_Affairs_Resource:%7E:text=APPENDIX%204.%0AUSE%20OF%20DOW%20OR%20U.S.%20DEPARTMENT%20OF%20VETERANS%20AFFAIRS%20RESOURCES

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FY26 Amyotrophic Lateral Sclerosis Therapeutic Idea Award 13

○ Attachment 2: Supporting Documentation: Combine and upload as a single file named “Support.pdf”.

There are no page limits for these components unless otherwise noted. Include only components described below; inclusion of items not requested or viewed as an extension of the Project Narrative will result in the removal of those items or may result in administrative withdrawal of the application.

References Cited: List the references cited in the Project Narrative using a standard reference format (include URLs, if available).

List of Abbreviations, Acronyms and Symbols: Provide a list of abbreviations, acronyms and symbols.

Facilities, Existing Equipment and Other Resources: Describe the facilities and equipment available for performance of the proposed project; include any additional facilities or equipment proposed for acquisition at no cost to the award. Indicate whether government-furnished facilities or equipment are proposed for use. If so, reference the original or present government award under which the facilities or equipment items are now accountable. A standardized form for this information does not exist.

Publications and/or Patents: Include a list of relevant publication URLs and/or patent abstracts. If articles are not publicly available, then copies of up to five published manuscripts may be included in Attachment 2. Extra items will not be reviewed.

Letters of Support (two-page limit per letter is recommended): Provide individual letters signed by collaborating individuals and/or organizational officials demonstrating that the PI has the support and resources necessary for the proposed work. Letters from the PI’s Department Chair, or appropriate organization official, should also confirm that the PI(s) meet eligibility criteria. If applicable, provide a letter of support, signed by the lowest-ranking person with approval authority, confirming participation of intramural DOW collaborator(s) and/or access to military populations, databases or DOW resources. If applicable, provide a letter of support signed by the VA Facility Director(s), or an individual designated by the VA Facility Director(s), confirming access to VA patients, resources and/or VA research space.

Sex as a Biological Variable Strategy (two-page limit is recommended):

Describe the strategy for how sex will be considered as a biological variable. This strategy should include a brief discussion of what is currently known regarding sex differences in the applicable research area. Clearly articulate how sex as a biological variable will be factored into the data analysis plan and how data will be collected and disaggregated by sex. If needed, provide a strong rationale for proposing a single-sex study, based on justification from scientific literature, preliminary data or other relevant considerations. Refer to the CDMRP Directive on Sex as a Biological Variable in Research for additional information.

○ Attachment 3: Technical Abstract (one-page limit): Upload as “TechAbs.pdf”.

Write the technical abstract using the outline below. Clarity and completeness within the space limits are highly important.

https://cdmrp.health.mil/pubs/pdf/CDMRP%20SABV%20Directive_Revised_MAR2025_signed.pdf https://cdmrp.health.mil/pubs/pdf/CDMRP%20SABV%20Directive_Revised_MAR2025_signed.pdf https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01#_Recipient_Qualification_Restriction_Info:%7E:text=%C2%B7-,Supporting%20Documentation%3A,-Combine%20and%20attach https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01#_Recipient_Qualification_Restriction_Info:%7E:text=%C2%B7-,Technical%20Abstract%3A,-Attach%20as%20%E2%80%9CTechAbs

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FY26 Amyotrophic Lateral Sclerosis Therapeutic Idea Award 14

Background: Present the scientific rationale behind the proposed research project.

Clearly define the goals of the effort/study as it relates to ALS drug or therapy discovery.

Hypothesis/Objective(s): State the hypothesis to be tested and/or objective(s) to be reached.

Specific Aims: State the specific aims of the study.

Study Design: Describe the study design, including appropriate controls.

Impact and Innovation: Briefly describe how the research is innovative and/or impactful, highlighting its potential to advance future avenues of therapeutic investigation.

Biomarker(s): State the biomarker to be investigated within the study.

Relevance to Military Health: Briefly describe how the proposed research is relevant to Service Members, Veterans and their Families.

○ Attachment 4: Lay Abstract (one-page limit): Upload as “LayAbs.pdf”.

The lay abstract should address the points outlined below in a manner that is readily understood by readers without a background in science or medicine. Avoid overuse of scientific jargon, acronyms and abbreviations. Do not duplicate the technical abstract.

– Summarize the goals, objectives, and rationale for the proposed research as it relates to ALS drug or therapy discovery.

– What types(s) of ALS patients will the research help, and how will it help them?

– What are the potential applications, benefits and risks of the anticipated outcomes?

– How is the proposed research innovative?

– What are the likely contributions of the proposed research project to advancing research, patient care and/or quality of life?

– How is the proposed research relevant to Service Members, Veterans and their

Families?

○ Attachment 5: Statement of Work (three-page limit): Upload as “SOW.pdf”.

Refer to eBRAP for the Suggested SOW Format.

For guidance on preparing the SOW, refer to Example: Assembling a Generic Statement of Work. Include milestones for data or research resource(s) sharing.

○ Attachment 6: Impact Statement (one-page limit): Upload as “Impact.pdf”. Describe how the proposed work will impact development of therapeutics for ALS. Articulate a pathway to making a clinical impact for individuals with, or at risk for, ALS. Impact should address the points outlined below in a manner that will be readily understood by readers without a background in science or medicine. Avoid overuse of scientific jargon, acronyms and abbreviations.

Specifically highlight how the research will achieve the following by the end of the performance period:

– Advance the development of a groundbreaking ALS therapeutic, including for specific subset populations.

https://ebrap.org/eBRAP/public/Program.htm#:%7E:text=Suggested%20SOW%20Format https://ebrap.org/eBRAP/public/Program.htm#:%7E:text=Example%3A%20Assembling%20a%20Generic%20Statement%20of%20Work https://ebrap.org/eBRAP/public/Program.htm#:%7E:text=Example%3A%20Assembling%20a%20Generic%20Statement%20of%20Work https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01#_Recipient_Qualification_Restriction_Info:%7E:text=%C2%B7-,Lay%20Abstract%3A,-Attach%20as%20%E2%80%9CLayAbs https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01#_Recipient_Qualification_Restriction_Info:%7E:text=%C2%B7-,Statement%20of%20Work%3A,-Attach%20as%20%E2%80%9CSOW

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FY26 Amyotrophic Lateral Sclerosis Therapeutic Idea Award 15

– Show potential for application in the clinic and ultimate impact on ALS patient populations.

– Advance biomarkers with the potential for meaningful treatment outcomes in parallel with the main therapeutic development effort.

– Describe how knowledge, information, products, or technologies gained from the proposed research is of significance to Service Members, Veterans and/or their Families.

– If applicable, describe how the anticipated outcomes of the proposed study will make an impact in understanding health differences between sexes.

Key points may be bulleted to emphasize the main study goals. Inclusion of a simple diagram of the proposed study, if plausible, is encouraged.

○ Attachment 7: Data and Research Resources Sharing Plan (one-page limit):

Upload as “Sharing.pdf”. Describe how data and resources generated during the performance of the project will be shared with the research community. Describe whether the proposed plan for data sharing includes existing, publicly available, curated ALS repositories/data platforms or other resources with relevant repository parameters and mechanisms for broad access to data and samples; and whether the plan describes organizational and technical capabilities sufficient to share project data in a timely manner. Identify and provide the rationale for any data or resources that will not be shared (e.g., for intellectual property, feasibility, cost, or other considerations). A list of suitable resources can be found on the ALSRP web page.

Do not submit a copy of the NIH Data Management and Sharing Plan or duplicate the Data Management Plan which will be requested only after a recommendation for funding is made.

Refer to the CDMRP Directive on Sharing Data and Research Resources for more information about the CDMRP’s expectations for making data and research resources publicly available. The government reserves the right to identify repositories for submission of data for archive. Any costs associated with submission will be addressed during award negotiations. Note that this document may be used in programmatic review deliberations.

○ Attachment 8: Biomarker Statement (four-page limit): Upload as “Biomarker.pdf”.

Preliminary biomarker characterization must address qualification criteria described in relevant ALS biomarker literature. See Section 3.2.1, Key Elements for the TIA, for more information on relevant ALS biomarker literature.

Provide the following information:

– Biomarker(s) Description: Describe the biomarker(s) and the theoretical or empirical basis for its potential utility. Biomarkers may reference levels of analytes in fluids or samples, radiologically measured parameters, or any other objectively measured values used to reach a single interpretation. Specify the aspect of the biomarker that is measured and the form in which it is used for biological interpretation.

– Purpose in ALS Drug Development: Describe how the proposed marker(s) will demonstrate target engagement, help refine individual patient or patient subgroup selection, and/or clarify the mechanism-specific biological impact of the novel ALS therapeutic. Describe the extent to which the marker results will be used to steer the development process. Describe potential regulatory considerations for use in ALS https://cdmrp.health.mil/alsrp/resources/FY24%20ALSRP%20Research%20Resource%20database%2020240410.pdf https://ebrap.org/eBRAP/public/Program.htm#:%7E:text=Directive%20on%20Sharing%20Data%20and%20Research%20Resources

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FY26 Amyotrophic Lateral Sclerosis Therapeutic Idea Award 16 clinical trials. Explain how the biomarker characterization addresses qualification criteria described in relevant ALS biomarker literature.

– Describe how easily and reliably the biomarker may be implemented in eventual clinical trials of the proposed novel therapeutic, including regulatory considerations.

– The inclusion of a decision-tree diagram that explicitly illustrates the application of the biomarker(s) and includes the actions that would be taken based on the results is recommended.

○ Attachment 9: Animal Research Plan (three-page limit), if applicable: Upload as “AnimalPlan.pdf”. Attachment 9 is only applicable and required for applications proposing animal studies. If the proposed study involves animals, a summary describing the animal research that will be conducted must be included in the application. Consult the ARRIVE guidelines 2.0 (Animal Research: Reporting In Vivo Experiments) to ensure relevant aspects of rigorous animal research are adequately planned for and, ultimately, reported. The Animal Research Plan may not be an exact replica of the protocol(s) submitted to the Institutional Animal Care and Use Committee (IACUC). The Animal Research Plan should address the following points to achieve reproducible and rigorous results for each proposed animal study:

– Describe consideration of the guidelines for working with ALS animal models.

– Briefly describe the research objective(s) of the animal study. Explain how and why the animal species, strain, and model(s) being used can address the scientific objectives and, where appropriate, the study’s relevance to human biology.

– For efficacy studies, provide the rationale for the dose and route of administration for the drug(s).

– Summarize the procedures to be conducted. Describe how the study will be controlled.

– Describe the randomization and blinding procedures for the study, and any other measures to be taken to minimize the effects of subjective bias during animal treatment and assessment of results. If randomization and/or blinding will not be utilized, provide justification.

– Provide a sample size estimate for each study arm and the method by which it was derived, including power analysis calculations.

– Describe how data will be handled, including rules for stopping data collection, criteria for inclusion and exclusion of data, how outliers will be defined and handled, statistical methods for data analysis and identification of the primary endpoint(s).

○ Attachment 10: Representations (Grants.gov submissions only): Upload as “RequiredReps.pdf”. All extramural applicants must complete and submit the Required Representations document available on eBRAP.

○ Attachment 11: Suggested Intragovernmental/Intramural Budget Form (if applicable): Upload as “IGBudget.pdf”. If an intramural DOW organization will be a collaborator in the performance of the project, complete a separate budget for that organization using the Suggested Intragovernmental/Intramural Budget form available on eBRAP.

https://arriveguidelines.org/arrive-guidelines https://ebrap.org/eBRAP/public/Program.htm#:%7E:text=Required%20Representations https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01#_Definition_List:%7E:text=federal%20government%20organization.-,Intramural%20DOW%20Organization%3A,-A%20subset%20of https://ebrap.org/eBRAP/public/Program.htm#:%7E:text=Suggested%20Intragovernmental/Intramural%20Budget https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01#_Recipient_Qualification_Restriction_Info:%7E:text=B.%C2%A0%C2%A0%C2%A0%C2%A0%C2%A0%C2%A0%C2%A0%C2%A0%20Representations https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01#_Recipient_Qualification_Restriction_Info:%7E:text=Suggested%20Intragovernmental/Intramural%20Budget%20Form%2C%20if%20applicable%3A

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FY26 Amyotrophic Lateral Sclerosis Therapeutic Idea Award 17

(c) Additional Application Materials:

The following are additional forms for application submission. Follow the instructions specific to the submission portal, as found within the GAI.

i. Research & Related Senior/Key Person Profile (Expanded)

○ Biographical Sketch

○ Current/Pending Support

Intragovernmental applicants must include their internally supported research and development programs.

ii. Research &…