2020 Request for Proposals

Harrington Discovery Institute

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

Average Award

Up to $600,000 over 2 years with dedicated support 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.

Letter of Intent: May 18th, 2020, 5:00 PM EDT (Due to the emerging COVID-19 pandemic, we have extended the deadline. Letters will be reviewed on a rolling basis starting March 31st)
Full Proposal: August 10th, 2020, 5:00 PM EDT

Award decisions are anticipated by December 2020.

Eligibility Criteria

  • Academic investigators at accredited medical centers, research institutions, and universities in the United States, Canada and United Kingdom only are eligible to apply.
  • Lead investigator must have an MD, a PhD, or equivalent.
  • Proposals should show potential to advance discovery into meaningful therapeutics to treat, prevent, or slow Alzheimer’s disease or related dementias.
  • Team should possess intellectual property (IP) or have potential for novel IP that has not yet been licensed to a for-profit entity.
  • Researchers working on drug development programs that are relevant to but not presently focused on the Alzheimer’s field are encouraged to apply.

Funding Priorities

Drug Targets
The 2020 ADDF-Harrington Scholar RFP places high priority on targets related to emerging therapeutic areas for dementia, particularly:

  • Proteostasis (autophagy, lysosomal biogenesis, proteasomal degradation, post-translational modification associated with proteostasis, protein folding/misfolding, ER stress, extracellular clearance)
  • Neurovascular health (blood brain barrier function and integrity, cerebral hypoperfusion, nutrient supply to the brain, endothelial interaction with pericytes and astrocytes)

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

  • Neuroprotection
  • Synaptic activity and neurotransmitters
  • Inflammation
  • Mitochondria & metabolic function
  • ApoE
  • Epigenetics
  • Other aging targets (e.g. senescent cells)

Please note: This RFP does not support anti-amyloid approaches (e.g. Abeta vaccines, beta- or gamma-secretase inhibitors) or cholinesterase inhibitors.

Stage of Discovery
The ADDF-Harrington Scholar award supports programs at the hit-to-lead optimization stage through investigational new drug (IND)-enabling studies. Hit molecules must already be identified at the time of application.

Applicants are encouraged 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 of action. Additionally, where animal model data are reported, please include PK data supporting choice of dosing and study design.  

This RFP does not support target discovery, assay development or high throughput screening campaigns.


Targets: Applicants are encouraged to specifically address these areas in their proposal:

  • Is there human genetic evidence linking the target to Alzheimer’s disease or related dementias?
  • 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 expression or activity in human disease specimens that correlate with disease severity and cognitive impairment?
  • Does manipulation (genetic or pharmacologic) of the target in disease-relevant in vitro (e.g. primary cultured neurons/glia or cells derived from patient iPSCs) or in vivo models ameliorate disease phenotypes?
  • Are there direct measures of target engagement that can be used experimentally and 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?

Therapeutic Modality: All novel drug programs including small molecules and biologics (including ASOs and nucleic acids).

Chemistry: For non-biologic entities, applicants are encouraged to address 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 having 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 studies 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 your proposal).
  • Include measures of target engagement in the proposed animal study design

Applicants are expected to follow the recommendations outlined in Shineman (2011) and Snyder (2016) when developing the animal study design. 

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 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?
  • 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.


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 these areas remain eligible for funding, as scholars receive guidance from Harrington Discovery Institute pharmaceutical industry experts.


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. Harrington Discovery Institute will hold an annual symposium each spring in Cleveland, OH that all Harrington Scholars, including ADDF-Harrington Scholars, are required to attend during each year of the grant period. They are expected to present their project and/or findings-to-date. Expenses for travel and lodging will be provided by Harrington Discovery Institute subject to the terms of the Harrington Discovery Institute Grant Agreement.

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.

Applications and award budgets should be built around milestones. Milestones are key points in a project that represent reliable, quantifiable indicators/deliverables of progress and are used to make decisions on further funding. If an award is made, the Harrington Discovery Institute Therapeutics Development Team will work with recipients to help refine and manage milestones.

The project must be structured to deliver a lead product with strong potential for clinical and commercial application.

Awards are conditional on:

  • Willingness to work collaboratively with the Harrington Discovery Institute Therapeutics Development Team staff
  • Timely submission of financial and progress reports
  • Participation in the Annual Scientific Symposium, organized by Harrington Discovery Institute in Cleveland, Ohio in May of each year

Continued support is dependent upon favorable scientific review of progress reports, milestones being met appropriately, and continued relevance of the work to the mission of the Alzheimer’s Drug Discovery Foundation.

Intellectual Property
Harrington Discovery Institute and ADDF do not claim rights to patents on discoveries, copyrights or trademarks to other intellectual property created as a result of work sponsored by ADDF-Harrington Scholar Awards (“Intellectual Property”).

On all aspects of Intellectual Property, Principal Investigators are encouraged to confer with their technology transfer office and/or office of sponsored programs for guidance. Grantees should take measures to ensure protection of Intellectual Property when appropriate and are required to make prompt disclosure of discoveries to the public.

Project Administration
Harrington Discovery Institute and ADDF do not claim rights to patents on discoveries, copyrights or trademarks to other intellectual property created as a result of work sponsored by ADDF-Harrington Scholar Awards (“Intellectual Property”).

On all aspects of Intellectual Property, Principal Investigators are encouraged to confer with their technology transfer office and/or office of sponsored programs for guidance. Grantees should take measures to ensure protection of Intellectual Property when appropriate and are required to make prompt disclosure of discoveries to the public.


Review the Application Instructions for steps on applying.





For program-related inquiries, please contact:
Meriel Owen, PhD, Scientific Program Officer

Bronwyn J. Monroe, Director, Programs
Website: www.harringtondiscovery.org/addf

For application submission inquiries, please contact:
Grants and Contracts Team