Drug Development Request for Proposals (RFP)

Drug Development Request for Proposals (RFP) is sponsored by Alzheimer's Drug Discovery Foundation (ADDF). The ADDF provides funding to academic centers and biotechs from around the world that are advancing therapeutic and biomarker development for Alzheimer's and related dementias.

Drug Development RFP | Alzheimer's Drug Discovery Foundation The Drug Development RFP supports investigational new drug (IND)-enabling studies (or the international equivalent) and early-phase clinical trials that test promising pharmacological interventions and devices for Alzheimer’s disease (AD) and related dementias.

This funding opportunity concentrates on diverse drug mechanisms and modes of action related to the biology of aging and other emerging therapeutic areas for dementia. ADDF strategic priorities include: Combination therapies of two or more drugs to be administered together or development of combination products.

This may include: co-development of two or more new investigational drugs a single new investigational drug in combination with a previously approved anti-amyloid monoclonal antibody fixed combinations of two previously approved drugs Disease-modifying and symptomatic agents 1.

Early-stage human clinical trials including: Phase 0 micro- or sub-therapeutic-dosing studies Phase 1 trials in healthy subjects or patients Biomarker-based proof-of-concept studies (generally phase 1b or phase 2a trials) designed to assess target engagement and downstream pharmacologic effects 2.

IND (or international equivalent) – enabling studies including: Non-GLP and GLP pharmacology and toxicology studies, pre-formulation, and GMP manufacture of API and/or drug product required for regulatory packages.

Funding is available for preparation of traditional and exploratory IND (or international equivalent) applications Long-term toxicology studies to enable longer-term dosing in phase 2 trials GMP manufacturing and testing of API and/or drug product required to move into phase 2 or phase 3 trials For clinical trial applications, if IND-enabling work is in progress, funding for clinical studies would be contingent upon an IND (or equivalent) successfully going into effect.

Type of therapy: Novel, repurposed and repositioned drugs, as well as natural products and devices will be considered. Therapeutic modalities of interest include small molecules, peptides, antibodies, gene therapies, antisense oligonucleotides, and stem cells. Other non-pharmacologic interventions, such as diet, meditation, and exercise, will not be considered.

A detailed landscape analysis to compare competition related to the mode or mechanism of action is strongly encouraged. Drug mechanisms or modes of action: Novel drug mechanisms and modes of action related to the biology of aging and other emerging therapeutic areas for dementia are considered high priority.

These include, but are not limited to: Mitochondrial & metabolic function Synaptic activity and neurotransmitters Other mechanisms and modes of action related to the biology of aging (e.g. senescent cells) Other novel mechanisms or modes of action that are supported by compelling evidence demonstrating a rational biological connection to the disease process Please note: Anti-amyloid approaches (e.g., anti-amyloid aggregation, beta-amyloid vaccines, beta- or gamma-secretase inhibitors) and cholinesterase inhibitor proposals will not be considered 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 strongly 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). Up to $5,000,000 based on stage and scope of research.

For studies requiring additional support, co-funding from other funding agencies or investors is encouraged. Payment structure will be negotiated and based on milestone achievements and recruitment. Only direct costs are allowed.

Please review our Funding Policies 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 of the aspects listed below.

Please note: ADDF prioritizes novel drug candidates with composition of matter intellectual property (IP) and repurposed or repositioned drugs with strategies to develop novel IP.

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 AD or related dementias and should specifically address these questions in the proposal: Is the mechanism or 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 Preliminary data: Applicants are encouraged to include data around the following: Supportive preclinical efficacy data in relevant animal models Evidence of blood-brain barrier penetration (for CNS targeted therapies) Preclinical and, if available, clinical PK/PD data on dose optimization for the intended route of administration and dosing regimen Preclinical, and if available, clinical safety data.

Proposals should include plans to address remaining safety concerns if any are identified in earlier studies Clinical population: Proposals including patients should provide justification for the selected clinical population and how enrollment criteria such as clinical subtype, stage of severity, known genetics (e.g. ApoE status), and neuropathology (e.g. amyloid positivity) relate to the proposed mode of action.

Applicants must provide information about recruitment of the target population to demonstrate that a sufficient number of patients are available to meet recruitment goals.

Expectations for biomarker-based proof-of-concept studies: Provide justification for the dose(s) selected Design studies to answer specific questions about a therapy’s activity, including whether an intervention is safe, engages its target, induces expected downstream pharmacological effects, and leads to changes on disease-related measures Include biomarker outcomes that align with the proposed mechanism or mode of action and, where possible, are predictive of clinical efficacy Include clinical assessments that align with the appropriate domains of the clinical syndrome, stage of disease, and mechanism of action.

Although these studies may not be powered to detect differences in clinical outcomes, the inclusion of cognitive and neuropsychological endpoints may be informative as exploratory outcomes. Expected directional changes that correlate with biomarker changes may be observed and can inform planning for subsequent studies Engage a biostatistician early in the development of the study design.

Statisticians can help to determine the appropriate study design options and sample size calculations for these smaller biomarker-based studies, particularly when novel biomarkers without established effect sizes are used Investigative team: Clinical trials often require resources beyond those available at a single organization and collaboration with other investigators and contract research organizations and consultants are encouraged.

Please note: All clinical trials receiving ADDF funding must register and submit results for “applicable clinical trials” on the ClinicalTrials. gov Protocol Registration and Results System Information website. Review the Application Instructions for steps on applying.

For inquiries, please contact: ADDF Grants and Mission-Related Investments Team Alzheimer's Drug Discovery Foundation A GuideStar-Rated Charity 57 West 57th Street, Suite 904