Neuroimaging and CSF Biomarker Program

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

Funding is open to researchers and clinicians worldwide at:

• Academic medical centers and universities or nonprofits. Industry partnerships are encouraged.
• Biotechnology companies. Existing companies and new startups are both eligible.
• NOTE: Funding is provided through mission-related investments that require return on investment based upon scientific and/or business milestones (see Our Research Strategy for more information).

Awad Amount
Up to $600,000 based on stage and scope of research.

Award Duration
One year with potential for follow-on funding.

Allowable costs
Only direct costs are allowed. Please review our Funding Policies

The ADDF focuses on advancing drug development for Alzheimer’s and related dementias and the biomarker tools that aid in this process. This RFP prioritizes biomarker programs that define a specific use and have potential for commercial and clinical translation, with an emphasis on clinical trials (see the Evaluation section below). The RFP supports advancement of neuroimaging and CSF biomarkers that can do one or more of the following:

1. Demonstrate target engagement for novel therapeutics
   Biomarkers that can serve as direct measures of target engagement for novel drugs in clinical development. High priority will be given to projects advancing biomarkers that can be used as specific companion biomarkers for therapies currently in the development pipeline. Identification of such therapies strengthens an application.
2. Detect signs of disease earlier and monitor progression
   Programs developing sensitive biomarkers that can detect disease earlier than currently available biomarkers. This includes biomarkers that can predict and monitor conversion from cognitively healthy to mild cognitive impairment (MCI) or MCI to Alzheimer’s disease. We also seek prognostic markers that can predict rates of cognitive decline.
3. More accurately diagnose and distinguish between dementia subtypes
   Many types of dementias can present with similar clinical features, and patients often show overlapping pathologies. At present, it is challenging to distinguish between dementia subtypes and proteinopathies. Biomarkers that can distinguish between subtypes and stratify patients in clinical trials are of high priority.

MODALITY-SPECIFIC PRIORITIES

Neuroimaging:

• Positron emission tomography (PET): These projects should focus on ligands for target engagement and pharmacodynamic measurements of novel and repurposed therapeutics. This RFP will support pharmacokinetics, safety, synthesis, and clinical development of novel PET ligands. The investigative team should include individuals with experience in developing PET ligands for human use.
• Magnetic resonance imaging (MRI): The proposed structural or functional approach should already have proof-of-concept data in human patients and be translatable for clinical use. Approaches that can measure novel targets and are significant improvements upon what is currently available in MR techniques are of higher priority.
• Magnetic resonance spectroscopy (MRS): The ability to detect specific molecules or proteins relevant to disease or a specific drug in development should be demonstrated in the preliminary data section of the application.

Cerebrospinal fluid (CSF) biomarkers can be a single analyte or panel of analytes; however, the proposed signature should have proof-of-concept data in human patient samples and the specific analyte combination should be well justified.

Functional activity measures applicable to this RFP include electroencephalogram (EEG), magnetoencephalography (MEG), and transcranial magnetic stimulation (TMS). Only highly novel techniques or analyses for EEG, MEG and TMS will be considered. These proposals must meet the following criteria:

• The proposed approach is an improvement on already existing functional measures used in clinical practice for diagnosing and monitoring dementias
• The biomarker and its biological connection to the disease should be established and clearly described
• Proof-of-concept data should be completed in human patients

Other novel approaches: The biomarker should already be identified and validated in at least a small number of human samples.

All proposals should address the following:

Context of use: This RFP will consider all context of use categories that will advance drug development for Alzheimer's and related dementias. These categories, as defined by the FDA, include diagnostic, monitoring, predictive, prognostic, pharmacodynamic/response, and susceptibility/risk biomarkers. The expected context of use, which defines a biomarker's intended clinical use, should be described in the application. The development plan should be appropriate for the described context of use.

How the proposed biomarker compares to currently available biomarkers: PET imaging and CSF markers of amyloid and tau can distinguish between Alzheimer’s disease and healthy control individuals with high specificity and sensitivity. The applicant must demonstrate the advantage of their approach with these tests in mind (cheaper, easier to use, less invasive, etc.), and how it compares to the sensitivity/specificity of what is currently available (CSF Aβ, CSF tau, PET scans, MMSE, etc.).

Potential for commercial and clinical translation: The path to commercialization and clinical use should be considered in all proposals. Applicants should clearly state how the proposed biomarker would fit into the current clinical landscape. The applicant should articulate where in the path to commercialization the study falls and outline the proposed plan forward. Clear milestones and go/no-go decision points should be provided. Identification of potential future commercial partners is encouraged.

In addition, all proposals will be evaluated for:

• Novelty and biological plausibility linking the biomarker to disease pathophysiology in human studies
• Scientific and technical merit of the proposed approach
• Strength of preliminary data using the proposed biomarker in preclinical and human samples
• Level of innovation
• Feasibility, research design and methodology
• Investigator, organizational capabilities, and budget for the project