Harrington Discovery Institute

The ADDF-Harrington Scholar Program seeks to accelerate translation of innovative research with potential to prevent, treat, or cure Alzheimer's disease.

This collaboration between the Alzheimer's Drug Discovery Foundation (ADDF) and Harrington Discovery Institute provides award recipients with both research funding and committed project support by a team of pharmaceutical industry experts.
This is a special funding opportunity separate from ADDF's Core Funding Programs.

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Deadlines

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

Letter of Intent: April 12, 2019
Full Proposal: July 19, 2019

Average Award

Up to $600,000 over 2 years


Eligibility Criteria

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

Funding Priorities

Drug Targets

For the 2019 ADDF-Harrington Scholar RFP, targets related to proteostasis are of high priority.

These include, but are not limited to:

  • Autophagy
  • Lysosomal biogenesis
  • Proteasomal degradation
  • Post-translational modifications associated with proteostasis
  • Protein folding/misfolding
  • Endoplasmic reticulum stress
  • Extracellular clearance

Although targets of proteostasis show high potential for the treatment of Alzheimer's disease and related dementias, the field faces several challenges including a limited number of specific druggable targets for novel small molecules and a lack of translatable biomarkers that could be used in future clinical trials. For these reasons, there is a high interest in proposals that show promise in this area.

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

  • Neuroprotection
  • Inflammation
  • Vascular function
  • Mitochondria & metabolic function
  • APOE
  • Epigenetics

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

This RFP aims to support hit-to-lead optimization through investigational new drug (IND)-enabling studies.

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


EXPECTATIONS

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?
 

Chemistry

Priority will be given to novel drug programs that have addressed 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 <10┬ÁM 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, et al. and Snyder, et al. 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.


SELECTION

In addition to the above criteria, projects will be assessed on:

  • Quality of the science and the scientists
  • Novelty and innovative quality 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.


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 the 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, Ohio 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.

Award decisions are anticipated by December 2019.

 

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 Innovation Support Center will work with recipients to help refine and manage the 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 Innovation Support Center 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 then are required to make prompt disclosure of discoveries to the public.

 

Project Administration

Grants are funded by the ADDF upon recommendation from the ADDF-Harrington Program Joint Steering Committee. Innovation Support Center guidance is provided and underwritten by Harrington Discovery Institute. The ADDF-Harrington Program, and its review panels and Scientific Advisory Board members do not assume responsibility for the conduct of the project or the acts of the Principal Investigator, since both are under the direction and control of the Principal Investigator's institution and subject to the institution's medical and scientific policies.

The ADDF-Harrington Initiative reserves the right to refine and amend policies as required.


APPLICATION SUBMISSIONS

Review the Application Instructions for steps on applying.

 

 

For program-related inquiries, please contact:
Meriel Owen, PhD, Scientific Program Officer
mowen@alzdiscovery.org

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

For application submission inquiries, please contact:
Grants and Contracts Team
grants@alzdiscovery.org