Diagnostics Accelerator

NOTE - Due to the COVID-19 pandemic, we understand there may be delays in submitting applications. We will consider an extension if delays are anticipated. Please email your scientific point person listed at the end of this RFP.

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

Average Award
Up to $600,000 based on stage and scope of research.
Payment structure will be negotiated and based on milestone achievements.

Average Duration
One year with potential for follow-on funding.
Multi-year proposals can be considered.

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

Funding is open to researchers and clinicians worldwide at:

• Academic medical centers and universities or nonprofits. Industry partnerships are encouraged.
• Biotechnology companies. Funding is provided through mission-related investments that require return on investment based upon scientific and/or business milestones. Existing companies and new startups are both eligible.

The strongest proposals will provide a clear rationale for targeting the proposed mode or mechanism of action and include supportive preclinical data, study outcomes that can measure pharmacokinetic/pharmacodynamic relationships and evidence of target engagement, a testable hypothesis with well-defined go/no-go decision points, an experienced team with appropriate expertise and resources necessary to carry out the proposed research.

The following guidance may assist you in developing a strong application that allows reviewers to better evaluate the science and merit of your proposal. The strongest proposals will contain many or all these aspects listed below, although we recognize that the field is still in need of a better understanding of underlying biological mechanisms. Any approaches with a sound biological rationale and well justified outcome measures will be considered.

Mechanisms or modes of action: Applicants are encouraged to provide a clear rationale and compelling evidence for targeting the proposed mode or mechanism of action in AD, FTD, or related dementias and should specifically address these questions in their proposal:

• Is the mechanism and mode of action novel? How is the target biology more compelling than other related targets that have been tested for the disease?
• Is there human genetic evidence linking the target biology to the disease?
• Is the target expressed in disease-relevant regions of the brain (or where applicable, in the periphery) in humans and/or animal models?
• Are there changes in target mRNA/protein expression or activity in human disease specimens, and do they correlate with disease severity and cognitive functions?
• Does genetic and/or pharmacological manipulation of the target in disease-relevant in vitro (e.g., primary cultured neurons/glia or cells derived from patient iPSCs) or in vivo models alter disease phenotypes?
• If the molecular target is unknown, the strength of the evidence for the mode of action and its link to disease pathophysiology will be evaluated. The applicant should summarize the existing evidence in the proposal.

Chemistry: For non-biologic entities applicants are encouraged to include data around many or all of the following:

• Lead molecule or series has in vitro biological activity in the nanomolar range for biochemical assays (where the molecular target is known) and <10µM in cell-based/phenotypic assays based on the target
• Chemical structures of leads have been assessed for structural liabilities
• Adequate solubility and scale-up feasibility has been demonstrated
• Selectivity among related and unrelated family members has been assessed
• Initial in vitro ADMET (absorption, distribution, metabolism, excretion, toxicity) profiling indicates sufficient drug-like properties

Preclinical efficacy studies: Applications that include preclinical efficacy should:

• Provide data demonstrating blood-brain barrier penetration in cases of CNS targets
• Justify dosing administration and regimen with in vivo PK/PD data. If this data is not yet available, a PK/PD study aim should be included in the proposal. In most cases, a PK/PD study should be performed prior to efficacy studies to inform the dosing regimen selected.
• Include measures of direct and indirect target engagement that can be used preclinically and clinically. Outcomes that assess pharmacodynamic responses related to the target biology will be prioritized. For example, inflammation targeted drug proposals should prioritize biochemical and immunohistochemical markers related to the target biology over behavioral outcomes.
• Please note: Applicants are expected to follow the recommendations outlined in Shineman (2011) and Snyder (2016) when developing the animal study design.
• Please note: The ADDF strongly encourages researchers to use the Alzheimer’s Disease Preclinical Efficacy Database (AlzPED), to survey the literature on the preclinical testing of drugs for Alzheimer’s disease and, to raise their awareness about the critical data, design elements, and methodology required for rigorous, reproducible and translatable preclinical studies.

Animal models: There are numerous available models of Alzheimer’s disease and related dementias, including aged animals and transgenic models with a host of different transgenes expressed alone or in combination. Each of these models reflect different aspects of disease, which vary from the number and types of phenotypes observed to their onset and severity; however, none of these models recapitulate all aspects of human disease. Instead, the appropriate model can provide valuable information on how the therapeutic engages with its target and its ability to modify phenotypes related to its mode of action. Reviewers will evaluate the rationale for the proposed animal model using the following criteria:

• How well characterized is the animal model? Has it been characterized in the applicant’s or collaborator’s lab, or is there historical control data available from the contract research organization (CRO) that will run the study?
• Does the model mimic one or more human symptoms of the primary disease indication?
• Does the model exhibit the appropriate phenotype(s) to measure target engagement (e.g. a drug intended to reduce pro-inflammatory cytokines in the brain should be tested in a model shown to exhibit elevated pro-inflammatory cytokine levels)?
• Does the model exhibit other phenotypes relevant to the mode of action that can be measured as secondary outcomes (e.g. synaptic changes, mitochondrial defects, neuronal loss, plaques, tangles, cognitive defects, etc.)?

Please visit Alzforum’s Research Model Database for a select listing of rodent models of neurodegenerative diseases. On occasion, the ADDF will consider canine and non-human primate models for preclinical efficacy testing if there is sufficient justification for testing in larger animals at this stage of development.

For programs testing repurposed/repositioned drugs, provide a clear rationale for the need to perform the proposed aims in animal models instead of testing directly in human clinical studies. Proposals testing repurposed or repositioned therapies should provide a discussion around the known side effects and how well tolerated by the intended clinical population. Plans to develop novel IP around the repurposing/repositioning strategy should be considered.

Investigative team: The preclinical drug development process will likely require resources beyond those available at a single organization and collaborations with other investigators, CROs, and consultants are encouraged.