Diagnostics Accelerator and Target ALS Foundation Biomarker Discovery RFP

Modalities: Protein and molecular biomarkers in blood and other peripheral fluids, including saliva, urine and ocular biomarkers are encouraged. Digital biomarker approaches are also of high interest. The development of CSF and neuroimaging biomarkers will not be considered for this program; however, we encourage the use of these modalities to validate proposed biomarkers. Proposals to support or create longitudinal cohorts will not be considered, but we welcome applications utilizing existing patient cohorts. In addition, it is expected that applicants will have some supporting data collected to support their proposed research and/or an existing prototype device or app developed in the case of digital biomarkers, commensurate with the project stage and justified budget as described below.

Biomarker targets: Proposed approaches will be evaluated on biological plausibility linking the biomarker to disease pathophysiology. Examples of target areas of interest include:

Peripheral Biomarkers of Interest

• Misfolded proteins (e.g., TDP-43) and related biological pathways
• Dipeptide repeats
• Neuroinflammation
• Progranulin
• Ocular biomarkers (e.g., retinal vasculature, choroidal thickness, retinal nerve fiber layer thinning etc.)

Digital Symptom Domain of Interest

• Gait and gross motor movement
• Sleep patterns and characteristics
• Strength (e.g., handheld dynamometry)
• Speech and swallowing
• Instrumental Activities of Daily Living (IADL)
• Fatigue

Neurofilament is out of scope for this call, as the current stage of biomarker development for neurofilament is more advanced and this type of study will be supported by the main Diagnostics Accelerator peripheral call for proposals. Projects aligned with the target areas described above will be prioritized. Other novel approaches that are supported by compelling evidence that demonstrate a rational biological connection to the disease process may be considered. Applicants will be asked to demonstrate biological connection by citing existing scientific literature and providing supporting clinical evidence generated in the researcher’s laboratories. Applications with data in other neurodegenerative diseases (e.g., Parkinson’s disease, Traumatic Brain Injury, etc.) will be considered along with the demonstration of biological connection to Alzheimer’s disease, FTD and ALS. Applicants with a research hypothesis, but lacking supporting data, will not be considered.

The expected context of use, as defined by the FDA, which defines a biomarker's intended use clinically as a diagnostic or in drug development, should be described in the application. Additionally, the applicant should articulate where within the path to commercialization the study falls and what is the proposed plan forward to bring the biomarker to patients.

Each LOI should be a maximum of one to two pages. The LOI should clearly identify the scientists involved (with a short paragraph about the expected contribution of each) and a defined set of scientific objectives with explicit milestones. Where appropriate, investigators should provide a signed commitment from a repository to enable access to requisite biofluid samples to successfully carry out the project.

An investigator can submit a maximum of two LOIs if each application is focused on a distinct project. A given laboratory can be a member of up to two LOIs.

All proposals will be evaluated on scientific and technical merit, level of innovation and investigator and organizational capabilities. Additionally, proposals will be evaluated on the following criteria:

• Context of Use: a concise description of the biomarker's specified use in drug development
• Methodological considerations (for peripheral projects): Including sample collection and storage, quality and reliability of the assay used, and strategy for maximizing reproducibility
• Samples or subjects: Obtained from well-characterized cohorts and, when possible, should include individuals from minority and disparity populations

Full proposals should be concise and consistent with a clear exposition of the goals and main steps of the project. The total length should not exceed two pages per participating lab (i.e. up to eight pages in Arial 11 pt for a project involving four labs). The project leader can choose to use the allowable space as they deem fit to best present the project plan. The total length includes the following sections: specific aims; background and biological rationale; research plan; statement of relevance to Alzheimer’s disease or FTD and ALS, and biomarker strategy; a bullet list indicating the specific involvement of each partner; a table indicating milestones for the first two years of the project. Preliminary data will be helpful but are not required.

The following sections are required but will not count towards the page limit:

• References and cited literature
• Two-page biosketches for all collaborating lab PIs.
• A budget and personnel justification (see attached budget template).
• A signed agreement with a biofluid repository ensuring access to biofluid samples necessary to successfully complete the project will be required for a project to be considered for funding. The Diagnostics Accelerator and Target ALS will work with investigators to facilitate contact with biofluid repositories to provide access to biofluid samples with no reach through on the data and intellectual property generated by the collaborative. Funding for successful projects will only be initiated once the material transfer agreements have been fully executed between the investigator(s) and a biorepository.
• Collaborative project agreement defining the terms of information sharing and IP between different members of the collaborative project will be required. This is not required at the time of submission, but the proposal should outline the strategy that will be employed to reach such an agreement between the partners. Funding through Target ALS asks for no reach-through but strongly encourages collaborative projects to make data and reagents broadly available to the broader research community within a reasonable time.

Please note: Late-stage proposals to support the validation of proposed biomarkers can be considered via the Diagnostics Accelerator’s peripheral biomarker call for proposals, and will be invited to join this group of funded collaborative projects at a joint meeting if funded, but will not be funded via this call. This would include, for example, validation of biomarkers (i.e. Neurofilament Light or NfL) or research projects proposing to bring such biomarker tests to market as an LDT or IVD.

Must be received by 5:00 pm EST on the deadline date.

Letters of intent will be accepted from the 5th of January, 2022, and reviewed on a rolling basis up until the deadline. Any applications received after this deadline may be reviewed at the discretion of the Consortium.

Deadlines

Request for Proposals Issued
Wednesday, January 5, 2022

Deadline for Submission of Letters of Intent
Wednesday, March 2, 2022

Full Proposals Solicited
Friday, March 11, 2022

Deadline for Submission of Full Proposals
Friday, May 6, 2022

Funding Decisions Announced
Friday, May 27, 2022

The Diagnostics Accelerator and Target ALS aim to foster an ongoing network and community of researchers dedicated to advancing biomarkers for neurodegenerative diseases. As such, investigators funded through this joint partnership will become part of The Diagnostics Accelerator and Target ALS Consortium. Investigators who are part of this consortium will be required to:

• Participate in an annual joint meeting between the Diagnostics Accelerator and Target ALS (held in the first week of May each year) and present project progress including unpublished data (in-person if possible; virtual options available as the COVID-19 pandemic persists).
• Participate in the annual Diagnostics Accelerator Conference (held each fall) and other activities such as routine tele/videoconferences to facilitate interaction and collaboration.
• Be linked to the other researchers funded as part of this Consortium via ADDF and Target ALS-organized interactions and meetings with the intent to accelerate the exchange of ideas, encourage sharing of commonly useful knowledge and methods, facilitate collaboration, and provide networking opportunities for trainees.
• Report annually on efforts towards integration and collaboration with other funded investigators, as well as observations on successes/challenges of such integration.
• Applicants are encouraged to outline strategies for communication and interaction with other funded researchers in the proposal, potentially including ways to encourage interaction, augment or expand study findings, share training opportunities for fellows and junior investigators, etc.