HT942526ALSRPTDA_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 Development Award

Funding Opportunity Number: HT942526ALSRPTDA

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 Development 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 Development 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/#:~:text=Frequently%20Asked%20Questions%20%C2%BB https://cdmrp.health.mil/#:~:text=Guide%20for%20Intragovernmental%20%26%20Intramural%20Applicants https://ebrap.org/eBRAP/public/Program.htm#:~: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 Development Award 4

1. Basic Information About the Funding Opportunity

Summary: The fiscal year 2026 (FY26) Amyotrophic Lateral Sclerosis Research Program (ALSRP) Therapeutic Development Award (TDA) supports research ranging from preclinical validation of therapeutic leads through U.S. Food and Drug Administration (FDA) Investigational New Drug (IND)-enabling studies. The proposed studies are expected to be empirical in nature and product-driven. Applicants with limited amyotrophic lateral sclerosis (ALS) experience are strongly encouraged to include collaborators with substantial experience in the relevant ALS model systems, endpoints and pathophysiology.

Applications supported by this award must begin with lead compounds in hand and must already demonstrate proof-of-concept efficacy data in at least one appropriate preclinical model system of ALS, including whole-animal and cellular model systems.

Distinctive Features: Mechanism-specific, predictive/cohort-selective, target engagement and pharmacodynamic biomarker development, in parallel to the main therapeutic effort, is a critical component of the FY26 ALSRP Therapeutic Development Award. If appropriate mechanism-specific biomarkers are already available or currently in development, how the existing biomarkers will improve trial design, patient selection, and efficiency or interpretation of the proposed ALS therapeutic approach must be apparent in the application. Development of biomarkers for the purposes of diagnosis, prognosis, or measurement of general disease progression without consideration of the therapeutic development process will not be supported.

Therapeutic candidates which have already been granted an IND are not appropriate for this mechanism.

Funding Details: The Congressionally Directed Medical Research Programs (CDMRP) expects to allot roughly $12.0 million (M) to fund approximately six Therapeutic Development Award applications with total cost caps of $2.0M per award. The maximum period of performance is three 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: HT942526ALSRPTDA

Assistance Listing Number: 12.420

Basic Information | Eligibility | Program Description | Application Contents and Format | Submission Requirements

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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:~:text=pre%2Dapplication%20submission.-,Extramural%20Organization%3A,-A%20foreign%20or https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01#_Definition_List:~: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:~: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 Development Award mechanism was first offered in FY07. Since then, 313 Therapeutic Development Award applications were received, and 49 were recommended for funding.

3.2. Intent of the Therapeutic Development Award

The FY26 ALSRP Therapeutic Development Award supports research ranging from preclinical validation of therapeutic leads through FDA IND-enabling studies. The proposed studies are expected to be empirical in nature and product-driven. Applicants with limited ALS experience are strongly encouraged to include collaborators with substantial experience in the relevant ALS model systems, endpoints and pathophysiology. Candidate therapeutics that already have been granted an IND are not appropriate for the TDA.

Applications supported by this award must begin with lead compounds in hand and must already demonstrate proof-of-concept efficacy data in at least one appropriate preclinical model system of ALS, including whole-animal and cellular model systems.

Examples of activities that will be supported by this award include:

• Lead optimization, including confirmation of candidate therapeutics obtained from screening or by other means, such as optimization of potency and pharmacological properties and testing of derivatives and sister compounds.

• Validation of preliminary efficacy findings, building on initial discoveries from pilot studies through expansion on assessed ALS model systems, extended dose-response characterization or extended timepoints to more robustly establish therapeutic potential.

• IND-enabling studies to include: compound characterization; absorption, distribution, metabolism, and excretion studies; studies on formulation and stability leading to Good Manufacturing Practice (GMP) production methods; and dose/response and toxicology studies in relevant model systems.

• Confirmation of candidate therapeutics obtained from screening or by other means, including optimization of potency and pharmacological properties and testing of derivatives and sister compounds.

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Applications supported by this award must begin with lead compounds in hand and must include preliminary data relevant to the phase of development, such as:

• Proof of identity and purity.

• Selectivity for the intended target over closely related targets.

• Availability of primary and secondary in vitro bioactivity assays for optimization or structure– activity relationship studies.

• Availability of clear efficacy data in at least one appropriate preclinical ALS model, with adequate power and methods.

3.2.1. Key Elements for the TDA

Mechanism-specific, predictive/cohort-selective, target engagement, and pharmacodynamic biomarker development, in parallel to the main therapeutic effort, is a critical component of the FY26 ALSRP Therapeutic Development Award (TDA).

If appropriate mechanism-specific biomarkers are already available or currently in development, how the existing biomarkers will improve trial design, patient selection, and efficiency or interpretation of the proposed ALS therapeutic approach must be apparent in the application.

Development of biomarkers for the purposes of diagnosis, prognosis, or measurement of general disease progression without consideration of the therapeutic development process will not be supported. Applicants seeking support for biomarker development independent of therapeutic development are encouraged to apply for the FY26 ALSRP Clinical Outcomes and Biomarkers Award (Funding Opportunity Number HT942526ALSRPCOBA).

Applicants are encouraged to consult the following resources for additional information regarding biomarker Context of Use (COU) in ALS clinical trials:

• 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.

For further information on new drug applications, biologics license applications, or applications for supplemental indications on the evidence to be provided to demonstrate effectiveness, it is recommended that applicants consult the following resource:

• FDA Center for Biologics Evaluation and Research, Demonstrating Substantial Evidence of Effectiveness for Human Drug and Biological Products (FDA, 2019), 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

Basic Information | Eligibility | Program Description | Application Contents and Format | Submission Requirements

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FY26 Amyotrophic Lateral Sclerosis Therapeutic Development Award 8 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/demonstrating-substantial-evidence-effectiveness-human-drug-and-biological-products.

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.

3.2.2. Other Important Considerations for the TDA

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 relationship between ALS and military service, with a higher rate of incidence in the Veteran population, without any known reason(s) 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, 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.

Clinical trials are not allowed within this funding opportunity. However, validation of treatment approaches in appropriately powered and controlled studies using biological correlates of disease activity and progression in preexisting, de-identified human specimens from well-characterized patient cohorts is permitted and is encouraged. Examples of acceptable sources for preexisting biosamples or datasets include controlled clinical trials, observational studies, publicly available biorepositories, and registries. A list of suitable resources can be found on the ALSRP web page. Other resources may be used, provided they have an adequate description of repository parameters and mechanisms for broad access. Active-duty military and/or Veteran patient populations or resources should be considered.

All clinical specimens must exist at the time of application submission; collection of new specimens will not be supported.

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.

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 highly 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).

https://www.fda.gov/regulatory-information/search-fda-guidance-documents/demonstrating-substantial-evidence-effectiveness-human-drug-and-biological-products https://www.fda.gov/regulatory-information/search-fda-guidance-documents/demonstrating-substantial-evidence-effectiveness-human-drug-and-biological-products https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01#_Definition_List:~:text=or%20hardware%20procurement.-,Clinical%20Trial%3A,-As%20defined%20in https://cdmrp.health.mil/alsrp/resources/FY24%20ALSRP%20Research%20Resource%20database%2020240410.pdf https://www.strobe-statement.org/ https://www.nature.com/articles/s41591-025-03635-5#:~: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

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3.4. Funding Details

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

Cost Cap: The application’s total costs budgeted for the entire period of performance should not exceed $2.0M. 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 three 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 Development 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:~: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 DOW 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:

○ Rationale for Candidate Therapeutic: Concisely state the project’s objectives to support development of a candidate therapeutic. Describe the lead compound(s) already in hand and include preliminary data relevant to the phase of development, including relevant physical, chemical, and/or biological properties and efficacy in at least one relevant ALS model with adequate power and methods.

○ Clinical Impact: State explicitly how the proposed work will have significant clinical impact on the target population, including specific ALS subtypes. Outline, in general terms, steps to transition the study outcomes to therapeutic application.

○ Research Strategy (including a biomarker-driven approach): Describe the project’s specific aims supporting development of a candidate therapeutic. Mechanism-specific predictive/cohort-selective, target engagement, and pharmacodynamic biomarker development, in parallel to the main therapeutic effort, is a critical component of the research strategy. If mechanism-specific biomarkers are already available or currently in development, how the existing biomarkers will improve trial study design, patient selection, and efficiency or interpretation of the proposed ALS therapeutic approach must be described. The existence or inclusion of mechanism-specific biomarker development in the Research Strategy is a requirement for all Therapeutic Development Award applications, including research strategies focused on translational efficacy or on Chemistry, Manufacturing and Controls processes.

https://ebrap.org/eBRAP/public/index.htm https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01#Appendix2:~:text=APPENDIX%202.%0AFORMATTING%20GUIDELINES https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01#_Full_App_Submission_Grants:~: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:~: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.

– Rationale for Candidate Therapeutic: Provide background information supporting validation and further development of a proposed lead compound(s) and its putative mechanism of action as a viable therapeutic approach. Explain how the proposed study is empirical in nature and product driven.

▪ Confirm whether the lead compound(s) is already in hand. Provide the chemical (or biological) identities of the lead molecules(s) or limited group of specific lead compounds.

▪ Provide proof of identity and purity of the lead(s) (for small molecules, typically >95% by nuclear magnetic resonance, liquid chromatography-mass spectrometry [LC-MS], melting point, etc., with no single impurity >0.5%. For biologics, often by high-performance liquid chromatography, LC-MS, immunochemistry, nucleotide or amino acid sequence analysis, etc.). Describe other physical, chemical, and/or biological properties of the lead(s) as appropriate.

▪ Provide clear efficacy data in at least one relevant preclinical ALS model, with adequate power analysis data and brief description of methods.

https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01#_Recipient_Qualification_Restriction_Info:~:text=APPENDIX%202.%0AFORMATTING%20GUIDELINES https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01#_Recipient_Qualification_Restriction_Info:~: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:~: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:~:text=eBRAP%20User%20Name-,Biographical%20Sketch,-%3A%20This%20file

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– Hypothesis or Objective: State the hypothesis to be tested or the objective to be reached.

– Research Strategy and Specific Aims: Concisely explain the project’s specific aims to be funded by this award. Provide a well-developed, well-integrated research plan that explains how the research plan will meet the research goals and milestones. Describe the study design, methods, models, and analyses (including statistical analysis of appropriate controls) in sufficient detail for assessment of feasibility. Explain how the study design and methods support rational design, translatability and promise of the approach. Describe how each study is designed to achieve reproducible and rigorous results, including controls.

▪ Briefly introduce the existing or proposed biomarker(s) and its Contexts of Use.

Additional details of the biomarker effort(s) should be provided in Attachment 6, Biomarker Statement.

▪ For efficacy studies involving preclinical ALS models, describe the rationale for the choice of model(s) and the dose(s) of the drug.

▪ Describe the chemical synthetic pathways associated with proposed lead compound(s) and the feasibility of modification and/or formulation of potential delivery systems.

▪ Provide data to support use of primary and secondary in vitro bioactivity studies for optimization or structure–activity relationships.

▪ Provide data to support target selectivity, engagement, and desirable activity at the intended target.

▪ Describe the statistical plan, including methods and power analysis, for the proposed research.

▪ Consult appropriate guidelines to ensure relevant aspects of rigorous and reproducible research are adequately planned for and, ultimately, reported.

▪ Address potential pitfalls and problem areas and present alternative methods and approaches.

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

– Clinical Impact: Briefly state how the proposed work will have significant clinical impact and advance the development of a novel ALS therapeutic. Describe the target population. Briefly outline, in general terms, steps to transition the study outcomes to therapeutic application. Additional details describing impact should be provided in Attachment 7, Impact Statement.

– Transition Readiness: Specify the current stage of the candidate therapeutic within the FDA IND-enabling pathway, or international equivalent. Explain how the proposed approach will prepare the candidate therapeutic for the transition to clinical studies. Additional details describing a transition plan should be provided in Attachment 8, Transition Plan.

– 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, regulatory

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FY26 Amyotrophic Lateral Sclerosis Therapeutic Development Award 13 expert, patient advocate). Inclusion of a biomarker interpretation expert is highly encouraged.

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.

○ 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 https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01#_Use_Of_DOW_Dept_Veterans_Affairs_Resource:~:text=APPENDIX%204.%0AUSE%20OF%20DOW%20OR%20U.S.%20DEPARTMENT%20OF%20VETERANS%20AFFAIRS%20RESOURCES https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01#_Recipient_Qualification_Restriction_Info:~:text=%C2%B7-,Supporting%20Documentation%3A,-Combine%20and%20attach

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FY26 Amyotrophic Lateral Sclerosis Therapeutic Development Award 14 other relevant considerations. Refer to the CDMRP Directive on Sex as a Biological Variable in Research for additional information.

Research Sharing Plan: Describe the type of data or research resources (e.g., bio-specimen, analysis tool/software, training material) to be made publicly available as a result of the proposed work. Describe the mechanism (e.g., direct sharing, repository, mixed mode) by which data and resources generated during the period of performance will be shared with the ALS research community and other affected communities, including clinical research participants. Include the name of the repository(ies) where scientific data and resources arising from the proposed study will be archived, if applicable. 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). The plan should also protect participant privacy, confidential and proprietary data, and performer/third-party intellectual property.

Provide a milestone plan for disseminating data/results including when data and resources will be made available to other users. In cases where the study participant could potentially derive medical or other benefit from the information, explain whether the results of screening and/or study participation will be shared with the participant or their primary care provider, including results from any screening or diagnostic tests performed as part of the study.

Do not submit a copy of the National Institutes of Health (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.

o 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.

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

Clearly define the goals of the effort/study.

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.

Product: Describe the therapeutic product to be developed and the validated biomarker(s) or biomarker development/characterization proposed.

Impact: Summarize briefly how the proposed project will impact ALS therapeutic development and the ALS community.

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 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/Program.htm#:~:text=Directive%20on%20Sharing%20Data%20and%20Research%20Resources https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01#_Recipient_Qualification_Restriction_Info:~: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:~:text=%C2%B7-,Technical%20Abstract%3A,-Attach%20as%20%E2%80%9CTechAbs

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FY26 Amyotrophic Lateral Sclerosis Therapeutic Development Award 15 overuse of scientific jargon, acronyms and abbreviations. Do not duplicate the technical abstract.

– Summarize the goals, objectives and rationale for the proposed research.

– What population will the research help, and how will it help them?

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

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

– What type of ALS patients will it help, how will it help them, and when will this likely happen?

– 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: Biomarker Statement (no page limit): Required for all applications.

Upload as “Biomarker.pdf”. Development of mechanism-specific (1) predictive/ cohort-selective, (2) target engagement, and (3) pharmacodynamic biomarkers should be incorporated into the application. If mechanism-specific biomarkers are already available or currently in development, how the existing biomarkers will improve trial design, patient selection, and efficiency or interpretation of the proposed ALS therapeutic approach must be described. Preliminary biomarker characterization must address qualification criteria described in relevant ALS biomarker literature. See Section 3.2.1, Key Elements for the TDA, 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 biomarkers will demonstrate target engagement, help refine individual patient or patient subgroup selection, and/or clarify the mechanism-specific biological impact of a potential therapeutic. Describe the extent to which the biomarker results will be used to steer the development process. Describe how the preliminary biomarker characterization addresses qualification criteria described in relevant ALS biomarker literature.

– The inclusion of a decision-tree diagram that explicitly illustrates the application of the biomarkers and includes the actions that would be taken based on the biomarker results is recommended. Describe how easily and reliably the biomarkers may be implemented in eventual clinical trials of the proposed novel therapeutic. Include a description of regulatory considerations for use in future ALS clinical trials.

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

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FY26 Amyotrophic Lateral Sclerosis Therapeutic Development Award 16

○ Attachment 7: 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. This section should be written in a manner readily understood by readers without a background in science or medicine. Overly technical jargon should be avoided and technical terms, if any, should be defined.

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

– Advance the development of a groundbreaking ALS therapeutic.

– Further validate biomarkers in parallel with the main therapeutic effort for use in eventual clinical trials.

– Prime the therapeutic and/or biomarker for rapid clinical implementation in the intended patient populations (including subpopulations).

– Lead to meaningful improvements in patient care.

– Describe how knowledge, information, products, or technologies gained from the proposed research advance research that 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 presented as bullet points to emphasize the main study goals.

Inclusion of a simple diagram of the proposed study, if plausible, is encouraged.

○ Attachment 8: Transition Plan (three-page limit): Upload as “Transition.pdf”.

Provide information on potential methods and strategies to feasibly move the project’s findings to the next phase of development (clinical trials, commercialization, and/or delivery to the civilian or military market) after successful completion of the award.

Outline the regulatory strategy, including steps required to achieve regulatory submissions (e.g., IND). The ALSRP evaluates TDA success based on whether the candidate therapeutic is ready for IND/IDE submission or further optimization upon completion of the award. A Regulatory Compliance Specialist or Technology Transfer Expert may be recruited to peer review the application.

The post-award transition plan should include the components listed below.

– The development and/or commercialization strategy.

– The planned indication for the product label, if appropriate, and an outline of the development plan required to support that indication. Describe in detail the FDA regulatory strategy, to include considerations for compliance with Good Manufacturing Practice, Good Laboratory Practice, and Good Clinical Practice guidelines, if appropriate.

– A description of the scientific or technical requirements needed to advance the research findings, such as manufacturing readiness, analytical validation, assay reproducibility, device classification analysis, etc.

– An assessment of the opportunities available and potential barriers that would impact the progress of commercializing and/or translating the study results into clinical practice.

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FY26 Amyotrophic Lateral Sclerosis Therapeutic Development Award 17

– A timeline with defined milestones and deliverables describing the expected post-award progress of the results toward the next phase of development and eventual clinical impact. This may include a sequenced development pathway, defined regulatory inflection points and realistic time-to-execution assumptions.

– Details of the funding strategy that will be used to bring the outcomes to the next phase of development.