The ADDF-Harrington Scholar Program is dedicated to advancing academic discoveries into medicines for Alzheimer’s disease and related dementias. This award provides funding and project support by a team of pharmaceutical industry experts through a collaboration with the Alzheimer’s Drug Discovery Foundation (ADDF) and the Brain Health Medicines Centers of the Harrington Discovery Institute. This is a special funding opportunity separate from ADDF’s Therapeutic Funding Programs.

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).

Average Award

The award typically entails up to $600,000 over 2 years with dedicated support for milestone-driven projects from a team of industry veterans with capabilities that include medicinal chemistry, pharmacology & toxicology, and business development. The expertise of each team is tailored to the specific needs of the project during the two-year award period.

DEADLINES

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

Letter of Intent: June 8, 2026
Full Proposal: August 17, 2026

Award decisions are anticipated by March 2027.

Funding Priorities

Drug Targets
The ADDF-Harrington Scholar RFP places high priority on targets related to emerging therapeutic areas for dementia, particularly:

• Proteostasis (including autophagy, lysosomal biogenesis, proteasomal degradation, post-translational modification associated with proteostasis, protein folding/misfolding, ER stress, extracellular clearance)
• Senescence (including cells that have halted division, shifted towards a secretory phenotype, altered morphology and epigenetics, and decreased apoptosis)

Other novel targets are encouraged. These include, but are not limited to:

• Epigenetics
• Vascular pathology
• Neuroprotection
• Synaptic activity and neurotransmitters
• Inflammation
• Mitochondrial health
• Antioxidant defense
• Metabolic function and brain energy
• Brain insulin resistance
• ApoE
• Glymphatic clearance
• Postnatal neurogenesis
• Other aging targets

Therapeutic targets with a clear marker of target engagement, either established or in development will be considered of high priority.

The ADDF-Harrington Scholar Program does not support anti-amyloid approaches (e.g. Abeta vaccines, beta- or gamma-secretase inhibitors) or cholinesterase inhibitors. Approaches targeting tau will be considered if it is clearly demonstrated how they are distinct from those already in clinical development.

Stage of Discovery
The ADDF-Harrington Scholar Program supports research ranging from the hit-to-lead optimization stage through investigational new drug (IND)-enabling studies. A lead structural series must already be identified at the time of application.

Applicants are asked to provide hit validation data, including dose-response curves, analog structure-activity relationship (SAR) results, and comparison data against known molecules with a similar mechanism or mode of action.

When animal model data are reported, detailed study design including rationale for choice of animal model, power analysis to determine number of animals, balanced investigation of sexes or rationale for studying only one sex, and PK data supporting choice of dosing regimen should be described.

The ADDF-Harrington Scholar Program does not support target discovery, assay development, or high throughput screening campaigns.

EXPECTATIONS

Mechanisms or modes of action: Applicants are encouraged to provide a clear rationale and compelling evidence for targeting the proposed mechanism or mode of action in Alzheimer’s disease or related dementias. They should specifically address the following questions in the proposal:

• Is there human genetic evidence linking the molecular target to Alzheimer’s disease or related dementias?
• Is the molecular 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 expression or activity in human disease specimens that correlate with disease severity and cognitive impairment?
• Does genetic or pharmacologic 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 phenotype(s)?
• Are there direct measures of target engagement or primary pharmacodynamic activity that can be used experimentally and potentially in humans?
• What is uniquely compelling about the target in comparison to other targets that have been tested for Alzheimer’s disease or related dementias?
• If the molecular target is unknown, what is the strength of the evidence for the mode of action and its link to Alzheimer’s disease or related dementia? The applicant should summarize the existing evidence in the proposal.

Therapeutic Modality: The ADDF-Harrington Scholar Program supports all novel drug programs, including small molecules, antibodies, peptides, oligonucleotides, and gene therapies.

Chemistry: For non-biologic entities, applicants are encouraged to address the following questions, if applicable:

• Does the lead molecule or series have 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 having been assessed for structural liabilities?
• Have adequate solubility and scale-up feasibility for the lead molecule(s) been demonstrated?
• Has selectivity among related and unrelated family members been assessed?
• Does in vitro ADMET (absorption, distribution, metabolism, excretion, toxicity) profiling indicate sufficient drug-like properties

Preclinical efficacy studies: Applications that include preclinical efficacy studies should:

• Demonstrate 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 your 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.

Applicants are expected to follow the recommendations outlined in Shineman (2011) and Snyder (2016) when designing their animal 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. It is recognized that a limitation of the field is that there is no perfect animal model of Alzheimer’s disease. Rather, each model reflects different aspects of disease, which vary from the number and types of phenotypes observed to their onset and severity. However, the appropriate model can provide valuable information about 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?
• Which symptoms or pathologies of the human disease does the model mimic?
• Does the model exhibit the appropriate phenotype(s) to measure target engagement?
• 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, blood-brain barrier deterioration, neuroinflammation, oxidative damage, neuronal loss, plaques, tangles, cognitive defects, etc)?

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

SELECTION

In addition to the above criteria, project assessment will be based on:

• Quality of the science and the scientist
• Novelty and innovation of the work
• Potential for impact on human health

Highly compelling proposals with some gaps in any of these areas remain eligible for funding, as scholars receive guidance from Harrington Discovery Institute pharmaceutical industry experts.

MORE INFORMATION

Confidentiality
Members of the ADDF and Harrington Discovery Institute review panels and Scientific Advisory Boards complete mutual Confidentiality & Disclosure Agreements to protect confidential applicant submissions.

Non-public applicant information is kept confidential and limited in distribution to the reviewers and Harrington Discovery Institute and ADDF administrative teams. The executive summary, applicant’s name, project title, and institutional affiliation for ADDF-Harrington Scholars may be used by ADDF and Harrington Discovery Institute for publicity and marketing purposes (on the ADDF and Harrington Discovery Institute website, news releases, etc.) at ADDF’s and Harrington Discovery Institute's sole discretion.

Annual Scientific Symposium
Part of Harrington Discovery Institute’s mission is to build a broad connected community of scientists to promote interaction among awardees as well as with other preeminent scientists. Each spring, Harrington Discovery Institute holds an annual symposium in Cleveland, OH that all Harrington Scholars, including ADDF-Harrington Scholars, are required to attend, subject to the terms of the Grant Agreement. They may be asked to present their project and/or findings-to-date.

Use of Funds
The awards are provided as milestone-driven payments totaling up to $600,000 over two years. Progress will be reviewed regularly by an oversight committee.

AI Based Application Success Predictor

⚠️ Common Weaknesses in Unsuccessful Applications

Too basic or exploratory (e.g., mechanistic cell biology with no clear therapeutic angle).

Weak or unconvincing preclinical evidence.

No defined milestones or poor go/no-go plan.

Unprotected IP or uncertain freedom-to-operate.

Overly ambitious (Phase 2 trial readiness claimed without sufficient preclinical data).

Unclear link to Alzheimer’s pathology.

📊 Patterns in Funded Projects (2016–2024)

💡 Top Predictors Summarized

Therapeutic translation focus (drug discovery to early clinical)

Strong and relevant preclinical data

Clear Alzheimer’s/ADRD mechanistic link

Defined milestones and timelines

Solid IP position and commercialization pathway

Experienced, translationally balanced team

Fit with ADDF program scope

Collaborative, cross-disciplinary partnerships

📈 Example Funded Projects

Yale University: small molecule targeting neuroinflammation pathway for AD — strong animal data, IND-ready plan.

Cognito Therapeutics: noninvasive neuromodulation therapy; robust translational path, AD relevance clear.

Oryzon Genomics: repurposed LSD1 inhibitor for cognitive decline.

NeuroDex: exosome-based diagnostic for AD — fit under Diagnostics Accelerator.